Sequence and Phylogenetic Analysis of the Untranslated Promoter Regions for HLA Class I Genes. J Immunol, pii: 1601679: (2017).

Publication Latest Publications

Title: Sequence and Phylogenetic Analysis of the Untranslated Promoter Regions for HLA Class I Genes
Authors: Ramsuran V, Hernandez-Sanchez PG, O'hUigin C, Sharma G, Spence N, Augusto DG, Gao X, Garcia-Sepulveda CA, Kaur G, Mehra NK, Carrington M,.
Journal: J Immunol,pii: 1601679: (2017)

Journal Impact Factor (I.F.): 4.92
Number of citations (Google Scholar): 3

Abstract

Polymorphisms located within the MHC have been linked to many disease outcomes by mechanisms not yet fully understood in most cases. Variants located within untranslated regions of HLA genes are involved in allele-specific expression and may therefore underlie some of these disease associations.

We determined sequences extending nearly 2 kb upstream of the transcription start site for 68 alleles from 57 major lineages of classical HLA class I genes. The nucleotide diversity within this promoter segment roughly follows that seen within the coding regions, with HLA-B showing the highest (?1.9%), followed by HLA-A (?1.8%), and HLA-C showing the lowest diversity (?0.9%). Despite its greater diversity, HLA-B mRNA expression levels determined in 178 European Americans do not vary in an allele- or lineage-specific manner, unlike the differential expression levels of HLA-A or HLA-C reported previously.

Close proximity of promoter sequences in phylogenetic trees is roughly reflected by similarity of expression pattern for most HLA-A and -C loci. Although promoter sequence divergence might impact promoter activity, we observed no clear link between the phylogenetic structures as represented by pairwise nucleotide differences in the promoter regions with estimated differences in mRNA expression levels for the classical class I loci. Further, no pair of class I loci showed coordinated expression levels, suggesting that distinct mechanisms across loci determine their expression level under nonstimulated conditions.

These data serve as a foundation for more in-depth analysis of the functional consequences of promoter region variation within the classical HLA class I loci.

Download: Full text paper

Citation: Ramsuran V, Hernandez-Sanchez PG, O'hUigin C, Sharma G, Spence N, Augusto DG, Gao X, Garcia-Sepulveda CA, Kaur G, Mehra NK, Carrington M,. Sequence and Phylogenetic Analysis of the Untranslated Promoter Regions for HLA Class I Genes J Immunol,pii: 1601679: (2017).


Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration
Journal: EBioMedicine (2017)

High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients
Journal: Clinical Infectious Diseases (2017)

Virological Outcomes of Second-line Protease Inhibitor-Based Treatment for Human Immunodeficiency Virus Type 1 in a High-Prevalence Rural South African Setting: A Competing-Risks Prospective Cohort Analysis
Journal: Clinical Infectious Diseases (2017)
All publications...


Page design updated by Tulio de Oliveira, 2013