Where the Crossovers are: Recombination distributions in mammals 경원
Overview Nonrandom recombination events: most recombination events occure at highly localized hot spot. Characterize the frequency and spatial distribution of meiotic recombination events. The classic tools; difficult in detecting low frequency events.
Crossover distributions in mammals – an historical perspective Genetic versus physical distances: centimorgans per megabase pair Cytological studies: observing CHIASMATA or detecting of chromosome-associated protein complex involved in recombination. Pedigree and linkage disequilibrium (LD) analysis: pedigree approaches guided by LD analysis
Characterizing mammalian hot spots Development of SNP sequencing: inclease marker density Sperm DNA – allows many meiotic products, detect very low-frequency recombination. 약 0.5 kb 정도의 resolution을 가지는 hot spot location을 detecting 결점은 male에서만 사용가능 하다는 것이다.
Measure of LD Definition: A measure of whether alleles at two loci coexist in a population in a nonrandom fashion. Strong LD 는 두 loci 사이에 재조합이 거의 일어나지 않는 것을 의미한다. Dij= xij-piqj D’=Dij/Dmax (D’=1; complete LD,D’=0; free association)
D’ example SNP1: C 와 G의 빈도가 각각 0.90, 0.10 SNP2: A와 T의 빈도가 각각 0.55, 0.45 4가지 가능한 조합 (CA, CT, GA, GT) 기대되는 haplotype (0.495, 0.405, 0.055, 0.045) 관찰된 haplotype (0.450, 0.450, 0.100, 0) LD 값은 D는 각각 -0.045, 0.045, 0.045, -0.045) D’은 -1 ~ 1 여기서 절대값으로 구한 D’이 일반화된 LD 값이된다. LD 값이 1이면 완벽한 LD 임을 나타내고, LD값이 0이면 LD가 없음을 나타낸다.