Browsing by Author "Warnich, Louise"
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- ItemChromosome 22q11 in a Xhosa schizophrenia population(Health and Medical Publishing Group (HMPG), 2012-03) Koen, Liezl; Niehaus, Dana J. H.; Wright, Galen; Warnich, Louise; De Jong, Greetje; Emsley, Robin A.; Mall, SumayaChromosome 22q11 aberrations substantially increase the risk for developing schizophrenia. Although micro-deletions in this region have been extensively investigated in different populations across the world, little is known of their prevalence in African subjects with schizophrenia. We screened 110 African Xhosa-speaking participants with schizophrenia for the presence of micro-deletions. As further verification for the presence or absence of 22q11 microdeletions, we screened 238 Xhosa schizophrenia patients and 240 healthy Xhosa individuals from a larger schizophrenia candidate 22q11 gene study using molecular analyses. Data from molecular and cytogenetic analyses confirmed the absence of 22q11 microdeletions in the Xhosa schizophrenia samples. Although the absence of chromosome 22q11 micro-deletions in this group of patients does not exclude the possibility that it may occur in Xhosa schizophrenia patients, we concluded an extremely low prevalence. Our findings suggest that unique susceptibility loci may be present in this group.
- ItemDie isolasie en karakterisering van mens genomiese DNA fragmente(Stellenbosch : Stellenbosch University, 1984) Warnich, Louise; Stellenbosch University. Faculty of . Dept. of .
- ItemIntroduction of the AmpliChip CYP450 Test to a South African cohort : a platform comparative prospective cohort study(BioMed Central, 2013-01) Dodgen, Tyren M.; Hochfeld, Warren E.; Fickl, Heidi; Asfaha, Sahle M.; Durandt, Chrisna; Rheeder, Paul; Drogemoller, Britt I.; Wright, Galen E. B.; Warnich, Louise; Labuschagne, Christiaan D. J.; Van Schalkwyk, Antoinette; Gaedigk, Andrea; Pepper, Michael S.Abstract Background Adverse drug reactions and lack of therapeutic efficacy associated with currently prescribed pharmacotherapeutics may be attributed, in part, to inter-individual variability in drug metabolism. Studies on the pharmacogenetics of Cytochrome P450 (CYP) enzymes offer insight into this variability. The objective of this study was to compare the AmpliChip CYP450 Test® (AmpliChip) to alternative genotyping platforms for phenotype prediction of CYP2C19 and CYP2D6 in a representative cohort of the South African population. Methods AmpliChip was used to screen for thirty-three CYP2D6 and three CYP2C19 alleles in two different cohorts. As a comparison cohort 2 was then genotyped using a CYP2D6 specific long range PCR with sequencing (CYP2D6 XL-PCR + Sequencing) platform and a PCR-RFLP platform for seven CYP2C19 alleles. Results Even though there was a low success rate for the AmpliChip, allele frequencies for both CYP2D6 and CYP2C19 were very similar between the two different cohorts. The CYP2D6 XL-PCR + Sequencing platform detected CYP2D6*5 more reliably and could correctly distinguish between CYP2D6*2 and *41 in the Black African individuals. Alleles not covered by the AmpliChip were identified and four novel CYP2D6 alleles were also detected. CYP2C19 PCR-RFLP identified CYP2C19*9,*15, *17 and *27 in the Black African individuals, with *2, *17 and *27 being relatively frequent in the cohort. Eliminating mismatches and identifying additional alleles will contribute to improving phenotype prediction for both enzymes. Phenotype prediction differed between platforms for both genes. Conclusion Comprehensive genotyping of CYP2D6 and CYP2C19 with the platforms used in this study, would be more appropriate than AmpliChip for phenotypic prediction in the South African population. Pharmacogenetically important novel alleles may remain undiscovered when using assays that are designed according to Caucasian specific variation, unless alternate strategies are utilised.
- ItemMolecular characterisation of a low-frequency mutation in exon 8 of the human low-density lipoprotein receptor gene(Health & Medical Publishing Group, 1989) Kotze, M. J.; Langenhoven, E.; Warnich, Louise; Marx, M. P.; Retief, A. E.The prevalence of familial hypercholesterolaemia (FH), an autosomal dominant disease characterised by raised low-density lipoprotein (LDL) cholesterol levels, is at least five times higher in the white Afrikaner population than in most other population groups in the world. A founder gene effect has been suggested to explain this abnormally high frequency. Detection of a polymorphic Stu I site in the 5' region of the LDL receptor gene and association of both restriction fragment length polymorphism alleles with FH in Afrikaners, indicated the existence of at least two founder members of the disease in this population. DNA from a hetero-allelic FH homozygote from this South African group has been analysed through genomic cloning and sequencing. The DNA polymorphic site is caused by a single guanine to adenine transition within exon 8 of the LDL receptor gene and can be used in the determination of haplotype-associated defects.
- ItemPharmacogenomic research in South Africa : lessons learned and future opportunities in the rainbow nation(Bentham Science, 2011-09) Warnich, Louise; Drogemoller, Britt I.; Pepper, Michael S.; Dandara, Collet; Wright, Galen E.B.ENGLISH ABSTRACT: South Africa, like many other developing countries, stands to benefit from novel diagnostics and drugs developed by pharmacogenomics guidance due to high prevalence of disease burden in the region. This includes both communicable (e.g., HIV/AIDS and tuberculosis) and non-communicable (e.g., diabetes and cardiovascular) diseases. For example, although only 0.7% of the world’s population lives in South Africa, the country carries 17% of the global HIV/AIDS burden and 5% of the global tuberculosis burden. Nobel Peace Prize Laureate Archbishop Emeritus Desmond Tutu has coined the term Rainbow Nation, referring to a land of wealth in its many diverse peoples and cultures. It is now timely and necessary to reflect on how best to approach new genomics biotechnologies in a manner that carefully considers the public health needs and extant disease burden in the region. The aim of this paper is to document and review the advances in pharmacogenomics in South Africa and importantly, to evaluate the direction that future research should take. Previous research has shown that the populations in South Africa exhibit unique allele frequencies and novel genetic variation in pharmacogenetically relevant genes, often differing from other African and global populations. The high level of genetic diversity, low linkage disequilibrium and the presence of rare variants in these populations question the feasibility of the use of current commercially available genotyping platforms, and may partially account for genotypephenotype discordance observed in past studies. However, the employment of high throughput technologies for genomic research, within the context of large clinical trials, combined with interdisciplinary studies and appropriate regulatory guidelines, should aid in acceleration of pharmacogenomic discoveries in high priority therapeutic areas in South Africa. Finally, we suggest that projects such as the H3Africa Initiative, the SAHGP and PGENI should play an integral role in the coordination of genomic research in South Africa, but also other African countries, by providing infrastructure and capital to local researchers, as well as providing aid in addressing the computational and statistical bottlenecks encountered at present.
- ItemThe potential role of regulatory genes (DNMT3A, HDAC5, and HDAC9) in antipsychotic treatment response in South African schizophrenia patients(Frontiers Media, 2019-10-07) O’Connell, Kevin Sean; McGregor, Nathaniel Wade; Emsley, Robin A.; Seedat, Soraya; Warnich, LouiseENGLISH ABSTRACT: Despite advances in pharmacogenetics, the majority of heritability for treatment response cannot be explained by common variation, suggesting that factors such as epigenetics may play a key role. Regulatory genes, such as those involved in DNA methylation and transcriptional repression, are therefore excellent candidates for investigating antipsychotic treatment response. This study explored the differential expression of regulatory genes between patients with schizophrenia (chronic and antipsychotic-naïve first-episode patients) and healthy controls in order to identify candidate genes for association with antipsychotic treatment response. Seven candidate differentially expressed genes were identified, and four variants within these genes were found to be significantly associated with treatment response (DNMT3A rs2304429, HDAC5 rs11079983, and HDAC9 rs1178119 and rs11764843). Further analyses revealed that two of these variants (rs2304429 and rs11079983) are predicted to alter the expression of specific genes (DNMT3A, ASB16, and ASB16-AS1) in brain regions previously implicated in schizophrenia and treatment response. These results may aid in the development of biomarkers for antipsychotic treatment response, as well as novel drug targets.
- ItemThe DNA sequence analysis of polymorphic markers for improved high resolution mapping of important gene loci(Stellenbosch : Stellenbosch University, 1993) Warnich, Louise; Stellenbosch University. Faculty of . Dept. of .
- ItemWhole-genome sequencing for an enhanced understanding of genetic variation among South Africans(Nature Research (part of Springer Nature), 2017) Choudhury, Ananyo; Ramsay, Michele; Hazelhurst, Scott; Aron, Shaun; Bardien, Soraya; Botha, Gerrit; Chimusa, Emile R.; Christoffels, Alan; Gamieldien, Junaid; Sefid-Dashti, Mahjoubeh J.; Joubert, Fourie; Meintjes, Ayton; Mulder, Nicola; Ramesar, Raj; Rees, Jasper; Scholtz, Kathrine; Sengupta, Dhriti; Soodyall, Himla; Venter, Philip; Warnich, Louise; Pepper, Michael S.ENGLISH ABSTRACT: The Southern African Human Genome Programme is a national initiative that aspires to unlock the unique genetic character of southern African populations for a better understanding of human genetic diversity. In this pilot study the Southern African Human Genome Programme characterizes the genomes of 24 individuals (8 Coloured and 16 black southeastern Bantu-speakers) using deep whole-genome sequencing. A total of ~16 million unique variants are identified. Despite the shallow time depth since divergence between the two main southeastern Bantu-speaking groups (Nguni and Sotho-Tswana), principal component analysis and structure analysis reveal significant (p < 10−6) differentiation, and FST analysis identifies regions with high divergence. The Coloured individuals show evidence of varying proportions of admixture with Khoesan, Bantu-speakers, Europeans, and populations from the Indian sub-continent. Whole-genome sequencing data reveal extensive genomic diversity, increasing our understanding of the complex and region-specific history of African populations and highlighting its potential impact on biomedical research and genetic susceptibility to disease.