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A total of 267 families with two or more siblings with multiple sclerosis (MS) were genotyped with 14 restriction fragment length polymorphisms at the TCR ß locus. A nonparametric linkage analysis of the data showed no evidence for linkage to this locus (mlod=0.11). No significant allelic or haplotype transmissions were observed in the total sample of 565 patients. After stratification for the presence of HLA DRB1*15, an association was observed between the BV25S1*1-BV26S1*1-BV2S1*1 haplotype and MS (P=0.00089). This was not significant upon correction for multiple comparisons. It was also not significant when the haplotype frequency in affected individuals was compared to a normal control sample (P=0.77). Furthermore, the associated haplotype was followed-up in an independent sample of 97 nuclear families with a single DRB1*15-positive child with MS. The BV25S1*1-BV26S1*1-BV2S1*1 haplotype did not show significant evidence for transmission distortion but the same trend was seen (P=0.21). There were no significant associations observed in the DRB1*15-negative patients and no detectable difference was seen in the DRB1*15-positive BV25S1*1-BV26S1*1-BV2S1*1 association when comparing different subgroups based on clinical course of MS. These results show no evidence for linkage and fail to establish an association between MS susceptibility and the TCR ß locus.Genes and Immunity (2004) 5, 337-342. doi:10.1038/sj.gene.6364091 Published online 3 June 2004 [ABSTRACT FROM AUTHOR]

Two polymorphisms of the CTLA-4 gene were genotyped in 232 sibling pairs affected with multiple sclerosis (MS) from 185 families. The CTLA-4 polymorphisms genotyped were a 3' untranslated (AT)(n) microsatellite and an alanine/threonine RFLP of exon 1. There was no evidence observed for linkage by either identity-by-descent (ibd) or identity-by-state (ibs) methods. A transmission disequilibrium test (TDT) was performed and no preferential transmission of alleles was observed. Upon stratification of patients, there was no preferential transmission observed based upon gender, by presence or absence of HLA*DRB1*15, by ethnicity or by clinical course of the disease. CTLA-4 does not appear to be a major MS susceptibility locus in Canadian multiplex families.