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Identification of the modulators of cardiac ion channel function
Thesis (MScMedSc (Biomedical Sciences. Molecular Biology and Human Genetics))--University of Stellenbosch, 2009.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : University of Stellenbosch
2009
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| _version_ | 1867613966969077760 |
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| access_status_str | Open Access |
| author | Carstens, Johanna J. |
| author2 | Corfield, Valerie A. |
| author_browse | Carstens, Johanna J. Corfield, Valerie A. |
| author_facet | Corfield, Valerie A. Carstens, Johanna J. |
| author_sort | Carstens, Johanna J. |
| collection | Thesis |
| dc_rights_str_mv | University of Stellenbosch |
| description | Thesis (MScMedSc (Biomedical Sciences. Molecular Biology and Human Genetics))--University of Stellenbosch, 2009. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/2163 |
| 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 | 2009 |
| publishDateRange | 2009 |
| publishDateSort | 2009 |
| 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:10019.1/2163 Identification of the modulators of cardiac ion channel function Carstens, Johanna J. Corfield, Valerie A. Durrheim, Glenda A. University of Stellenbosch. Faculty of Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics. Long QT Syndrome Ion channels HERG Protein-protein interactions Dissertations -- Medicine Theses -- Medicine Biomedical Sciences Molecular Biology and Human Genetics Thesis (MScMedSc (Biomedical Sciences. Molecular Biology and Human Genetics))--University of Stellenbosch, 2009. The human ether-à-go-go-related gene (HERG) encodes the protein underlying the cardiac potassium current IKr. Mutations in HERG may produce defective channels and cause Long QT Syndrome (LQTS), a cardiac disease affecting 1 in 2500 people. The disease is characterised by a prolonged QT interval on a surface electrocardiogram and has a symptomatic variability of sudden cardiac death in childhood to asymptomatic longevity. We hypothesised that genetic variation in the proteins that interact with HERG might modify the clinical expression of LQTS. Yeast two-hybrid methodology was used to screen a human cardiac cDNA library in order to identify putative HERG N-terminus ligands. Successive selection stages reduced the number of putative HERG ligandcontaining colonies (preys) from 268 to 8. Putative prey ligands were sequenced and identified by BLAST-search. False positive ligands were excluded based on their function and subcellular location. Three strong candidate ligands were identified: Rhoassociated coiled-coil containing kinase 1 (ROCK1), γ-sarcoglycan (SGCG) and microtubule-associated protein 1A (MAP1A). In vitro co-immunoprecipitation (Co-IP) and mammalian two-hybrid (M2H) analyses were used to validate these proposed interactions, but failed to do so. This should be further investigated. Analysis of confirmed interactions will shed light on their functional role and might contribute to understanding the symptomatic variability seen in LQTS. 2009-02-19T12:20:50Z 2010-06-01T08:41:55Z 2009-02-19T12:20:50Z 2010-06-01T08:41:55Z 2009-03 Thesis http://hdl.handle.net/10019.1/2163 en University of Stellenbosch application/pdf Stellenbosch : University of Stellenbosch |
| spellingShingle | Long QT Syndrome Ion channels HERG Protein-protein interactions Dissertations -- Medicine Theses -- Medicine Biomedical Sciences Molecular Biology and Human Genetics Carstens, Johanna J. Identification of the modulators of cardiac ion channel function |
| title | Identification of the modulators of cardiac ion channel function |
| title_full | Identification of the modulators of cardiac ion channel function |
| title_fullStr | Identification of the modulators of cardiac ion channel function |
| title_full_unstemmed | Identification of the modulators of cardiac ion channel function |
| title_short | Identification of the modulators of cardiac ion channel function |
| title_sort | identification of the modulators of cardiac ion channel function |
| topic | Long QT Syndrome Ion channels HERG Protein-protein interactions Dissertations -- Medicine Theses -- Medicine Biomedical Sciences Molecular Biology and Human Genetics |
| url | http://hdl.handle.net/10019.1/2163 |
| work_keys_str_mv | AT carstensjohannaj identificationofthemodulatorsofcardiacionchannelfunction |