Monday October 09 12:34 PM EDT
By Robert Preidt
MONDAY, Oct. 9 (HealthSCOUT) -- A five-year, $20-million worldwide effort is underway to catalog a human gene complex considered the Rosetta stone of immunology.
The human leukocyte antigen (HLA) gene complex comprises the most diverse and variable region in the human genome and holds clues to many unsolved medical questions, including why transplants sometimes fail despite close donor-recipient matches, why vaccines protect some people better than others and why some people are more susceptible to specific diseases.
"This is really the first big project to look at the diversity of this gene complex in different populations and different diseases," says Shiv Prasad, program officer for the Division of Allergy, Immunology and Transplantation at the National Institute of Allergy and Infectious Diseases (NIAID). The institute is part of the National Institutes of Health (NIH) in Bethesda, Md., which is leading the initiative.
The $20 million will go to the International Histocompatibility Working Group (IHWG) and will involve a network of at least 200 laboratories in more than 70 countries, says Prasad.
The IHWG has a 36-year history and has developed much of the technology and terminology for the HLA gene complex, Prasad says.
He says while quite a bit is known about the HLA gene complex, there are still many questions. For example, while about 220 genes are known in the HLA gene complex, as many as 40 potential new genes have yet to be identified.
Collecting information about people around the world may give researchers a better idea of how and why the HLA gene complex affects a person's immune system.
"For example, looking at the differences in this gene complex in individuals with a certain auto-immune disease (such as arthritis or Type I diabetes), compared to healthy individuals," Prasad says.
A large, international group is able to gather examples from many places around the world a lot more effectively than one lab could, Prasad says.
The goal of the five-year project is to establish a huge data base of the HLA gene complex and its association with various diseases and other immune-system issues, he says.
The HLA gene complex encodes proteins that stud the surface of cells, marking those cells as unique to an individual. Anything not marked as part of that individual, including foreign matter like viruses and bacteria, cancerous cells and transplanted tissue, is attacked by the immune system.
Even organs and tissue from a close relative can display different HLA markers. A perfect HLA-type match exists only between identical twins.
The effectiveness of your immune defenses depends largely on your HLA gene complex. And the HLA genes are suspected of involvement when your immune system mistakenly targets your body's own cells as foreign, leading to autoimmune disorders like multiple sclerosis, rheumatoid arthritis and Type I diabetes.
"There will be many different laboratories, all of whom are experts in their own right and have a lot of expertise at testing and working with this HLA complex," says Eric Mickelson, the manager of the Human Immunogenetics Program Laboratory at the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle, Wash.
"Therefore, the chances are that there will be significant advances in our knowledge of the HLA complex," he says.
Mickelson works with Dr. John A. Hansen, head of the FHCRC's Human Immunogenetics Program, who's in charge of the international project.
The effort to catalog the HLA gene complex is especially relevant with the successful mapping of the human gene code, Mickelson says.
"This database will interface very nicely and successfully with the
Human Genome Project," he says.