London, October 18 : The International HapMap Consortium has issued two reports on the analysis of its second-generation map of human genetic variation, which contains three times more markers than the initial version they had unveiled in 2005.

In the two papers, the consortium describes how the higher resolution map offers greater power to detect genetic variants involved in common diseases, explore the structure of human genetic variation, and learn how environmental factors like infectious agents have shaped the human genome.

“Thanks to this consortium’s pioneering efforts to map human genetic variation, we are already seeing a windfall of results that are shedding new light on the complex genetics of common diseases,” Nature magazine quoted Dr. Francis S. Collins, Director of the National Human Genome Research Institute (NHGRI) that is leading the US component of the project, as saying.

“This new approach to research, called genome-wide association studies, has recently uncovered new clues to the genetic factors involved in type 2 diabetes, cardiovascular disease, prostate cancer, multiple sclerosis and many other disorders. These results have opened up new avenues of research, taking us to places we had not imagined in our search for better ways to diagnose, treat and prevent disease,” he added.

The Phase II HapMap contains more than 3.1 million genetic variants, called single nucleotide polymorphisms (SNPs), three times than the approximately one million SNPs contained in the initial version.

The researchers behind the project strongly insist that the more SNPs that are on the map, the more precisely scientists can focus their hunts for genetic variants involved in disease.

They have revealed that the Phase II HapMap was produced using the same DNA samples as were used in Phase I. That DNA came from blood collected from 270 volunteers from four geographically diverse populations—Yoruba people in Nigeria, Japanese in Tokyo, Han Chinese in Beijing, and Utah residents with ancestry from northern and western Europe.

According to the consortium, the Phase II HapMap captures 25 to 35 per cent of common genetic variation in the populations surveyed.

The consortium has also confirmed that use of Phase II HapMap data has helped improve the coverage of various commercial technologies currently being used to identify disease-related variants in genome-wide association studies.

However, the researchers have revealed that current technologies tend to provide better coverage in non-African populations than in African populations because of the greater degree of genetic variability in African populations.

The overview paper also reports that the Phase II HapMap has provided new insights into the structure of human genetic variation. According to it, one new finding was the surprising extent of recent common ancestry found in all of the population groups.

The researchers took the advantage of the map’s increased resolution and identified stretches of identical DNA between pairs of donor chromosomes, and then compared these stretches both within and across individuals. They found that 10 to 30 per cent of the DNA segments analysed in each population showed shared regions indicating descent from a common ancestor within 10 to 100 generations.

A related study published in the magazine describes how the enhanced map can help pinpoint pivotal changes in the human genome that arose in recent history.

With the help of the Phase II HapMap data, a team led by researchers at the Broad Institute of MIT and Harvard have identified hundreds of genomic regions that carry the hallmarks of recent positive natural selection. These regions are large, often extending for millions of nucleotides and including multiple genes.

The researchers also identified DNA variations in African populations that may be linked to resistance to Lassa fever, a viral infection common in Western Africa. These changes lie in two genes, LARGE and DMD, which are involved in viral entry into cells.

“Human history and the genome have been dramatically shaped by environmental factors, diet and infectious disease. The gene variants identified in our study open new windows on these evolutionary forces and provide a launching point for future biological studies of human adaptation,” said co-first author Dr. Pardis Sabeti, who is a postdoctoral fellow at the Broad Institute of MIT and Harvard. (ANI)