Novel sequence feature variant type analysis of the HLA genetic association in systemic sclerosis

Human Molecular Genetics 19 (4):707-719 (2009)
  Copy   BIBTEX


Significant associations have been found between specific human leukocyte antigen (HLA) alleles and organ transplant rejection, autoimmune disease development, and the response to infection. Traditional searches for disease associations have conventionally measured risk associated with the presence of individual HLA alleles. However, given the high level of HLA polymorphism, the pattern of amino acid variability, and the fact that most of the HLA variation occurs at functionally important sites, it may be that a combination of variable amino acid sites shared by several alleles (shared epitopes) are better descriptors of the actual causative genetic variants. Here we describe a novel approach to genetic association analysis in which genes/proteins are broken down into smaller sequence features and then variant types defined for each feature, allowing for independent analysis of disease association with each sequence feature variant type. We have used this approach to analyze a cohort of systemic sclerosis patients and show that a sequence feature composed of specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk for systemic sclerosis.



External links

  • This entry has no external links. Add one.
Setup an account with your affiliations in order to access resources via your University's proxy server

Through your library

Similar books and articles

Flat Morley sequences.Ludomir Newelski - 1999 - Journal of Symbolic Logic 64 (3):1261-1279.
Flat Morley Sequences.Ludomir Newelski - 1999 - Journal of Symbolic Logic 64 (3):1261-1279.
Subversive Reflections on the Human Genome Project.Alex Rosenberg - 1994 - PSA: Proceedings of the Biennial Meeting of the Philosophy of Science Association 1994:329 - 335.
Genetic Nondiscrimination and Health Care as an Entitlement.B. M. Kious - 2010 - Journal of Medicine and Philosophy 35 (2):86-100.
Functional Labelling With Polysemous Verbs.Violeta Stojicic - 2008 - Facta Universitatis, Series: Linguistics and Literature 6 (1):27-34.


Added to PP

261 (#46,847)

6 months
32 (#39,834)

Historical graph of downloads
How can I increase my downloads?

Author's Profile

Barry Smith
State University of New York, Buffalo

Citations of this work

No citations found.

Add more citations

References found in this work

No references found.

Add more references