A New Phase for Human Genomics

Researchers have published the most detailed map of human genetic variation so far. Scientists will use this resource to help identify genetic contributions to rare and common diseases.

Genetically, any 2 people are more than 99% alike. The variations between people can help explain differences in susceptibility to disease, response to drugs or reaction to environmental factors. Variations can be as small as single differences in DNA sequence—known as single nucleotide polymorphisms (SNPs)—or as large as whole sections of the genome being copied or moved to another part of the genome.

The HapMap Project has already helped researchers identify many candidate genetic regions associated with disease. A more detailed map would allow researchers to pinpoint regions with greater precision and provide a set of candidate genes and variants in those regions for further study. The 1000 Genomes Project is an international consortium launched in 2008 to explore genetic variation more comprehensively in populations worldwide. NIH's National Human Genome Research Institute (NHGRI) is one of several organizations funding the effort.

The researchers used 3 strategies in the project’s pilot phase: "low-coverage" whole-genome sequencing of 179 people from 4 populations; more detailed "high-coverage" sequencing of 2 mother–father–child trios; and exon sequencing of 697 people from 7 populations. Exons are the parts of the genome with instructions for producing proteins, the building blocks of the body. The complete set of exons, the "exome," makes up just a small fraction of the human genome—about 1%.

Results from 1000 Genomes Project's pilot phase appeared in Nature on October 28, 2010. The researchers detected about 15 million SNPs, 1 million short insertions and deletions, and more than 20,000 structural variants. Half the genetic variations had previously been identified, but half were new. The results show that low-coverage sequencing can adequately uncover variation in a large sample.

The new map produced some surprising findings. On average, each person carries between 250 and 300 genetic changes that would lead a gene to stop working. Each person also carries between 50 and 100 genetic variations that have previously been tied to an inherited disease. The mother-father-daughter study allowed the calculation of a more precise mutation rate in humans. It revealed that each person has approximately 60 new mutations not found in either parent.

"The 1000 Genomes Project pilot studies have laid a critical foundation for creating a comprehensive map of human genetic variation," says consortium co-chair Dr. Richard Durbin of the Wellcome Trust Sanger Institute.

With the completion of the pilot phase, the 1000 Genomes Project has now moved into full-scale studies. Primary sequence data from more than 1,000 people are already available from the project web site, and researchers around the world can use these findings in their studies. The project plans to eventually sequence 2,500 samples from major population groups across the world.