Identifying Cis-Regulatory Elements Around The ARMS2 Locus

Joseph Corbo, MD, PhD Washington University, School of Medicine


Recent genetics studies have delineated a 23.3 Kb region around the ARMS2 locus that contains DNA sequence variants that are strongly associated with a person's susceptibility to age-related macular degeneration (AMD). We propose to identify all of the photoreceptor-specific gene regulatory elements in this 23.3 Kb region and to test whether sequence variants within these regions found in AMD patients affect the activity of these elements. In this manner it should be possible to determine which sequence variants are likely to cause disease, thus facilitating the genetic diagnosis of AMD.

Project Details

DNA changes that can predispose patients to age-related macular degeneration (AMD) come in two varieties: those which affect sequences that encode proteins (so-called, 'coding' changes) and those which affect sequences that control the expression of genes ('non-coding' changes). Although a lot is known about 'coding' changes, 'non-coding' changes are relatively poorly understood. Our research aims to develop a better understanding of the effects of 'non-coding' changes on a person's susceptibility to AMD. We plan to first map the location of 'cis-regulatory elements' which control the expression of genes relevant to AMD. Then, we will determine which DNA changes found in AMD patients are associated with changes in the expression of these AMD genes. Once we have successfully completed this research, we should be able to more accurately diagnose AMD and predict which patients are likely to be affected by it by being able to more precisely map the effects of their DNA changes on AMD gene expression. The financial support of the BrightFocus Foundation is critical to furthering our understanding of this devastating disease.