Browsing by Author "Arieff, Zainunisha"

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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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    Defining the African green monkey (Chlorocebus Aethiops): expression behaviour of selected lipid metabolism genes in response to niacin
    (University of Western Cape, 2012) Chauke, Chesa Gift; Arieff, Zainunisha; Seier, Jürgen; Kaur, Mandeep
    In this century most major medical advances have resulted in part from research on animals and non-human primates such as the African green monkey and therefore often serve as a critical link between basic research and human clinical application. Due to its close evolutionary relationship to humans, the African green monkey is known to be an excellent and most sought after models for studies of human cardiovascular disease (CVD). While the human genome project and some others related to model organisms are very well advanced or even complete, little sequence information has been acquired for the African green monkey. Given the importance of this species in biomedical research generally and CVD specifically, and the fundamental significance of sequence data, it is critical that this paucity of genome information concerning this specific animal model be addressed in order to better define the molecular basis and to further understand the mechanism of cholesterol metabolism in this species which will also contribute immensely to primatology. There is a growing interest in the role of genetic polymorphisms in predicting susceptibility to disease and responsiveness to drug interventions. Since plasma lipid abnormalities are risk factors for coronary atherosclerosis, determination of these plasma lipid concentrations, especially for genes involved in lipid transport and metabolism may be influenced by genetic variations. In this study, the African green monkey was used as a model to evaluate the effect of niacin on plasma lipids and reverse cholesterol transport by examine gene expression and the influence of several polymorphisms found in genes that are involved in cholesterol metabolism in humans. A survey of genetic variation spanning ten prioritised “candidate” genes was conducted, all of which are known to produce proteins that play key roles in the reverse cholesterol pathway (RCT), and in the homeostatic regulation of blood lipid profiles related to cardiovascular health and disease. everse transcription polymerase chain reaction (RT-PCR) was used to evaluate mRNA expression of those “candidate” genes. Twenty two coincident singlenucleotide polymorphisms (cSNPs), reported to play a vital role in RCT, were genotyped within these genes. This study’s findings implicate a subset of six of the twenty two genetic variants, spanning five “candidate” genes. To assess possible involvement of these prioritised “candidate” genes and their polymorphisms, biochemical analyses of known risk factors of coronary artery disease such as HDL-C and LDL-C were conducted. Eight healthy African green monkeys were entered in this study of which four were treated with niacin at an escalating dosage. Their mean lipid-lowering response following drug therapy was analysed, compared to those with the same genotype in a control group. Niacin treatment was associated with a considerable reduction in LDL-Cholesterol, up-regulation of HDL synthesis, and increase of apo A-1 levels. Gene expression had minimal effect on niacin treatment, except CYP7A1 which was down-regulated at the same time when considerable change in HDL-C, LDL-C and apoA-1 levels was observed. The presence of CYP7A1:Asn233Ser polymorphism may have played a critical role in metabolising niacin and influencing the up-regulation of HDL-C synthesis in the African green monkey. Although cholesterol lowering alone may explain the anti-atherosclerotic effect of niacin on HDL-C, in this study, gene expression data also shed some light in supporting the hypothesis that genetic variants may influence the expression of genes involved in RCT, which may also have played a role in the anti-atherosclerotic effect of the drug.
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    Genetic variation of rana fuscigula in Southern Africa
    (University of the Western Cape, 1994) Arieff, Zainunisha; Channing, Alan
    Naturalists have long been engaged in describing and explaining diversity in the biological world. The discovery of the molecular basis of inheritance has led to rapid increase in the use of biological macromolecules in these investigations. Scientists now routinely investigate the DNA of a range of organisms. The elationships between taxa and the phylogeny of groups is determined by examining the differences and similarities between them. These differences are then appropriately analyzed. lt is important to understand the natural variation within a group, before the differences between groups can be established. This study aims to determine the molecular differences between individuals at the extreme edges of the distribution of a species. This will serve as a molecular baseline, from which other studies can proceed. The experimental species is the trog Rana fuscigula, which has a range restricted to southern Namibia and South Africa. lt was thus possible to collect material from the edge of the distribution assuming that maximum genetic difference would be found between individuals at the edge of the range