Dataset Information

Description of two new HLA-C alleles in a black South African population.

ABSTRACT: Two new HLA-C alleles, Cw*0333 and Cw*0217, were identified in a Black South African population. HLA-Cw*0333 differs from Cw*030201 by an A-->G substitution at nucleotide 323, yielding an unusual missense substitution of Cys for the conserved Tyr-84 at the antigen cleft terminus. Molecular modeling suggests that this alters the predicted interactions of this critical residue with the opposite alpha(2)-helix, the peptide COOH terminus and possibly KIR2DL2. The second allele, Cw*0217, differs from Cw*0205 by an A-->T substitution at nucleotide 368, resulting in a Tyr-->Phe substitution at residue 99 of the HLA-C beta-pleated sheet that likely influences peptide side-chain binding. Both Cw*0333 and Cw*0217 appear to have arisen by missense mutations, respectively, from the HLA-B*5801-Cw*0302 and B*080101-Cw*0205 haplotypes.

SUBMITTER: Minevich G

PROVIDER: S-EPMC2364731 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Description of two new HLA-C alleles in a black South African population.

Minevich G G Kuhn L L Polistena C C Nuara J J Winchester R R

Tissue antigens 20071029 1

Two new HLA-C alleles, Cw*0333 and Cw*0217, were identified in a Black South African population. HLA-Cw*0333 differs from Cw*030201 by an A-->G substitution at nucleotide 323, yielding an unusual missense substitution of Cys for the conserved Tyr-84 at the antigen cleft terminus. Molecular modeling suggests that this alters the predicted interactions of this critical residue with the opposite alpha(2)-helix, the peptide COOH terminus and possibly KIR2DL2. The second allele, Cw*0217, differs from ...[more]

PMID: 17971053

Similar Datasets

Project description:Spinal muscular atrophy (SMA) is a neuromuscular disorder, characterized by muscle atrophy and impaired mobility. A homozygous deletion of survival motor neuron 1 (SMN1), exon 7 is the main cause of SMA in ~94% of patients worldwide, but only accounts for 51% of South African (SA) black patients. SMN1 and its highly homologous centromeric copy, survival motor neuron 2 (SMN2), are located in a complex duplicated region. Unusual copy number variations (CNVs) have been reported in black patients, suggesting the presence of complex pathogenic rearrangements. The aim of this study was to further investigate the genetic cause of SMA in the black SA population. Multiplex ligation-dependent probe amplification (MLPA) testing was performed on 197 unrelated black patients referred for SMA testing (75 with a homozygous deletion of SMN1, exon 7; 50 with a homozygous deletion of SMN2, exon 7; and 72 clinically suggestive patients with no homozygous deletions). Furthermore, 122 black negative controls were tested. For comparison, 68 white individuals (30 with a homozygous deletion of SMN1, exon 7; 8 with a homozygous deletion of SMN2, exon 7 and 30 negative controls) were tested. Multiple copies (>2) of SMN1, exon 7 were observed in 50.8% (62/122) of black negative controls which could mask heterozygous SMN1 deletions and potential pathogenic CNVs. MLPA is not a reliable technique for detecting carriers in the black SA population. Large deletions extending into the rest of SMN1 and neighboring genes were more frequently observed in black patients with homozygous SMN1, exon 7 deletions when compared to white patients. Homozygous SMN2, exon 7 deletions were commonly observed in black individuals. No clear pathogenic CNVs were identified in black patients but discordant copy numbers of exons suggest complex rearrangements, which may potentially interrupt the SMN1 gene. Only 8.3% (6/72) of clinically suggestive patients had heterozygous deletions of SMN1, exon 7 (1:0) which is lower than previous SA reports of 69.5%. This study emphasizes the lack of understanding of the architecture of the SMN region as well as the cause of SMA in the black SA population. These factors need to be taken into account when counseling and performing diagnostic testing in black populations.

Project description:BackgroundDNA methylation is associated with non-communicable diseases (NCDs) and related traits. Methylation data on continental African ancestries are currently scarce, even though there are known genetic and epigenetic differences between ancestral groups and a high burden of NCDs in Africans. Furthermore, the degree to which current literature can be extrapolated to the understudied African populations, who have limited resources to conduct independent large-scale analysis, is not yet known. To this end, this study examines the reproducibility of previously published epigenome-wide association studies of DNA methylation conducted in different ethinicities, on factors related to NCDs, by replicating findings in 120 South African Batswana men aged 45 to 88 years. In addition, novel associations between methylation and NCD-related factors are investigated using the Illumina EPIC BeadChip.ResultsUp to 86% of previously identified epigenome-wide associations with NCD-related traits (alcohol consumption, smoking, body mass index, waist circumference, C-reactive protein, blood lipids and age) overlapped with those observed here and a further 13% were directionally consistent. Only 1% of the replicated associations presented with effects opposite to findings in other ancestral groups. The majority of these inconcistencies were associated with population-specific genomic variance. In addition, we identified eight new 450K array CpG associations not previously reported in other ancestries, and 11 novel EPIC CpG associations with alcohol consumption.ConclusionsThe successful replication of existing EWAS findings in this African population demonstrates that blood-based 450K EWAS findings from commonly investigated ancestries can largely be extrapolated to ethnicities for which epigenetic data are not yet available. Possible population-specific differences in 14% of the tested associations do, however, motivate the need to include a diversity of ethnic groups in future epigenetic research. The novel associations found with the enhanced coverage of the Illumina EPIC array support its usefulness to expand epigenetic literature.

Dataset Information

Description of two new HLA-C alleles in a black South African population.

Publications

Description of two new HLA-C alleles in a black South African population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets