title: Local and sex-specific biases in crossover vs. noncrossover outcomes at meiotic recombination hot spots in mice.
abstract: Meiotic recombination initiated by programmed double-strand breaks (DSBs) yields two types of interhomolog recombination products, crossovers and noncrossovers, but what determines whether a DSB will yield a crossover or noncrossover is not understood. In this study, we analyzed the influence of sex and chromosomal location on mammalian recombination outcomes by constructing fine-scale recombination maps in both males and females at two mouse hot spots located in different regions of the same chromosome. These include the most comprehensive maps of recombination hot spots in oocytes to date. One hot spot, located centrally on chromosome 1, behaved similarly in male and female meiosis: Crossovers and noncrossovers formed at comparable levels and ratios in both sexes. In contrast, at a distal hot spot, crossovers were recovered only in males even though noncrossovers were obtained at similar frequencies in both sexes. These findings reveal an example of extreme sex-specific bias in recombination outcome. We further found that estimates of relative DSB levels are surprisingly poor predictors of relative crossover frequencies between hot spots in males. Our results demonstrate that the outcome of mammalian meiotic recombination can be biased, that this bias can vary depending on location and cellular context, and that DSB frequency is not the only determinant of crossover frequency.
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA;
authors.forename: Esther
authors.initials: E
authors.lastname: de Boer
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA;
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Keeney
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D053903:DNA Breaks, Double-Stranded; D005260:Female; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic; D012737:Sex Factors
keywords: Spo11; crossing over; gene conversion; hot spot; meiosis; recombination