Mitochondrial DNA polymorphisms in Southern African populations.

A thesis submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy.The subject of this thesis is mitochondrial DNA (mtDNA) variation in southern African populations. The purpose of this study was twofold. Firstly, mtDNA variations were used to investigate the genetic affinities of Negroid, Khoisan, Caucasoid and "Coloured" populations in an attempt to refine theories on southern African population affinities and prehistory. MtDNA variations were detected using two different methods. The first method makes use of restriction fragment length polymorphisms (RFLPs) detected with the restriction enzymes Hpal, BamUI, Haell, Mspl, Avail and Hindi in 795 unrelated individuals from twenty ethnic groups within the Khoisan, Negroid, Caucasoid and "Coloured" populations from South Africa and Namibia. The combinations of the various restriction enzyme patterns (morphs) for the enzymes Hpal, Bam HI, Hae II, Mspl, Avail and Hindi (in this order), were used to derive the mtDNA type for each individual studied. This resulted in the discovery of 52 distinct mtDNA types: 30 of which had been previously reported, 28 out of 32 resulted from new combinations of enzyme morphs and 4/32 were due to the discovery of new enzyme morphs (MspI-17 in the Ashkenazi Jewish population and AvaII-31, AvaII-32 and AvaII-33 in the South African "Coloured" population). The second method involves sequencing approximately 750 base pairs of mtDNA contained within the two hypervariable segments within the non-coding control region of the mtDNA molecule in 144 individuals, most of whom where investigated for mtDNA RFLP variations. Pairwise comparisons of mtDNA sequences revealed 119 variant sites which gave rise to 129 unique mtDNA types.WHSLYP201

Drafting a Code of Conduct for Research under the Protection of Personal Information Act No. 4 of 2013

No abstrac

Lemba origins revisited: Tracing the ancestry of Y chromosomes in South African and Zimbabwean Lemba

Background. Previous historical, anthropological and genetic data provided overwhelming support for the Semitic origins of the Lemba, a Bantu-speaking people in southern Africa.Objective. To revisit the question concerning genetic affinities between the Lemba and Jews.Methods. Y-chromosome variation was examined in two Lemba groups: one from South Africa (SA) and, for the first time, a group from Zimbabwe (Remba), to re-evaluate the previously reported Jewish link.Results. A sample of 261 males (76 Lemba, 54 Remba, 43 Venda and 88 SA Jews) was initially analysed for 16 bi-allelic and 6 short tandem repeats (STRs) that resulted in the resolution of 102 STR haplotypes distributed across 13 haplogroups. The non-African component in the Lemba and Remba was estimated to be 73.7% and 79.6%, respectively. In addition, a subset of 91 individuals (35 Lemba, 24 Remba, 32 SA Jews) with haplogroup J were resolved further using 6 additional bi-allelic markers and 12 STRs to screen for the extended Cohen modal haplotype (CMH). Although 24 individuals (10 Lemba and 14 SA Jews) were identified as having the original CMH (six STRs), only one SA Jew harboured the extended CMH.Conclusions. While it was not possible to trace unequivocally the origins of the non-African Y chromosomes in the Lemba and Remba, this study does not support the earlier claims of their Jewish genetic heritage.

The effects of outsourcing the logistics function at South African manufacturing companies.

MBA University of KwaZulu-Natal, Durban 2013.Logistics is an integral part of every economy and every business entity. The worldwide trend in globalisation has led many organisations to outsource their logistics function to third-party logistics (3PL) companies and focus on their core competencies. It is therefore imperative that organisations fully understand the implications of outsourcing so that a well thought-out strategy will derive the maximum benefit. Whilst much is known about 3PL from an international perspective, knowledge from a South African perspective is limited which raised the question, “what effect does outsourcing the logistics function have on South African manufacturing companies?” The objective of this study was to identify the factors that organisations considered important in the decision to outsource. Further, benefits and limitations of outsourcing were identified. As 3PL is a strategic decision, senior managers were considered as a source of data. Due to their time constraints, it was felt that participating in a survey may prove fruitless. Therefore, a qualitative study was conducted. The objectives were achieved by conducting face-to-face interviews with senior managers of 15 companies across various industries in South Africa who had outsourced their logistics functions to 3PL service providers. The challenges and experiences collected from these interviews are presented in this study. The main conclusion drawn from this study is that the participants are in a better position than before they had outsourced logistics. Some companies achieved financial benefits, while some realised benefits such as increased efficiencies and economies of scale, and some realised a combination of both. The data analysis confirmed that while there are many benefits that accrue to companies who outsource, there are also numerous challenges and major risk factors that have to be overcome. Several recommendations have been made for companies contemplating outsourcing the logistics function

A Genomic Portrait of Haplotype Diversity and Signatures of Selection in Indigenous Southern African Populations

We report a study of genome-wide, dense SNP (∼900K) and copy number polymorphism data of indigenous southern Africans. We demonstrate the genetic contribution to southern and eastern African populations, which involved admixture between indigenous San, Niger-Congo-speaking and populations of Eurasian ancestry. This finding illustrates the need to account for stratification in genome-wide association studies, and that admixture mapping would likely be a successful approach in these populations. We developed a strategy to detect the signature of selection prior to and following putative admixture events. Several genomic regions show an unusual excess of Niger-Kordofanian, and unusual deficiency of both San and Eurasian ancestry, which were considered the footprints of selection after population admixture. Several SNPs with strong allele frequency differences were observed predominantly between the admixed indigenous southern African populations, and their ancestral Eurasian populations. Interestingly, many candidate genes, which were identified within the genomic regions showing signals for selection, were associated with southern African-specific high-risk, mostly communicable diseases, such as malaria, influenza, tuberculosis, and human immunodeficiency virus/AIDs. This observation suggests a potentially important role that these genes might have played in adapting to the environment. Additionally, our analyses of haplotype structure, linkage disequilibrium, recombination, copy number variation and genome-wide admixture highlight, and support the unique position of San relative to both African and non-African populations. This study contributes to a better understanding of population ancestry and selection in south-eastern African populations; and the data and results obtained will support research into the genetic contributions to infectious as well as non-communicable diseases in the region

Development of a single base extension method to resolve Y chromosome haplogroups in sub-Saharan African populations

<p>Abstract</p> <p>Background</p> <p>The ability of the Y chromosome to retain a record of its evolution has seen it become an essential tool of molecular anthropology. In the last few years, however, it has also found use in forensic genetics, providing information on the geographic origin of individuals. This has been aided by the development of efficient screening methods and an increased knowledge of geographic distribution. In this study, we describe the development of single base extension assays used to resolve 61 Y chromosome haplogroups, mainly within haplogroups A, B and E, found in Africa.</p> <p>Results</p> <p>Seven multiplex assays, which incorporated 60 Y chromosome markers, were developed. These resolved Y chromosomes to 61 terminal branches of the major African haplogroups A, B and E, while also including a few Eurasian haplogroups found occasionally in African males. Following its validation, the assays were used to screen 683 individuals from Southern Africa, including south eastern Bantu speakers (BAN), Khoe-San (KS) and South African Whites (SAW). Of the 61 haplogroups that the assays collectively resolved, 26 were found in the 683 samples. While haplogroup sharing was common between the BAN and KS, the frequencies of these haplogroups varied appreciably. Both groups showed low levels of assimilation of Eurasian haplogroups and only two individuals in the SAW clearly had Y chromosomes of African ancestry.</p> <p>Conclusions</p> <p>The use of these single base extension assays in screening increased haplogroup resolution and sampling throughput, while saving time and DNA. Their use, together with the screening of short tandem repeat markers would considerably improve resolution, thus refining the geographic ancestry of individuals.</p

Hierarchical Patterns of Global Human Y-Chromosome Diversity

We examined 43 biallelic polymorphisms on the nonrecombining portion of the Y chromosome (NRY) in 50 human populations encompassing a total of 2,858 males to study the geographic structure of Y-chromosome variation. Patterns of NRY diversity varied according to geographic region and method/level of comparison. For example, populations from Central Asia had the highest levels of heterozygosity, while African populations exhibited a higher level of mean pairwise differences among haplotypes. At the global level, 36% of the total variance of NRY haplotypes was attributable to differences among populations (i.e., Phi(ST) = 0.36). When a series of AMOVA analyses was performed on different groupings of the 50 populations, high levels of among-groups variance (Phi(CT)) were found between Africans, Native Americans, and a single group containing all 36 remaining populations. The same three population groupings formed distinct clusters in multidimensional scaling plots. A nested cladistic analysis (NCA) demonstrated that both population structure processes (recurrent gene flow restricted by isolation by distance and long-distance dispersals) and population history events (contiguous range expansions and long-distance colonizations) were instrumental in explaining this tripartite division of global NRY diversity. As in our previous analyses of smaller NRY data sets, the NCA detected a global contiguous range expansion out of Africa at the level of the total cladogram. Our new results support a general scenario in which, after an early out-of-Africa range expansion, global-scale patterns of NRY variation were mainly influenced by migrations out of Asia. Two other notable findings of the NCA were (1) Europe as a "receiver" of intercontinental signals primarily from Asia, and (2) the large number of intracontinental signals within Africa. Our AMOVA analyses also supported the hypothesis that patrilocality effects are evident at local and regional scales, rather than at intercontinental and global levels. Finally, our results underscore the importance of subdivision of the human paternal gene pool and imply that caution should be exercised when using models and experimental strategies based on the assumption of panmixia