Further localization of a multiple sclerosis susceptibility gene on chromosome 7q using a new T cell receptor beta-chain DNA polymorphism.
Multiple sclerosis (MS) has been associated with particular HLA haplotypes and has recently been reported to also be associated with the T cell receptor (TCR) beta-chain complex. We have tried to determine the source of the TCR-beta/MS association by exploiting the pattern of linkage disequilibrium within the TCR-beta complex. We describe a new DNA polymorphism with the TCR variable region gene segment V beta 15 which appears to localize between the constant region and V beta 11. When the distribution of V beta 11-V beta 15 haplotypes in MS patients was compared to healthy controls, the strength of the V beta 11-V beta 15 MS association (p = 0.107) was much less than the MS association with the adjacent V beta 8-V beta 11 haplotype (p = 0.0010). On the basis we exclude an MS susceptibility gene telomeric to V beta 11. The reported MS association with the TCR-beta gene complex therefore does not appear to be due to genes within the diversity, joining, or constant region but more likely involves a specific gene(s) within the variable region.
Charmley
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Division of Biology, California Institute of Technology, Pasadena 91125.
Beall
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Concannon
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Hood
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Gatti
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D000483:Alleles; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D005787:Gene Frequency; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta
D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta