Investigating Sandhoff Disease in Saskatchewan

dc.contributor.advisorYost, Christopher
dc.contributor.advisorAntonishyn, Nick Anthony
dc.contributor.authorFitterer, Braden Bernard
dc.contributor.committeememberStavrinides, John
dc.contributor.committeememberSomers, Christopher
dc.contributor.externalexaminerMahuran, Don J.
dc.descriptionA Thesis Submitted to the Faculty of Graduate Studies and Research in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Biology, University of Regina. xii, 142p.en_US
dc.description.abstractSandhoff disease is an autosomal recessive lysosomal storage disease caused by mutations in the HEXB gene detrimentally affecting the enzyme β-hexosaminidase. A high incidence of Sandhoff disease has been reported in northern Saskatchewan. The variant of the disease present in the province causes the death of infants before 4 years of age. In order to ameliorate the impact of this disease on the families and communities where it occurs the following steps were taken. Initially, genetic analysis of the HEXB gene from affected patients revealed a common variant shared among 4 individuals. That genetic information was used to develop a diagnostic molecular assay (Chapter 2). A novel synthetic substrate specific for the hydrolytic activity of β-hexosaminidase was obtained and used to develop a biochemical assay for measuring enzyme activity (Chapter 3). Finally, a retrospective study was designed using residual dried blood spots from the Saskatchewan Newborn Screening Program. The two assays were used to screen the dried blood spots for Sandhoff disease carriers in the northern Saskatchewan communities and the frequency of disease-causing alleles was estimated (Chapter 4). A high carrier frequency for Sandhoff disease causing mutations was found during the retrospective analysis coinciding with the high incidence of Sandhoff disease previously reported. As such the assays developed throughout this project may serve as the basis for a preventative carrier screening program for Sandhoff disease in Saskatchewan.en_US
dc.description.uriA Thesis Submitted to the Faculty of Graduate Studies and Research In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy *, University of Regina. *, * p.en
dc.publisherFaculty of Graduate Studies and Research, University of Reginaen_US
dc.titleInvestigating Sandhoff Disease in Saskatchewanen_US
dc.typeThesisen of Biologyen_US of Reginaen of Philosophy (PhD)en_US
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