An international consortium of researchers has assembled a database of human genetic variations, creating a tool that could revolutionize the search for genes that cause many common diseases. But without careful self-regulation, the geneticists say, the information could also result in a flood of misleading or inconclusive results.
Called the HapMap, the database catalogs more than three million points of genetic variation based on samples from 269 people in Nigeria, China, Japan, and Utah. More than 200 scientists in Canada, China, Japan, Nigeria, the United Kingdom, and the United States participated in the project. The first phase of the project, reporting more than one million differences, was published in the October 27 issue of Nature, based on data analysis led by Peter Donnelly of the University of Oxford in England and David Altshuler, director of the program in Medical and Population Genetics of the Broad Institute of Harvard and MIT in Cambridge, MA.
“We need this background information on variation in the human genome just to begin to address the questions that we want to ask – like what are the genes involved in breast and prostate cancer and diabetes,” says Brian E. Henderson, dean of the Keck School of Medicine at the University of Southern California.
“It’s a very powerful tool,” agrees Charles Langley, a population geneticist at the University of California, Davis. “Human medical genetics is finally addressing a much bigger public health issue, which is the genetic basis of common diseases.”
Approximately six billion chemical building units, called nucleotides, comprise the human genome. Although roughly 99.9 percent of the sequence of those nucleotides is identical between any two humans, that still leave millions of differences at individual points in the DNA, called single nucleotide polymorphisms, or SNPs. It is these variations that account for many of the genetically determined differences between humans.
Researchers could find which of these changes relate to a particular disease by sequencing and comparing entire genomes (and every SNP) among thousands of affected and unaffected people. However, in practice, this would be expensive and time consuming.
In 2001, Mark J. Daly, then at the Whitehead Institute, now an associate member at the nearby Broad Institute, found that such genetic differences are inherited in large blocks, called haplotypes (hence the term “HapMap”). While there may be hundreds of SNPs within a region of DNA, all of them are linked, so that everyone who has an “A” nucleotide rather than a “G” at a particular location in a chromosome will have the same genetic variants at other SNPs in that region. And for many haplotypes, only three or four patterns of variation exist.
With a catalog of these blocks, geneticists could more effectively identify gene variants involved in common diseases such as diabetes, cancer, heart disease, and psychiatric illnesses.