More MS news articles for October 1999

Scientists identify gene cluster linked to disease

Thursday, October 28, 1999

By CAROL SMITH
SEATTLE POST-INTELLIGENCER REPORTER

Seattle researchers have finally decoded a region of the human genome that may prove to be one of the main repositories of disease genes.

This area of the genome has been the focus of intense research as scientists have sought to unravel the secret of why some people get certain diseases and others don't.

"For three decades, (researchers) have been studying this small part of the genome," said geneticist Dan Geraghty, a Fred Hutchinson researcher and co-author of the paper. "It's so important in that it (governs) one of the body's frontline defenses against pathogens."

The sequencing information, which is being published in today's journal Nature, was done by a consortium of scientists who had been competing with one another to be the first to publish the sequence, but elected instead to publish as a group.

Other scientists in the consortium included Lee Rowen, Marta Janer and Leroy Hood at the University of Washington, H. Inoko of Tokai University School of Medicine in Japan and Stephen Beck of The Sanger Centre in England.

The cluster of more than 300 genes, called the MHC, is located on a tiny fraction of the body's sixth chromosome, but it is one of the most densely loaded with genes that help protect or predispose the body to disease.

The MHC is associated with more diseases than any other region of the human genome, including most, if not all, autoimmune conditions, researchers said.

"I think there will be many people looking forward to having that whole sequence in the public domain," said Rowen, research scientist in the Multimegabase sequencing center at the UW. "It's so gene-rich, it will allow people to do further biology. There's quite a gold mine of discovery still to be had there."

Some diseases that are linked to genes in the MHC region:

Rheumatoid arthritis
Grave's disease
Insulin-dependent diabetes
Multiple sclerosis
Narcolepsy
Psoriasis
Lupus

Conditions believed to be influenced by genes in the MHC region range from cancer and autoimmune diseases to reading and sleeping disorders.

"This new knowledge should rapidly lead to straightforward and accurate diagnostic tests based on actual gene sequences," Geraghty said. "This should make it easier for doctors to influence the progression of some diseases by giving lifestyle advice."

Such genetic testing will give doctors the means to tell people in advance whether they are predisposed to get certain conditions.

"Genetic testing is going to be one of the most important diagnostic tools that a doctor has in a matter of one to two decades," he said.

But it also raises social questions. Privacy experts are concerned, for example, that such information could lead insurance companies to exclude people from coverage.

In the longer term, society is going to have to deal with the privacy issues, Geraghty said.

"People will have to find a way to separate an individual's medical record from insurance company calculations."

An individual's genetic information belongs to the individual, he said. "It should be used by them for their own benefit."

In the meantime, however, the sequencing information gives researchers a powerful new tool for developing better treatments for diseases.

In addition to certain disease-predisposition genes, for example, the MHC region also contains the key genes that determine whether two people are compatible for an organ or bone marrow transplant, leading researchers to believe they will be able to fine-tune and improve the matching process.

And about 40 percent of the MHC genes are believed to be involved in regulating aspects of the immune system, including the body's ability to distinguish between its own tissues and foreign pathogens.

Without that fundamental ability, the body turns on itself, creating a host of "autoimmune" diseases, ranging from rheumatoid arthritis to multiple sclerosis.

Understanding the way the MHC genes help control the immune system could help researchers tailor better, cheaper and faster ways to fight disease, Geraghty said.

"This is digital medicine, vs. analog."
 

P-I reporter Carol Smith can be reached at 206-448-8070 or carolsmith@seattle-pi.com