Browsing by Author "van der Merwe, Lize"

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    Association analysis of two single-nucleotide polymorphisms of the RELN gene with autism in the South African population
    (Mary Ann Liebert, Inc., 2013) Sharma, Jyoti Rajan; Arieff, Zainunisha; Gameeldien, Hajirah; Davids, Muneera; Kaur, Mandeep; van der Merwe, Lize
    BACKGROUND: Autism (MIM209850) is a neurodevelopmental disorder characterized by a triad of impairments, namely impairment in social interaction, impaired communication skills, and restrictive and repetitive behavior. A number of family and twin studies have demonstrated that genetic factors play a pivotal role in the etiology of autistic disorder. Various reports of reduced levels of reelin protein in the brain and plasma in autistic patients highlighted the role of the reelin gene (RELN) in autism. There is no such published study on the South African (SA) population. AIMS: The aim of the present study was to find the genetic association of intronic rs736707 and exonic rs362691 (single-nucleotide polymorphisms [SNPs] of the RELN gene) with autism in a SA population. METHODS: Genomic DNA was isolated from cheek cell swabs from autistic (136) as well as control (208) subjects. The TaqMan® Real-Time polymerase chain reaction and genotyping assay was utilized to determine the genotypes. RESULTS: A significant association of SNP rs736707, but not for SNP rs362691, with autism in the SA population is observed. CONCLUSION: There might be a possible role of RELN in autism, especially for SA populations. The present study represents the first report on genetic association studies on the RELN gene in the SA population.
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    Association between pro-inflammatory alleles and allergic phenotypes in Xhosa adolescents
    (Wiley, 2018) Laurence, Craig; van der Merwe, Lize; Zhang, Guicheng; Le Souef, Peter; Levin, Michael
    BACKGROUND: Significant differences exist in the prevalence, spectrum, and severity of allergic diseases between developing and developed countries and between subpopulations within single countries. These discrepancies likely result from a complex interaction between genetic and environmental factors. However, the precise nature of the contribution of ethnicity to genetic differences in the predisposition to allergic disease is not yet fully understood. In particular, there is a paucity of literature regarding the genetic determinants of allergic disease in people of black African origin with little or no genetic admixture. OBJECTIVE: We aimed to analyze associations between 27 single nucleotide polymorphisms (SNPs) and allergy phenotypes in the local Xhosa population. METHODS: A convenience sample of 213 Xhosa teenagers was enrolled at a local high school. Phenotypic data were collected in the form of a symptom questionnaire, skin prick tests for common food and aeroallergens, total serum IgE, and IgE to Ascaris lumbricoides. In addition, genotyping was performed to establish the prevalence of putative pro-inflammatory alleles. RESULTS: We demonstrated several significant associations between polymorphisms and allergy phenotypes. In particular, 2 polymorphisms in the IL-10 gene (IL10 -592A> C and IL10 -1082A> G) and 1 in the IL-4 gene (IL4 -589C> T) showed multiple associations with allergic sensitization and asthma phenotypes. Other polymorphisms, across a multitude of genes with discrepant functions, showed less consistent associations. CONCLUSION: This study represents an important first step in genotype/phenotype association in this population. Further research is required to confirm or refute our findings.
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    Associations between human leukocyte antigen class I variants and the Mycobacterium tuberculosis subtypes causing disease
    (Oxford University Press, 2013) Salie, Muneeb; van der Merwe, Lize; Möller, Marlo; Daya, Michelle; van der Spuy, Gian D.; van Helden, Paul D.; Martin, Maureen P.; Gao, Xiao-jiang; Warren, Robin M.; Carrington, Mary; Hoal, Eileen G.
    BACKGROUND. The development of active tuberculosis disease has been shown to be multifactorial. Interactions between host and bacterial genotype may influence disease outcome, with some studies indicating the adaptation of M. tuberculosis strains to specific human populations. Here we investigate the role of the human leukocyte antigen (HLA) class I genes in this biological process. METHODS. Three hundred patients with tuberculosis from South Africa were typed for their HLA class I alleles by direct sequencing. Mycobacterium tuberculosis genotype classification was done by IS6110 restriction fragment length polymorphism genotyping and spoligotyping. RESULTS. We showed that Beijing strain occurred more frequently in individuals with multiple disease episodes (P < .001) with the HLA-B27 allele lowering the odds of having an additional episode (odds ratio, 0.21; P = .006). Associations were also identified for specific HLA types and disease caused by the Beijing, LAM, LCC, and Quebec strains. HLA types were also associated with disease caused by strains from the Euro-American or East Asian lineages, and the frequencies of these alleles in their sympatric human populations identified potential coevolutionary events between host and pathogen. CONCLUSIONS. This is the first report of the association of human HLA types and M. tuberculosis strain genotype, highlighting that both host and pathogen genetics need to be taken into consideration when studying tuberculosis disease development.
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    BDNF Val66Met and DRD2 Taq1A polymorphisms interact to influence PTSD symptom severity: A preliminary investigation in a South African population
    (Elsevier, 2013) Hemmings, Sian M.J.; Martin, Lindi I.; Klopper, Marisa; van der Merwe, Lize; Aitken, Lisa; de Wit, Erika; Black, Gillian F.; Hoal, Eileen G.; Walzl, Gerhard; Seedat, Soraya
    BACKGROUND: We evaluated the role that selected variants in serotonin transporter (5-HTT), dopamine receptor 2 (DRD2) and brain-derived neurotrophic factor (BDNF) genes play in PTSD symptom severity in an at-risk population. We also investigated the interaction between the genetic variants to determine whether these variables and the interactions between the variables influenced the severity of PTSD symptoms. METHODS: PTSD symptoms were quantitatively assessed using the Davidson Trauma Scale (DTS) in 150 participants from an at-risk South African population. All participants were genotyped for the 5-HTTLPR, DRD2 Taq1A and BDNF Val66Met polymorphisms. Gene–gene interactions were investigated using various linear models. All analyses were adjusted for age, gender, major depressive disorder diagnosis, level of resilience, level of social support and alcohol dependence. RESULTS: A significant interaction effect between DRD2 Taq1A and BDNF Val66Met variants on DTS score was observed. On the background of the BDNF Val66Val genotype, DTS score increased significantly with the addition of a DRD2 Taq1A A1 allele. However, on the BDNF Met66 allele background, the addition of an A1 allele was found to reduce total DTS score. CONCLUSIONS: This study provides preliminary evidence for an epistatic interaction between BDNF Val66Met and DRD2 Taq1A polymorphisms on the severity of PTSD symptoms, where both too little and too much dopamine can result in increased PTSD symptom severity.
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    BDNF Val66Met modifies the risk of childhood trauma on obsessive-compulsive disorder
    (Elsevier, 2013) Hemmings, Sian Megan Joanna; Lochner, Christine; van der Merwe, Lize; Cath, Danielle C.; Seedat, Soraya; Stein, Dan J.
    Childhood trauma has been linked to the development of later psychopathology, including obsessive-compulsive disorder (OCD). Although evidence exists to suggest that genetic and environmental factors are involved in the aetiology of OCD, little attention has been paid to the interactions that exist between genes and environment. The aim of this study was to investigate gene-by-environment interactions between childhood trauma and the BDNF Val66Met variant in patients with OCD. Childhood trauma was assessed in 134 OCD patients and 188 controls using the Childhood Trauma Questionnaire (CTQ). Linear regression models were used for statistical analyses. Geneeenvironment interactions were estimated by including a combined genotype and CTQ score in the models as interaction terms. All analyses were adjusted for age, gender, CTQ minimisation-denial score and home language by including them in the logistic regression models as covariates. Childhood trauma, specifically emotional abuse and neglect, increased the odds of having OCD significantly (p < 0.001). Although no significant association was observed between BDNF Val66Met and the development of OCD, interaction analysis indicated that the BDNF Met-allele interacted with childhood emotional abuse to increase the risk of OCD significantly in a dose-dependent manner (p < 0.024). To our knowledge, this is one of the first studies to investigate geneeenvironment interactions in OCD, and the findings indicate the importance of collating genetic and environmental variables in future studies.
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    A Panel of Ancestry Informative Markers for the Complex Five-Way Admixed South African Coloured Population
    (PloS, 2013) Daya, Michelle; van der Merwe, Lize; Galal, Ushma; Möller, Marlo; Salie, Muneeb; Chimusa, Emile R.; Galanter, Joshua M.; van Helden, Paul D.; Henn, Brenna M.; Gignoux, Chris R.; Hoal, Eileen G.
    Admixture is a well known confounder in genetic association studies. If genome-wide data is not available, as would be the case for candidate gene studies, ancestry informative markers (AIMs) are required in order to adjust for admixture. The predominant population group in the Western Cape, South Africa, is the admixed group known as the South African Coloured (SAC). A small set of AIMs that is optimized to distinguish between the five source populations of this population (African San, African non-San, European, South Asian, and East Asian) will enable researchers to cost-effectively reduce false-positive findings resulting from ignoring admixture in genetic association studies of the population. Using genome-wide data to find SNPs with large allele frequency differences between the source populations of the SAC, as quantified by Rosenberg et. al's -statistic, we developed a panel of AIMs by experimenting with various selection strategies. Subsets of different sizes were evaluated by measuring the correlation between ancestry proportions estimated by each AIM subset with ancestry proportions estimated using genome-wide data. We show that a panel of 96 AIMs can be used to assess ancestry proportions and to adjust for the confounding effect of the complex five-way admixture that occurred in the South African Coloured population.
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    Patient-Control Association Study of the Leucine-Rich Repeat Kinase 2 (LRRK2) Gene in South African Parkinson's Disease Patients
    (National Institute of Health, 2013) Bardien, Soraya; Blanckenberg, Janine; van der Merwe, Lize; Farrer, Matthew J.; Ross, Owen A.
    The leucine-rich repeat kinase 2 (LRRK2) gene is of interest to Parkinson's disease (PD) as it has been implicated in both familial and sporadic forms of the disorder.1 PD-susceptibility alleles in LRRK2 appear to be ethnic-specific with G2385R,2 R1628P3 and A419V4 identified in Asian populations, whereas M1646T is found in Caucasians.4 A haplotype protecting against development of PD is present in Chinese (N551K-R1398H)5 and Caucasians (N551K-R1398H-K1423K).4 Further studies are necessary to investigate the contribution of LRRK2 to PD-susceptibility in various populations worldwide.
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    The statistical theory underlying human genetic linkage analysis based on quantitative data from extended families
    (University of the Western Cape, 2010) Galal, Ushma; van der Merwe, Lize; Blignaut, Renette; Dept. of Statistics; Faculty of Science
    Traditionally in human genetic linkage analysis, extended families were only used in the analysis of dichotomous traits, such as Disease/No Disease. For quantitative traits, analyses initially focused on data from family trios (for example, mother, father, and child) or sib-pairs. Recently however, there have been two very important developments in genetics: It became clear that if the disease status of several generations of a family is known and their genetic information is obtained, researchers can pinpoint which pieces of genetic material are linked to the disease or trait. It also became evident that if a trait is quantitative (numerical), as blood pressure or viral loads are, rather than dichotomous, one has much more power for the same sample size. This led to the development of statistical mixed models which could incorporate all the features of the data, including the degree of relationship between each pair of family members. This is necessary because a parent-child pair definitely shares half their genetic material, whereas a pair of cousins share, on average, only an eighth. The statistical methods involved here have however been developed by geneticists, for their specific studies, so there does not seem to be a unified and general description of the theory underlying the methods. The aim of this dissertation is to explain in a unified and statistically comprehensive manner, the theory involved in the analysis of quantitative trait genetic data from extended families. The focus is on linkage analysis: what it is and what it aims to do. There is a step-by-step build up to it, starting with an introduction to genetic epidemiology. This includes an explanation of the relevant genetic terminology. There is also an application section where an appropriate human genetic family dataset is analysed, illustrating the methods explained in the theory sections.