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[医学]医学遗传学:种群的遗传与变异
Genetic Variation in Populations ZHANG Xian-Ning, PhD E-mail: zhangxianning@zju.edu.cn Tel Office: A713, Research Building 2008/09 Learning Objectives The nature and amount of genetic variation in human populations, and the role of genetic variation in liability to disease. Ethnic Groups: Caucasoid, Negroid, Mongoloid Genes in Human Populations Study of distribution and frequency of genes in populations reasons for different gene frequencies in different populations ‘burden of genetic disease’ is related to frequency and severity of genetic disorders- to an individual and to the population as a whole. Mendelian population An interbreeding population of sexually reproducing individuals sharing a common gene pool. Gene pool, genotypes, and gene frequency Hardy Weinberg Equilibrium The law that relates allele frequency to genotype frequency, used in population genetics to determine allele frequency and heterozygote frequency when the incidence of a disorder is known. assumes: large population random mating no new mutations no immigration in or out. (p2 + 2pq + q2 = 1) Observed frequency of recessive disease in population is q2 (e.g., frequency of PKU = 1/10000) q2 = 1/10 000 therefore: q = 1/100 (*this is not the carrier frequency) Since p + q = 1 p = 1 – q = 1 – 1/100 = 99/100 Carrier frequency (2pq) 2pq = 2 (99/100 x 1/100) = 2(~1 x 1/100) = 2/100 = 1/50 Probability that a couple will have a child with PKU (i.e. q2) is therefore 1/50 x 1/50 x ? = 1/10 000 Exceptions to Hardy Weinberg Assumptions Migration – introduction / loss of alleles Mutations – may occur at different frequency in different populations 3. Small population size - genetic isolate / founder effect 4. Non-random mating - consanguinity - assortative mating(=non-random mating) Factors that disturb H
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