Linkage analysis in multiple sclerosis of chromosomal regions syntenic to experimental autoimmune disease loci

Multiple sclerosis is a demyelinating disorder of the central nervous syste m with a putative autoimmune aetiology in which several genes are thought t o be involved. Four published genomic screens have confirmed that a gene in fluencing MS resides within or close to the HLA class II region in 6p21. St ill, this locus is likely to confer only a part of the genetic susceptibili ty in MS. Further, all four studies identified a number of other regions wi th possible linkage. We have investigated eight chromosomal intervals synte nic to loci of importance for experimental autoimmune model diseases in the rat in 74 Swedish MS families. Possible linkage (a non-parametric linkage NPL score of 1.16 by GENEHUNTER computer package) was observed with markers in 12p13.3, a region syntenic to the rat Oia2 locus which is importance fo r oil induced arthritis (OIA). Four markers in the T cell receptor beta cha in gene region in 7q35 showed possible linkage (highest NPL score of 1.16). This locus is syntenic to the rat Cia3 locus (collagen induced arthritis). These two loci at least partially overlap with chromosomal regions showing indicative evidence for linkage in the previous MS genomic screens. Indeed , both Oia2 and Cia3 were recently found to be linked also with experimenta l autoimmune encephalomyelitis, a commonly used model for MS. Markers in 2p 12, 3p25, 10q11.23, 17q21-25, 19q13.1, and 22q12-13 failed to provide evide nce for linkage. We conclude that evidence is amounting that 12p13-12 and 7 q34-36 may harbour genes with an importance for MS. The synteny with experi mental loci may eventually facilitate their identification.