Schneider, S. R.Spies, J. J.Malan, Clement2015-08-202015-08-202014-06http://hdl.handle.net/11660/982English: Inadequate information on the allelic frequency of neurotransmitter genes exist among South African ethnic groups. The analyses of neurotransmitter genes with populations world-wide have benefited behaviour, population and medical fields. Population genetic fields have benefited due to increased information on population differentiation, structure and variation. Neuropsychiatric and behavioural disorders are prevalent among South African populations. In addition, research on neurotransmitter genes is limited for South African populations. Information on South African populations is inadequately based on one or two population groups and a limited number of neurotransmitter genes. This lack of information prompted the analyses of the Khwe, Xhosa, Sotho and Afrikaner ethnic groups with the DRD4, MAO-A and 5-HTT (5-HTTLPR) in the current study. Volunteers from the mentioned South African populations provided saliva samples. In total, 349 individuals were successfully analysed for the DRD4 VNTR, MAO-A-uVNTR and 5-HTTLPR. Significant genetic diversity was determined among the different populations. The Xhosa and Sotho are the closest related populations in the study followed by the Xhosa and Khwe. The Afrikaner population, an African population with mostly European ancestral heritage is the most genetic divergent population. From the analysis of the South African populations a hypothesis was constructed that the DRD4 and 5-HTTLPR allele frequencies may be associated with historic migration distance due to novelty seeking. It was theorised that populations that have migrated the greatest distance from Africa would have the highest levels of novelty seeking alleles. With the use of the South African populations and world-wide populations from revised literature positive correlations were identified for the S allele of the 5-HTTLPR. Positive correlations were also determined for the 7-repeat, >5-repeat and the combined 2- and >5-repeat alleles of the DRD4 VNTR. The 4-repeat allele of the DRD4 VNTR was determined the greatest among the analysed Khwe, Xhosa, Sotho and Afrikaner ethnic groups. The Khwe population had the highest frequency (0.711) for the 4-repeat allele among the analysed populations. The Khwe, Xhosa and Sotho populations DRD4 frequencies were similar to other African populations. The Afrikaner population has similar frequencies to its ancestral populations for the DRD4 VNTR. A remarkable finding of the study is the high frequencies of the long 5-HTTLPR alleles (L, VL and XL) in the Khwe population. The Khwe 5-HTTLPR allele frequencies are similar to that of the pygmy Mbuti population from central Africa. The Khwe is the most genetically diverse population analysed in this study and is possibly associated with the first modern humans. In contrast to the Khwe, the Afrikaner population has reduced L allele frequencies and less genetic diversity. The 4.5- and 3.5-repeat MAO-A-uVNTR alleles were the most common among the analysed populations. A significant finding in this study was that the Khwe, Xhosa and Sotho 3.5-repeat allele frequencies were significantly reduced compared to African Americans. The analysis of the study populations with the MAO-A-uVNTR provided information to an area that is lacking. Few correlations were previously possible due to the MAO-A-VNTR not being analysed in African populations. This study proved that allele frequencies for neurotransmitter genes differ between South African ethnic groups. A high degree of genetic relation was determined among linguistically related groups (Xhosa and Sotho) compared to non-related groups (Afrikaner). Neurotransmitter genes were determined significant factors in past human migrations. Novelty seeking alleles were associated with populations that migrated great distances.Afrikaans: Daar bestaan tans onvoldoende inligting in verband met neuro-oordrag gene onder Suid-Afrikaanse etniese groepe. Die ontleding van neuro-oordrag gene onder bevolkings wêreldwyd het gedrag, bevolking en mediese studievelde in die betrokke lande gebaat. Genetiese bevolkingstudies het voordeel getrek deur die verhoogde inligting oor die onderskeid, struktuur en variasie in die bevolkings. Neuropsigiatriese afwykings en gedragsafwykings is algemeen onder Suid-Afrikaanse bevolkings. Daarbenewens is navorsing oor neuro-oordrag gene beperk vir Suid-Afrikaanse bevolkings. Neuro-oordrag inligting van Suid-Afrikaanse bevolkings is onvolledig en meestal gebaseer op „n beperkte aantal neuro-oordrag gene en fokus slegs op een of twee bevolkingsgroepe. Derhalwe is hierdie studie van die DRD4, MAO-A en 5-HTT (5-HTTLPR) gebiede op die Khwe, Xhosa, Sotho en Afrikaner etniese groepe uitgevoer. Vrywilligers van die betrokke Suid-Afrikaanse bevolkings groepe het speeksel monsters voorsien. ʼn Totaal van 349 monsters is suksesvol ontleed vir die DRD4, MAO-A en 5-HTTLPR. Die genetiese diversiteit tussen die verskillende bevolkings is beduidend. Die Xhosa en Sotho is die mees verwante bevolkings in die studie, gevolg deur die Xhosa en Khwe. Die Afrikaner-bevolking, 'n Afrika-bevolking met ʼn Europese oorsprong, is die mees geneties divergerende bevolking. Die data het gelei tot die formulering van 'n hipotese dat die DRD4 „VNTR‟ en 5-HTTLPR alleelfrekwensies geassosieer kan word met historiese migrasie afstand, moontlik as gevolg van ʼn verhoogde drang na die soek van nuwe ervarings („novelty seeking‟). Dit word beweer dat bevolkings wat oor die grootste afstand uit Afrika migreer het, die hoogste vlak van die drang na nuwe ervarings sou hê. Deur die Suid-Afrikaanse bevolking met wêreld-wye bevolkings te kombineer, is positiewe korrelasies tussen die afstande en die alleelfrekwensie geïdentifiseer vir die S alleel van die 5-HTTLPR. Positiewe korrelasies is ook geïdentifiseer vir die 7-, >5- en die gekombineerde 2- en >5-herhaling allele van die DRD4 „VNTR‟. Dit was bepaal dat die 4-herhaling alleel van die DRD4 „VNTR‟ die hoogste frekwensie onder die Khwe, Xhosa, Sotho en Afrikaner etniese groepe het. Die Khwe bevolking het die hoogste frekwensie (0.711) vir die 4-herhaling alleel onder die studie bevolkings. Die DRD4 frekwensie van die Khwe, Xhosa en Sotho bevolkings is soortgelyk aan ander Afrika-bevolkings. Die Afrikaner-bevolking het soortgelyke frekwensies as sy voorvaderlike bevolkings vir die DRD4 „VNTR‟. 'n Merkwaardige bevinding van die studie is die hoë frekwensies van die lang 5-HTTLPR alleel („L‟, „XL‟ en „VL‟) in die Khwe bevolking. Khwe frekwensies is soortgelyk aan dié van die dwerg Mbuti bevolking van Sentraal-Afrika. Die Khwe is die mees genetiese diverse bevolking ontleed in hierdie studie en hou moontlik verband met die eerste moderne mense. In teenstelling met die Khwe, het die Afrikaner-bevolking „n verminderde „L‟ alleelfrekwensie en minder genetiese diversiteit. Die 4.5- en 3.5-herhaling MAO-A-„uVNTR‟ allele was die mees algemeen onder die studie bevolkings. 'n Beduidende bevinding in die studie was dat die Khwe, Xhosa en Sotho 3.5-herhaling alleelfrekwensies aansienlik minder is in vergelyking met Afro-Amerikaners. Die ontleding van die studie bevolkings met die MAO-A-„uVNTR‟ het inligting verskaf om 'n gebied wat te kort het. Net „n paar korrelasies was voorheen moontlik as gevolg van die MAO-A-„uVNTR‟ wat nie in Afrikaanse bevolkings ontleed was nie. Hierdie studie bewys dat alleelfrekwensies vir neuro-oordrag gene verskil tussen Suid-Afrikaanse etniese groepe. 'n Hoë graad van genetiese verhouding is bepaal onder taalkundig verwante groepe (Xhosa en Sotho) in vergelyking met nie-verwante groepe (Afrikaner). Neuro-oordrag gene was belangrike faktore bepaal onder menslike migrasies van die verlede. n‟ Verhoogde drang na nuwe ervaring allele hou verband met bevolkings wat lang afstande gemigreer het.enAfrikanerAllele frequencyDopamine Receptor D4Ethnic groupsKhweMonoamine Oxidase ASerotonin transporter-linked polymorphic regionSothoXhosaDissertation (M.Sc. (Genetics))--University of the Free State, 2014NeurotransmittersCognitive neurosciencesHuman population genetics -- South AfricaDissertationUniversity of the Free State