A key to the success of genetic maps is that this stitching occurs only at specific locations in the genome. In a landmark set of papers, Myers and his colleagues previously identified a particular DNA code, or motif, that attracted the recombination machinery. Knowing the motif, a string of 13 DNA letters, researchers could zero in on the exact locations where recombination typically occurredthe "recombination hotspots."
"When recombination goes wrong, it's known that this can lead to mutations causing congenital diseases, for example diseases like Charcot-Marie-Tooth disease, or certain anemias. We found the same 13-base motif marking many of these disease-mutation sites," said Myers.
Reich, who is also a senior associate member of the Broad Institute, said the places in the genome where there are recombination hotspots can also be disease hotspots.
"Charting recombination hotspots can thus bring us to the places in the genome that cause disease," he said.
The researchers discovered that the 13 base-pair motif responsible for many 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.
These findings are expected to help researchers understand the roots of congenital conditions that occur more often in African-Americans (due to mutations at the hotspots that are more common in African-Americans), and also to help discover new disease genes in all populations, because of the ability to map these genes more precisely.
The new map is so accurate specifically because so many African-Americans have both African and European genes, due to racial mixing during the last couple of hundred years. Reich and Myers are experts in
|Contact: Jack Mazurak |
University of Mississippi Medical Center