CMSC Alumna of the Year

Integrating exome sequencing, mRNA-seq, and microRNA-seq to identify genes and mechanisms in optic nerve degeneration
In glaucoma, progressive optic nerve degeneration can lead to irreversible vision impairment and eventual blindness, despite treatment. Genetic causes and influences are not yet clear in primary open angle glaucoma (POAG), the most prevalent form of the disease in North America, Europe, and several other parts of the world. The genetics of POAG are complex; to date, no single causative genomic variant has been established as causing the disease.
Genome-wide sequencing of exons from protein coding and non-coding genes in 333 patients with primary open angle glaucoma revealed over 100 associated SNP sites in over 70 genes. To rank and prioritize genes and generate hypotheses about molecular mechanisms disrupted by associated variant sites, mRNA and small RNA (microRNA) were sequenced from ocular tissues relevant to the disease.
Analysis protocols and techniques for integrated data interpretation to construct putative regulatory networks underlying disease will be discussed. The approach revealed two strong candidate models explaining neurodegeneration in POAG. Data collection and analysis methods are generally applicable beyond glaucoma to other chronic, progressive diseases associated with aging.In glaucoma, progressive optic nerve degeneration can lead to irreversible vision impairment and eventual blindness, despite treatment. Genetic causes and influences are not yet clear in primary open angle glaucoma (POAG), the most prevalent form of the disease in North America, Europe, and several other parts of the world. The genetics of POAG are complex; to date, no single causative genomic variant has been established as causing the disease.