A consortium led by scientists at Oxford University and Harvard Medical School has constructed the world’s most detailed genetic map. The map is the first to include data from African Americans and will help scientists understand certain inherited diseases.

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 during which this reshuffling occurs is known as ‘recombination’. Almost all such maps have been developed from people of European ancestry and this new map is the first constructed from African American recombination genomic data.

A report of the research is published in this week’s Nature.

‘The landscape of recombination has shifted in African Americans compared with Europeans,’ said Anjali Hinch, first author of the paper and a post-graduate student at Oxford University’s Wellcome Trust Centre for Human Genetics (WTCHG). Dr Simon Myers of Oxford University’s Department of Statistics and WTCHG, who co-led the study with Professor David Reich at Harvard Medical School, said: ‘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.\’

Recombination, together with mutation, accounts for all the genetic and physical variety we see within species. But whilst ‘mutation’ refers to the errors introduced into single locations within genomes when cells divide, ‘recombination’ refers to the process by which huge chunks of chromosomes are stitched together during sexual reproduction. However, this stitching process only occurs at specific locations. In earlier work Myers and 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 occurred – so-called \’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 Dr Myers.

‘We found the same 13 base motif marking many of these disease mutation sites,’ said Professor 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 recognised by a version of the recombinational machinery that occurs almost exclusively in people of African ancestry.

These findings are expected to help researchers understand the roots of congenital conditions that occur more often in African Americans, and also to help discover new disease genes in all populations, because of the ability to map these genes more precisely.