A collaborative effort of The Broad Institute of MIT and Harvard and The Partners MS Center of Brigham & Women's Hospital and Massachusetts General Hospital
A whole genome admixture scan for the multiple sclerosis genes -- Scanning for MS genes in genetic material from patients whose ancestry contain a mix of populations at high risk and at low risk for MS.
Although MS is not inherited directly, there appears to be a genetic predisposition to developing the disease. Evidence indicates that a single gene alone does not determine the risk of getting MS. Many separately inherited genes appear to contribute to MS susceptibility, making the search more complex. We are using a new and powerful technique called “admixture mapping” to identify MS genes.
As it relates to MS, admixture mapping involves studying the genetic basis of MS in populations with mixed racial ancestry. MS in African-Americans is clinically similar to that seen in European-Americans (Caucasians). However, African-Americans have only one-half the risk of developing MS when compared to those of European extraction. Continental Africans have an even lower rate of MS than African-Americans. These facts suggest that genetic susceptibility to MS in African-Americans may lie in the genetic material that might have been inherited from a European ancestor.
Our team, along with our collaborators, Jorge Oksenberg, PhD, and Stephen Hauser, MD (University of California at San Francisco) is studying genetic material from 1000 African-Americans with MS. We are identifying which parts are of European ancestry, and are looking for small overlapping regions that may contain MS genes.
This study should help to identify MS genes not only in African-Americans but will help to pinpoint MS susceptibility genes in the general population as well, and may provide targets for the development of new drugs for MS.
A multi-disciplinary effort to take the next big step to finding MS genes and correlate them with clinical findings, to find the cause of MS.
A major effort has been under way for over a decade to search for the genetic underpinnings of multiple sclerosis - the inherited set of genes that make people susceptible to developing the disease. If successful, it would give scientists a roadmap to the cause of MS, as well as concrete targets for new therapies and possibly even ways to prevent the disease.
But this painstaking search, involving analysis of the genome and the banking of thousands of DNA samples from patients and family members, has not yet borne fruit beyond a few possible "hot spots" on several areas of the ribbon-like chromosomes which require further exploration.
Harvard Medical School's Dr. David A. Hafler, an expert in MS and MS immunology, forged the collaboration with Dr. Eric Lander (MIT's Whitehead Institute), who spearheaded the recently completed mapping of the human genome, and Dr. Stephen Hauser (University of California at San Francisco), who has been developing MS family data and pioneered an MS DNA Bank. The team has just received the Palmer Collaborative MS Research Center Award: MS Targeted Haplotype Project to pool expertise and resources in attempts to speed work toward discovering MS genes.
The collaborators are taking a three-pronged approach to solving this problem, focusing on genetics, clinical aspects of disease and profiles of . immune activity. Dr. Lander, is turning his focus on multiple sclerosis as a test case for using a new approach called haplotype mapping to find multiple genes conferring susceptibility to a disease. Haplotype mapping involves identifying and mapping on chromosomes blocks of genes, called haplotypes, which are inherited together within individuals. This provides a new method for finding disease genes. His team is beginning a major, government-supported $20-million effort to map haplotypes across the entire human genome, and during the course of this effort, this Center Award will draw the team's attention to mapping haplotypes in chromosome regions of interest in MS.
Feeding into this genetics work will be a massive effort by Dr. Hafler's team to catalogue clinical information and profiles of immunological status of thousands of individuals with MS. Tying it all together will be databases developed by Dr. Hauser's team to link the genetics data with clinical findings and immunological profiles.
Using this new Collaborative MS Research Center award, the team will set the stage to search for MS genes and correlate these findings with clinical/immune aspects in an effort to speed the discovery of the underlying cause of the disease.
© 2005 BWH MS Genetics