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Genetics, MF Threshold -dist. not continuous -no mendelian pattern -only some genos express phenos ???? Explains sex bias in MF traits M-cleft lip, hirschspring dz F-spina bifida, anencephaly recurrence determined empirically, no pattern of Mendelian inheritance -but some Mendelian component eg. alcoholism, obesity, heart dz polygenic-multiple genes cause variation multifactorial-multiple genes+env=varied trait Malformations cleft lip/palate, NTD, Congenital Heart defect hearing loss 4 types Continuous Variation-eg height, chol follow bell curve-additive genes to pheno from many genes, each is mendelian, MF Threshold -dist. not continuous -no mendelian pattern -only some genos express phenos ???? Susc. genes predispose to common dz -not enough for dz with env factors->dz -use SNPs to find susc genes, no pattern of Mendelian inheritance -but some Mendelian component eg. alcoholism, obesity, heart dz polygenic-multiple genes cause variation multifactorial-multiple genes+env=varied trait Malformations cleft lip/palate, NTD, Congenital Heart defect hearing loss ???? Alzheimer's -adult-onset, slowly progressing -most common dementia -amyloid plaques on autopsy, MF Threshold -dist. not continuous -no mendelian pattern -only some genos express phenos ???? eg Pyloric Stenosis -narrowed pylorus -projectile vomiting, constip wt loss -threshold F>M ->F more likely to have affected kids -because more dz-causing factors -sons more affected than daughters, no pattern of Mendelian inheritance -but some Mendelian component eg. alcoholism, obesity, heart dz polygenic-multiple genes cause variation multifactorial-multiple genes+env=varied trait Malformations cleft lip/palate, NTD, Congenital Heart defect hearing loss ???? 2 Hit Hypothesis -Cancer breast-BRCA1, BRCA2 colon-APC, HNPCC -freq 1st mut & 2ndmut -2 events required normally, rare 1st mut, ->frequent 2nd mut, MF Threshold -dist. not continuous -no mendelian pattern -only some genos express phenos ???? Neural Tube Defects -doesn't close at 4th wk -folic acid helps prevent (also helps clefts, CHD, conotrunc heart defects), no pattern of Mendelian inheritance -but some Mendelian component eg. alcoholism, obesity, heart dz polygenic-multiple genes cause variation multifactorial-multiple genes+env=varied trait Malformations cleft lip/palate, NTD, Congenital Heart defect hearing loss ???? Cor. Artery Dz -caused by atherosclerosis -genetic-lipid breakdown genes -env factors-cigs, HTN, high chol -fam Hx increases risk 2-7X -exercise/low fat diet prevent, Multifactorial (from Outline) -common-600/1000 ???? no pattern of Mendelian inheritance -but some Mendelian component eg. alcoholism, obesity, heart dz polygenic-multiple genes cause variation multifactorial-multiple genes+env=varied trait Malformations cleft lip/palate, NTD, Congenital Heart defect hearing loss, Principles of screening: inexpensive useful for large pops select subset of pop for spec. test centers for treatment in place newborn-condition treatable Results sensitivity=(true pos)/(false neg+true pos)