Genetics

Review and Alterations

Terminology

Chromosome: types, number Haploid, Diploid Gene, Allele, Loci Homozygous, Heterozygous Karyotype, Phenotype, Genotype Carrier, Dominant, Recessive Nucleic Acids, Base Pairs Replication: DNA, mitosis, meiosis Protein Synthesis

Transcription Translation

Chromosome Pairs in Species

Chromosome Types

Chromosome #: Long to Short

Human Karyotype

Chromosome Arms and Centromere

Homologous Chromosomes

Allele and Loci

Homozygous and Heterozygous

Phenotype and Genotype

Carrier, Dominant, Recessive

Chromosome structure

Chromosome vs Chromatin

Looped Domains and Chromatin

Histones and Nucleosomes

DNA

DNA structure

Gene

1.5% of Genome DNA base pairs (~ 100,000) Encode a product

(protein, tRNA, rRNA)

Responsible for a measurable trait

Introns Exons

DNA Base Pairs

Nucleoside

DNA Replication

Cell Cycle Review

Mitosis

Meiosis

Mitosis and Meiosis Compared

Meiosis I: Normal

Non Disjunction

Chromosome Disorders Chromosome Number

Euploid (2N) Polyploid (exact multiple)

Triplody (3N) Tetraplody (4N)

Anueploid (not exact multiple) Trisomic (n + 1)

Autosomes Down’s Syndrome

Sex Chromosomes Klinefelter

Monosomic (n-1) Sex Chromosome

Turner Mosaics (not all cells

affected) Somatic Gonadal

Anaphase

Extra Chromosomal Disorders

Down Syndrome (Trisomy 21)

Anueploid

Chromosome Abnormalities

Structure Break and

reassemble abnormally

Inversion Translocation Insertion Deletion Duplication

Inversions

Translocations

Translocation in Meiosis

Insertions and Deletions

Insertion

Deletion

1, 2, or 3 base pairs are deleted

Frameshift reading

Chromosome Deletions

Deletion example

Prader-Willi / Angelman Syndromes

Cancers caused by Deletions

Wilms Tumor

Duplications

Doubling section of genome

Unequal Crossing over

Multiple repeats of nucleotides

DNA section duplicated

Huntington’s CAG repeated

Fragile X CGG repeated

MD CTG repeated

Chromosomal Mutation Summary

DNA Transcription

Transcription Steps

Translation

DNA codon for AA

DNA Damage

Mutation:

Define S phase Types

Single Base Pair substitution

Missense Nonsense Silent

Frame shift Spontaneous Induced

Base Pair Substitution (point mutation)

Transition Purine for Purine Pyrimadine for

Pyrimadine Transversion

Purine for Pyrimadine

Pyrimadine for Purine

Transition

Nonsense Mutation

Transversion: UGC to UGA

Nonsense mutations result in stop codons

Nonsense Mutations

Codon changed Stop codon is read

TAA TAG TGA

Missense Mutation

Transversion: UGC to UGG

Missense Mutation

Miscoding of AA can lead to diseases such as SSA and CF

Silent Mutation

Frame Shift

Mutation Summary

Spontaneous Mutations

Depurination Deamination Oxidation

damage to DNA

Spontaneous Mutations in the population

Depurination and Deamination

Depurination Deamination

Induced Mutations

Mutagentic Base Analog

Chemical Agents Ultraviolet

Radiation Ionizing Radiation

Induced Mutations

Base Analog Mutagen

UV

Ionizing Radiation

Mendelian Inheritance Patterns

Dominant / Recessive

CoDominance Incomplete

Dominance Sex Linked Multifactoral

Dominant, Recessive, Sex-linked

Sex-Linked Punnett Square

CoDominance: Blood Types

Incomplete Dominance: SSA

Incomplete Dominance: OI

Genetic Disorders: Single Gene

Autosomal Dominant

Autosomal Recessive

X-linked dominant X-linked recessive

Hereditary Map of Autosomal Dominant Traits

Autosomal Dominant

Achondroplastic dwarfism Abnormal endochondrial bone formation causing dwarfism

vonWillibrand’s Disease Factor VIII defect causing bleeding disorders

Neurofibromatosis Increased neurofibromatoma

Polycystic Kidney Disease Cystic enlargement, hematuria, hypertension, and possible renal failure

Alzheimers (10% of cases) dementia

Machado-Joseph Spinocerebellar degeneration

Marfan syndrome Abnormal fibrillin causing excessive bone growth, ocular disorders, & cardiac defects

Huntington Disease

Basal ganglia

Huntington brain compared to normal

Hydrocephalus

Hydrocephalus brain image

Polycystic Kidney Disease

PKD

Cat kidney Human kidney

Neurofibromatosis

Neurofibromatosis Clinical Signs

Marfan Syndrome

Abnormal fibrillin,Affects elastic C.T.

Osteogenesis Imperfecta

Autosomal Dominant: Metabolic

Familial hypercholesterolemia Acute intermittent porphyria

Familial Hypercholesterolemia

Polydactylia

Autosomal Dominant Gene Therapy

Autosomal Recessive

Albinism Tyrosine can not be changed to melanin for pigment

Sickle Cell Anemia Amino acid substitution in beta chain of hemoglobin, sickling

X and Y Chromosomes

X-linked Disease Pedigree

Sex-Linked

Sex Linked

Disease Symptoms

DMD (Xp21) Muscular weakness and degeneration due to lack of dystrophin protein

Menkes (Xq12-q13) Copper storage disease that leads to neurodegeneration and CT disorders

Color Blindness Defective function of cones for red and green color vision

Hemophilia A (Xq28) Bleeding disorder due to a Factor VIII deficiency

Fabry (X Temperature intolerance, enlarged heart, whole body pain, depression, vomiting / diarrhea

SCID (Xq13.1) Immune deficiency impairment, death

X-linked Diseases

Hemophilia

Duchenne Muscular Dystrophy

Absence of Dystrophin causes membrane to leak CPcausing weakness associated with DMD

X-Linked SCID Inheritance

Most common form

Mutation in IL-2 receptor gene

Lymphopenia Absence of T cells Absence of NK cells Abnormal B cells

Other X-linked Immune Diseases

Loci on X and Y Chromosomes

Fun Y Chromosome loci

Multifactoral Inheritance

Several Genes Environmental factors Cluster in families Examples

Cleft lip or palate Congenital heart disease Club foot Pyloric Stenosis

Multifactoral

Gene Map of Disease Loci

Chromosome 4 Conditions

Epigenetic Alterations

Methylated DNA is inactivated

Gene Expression

Cell Cycle

Mitochondria

Mitochondrial DNA (mtDNA)

Chromosomes in Mitochondria

Heavy Strand

Light Strand

DNA compared

Inheritance Patterns Compared

Results of Inheritance Patterns

Mitochondrial DNA disorders

Mitochondrial Genetic Diseases

Additional Terminology

Congenital Defect Mutagen Teratogen Carcinogen Hot Spots Cloning

Genetic Testing

Karyotyping of Sample

Genetic Counseling

Gene Therapy

Questions?