Dataset Information

Genetic variability in markers of HLA-C expression in two diverse South African populations.

ABSTRACT: An insertion-deletion (indel) polymorphism within the 3' untranslated region (UTR) of HLA-C has been shown to be involved in the regulation of HLA-C expression. Individuals who carry a deletion at this position exhibit increased HLA-C expression, which associates with lower viral set point in HIV-1 infected individuals. This 263 indel (rs67384697) is reported to be in strong linkage disequilibrium (LD) with a single nucleotide polymorphism (SNP) 35 kilobases upstream of HLA-C (-35T/C; rs9264942) in Caucasian individuals, making this SNP a potential marker for both HLA-C expression and HIV-1 disease progression. We therefore examined genetic variation within the HLA-C 3' UTR of 265 Black and Caucasian South Africans by direct sequencing and identified haplotypes encompassing the 263 indel and another indel at position 230 in both populations. Concomitant evaluation of variability at the -35 SNP revealed this polymorphism to be an inappropriate marker for the 263 indel in these populations. These findings provide important insights into genetic variability within the regulatory regions of HLA-C that have potential implications for our understanding of the regulation of HLA-C expression and its impact on HIV-1 disease progression.

SUBMITTER: Gentle NL

PROVIDER: S-EPMC3702582 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic variability in markers of HLA-C expression in two diverse South African populations.

Gentle Nikki L NL Paximadis Maria M Puren Adrian A Tiemessen Caroline T CT

PloS one 20130705 7

An insertion-deletion (indel) polymorphism within the 3' untranslated region (UTR) of HLA-C has been shown to be involved in the regulation of HLA-C expression. Individuals who carry a deletion at this position exhibit increased HLA-C expression, which associates with lower viral set point in HIV-1 infected individuals. This 263 indel (rs67384697) is reported to be in strong linkage disequilibrium (LD) with a single nucleotide polymorphism (SNP) 35 kilobases upstream of HLA-C (-35T/C; rs9264942) ...[more]

PMID: 23861805

Similar Datasets

Project description:Objectives Reliable identification of population-specific variants is important for building the single nucleotide polymorphism (SNP) profile. In this study, genomic variation using allele frequency differences of pharmacologically important genes for Gujarati Indians in Houston (GIH) and Indian Telugu in the U.K. (ITU) from the 1000 Genomes Project vis-à-vis global population data was studied to understand its role in drug response. Methods Joint genotyping approach was used to derive variants of GIH and ITU independently. SNPs of both these populations with significant allele frequency variation (minor allele frequency ≥ 0.05) with super-populations from the 1000 Genomes Project and gnomAD based on Chi-square distribution with p-value of ≤ 0.05 and Bonferroni’s multiple adjustment tests were identified. Population stratification and fixation index analysis was carried out to understand genetic differentiation. Functional annotation of variants was carried out using SnpEff, VEP and CADD score. Results Population stratification of VIP genes revealed four clusters viz., single cluster of GIH and ITU, one cluster each of East Asian, European, African populations and Admixed American was found to be admixed. A total of 13 SNPs belonging to ten pharmacogenes were identified to have significant allele frequency variation in both GIH and ITU populations as compared to one or more super-populations. These SNPs belong to VKORC1 (rs17708472, rs2359612, rs8050894) involved in Vitamin K cycle, cytochrome P450 isoforms CYP2C9 (rs1057910), CYP2B6 (rs3211371), CYP2A2 (rs4646425) and CYP2A4 (rs4646440); ATP-binding cassette (ABC) transporter ABCB1 (rs12720067), DPYD1 (rs12119882, rs56160474) involved in pyrimidine metabolism, methyltransferase COMT (rs9332377) and transcriptional factor NR1I2 (rs6785049). SNPs rs1544410 (VDR), rs2725264 (ABCG2), rs5215 and rs5219 (KCNJ11) share high fixation index (≥ 0.5) with either EAS/AFR populations. Missense variants rs1057910 (CYP2C9), rs1801028 (DRD2) and rs1138272 (GSTP1), rs116855232 (NUDT15); intronic variants rs1131341 (NQO1) and rs115349832 (DPYD) are identified to be ‘deleterious’. Conclusions Analysis of SNPs pertaining to pharmacogenes in GIH and ITU populations using population structure, fixation index and allele frequency variation provides a premise for understanding the role of genetic diversity in drug response in Asian Indians.

Dataset Information

Genetic variability in markers of HLA-C expression in two diverse South African populations.

Publications

Genetic variability in markers of HLA-C expression in two diverse South African populations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets