Year: 2010
Type: dissertation
Study design: Observational Study
Abstract: Genetic variation plays an important role in determining an individual’s \nsusceptibility to infectious disease. PSIP1 encodes LEDGF/p75, which stably \nassociates with the core domain of HIV-1 integrase via a highly-conserved \nintegrase binding domain (IBD) located in its C-terminal. Through this \ninteraction, the protein tethers HIV-1 IN to chromosomes at sites corresponding to \nregions of high LEDGF/p75-mediated transcription. Genetic variation within \nPSIP1 was identified and characterized in black South Africans to establish \nwhether variation in this influences an individual’s susceptibility to HIV infection. \nPCR assays were designed to amplify regions within the upstream non-coding \nregion, IBD and DNA-binding domains of the gene and selected polymorphisms \nwere then genotyped using allele-specific PCR, RFLP-PCR and \nPyrosequencing™ assays. Three insertion-deletion (indel) and eight single \nnucleotide polymorphisms (SNP) where identified through sequencing. Four of \nthe SNPs had been recorded previously, while the seven other polymorphisms had \nnot and appear to be unique to our population. Differences in allelic and genotypic \nfrequencies where found between the various ethnic groups represented in this \nstudy, which were reflected in the underlying haplotype structure within this gene, \nsuggesting that genetic substructure exists within the black South African \npopulation. Differences in allele and genotype frequencies were also seen between \nHIV+ individuals and the general population. Thus variation within PSIP1 may \ninfluence an individual’s susceptibility to HIV-1 infectivity and/or rate of disease progression.
Author: Nikki L. Gentle
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: National Research Foundation
OpenAlex ID: W2152812476