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Genome-wide Studies Reveal Genetic Recombination Clues

NEW YORK (GenomeWeb News) – Two new genome-wide analyses are helping scientists understand genetic recombination, the process by which genes get shuffled and combined during the formation of egg and sperm cells.
The studies, both published online today in the journal Science, confirmed some things scientists already knew about recombination — such as the existence of so-called hotspots where recombination tends to occur. But they’re also providing new insights into the process, suggesting that crossover events, though highly variable, are partly inherited, as well as identifying gene variants with a role in controlling the rate of recombination.
Recombination is the process by which chromosomes swap genetic information during meiosis, a type of cell division that transforms diploid cells to haploid reproductive cells. While too little recombination can impair proper chromatid separation, too much can cause chromosomal rearrangements. 
In the first study, done at the University of Chicago, researchers used large-scale, high-resolution SNP analysis on 725 members of a Hutterite community, a genetically similar population of European descendents who settled in the Dakotas, using an Affymetrix GeneChip Mapping 500k array set. Since the individuals came from 82 overlapping nuclear families, the researchers could determine recombination events within families.
The data confirmed previous findings suggesting that recombination tends to occur at particular “hotspots.” In fact, the study found that about 60 percent of the recombination events they saw occurred at previously identified hotspots. Nevertheless, their map indicates that recombination — even at hotspots — is extremely variable, though there are some heritability patterns in the way individuals use historical recombination hotspots.
As Graham Coop, University of Chicago post-doctoral fellow and lead author of the study, points out, this is not the first genome-wide recombination study. But the team believes the chip technology they used allows greater resolution than previously available. “What’s different about our study is that, because we’re using the SNP array, we get 500,000 markers,” he told GenomeWeb Daily News.
In the future, the group hopes to do association mapping to help work out the genetic basis of variation in recombination and hotspot use.
Meanwhile, researchers from Decode Genetics in Iceland used a genome-wide search to pinpoint two gene variants apparently influencing genome-wide recombination rates. The group, which also published its findings in today’s issue of Science, suggests these SNPs consequently act as evolutionary motors, since recombination contributes to the genetic diversity that allows adaptation to changing environments.
That group evaluated more than 309,241 SNPs in 1,887 male and 1,702 female subjects using the Illumina Hap300 chip. After narrowing down their search to three candidate SNPs, the researchers examined these in larger groups, eventually genotyping nearly 20,000 people to generate estimates of how the variants affect recombination rates.
The two SNPs that the group ultimately focused on are both located within a poorly understood gene called RNF212 on chromosome 4p16. The group went on to estimate the rate of recombination in each and found that the first, rs3796619, accounted for about 22 percent of the paternal variability in men, while rs1670533 explains approximately six-and-a-half percent of maternal variability. Interestingly, they found that the mutations that increased recombination rates in men actually decreased them in women.
“Biologically, the processes of male and female recombination are different, which may allow such variants to exist,” lead author Augustine Kong and his colleagues wrote. “These variants could serve a key function from an evolutionary perspective, as they allow the transfer of the recombination contribution from one sex to the other with minimal impact on the average recombination rate for the population as a whole.”

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