High-resolution haplotype structure in the human genome Mark J. Daly.Eric S. Lander et al. Nature Genetics Vol.29 Oct. 2001 Haplotype Blocks and Linkage Disequilibrium in the Human Genome Jeffrey D.Wall aaand Jonathan K.Pritchard Nature Reviews Vol 4 Aug. 2003 Pooja Manchanda Biology Dept. Boston College

Haplotype Blocks: Sets of consecutive sites between which there is little or no evidence of historical recombination. These are regions with limited haploid diversity. Span up to 100kB and contain multiple common SNPs. Have only few (2-4) haplotypes. They separated by regions of numerous recombination events.

Pairwise Linkage Disequilibrium: The strength of association between alleles at two different markers. Two imp. measures are: R2 and D’ Both range from 0( no diseeq.) to 1 (complete diseq.) D’=1 if two or three haplotypes are present. (strong LD) D’<1 if all four possible haplotypes are present. (weak LD) R2 represents the statistical correlation between two sites. R2 =1 if only two haplotypes are present. It is most relevant measure for association mapping. Inveresely proportional to sample size.

Pairwise plots for representative regions from different studies

European-American African-American East Asian Sub-Saharan African sample EGP SNP Seattle SNP study The proportion of sequence contained in haplotype blocks of various sizes.

Summary LD is the non random association of alleles at diffeent sites. LD in the human genome can be summarized by a series of discrete haplotype blocks. Some regions of the genome shows well defined haplotype block and some contains no haplotype blocks. Recombination hotspots generally create haplotype block boundaries. Extent of strong LD is lower in African than in non African samples.