title: Novel interferon regulatory factor-1 polymorphisms in a Kenyan population revealed by complete gene sequencing.
abstract: 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.
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Room 514, 730 William Avenue, Winnipeg, MB, Canada, R3E 0W3.
authors.forename: Hezhao
authors.initials: H
authors.lastname: Ji
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Room 514, 730 William Avenue, Winnipeg, MB, Canada, R3E 0W3.
authors.forename: Terry Blake
authors.initials: TB
authors.lastname: Ball
authors.affiliation: Department of Microbiology, University of Nairobi, Nairobi, Kenya.
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.affiliation: 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.
authors.forename: Francis Allan
authors.initials: FA
authors.lastname: Plummer
mesh_terms: 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
chemical_list: D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins