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DNA length polymorphism 5′ to the myelin basic protein gene is associated with multiple sclerosis
Author(s) -
Boylan Kevin B.,
Takahashi Naoki,
Paty Donald W.,
Sadovnick Adele D.,
Diamond Marc,
Hood Leroy E.,
Prusiner Stanley B.
Publication year - 1990
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410270311
Subject(s) - allele , biology , genetics , restriction fragment length polymorphism , exon , gene , population , multiple sclerosis , myelin basic protein , microbiology and biotechnology , genomic dna , coding region , myelin , genotype , medicine , immunology , endocrinology , central nervous system , environmental health
A site of DNA polymorphism linked to the myelin basic protein gene, identified as restriction fragment length polymorphism, was analyzed in a population‐based study comparing patients with clinically definite multiple sclerosis (MS) and population‐matched control subjects. A 0.9‐kilobase (kb) genomic DNA fragment ( Eco G) encompassing the first exon of the human myelin basic protein gene, located on the long arm of chromosome 18, identified ten alleles arising from a region of DNA, 1.5 kb 5′ to the myelin basic protein gene first exon coding region. Produced by Rsa I digests and ranging in length from 2.05 to 2.15 kb, these alleles vary in size by up to 100 base pairs due to insertion or deletion, or both, from a 1‐kb length of repetitive DNA. Allele frequencies among 65 patients with MS were compared with those of 63 control subjects. Chi square for these data was significant ( p <0.001), largely due to a preponderance in the patients with MS of alleles in the 2.14‐ to 2.15‐kb range. Comparison of the numbers of patients with MS and control subjects bearing specific alleles showed that 45% of the patients carried at least one allele of 2.14 to 2.15 kb as opposed to 19% of control subjects ( p <0.005). These data, while preliminary, suggest that patients with MS differ from population‐matched control subjects with respect to DNA polymorphism linked to the myelin basic protein gene. Although no pathogenic relationship between this polymorphism and MS can be presupposed, this finding raises the possibility that the myelin basic protein gene or some other myelin basic protein‐linked locus may be a factor in susceptibility to MS.