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Understanding recombination rate variation is very important for studying genome diversity and evolution, and for investigation of phenotypic association and genetic diseases. Recombination hotspots have been observed in many species and are well studied in yeast. Recent study demonstrated that recombination hotspots are also a ubiquitous feature of the human genome. But the nature of human hotspots remains largely unknown. We have developed and validated a novel computational method for testing the existence of hotspots as well as for localizing them with either unphased or phased genotyping data. To study the characteristics of hotspots within or close to genes, we scanned for unusually high levels of recombination using the European population samples in the SeattleSNPs database, and found evidence for the existence of human alpha hotspots similar to those of yeast. This type of hotspots, found at promoter regions, accounts for about half of the total detected and appears to depend on some specific transcription factor binding sites (such as CGGC). These characteristics can explain the observed weak correlation between hotspots and GC-content, and their variation may contribute to the diversity of hotspot distribution among different individuals and species. These long-sought putative human alpha recombination hotspots should deserve further experimental investigations.

Evidence and characteristics of putative human α recombination hotspots