Researchers report a big leap in mapping genetic variants

Researchers have found more than 15 million places in the human genome where the genetic code differs from person to person, providing a catalog of hot spots for genetic change that should speed the search for genetic causes of such complex disorders as diabetes, Alzheimer’s and heart disease.

Only 10 years after scientists laboriously unraveled the first sequence of a human genome, an international team said Wednesday that they had sequenced the bulk of the genomes from more than 800 people in the pilot stage of the so-called 1000 Genomes Project, which aims to complete 2,500 sequences by the end of 2012 at a cost of $120 million.

More than 99% of the human genome is identical in all of the Earth’s nearly 7 billion inhabitants; it is in that minuscule 1% left over that individual physical characteristics such as eye color, height and disease propensity lie hidden. The research team reported that it has identified 95% of the individual places in the genome where such information is stored and is well on its way to discovering all of them.

The key to this progress is the development of powerful new DNA-sequencing machines that enable researchers to accomplish in hours feats that used to require months or even years at a fraction of the cost.


“In the last 10 years, DNA sequencing technology has advanced dramatically so that it becomes feasible to systematically sequence many people to find genetic variants and build a catalog which we can use as a basis for investigations into disease genetics and which variants may be functional,” Richard Durbin of the Wellcome Trust Sanger Institute in England, co-chairman of the project, said at a news conference.

The human genetic blueprint, or genome, is composed of an estimated 20,000 to 25,000 genes encoded in a chain of about 3.1 billion individual chemicals called bases. The initial effort to decode, or sequence, the genome of one individual took more than 10 years and cost more than $3 billion.

But researchers reported Wednesday in the journal Nature that their pilot project now included the entire genomes of 179 people of European, West African and East Asian ancestry as well as the gene-coding regions of an additional 697 people. The resulting information on more than 4.5 trillion bases of DNA sequences is enough to fill 400,000 books the size of the New York City telephone directory.

The results have produced a number of surprises.


Among the individuals whose genomes were fully sequenced were two families of father, mother and daughter. The team found that each daughter had about 60 genetic variants that were not inherited from either parent and apparently arose on their own.

The team also discovered that, on average, each person carries 250 to 300 genetic changes that would cause a gene to stop working normally, and about 50 to 100 genetic variations that have already been associated with an inherited disease. No person carries a perfect set of genes; the fact that everyone has two copies of each gene prevents most of those variations from being problems.

The complete list of genetic variants will give researchers powerful new tools not only for discovering the genetic roots of diseases but also for identifying mutations in tumors and other disorders such as heart disease that will respond to specific drugs, theoretically opening a new era of targeted treatments, the researchers said.

In a separate study released online Wednesday by the journal Science, geneticist Evan Eichler of the University of Washington in Seattle and his colleagues reported that they had found a way to identify multiple copies of genes, a feat that is not achievable by conventional sequencing.


They found that the presence of multiple copies of some genes may be associated with an increased tendency to develop certain diseases. The accumulation of extra copies of genes associated with brain development may have helped humans evolved from lower primates, they said.