Evidence for substantial fine-scale variation in recombination rates across the human genome

Nat Genet. 2004 Jul;36(7):700-6. doi: 10.1038/ng1376. Epub 2004 Jun 6.


Characterizing fine-scale variation in human recombination rates is important, both to deepen understanding of the recombination process and to aid the design of disease association studies. Current genetic maps show that rates vary on a megabase scale, but studying finer-scale variation using pedigrees is difficult. Sperm-typing experiments have characterized regions where crossovers cluster into 1-2-kb hot spots, but technical difficulties limit the number of studies. An alternative is to use population variation to infer fine-scale characteristics of the recombination process. Several surveys reported 'block-like' patterns of diversity, which may reflect fine-scale recombination rate variation, but limitations of available methods made this impossible to assess. Here, we applied a new statistical method, which overcomes these limitations, to infer patterns of fine-scale recombination rate variation in 74 genes. We found extensive rate variation both within and among genes. In particular, recombination hot spots are a common feature of the human genome: 47% (35 of 74) of genes showed substantive evidence for a hot spot, and many more showed evidence for some rate variation. No primary sequence characteristics are consistently associated with precise hot-spot location, although G+C content and nucleotide diversity are correlated with local recombination rate.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Genome, Human*
  • Humans
  • Polymorphism, Single Nucleotide
  • Recombination, Genetic*