【高血压英文PPT精品课件】 Bimodality.pptVIP

;;Bimodality: Hallmark of a major gene effect on a quantitative trait.;Bimodality: Hallmark of a major gene effect on a quantitative trait.; Polygenic Traits;;CHGA genetic variation: Risk factor for hypertensive ESRD in blacks;;“Intermediate” in time and causality ;Twins: window into heritability (h2) of any phenotype; Total mole count for MZ and DZ twins;;Family studies (twin pairs, pedigrees). Fam hx as a risk factor. In 1st degree relatives: Parents, siblings. Heritability (h2): Fraction of trait variance accounted for by genetic variance. VP = VG + VE h2 = VG/VP Estimate h2 from twin pair (or pedigree) studies: Type of twin pair Allele sharing across the genome. MZ = monozygotic = identical. 100% DZ = dizygotic = fraternal ~50% (on average), like any sib pair Quick-and-dirty algorithm: h2 = VG/VP = 2(RMZ – RDZ) ;; West J Med. 1984 Dec;141(6):799-806. Understanding genetic and environmental risk factors in susceptible persons. Williams RR.;;; ;Linkage Markers…;Thomas Hunt Morgan – discoverer of linkage;Idiosyncratic features of genetic linkage (= meiotic co-segregation). Units. Metric = meiotic recombination (~50 meioses/generation). Units of genetic distance = recombination during meiosis (cM). cM = (recombinant meioses/total meioses)*100 E.g.: [8/(8+86)]*100 =(8/94)*100 = 8.5 cM 1 cM ~ 1 Mb Range ~0.5-2.0 Varies by species, sex, chromosomal region (meiotic “hot spots”) Significance. “LOD” scores. LOD = Log10 of the odds ratio for linkage Odds ratio: Co-segregation (marker and trait) Not Significant: LOD 3.0 (i.e., odds ratio 1000/1) Why 3.0? ~50 “linkage groups” (meiotic breaks/generation), target ?=0.05. 1/50*1/20=1/1000. ;Genetic linkage: Meiotic recombination distance in cM;Mouse SBP crosses: “Genome scan” ? linkage.;;J Clin Invest. 1996 May 1;97(9):2111-8. Quantitative trait locus mapping of human blood pressure to a g