Identification of a common founder couple for 40 South African Afrikaner families with Parkinson’s disease

Background. Afrikaners are a unique ethnic group in South Africa (SA) with well-documented ancestral records spanning a period of over 350 years. They are mainly descended from Dutch, German and French settlers to SA in the 17th and 18th centuries. Today several disorders in this population occur at relatively high frequencies as a result of founder effects.Objective. To determine whether a founder effect for Parkinson’s disease (PD) is present in the Afrikaner population.Methods. Study participants were recruited from the Movement Disorders Clinic at Tygerberg Hospital in Cape Town, SA, and from support groups of the Parkinson’s Association of South Africa. Standard methods for genealogical research in SA on hereditary diseases were used including interviews and searches in sources such as state archives, the Huguenot Museum in Franschhoek, marriage and baptismal records, and tombstone inscriptions.Results. For 40 of the PD families, there was only a single most recent ancestral couple common to all of the families. On average there are between three and four ancestral lines to the founder couple per proband (range 1 -14).Conclusion. If genetic studies confirm the presence of a founder effect for PD in Afrikaners, this would imply that there is a large number of individuals from this ethnic group who may potentially be at risk of developing this debilitating condition. This study illustrates and reinforces the concept that genealogical analysis is a powerful tool for identification of founder effects for various disorders in the Afrikaner population

High diversity, inbreeding and a dynamic Pleistocene demographic history revealed by African buffalo genomes

CITATION: De Jager, D., et al. 2021. High diversity, inbreeding and a dynamic Pleistocene demographic history revealed by African buffalo genomes. Scientific Reports, 11:4540, doi:/10.1038/s41598-021-83823-8.The original publication is available at https://www.nature.comPublication of this article was funded by the Stellenbosch University Open Access FundGenomes retain records of demographic changes and evolutionary forces that shape species and populations. Remnant populations of African buffalo (Syncerus caffer) in South Africa, with varied histories, provide an opportunity to investigate signatures left in their genomes by past events, both recent and ancient. Here, we produce 40 low coverage (7.14×) genome sequences of Cape buffalo (S. c. caffer) from four protected areas in South Africa. Genome-wide heterozygosity was the highest for any mammal for which these data are available, while differences in individual inbreeding coefficients reflected the severity of historical bottlenecks and current census sizes in each population. PSMC analysis revealed multiple changes in Ne between approximately one million and 20 thousand years ago, corresponding to paleoclimatic changes and Cape buffalo colonisation of southern Africa. The results of this study have implications for buffalo management and conservation, particularly in the context of the predicted increase in aridity and temperature in southern Africa over the next century as a result of climate change.https://www.nature.com/articles/s41598-021-83823-8Publisher's versio

A Mobile Holistic Enterprise Transformation Framework

Mobile phones and tablets shipments are surpassing those of the PC category, as well as in relation to Internet usage as of 2016; all details which have made mobile adoption a priority for many enterprises and a challenge for them as well. Many enterprises have fallen into a paradox of spending on creating and updating mobile services, and gaining less than expected in return. Reasons for this include the lack of vision, and the lack of a clearly defined, well communicated mobile strategy. Enterprise Architecture ‘EA’ facilitates a successful transformation by controlling and managing the transitions in order to arrive at a clearly defined future state. It is regarded as the science of change to many. However, EA frameworks are very comprehensive and require weeks of training and resources, and are often too generic for mobile transformation. Therefore, an EA-based mobile holistic enterprise framework has been developed to support enterprises in making mobile initiatives a priority. The proposed framework ensures a clearly defined, well-communicated, holistic future state that is continually evaluated, as opposed to many of the existing frameworks. The proposed Mobile Holistic Enterprise Architecture Framework - ‘MHETF’ - is based on the realisation of the capabilities of smartphones that are aimed at individual average consumers (the backbone of the current mobile trend). The capabilities are categorised and translated into four sets of services categories for business use. They are linked to another two components of the framework which are: (i) the categorisation of goals and objectives that are incorporated into the Balanced Scorecard for evaluation at a later stage in planning, and continually referred to during transitions and (ii) the categorisation of the implementation forms (categorisation of end solutions’ functionalities). The framework is supported by EA inter-operability and maturity models to ensure continuity and alignment with the existing initiatives, the enterprise’s strategic objectives, and the change required in the scope of transformation. An evaluation for the available enterprise architecture frameworks was carried out and resulted in the selection of The Open Group Architecture Framework (TOGAF). The decision was also commended by the participants in the case study evaluation due to their familiarity with this framework, which is being adopted as the Saudi E Government Standard in contrast to the other major frameworks of Zachman and Federal Enterprise Architecture (FEA). MHETF has been applied to three case studies in the Kingdom of Saudi Arabia; two applications for a leading national outsourcing company, and the third for the outpatient clinics in a large hospital in the capital city of Riyadh. The results have shown major improvements in the four goal areas of mobile transformation; productivity, processes, satisfaction improvement and facilitating new opportunities. Eventually, the final evolution has shown that the participants are satisfied with the framework overall, and indicates that the framework changed their perspective of the power of mobile applications significantly, is relatively easy to understand, and that they are planning to adopt it for future mobile initiatives

African wild dogs (Lycaon pictus) from the Kruger National Park, South Africa are currently not inbred but have low genomic diversity

African wild dogs (Lycaon pictus) have undergone severe population reductions and are listed as endangered on the International Union for Conservation of Nature Red List. Small, isolated populations have the potential to suffer from threats to their genetic diversity that may impact species viability and future survival. This study provides the first set of population-wide genomic data to address conservation concerns for this endangered species. Whole genome sequencing data were generated for 71 free-ranging African wild dogs from the Kruger National Park (KNP), South Africa, and used to estimate important population genomic parameters. Genomic diversity metrics revealed that variation levels were low; however, this African wild dog population showed low levels of inbreeding. Very few first- and second-order relationships were observed in this cohort, with most relationships falling into the third-order or distant category. Patterns of homozygosity could have resulted from historical inbreeding or a loss in genome variation due to a population bottleneck. Although the results suggest that this stronghold African wild dog population maintains low levels of inbreeding, likely due to their cooperative breeding system, it may lead to a continuous population decline when a reduced number of suitable mates are available. Consequently, the low genomic variation may influence species viability over time. This study highlights the importance of assessing population genomic parameters to set conservation priorities. Future studies should include the investigation of the potential of this endangered species.https://www.nature.com/srepdm2022Veterinary Tropical Disease

An investigation into the molecular aetiology of Parkinson's disease in South African patients

Thesis (MScMedSc)--Stellenbosch University, 2013.ENGLISH ABSTRACT: Parkinson's disease (PD) is a severely debilitating neurodegenerative disorder that results in motor circuit dysregulation and ultimately, causes impairment of movement. This condition is due to the selective degradation of the dopaminergic neurons in the substantia nigra pars compacta in the midbrain, which subsequently results in the pathological symptoms namely bradykinesia, resting tremor, postural instability and rigidity. It was initially hypothesized that individuals who develop PD were exposed to an environmental trigger(s) that caused the onset of the disease, but more recently, a significant genetic component, coupled to environmental factors have been implicated in disease pathogenesis. Currently, there are eight genes (Parkin, PINK1, LRRK2, SNCA, DJ-1, ATP13A2, EIF4G1 and VPS35) that have been directly implicated in PD. Worldwide, the prevalence of neurodegenerative disorders is increasing as populations are living longer. In Europe, Canada and USA, it has been projected that the prevalence of PD may increase by a factor of two between 2010 and 2050; approximately a 92% increase. In Tanzania (the only study done in sub-Saharan Africa) an even larger increase of 184% between 2005 and 2025 is predicted, due to the fact that the speed of populations ageing in developing countries, will exceed that of developed countries. Research into the causes and risk factors underlying neurodegenerative disorders such as PD is therefore urgently needed for policy makers and governments in developing nations to take appropriate action to deal with this impending health care problem. The aim of the present study was to investigate the molecular aetiology of a group of South African PD patients. A total of 262 patients from various ethnic backgrounds were recruited for the study, and 35% had a positive family history of PD with the average age at onset (AAO) being 54.3 years of age (SD = 12.5 years). Mutation screening of the known PD genes (Parkin, PINK1, LRRK2, SNCA and DJ-1) was performed using high resolution melt and Sanger sequencing. Genotyping was done using fluorescently-labelled PCR primers followed by electrophoresis on an ABI 3130xl genetic analyser (for CTG repeats in JPH3) and with a KASP™ Genotyping Assay (for a 16bp indel in DJ-1). In order to identify a novel PD-causing gene, whole exome sequencing (WES) was conducted on three Afrikaner probands with an Illumina Genome Hiseq 2000TM and the sequences were aligned using the NCBI Human Reference Genome 37.2. The BORG (Bio-Ontological Relationship Graph) semantic database, which models the relationship of human and model organism genes to functions, pathways and phenotypes, was used to filter and prioritise genetic variants shared between the three PD exomes. It was determined that the known PD genes do not play a significant role in disease pathogenesis in the South African patients as only 15/262 (5.7%) of the patients harboured mutations: seven in Parkin, one in PINK1, six in LRRK2 and one in SNCA. Only one of the patients harboured a 16bp indel variant at the transcription start site of DJ-1. None of the Black PD patients had pathogenic repeat expansions in JPH3 thereby excluding Huntington disease-like 2 as a cause of the disease phenotype. Genealogical analysis revealed that six of the apparently unrelated Afrikaner PD probands were related to a founder couple that immigrated to South Africa in the 1600s which suggests that there is a possible founder effect for the disease. Bioinformatics analysis of WES data on three of the probands identified 21 variants in 12 genes that were present in all three PD exomes and fulfilled various criteria. Sanger sequencing was used for verification of five variants and of these, two (in CDC27 and NEDD4) were found to be artefacts. The remaining three (in HECDT1, TBCC and RNF40) were excluded based on the lack of cosegregation with disease and the high frequency of the allele in controls. Further work is necessary to verify the presence of the remaining sixteen variants and to characterise each of them for their possible pathogenicity. The discovery of novel PD-causing genes is important as this may shed light on the pathways or processes that are involved. A current hypothesis implicates the lysosome-dependent pathway as a unifying biochemical pathway that can account for the phenotypic spectrum within PD. Notably, although Mendelian forms are thought to account for only about 10- 15% of cases, the study of Mendelian inherited variants is likely to provide insight into the pathophysiology of the more common sporadic form of this condition. Dissecting the key molecular mechanisms underlying PD will provide critical information for improved treatment strategies and drug interventions that will ultimately prevent or halt neuronal cell loss in susceptible individuals.AFRIKAANSE OPSOMMING: Parkinson se siekte (PS) is 'n erge neurodegeneratiewe bewegings-siekte, wat motorstroombaan disregulasie veroorsaak. Dit lei uiteindelik tot beperkte bewegings vermoëns. Hierdie toestand word veroorsaak weens die selektiewe agteruitgang van die dopaminergeniese neurone in die substantia nigra pars compacta in die midbrein, wat later lei tot die patologiese simptome naamlik: bradykinesia, rustende spiersametrekkings, posturale onstabiliteit en rigiditeit. Daar is aanvanklik vermoed dat individue wat PS ontwikkel, aan 'n omgewingsfaktor(e) blootgestel is wat die aanvang van die siekte veroorsaak het, terwyl meer onlangs is daar 'n aansienlike genetiese komponent tesame met omgewingsfaktore geïdentifiseer, wat betrokke is by die patogenese van die siekte. Tans is daar agt gene (Parkin, PINK1, LRRK2, SNCA, DJ-1, ATP13A2, EIF4G1 en VPS35) wat direk by PS geïmpliseer is. Wêreldwyd is daar ‗n toenemende voorkoms van neurodegeneratiewe siektes aangesien bevolkings langer leef. In Europa, Kanada en die VSA, is daar geprojekteer dat die voorkoms van PS tussen 2010 en 2050 met 'n faktor van twee verhoog kan word. Dit is ongeveer 'n 92%- verhoging. In Tanzanië (die enigste studie wat tot dusver in sub-Sahara Afrika gedoen is) word daar selfs ‗n groter toename, van 184% tussen 2005 en 2025 voorspel. Dit is te danke aan die feit dat die bevolkings- veroudering in ontwikkelende lande die van ontwikkelde lande sal oorskry. Ondersoeke na die oorsake en risiko-faktore onderliggend aan neurodegeneratiewe siektes, byvoorbeeld PS, word dus dringend benodig deur beleidmakers en regerings in ontwikkelende lande, sodat hulle die nodige stappe kan neem om hierdie dreigende gesondheidsorg-probleem op te los. Die doel van die huidige studie was om ondersoek in te stel na die molekulêre etiologie van 'n groep Suid-Afrikaanse PS pasiënte. 'n Totaal van 262 pasiënte van verskillende etniese agtergronde, is gewerf vir die studie. Hiervan het 35% 'n positiewe familiegeskiedenis van PS en die gemiddelde aanvangs ouderdom (AAO) was 54,3 jaar (SD = 12,5 jaar). Mutasie-analise van die bekende PS gene is uitgevoer met behulp van hoë resolusie smelt en Sanger volgordebepaling. Genotipering is gedoen met behulp van fluoresserend geëtiketteerde PKR inleiers met elektroforese, op 'n ABI 3130xl genetiese analiseerder (CTG herhalings in JPH3), en met 'n KASP ™ Genotipering toets (vir 'n 16bp indel in DJ-1). Ten einde, om 'n nuwe PSveroorsakende geen te identifiseer was heel eksoom volgordebepaling (WES) uitgevoer op drie Afrikaner PS positiewe pasiënte met 'n Illumina Genome Hiseq 2000™ en die volgorders is gerangskik met behulp van die NCBI Menslike Verwysings Genoom 37.2. Die BORG (Bio- Ontologiese Verhoudings Grafiek) semantiese databasis, wat gebaseer is op die verhouding van die mens en model organisme gene funksies, paaie en fenotipes, en is gebruik om genetiese variante, wat gedeel word tussen die drie PS exome te filtreer en te prioritiseer. Daar is vasgestel dat die bekende PS gene nie 'n belangrike rol in die patogenese van die siekte in die Suid-Afrikaanse pasiënte speel nie. Dit is aangesien slegs 15/262 (5.7%) van die pasiënte bekende mutasies dra: sewe in Parkin, een in PINK1, ses in LRRK2 en een in SNCA. Slegs een van die pasiënte het 'n 16bp delesie variant in die transkripsie promotor area van DJ-1 gedra. Geen van die Swart PS pasiënte het patogeniese herhalings in JPH3 vertoon nie. Gevolglik is Huntington siekte-agtige 2 uitgesluit as 'n oorsaak van die siekte fenotipe. Genealogiese analise het getoon dat ses van die skynbaar onverwante Afrikaner PS pasiënte verwant is aan 'n stigter paartjie wat in die 1600's na Suid-Afrika geïmigreer het, wat daarop dui dat daar 'n moontlike stigter effek vir die siekte is. Bioinformatiese analise van WES data vir drie van die pasiënte, het 21 variante in 12 gene geïdentifiseer, wat in al drie PS exome teenwoordig was en verskeie kriteria vervul het. Sanger volgordebepaling is gebruik vir die bevestiging van vyf variante en van hierdie, is twee (in CDC27 en NEDD4) bevind om artefakte te wees. Die oorblywende drie (in HECDT1, TBCC en RNF40) is uitgesluit gebaseer op die gebrek aan gesamentlike-segregasie met die siekte en die hoë frekwensie van die allele in die kontrole groep. Verdere werk is nodig om die teenwoordigheid van die oorblywende variante te verifieer en om elkeen van hulle te karakteriseer vir hulle moontlike patogenisiteit. Die ontdekking van die nuwe PS-veroorsakende gene is belangrik aangesien dit lig kan werp op die stelsels of prosesse wat betrokke is. 'n Huidige hipotese impliseer die lisosoom-afhanklike pad as 'n verenigende biochemiese padweg, wat verantwoordelik is vir die fenotipiese spektrum binne PS. Alhoewel Mendeliese vorms vermoedelik verantwoordelik is vir slegs omgeveer 10-15% van die gevalle, is die studie van Mendelse gene geneig om insig te verkry in die patofisiologie van die meer algemene sporadiese vorm van hierdie toestand. Ontleding van die kern molekulêre meganismes onderliggend aan PS sal kritiese inligting vir beter strategieë vir behandeling en geneesmiddel-intervensies voorsien, wat gevolglik neuronale sel verlies in vatbare individue sal voorkom of beëindig.Medical Research CouncilNational Research FoundationHarry Crossley Foundatio

Identification of novel Parkinson’s disease genes in the South African population using a whole exome sequencing approach

Thesis (PhD)--Stellenbosch University, 2016.ENGLISH SUMMARY: Parkinson’s disease (PD) is a progressive and severely debilitating neurodegenerative disorder that is characterised by a range of motor symptoms and the selective loss of dopaminergic neurons in the substantia nigra. While the aetiology of PD remains poorly understood, it is hypothesised to involve a combination of various environmental, genetic and cellular factors that independently or collectively contribute to neurodegeneration and ultimately disease. To date, a number of genes including Parkin, PINK1, LRRK2, SNCA, DJ-1, ATP13A2 and VPS35 that have been directly associated with disease and investigations of their functions have provided significant insights into the pathobiology of PD. However, these genes do not play a significant role in the South African PD cohort and for this reason, novel genes and pathogenic mutations must be investigated and identified. This will aid in early diagnosis of patients and also ultimately for the design of more effective therapeutic strategies to treat this debilitating and poorly understood chronic systemic disorder. The present study aimed to identify novel PD-causing mutations in the South African Afrikaner population using a genealogical and whole exome sequencing (WES) approach.. The Afrikaner are unique to South Africa and are known to have undergone a bottleneck in the 1800s which has led to genetic founder effects for a number of different disorders in this particular group. Additionally, we further aimed to determine whether the identified putative disease-causing mutation(s) could be attributed to the development of PD in other South African ethnic groups. A total of 458 patients were recruited, of which 148 were self-identified as Afrikaner. From these, a total of 48 Afrikaner probands were subjected to extensive genealogical analyses and 40 of them could be traced back to a single common couple. For this reason, it was hypothesised that the disorder in these patients may be due to a genetic founder effect. The use of a whole genome SNP array confirmed the relatedness of the individuals to varying degrees (8 to 12 generations back) and subsequently three of the probands and one affected sibling were selected for WES. The selected individuals were sequenced using the Illumina Genome Hiseq 2000TM and approximately 78 000 variants were identified for each individual. Numerous bioinformatics tools were used to scrutinize the variants but none were able to produce a candidate list of plausible disease-causing variants. All variants identified were either present at high frequency, did not co-segregate with the disorder or were artefacts. In order to facilitate and expedite the variant prioritisation process, a novel method for the filtration of WES data was designed in-house. This strategy named TAPER™ (Tool for Automated selection and Prioritisation for Efficient Retrieval of sequence variants) implements a set of logical steps by which to prioritise candidate variants that could be pathogenic. It is primarily aimed at the support of resource-constrained scientific environments with limited bioinformatics capacity. As a proof of concept various independent WES datasets for PD, severe intellectual disability and microcephaly as well as ataxia and myoclonic epilepsy were used, and TAPER™ was able to successfully prioritise and identify the causal variants in each case. Through the use of TAPER™, two putative candidate variants in SYNJ1 and USP17 were identified. The homozygous V1405I variant in SYNJ1 was found only in the affected sibling pair and in none of the 458 patients and 690 control individuals that had been screened. This variant is predicted to be deleterious across multiple platforms and has a CADD score of 29.40 and may alter synaptic vesicle recycling. The homozygous C357S variant in USP17 was found in 18/458 probands (12 Afrikaner, two white and four mixed ancestry) but was identified in 0.14% of the controls (1/184 Afrikaner, 0/160 white, 0/180 mixed ancestry and 0/160 black). This variant is also anticipated to be deleterious across multiple platforms and has a CADD score of 34.89. In summary, the results of the present study reveal that PD in the 40 South African Afrikaner patients studied is not due to a founder effect, but highlights two variants of interest for future studies. Further work is necessary to analyse both of these variants and to assess their possible effect on protein structure and function. The discovery of novel PD-causing genes is important as this allows for the generation of disease-linked protein networks, thereby facilitating identification of additional disease genes and subsequently providing insights into the underlying pathobiology. Moreover, this knowledge is critical for the development of improved treatment strategies and drug interventions that will ultimately prevent or halt neuronal cell loss in susceptible individuals. Although the present study did not conclusively identify a novel PD-causing gene, it does provide a solid foundation for future work in our laboratory in the challenging and rapidly evolving research area of WES and bioinformatics, and its application to studies on PD.AFRIKAANSE OPSOMMING: Parkinson se siekte (PS) is ʼn erg aftakelende neuro-degeneratiewe siekte wat gekenmerk word deur 'n verskeidenheid van simptome en uiteindelik die inkorting van beweging veroorsaak. Hierdie toestand is die gevolg van selektiewe degenerasie van die dopaminergiese neurone substantia nigra pars compacta in die midbrein. Dit lei tot patologiese simptome naamlik bradikinese, rus tremore, posturale onstabiliteit en rigiditeit. Aanvanklik was die hipotese dat persone wat PS ontwikkel blootgestel was aan omgewingsverwante snellers wat die aanvang van die siekte veroorsaak. Maar onlangse bewyse dui daarop beide omgewing- en genetiese faktore speel ʼn rol in die patogenese van die siekte. Tans is daar sewe gene (Parkin, PINK1, LRRK2, SNCA, DJ-1, ATP13A2 en VPS35) wat direk betrokke is by PD. Die doel van die huidige studie is om ʼn 'n PS oorsaak-mutasies in die Suid-Afrikaanse Afrikaner bevolking te identifiseer met behulp van 'n genealogiese en die heel eksoom volgorde-benadering (WES). Die Afrikaner is uniek aan Sui Afrika en het in die 1800s ń genetiese knelpunt ondervind wat tot genetiese stigterseffek gelei het. Daarbenewens het ons verder ten doel om te bepaal of die geïdentifiseerde vermeende siekte-veroorsakende mutasie(s) toegeskryf kan word aan die ontwikkeling van PS in ander Suid-Afrikaanse etniese groepe. ʼn Totaal van 458 pasiënte is vir die studie gewerf, waarvan 148 self-geïdentifiseerde Afrikaners is. ʼn Totaal van 48 Afrikaner probandi was onderworpe aan genealogiese analise en 40 van hulle kon teruggevoer word na 'n enkele gemeenskaplike voorouer. Dit word dus veronderstel dat die individue aan mekaar verwant is en dat PS weens ń stigterseffek is. Die gebruik van 'n hele genoom SNP verskeidenheid bevestig die verwantskap van die individue in verskillende grade (tussen 8 en 12 generasies) en daarvolgens is drie van die probandi en een geaffekteerde bloedverwant gekies vir WES. Die gekose eksooms is georden volgens die Illumina Genome Hiseq 2000TM en ongeveer 78 000 variante is geïdentifiseer vir elke individu. Verskeie bio-informatika instrumente is gebruik om die variante wat deur WES verkry is te bestudeer maar geen een was in staat om ʼn beweerde lys van geloofwaardige siekte-veroorsakende variante te identifiseer nie. Ten einde die variante identifikasie proses te ondersteun, is ʼn nuwe metode vir filtrasie van WES-data ontwikkel, naamlik TAPER™ (Tool for Automated selection and Prioritization for Efficient Retrieval of sequence variants). TAPER™ implementeer ʼn stel logiese stappe waardeur kandidaat variante gekies word wat met die siekte geassosieer word; dit het ten doel om ondersteuning te bied aan wetenskaplike omgewings met beperkte bioinformatika kapasiteit. Verder is die sukses van TAPER™ geëvalueer op reeds bestaande data-stelsels wat die konsep bewys. Met behulp van TAPER™ is twee waarskynlike kandidaat variante in SYNJ1 en USP17 geïdentifiseer. Die V1405I variant in SYNJ1 is slegs in ʼn geaffekteerde bloedverwant paar gevind en in geen van die 458 pasiënte of 690 gekeurde kontrole groep individue. Dit word voorspel dat hierdie variant skadelik is en het ń CADD telling van 29.40. Die C357S variant is homosigoties in USP17 in 18/458 probandi (12 Afrikaner, twee wit en vier gemengde afkoms) gevind is. Maar dit is ook geïdentifiseer in 0.14% van die kontrole individu (1/184 Afrikaner, 0/160 wit, 0/180 gemengde afkoms en 0/160 swart) wat verkry is van die Westelike Provinsie Bloedoortappingsdienste. Dit word voorspel dat hierdie variant skadelik is en het ń CADD telling van 34.89. Die resultate van die huidige studie toon dat PD in die Suid-Afrikaanse Afrikaner nie die oorsprong het by 'n stigterslid nie, maar beklemtoon twee variante van belang. Verdere werk is nodig om elkeen van die variante te analiseer en hul moontlike patogenese te ondersoek. Die ontdekking van nuwe PS veroorsakende gene is belangrik omdat dit help met die ontwikkeling van siekte-verwante proteïen netwerke, en om sodoende addisionele gene te identifiseer in sleutel siekte prosesse en gevolglik kern biologiese insig in onderliggende prosesse te verskaf. Alhoewel die huidige studie nie ń nuwe PS-veroorsakende geen geïdentifiseer het nie, dit bied wel ń ferm platform vir toekomstige navorsing in die uitdagende en versnellende veranderende velde van WES en bioinformatika en die toepassing daarvan op PS studies

Identification of a common founder couple for 40 South African Afrikaner families with Parkinson’s disease

Please cite as follows: Geldenhuys, G. et al. 2014. Identification of a common founder couple for 40 South African Afrikaner families with Parkinson’s disease. South African Medical Journal,104(6):413-419, doi:10.7196/SAMJ.7747.The original publication is available at http://samj.org.zaBackground. Afrikaners are a unique ethnic group in South Africa (SA) with well-documented ancestral records spanning a period of over 350 years. They are mainly descended from Dutch, German and French settlers to SA in the 17th and 18th centuries. Today several disorders in this population occur at relatively high frequencies as a result of founder effects. Objective. To determine whether a founder effect for Parkinson’s disease (PD) is present in the Afrikaner population. Methods. Study participants were recruited from the Movement Disorders Clinic at Tygerberg Hospital in Cape Town, SA, and from support groups of the Parkinson’s Association of South Africa. Standard methods for genealogical research in SA on hereditary diseases were used including interviews and searches in sources such as state archives, the Huguenot Museum in Franschhoek, marriage and baptismal records, and tombstone inscriptions. Results. For 40 of the PD families, there was only a single most recent ancestral couple common to all of the families. On average there are between three and four ancestral lines to the founder couple per proband (range 1 -14). Conclusion. If genetic studies confirm the presence of a founder effect for PD in Afrikaners, this would imply that there is a large number of individuals from this ethnic group who may potentially be at risk of developing this debilitating condition. This study illustrates and reinforces the concept that genealogical analysis is a powerful tool for identification of founder effects for various disorders in the Afrikaner population.http://samj.org.za/index.php/samj/article/view/7747Publisher's versio

A new tool for prioritization of sequence variants from whole exome sequencing data

CITATION: Glanzmann, B. et al. 2016. A new tool for prioritization of sequence variants from whole exome sequencing data. Source Code for biology and Medicine, 11:10, doi:10.1186/s13029-016-0056-8.The original publication is available at http://scfbm.biomedcentral.com/Publication of this article was funded by the Stellenbosch University Open Access Fund.Background: Whole exome sequencing (WES) has provided a means for researchers to gain access to a highly enriched subset of the human genome in which to search for variants that are likely to be pathogenic and possibly provide important insights into disease mechanisms. In developing countries, bioinformatics capacity and expertise is severely limited and wet bench scientists are required to take on the challenging task of understanding and implementing the barrage of bioinformatics tools that are available to them. Results: We designed a novel method for the filtration of WES data called TAPER™ (Tool for Automated selection and Prioritization for Efficient Retrieval of sequence variants). Conclusions: TAPER™ implements a set of logical steps by which to prioritize candidate variants that could be associated with disease and this is aimed for implementation in biomedical laboratories with limited bioinformatics capacity. TAPER™ is free, can be setup on a Windows operating system (from Windows 7 and above) and does not require any programming knowledge. In summary, we have developed a freely available tool that simplifies variant prioritization from WES data in order to facilitate discovery of disease-causing genes.Publishers versio