Virus restriction gene variants and their possible role in neurocognitive function in children born to HIV-infected mothers

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dc.contributor.advisorDandara, Colleten_ZA
dc.contributor.authorMhandire, Kudakwasheen_ZA
dc.date.accessioned2014-07-28T14:52:33Z
dc.date.available2014-07-28T14:52:33Z
dc.date.issued2012en_ZA
dc.descriptionIncludes abstract.
dc.descriptionIncludes bibliographical references.
dc.description.abstractHost genetic variation is an important determinant of HIV infection, disease progression and HIV-associated neurocognitive deficits. However, there is no sufficient knowledge on the role of genetic variants especially among African populations. This study is focused on investigating variation in HIV/AIDS restriction genes; CCR2, CX3CR1, SDF1, RANTES, APOBEC3G and MBL2 and their possible role in HIV infection and neurocognitive function among children born to HIV infected mothers, recruited in Harare, Zimbabwe. A total of 116 children comprising of 73 perinatally exposed to HIV (34 who were born infected and 39 who were uninfected) and 43 unexposed controls were recruited in 2011(at ages 7-9 years) from a cohort of mother-baby pairs that has been followed up since 2002. The demographic characteristics of the recruited children were captured from their medical records. A McCarthy Scale of Children‟s Abilities (MSCA) was administered to determine each child‟s neurocognitive status. Genotyping for allelic variants was done using PCR-RFLP, SNaPshot® and Sanger DNA sequencing. Statistical analysis was carried out to determine association between genotypes, HIV status and neurocognitive function. The observation of different genetic variants or combinations of genotypes between the HIV-exposed and infected group and that of the HIV-exposed but uninfected group may be a pointer to critical pathways in differential HIV susceptibility. Exposure and infection with HIV is controlled by a multitude of genes/processes, thus, SNPs are unlikely to show statistically significant effects individually and may be more useful in a multifactorial model, as observed from comparisons of genotype combinations and haplotypes. The role of host genetic variation on neurocognitive function remains disputed but our observations suggest innate immune factors such as MBL2 may have a pronounced effect. Therefore, it may be possible to genotype for a suite of genes and use them as markers of either HIV susceptibility or neuro-developmental patterns.en_ZA
dc.identifier.apacitationMhandire, K. (2012). <i>Virus restriction gene variants and their possible role in neurocognitive function in children born to HIV-infected mothers</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Human Genetics. Retrieved from http://hdl.handle.net/11427/3100en_ZA
dc.identifier.chicagocitationMhandire, Kudakwashe. <i>"Virus restriction gene variants and their possible role in neurocognitive function in children born to HIV-infected mothers."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Human Genetics, 2012. http://hdl.handle.net/11427/3100en_ZA
dc.identifier.citationMhandire, K. 2012. Virus restriction gene variants and their possible role in neurocognitive function in children born to HIV-infected mothers. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Mhandire, Kudakwashe AB - Host genetic variation is an important determinant of HIV infection, disease progression and HIV-associated neurocognitive deficits. However, there is no sufficient knowledge on the role of genetic variants especially among African populations. This study is focused on investigating variation in HIV/AIDS restriction genes; CCR2, CX3CR1, SDF1, RANTES, APOBEC3G and MBL2 and their possible role in HIV infection and neurocognitive function among children born to HIV infected mothers, recruited in Harare, Zimbabwe. A total of 116 children comprising of 73 perinatally exposed to HIV (34 who were born infected and 39 who were uninfected) and 43 unexposed controls were recruited in 2011(at ages 7-9 years) from a cohort of mother-baby pairs that has been followed up since 2002. The demographic characteristics of the recruited children were captured from their medical records. A McCarthy Scale of Children‟s Abilities (MSCA) was administered to determine each child‟s neurocognitive status. Genotyping for allelic variants was done using PCR-RFLP, SNaPshot® and Sanger DNA sequencing. Statistical analysis was carried out to determine association between genotypes, HIV status and neurocognitive function. The observation of different genetic variants or combinations of genotypes between the HIV-exposed and infected group and that of the HIV-exposed but uninfected group may be a pointer to critical pathways in differential HIV susceptibility. Exposure and infection with HIV is controlled by a multitude of genes/processes, thus, SNPs are unlikely to show statistically significant effects individually and may be more useful in a multifactorial model, as observed from comparisons of genotype combinations and haplotypes. The role of host genetic variation on neurocognitive function remains disputed but our observations suggest innate immune factors such as MBL2 may have a pronounced effect. Therefore, it may be possible to genotype for a suite of genes and use them as markers of either HIV susceptibility or neuro-developmental patterns. DA - 2012 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Virus restriction gene variants and their possible role in neurocognitive function in children born to HIV-infected mothers TI - Virus restriction gene variants and their possible role in neurocognitive function in children born to HIV-infected mothers UR - http://hdl.handle.net/11427/3100 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/3100
dc.identifier.vancouvercitationMhandire K. Virus restriction gene variants and their possible role in neurocognitive function in children born to HIV-infected mothers. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Human Genetics, 2012 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/3100en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Human Geneticsen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherHuman Geneticsen_ZA
dc.titleVirus restriction gene variants and their possible role in neurocognitive function in children born to HIV-infected mothersen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMMeden_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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