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Vol. 10, Issue 9, 1319-1332, September 2000

Patterns of Meiotic Recombination on the Long Arm of Human Chromosome 21

Audrey Lynn,1 Carl Kashuk,1,6 Michael B. Petersen,2,3 Jeffrey A. Bailey,1 David R. Cox,4 Stylianos E. Antonarakis,5 and Aravinda Chakravarti1,6,7

1 Department of Genetics and Center for Human Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA; 2 Department of Genetics, Institute of Child Health, Athens GR-11527, Greece; 3 Department of Medical Genetics, The John F. Kennedy Institute, Danish Center for Human Genome Research, Glostrup DK-26000, Denmark; 4 Department of Genetics and Stanford Human Genome Center, Stanford University, Stanford, California, USA; 5 Department of Medical Genetics, University of Geneva Medical School, Geneva 4CH-1211, Switzerland

In this study we quantify the features of meiotic recombination on the long arm of human chromosome 21. We constructed a 67.3-centimorgan (cM) high-resolution, comprehensive, and accurate genetic linkage map of chromosome 21q using 187 highly polymorphic markers covering almost the entire long arm; 46 loci, consisting of mutually recombining marker sets, were ordered with greater than 1000:1 odds and with average interlocus distance of 1.46 cM. These markers were used to accurately identify all exchanges in 186 female and 160 male meioses and to show (1) significant excess of recombination in female versus male meioses, (2) an overall decline in female:male recombination between the centromere and the telomere, (3) greater positive chiasma interference in male than in female meioses, and (4) lack of correlation between exchange frequency and parental age. By comparing the genetic map with the 21q sequence map, we show a general trend of increasing male, but near-constant female, recombination versus physical distance across 21q, explaining the gender-specific recombination effect. The recombination rate varies considerably between genders across 21q but is the greatest (eightfold) in the pericentromeric region, with a rate of approximately 250 kb/cM in females and approximately 2125 kb/cM in males. We used information on the locations of all exchanges to construct an empirical map function that confirms the statistical findings of positive interference. These analyses reveal that occurrence of recombination on 21q is not only gender-specific but also region-specific and that recombination suppression at the centromere is not universal. We also find evidence that male exchange location is highly correlated with gene density.

6 Present address: McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.

7 Corresponding author.

10:1319-1332 ©2000 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/00 $5.00
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