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Cataloging Human Genetic Variation

The world's largest, most detailed catalog of human genetic variation—used by disease researchers around the world—has more than doubled in size. The newly published information will provide deeper insights into the genomic basis of human disease.

Genetically, people are more than 99% alike. Although most of the variations between us have little or no effect, others can contribute to disease. The goal of the 1000 Genomes Project is to identify and compile variants in the human genome that are harbored by at least 1 in 50 people. NIH's National Human Genome Research Institute (NHGRI) helps fund and direct this international public-private consortium of scientists.

In the November 1, 2012, issue of Nature, the scientists described their latest map of genetic variation. They combined whole-genome sequencing with more detailed sequencing of the protein-coding regions of the genome—the “exome.” So far, the consortium has sequenced the genomes of over 1,000 people from 14 populations in Europe, East Asia, sub-Saharan Africa and the Americas. Ultimately, the scientists will study more than 2,500 people from 26 populations.

The new map includes 38 million single differences in DNA sequence, known as single nucleotide polymorphisms, or SNPs. It also includes 1.4 million short insertions or deletions of DNA (as small as a single base or as large as 50 bases) and 14,000 large deletions of DNA.

The researchers found that people from different populations have different profiles of rare variants. The patterns of rare variants differed by geography.

“Project researchers discovered that each person carries a handful of rare variants that would currently be recognized as disease-causing and a few hundred more rare variants that are likely to have a detrimental effect on how genes work,” says Dr. Gilean McVean of the University of Oxford in England, co-leader of the project’s analysis group. “It’s fortunate that most of us usually carry only 1 copy of these variants since 2 copies might lead to disease.”

All of the 1000 Genomes Project information is freely available on the Internet through public databases. The 2012 dataset will be followed by the last addition in 2013. This growing catalog will continue to help researchers pinpoint genetic variants associated with disease. Identifying the genetic underpinnings of disease can help lead to new diagnostic tests and treatments.

“With this project, we have succeeded in making sure that information about our shared genetic heritage, and the common DNA variants we carry, are freely available for researchers to use to benefit patients around the world,” says project co-leader Dr. David Altshuler of Massachusetts General Hospital and the Broad Institute. “Moreover, the tools and methods that this project has helped foster are being used now in disease-oriented genetics research and will be used increasingly in clinical care.”