Mapping Human Genetic Variation

GENOMICS

A research team has carried out one of the most detailed analyses to date of patterns of genetic variation in people of different ethnicities. The work represents a significant step toward the ability to identify genes that underlie individual or group variations in susceptibility to disease.

Genomes of different individuals are well over 99% identical. The most typical variations are changes called single-nucleotide polymorphisms (SNPs), in which one or another of two DNA bases is found at an identical genomic location in different people.

SNPs or patterns of SNPs can be associated with different traits, such as variations in disease susceptibility or drug responsiveness. However, the relationship between SNP variations and disease risk in people of different ethnicities is currently unclear.

Now, Chief Scientific Officer David R. Cox of Perlegen Sciences, Mountain View, Calif., and coworkers have used DNA chip technology to analyze 1.59 million SNPs in each of 71 people from three groups: European, African American, and Han Chinese [Science, 307, 1072 (2005)]. The result is a publicly accessible data set that manages to capture most human genetic variation, despite the small number of individuals involved.

In a commentary, sociology professor Troy Duster of New York University observes that the study is "designed to help better understand the molecular basis of disease." A drug combination called BiDil was recently found effective against heart disease in African Americans only and could become the first race-specific drug, but studies like that of Cox and coworkers could make much finer distinctions possible, he notes.

In another commentary, associate professor of genetics and of medicine David M. Altshuler of Harvard Medical School and molecular biology and genetics professor Andrew G. Clark of Cornell University point out that a public data set of more than 1 million SNPs in each of 270 people has been generated by the International HapMap Consortium. This and the Perlegen data--plus new rapid and inexpensive SNP analysis techniques--"are paving the way for comprehensive association studies involving common human genetic variations," they write.