Novel sequence feature variant type analysis of the HLA genetic association in systemic sclerosis.
Document Type
Article
Publication Date
2010
Keywords
HLA-Antigens, HLA-DR-Antigens, Humans, Molecular-Conformation, Scleroderma-Systemic
First Page
707
Last Page
719
JAX Source
Hum Mol Genet 2010 Feb; 19(4):707-19.
Abstract
We describe a novel approach to genetic association analyses with proteins sub-divided into biologically relevant smaller sequence features (SFs), and their variant types (VTs). SFVT analyses are particularly informative for study of highly polymorphic proteins such as the human leukocyte antigen (HLA), given the nature of its genetic variation: the high level of polymorphism, the pattern of amino acid variability, and that most HLA variation occurs at functionally important sites, as well as its known role in organ transplant rejection, autoimmune disease development and response to infection. Further, combinations of variable amino acid sites shared by several HLA alleles (shared epitopes) are most likely better descriptors of the actual causative genetic variants. In a cohort of systemic sclerosis patients/controls, SFVT analysis shows that a combination of SFs implicating specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk.
Recommended Citation
Karp DR,
Marthandan N,
Marsh SG,
Ahn C,
Diehl AD,
Feolo M,
Thomson G,
Waller MJ,
et a.
Novel sequence feature variant type analysis of the HLA genetic association in systemic sclerosis. Hum Mol Genet 2010 Feb; 19(4):707-19.