Disease risk as a quantitative trait Susceptibility and protective genes influence the liability(risk) of developing a polygenic disease Distribution of liability in the general population Distribution of liability in the Threshold sibs of affected people +-unaffected4IH-affected Average liability Average liability High liability in general mong sibs of liability population affected people
Disease risk as a quantitative trait: Susceptibility and protective genes influence the liability (risk) of developing a polygenic disease
Model for schizophrenia liability Average Threshold for liability schizophrenia AL General population Third-degree relatives 9 First-degree relatives children 13% afirst cousins 2% .general population = 1% AL T Combined liability for developing schizophrenia
Model for schizophrenia liability
Factors that obscure patterns of disease inheritance Phenocopy Variable penetrance and expressivity Locus heterogeneity Allelic heterogeneity Environmental influences
Factors that obscure patterns of disease inheritance • Phenocopy • Variable penetrance and expressivity • Locus heterogeneity • Allelic heterogeneity • Environmental influences
C. Genes in populations DNA polymorphisms Allele and genotypes frequencies Ethnic differences in allele frequencies and susceptibility to disease · Out of africa
C. Genes in populations • DNA polymorphisms • Allele and genotypes frequencies • Ethnic differences in allele frequencies and susceptibility to disease • Out of Africa
DNA polymorphisms Primer 1 ACACAC…ACAC L b百 5 26(AC)4 (AC)B(AC)26 Variable number of tandem repeats Allele 1 Allele 2 H A|le4卜 Probe Single nucleotide Microsatellites Minisatellites polymorphisms (SNPS Technically, a polymorphism is a genetic variant that is present in a population at a frequency of>1%
DNA polymorphisms Single nucleotide Microsatellites Minisatellites polymorphisms (SNPs) Technically, a polymorphism is a genetic variant that is present in a population at a frequency of > 1%