Brown JJ, Ollier WER, Thomson W, Matthews J, Carter S, Binns M, Pinchbeck G, Clegg
Tissue Antigens. 2006;67( 5):377-82.
Tumour necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine that plays
a crucial role in the regulation of inflammatory and immune responses. In all vertebrate
species the genes encoding TNF-alpha are located within the major histocompatability
complex. In the horse TNF-alpha has been ascribed a role in a variety of important
disease processes. Previously two single nucleotide polymorphisms (SNPs) have been
reported within the 5' un-translated region of the equine TNF-alpha gene. We have
examined the equine TNF-alpha promoter region further for additional SNPs by analysing
DNA from 131 horses (Equus caballus), 19 donkeys (E. asinus), 2 Grant's zebras (E.
burchellii boehmi) and one onager (E. hemionus). Two further SNPs were identified
at nucleotide positions 24 (T/G) and 452 (T/C) relative to the first nucleotide of
the 522 bp polymerase chain reaction product. A sequence variant at position 51 was
observed between equidae. SNaPSHOTtrade mark genotyping assays for these and the two
previously reported SNPs were performed on 457 horses comprising seven different breeds
and 23 donkeys to determine the gene frequencies. SNP frequencies varied considerably
between different horse breeds and also between the equine species. In total, nine
different TNF-alpha promoter SNP haplotypes and their frequencies were established
amongst the various equidae examined, with some haplotypes being found only in horses
and others only in donkeys or zebras. The haplotype frequencies observed varied greatly
between different horse breeds. Such haplotypes may relate to levels of TNF-alpha
production and disease susceptibility and further investigation is required to identify
associations between particular haplotypes and altered risk of disease.