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Human Molecular Genetics, 2002, Vol. 11, No. 19 2251-2256
© 2002 Oxford University Press

Multiple susceptibility loci for multiple sclerosis

The Multiple Sclerosis Genetics Group, Jonathan L. Haines1,*, Yuki Bradford1, Melissa E. Garcia1, Allison D. Reed1, Elizabeth Neumeister1, Margaret A. Pericak-Vance2, Jacqueline B. Rimmler2, Marissa M. Menold2, Eden R. Martin2, Jorge R. Oksenberg3, Lisa F. Barcellos3, Robin Lincoln3 and Stephen L. Hauser3

1Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232, USA, 2Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA and 3Department of Neurology, University of California, San Francisco, CA 94143, USA

Received April 18, 2002; Accepted July 5, 2002

Multiple sclerosis (MS) is a common and frequently disabling autoimmune disorder mediated by autoaggressive T cells and autoantibodies that target central nervous system myelin. While numerous studies have demonstrated a strong genetic component to MS, it has been difficult to identify the specific genes involved. Several genomic screens have been undertaken to locate such genes, but have not provided consistent gene localization, except for the MHC on chromosome 6p21 and a locus on chromosome 19q13. To determine which of the original genomic locations presented in the US genome screen could be replicated, a more detailed analysis of additional families was performed. The results, derived from a population of 266 affected individuals belonging to 98 multiplex families, continue to support linkage to chromosomes 6p21, 6q27, and 19q13 with LOD scores>3.0, and suggest that regions on chromosomes 12q23–24 and 16p13 may also harbor susceptibility loci for MS. Analysis taking into account the known HLA-DR2 association identified two additional potential linkage regions on chromosomes 7q21–22 and 13q33–34. These regions can now be targeted for detailed study to identify the underlying MS susceptibility genes.

* To whom correspondence should be addressed at: Program in Human Genetics, 519 Light Hall, Vanderbilt University Medical Center, Nashville, TN 37232-0700, USA. Tel: +1 6153438555; Fax: +1 6153438619; Email: jonathan{at}phg.mc.vanderbilt.edu


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