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Medical GeneticsMedical Genetics

Department of Medical Genetics Peking University

Tao Zhang

2Genetics in Medicine 7th ed., 2007

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IntroductionIntroduction

3. Nature, Nurture or Both

Gene expression is the process by which inheritable information from a g is made into p or R .Gene expression is the process by which inheritable information from a gene is made into protein or RNA.

What the relationship among genes, phenotype and environment?In plain language gene expression is how a gene works. Gene expression functions in the environment of the living organism. If the environmental factors are not correct then the characteristic produced by the gene may not be expressed. The way an organism physically looks is called its phenotype. The phenotype is determined by genes but is influenced by toe organisms’ environment.

An allele is an alternative form of a gene (one member of a pair) that is located at a specific position on a specific chromosome.

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Heredity and Variation—Heredity and Variation— all living organismsall living organisms

hereditary hereditary factorfactor Theory ofTheory of GeneGene

Genetics is a diverse subject concerned with variation and heredity in all living organisms.

Human genetics is the science of variation and heredity in human beings.

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MEDICAL GENETICSMEDICAL GENETICSMedical Genetics is the application

of genetics to medical practice. Diseases — Inheritance

Clinical Genetics

Diagnosis Prevention Counseling Treatment

1865, Mendel G1865, Mendel G

Law of SegregationLaw of Segregation

Law of Independent AssortmentLaw of Independent Assortment

A Brief History of GeneticsA Brief History of Genetics

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1865, Mendel G1865, Mendel G

Experiments in Plant HybridizationExperiments in Plant Hybridization

1. Law of Dominance: - In a cross of parents that are pure for contrasting traits, only one form of the trait will appear in the next generation.

  - Offspring that are hybrid for a trait will have only the dominant trait in the phenotype.

2. Law of Segregations: - During the formation of gametes (eggs or sperm), the two alleles (hereditary units) responsible for a trait separate from each other. 

- Alleles for a trait are then "recombined" at fertilization, producing the genotype for the traits of the offspring.

3. Law of Independent Assortment:- Alleles for different traits are distributed to sex cells (& offspring) independently of one another.

Image: Gregor Mendel, Mendel's Principles of Heredity: A Defense by

Bateson, WilliamFrom the Virtual Cell Biology Classroom on ScienceProfOnline.com

1902, Garrod AE1902, Garrod AE Inborn errors of metabolismInborn errors of metabolism::

alkaptonuria(AR)alkaptonuria(AR)

1908, Hardy GH & Weinberg W1908, Hardy GH & Weinberg W Law of Genetic EquilibriumLaw of Genetic Equilibrium

1909, Nilsson-Ehle H1909, Nilsson-Ehle H Multifactorial inheritanceMultifactorial inheritance

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Law of Linkage and Crossing OverLaw of Linkage and Crossing Over

Theory of Gene (1926)Theory of Gene (1926)1933

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1944, Avery OT, et al1944, Avery OT, et al

DNA is the genetic materialDNA is the genetic material

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1953, Watson JD & Crick FHC 1953, Watson JD & Crick FHC

21962

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DNA double helix structureDNA double helix structure

X-ray diffraction photograph of the DNA crystal taken by scientist Rosalind Franklin.

http://www.expeditions.udel.edu/extreme08/genomics/history.phphttp://en.wikipedia.org/wiki/DNA

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1949,Pauling L

Sickle cell disease; molecular diseaseSickle cell disease; molecular disease

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1952, Hsu TC 1952, Hsu TC 徐道觉

hypotonic shockhypotonic shock

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1956, Tjio JH 1956, Tjio JH 蒋有兴 ; A.Levan2N = 462N = 46

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1979, Kan YW 1979, Kan YW 简悦威

Sickle cell diseaseSickle cell disease,Thalassemia

Gene diagnosis (RFLP)Gene diagnosis (RFLP)

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1993

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1991, Anderson WF1991, Anderson WF Gene therapyGene therapy

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Human Genome ProjectHuman Genome Project19901990 ～～ 2004.102004.10

26Laboratory in China for 1% Laboratory in China for 1%

SequencingSequencing

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2002.10 ～ 2005.10

Laboratory in China for Laboratory in China for 10% Sequencing10% Sequencing

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functional genomics （功能基因组学）comparative genomics （比较基因组学）environmental genomics （环境基因组学）Proteomics （蛋白质组学）model-organism genomics( 模式生物基因组学） ………

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Gene NetworksGene Networks （基因网络）（基因网络）

32Waterland RA, Jirtle RA. Transposable elements: targets for early Waterland RA, Jirtle RA. Transposable elements: targets for early

nutritional effects on epigenetic gene regulation . Mol. Cell. Biol. , 2003, nutritional effects on epigenetic gene regulation . Mol. Cell. Biol. , 2003, 23:5293-530023:5293-5300

Epigenetics Epigenetics

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EPIGENETICSEPIGENETICS Regulation of gene expression without changes in DNA sequences Epigenetic inheritance （表观遗传） Epigenetics （表观遗传学）

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Geneticstructure

Environmental conditions

35Any disease is the result of the combined action of genes and environment

Nature and Nurture

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GENETIC DISORDERSGENETIC DISORDERS

The diseases are caused by genetic factor. genes or chromosomes

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CLASSIFICATION OF GENETIC CLASSIFICATION OF GENETIC DISEASESDISEASES

Single-gene disorders(单基因病） Polygenic disorders （多基因病） Chromosomal disorders （染色体病） Genetic diseases of mitochondria (Mt) （线粒体遗传病） Somatic cell Genetic disorders （体细胞遗传病）

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SINGLE-GENE DISORDERSSINGLE-GENE DISORDERS

Single-gene (or monogenic) disorders result from the mutation of gene.

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PKU PKU (AR)(AR)

苯丙氨酸羟化酶（ PAH ）基因突变基因定位于 12q24.1 ， 85kb, 13 外

显子

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Huntington chorea Huntington chorea (AD)(AD)

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DMDDMD(XR)(XR)

假肥大型肌营养不良Xp21.2-p21.3, 75 exon,

2300kb

OMIM OMIM Statistics for September 9, 2009Statistics for September 9, 2009

Autosomal 18419Autosomal 18419 X-linked 1113X-linked 1113 Y-linked 59Y-linked 59 Mitochondrial 63 19654

http://www.ncbi.nlm.nih.gov/entrez/Omim/mimstats.htmlhttp://www.ncbi.nlm.nih.gov/entrez/Omim/mimstats.html

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OMIMOMIM

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POLYGENIC POLYGENIC DISORDERSDISORDERS

Genetic background Environmental

factors Congenital defects Common diseases.

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Schizophrenia 精神分裂症

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cleft lip ± cleft palate

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CHROMOSOMAL DISORDERSCHROMOSOMAL DISORDERS Diseases caused by

chromosomal abnormalities

growth retardation mental retardation somatic abnormalities

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Mutation of Mt genes

Maternal heredity

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Leber hereditary optic Leber hereditary optic neuropathyLeberneuropathyLeber 遗传性视神经病变遗传性视神经病变

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SOMATIC CELL GENETIC SOMATIC CELL GENETIC DISORDERSDISORDERS

Result from the altered genetic materials in somatic cells.

Tumor & congenital Tumor & congenital malformationmalformation

52RB 基因： 13q14.1, 27 exon

Use library resources to define the following words and write their definitions using your own words. allele: genes: dominant : recessive: homozygous: heterozygous: genotype: phenotype: Mendelian Inheritance:

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