A Comprehensive Map of Human Genetic Diversity

Even though we differ from each other by only about 0.1 percent of our DNA, those minute differences have a huge impact.

Researchers say they have now captured a record 95 percent of all human genetic diversity. The research is the first phase of a global collaboration called the 1,000 genomes project, an effort to sequence 2,500 human genomes from different populations using new technologies.

“We identified more than 15 million genetic differences, more than half have never been seen before,” says Richard Durbin, a scientist at the Wellcome Trust Sanger Institute, in the United Kingdom, and co-chair of the 1,000 Genomes consortium. Durbin says that number is likely to double as they analyze new data from 1,000 genomes.

Having access to this kind of information will help scientists as they search for genetic changes that can increase risk for different diseases. It will also shed light on the details of human evolution, allowing researchers to pinpoint the parts of the genome that have been most recently subjected to selective pressures.

The initial findings show that everyone carries 250 to 300 mutations that alter the function of the protein that the gene produces. Approximately 50 to 100 of these mutations occur in genes that have previously been linked to inherited diseases. (But because everyone has two copies of each gene–one from their mother and one from their father–as long as an individual carries one normal copy, they are likely to be healthy.)

In the pilot phase of the project, scientists sequenced the genomes of 179 people and the protein-coding genes of 697 people from different parts of the globe. The research, published today in the journal Nature, generated more than 4.5 terabases (4.5 million million base letters) of information. It is also publicly available for further analysis through an online database. Researchers have now moved on to the second phase of the project; to sequence the genomes of 2,500 people, aiming to capture 98 to 99 percent of genetic diversity by the project’s completion in 2012.

When the human genome project was published a decade ago, in contrast, scientists had identified only about five percent of the genetic variation in the human species. With the creation of the HapMap–a genetic database that captured the most common genetic mutations, those present in at least five to ten percent of the population–over the following five years, that number grew to 40 or 50 percent.

The data from the project has already been put to use. Evan Eichler and colleagues from the University of Washington, in Seattle, used the findings to develop new methods to analyze repetitive portions of the genome, known as copy number variations. These regions, which encompass about 15 percent of the genome, have been extremely difficult to study using traditional methods. But recent research suggests they play a major role in human health; specific copy number variations have been linked to autism, schizophrenia and other disorders.

Eichler’s team found that these regions vary highly between different ethnic groups, more so than the genome as a whole. They were also able to pinpoint specific differences that evolved since humans branched off from our ancestors. “When we compare humans to great apes, we can clearly identify genes and gene families that have expanded specifically in our lineage since we separated from chimp and gorilla,” says Eichler. “It’s a tantalizing set of genes in terms of neural development and neural migration.” The research was published today in the journal Science.