No evidence for transmission disequilibrium between a new marker at the myelin basic protein locus and multiple sclerosis in French patients

Coppin, Hélène; Mt, Ribouchon; Bausero, Pedro; Pessac, Bernard; Fontaine, Bertrand; Sémana, G.; Clanet, M.; Mp, Roth

doi:10.1038/sj.gene.6363698

Cited by 3 publications

(1 citation statement)

References 33 publications

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“…A different intragenic dinucleotide marker (with two common alleles) was used in a recent French study, but no evidence for association was found. 35 In addition to our studies from Finland, an association has been found in a Canadian data set, in which the longest allelic forms of the whole STR were Figure 3 Location of the study centers. The subregion surrounding Seinäjoki represents the Southern Ostrobothnian area that was used to define the Bothnia families.…”

Section: Discussionmentioning

confidence: 99%

Linkage disequilibrium between the MBP tetranucleotide repeat and multiple sclerosis is restricted to a geographically defined subpopulation in Finland

et al. 2003

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We have previously found evidence for linkage as well as allelic and haplotype association between the myelin basic protein (MBP) gene and multiple sclerosis (MS). These findings have, however, not been reproduced in other populations. Here, we have analyzed association between MBP and MS in a new set of 349 Finnish triad families. Families with a parent born in the Southern Ostrobothnian region in western Finland (Bothnia families, n ¼ 98) were analyzed as a separate group since our previous studies included a high proportion of patients and families from this high-incidence region. Other families (n ¼ 251) were collected at five hospitals in southern, eastern, and northern Finland. The MBP short tandem repeat was genotyped, and haplotype patterns were verified by sequencing. In the Bothnia families, the previously detected associations with the 1.27 kb allele and haplotype 1.27-B10 were confirmed (P ¼ 0.01 and 0.02, respectively), whereas in the other families there was not even a trend toward association. These results demonstrate a geographic/genealogical restriction in the association between MS and the MBP short tandem repeat, highlight the importance of genealogical information in genetic studies of complex traits, and may provide an explanation why the association has not been found in many other populations.

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Section: Discussionmentioning

confidence: 99%

Linkage disequilibrium between the MBP tetranucleotide repeat and multiple sclerosis is restricted to a geographically defined subpopulation in Finland

et al. 2003

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References

2006

McAlpine's Multiple Sclerosis

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Genetics of Multiple Sclerosis

Giordano

D’Alfonso

Momigliano–Richiardi

2002

American Journal of PharmacoGenomics

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Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system caused by an interplay of environmental and genetic factors. The only genetic region that has been clearly demonstrated by linkage and association studies to contribute to MS genetic susceptibility is the human leukocyte antigen (HLA) system. The majority of HLA population studies in MS have focused on Caucasians of Northern European descent, where the predisposition to disease has been consistently associated with the class II DRB1*1501-DQA1*0102-DQB1*0602 haplotype. A positive association with DR4 was detected in Sardinians and in other Mediterranean populations. Moreover DR1, DR7, DR11 have been found to be protective in several populations. Systematic searches aimed at identifying non-HLA susceptibility genes were undertaken in several populations by means of linkage studies with microsatellite markers distributed across the whole genome. The conclusion of these studies was that there is no major MS locus, and genetic susceptibility to the disease is most likely explained by the presence of different genes each conferring a small contribution to the overall familial aggregation. The involvement of several candidate genes was tested by association studies, utilizing either a population-based (case control) or a family-based (transmission disequilibrium test) approach. Candidate genes were selected mainly on the basis of their involvement in the autoimmune pathogenesis and include immunorelevant molecules such as cytokines, cytokine receptors, immunoglobulin, T cell receptor subunits and myelin antigens. With the notable exception of HLA, association studies met only modest success. This failure may result from the small size of the tested samples and the small number of markers considered for each gene. New tools for large scale screening are needed to identify genetic determinants with a low phenotypic effect. Large collaborative studies are planned to screen several thousands of patients with MS with several thousands of genetic markers. The tests are increasingly based on the DNA pooling procedure.

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No evidence for transmission disequilibrium between a new marker at the myelin basic protein locus and multiple sclerosis in French patients

Cited by 3 publications

References 33 publications

Linkage disequilibrium between the MBP tetranucleotide repeat and multiple sclerosis is restricted to a geographically defined subpopulation in Finland

Linkage disequilibrium between the MBP tetranucleotide repeat and multiple sclerosis is restricted to a geographically defined subpopulation in Finland

References

Genetics of Multiple Sclerosis

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