A Gambian TNF haplotype matches the European HLA-A1,B8,DR3 and Chinese HLA-A33,B58,DR3 haplotypes.
Caucasians carry TNFA-308*2 in the 8.1 ancestral haplotype (AH) (HLA-A1,B8,DR3). In Gambians, TNFA-308*2 occurs without HLA-B8 or -DR3, suggesting an independent effect of TNFA-308 on disease. Hence we sought a segment of the 8.1 AH in Gambians. BAT1 (intron 10)*2 was selected as a specific marker of the haplotype and was found with TNFA-308*2 in Gambians. Samples homozygous at TNFA-308 and BAT1 (intron 10) demonstrated identity between the African TNFA-308*2 haplotype, the 8.1AH and the Asian diabetogenic 58.1AH (HLA-A33,B58,DR3) across a region spanning BAT1, ATP6G, IKBL, LTA, TNFA, LTB, LST-1 and AIF-1. Conservation of this block in geographically distinct populations suggests a common evolutionary origin and challenges current views of the role of TNFA-308*2 in disease.
Price
P
P
School of Pathology and Surgery, University of Western Australia, Nedlands, Australia. pprice@cyllene.uwa.edu.au
Bolitho
P
P
Jaye
A
A
Glasson
M
M
Yindom
L-M
LM
Sirugo
G
G
Chase
D
D
McDermid
J
J
Whittle
H
H
D044466:Asian People / Q000235:genetics; D015415:Biomarkers; D002681:China; D005714:Gambia; D015788:HLA-A1 Antigen / Q000235:genetics* / Q000276:immunology; D015795:HLA-B8 Antigen / Q000235:genetics* / Q000276:immunology; D015803:HLA-DR3 Antigen / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007438:Introns; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D044465:White People / Q000235:genetics
D015415:Biomarkers; D015788:HLA-A1 Antigen; D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D014409:Tumor Necrosis Factor-alpha