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Medical Genetics
Mohammed El-KhateebDental Postgraduate
MG - Lec 13ed July 2013
OBJECTIVES
Basic understanding of clinical genetics
Be able to draw and understand a family tree
Have awareness of when you should be considering a genetic condition
Have a working knowledge of the most important genetic conditions
Know how amp when to refer to local specialist genetics services
Whatrsquos a ___bull Genetics Is the branch of biology that deals
with heredity and variation in all living organisms
bull The subfields of genetics
Human genetics
Animal genetics
Plant genetics
Medical genetics
Whatrsquos a ___bull Medical Genetics
Is the science or study of biological
variation as it pertains to health and
disease in human beings
Any application of genetic principles to medical
practice
ldquoGenetics ndash study of individual genes and their effectsrdquo
Includes studies of inheritance mapping disease
genes diagnosis treatment and genetic counseling
History of Medical Genetics
bull Early Genetics - Biblical Talmud
bull Mendel - 1860s
bull Modern Experimental Genetics - 1900s
bull Maize drosophila mouse
bull Medical Genetics - 1960s to the
present
Foundations of Heredity
Science Variable traits are inherited
Gene ndash trait-specific unit of heredity
Alternative versionsof a gene (alleles)determine the trait
Each parent transmitsan allele to the offspring
Gregor Mendel Charles Darwin
Mendel studies seven characteristics
in the garden pea
Mendel deduced the underlying principles
of genetics from these patterns
1 Segregation
2 Dominance
3 Independent assortment
Alleles alternative versions of a gene
The gene for a particular inherited character resides at a specific locus
(position) on homologous chromosome
For each character an organism
inherits two alleles one from each
parent
bull Prenatal Geneticsbull 1970s - Prenatal Ultrasound amp Amniocentesis
bull Inheritance of Genetically Complex Disordersbull Non-Mendelian Geneticsndash Genomic Imprintingndash Triple Nucleotide Repeatsndash Mitochondrial Inheritancebull 1990s - Neuropsychiatric Disorders Diabetes
Cardiovascular
ndash Interaction of genes with environmental triggers
Medical Genetics 1960s to the present
bull DNA Genetics
bull 1953 - Watson and Crickrsquos Double Helix
bull 1992 ndash2003 Human Genome Project
bull 2003 -gt the future of medical dx amp tx
C19th Mendel discovers basis of inheritance
Darwinrsquos theory of natural selection
1953 Watson and Crick discover structure of DNA
1985 PCR
1986 Duchenne muscular dystrophy gene
1989 Cystic Fibrosis gene
1998 Decision to sequence entire human genome
2001 Human genome sequence completed
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
OBJECTIVES
Basic understanding of clinical genetics
Be able to draw and understand a family tree
Have awareness of when you should be considering a genetic condition
Have a working knowledge of the most important genetic conditions
Know how amp when to refer to local specialist genetics services
Whatrsquos a ___bull Genetics Is the branch of biology that deals
with heredity and variation in all living organisms
bull The subfields of genetics
Human genetics
Animal genetics
Plant genetics
Medical genetics
Whatrsquos a ___bull Medical Genetics
Is the science or study of biological
variation as it pertains to health and
disease in human beings
Any application of genetic principles to medical
practice
ldquoGenetics ndash study of individual genes and their effectsrdquo
Includes studies of inheritance mapping disease
genes diagnosis treatment and genetic counseling
History of Medical Genetics
bull Early Genetics - Biblical Talmud
bull Mendel - 1860s
bull Modern Experimental Genetics - 1900s
bull Maize drosophila mouse
bull Medical Genetics - 1960s to the
present
Foundations of Heredity
Science Variable traits are inherited
Gene ndash trait-specific unit of heredity
Alternative versionsof a gene (alleles)determine the trait
Each parent transmitsan allele to the offspring
Gregor Mendel Charles Darwin
Mendel studies seven characteristics
in the garden pea
Mendel deduced the underlying principles
of genetics from these patterns
1 Segregation
2 Dominance
3 Independent assortment
Alleles alternative versions of a gene
The gene for a particular inherited character resides at a specific locus
(position) on homologous chromosome
For each character an organism
inherits two alleles one from each
parent
bull Prenatal Geneticsbull 1970s - Prenatal Ultrasound amp Amniocentesis
bull Inheritance of Genetically Complex Disordersbull Non-Mendelian Geneticsndash Genomic Imprintingndash Triple Nucleotide Repeatsndash Mitochondrial Inheritancebull 1990s - Neuropsychiatric Disorders Diabetes
Cardiovascular
ndash Interaction of genes with environmental triggers
Medical Genetics 1960s to the present
bull DNA Genetics
bull 1953 - Watson and Crickrsquos Double Helix
bull 1992 ndash2003 Human Genome Project
bull 2003 -gt the future of medical dx amp tx
C19th Mendel discovers basis of inheritance
Darwinrsquos theory of natural selection
1953 Watson and Crick discover structure of DNA
1985 PCR
1986 Duchenne muscular dystrophy gene
1989 Cystic Fibrosis gene
1998 Decision to sequence entire human genome
2001 Human genome sequence completed
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Whatrsquos a ___bull Genetics Is the branch of biology that deals
with heredity and variation in all living organisms
bull The subfields of genetics
Human genetics
Animal genetics
Plant genetics
Medical genetics
Whatrsquos a ___bull Medical Genetics
Is the science or study of biological
variation as it pertains to health and
disease in human beings
Any application of genetic principles to medical
practice
ldquoGenetics ndash study of individual genes and their effectsrdquo
Includes studies of inheritance mapping disease
genes diagnosis treatment and genetic counseling
History of Medical Genetics
bull Early Genetics - Biblical Talmud
bull Mendel - 1860s
bull Modern Experimental Genetics - 1900s
bull Maize drosophila mouse
bull Medical Genetics - 1960s to the
present
Foundations of Heredity
Science Variable traits are inherited
Gene ndash trait-specific unit of heredity
Alternative versionsof a gene (alleles)determine the trait
Each parent transmitsan allele to the offspring
Gregor Mendel Charles Darwin
Mendel studies seven characteristics
in the garden pea
Mendel deduced the underlying principles
of genetics from these patterns
1 Segregation
2 Dominance
3 Independent assortment
Alleles alternative versions of a gene
The gene for a particular inherited character resides at a specific locus
(position) on homologous chromosome
For each character an organism
inherits two alleles one from each
parent
bull Prenatal Geneticsbull 1970s - Prenatal Ultrasound amp Amniocentesis
bull Inheritance of Genetically Complex Disordersbull Non-Mendelian Geneticsndash Genomic Imprintingndash Triple Nucleotide Repeatsndash Mitochondrial Inheritancebull 1990s - Neuropsychiatric Disorders Diabetes
Cardiovascular
ndash Interaction of genes with environmental triggers
Medical Genetics 1960s to the present
bull DNA Genetics
bull 1953 - Watson and Crickrsquos Double Helix
bull 1992 ndash2003 Human Genome Project
bull 2003 -gt the future of medical dx amp tx
C19th Mendel discovers basis of inheritance
Darwinrsquos theory of natural selection
1953 Watson and Crick discover structure of DNA
1985 PCR
1986 Duchenne muscular dystrophy gene
1989 Cystic Fibrosis gene
1998 Decision to sequence entire human genome
2001 Human genome sequence completed
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Whatrsquos a ___bull Medical Genetics
Is the science or study of biological
variation as it pertains to health and
disease in human beings
Any application of genetic principles to medical
practice
ldquoGenetics ndash study of individual genes and their effectsrdquo
Includes studies of inheritance mapping disease
genes diagnosis treatment and genetic counseling
History of Medical Genetics
bull Early Genetics - Biblical Talmud
bull Mendel - 1860s
bull Modern Experimental Genetics - 1900s
bull Maize drosophila mouse
bull Medical Genetics - 1960s to the
present
Foundations of Heredity
Science Variable traits are inherited
Gene ndash trait-specific unit of heredity
Alternative versionsof a gene (alleles)determine the trait
Each parent transmitsan allele to the offspring
Gregor Mendel Charles Darwin
Mendel studies seven characteristics
in the garden pea
Mendel deduced the underlying principles
of genetics from these patterns
1 Segregation
2 Dominance
3 Independent assortment
Alleles alternative versions of a gene
The gene for a particular inherited character resides at a specific locus
(position) on homologous chromosome
For each character an organism
inherits two alleles one from each
parent
bull Prenatal Geneticsbull 1970s - Prenatal Ultrasound amp Amniocentesis
bull Inheritance of Genetically Complex Disordersbull Non-Mendelian Geneticsndash Genomic Imprintingndash Triple Nucleotide Repeatsndash Mitochondrial Inheritancebull 1990s - Neuropsychiatric Disorders Diabetes
Cardiovascular
ndash Interaction of genes with environmental triggers
Medical Genetics 1960s to the present
bull DNA Genetics
bull 1953 - Watson and Crickrsquos Double Helix
bull 1992 ndash2003 Human Genome Project
bull 2003 -gt the future of medical dx amp tx
C19th Mendel discovers basis of inheritance
Darwinrsquos theory of natural selection
1953 Watson and Crick discover structure of DNA
1985 PCR
1986 Duchenne muscular dystrophy gene
1989 Cystic Fibrosis gene
1998 Decision to sequence entire human genome
2001 Human genome sequence completed
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
History of Medical Genetics
bull Early Genetics - Biblical Talmud
bull Mendel - 1860s
bull Modern Experimental Genetics - 1900s
bull Maize drosophila mouse
bull Medical Genetics - 1960s to the
present
Foundations of Heredity
Science Variable traits are inherited
Gene ndash trait-specific unit of heredity
Alternative versionsof a gene (alleles)determine the trait
Each parent transmitsan allele to the offspring
Gregor Mendel Charles Darwin
Mendel studies seven characteristics
in the garden pea
Mendel deduced the underlying principles
of genetics from these patterns
1 Segregation
2 Dominance
3 Independent assortment
Alleles alternative versions of a gene
The gene for a particular inherited character resides at a specific locus
(position) on homologous chromosome
For each character an organism
inherits two alleles one from each
parent
bull Prenatal Geneticsbull 1970s - Prenatal Ultrasound amp Amniocentesis
bull Inheritance of Genetically Complex Disordersbull Non-Mendelian Geneticsndash Genomic Imprintingndash Triple Nucleotide Repeatsndash Mitochondrial Inheritancebull 1990s - Neuropsychiatric Disorders Diabetes
Cardiovascular
ndash Interaction of genes with environmental triggers
Medical Genetics 1960s to the present
bull DNA Genetics
bull 1953 - Watson and Crickrsquos Double Helix
bull 1992 ndash2003 Human Genome Project
bull 2003 -gt the future of medical dx amp tx
C19th Mendel discovers basis of inheritance
Darwinrsquos theory of natural selection
1953 Watson and Crick discover structure of DNA
1985 PCR
1986 Duchenne muscular dystrophy gene
1989 Cystic Fibrosis gene
1998 Decision to sequence entire human genome
2001 Human genome sequence completed
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Foundations of Heredity
Science Variable traits are inherited
Gene ndash trait-specific unit of heredity
Alternative versionsof a gene (alleles)determine the trait
Each parent transmitsan allele to the offspring
Gregor Mendel Charles Darwin
Mendel studies seven characteristics
in the garden pea
Mendel deduced the underlying principles
of genetics from these patterns
1 Segregation
2 Dominance
3 Independent assortment
Alleles alternative versions of a gene
The gene for a particular inherited character resides at a specific locus
(position) on homologous chromosome
For each character an organism
inherits two alleles one from each
parent
bull Prenatal Geneticsbull 1970s - Prenatal Ultrasound amp Amniocentesis
bull Inheritance of Genetically Complex Disordersbull Non-Mendelian Geneticsndash Genomic Imprintingndash Triple Nucleotide Repeatsndash Mitochondrial Inheritancebull 1990s - Neuropsychiatric Disorders Diabetes
Cardiovascular
ndash Interaction of genes with environmental triggers
Medical Genetics 1960s to the present
bull DNA Genetics
bull 1953 - Watson and Crickrsquos Double Helix
bull 1992 ndash2003 Human Genome Project
bull 2003 -gt the future of medical dx amp tx
C19th Mendel discovers basis of inheritance
Darwinrsquos theory of natural selection
1953 Watson and Crick discover structure of DNA
1985 PCR
1986 Duchenne muscular dystrophy gene
1989 Cystic Fibrosis gene
1998 Decision to sequence entire human genome
2001 Human genome sequence completed
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Mendel studies seven characteristics
in the garden pea
Mendel deduced the underlying principles
of genetics from these patterns
1 Segregation
2 Dominance
3 Independent assortment
Alleles alternative versions of a gene
The gene for a particular inherited character resides at a specific locus
(position) on homologous chromosome
For each character an organism
inherits two alleles one from each
parent
bull Prenatal Geneticsbull 1970s - Prenatal Ultrasound amp Amniocentesis
bull Inheritance of Genetically Complex Disordersbull Non-Mendelian Geneticsndash Genomic Imprintingndash Triple Nucleotide Repeatsndash Mitochondrial Inheritancebull 1990s - Neuropsychiatric Disorders Diabetes
Cardiovascular
ndash Interaction of genes with environmental triggers
Medical Genetics 1960s to the present
bull DNA Genetics
bull 1953 - Watson and Crickrsquos Double Helix
bull 1992 ndash2003 Human Genome Project
bull 2003 -gt the future of medical dx amp tx
C19th Mendel discovers basis of inheritance
Darwinrsquos theory of natural selection
1953 Watson and Crick discover structure of DNA
1985 PCR
1986 Duchenne muscular dystrophy gene
1989 Cystic Fibrosis gene
1998 Decision to sequence entire human genome
2001 Human genome sequence completed
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Mendel deduced the underlying principles
of genetics from these patterns
1 Segregation
2 Dominance
3 Independent assortment
Alleles alternative versions of a gene
The gene for a particular inherited character resides at a specific locus
(position) on homologous chromosome
For each character an organism
inherits two alleles one from each
parent
bull Prenatal Geneticsbull 1970s - Prenatal Ultrasound amp Amniocentesis
bull Inheritance of Genetically Complex Disordersbull Non-Mendelian Geneticsndash Genomic Imprintingndash Triple Nucleotide Repeatsndash Mitochondrial Inheritancebull 1990s - Neuropsychiatric Disorders Diabetes
Cardiovascular
ndash Interaction of genes with environmental triggers
Medical Genetics 1960s to the present
bull DNA Genetics
bull 1953 - Watson and Crickrsquos Double Helix
bull 1992 ndash2003 Human Genome Project
bull 2003 -gt the future of medical dx amp tx
C19th Mendel discovers basis of inheritance
Darwinrsquos theory of natural selection
1953 Watson and Crick discover structure of DNA
1985 PCR
1986 Duchenne muscular dystrophy gene
1989 Cystic Fibrosis gene
1998 Decision to sequence entire human genome
2001 Human genome sequence completed
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Alleles alternative versions of a gene
The gene for a particular inherited character resides at a specific locus
(position) on homologous chromosome
For each character an organism
inherits two alleles one from each
parent
bull Prenatal Geneticsbull 1970s - Prenatal Ultrasound amp Amniocentesis
bull Inheritance of Genetically Complex Disordersbull Non-Mendelian Geneticsndash Genomic Imprintingndash Triple Nucleotide Repeatsndash Mitochondrial Inheritancebull 1990s - Neuropsychiatric Disorders Diabetes
Cardiovascular
ndash Interaction of genes with environmental triggers
Medical Genetics 1960s to the present
bull DNA Genetics
bull 1953 - Watson and Crickrsquos Double Helix
bull 1992 ndash2003 Human Genome Project
bull 2003 -gt the future of medical dx amp tx
C19th Mendel discovers basis of inheritance
Darwinrsquos theory of natural selection
1953 Watson and Crick discover structure of DNA
1985 PCR
1986 Duchenne muscular dystrophy gene
1989 Cystic Fibrosis gene
1998 Decision to sequence entire human genome
2001 Human genome sequence completed
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
bull Prenatal Geneticsbull 1970s - Prenatal Ultrasound amp Amniocentesis
bull Inheritance of Genetically Complex Disordersbull Non-Mendelian Geneticsndash Genomic Imprintingndash Triple Nucleotide Repeatsndash Mitochondrial Inheritancebull 1990s - Neuropsychiatric Disorders Diabetes
Cardiovascular
ndash Interaction of genes with environmental triggers
Medical Genetics 1960s to the present
bull DNA Genetics
bull 1953 - Watson and Crickrsquos Double Helix
bull 1992 ndash2003 Human Genome Project
bull 2003 -gt the future of medical dx amp tx
C19th Mendel discovers basis of inheritance
Darwinrsquos theory of natural selection
1953 Watson and Crick discover structure of DNA
1985 PCR
1986 Duchenne muscular dystrophy gene
1989 Cystic Fibrosis gene
1998 Decision to sequence entire human genome
2001 Human genome sequence completed
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
C19th Mendel discovers basis of inheritance
Darwinrsquos theory of natural selection
1953 Watson and Crick discover structure of DNA
1985 PCR
1986 Duchenne muscular dystrophy gene
1989 Cystic Fibrosis gene
1998 Decision to sequence entire human genome
2001 Human genome sequence completed
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
April 2003
Human Genome Project determined the entire DNA
sequence of a human(3 billion letters)
What is DNA Day
April 1953
Drs James Watson and Francis Crick determined
the structure of DNA(double helix)
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
What is DNA bull Its a history book - a narrative of the journey of
our species through time
bull Its a shop manual with an incredibly detailed blueprint for building every human cell
bull And its a transformative textbook of medicine with insights that will give health care providers immense new powers to treat prevent and cure disease
Francis Collins
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Importance of Genetics to Medicine
gt12 million Americans with genetic disorders (GD)
80 of MR due to genetic component
2-3 background population risk for a major birth
defect (BD)
15 overall miscarriage risk for any pregnancy
25-50 first trimester miscarriage risk
30-50 first trimester losses due to chromosome
anomalies
gt30 pediatric hospital admissions due to GD
GD affect all major systems any age any race
male or female
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Importance of Genetics to Medicine
Changing focus of medicine
primary care physicians vs specialists
prevention vs treatment
genetic causation for both rare and common diseases
Human Genome Project
designer drugs
Problem based approach taken in medical
schools
Genetics as the link between basic research amp clinical observation
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Importance of Genetics to Medicine
Triple themeGenetic traits as they segregate through families
allows insights into health of the population
Flow of information from DNA to RNA to protein
links genetics to physiology
Ethical issues linked to treatment therapy
options research decision-making and quality of
life
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
What are Genetic Variations
bull Variations are simply differences in genetic sequence
bull Variation can be seen at every genetic level
In the DNA
In the genes
In the chromosomes
In the proteins
In the function of proteins
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Classification of genetic disorders
bullSingle gene
bullChromosomal
bullMitochondrial
bullMultifactorial
bullSomatic mutations (cancer)
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Single Gene Defects
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Basic Gene Structure
Promoter
Initiation
codon
ATG
Start of transcription
Termination codon
UAA
UAG
UGA
Polyadenylation signal
5rsquo untranslated region
3rsquo untranslated region
Exons
Introns
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Sickle Cell
Anemia
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Inheritance
D
R
X
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Single-Gene ldquoMendelianrdquo
Disordersbull Structural proteins
bullOsteogenesis imperfecta and Ehlers-Danlos (collagens) Marfansyndrome (fibrillin) Duchenne and Becker muscular dystrophies (dystrophin)
bull Enzymes and inhibitorsbullLysosomal storage diseases SCID (adenosine deaminase) PKU
(phenylalanine hydroxylase) Alpha-1 antitrypsin deficiency
bull ReceptorsbullFamilial hypercholesterolemia (LDL receptor)
bull Cell growth regulationbullNeurofibromatosis type I (neurofibromin) Hereditary
retinoblastoma (Rb)
bull TransportersbullCystic fibrosis (CFTR) Sickle cell disease (Hb) Thalassemias
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Single gene disorders
bull Single mutant gene has a large effect
on the patient
bull Transmitted in a Mendelian fashion
bull Autosomal dominant autosomal
recessive X-linked Y-linked
bull Osteogenesis imperfecta - autosomal
dominant
bull Sickle cell anaemia - autosomal recessive
bull Haemophilia - X-linked
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Fertilization Diploid Genome
bull Each parent contributes one genome copy
bull Offspring cells have two near-identical copies
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Genes amp chromosomes
Chromosomesbull Linear agglomerates
of proteins amp DNA
in the cellrsquos nucleus
bull Distributed evenly
upon division
bull Morgan (1910)
Genes reside along
the chromosomes
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Meiosis KM 28
Mitosis vs meiosis
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Cell Cycle
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Chromosomes
Homologous chromosome one of a matching pair of
chromosomes one inherited from each parent
Sister chromatids are identical
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Chromosome Number Constancy in Different Species
Buffalo 60 Cat 38 Dog 78 Donkey 62 Goat 60 Horse 64 Human beings 46 Pig 38 Sheep 54
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Pair of homologous
chromosomes
Sister
chromatids
Centromere
Genetic Material (chromosomes pairs)
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
ISCN 1995International System for Human Cytogenetic Nomenclature
Group A (1-3)
Group B (4-5)
Group C (6-12 X)
Group D (13-15)
Group E (16-18)
Group F (19-20)
Group G (21-22)
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Chromosomal RearrangementsbullNumerical chromosome changesaneuploidy
Result from errors occurring during meiotic or mitotic segregation
bull Structural chromosome changes
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Multifactorial inheritance
bull Familial clustering which does not conform to any recognized pattern of Mendelian inheritance
bull Determined by the additive effects of many genes at different loci together with the effect of environment
bull Examples include congenital malformations asthma schizophrenia diabetes hypertension
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
GENETIC ENVIRONMENTAL
Duchenne muscular dystrophy
HaemophiliaOsteogenesis imperfecta
Club footPyloric stenosisDislocation of hip
Peptic ulcerDiabetes
Tuberculosis
PhenylketonuriaGalactosaemia
Spina bifidaIschaemic heart diseaseAnkylosing spondylitis
Scurvy
The contributions of genetic and environmental factors to human diseases
RareGenetics simple
UnifactorialHigh recurrence rate
CommonGenetics complexMultifactorialLow recurrence rate
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Polygenic diseases
The most common yet still the least
understood of human genetic
diseases
Result from an interaction of multiple
genes each with a minor effect
The susceptibility alleles are common
Type I and type II diabetes autism
osteoarthritis
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Population Genetics
bull Identifies how much genetic variation
exists in populations
bull Investigates factors such as migration
population size and natural selection that
change the frequency of a specific gene
over time
bull Coupled with DNA technology
investigates evolutionary history and
DNA identification techniques
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Non-Traditional Inheritence
Mitochondrial genes
Trinucleotide repeats
Genetic imprinting
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Mitochondrial Inheritance
bull Matrilineal mode of inheritance only mother passes mitochondrial DNA to offspring
bull Higher spontaneous mutations than nuclear DNA
bull affects both males and females but transmitted only through females
bull range of phenotypic severity due to heteroplasmy
bull Example diabetes mellitus with sensorineuronaldeafness
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Human Genome
Project (HGP)
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Human Genome Project
bull Initiated by the same laboratories that
brought you thermonuclear devices
bull 1990 taken over by NIH
bull Actually involved sequencing many
genomes
bull First draft sequence in 2001 ldquocompletedrdquo in
2003 (public effort and Celera Corp)
bull DNA sequence in any two human beings is
999 identical only 01 is unique
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
The human Genome project GoalsThe study of the genome
To determine the DNA sequence (exact order of ATGC) For all the DNA in human
To determine which segment of DNA represent individual genes (Protein Coding Unit
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Model organisms
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Mapping Human Genetic-
based Diseases
bull Thousands
known
bull Most genes
mapped
and
sequenced
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Chromosome Count
1 1309
2 848
3 710
4 517
5 618
6 793
7 610
8 475
9 503
10 494
11 818
12 702
Chromosome Count
13 250
14 426
15 399
16 548
17 770
18 190
19 843
20 337
21 144
22 330
X 724
Y 46
OMIM Synopsis of the Human Gene Map(Updated 8 June 2012)
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Prefix Autosomal X Linked Y LinkedMitochondr
ialTotals
Gene description 13197 641 48 35 13921
+ Gene and phenotype
combined146 5 0 2 153
Phenotype description
molecular basis known3216 263 4 28 3511
Phenotype description or
locus molecular basis
unknown
1631 136 5 0 1772
Other mainly phenotypes
with suspected mendelian
basis
1779 126 2 0 1907
Totals 19969 1171 59 65 21264
Number of Entries in OMIM (Updated 7 June 2013)
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Applications of the Human Genome
Project
bull Genetic testing ( diagnostic presymptomatic screening prenatal)
bull Gene therapy
bull Pharmacogenomics Moving Away from ldquoOne-Size-Fits-Allrdquo Therapeutics
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Diagnosis and Prevention of
Genetic Diseases
Diagnosis
bull Chromosomal Abberations
bull Single Gene Disorders
Preventions
bull Genetic Counseling
bull Prenatal Dignosis
bull Preimplantation Diagnosis
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
New Technologies
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Technology Advancement
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
iPad
2012
ENIAC
1946
Technological Advances
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
Oxford Nanopore MinION
2012
Applied Biosystems 3730 DNA Analyzers
2002
Genome Sequencing Technology
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
bull Because of major technological advances the cost of sequencing a human genome has fallen rapidly
bull And within the next 5 years the cost of sequencing a human genome will be under $1000 and will take only hours or days
bull When the cost is low enough perhaps reading human genomes will be as routine as blood tests and easy enough to be carried out in your doctorrsquos office
