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The T-cell receptor beta locus and susceptibility to multiple sclerosis
N W Wood1, S J Sawcer, H F Kellar-Wood
1University of Cambridge Neurology unit, Addenbrooke's Hospital, UK.
Neurology
|October 1, 1995
Summary
Genetic variations in the T-cell receptor (TCR) beta locus were studied in multiple sclerosis (MS) families. Linkage analysis showed weak evidence for TCR beta linkage, particularly in families with the HLA-DR15/DQ6 haplotype.
Area of Science:
- Human Genetics
- Immunology
- Neurology
Background:
- Conflicting results exist regarding the role of T-cell receptor (TCR) gene variations in multiple sclerosis (MS) etiology.
- The TCR beta locus on chromosome 7q32-35 is a candidate region for MS susceptibility genes.
Purpose of the Study:
- To investigate the potential linkage between the TCR beta locus and MS susceptibility in multiplex families.
- To examine if linkage is influenced by the presence of the HLA-DR15/DQ6 haplotype, a known MS risk factor.
Main Methods:
- Utilized affected sibling-pair analysis in multiplex MS families.
- Employed three restriction fragment length polymorphisms (RFLPs) and one microsatellite marker for the TCR beta locus.
- Stratified analyses based on concordance for the HLA-DR15/DQ6 haplotype.
Main Results:
- RFLP analysis across 127 families showed no evidence of linkage.
- Microsatellite analysis in 86 families provided weak evidence for linkage (LOD score 0.98, p < 0.05).
- Stratification by HLA-DR15/DQ6 concordance significantly altered haplotype sharing patterns for both RFLP and microsatellite markers (p < 0.05 and p < 0.01, respectively), suggesting a gene-environment interaction.
Conclusions:
- The TCR beta locus may play a minor role in MS susceptibility, potentially interacting with the HLA-DR15/DQ6 haplotype.
- Further investigation with larger sample sizes and denser marker coverage is warranted to confirm these findings.