医学遗传学课件：5 Genetics of Disorders with Complex Inheritance

1、 质量性状质量性状): 数量性状数量性状): 120 cm 165 cm aa AA / Aa Height distribution of Pituitary dwarf vs normal population Pituitary dwarf Qualitative Trait AABBCC X AABBCC AABBCC 0 1 2 3 4 5 6 1 6 15 20 15 6 1 F1 F2 diabetes hypertension schizophrenia myocardial infarction cleft palate neural tube defects obesity

2、 Most common diseases Alzheimer disease cancer most of common diseases common congenital malformation neural tube defects Environment Complex diseases Genes Minor gene ( Additive effect ( Susceptibility ( Liability ( Threshold ( As the number of loci increases, the Liability distribution looks incre

3、asingly like a Normal distribution, also called Gaussian Distribution or the Bell-shaped Curve. Liability distribution 1. Edward formula： f = p f: The recurrence risk for first degree relatives p: The frequency of disease among general population Frequency= 0.1% 1% Heritability=70%80% First degree r

4、elatives of probands H Cleft lip P=0.17% H=76% %4 %17. 0 f f Pf %4 %17. 0 f f Pf %4 %17. 0 Pf 2. The risk increases with the number of affected relatives 3. The risk increases with the severity of the malformation or disease. 4. The recurrence risk for relatives will decline sharply as the degree of relatedness decreases. 5. When the sex ratio of affected probands deviates significantly from unity,offspring of affected proba