Meiotic crossover hotspots contained in haplotype block boundaries of the mouse genome

  1. Liisa Kauppi*,,
  2. Maria Jasin, and
  3. Scott Keeney*
  1. *Molecular Biology and
  2. Developmental Biology Programs, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, NY 10021
  1. Edited by Kathryn V. Anderson, Sloan–Kettering Institute, New York, NY, and approved July 6, 2007 (received for review March 2, 2007)

Abstract

Fertility requires successful chromosome segregation in meiosis, which in most sexual organisms depends on the formation of appropriately placed crossovers. The nonrandom genome-wide distributions of meiotic recombination events have been examined at the molecular level experimentally in yeast and by inference from linkage disequilibrium patterns in humans. Thus far, no method has existed for pinpointing sites of crossing-over on a genome-wide scale in an experimentally tractable animal whose genome size and complexity models that of humans. Here, we present a genomic approach to identify mouse crossover hotspots, based on targeting haplotype block boundaries. This represents a previously undescribed method potentially applicable to large-scale mouse hotspot identification. Using this method, we have successfully predicted the location of two previously uncharacterized crossover hotspots in male mice. As increasing amounts of single-nucleotide polymorphism data emerge, this approach will be useful for investigating the recombination landscape of the mouse genome.

Footnotes

  • To whom correspondence should be addressed. E-mail: kauppil{at}mskcc.org
  • Author contributions: L.K., M.J., and S.K. designed research; L.K. performed research; L.K., M.J., and S.K. analyzed data; and L.K. and S.K. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/cgi/content/full/0701965104/DC1.

  • Abbreviations:
    ASO,
    allele-specific oligonucleotide;
    LD,
    linkage disequilibrium.
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