Novel interferon regulatory factor-1 polymorphisms in a Kenyan population revealed by complete gene sequencing.
Variation in susceptibility to HIV-1 infection depends on numerous factors, and host genetic variation has been well-described as an important component. As a transcriptional regulator, interferon regulatory factor 1 (IRF-1) plays a key role in both innate and adaptive immunity against viral infection. IRF-1 has also been shown to directly interact with HIV-1 5' LTR and efficiently initiate or amplify HIV-1 replication. By complete gene sequencing, we investigated genetic polymorphism of the IRF-1 gene in an HIV-1-endemic Kenyan population. This population displayed extensive genetic diversity at the IRF-1 locus. Fifty-three single nucleotide polymorphisms (SNPs) were identified in this population, including 26 novel SNPs. Two insertion and one deletion polymorphisms in IRF-1 were also identified. Linkage disequilibrium (LD) among these genetic variations was shown to be common in IRF-1. The functional consequences of these mutations in the context of HIV-1/AIDS remain to be determined. We also identified 35 consistent discrepancies between IRF-1 GenBank sequences and our population based sequencing data, suggesting that the previously submitted GenBank data were not representative of the majority of human IRF-1 sequences.
Ji
Hezhao
H
Department of Medical Microbiology, University of Manitoba, Room 514, 730 William Avenue, Winnipeg, MB, Canada, R3E 0W3.
Ball
Terry Blake
TB
Department of Medical Microbiology, University of Manitoba, Room 514, 730 William Avenue, Winnipeg, MB, Canada, R3E 0W3.
Kimani
Joshua
J
Department of Microbiology, University of Nairobi, Nairobi, Kenya.
Plummer
Francis Allan
FA
Department of Medical Microbiology, University of Manitoba, Room 514, 730 William Avenue, Winnipeg, MB, Canada, R3E 0W3. plummerf@cc.umanitoba.ca.|National Microbiology Laboratory, Canadian Science Center for Human and Animal Health, Winnipeg, MB, Canada. plummerf@cc.umanitoba.ca.
D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007630:Kenya; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins