A genome screen for multiple sclerosis in Italian families

Abstract

We have screened the whole genome for linkage in 40 Italian multiplex families with multiple sclerosis using 322 markers. The GENEHUNTER-PLUS program was used to analyse these data and revealed eight regions of potential linkage where the lod score exceeds the nominal 5% significance level (0.7). No region of linkage with genome-wide significance was identified and none of the markers showed evidence of statistically significant transmission disequilibrium. Overall these results have refined the linkage data relating to this disease in Italians modestly supporting some previously identified areas of interest and helping to exclude others.

A genome-wide screen for linkage in Nordic sib-pairs with multiple sclerosis

“…27 This region has also shown suggestive and potential linkage respectively in recently published studies of sibpairs with multiple sclerosis from Sardinia 16 and Italy. 17 Another region of interest in this respect is 6q21 on the long arm of chromosome 6, where our results show a peak lod score of 1.2. This is the same region as another susceptibility locus in insulin dependent diabetes mellitus (IDDM15).…”

“…11 In multiple sclerosis, six whole genome screens for linkage have now been performed. [12][13][14][15][16][17] No one has shown unequivocal linkage, but most have identified more regions of potential linkage than expected by chance and together they provide the best available summary of the likely location of the relevant genes. 18 The high prevalence of multiple sclerosis (120/100 000) in Scandinavia 19 and the striking correlation between its global geographical distribution and the migration pattern of northern Europeans 20 suggest that important susceptibility alleles may have arisen in Scandinavia and been disseminated by their descendants-the so-called 'Viking hypothesis'.…”

Examination of seven candidate regions for multiple sclerosis: strong evidence of linkage to chromosome 1q44

“…2 Nearby markers have also demonstrated suggestive linkage and/or association in several other MS screens conducted in a variety of study populations. [4][5][6][7][8] There is also evidence for linkage to 1q43-44 in the autoimmune diseases rheumatoid arthritis [9][10][11] and systemic lupus erythematosus, [12][13][14][15] suggesting the potential presence of a gene for general autoimmune processes in this region. Interestingly, all of these markers demonstrating linkage in the MS, rheumatoid arthritis, and systemic lupus erythematosus screens are within 6 Mb of the peak marker from our genomic screen and follow-up.…”

Mapping candidate non-MHC susceptibility regions to multiple sclerosis

“…This region contains extensive clustering of markers associated in all populations, with the exception of the Southern and Eastern European populations of Hungary, Italy, Sardinia and Turkey, which did not show linkage or association in the region. 10,11,13,15 Associations seem to extend between markers D6S265 and TAP1. Each marker is associated in only a subgroup of populations indicating the presence of variations in LD patterns in the region.…”

“…1 Since then, whole genome linkage studies have been carried out in different populations including, American, 2,3 Australian, 4 British, 5,6 Canadian, 7,8 Finnish, 9 French, 2 Italian, 10 Sardinian, 11 Scandinavian 12 and Turkish. 13 These studies used low-density linkage mapping panels averaging 400 microsatellite markers at 10 Mb spacing.…”