Genetic determinants underlying rare diseases identified using next-generation sequencing technologies

Rare disorders affect less than one in 2000 individuals, placing a huge burden on individuals, families and the health care system. Gene discovery is the starting point in understanding the molecular mechanisms underlying these diseases. The advent of next-generation sequencing has accelerated discovery of disease-causing genetic variants and is showing numerous benefits for research and medicine. I describe the application of next-generation sequencing, namely LipidSeq™ ‒ a targeted resequencing panel for the identification of dyslipidemia-associated variants ‒ and whole-exome sequencing, to identify genetic determinants of several rare diseases. Utilization of next-generation sequencing plus associated bioinformatics led to the discovery of disease-associated variants for 71 patients with lipodystrophy, two with early-onset obesity, and families with brachydactyly, cerebral atrophy, microcephaly-ichthyosis, and widow’s peak syndrome. Understanding these variants and their contribution to disease can increase understanding of disease mechanisms and help with the development of therapeutic interventions in the future.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Biochemistry

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2018

Author dc:creator

• Ho, Rosettia

Advisor dc:contributor.advisor

• Hegele, Robert A.

• Next-generation sequencing
• Genetic disease
• Rare disease
• Mendelian disease
• Variant discovery
• Copy-number variation

Language dc:language.iso

en_ca

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/28298

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/28298