Whole exome sequencing analysis of intracranial aneurysm in multiplex families from Newfoundland and Labrador

• Main Author: Powell, Amy E.
• Format: Thesis
• Language: English
• Published: Memorial University of Newfoundland 2016
• Subjects: Newfoundland
• Online Access: https://research.library.mun.ca/12036/; https://research.library.mun.ca/12036/1/thesis.pdf

Intracranial aneurysm (IA) is a vascular condition characterized as a saccular dilatation of the cerebral artery wall. The purpose of this study was to identify genetic variants that cause susceptibility to IA in two multiplex families from Newfoundland and Labrador. Whole exome sequencing was completed for 12 affected individuals from families R1352 and R1256. A filtering strategy was then implemented to identify and prioritize rare variants that were shared by multiple affected family members. In family R1352, two variants were identified as top candidates: C4orf6 c.1A>G, and GIGYF2 c.3494A>G. Both were present in 6/7 exomes from the family, and passed all filtering steps. In family R1256, SPDYE4 c.103C>T was identified as a variant of interest, as it segregated in 10/11 affected individuals. Though each variant exhibited incomplete segregation, all three were absent from 100 local population controls. The absence of a definitive candidate variant in the exome suggests that further study is necessary to gain better understanding of the genetic etiology of this disease.