When the International HapMap Consortium, led by the National Institutes of Health (NIH; Bethesda, Maryland), launched in late 2002 its project to complete a map of common patterns of human genetic variations or haplotypes it set September 2005 as its deadline.
But the group said recently that by the end of this month it will reach completion of its first draft of the human haplotype map, termed "HapMap." HapMap will consist of 1 million markers of genetic variation, called single nucleotide polymorphisms, or SNPs.
Now, the group has been boosted with an additional $3.3 million in public/private funding, including at least $1.2 million of "in kind" services from Perlegen (Mountain View, California).
And there are plans to create "an even more powerful map," the group said. The consortium's new goal is to build an "improved version" of the HapMap about five times denser than originally conceived. The new effort will increase the density of SNPs from the current average of one every 3,000 bases to about one every 600 bases.
"This will help us create a far more powerful HapMap than we ever imagined," said Francis Collins, MD, PhD, director of the National Human Genome Research Institute (NHGRI), part of the NIH, in a statement. "The payoff will be a better understanding of the genetic risk factors underlying a wide range of diseases and conditions."
In the proposed Phase II of the project, Perlegen will test another 4.6 million SNPs from publicly available databases and add that information to the map, which is expected to help those companies active in the drive toward personalized medicine.
Last September, Perlegen reported that it had received a $6.1 million award from NHGRI to add data on 2.25 million additional SNPs to HapMap.
To create the HapMap, DNA was taken from blood samples from volunteer donors in several populations from around the world Han Chinese in Beijing; Japanese in Tokyo; Yoruba in Ibadan, Nigeria; and Utah residents with ancestry from northern and western Europe. No medical or personal identifying information was obtained from the 270 donors, the samples identified only by the population from which they were collected.
"The SNPs that we're using now are SNPs that people knew about already, but . . . now we're typing them in terms of these 270 people. By doing that, [it] is very helpful in terms of being able to understand, for example, the frequency of those SNPs," Paul Cusenza, vice president, alliance management, at Perlegen, told Diagnostics & Imaging Week.
It's all about finding patterns that is, those which are more frequent and those that are rare.
When these 4.6 million SNPs are completed in September, all the findings will be made public through the consortium, with the data available at the HapMap Coordination Center at the Cold Spring Harbor Laboratory and the JSNP Database in Japan. (This public disclosure compares to the practice of some companies in the area of genetic markers that discover them and then make them proprietary.)
By looking at these SNPs and typing them, the consortium is benefiting any person or company that is doing research in this area, Cusenza noted.
Perlegen, formed in late 2000 as a spin-off from Affymetrix (Santa Clara, California), is focused on the business of enabling companies to bring more drugs to market through the use of diagnostic markers, gained through the knowledge of SNPs. This in turn helps to determine which drugs can be brought to market despite their producing adverse reactions in some people.
According to Cusenza, if a drug company has a product that has a 4% adverse event rate, this need not deprive the other 96% for whom the drug is efficacious, based on a personalized medicine approach. "What we do is help make [personalized medicine] a true reality," he said.
Using the knowledge of the patterns and frequencies of SNPs, a company could make a diagnostic test enabling a physician to determine whether or not a drug will likely have an adverse impact on a patient. This information could be used also to reveal whether a patient, based on his or her DNA, would likely be helped by a medicine.
With this strategy increasingly known as "theranostics" the FDA could approve both a drug and diagnostic, in combination. And this combination approach could provide faster decision-making to determine if a drug will work for those in life-or-death situations.
The HapMap consortium includes researchers in six countries: Japan, the UK, Canada, China, Nigeria and the U.S.
In addition to financing provided to Perlegen, additional support was provided to the following organizations: the Wellcome Trust (London), $624,000; Genome Canada/Genome Quebec, $260,000; Bristol-Myers Squibb (New York), $100,000; and Pfizer (New York), $100,000.
"Researchers are already using HapMap data to accelerate the search for genes involved in common diseases, as well as genes involved in drug responsiveness," Karen Kennedy, PhD, science program manager at the Wellcome Trust, said in a statement. "When the more comprehensive version of the HapMap is completed this fall, such studies will be able to be carried out with even greater speed and efficiency."