Scientists from deCODE genetics today publish in Nature the highest resolution recombination map of the human genome yet developed. Recombination is the reshuffling of the genome that occurs in the formation of eggs and sperm: we inherit one version of each chromosome from each of our parents, and create novel blends of the two that we pass on to our offspring. This process is fundamental to generating human diversity, providing novel configurations of the genome that enable the species to adapt to ever-changing environments. The map is published and made freely available to the scientific community at http://www.nature.com, and at http://www.decode.com/addendum, where updates will be provided.
In 2002, deCODE created a 6000-marker framework recombination map that enabled the correct assembly of the first sequence of the human genome. The map published today, which is put into the public domain as deCODE and other institutions begin to sequence and analyze large numbers of whole genomes, was constructed using 300,000 single-letter markers, or SNPs. It incorporates data from more than 15,000 parent-offspring pairs participating in deCODE's gene discovery work in Iceland to show in high resolution where recombinations tend to take place. Among the findings are that some 15% of male and female recombination hotspots are unique to each sex. Moreover, women tend to contribute more to generating new combinations of genes, while men are doing more to create new versions of the genes themselves. So too, new variations in the PRDM9 gene have been identified that correlate with differences between individuals in how evenly recombinations are spread across the genome, and with different distributions of recombinations between people of African and European origin.
"This map is to me a thing of beauty. We are looking in quite high definition at the ingenious processes driving the generation of human diversity. From our previous work we have seen in basic terms that recombination is different between women and men, and between individuals and families. There are genetic factors that increase recombination in one sex while decreasing it in the other; women recombine at 1.6 times the rate of men; and women who recombine more tend to have more children. So we knew that nature is putting a premium on the generation of diversity. Here we see in detail the variations involved in generating variation, from women and men playing complementary roles in generating new versions and new configurations of genes, to differences in versions of PRDM9 between Africans and Europeans," said Kari Stefansson, deCODE CEO and senior author on the paper.
The construction of this map was made possible by the unique breadth and comprehensiveness of deCODE's population genetics resources in Iceland, and by new methods developed by deCODE statisticians for determining the parental origins of genetic markers. Because this new map is built by looking directly at real recombination events in large numbers of real families, it provides the first detailed picture of recombination differences between the sexes and individuals. By contrast, other recent recombination maps have been constructed using data on linkage disequilibrium - the frequency with which strings of genetic markers tend to be inherited together - in large numbers of unrelated people. The virtue of the latter maps is that they provide an historical catalogue of recombination as our species has evolved; the new deCODE map provides the complementary view of what this process looks like in a real population at a specific point in time.
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