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

Abstract

3p26.3, 3q21.1, 4q12, 6p25.3, 6q21, 9q34.3, 10p15, 11p15.5, 12q21.3, 16p13.3, 17q25.3,. Although none of these regions reaches the level of genome-wide significance, the number observed exceeds the 10 that would be expected by chance alone. Our results significantly add to the growing body of linkage data relating to multiple sclerosis.

A genome screen for linkage in Australian sibling-pairs with multiple sclerosis

“…A region identified in the present study on chromosome 1q43-44 was also seen in the Italian screen, 14 and linkage at 4q31, 5q31, 7q33-34 and 18p11 was additionally observed in the American screen. 10 Similarly, our potential linkage on chromosome 16p matches that observed in the Nordic 13 and American screen, 10 as well as in a meta-analysis of the original American, Canadian and British linkage screens. 18 Since Australian MS linkage screen M Ban et al 16p was not identified in the two screens in Southern European populations, 14,15 this observation emphasises that alternate combinations of genes may determine susceptibility to multiple sclerosis in different populations (allelic and locus heterogeneity).…”

“…16,17 As the number of observed peaks greatly exceeds that expected by chance at both MLSX0.7 and X1.8, it is likely that at least some of these regions harbour susceptibility genes. This interpretation is further supported by the fact that two of the four regions providing suggestive linkage have previously featured in multiple sclerosis genome screens: a regions close to chromosome 6q26 was observed in the UK, 9 American, 10 Nordic 13 and Italian 14 genome screens, whereas the suggestive linkage on chromosome Xp11 was previously reported in the UK screen. 9 Several of our regions of potential linkage also coincide with those suggested in previous multiple sclerosis genome screens.…”

“…To date seven whole genome screens for linkage have been completed in multiple sclerosis, five in Northern European [9][10][11][12][13] and two in Southern European populations. 14,15 None of these screens identified statistically unequivocal evidence for linkage but nearly all found more regions of potential linkage than would be expected to have occurred by chance alone.…”

Genome-wide TDT analysis in a localized population with a high prevalence of multiple sclerosis indicates the importance of a region on chromosome 14q

“…14 Furthermore, a Finnish group has narrowed down candidate region on chromosome 17q22-24 to 2.5 Mb, a distance quite affordable for candidate gene analysis with current molecular biology techniques. 15 The 2q23-31 region showed a lod score of B1.0 in the previous Nordic sib-pairs study 16 and was supported also in the Finnish study. 11 This region is at approximately 10 cM distant from the CTLA-4 gene, which, in previous studies from several groups, was reported to be associated with MS. [17][18][19] Figure 2 Haplotype-based TDT analysis results for chromosome 14.…”

Multiple sclerosis genetics

“…Furthermore, one of these studies was unable to detect a signal even from the MHC . Follow-up studies using multiply affected families also failed to detect any convincing new MS susceptibility loci (Kuokkanen et al, 1997;Coraddu et al, 2001;Akesson et al, 2002;Ban et al, 2002;Eraksoy et al, 2003). Adding more microsatellite markers to the initial genome screens also failed to produce new MS-associated genes Dyment et al, 2004b;Kenealy et al, 2004).…”