Masters Degrees (Molecular Biology and Human Genetics)
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Browsing Masters Degrees (Molecular Biology and Human Genetics) by Author "Carelse Tofa, Kashefa"
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- ItemMolecular genetic analysis of the neurokinin B (TAC3) and neurokinin B receptor (TAC3) genes as candidates for pre-eclampsia(Stellenbosch : Stellenbosch University, 2004-12) Carelse Tofa, Kashefa; Hillermann, R.; Gebhardt, G. S.; Stellenbosch University. Faculty of Medicine & Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics.ENGLISH ABSTRACT: Hypertensive conditions of pregnancy, such as pre-eclampsia, are the principal direct cause of maternal morbidity and mortality and affect up to 10% of first pregnancies worldwide. The placenta is vital in the pathogenesis of pre-eclampsia since the condition only occurs in the presence of placental tissue and the only cure is delivery of the placenta and the fetus. It has been hypothesised that the placenta may be the source of a circulating factor(s), which transports freely in the maternal system, resulting in the multi-systemic and immunological responses that are characteristic of pre-eclampsia. Among the potential "circulating" candidates currently being investigated worldwide, is the tachykinin member, neurokinin B (NKB). The aim of this project was to use a novel approach and investigate the role of Neurokinin B in pre-eclampsia on a genetic level. This would be achieved by bioinformatie characterisation of the neurokinin B (TAC3) and neurokinin B receptor (TACR3) genes. Samples from thirty pre-eclampsia patients (of whom 10 also had abruptio placentae) and twenty control individuals were used for mutation detection analysis involving Multiphor gel electrophoresis and automated sequencing. Three sequence variants were identified in the TAC3 gene and include: (i) 5' UTR variant (-25 c-t); (ii) intronic variant IVS3-53 (t-g) and (iii) 3' UTR variant exon 7 (479, t-c). Only the -25 c-t variant had been reported before (SNP database). A further two variants were identified in the TACR3 gene: (i) exon 3 variant (nt 857, a-t) and (ii) 3' UTR variant, amplicon 5b (nt 1471, t-c), of which the latter had previously been reported in the SNP database. In the analysis of allele and genotype frequencies, only variant homozygosity for TAC3 -25 c-t could be associated with increased risk of pre-eclampsia (RR 3.33, p=0.03). Follow-up work will include extended genotyping in further stratified and larger patient cohorts and transfection studies to assess splicing potential and functional consequences of the mutant alleles. These data represent the first documented mutation screen of the TAC3 and TACR3 genes and report novel variants in patients with pre-eclampsia. This study contributes to the knowledge of neurokinin B as a circulatory molecule and confirms the heterogeneity of pre-eclampsia.