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Researchers create the world's most advanced genetic map

Boston, MA (July 20, 2011)A consortium led by scientists at the University of Oxford and Harvard Medical School has constructed the world's most detailed genetic map.

A genetic map specifies the precise areas in the genetic material of a sperm or egg where the DNA from the mother and father has been reshuffled in order to produce this single reproductive cell. The biological process whereby this reshuffling occurs is known as "recombination." While almost every genetic map built so far has been developed from people of European ancestry, this new map is the first constructed from African American recombination genomic data.

"This is the world's most accurate genetic map," said David Reich, professor of genetics at Harvard Medical School, who co-led the study with Simon Myers, a lecturer in the Department of Statistics at the University of Oxford.

The researchers were surprised to find that positions where recombination occurs in African Americans are significantly different from non-African populations.

"The landscape of recombination has shifted in African Americans compared with Europeans," said Anjali Hinch, first author and a post-graduate student at Oxford University's Wellcome Trust Centre for Human Genetics.

Simon Myers added, "More than half of African Americans carry a version of the biological machinery for recombination that is different than Europeans. As a result, African Americans experience recombination where it almost never occurs in Europeans."


An independent study that used a similar strategy to build a genetic map in African Americansled by University of California, Los Angeles, scientists Daniel Wegmann, Nelson Freimer and John Novembrewill be published in Nature Genetics.

Scientists have only recently begun to explore the genetic differences between individuals and populations and the role those differences play in human health. In that respect, the first draft of the human genome, completed a decade ago, was only a starting point for understanding the genetic origins of disease.


But this stitching process only occurs at specific locations. In a prior landmark set of papers, Myers and his colleagues identified a DNA code, or motif, that attracted part of the recombination machinery, a gene called PRDM9. Knowing the motif, a string of 13 DNA letters, researchers could zero in on the locations where recombination typically occurredthe "recombination hotspots."

"When recombination goes wrong, it can lead to mutations causing congenital diseases, for example diseases like Charcot-Marie-Tooth disease, or certain anemias," said Myers. "We found the same 13 base motif marking many of these disease mutation sites."

Explained Reich, "The places in the genome where there are recombination hotspots can thus also be disease hotspots. Charting recombination hotspots can thus identify places in the genome that have an especially high chance of causing disease."

The researchers discovered that the 13 base-pair motif that is responsible for many of the hotspots in Europeans accounts for only two thirds as much recombination in African Americans. They connected the remaining third to a new motif of 17 base pairs, which is recognized by a version of the recombinational machinery that occurs almost exclusively in people of African ancestry.




Said James Wilson, a professor at the University of Mississippi Medical Center who was responsible for coordinating the collaboration, "All the co-authors worked together in an incredibly collegial way to put together the enormous set of samples and high quality genetic data that made this study a success."


Contact: David Cameron
Harvard Medical School

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