Browsing by Author "Petersen, Desiree C."

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    African KhoeSan ancestry linked to high-risk prostate cancer
    (BMC (part of Springer Nature), 2019-06-04) Petersen, Desiree C.; Jaratlerdsiri, Weerachai; Van Wyk, Abraham; Chan, Eva K. F.; Fernandez, Pedro; Lyons, Ruth J.; Mutambirw, Shingai B. A.; Van der Merwe, Andre; Venter, Philip A.; Bates, William; Bornman, M. S. R.; Hayes, Vanessa M.
    Backgrounds: Genetic diversity is greatest within Africa, in particular the KhoeSan click-speaking peoples of southern Africa. South African populations represent admixture fractions including differing degrees of African, African-KhoeSan and non-African genetic ancestries. Within the United States, African ancestry has been linked to prostate cancer presentation and mortality. Together with environmental contributions, genetics is a significant risk factor for high-risk prostate cancer, defined by a pathological Gleason score ≥ 8. Methods: Using genotype array data merged with ancestry informative reference data, we investigate the contribution of African ancestral fractions to high-risk prostate cancer. Our study includes 152 South African men of African (Black) or African-admixed (Coloured) ancestries, in which 40% showed high-risk prostate cancer. Results: Genetic fractions were determined for averaging an equal African to non-African genetic ancestral contribution in the Coloured; we found African ancestry to be linked to high-risk prostate cancer (P-value = 0.0477). Adjusting for age, the associated African ancestral fraction was driven by a significant KhoeSan over Bantu contribution, defined by Gleason score ≥ 8 (P-value = 0.02329) or prostate specific antigen levels ≥20 ng/ml (Pvalue = 0.03713). Additionally, we observed the mean overall KhoeSan contribution to be increased in Black patients with high-risk (11.8%) over low-risk (10.9%) disease. Linking for the first time KhoeSan ancestry to a common modern disease, namely high-risk prostate cancer, we tested in this small study the validity of using KhoeSan ancestry as a surrogate for identifying potential high-risk prostate cancer risk loci. As such, we identified four loci within chromosomal regions 2p11.2, 3p14, 8q23 and 22q13.2 (P-value = all age-adjusted < 0.01), two of which have previously been associated with high-risk prostate cancer. Conclusions: Our study suggests that ancient KhoeSan ancestry may be linked to common modern diseases, specifically those of late onset and therefore unlikely to have undergone exclusive selective pressure. As such we show within a uniquely admixed South African population a link between KhoeSan ancestry and high-risk prostate cancer, which may explain the 2-fold increase in presentation in Black South Africans compared with African Americans.
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    Complex patterns of genomic admixture within Southern Africa
    (PLOS, 2013-03) Petersen, Desiree C.; Libiger, Ondrej; Tindall, Elizabeth A.; Hardie, Rae-Anne; Hannick, Linda I.; Glashoff, Richard H.; Mukerji, Mitali; Indian Genome Variation Consortium; Fernandez, Pedro; Haacke, Wilfrid; Schork, Nicholas J.; Hayes, Vanessa M.
    Within-population genetic diversity is greatest within Africa, while between-population genetic diversity is directly proportional to geographic distance. The most divergent contemporary human populations include the click-speaking forager peoples of southern Africa, broadly defined as Khoesan. Both intra- (Bantu expansion) and inter-continental migration (European-driven colonization) have resulted in complex patterns of admixture between ancient geographically isolated Khoesan and more recently diverged populations. Using gender-specific analysis and almost 1 million autosomal markers, we determine the significance of estimated ancestral contributions that have shaped five contemporary southern African populations in a cohort of 103 individuals. Limited by lack of available data for homogenous Khoesan representation, we identify the Ju/’hoan (n = 19) as a distinct early diverging human lineage with little to no significant non- Khoesan contribution. In contrast to the Ju/’hoan, we identify ancient signatures of Khoesan and Bantu unions resulting in significant Khoesan- and Bantu-derived contributions to the Southern Bantu amaXhosa (n = 15) and Khoesan !Xun (n = 14), respectively. Our data further suggests that contemporary !Xun represent distinct Khoesan prehistories. Khoesan assimilation with European settlement at the most southern tip of Africa resulted in significant ancestral Khoesan contributions to the Coloured (n = 25) and Baster (n = 30) populations. The latter populations were further impacted by 170 years of East Indian slave trade and intra-continental migrations resulting in a complex pattern of genetic variation (admixture). The populations of southern Africa provide a unique opportunity to investigate the genomic variability from some of the oldest human lineages to the implications of complex admixture patterns including ancient and recently diverged human lineages.
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    Effective Project Management of a Pan-African Cancer Research Network : Men of African Descent and Carcinoma of the Prostate (MADCaP)
    (American Society of Clinical Oncology, 2018) Odiaka, Emeka; Lounsbury, David W.; Adusei, Ben; Diallo, Thierno Amadou; Kane, Papa Moussa Sene; Rockson, Isabella; Okyne, Vicky; Irusen, Hayley; Pentz, Audrey; Makinde, Ifeoluwa; Ajibola, Olalekan Hafees; Petersen, Lindsay; McBride, Jo; Petersen, Desiree C.; Mante, Sunny; Agalliu, Ilir; Adebiyi, Akindele Olupelumi; Popoola, Olufemi; Yeboah, Edward; Mensah, James E.; Hsing, Ann; Fernandez, Pedro; Aisuodionoe- Shadrach, Oseremen; Joffe, Maureen; Singh, Elvira; Gueye, Serigne Magueye; Quintana, Yuri; Fortier, Brian; Rebbeck, Timothy R.; Andrews, Caroline
    Purpose Health research in low- and middle-income countries can generate novel scientific knowledge and improve clinical care, fostering population health improvements to prevent premature death. Project management is a critical part of the success of this research, applying knowledge, skills, tools, and techniques to accomplish required goals. Here, we describe the development and implementation of tools to support a multifaceted study of prostate cancer in Africa, focusing on building strategic and operational capacity. Methods Applying a learning organizational framework, we developed and implemented a project management toolkit (PMT) that includes a management process flowchart, a cyclical centerspecific schedule of activities, periodic reporting and communication, and center-specific monitoring and evaluation metrics. Results The PMT was successfully deployed during year one of the project with effective component implementation occurring through periodic cycles of dissemination and feedback to local center project managers. A specific evaluation was conducted 1 year after study initiation to obtain enrollment data, evaluate individual quality control management plans, and undertake risk log assessments and follow-up. Pilot data obtained identified areas in which centers required mentoring, strengthening, and capacity development. Strategies were implemented to improve project goals and operational capacity through local problem solving, conducting quality control checks and following compliancy with study aims. Moving forward, centers will perform quarterly evaluations and initiate strengthening measures as required. Conclusion The PMT has fostered the development of both strategic and operational capacity across project centers. Investment in project management resources is essential to ensuring high-quality, impactful health research in low- and middle-income countries.
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    Genetic aspects of HIV-1 risk in an African setting
    (Stellenbosch : Stellenbosch University, 2006-12) Petersen, Desiree C.; Hayes, Vanessa M.; Dean, Michael; Janse van Rensburg, Estrelita; Glashoff, Richard H.; Stellenbosch University. Faculty of Health Sciences. Dept. of Pathology. Medical Virology.
    Host susceptibility to human immunodeficiency virus-1 (HIV-1) infection and disease progression to acquired immunodeficiency syndrome (AIDS) varies widely amongst individuals. This observation led to the identification of host genetic factors playing a vital role in HIV-1 pathogenesis. Previous studies mainly focusing on Caucasian-based populations have indicated possible associations between genetic variants and host susceptibility to HIV-1/AIDS. The limited studies performed on African-based populations have emphasised the need for extensive investigation of both previously reported and particularly novel genetic variants within the older and genetically diverse Sub-Saharan African populations. In this study, the case-control samples were represented by African individuals of Xhosa descent, all residing in the Western Cape Province of South Africa. This included 257 HIV-1 seropositive patients and 110 population-matched HIV-1 seronegative controls. Mutational screening was performed in a subset of individuals for the entire coding regions of the CC chemokine receptor 5 (CCR5) and CC chemokine receptor 2 (CCR2) genes, and the 3’ untranslated region of the CXC chemokine ligand (CXCL12) gene, as previously reported (Petersen, 2002). Further analysis of these genes in a larger study sample involved the genotyping of previously identified mutations and single nucleotide polymorphisms (SNPs), which forms part of the present study. In addition, mutational screening was performed for the entire coding region of the CXC chemokine receptor 4 (CXCR4) gene, partial coding region of the mannose binding lectin (MBL) gene, and the promoter regions of interleukin 4 (IL4), interleukin 10 (IL10) and the solute carrier 11A1 (SLC11A1) genes. This was followed by genotyping of SNPs occurring in CCR5, CCR2, CXCL12, MBL, IL4, IL10, CX3C chemokine receptor 1 (CX3CR1), CC chemokine ligand 5 (CCL5) and tumour necrosis factor alpha (TNFα) genes. Significant associations were observed with HIV-1 susceptibility in the Xhosa population of South Africa. These included the CCR5-2733A>G, CX3CR1V249I, IL10-819C>T and IL10-592C>A SNPs being associated with a reduced risk for HIV-1 infection, while the CCR5-2135C>T and SDF1-3’G>A (CXCL12-3’G>A) SNPs were associated with increased susceptibility to HIV-1 infection. Furthermore, certain haplotypes for IL4 and IL10 showed association with reduced risk for HIV-1 infection. This included the identification of a novel IL4 haplotype restricted to the HIV-1 seronegative control group. This study emphasises the importance of considering genetic diversity across all populations, as certain HIV-1/AIDS associations appear to be restricted to specific ethnic groups. These findings have also provided an understanding for further elucidating the functional roles of genetic variants in determining HIV-1/AIDS susceptibility. Ultimately, such genetic association studies will contribute to establishing HIV-1/AIDS risk profiles for African-based populations from pandemic-stricken Sub-Saharan Africa.
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    The role of chemokine and chemokine receptor genes in genetic susceptibility to HIV infection in South Africa
    (Stellenbosch : Stellenbosch University, 2002-03) Petersen, Desiree C.; Hayes, Vanessa M.; Janse van Rensburg, Estrelita; Stellenbosch University. Faculty of Medicine & Health Sciences. Dept. of Pathology. Medical Virology.
    ENGLISH ABSTRACT: Please see fulltext for abstract