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. 2010 Dec 8;5(12):e15340.
doi: 10.1371/journal.pone.0015340.

Patterns of Recombination Activity on Mouse Chromosome 11 Revealed by High Resolution Mapping

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Free PMC article

Patterns of Recombination Activity on Mouse Chromosome 11 Revealed by High Resolution Mapping

Timothy Billings et al. PLoS One. .
Free PMC article

Abstract

The success of high resolution genetic mapping of disease predisposition and quantitative trait loci in humans and experimental animals depends on the positions of key crossover events around the gene of interest. In mammals, the majority of recombination occurs at highly delimited 1-2 kb long sites known as recombination hotspots, whose locations and activities are distributed unevenly along the chromosomes and are tightly regulated in a sex specific manner. The factors determining the location of hotspots started to emerge with the finding of PRDM9 as a major hotspot regulator in mammals, however, additional factors modulating hotspot activity and sex specificity are yet to be defined. To address this limitation, we have collected and mapped the locations of 4829 crossover events occurring on mouse chromosome 11 in 5858 meioses of male and female reciprocal F1 hybrids of C57BL/6J and CAST/EiJ mice. This chromosome was chosen for its medium size and high gene density and provided a comparison with our previous analysis of recombination on the longest mouse chromosome 1. Crossovers were mapped to an average resolution of 127 kb, and thirteen hotspots were mapped to <8 kb. Most crossovers occurred in a small number of the most active hotspots. Females had higher recombination rate than males as a consequence of differences in crossover interference and regional variation of sex specific rates along the chromosome. Comparison with chromosome 1 showed that recombination events tend to be positioned in similar fashion along the centromere-telomere axis but independently of the local gene density. It appears that mammalian recombination is regulated on at least three levels, chromosome-wide, regional, and at individual hotspots, and these regulation levels are influenced by sex and genetic background but not by gene content.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Recombination patterns on mouse chromosome 11.
A. Sex-averaged recombination map of chromosome 11. Recombination events were mapped to an average resolution of 225 Kb in two consecutive rounds. Recombination rates are presented as cM/Mb to adjust for interval size. B. Gene density on chromosome 11 (from ENSEMBL, www.ensembl.org ). The X-axis is to scale with 1A. The height of the peaks represents the relative gene density in 1-Mb intervals.
Figure 2
Figure 2. Sex-specific recombination map of chromosome 11.
A. Sex-specific recombination rates averaged over 2-Mb sliding window. B. Fine mapping of recombination activity. The entire chromosome was mapped at 225 Kb resolution and then highly active intervals showing sex-specific rates were mapped further to <50 kb resolution. The recombination rates are expressed as cM to account for these resolution differences. Female, red line above, male, blue line below. C. Expanded view of the region between 16.5-21.5 Mb. Hotspots with higher activity in female (red arrows) or male meiosis (a cluster marked with blue arrow) are shown. The p-values of the difference were determined by Fisher's exact test.
Figure 3
Figure 3. Sex Specificity of Interference.
A. Coefficient of coincidence (Z) as a function of intercrossover distance in Mb. B. Coefficient of coincidence (Z) as a function of intercrossover distance in µm of synaptonemal length at the pachytene stage of meiosis I. Female, red line; male, blue line.

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