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Identification of a suitable SNP for allele-specific silencing of the disease-causing gene in SCA1 patients in South Africa
Includes bibliographical references (leaves 118-132).
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| Format: | Thesis |
| Language: | English |
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Division of Human Genetics
2015
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| _version_ | 1867613970405261312 |
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| access_status_str | Open Access |
| author | Baine, Fiona Kebirungi |
| author2 | Greenberg, L J ; Bryer, Alan ; Wood, M ; Scholefield, Janine |
| author_browse | Baine, Fiona Kebirungi Greenberg, L J ; Bryer, Alan ; Wood, M ; Scholefield, Janine |
| author_facet | Greenberg, L J ; Bryer, Alan ; Wood, M ; Scholefield, Janine Baine, Fiona Kebirungi |
| author_sort | Baine, Fiona Kebirungi |
| collection | Thesis |
| description | Includes bibliographical references (leaves 118-132). |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/13436 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:44:36.537Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2015 |
| publishDateRange | 2015 |
| publishDateSort | 2015 |
| publisher | Division of Human Genetics |
| publisherStr | Division of Human Genetics |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/13436 Identification of a suitable SNP for allele-specific silencing of the disease-causing gene in SCA1 patients in South Africa Baine, Fiona Kebirungi Greenberg, L J ; Bryer, Alan ; Wood, M ; Scholefield, Janine Human Genetics Includes bibliographical references (leaves 118-132). Spinocerebellar ataxia 1 (SCA1) is part of a broader group of dominant neurodegenerative disorders caused by an unstable CAG trinucleotide repeat. There is no known cure for this disease and symptoms worsen progressively culminating in death. The disease-causing mutation in SCA1 occurs in the ATXN1 gene. The function of the gene product (the ataxin-1 protein) is unknown, however; the protein has been linked to RNA processing in the cell. The first part of this study followed on a 1997 report of two founder haplotypes in the Mixed Ancestry SCA1 families in the Western Cape of South Africa, using microsatellites. The aim was to narrow the region investigated in the previous study, and confirm the existence of founder haplotypes using a SNP-based haplotype. The SNPbased haplotype was constructed using 4 SNPs in individuals from 5 different families of Mixed Ancestry origin from the Western Cape and the two founder events were confirmed. The SNP-based haplotype also shows the existence of a minimum common interval and indicates regions of possible break-points which may be useful in determining the extent and origins of the two haplotypes. The second aim of the study was to preferentially silence the mutant transcript of the ATXN1 gene by targeting a single nucleotide difference. Two of the SNPs genotyped for the SNP-based haplotype were found to be heterozygous in over half of the patient cohort. Eight shRNA effector molecules were screened against short target sequences incorporating one of these SNPs. Results are promising, with significant discrimination achieved between the wild-type and mutant alleles by targeting this SNP. This study has shown that RNAi may be developed as a beneficial therapeutic technique for a subset of SCA1 patients in South Africa. 2015-07-14T08:50:40Z 2015-07-14T08:50:40Z 2010 Master Thesis Masters MSc http://hdl.handle.net/11427/13436 eng application/pdf Division of Human Genetics Faculty of Health Sciences University of Cape Town |
| spellingShingle | Human Genetics Baine, Fiona Kebirungi Identification of a suitable SNP for allele-specific silencing of the disease-causing gene in SCA1 patients in South Africa |
| thesis_degree_str | Master's |
| title | Identification of a suitable SNP for allele-specific silencing of the disease-causing gene in SCA1 patients in South Africa |
| title_full | Identification of a suitable SNP for allele-specific silencing of the disease-causing gene in SCA1 patients in South Africa |
| title_fullStr | Identification of a suitable SNP for allele-specific silencing of the disease-causing gene in SCA1 patients in South Africa |
| title_full_unstemmed | Identification of a suitable SNP for allele-specific silencing of the disease-causing gene in SCA1 patients in South Africa |
| title_short | Identification of a suitable SNP for allele-specific silencing of the disease-causing gene in SCA1 patients in South Africa |
| title_sort | identification of a suitable snp for allele specific silencing of the disease causing gene in sca1 patients in south africa |
| topic | Human Genetics |
| url | http://hdl.handle.net/11427/13436 |
| work_keys_str_mv | AT bainefionakebirungi identificationofasuitablesnpforallelespecificsilencingofthediseasecausinggeneinsca1patientsinsouthafrica |