Multiple sclerosis (MS)

Multiple sclerosis (MS) is a debilitating autoimmune and neurodegenerative disease affecting more than 400,000 individuals in the United States. In MS the immune system attacks the central nervous system leading to demylination of the nerves. Disease onset usually occurs in young adults, and it is more common in females. Almost any neurological symptom can appear with the disease, and often progresses to physical and cognitive disability. Although life span is only slightly shortened, most patients experience increasing disability and consequent deterioration in their quality of life.

Multiple sclerosis is caused by a complex interplay between several different genetic as well as environmental factors and has an increasing prevalence in populations residing at higher latitudes. The major histocompatibility complex (MHC) on chromosome 6 has been long associated with MS and both class1 and class II MHC susceptibility alleles exist. However, a recent genome-wide association study (GWAS) has identified non-MHC susceptibility loci with modest effects in MS. Two such loci include the Interleukins, IL2RA and IL7RA (which are common proteins involved in immune responses). Genetic evidence also indicates one allele of the vitamin D receptor (VDR) gene may be associated with MS susceptibility.

The Multiple Sclerosis Genetic Group (MSGG) is a collaborative effort between the members of The Hussman Institute for Human Genomics (HIHG) at the University of Miami, Vanderbilt University Medical Center, the University of California at San Francisco and UC Berkeley. In 1996, the MSGG completed one of the first genomic screens aimed at identifying the location of MS susceptibility regions. In two recent studies, the research team at (HIHG) led by Drs. Margaret Pericak-Vance and Jacob L. McCauley with external collaborators identified a MS susceptibility gene in interferon8 (IRF8) and several susceptibility genes in the tyrosine kinase 2 (TYK2) loci. The findings of the IRF8 study suggest that dysregulation of interferon responses may be one of the early events that contribute to the onset of MS. A single nucleotide polymorphism in the kinase domain of TYK2 gene detected from the TYK2 study implies dysregulation of the enzymatic pathway that may eventually affect protein functions in MS patients.

Thus, HIHG's continued efforts towards identification of MS susceptibility regions in different genes will help in developing better understanding of the genetic predisposition and better targeted therapies for the disease.

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