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Susceptibility to multiple sclerosis and the immunoglobulin heavy chain variable region
N W Wood1, S J Sawcer, H F Kellar-Wood
1University of Cambridge Neurology unit, Addenbrooke's Hospital, UK.
Journal of Neurology
|October 1, 1995
Summary
This study investigated the immunoglobulin heavy chain gene cluster
Area of Science:
- Genetics
- Immunology
- Neuroscience
Background:
- The immunoglobulin heavy chain gene cluster's role in multiple sclerosis (MS) susceptibility is not fully understood.
- Specific gene polymorphisms may influence MS risk.
Purpose of the Study:
- To investigate the association between VH-2 gene family haplotypes and multiple sclerosis (MS) susceptibility.
- To determine if linkage exists between the immunoglobulin heavy chain gene cluster and MS.
Main Methods:
- Examined a haplotype marker of three biallelic restriction fragment length polymorphism (RFLP) loci from the VH-2 gene family.
- Utilized the affected sibling pair method to assess evidence for linkage in 124 families with sibling pairs concordant for MS.
- Analyzed 178 unrelated MS patients and 159 unaffected controls.
Main Results:
- Observed a deviation from expected haplotype sharing probabilities in affected siblings (Z0=0.20, Z1=0.45, Z2=0.35).
- Provided evidence for weak linkage (P < 0.05) between the VH-2 loci and MS susceptibility.
- Found no significant allelic or haplotypic association with MS.
Conclusions:
- Linkage without population association suggests a susceptibility gene on chromosome 14q.
- The identified linkage is not attributed to the examined VH-2 polymorphisms.
- Further research is needed to identify the specific MS susceptibility gene.