Impaired Gene Cluster Singled Out in Multiple Sclerosis

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ANA: Impaired Gene Cluster Singled Out in

Multiple Sclerosis

By a Moyer, MedPage Today Staff

Writer

Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University

of Pennsylvania School of Medicine.

September 27, 2005

MedPage Today Action Points

* Explain to patients who ask that the genes of interest

are the major histocompatibility complex (MHC) genes, which normally help

discern autologous cells from bacteria and other pathogens.

* This study was published as an abstract and presented

orally at a conference. These data and conclusions should be considered to be

preliminary as they have not yet been reviewed and published in a peer-reviewed

publication.

Review

SAN DIEGO,

Sept. 27-The most complete genetic study to date of multiple sclerosis singles

out a cluster of genes on chromosome 6 as the only group to play a significant

role in MS.

These findings, presented today at the annual meeting of the American Neurological

Association, may constitute a turning point in the quest for an MS gene,

according to principal investigator Haines, Ph.D.

" No other region of the genome harbors a gene with a similar overall

influence on MS genetics, " said Dr. Haines in an oral presentation of the

study. Dr. Haines is director of the Human Genetics Program at Vanderbilt University

in Nashville, Tenn.

The genes that show so much promise are the major histocompatibility complex

(MHC) genes, a cluster that enables the body to distinguish autologous cells

from bacteria or other pathogens. When the MHC system is impaired, the body can

develop antibodies against autologous cells, as in MS. An interaction between a

variation in the MHC system and environmental challenges are the likely cause

of MS, he said.

Noting that previous studies have implicated the MHC system, Dr. Haines

distinguished the current research by the fact that for their linkage map, the

researchers had access to a larger study population than had been used in prior

MS genetics research.

The investigators typed 4,506 single nucleotide polymorphism markers found in

730 families in Australia,

Scandinavia, the United Kingdom,

and the U.S.

Among these families were 945 affected relative pairs.

The investigators found a highly significant linkage in the MHC region. The

mean information extraction in the study was 79.3%, suggesting that the

findings were highly consistent, according to Dr. Haines. The observed

Mendelian inconsistencies showed that, within the data set, the genotyping

error rate was 0.002%.

The findings not only further implicate the MHC system but also show the need

for larger data sets, Dr. Haines said. He suggested that future MS genetics

research should include 500 to 1,000 cases.

Primary source: American

Neurological Association. 130th annual meeting, September 25-28, 2005. San Diego, California.

Abstract # WiP #4. Presented September 27, 2005.

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