TY - JOUR
T1 - Genetic variation at the TNF-α promoter and malaria susceptibility in rhesus (Macaca mulatta) and long-tailed (Macaca fascicularis) macaques
AU - Flynn, Shannon
AU - Satkoski, Jessica
AU - Lerche, Nicholas
AU - Kanthaswamy, Sreetharan
AU - Smith, David Glenn
N1 - Funding Information:
The authors would like to thank Dr. Janet Foley for significant contributions to early drafts of this manuscript. Funding for this project was provided by the National Institutes of Health, grant numbers RR005090 and RR00169.
PY - 2009/9
Y1 - 2009/9
N2 - Polymorphisms within the promoter region of the TNF-α gene have been associated with altered expression of TNF-α and susceptibility to a variety of diseases in humans. Although macaques (Macaca spp.) are frequently used as models to study human diseases, little is known about the extent of genetic variation at the TNF-α locus and its consequences for disease susceptibility in these species. The TNF-α promoter region was sequenced in a sample of 40 macaques including five M. mulatta of Chinese and Indian ancestry and 35 M. fascicularis of Malaysian, Mauritian, Indonesian, and Philippine ancestry. These groups were chosen because they exhibit differences in their susceptibilities to severe malaria upon infection with Plasmodium parasites. Sequence analysis revealed a total of 14 single nucleotide polymorphisms (SNPs), five of which are newly described, and 20 unique haplotypes. In addition, the TFSEARCH program was used to investigate the potential of these polymorphisms to influence transcription factor binding. While both species exhibited a similarly high degree of genetic variability at the TNF-α promoter, AMOVA analysis and FST values indicated that most of the variation is shared between species and among populations. However, two of the most common haplotypes, describing 31.7% of the observed variation, and three potentially functional polymorphisms at positions -781, -535, and -10, were exclusive to M. fascicularis. Polymorphisms in the human ortholog of the TNF-α promoter which are known to be associated with malaria susceptibility in humans were not shared with macaques.
AB - Polymorphisms within the promoter region of the TNF-α gene have been associated with altered expression of TNF-α and susceptibility to a variety of diseases in humans. Although macaques (Macaca spp.) are frequently used as models to study human diseases, little is known about the extent of genetic variation at the TNF-α locus and its consequences for disease susceptibility in these species. The TNF-α promoter region was sequenced in a sample of 40 macaques including five M. mulatta of Chinese and Indian ancestry and 35 M. fascicularis of Malaysian, Mauritian, Indonesian, and Philippine ancestry. These groups were chosen because they exhibit differences in their susceptibilities to severe malaria upon infection with Plasmodium parasites. Sequence analysis revealed a total of 14 single nucleotide polymorphisms (SNPs), five of which are newly described, and 20 unique haplotypes. In addition, the TFSEARCH program was used to investigate the potential of these polymorphisms to influence transcription factor binding. While both species exhibited a similarly high degree of genetic variability at the TNF-α promoter, AMOVA analysis and FST values indicated that most of the variation is shared between species and among populations. However, two of the most common haplotypes, describing 31.7% of the observed variation, and three potentially functional polymorphisms at positions -781, -535, and -10, were exclusive to M. fascicularis. Polymorphisms in the human ortholog of the TNF-α promoter which are known to be associated with malaria susceptibility in humans were not shared with macaques.
KW - Macaques
KW - Malaria
KW - Polymorphisms
KW - Promoter
KW - Tumor necrosis factor-alpha
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U2 - 10.1016/j.meegid.2009.03.011
DO - 10.1016/j.meegid.2009.03.011
M3 - Article
C2 - 19570728
AN - SCOPUS:67651115796
SN - 1567-1348
VL - 9
SP - 769
EP - 777
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
IS - 5
ER -