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Analysis of genetic variants in the 5’ regulatory region of the ALAS1 gene in South African patients with Variegate Porphyria (VP)
Thesis (MSc (Genetics))—University of Stellenbosch, 2007.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : University of Stellenbosch
2007
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| _version_ | 1867613967378022400 |
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| access_status_str | Open Access |
| author | Du Plessis, Nelita |
| author2 | Warnich, L. |
| author_browse | Du Plessis, Nelita Warnich, L. |
| author_facet | Warnich, L. Du Plessis, Nelita |
| author_sort | Du Plessis, Nelita |
| collection | Thesis |
| dc_rights_str_mv | University of Stellenbosch |
| description | Thesis (MSc (Genetics))—University of Stellenbosch, 2007. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/2625 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:44:33.029Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2007 |
| publishDateRange | 2007 |
| publishDateSort | 2007 |
| publisher | Stellenbosch : University of Stellenbosch |
| publisherStr | Stellenbosch : University of Stellenbosch |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/2625 Analysis of genetic variants in the 5’ regulatory region of the ALAS1 gene in South African patients with Variegate Porphyria (VP) Du Plessis, Nelita Warnich, L. Zaahl, M. G. University of Stellenbosch. Faculty of Agrisciences. Dept. of Genetics. Porphyria -- South Africa -- Genetic aspects Dissertations -- Genetics Theses -- Genetics Thesis (MSc (Genetics))—University of Stellenbosch, 2007. The porphyrias are a group of genetic disorders arising from mutations in either one of the final seven genes encoding the haeme synthesis enzymes. These disease-causing mutations lead to an enzyme deficiency that disrupts normal haeme production, resulting in clinical features due to the subsequent accumulation of porphyrin precursors. Like most of the porphyrias, variegate porphyria (VP) is characterized by high inter- and intra- familial clinical variability, with no apparent genotype-phenotype correlation. The delta-aminolevulinate synthase-1 gene (ALAS1) is an apparent candidate gene to explain the variable clinical expression observed in VP, since it encodes the first and rate-determining enzyme of haeme synthesis. Several studies have defined important regulatory elements for the human-, rat- and chicken ALAS1 gene that regulate expression patterns of this gene. It was hypothesized that in VP individuals, variants within/near critical regulatory sites might alter the transcription rate of this gene, and consequently increase/decrease the amount of haeme precursors accumulating as a result of the defective haeme synthesis enzyme. The aim of this study was to identify genetic variants that could influence gene expression in the proximal promoter area of the ALAS1 gene, as well as the two ALAS1-drug responsive enhancer sequences (ADRES) located further upstream. DNA (2133 bp per patient) of 19 clinically defined VP patients was analysed by polymerase chain reaction (PCR) and semiautomated DNA sequencing. Subsequently, in silico analyses using appropriate software programs, and in vitro studies using the luciferase reporter system, were performed to investigate the functionality of the identified variants on ALAS1 gene transcription... Masters 2007-11-29T12:34:45Z 2010-06-01T08:53:56Z 2007-11-29T12:34:45Z 2010-06-01T08:53:56Z 2007-03 Thesis http://hdl.handle.net/10019.1/2625 en University of Stellenbosch 2698307 bytes application/pdf application/pdf Stellenbosch : University of Stellenbosch |
| spellingShingle | Porphyria -- South Africa -- Genetic aspects Dissertations -- Genetics Theses -- Genetics Du Plessis, Nelita Analysis of genetic variants in the 5’ regulatory region of the ALAS1 gene in South African patients with Variegate Porphyria (VP) |
| title | Analysis of genetic variants in the 5’ regulatory region of the ALAS1 gene in South African patients with Variegate Porphyria (VP) |
| title_full | Analysis of genetic variants in the 5’ regulatory region of the ALAS1 gene in South African patients with Variegate Porphyria (VP) |
| title_fullStr | Analysis of genetic variants in the 5’ regulatory region of the ALAS1 gene in South African patients with Variegate Porphyria (VP) |
| title_full_unstemmed | Analysis of genetic variants in the 5’ regulatory region of the ALAS1 gene in South African patients with Variegate Porphyria (VP) |
| title_short | Analysis of genetic variants in the 5’ regulatory region of the ALAS1 gene in South African patients with Variegate Porphyria (VP) |
| title_sort | analysis of genetic variants in the 5 regulatory region of the alas1 gene in south african patients with variegate porphyria vp |
| topic | Porphyria -- South Africa -- Genetic aspects Dissertations -- Genetics Theses -- Genetics |
| url | http://hdl.handle.net/10019.1/2625 |
| work_keys_str_mv | AT duplessisnelita analysisofgeneticvariantsinthe5regulatoryregionofthealas1geneinsouthafricanpatientswithvariegateporphyriavp |