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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Novel alleles at the lymphotoxin alpha (LTα) locus mark extended HLA haplotypes in native Africans
Human Immunology, Volume 62, No. 3, Year 2001
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Description
Genetic variations at the closely related tumor necrosis factor alpha (TNFα or TNF) and lymphotoxin alpha (LTα, formerly TNFβ) loci have been well documented in various human populations, and several haplotypes spanning the MHC class I and class II loci are known to carry specific TNF alleles. Genotyping of the TNFc microsatellite within the first intron of LTα in 285 Rwandans and 319 Zambians revealed two predominant alleles, c1 at frequencies of 0.598 and 0.683 and c2 at 0.384 and 0.307, respectively. Overall, the distribution of TNFc genotypes containing the major alleles conformed well to the Hardy-Weinberg equilibrium in both cohorts. Two previously unrecognized minor TNFc alleles were also detected: the first, designated c0, was found in 10 native Africans and was the only allele present in 10 chimpanzees; the second, designated c3, was seen in 6 other African patients. Further genotyping at loci for HLA class I, class II, and for transporters associated with antigen processing, subunit 1 (TAP1) in those 16 individuals suggested a tight, stable extended haplotype involving c0 and 26Asn (LTα)-TNF3 (TNF promoter -238A and -308G)-DRB1*1503-DQB1*0602-TAP1.2 (333Val)-TAP1.4 (637Gly). The c3 allele was observed on another extended haplotype with 26Thr (LTα)-TNF1 (TNF promoter -238G and -308G)-DQB1*0102-DQB1*0501-TAP1*0101 (333Ile and 637Asp). The c3-tagged haplotype further extended to Cw*15 at the HLA class I C locus, but no specific A or B alleles could be unambiguously assigned. Positive associations between c2 homozygosity and HIV-1 seronegative status in both Rwandans and Zambians (odds ratio = 2.03 and 2.00, p = 0.04 and 0.07, respectively) had little effect on the haplotype assignments. These findings suggest a preferential expansion of the human TNFc dinucleotide (CT/AG) repeat sequence and further imply the existence of two extended MHC lineages that have not been disrupted by recombinations. © American Society for Histocompatibility and Immunogenetics, 2001.
Authors & Co-Authors
Tang, Jianming
United States, Birmingham
The University of Alabama at Birmingham
Myracle, Angela D.
United States, Birmingham
The University of Alabama at Birmingham
Allen, Susan A.
United States, Birmingham
The University of Alabama at Birmingham
Karita, Etienne
Rwanda, Kigali
National Aids Control Program Rwanda
Musonda, Rosemary Mubanga
Zambia
Tropical Diseases Research Center
Fultz, Patricia N.
United States, Birmingham
The University of Alabama at Birmingham
Kaslow, Richard A.
United States, Birmingham
The University of Alabama at Birmingham
Statistics
Citations: 7
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1016/S0198-8859(00)00252-4
ISSN:
01988859
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study
Case-Control Study