Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biochemistry

Supervisor

Hegele, Robert A.

Abstract

Familial hypercholesterolemia (FH) is a genetic disorder of severely elevated low-density lipoprotein (LDL) cholesterol that is widely underdiagnosed and undertreated. To improve the identification of FH and initiate timely and appropriate treatment strategies, genetic testing is becoming increasingly offered worldwide as a central part of diagnosis. I describe three main ways providing a genetic diagnosis in FH can be improved. First, next-generation sequencing (NGS)-based approaches can be used to reliably identify large-scale variant types known as copy number variations (CNVs) in the LDL receptor gene (LDLR); second, NGS methodology can be further applied to extend CNV screening to additional FH-associated genes, which have remained uninvestigated but may harbor novel causative variation; and third, the interpretation of variants identified during the course of genetic testing can be improved with the establishment of an open-source database containing variants identified in FH patients worldwide.

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