The first set of talks at the MOHB in Boston yesterday evening was on personal genomics. Speakers including the Broad Institute’s David Altshuler and Leonid Kruglyak of Princeton vigorously defended the reputation of genome wide association studies (GWAS), which have come under some attack in the New York Times and other media outlets, recently. GWAS compare genomic markers in hundreds to thousands of individuals in order to find areas of the genome that associate with risk for common traits and diseases. They’ve produced hundreds of associations, but frustratingly for some, the genetic regions that have been fingered account for only a small percentage of the inherited risk for disease. Nature weighed in on this ‘missing heritability’ concept in the past (see here and here).
Altshuler takes umbrage with some, such as Mary Claire King at the University of Washington who have posited that very rare variants – unlikely to be found by GWAS – are where much of the heritability is hiding. Altshuler says he thinks that with projects like the 1,000 genomes project (which now plans to sequence upwards of 2,500 human genomes to various degrees of completion) a lot more human variation will be found and will begin to fill in more of the gaps in heritability. As costs of sequencing come down, he says, “We won’t have these debates about rare versus common variants.”
Capturing a real sense of human diversity in genomes will be important says Carlos Bustamante, now at Stanford University, and that should be done by sequencing more humans from diverse backgrounds (rather than just European backgrounds which have dominated the sequencer queues to date). His talk presented some new work looking closely at the sequence of an African American woman and a Mexican individual. Both individuals have a genome that is admixed, that is it contains a jumble of genetic elements from European and African origin in the case of the African American and Native American and European. Using computational tools, Bustamante’s group was able to deconvolute the ancestry of the genome in an easy to see way showing where stretches of DNA on the individuals’ genomes became mixed. The longer the stretches go without interruption, the more recent the admixture, says Bustamante, and they were roughly able to calculate the point at which cultures came together – lining up roughly with the Spanish exploration of the Americas (1470-1570) for the Mexican individual and the heyday of the middle passage (1690-1750) for the African American. It was a pleasing kind of “parlor trick” that these dates meshed so well with what we assume about history, he says. “We need continued sequencing of very diverse human genomes,” says Bustamante. It’s the only way we’ll be able to know what we’ve been missing.
