Date of Graduation


Document Type

Dissertation (PhD)

Program Affiliation

Human and Molecular Genetics

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Stephen P. Daiger, Ph.D.

Committee Member

James Hixson, Ph.D.

Committee Member

Alanna C. Morrison, Ph.D.

Committee Member

Hope Northrup, M.D.

Committee Member

John O’Brien, Ph.D.

Committee Member

Eric Swindell, Ph.D.


Retinitis pigmentosa (RP) is an inherited retinal disease that leads to degeneration of the retina through loss of rod and cone photoreceptor cells and subsequent loss of vision. RP affects approximately 1.5 million people world-wide. Mutations causing autosomal dominant retinitis pigmentosa (adRP) have been identified in 23 different genes. However, these mutations only account for approximately 70% of known adRP cases in Caucasians of Western-European origin and for an even smaller percentage of cases in other ethnicities. My research aims to increase the number of known genes associated with adRP by using an array of advanced genetic techniques to search for the disease-causing gene and mutation in a large African American family that has been clinically diagnosed with adRP. Sanger sequencing, targeted-capture next-generation sequencing (NGS), and multiplex ligation-dependent probe amplification (MLPA) were used to evaluate and eliminate the known adRP genes as the genetic cause of disease in this family. Whole-genome linkage mapping followed by fine-point haplotype analysis mapped the disease locus to a 7.7 mega-base region on chromosome 19q. Five candidate genes from within this disease locus were chosen based on their biological relevance to RP and analyzed for possible disease-causing mutations. Whole-exome sequencing and whole-genome sequencing were used to identify 63 rare variants located throughout the disease locus that segregate with disease in this family. Additional genetic and bioinformatic analyses were completed to evaluate these variants’ potential to be disease-causing.

Despite being unable to single-out the disease-causing mutation from among the variants found to segregate with disease in this family, the wealth of data produced in this study will provide necessary genetic information that will continue to aid others in the search for this family’s disease-causing gene. Once this novel adRP gene is identified, it will provide valuable insights that can be used in the diagnosis and prognosis of RP in this family and in other RP patients identified to have mutations in the same underlying gene. Of more importance, identification of the remaining disease-causing genes for adRP is necessary for the continued success that has been seen in the development of treatments and therapies for RP patients.


Retinitis pigmentosa, autosomal dominant, medical genetics, linkage, candidate gene sequencing, next-generation sequencing