Genomic and functional analyses of Newfoundland and Labrador families with intracranial aneurysms

Pennell, Julia (2021) Genomic and functional analyses of Newfoundland and Labrador families with intracranial aneurysms. Masters thesis, Memorial University of Newfoundland.

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The integrity of an arterial wall is impacted by various genetic, environmental, and physiological factors that predispose to intracranial aneurysm (IA) formation in certain individuals. In this study, whole exome sequencing was completed on a large cohort of families from the Newfoundland and Labrador population to identify genetic predispositions contributing to IA development. With the use of Sanger sequencing, HAL (c.959C>T; p.T320M) emerged as a favourable candidate variant, and morpholino mediated gene knockdown of hal in Danio rerio (zebrafish) demonstrated a dose-dependent hemorrhagic phenotype. The re-expression of wildtype HAL RNA in the hal morpholino background was able to rescue the hemorrhagic phenotype while mutant HAL RNA was not. These results suggest that the HAL (c.959C>T; p.T320M) variant could be contributing to IA development in Family R1262. Additional analysis of the HAL gene could help determine the extent of its involvement and contribute to an improved understanding of IA pathogenesis.

Item Type: Thesis (Masters)
Item ID: 15010
Additional Information: Includes bibliographical references (pages 180-194).
Keywords: intracranial, aneurysm, newfoundland
Department(s): Medicine, Faculty of > Clinical Disciplines > Genetics
Date: February 2021
Date Type: Submission
Digital Object Identifier (DOI):
Medical Subject Heading: Genetic Predisposition to Disease; Intracranial Aneurysm; Newfoundland and Labrador.

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