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Science 23 April 2004:
Vol. 304. no. 5670, pp. 581 - 584
DOI: 10.1126/science.1092500
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Reports

The Fine-Scale Structure of Recombination Rate Variation in the Human Genome

Gilean A. T. McVean,1*{dagger} Simon R. Myers,1* Sarah Hunt,2 Panos Deloukas,2 David R. Bentley,2 Peter Donnelly1

The nature and scale of recombination rate variation are largely unknown for most species. In humans, pedigree analysis has documented variation at the chromosomal level, and sperm studies have identified specific hotspots in which crossing-over events cluster. To address whether this picture is representative of the genome as a whole, we have developed and validated a method for estimating recombination rates from patterns of genetic variation. From extensive single-nucleotide polymorphism surveys in European and African populations, we find evidence for extreme local rate variation spanning four orders in magnitude, in which 50% of all recombination events take place in less than 10% of the sequence. We demonstrate that recombination hotspots are a ubiquitous feature of the human genome, occurring on average every 200 kilobases or less, but recombination occurs preferentially outside genes.

1 Department of Statistics, University of Oxford, Oxford OX1 3TG, UK.
2 Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.


* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: mcvean{at}stats.ox.ac.uk

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