An extension to a statistical approach for family based association studies provides insights into genetic risk factors for multiple sclerosis in the <it>HLA-DRB1 </it>gene
<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is a complex trait in which genes in the MHC class II region exert the single strongest effect on genetic susceptibility. The principal MHC class II haplotype that increases MS risk in individuals of Northern...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Book |
| Published: |
BMC,
2009-02-01T00:00:00Z.
|
| Subjects: | |
| Online Access: | Connect to this object online. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | <p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is a complex trait in which genes in the MHC class II region exert the single strongest effect on genetic susceptibility. The principal MHC class II haplotype that increases MS risk in individuals of Northern European descent are those that bear <it>HLA-DRB1*15</it>. However, several other <it>HLA-DRB1 </it>alleles have been positively and negatively associated with MS and each of the main allelotypes is composed of many sub-allelotypes with slightly different sequence composition. Given the role of this locus in antigen presentation it has been suggested that variations in the peptide binding site of the allele may underlie allelic variation in disease risk.</p> <p>Methods</p> <p>In an investigation of 7,333 individuals from 1,352 MS families, we assessed the nucleotide sequence of <it>HLA-DRB1 </it>for any effects on disease susceptibility extending a recently published method of statistical analysis for family-based association studies to the particular challenges of hyper-variable genetic regions.</p> <p>Results</p> <p>We found that amino acid 60 of the <it>HLA-DRB1 </it>peptide sequence, which had previously been postulated based on structural features, is unlikely to play a major role. Instead, empirical evidence based on sequence information suggests that MS susceptibility arises primarily from amino acid 13.</p> <p>Conclusion</p> <p>Identifying a single amino acid as a major risk factor provides major practical implications for risk and for the exploration of mechanisms, although the mechanism of amino acid 13 in the <it>HLA-DRB1 </it>sequence's involvement in MS as well as the identity of additional variants on MHC haplotypes that influence risk need to be uncovered.</p> |
|---|---|
| Item Description: | 10.1186/1471-2350-10-10 1471-2350 |