分子遗传学chapter 7 complex disease.pptVIP

* * * Alleles of Adjacent SNPs on a Chromosome form Haplotypes a. Short stretch of DNA for 4 different people – 3 SNPs are present b. Haplotypes made up of a combination of different alleles at 20 nearby SNPs c. Genotyping just 3 “tag” SNPs can distinguish all 4 haplotypes Variations in Chromosomes Within a Population Common Ancestor Emergence of New Variations Over Time time present Disease Mutation Creation of Haplotype Diversity(Mutations) Genetic Recombination(More diversity) Recombination breaks up haplotypes!! Father Mother Meiosis Cell division Recombinant Haplotype 1. Mutation Events 2. Recombination Events Factors Affecting Haplotypes 3 haplotypes 4 haplotypes 2 haplotypes Association Among Adjacent SNPs in a Population If SNPs are close together in the genome alleles will tend to be inherited together as haplotypes more often than for SNPs that are further apart. Why? – less chance that recombination will separate the alleles of SNPs that are close together ie. break up haplotypes! Association of alleles of SNPs that are close together is called linkage disequilibrium (LD) Linkage Disequilibrium (LD) Definition = the non-random association of alleles at two adjacent SNPs. A B A b a B a b Eg. Two adjacent SNPs (A and B) are genotyped in a population. Linkage Equilibrium There are 4 possible haplotypes A a B fAB faB fB b fAb fab fb fA fa Under linkage equilibrium fAB - fAfB = 0 faB - fafB = 0 fAb - fAfb = 0 fab - Fafb = 0 SNP 1 SNP 2 A B A b a B a b Eg. Two adjacent SNPs (A and B) are genotyped in a population. Linkage Equilibrium There are 4 possible haplotypes A a B fAB faB fB b fAb fab fb fA fa Under linkage disequilibrium fAB - fAfB ≠ 0 faB - fafB ≠ 0 fAb - fAfb ≠ 0 fab - Fafb ≠ 0 SNP 1 SNP 2 A B A b a B a b Eg. Two adjacent SNPs are genotyped in a population Linkage Disequilibrium (LD) There are 4 possible haplotypes A a B fAB faB fB b fAb fab fb fA fa Under linkage disequilibrium fAB = fAfB + D faB = fafB - D fAb = fAfb - D fab = fafb +