A vulnerability locus to multiple sclerosis maps to 7p15 in a region syntenic to an EAE locus in the rat.
Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system. Evidence from family studies indicates a strong genetic component. Despite many studies of candidate genes, only an association with the HLA-DRB1*1501-DQB1*0602 haplotype has been generally detected, and HLA linkage established by transmission disequilibrium testing. A genome-wide scan revealed suggestive linkage of MS with markers on chromosome 7p15 in HLA-DR15-nonsharing British families, in a region syntenic to a locus predisposing to experimental autoimmune encephalomyelitis in the rat. We therefore tested the 7p15 region as a candidate region for genetic susceptibility to MS in 104 French families with at least two affected siblings. We found evidence suggestive of a predisposing locus in families in which only one affected sibling or none of them carry the HLA-DR15 allele. Comparison of the results of the British and French groups suggests that the region of interest can be narrowed to a 2.45-cM interval.
Coppin
H
H
Unité de Physiopathologie Cellulaire et Moléculaire, Toulouse, France.
Ribouchon
M-T
MT
Fontaine
B
B
Edan
G
G
Clanet
M
M
Roth
M-P
MP
D000483:Alleles; D000818:Animals; D002875:Chromosomes; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D005260:Female; D005602:France; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009103:Multiple Sclerosis / Q000209:etiology / Q000235:genetics*; D051381:Rats; D006113:United Kingdom
D005819:Genetic Markers; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen