Psychiatric genetics in South Africa: cutting a rough diamond

Psychiatric disorders place a considerable healthcare burden on South African society. Incorporating genetic technologies into future treatment plans offers a potential mechanism to reduce this burden. This review focuses on psychiatric genetic research that has been performed in South African populations with regards to obsessive-compulsive disorder, schizophrenia and bipolar disorder. Preliminary findings from these studies suggest that data obtained in developed countries cannot necessarily be extrapolated to South African population groups. Psychiatric genetic studies in South Africa seem to involve relatively low-cost methodologies and only a limited number of large national collaborative studies. Future research in South Africa should therefore aim to incorporate highthroughput technologies into large scale psychiatric studies through the development of collaborations. On a global level, the vast majority of psychiatric genetic studies have been performed in non-African populations. South Africa, as the leading contributor to scientific research in Africa, may provide a foundation for addressing this disparity and strengthening psychiatric genetic research on the continent. Although the elucidation of the genetic architecture of psychiatric disorders has proved challenging, examining the unique genetic profiles found in South African populations could provide valuable insight into the genetics of psychiatric disorders.Keywords: Bipolar disorder; Obsessive-compulsive disorder; Pharmacogenetics; Psychiatric genetics; Schizophrenia; South African population

Identification of a novel functional deletion variant in the 5'-UTR of the DJ-1 gene

<p>Abstract</p> <p>Background</p> <p>DJ-1 forms part of the neuronal cellular defence mechanism against oxidative insults, due to its ability to undergo self-oxidation. Oxidative stress has been implicated in the pathogenesis of central nervous system damage in different neurodegenerative disorders including Alzheimer's disease and Parkinson's disease (PD). Various mutations in the <it>DJ-1 </it>(<it>PARK7</it>) gene have been shown to cause the autosomal recessive form of PD. In the present study South African PD patients were screened for mutations in <it>DJ-1 </it>and we aimed to investigate the functional significance of a novel 16 bp deletion variant identified in one patient.</p> <p>Methods</p> <p>The possible effect of the deletion on promoter activity was investigated using a Dual-Luciferase Reporter assay. The <it>DJ-1 </it>5'-UTR region containing the sequence flanking the 16 bp deletion was cloned into a pGL4.10-Basic luciferase-reporter vector and transfected into HEK293 and BE(2)-M17 neuroblastoma cells. Promoter activity under hydrogen peroxide-induced oxidative stress conditions was also investigated. Computational (<it>in silico</it>) <it>cis</it>-regulatory analysis of <it>DJ-1 </it>promoter sequence was performed using the transcription factor-binding site database, TRANSFAC via the PATCH™ and rVISTA platforms.</p> <p>Results</p> <p>A novel 16 bp deletion variant (g.-6_+10del) was identified in <it>DJ-1 </it>which spans the transcription start site and is situated 93 bp 3' from a Sp1 site. The deletion caused a reduction in luciferase activity of approximately 47% in HEK293 cells and 60% in BE(2)-M17 cells compared to the wild-type (<it>P </it>< 0.0001), indicating the importance of the 16 bp sequence in transcription regulation. The activity of both constructs was up-regulated during oxidative stress. Bioinformatic analysis revealed putative binding sites for three transcription factors AhR, ARNT, HIF-1 within the 16 bp sequence. The frequency of the g.-6_+10del variant was determined to be 0.7% in South African PD patients (2 heterozygotes in 148 individuals).</p> <p>Conclusion</p> <p>This is the first report of a functional <it>DJ-1 </it>promoter variant, which has the potential to influence transcript stability or translation efficiency. Further work is necessary to determine the extent to which the g.-6_+10del variant affects the normal function of the <it>DJ-1 </it>promoter and whether this variant confers a risk for PD.</p

Putting the treatment of paediatric schistosomiasis into context

Abstract Despite increased international efforts to control schistosomiasis using preventive chemotherapy, several challenges still exist in reaching the target populations. Until recently, preschool-aged children had been excluded from the recommended target population for mass drug administration, i.e. primary school children aged 6–15 years. Our studies and those of others provided the evidence base for the need to treat preschool-aged children that led to recommendations by the World Health Organization to include preschool-aged children in treatment programmes in 2010. The major challenge now lies in the unavailability of a child-size formulation of the appropriate anthelmintic drug, praziquantel. The currently available formulation of praziquantel presents several problems. First, it is a large tablet, making it difficult for young children and infants to swallow it and thus requires its breaking/crushing to allow for safe uptake. Second, it is bitter so it is often mixed with a sweetener to make it palatable for young children. Third, the current formulation of 600 mg does not allow for flexible dose adjustments for this age group. Thus, there is a need to formulate a child-appropriate praziquantel tablet. This paper discusses the target product profile for paediatric praziquantel, as well as knowledge gaps pertinent to the successful control of schistosome infection and disease in preschool-aged children

Sequence Analysis of the CYP3A4 Gene in the Xhosa Population

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Highly informative dinucleotide repeat polymorphism at the D11S29 locus on chromosome 11q23

The informativeness of locus D11S29 as a genetic marker was improved by the identification of a highly polymorphic (GT)(n) repeat within the locus. Ten alleles were identified in parents of 40 Centre d'Etude du Polymorphisme Humain families and the polymorphism information content (PIC) was 0.77. The increased PIC value thus enables refinement of the linkage map of 11q23.Articl

Morphological and molecular identification of economically important Tortricidae (Lepidoptera) on tropical and subtropical fruit in South Africa

Three tortricid species are of major economic importance to the South African tropical and subtropical fruit industry. They are the false codling moth, Thaumatotibia leucotreta, the macadamia nut borer, T. batrachopa, and the litchi moth, Cryptophlebia peltastica. Identification of these species is essential for phytosanitary purposes and to aid the management of population levels in the field. For this purpose, species identification was investigated using morphological and molecular genetic techniques. For each species, final instar larvae and pupae are described and illustrated. Diagnostic characters are given for each species and keys included to facilitate identification. In addition, as an alternative to morphological identification, a diagnostic 367-bp region of the mitochondrial cytochrome oxidase I (COI) gene was sequenced from individuals of the three species. The inclusion of both morphological and molecular keys provides a reliable means of identifying the tortricids of economic importance on tropical and subtropical fruit in South Africa.Articl

Morphological and molecular identification of economically important Tortricidae (Lepidoptera) on deciduous fruit tree crops in South Africa

Four tortricid species are of major economic importance on deciduous fruit tree crops in South Africa. They are codling moth, Cydia pomonella, oriental fruit moth, Grapholita molesta, false codling moth, Thaumatotibia leucotreta, and carnation worm, Epichoristodes acerbella. Pest management and phytosanitary practices are often hampered by the inability to distinguish between the immature stages of these four species. To address this need, the final instar larvae and pupae of E. acerbella are described and illustrated. The morphology of these immature stages of E. acerbella is compared with those of the aforementioned tortricid species. Keys are included to distinguish between the four species. In addition, as an alternative method of identification of any life stage, a means of discriminating between the four species, based on analysis of nucleotide sequences of the mitochondrial cytochrome oxidase I gene, is described.Articl

The use of Simple Sequence Repeats (SSRs) to identify commercially important potato (Solanum tuberosum L.) cultivars in South Africa

The morphological traits that are traditionally used to identify potato cultivars are not always reliable, especially when dealing with in vitro plants. Various molecular marker techniques have been described for cultivar identification, but the Simple Sequence Repeat (SSR) technique has certain qualities that render it highly suitable for this application. In this study five SSR primer sets were used to characterize twenty-four commercially important potato cultivars. All profiles were found to be reliable and no variation was found between clones of the same cultivar. The number of polymorphisms detected with each of the markers varied, but none of the primers yielded only monomorphic fragments. The multilocus primer, STIIKA produced unique profiles for each of the 24 primer sets. However, the complicated nature of the profiles limits its use for routine diagnostic purposes. The use of the markers STS and STU 69633 in combination yields unique profiles for 20 cultivars and the fact that they can be analysed simultaneously on one gel, saves time and costs. The present study thus confirms that SSRs can be employed in a routine profiling system to provide highly discriminative and standardized profiles for South African potato cultivars.Articl

Dinucleotide repeat polymorphism at the D5S99 locus on chromosome 5q33-34

We report a highly polymorphic, sequence-tagged microsatellite site (STMS) at the D5S99 locus that was previously identified by a less informative restriction fragment length polymorphism (RFLP). This marker, which was also localized to the physical map of chromosome 5q by fluorescent in situ hybridization (FISH), should assist in the precision mapping of genes in the area 5q33-34.Articl