05 Aug 2002

Single nucleotide polymorphisms, or SNPs, not only account for much of the variation among individual human genomes, but they may also explain why some of us are more susceptible to certain disorders like Alzheimer’s. In an advanced online publication in the August issue of Nature Genetics, David Altshuler and colleagues at the Whitehead Institute report that only a small fraction of SNPs arise by random mutation and that most SNPs are inherited. These findings should have a profound effect on those researchers hunting for genetic clues to disease.

The Whitehead team surveyed polymorphisms throughout the human genome and found that the rate of genetic variation between two loci correlates with the distance between them. They showed that over relatively short distances, say 100 bases, the correlation was excellent, but becomes very poor over longer distances (100 kilo bases). This observation prompted the researchers to examine the link between SNPs and inheritance, because genetic recombination, a feature of sexual reproduction, also correlates with distance between loci. In fact, the authors found that gene history accounts for at least 57 percent of the variation, whereas local mutation accounts for at most 25 percent.

But the data go one step further. It indicates that there is extreme variability in the rate of genetic recombination, even over small distances, thus providing data to support the long theorized notion of recombination “hot spots.”

These findings suggest that SNPs that are found in areas where recombination is rare will be inherited together and should be easy to track in the general population. This may make it easier for researchers to pinpoint associations between genes and disease.—Tom Fagan