Human haplotype block sizes are negatively correlated with recombination rates

Abstract

The International Haplotype Map ("HapMap") Project is motivated, in part, by the belief that the organization of the human genome, the mechanics of recombination, and the population-level behavior of alleles at adjacent loci should allow researchers to parse the genome into small segments, or "blocks," that show strong linkage disequilibrium (LD) between alleles at loci within those segments. The discovery and evidence for these blocks is to be based solely on the observed LD strength and patterns between alleles at adjacent loci throughout the genome. Although there are many factors that contribute to LD strength, we assessed the correlation between block structure, in terms of length and percentage of the genome assembled into blocks within a region, and recombination rate obtained from two independent sources. We found evidence of a striking negative correlation between the average recombination rate and average block length, suggesting that recombination rate is a strong contributor to haplotype block structure within the genome. We discuss the potential implications of this negative correlation in the context of the organization, properties, and potential ubiquity of a block-like structure in the human genome.

Figure 1

Scatter diagrams depicting the relationship between block structure and recombination rate using the haplotype block data from Gabriel et al. (2002) and the recombination rate data from Kong et al. (2002). (•) Block data obtained from the CEPH families. (○) Block data from the Yoruban samples. The solid and dashed lines are linear regression lines for block structures and recombination rates computed for the CEPH and Yoruban data, respectively. (A) The relationship between sex-averaged recombination rate and average block size. (B) The relationship between sex-averaged recombination rate and the size of the largest block observed in a region. (C) The relationship between sex-averaged recombination rate and percentage of sequence in a region found to be in a block.