recombination rates to be defined across the genome at a fine scale of resolution. Using a coalescent-based method to estimate variation in rates of recombination, the degree of fine scale variation was found to be very extensive (McVean et al. 2004). A genome-wide map of recombination was derived by Myers and colleagues using data on 1.6 million common SNPs for 24 unrelated
Americans of European ancestry, 23 African Americans, and 24 American Han Chinese (Hinds et al. 2005; Myers et al. 2005). This revealed marked local variation, with recombination being focused into narrow 'hotspots' such that more than 80% of recombination was found to occur in 10-20% of genomic sequence (Myers et al. 2005) (Fig. 9.8). In total more than 25 000 recombination hotspots were found across the genome (Myers et al. 2005).
The denser SNP set and larger population panels within Phase II HapMap meant that this estimate has since risen to nearly 33 000 recombination hotspots (Frazer et al. 2007). Recombination hotspots are found on average every 50-100 kb with similar rates of recombination estimated for males and females. Recombination is noted to occur preferentially outside but near to transcribed regions: peaks were noted 5' to the transcriptional start site and 3' to the gene, the latter being more pronounced (Fig. 9.9A) (Frazer et al. 2007). Striking differences in rates of recombination were noted between gene classes when gene function was considered, being highest in genes involved in defence and immunity (1.9 cM per megabase) and lowest among genes involved in essential cellular functions such as chaperones (Fig. 9.9B) (Frazer et al. 2007). Other characteristics of recombination hotspots include enrichment for GC content and particular mobile DNA elements such as the THE1A/B retrotrans-posons: when present within recombination hotspots, these elements show marked enrichment for a particular nucleotide sequence CCTCCCT (Fig. 9.9) (Myers et al. 2005; Frazer et al. 2007).
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