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Expanding existing tools to aid in the epidemiological study of populations with complex ancestry.
Thesis (PhD)--Stellenbosch University, 2022.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2022
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| _version_ | 1867613733922013184 |
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| access_status_str | Open Access |
| author | Van Eeden, Gerald Eduard |
| author2 | Moller, Marlo
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| author_browse | Moller, Marlo
Van Eeden, Gerald Eduard |
| author_facet | Moller, Marlo
Van Eeden, Gerald Eduard |
| author_sort | Van Eeden, Gerald Eduard |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2022. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/125163 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:40:50.669Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/125163 Expanding existing tools to aid in the epidemiological study of populations with complex ancestry. Van Eeden, Gerald Eduard Moller, Marlo Uren, Caitlin Van der Spuy, Gian Tromp, Gerard Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics. Human gene mapping Genetic recombination Nama (African people) -- Genealogy UCTD Thesis (PhD)--Stellenbosch University, 2022. ENGLISH ABSTRACT: The majority of available software tools used for human genetics epidemiology are developed under the assumption that the individuals within a population under study are homogenous. There is also an overrepresentation of individuals of European descent in genetic research. Considering the demographic disparities in health research and the historical focus on homogenous populations when developing tools for epidemiological research, two questions arise: (1) what tools exist to study populations with complex ancestry and (2) how can we expand on the available tools? Epidemiology is, however, a broad field with many subdisciplines, therefore, we decided to focus on two main areas: recombination inference and association studies; especially the neglected aspects of recombination inference and association studies, such as their application to populations with complex ancestry. The present study provides a guide for researchers toward the appropriate recombination rate inference software given their study population (Chapter 1). Recombination map inference is a complex topic and there is a clear need for an overview of the available methods that also acts as a guide for method selection. We then use this guide to infer a novel population-specific recombination map for the Nama (Chapter 2). To date no publicly available recombination maps exist for southern African populations. Therefore, future research in the Nama would benefit from this resource as demonstrated by the selection scan results that we present. To expand on the application of population-specific recombination maps, we investigate the effect of the method used for recombination map inference on the accuracy of local ancestry inference. We find that resources developed for populations other than the study population are not always transferable (Chapter 2 and 3) and that the validity of using publicly available maps as proxies for population specific maps would depend on the application of the recombination map (Chapter 2 and 3). Finally, we promote the inclusion of populations with complex ancestry in population and disease research by furthering our understanding of common models used in association studies (Chapter 4). Our results indicate that researchers should not look toward any one GWAS model as a catch-all for any study population, but should rather use multiple models in their analysis. We conclude with an overview of the findings from each chapter, comment on the limitations of this study and recommend directions for future research. Including populations with complex ancestry in epidemiological studies is often challenging and it requires the re-evaluation of current methods, but it will lead to the improvement of the quality 3 of research on these groups. This ultimately provides a better understanding of population genetics and it ensures a better foundation for the future of epidemiological research. AFRIKAANSE OPSOMMING: Die meerderheid van beskikbare sagteware wat vir menslike genetiese epidemiologie gebruik word, word ontwikkel onder die aanname dat die individue binne 'n populasie homogeen is. Daar is ook 'n oorverteenwoordiging van individue van Europese herkoms in genetiese navorsing. Gegewe die demografiese verskille in gesondheidsnavorsing en die historiese fokus op homogene bevolkings op die ontwikkeling van hulpbronne vir epidemiologiese navorsing, ontstaan daar twee vrae: (1) watter sagteware bestaan om bevolkings met komplekse herkoms te bestudeer en (2) hoe kan ons uitbrei op die beskikbare hulpbronne? Epidemiologie is egter 'n breë veld met baie subdissiplines, daarom het ons besluit om op twee hoofgebiede te fokus: die bepaling van rekombinasiekoers en assosiasiestudies; veral die verwaarloosde aspekte van die bepaling van die rekombinasiekoers en assosiasiestudies, soos die toepassing daarvan op bevolkings met komplekse herkoms. Die huidige studie bied 'n gids vir navorsers om die toepaslike rekombinasiekoers sagteware te vind gegewe hul studiepopulasie (Hoofstuk 1). Rekombinasiekoers bepaling is 'n komplekse onderwerp en daar is 'n duidelike behoefte aan 'n oorsig van die beskikbare metodes wat ook kan dien as 'n riglyn vir die keuse van die mees toepaslike metode. Ons gebruik dan hierdie gids om 'n nuwe bevolkingspesifieke rekombinasiekaart vir die Nama af te lei (Hoofstuk 2). Tot dusver bestaan daar geen rekombinasiekaarte vir suidelike Afrikaanse bevolkings wat tot die publiek beskikbaar is nie. Daarom sal toekomstige navorsing aangaande die Nama baat by hierdie bron, soos dit blyk uit die seleksieskanderingsresultate wat ons aanbied. Om uit te brei op die toepassing van bevolkingspesifieke rekombinasiekaarte, ondersoek ons die effek van die metode wat gebruik word vir rekombinasiekaart afleiding op die akkuraatheid van plaaslike herkoms afleiding. Ons vind dat hulpbronne wat ontwikkel is vir ander populasies as die studiepopulasie nie altyd oordraagbaar is nie (Hoofstuk 2 en 3) en dat die geldigheid van die gebruik van publieke rekombinasiekaarte as gevolmagtigdes vir bevolkingspesifieke rekombinasiekaarte afhang van die toepassing van die rekombinasiekaart (Hoofstuk 2 en 3). Laastens bevorder ons die insluiting van bevolkings met 'n komplekse herkoms in bevolkingsen siekte-navorsing deur die begrip van algemene modelle wat in assosiasiestudies gebruik word te versterk (Hoofstuk 4). Ons resultate dui daarop dat navorsers nie net moet aanvaar dat 'n enkele model van toepassing is op hul studiepopulasie nie, maar eerder verskeie modelle in hul analise moet gebruik. Ons sluit af met 'n oorsig van die resultate uit elke hoofstuk, lewer kommentaar op die beperkings van hierdie studie en maak voorstelle vir toekomstige navorsing. Dit is dikwels uitdagend om populasies met komplekse herkoms in epidemiologiese studies in te sluit en dit verg die her-evaluering van huidige metodes, maar dit sal lei tot die verbetering van die kwaliteit van navorsing op hierdie groepe. Dit bied dus 'n beter begrip van bevolkingsgenetika en verseker ‘n sterker grondslag vir die toekoms van epidemiologiese navorsing. Doctoral 2022-01-17T09:20:42Z 2022-04-29T12:56:47Z 2023-01-04T03:00:07Z 2022-01 Thesis http://hdl.handle.net/10019.1/125163 en_ZA Stellenbosch University 118 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Human gene mapping Genetic recombination Nama (African people) -- Genealogy UCTD Van Eeden, Gerald Eduard Expanding existing tools to aid in the epidemiological study of populations with complex ancestry. |
| title | Expanding existing tools to aid in the epidemiological study of populations with complex ancestry. |
| title_full | Expanding existing tools to aid in the epidemiological study of populations with complex ancestry. |
| title_fullStr | Expanding existing tools to aid in the epidemiological study of populations with complex ancestry. |
| title_full_unstemmed | Expanding existing tools to aid in the epidemiological study of populations with complex ancestry. |
| title_short | Expanding existing tools to aid in the epidemiological study of populations with complex ancestry. |
| title_sort | expanding existing tools to aid in the epidemiological study of populations with complex ancestry |
| topic | Human gene mapping Genetic recombination Nama (African people) -- Genealogy UCTD |
| url | http://hdl.handle.net/10019.1/125163 |
| work_keys_str_mv | AT vaneedengeraldeduard expandingexistingtoolstoaidintheepidemiologicalstudyofpopulationswithcomplexancestry |