May 5, 2008

Map of Structural Variation in the Human Genome

Image of brightly colored chromosomal pairs NHGRI

Researchers have produced the first sequence-based map of human genome “structural” variations—those spanning long stretches of the genetic code. The map will help researchers understand how these variations contribute to human health and disease.

The genetic maps that have emerged over the past few years, such as the HapMap, have catalogued the patterns of small-scale variations in the genome—those that involve single DNA letters, or bases. Recent studies, however, show that larger structural differences account for a great deal of the genetic variation among people. These include gains, losses and rearrangements of long stretches of DNA, ranging from a few thousand to a few million bases. Already, such variations have been linked to differences in susceptibility to HIV, the risk of coronary heart disease, schizophrenia and autism.

While previous work has uncovered some structural variation in the human genome, a sequence-based map provides much finer detail. A nationwide team of researchers, funded in part by NIH’s National Human Genome Research Institute (NHGRI), constructed the new map by analyzing the genomes of 8 people: 4 of African descent, 2 of Asian descent and 2 of European descent. The donor samples, collected as part of the International HapMap Project, were labeled by population group, with no medical or personal identifying information.

As they explained on April 30, 2008, in the journal Nature, the researchers mapped a total of 6.1 million small segments of DNA across the 8 genomes, using the human genome sequence that was completed in April 2003 as a reference.

The new map provides a detailed look at the locations of nearly 1,700 structural variations, roughly half of which had not been previously described. About half the variants were found in more than 1 person. The work uncovered 525 new inserted sequence stretches that weren’t in the human reference genome. Many of the new variations consist of differences in how many copies a person has of a certain gene, called copy number variation. 

“The structural variation map will give us a much better picture of genetic variation between each individual, and help us better understand these areas of the genome that are prone to large-scale changes over time,” said Dr. Evan Eichler of the University of Washington, who led the research.

Sequence data from the map are freely available online for other scientists to use in their own studies.

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