Linkage analysis of multiple sclerosis with candidate region markers in Sardinian and Continental Italian families

Previous genome screens in multiple sclerosis have shown some evidence of l inkage in scattered chromosomal regions. Although in no case the evidence o f each single study was compelling and although in general the linkage 'pea ks' of the different studies did not coincide, some regions can be consider ed likely candidates for the presence of MS risk genes because of the clust ering of MLS scores and homology with eae loci. We performed a linkage anal ysis of markers in these regions and of intragenic markers of some individu al candidate genes (HLA-DRB1, CTLA-4, IL9, APOE, BCL2, TNFR2). For the firs t time, Southern European populations were targeted, namely Continental Ita lians and Sardinians. A total of 69 multiplex families were typed for 67 ma rkers by a semi-automatic fluorescence-based assay. Results were analysed f or linkage by two non-parametric tests: GENEHUNTER and SimIBD. In general, the linkage scores obtained were low, confirming the conclusion that go gen e is playing a major role in the disease. However, some markers, in 2p11, 3 q21.1, 7p15.2 and 22q13.1. stood out as promising since they showed higher scores with one or the other test. This stimulates further association anal ysis of a large number of simplex families from the same populations.