DOI

10.17077/etd.0lhn-fnb1

Document Type

Dissertation

Date of Degree

Spring 2019

Degree Name

PhD (Doctor of Philosophy)

Degree In

Genetics

First Advisor

Scheetz, Todd

Second Advisor

Sheffield, Val

First Committee Member

Mullins, Robert

Second Committee Member

Darbro, Benjamin

Third Committee Member

Sohn, Elliott

Abstract

It is estimated that 4000 genetic diseases/syndromes affect humans with one third of these diseases involving the eye. Many eye disorders, such as age-related macular degeneration that affects an estimated 170 million elderly adults worldwide, are associated with genetic variants. Since the conception of the human genome project we have learned a great deal about the genetic make-up of the human race and have identified over ~20,000 genes. Over 270 of these genes have been implicated in retinal diseases alone with many more genes involved in other forms of ocular disease. Though we have made a great deal of progress in understanding the genetics of eye disease, there remain many eye diseases with significant evidence of genetic components for which a disease-causing gene has not been identified.

In my thesis research, I utilized computational tools and strategies to analyze microarrays and whole-exome sequencing to investigate the genetic causes of three different eye diseases. First, I utilized a combination of familial analyses and whole-exome sequencing to study the genetic cause of Keratoconus, a progressive cornea abnormality that can lead to distorted vision and light sensitivity. Second, I analyzed three different cohorts of patients with Bardet-Biedl syndrome (BBS), a syndromic retinopathy leading to blindness, using whole-exome sequencing to identify both known and novel genetic causes of BBS. Finally, I performed the largest whole-exome sequencing study at the time for Pigment Dispersion Syndrome (PDS), a disorder associated with glaucoma, and identified variants within previously established candidate genes and a novel candidate gene that is now the subject of further scientific investigation.

By using computational tools and strategies in tandem with high-quality bench research performed by fellow lab members, we have identified both candidate and known eye disease-causing genes/mutations and furthered the goal to cure blindness.

Keywords

Bardet-Biedl, Computational, Eye, Genetics, Next-Generation Sequencing

Pages

xiv, 131 pages

Bibliography

Includes bibliographical references (pages 107-131).

Copyright

Copyright © 2019 Wesley Andrew Goar

Included in

Genetics Commons

Share

COinS