Methylenetetrahydrofolate reductase (MTHFR) catalyses the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a carbon donor for the remethylation of homocysteine to methionine. A common mutation in MTHFR, 677C → T, which converts an alanine (A) to a valine (V) residue, is associated with increased plasma homocysteine and, consequently, is a risk factor for several vasculopathies. Recently, a second common mutation in MTHFR was reported (1298A → C) which converts a glutamate (E) to an alanine (A) residue in the C-terminal regulatory region. Thus study was designed to assess the in vitro and in vivo impact of this polymorphism. Site-directed mutagenesis of the human MTHFR cDNA was performed to create all four combinations of the two common MTHFR polymorphisms. Enzyme activity was assessed in a bacterial expression system. / Since the 1298A → C polymorphism is due to a mutation in the regulatory domain, a parallel study was performed involving the complete deletion of this region. / For in vivo assessment of the 1298A → C variant, we examined this mutation in three clinical populations. / Betaine-homocysteine methyltransferase (BHMT) is a second remethylation enzyme that converts betaine and homocysteine to dimethylglycine and methionine, respectively. This work represents the first report of sequence variants in the newly-cloned BHMT gene. Using SSCP analysis, three common base changes were identified in a panel of healthy controls. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.30768 |
| Date | January 1999 |
| Creators | Weisberg, Ilan S. |
| Contributors | Rozen, Rima (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Biology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001746282, proquestno: MQ64479, Theses scanned by UMI/ProQuest. |
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