Genome-wide association studies of macular telangiectasia type 2 (MacTel) show the strongest genetic linkage to a critical non-coding region within the 5q14.3 locus (Scerri et al., 2017). This region contains non-coding RNAs, but is devoid of protein coding genes. Dr. Cherry’s lab has identified two distal enhancers centered within this region that are evolutionarily conserved and are active in the adult human retina, macula and RPE/choroid. Additionally, they have determined that two non-coding RNAs within this region, LINC00461 and CTC-498M16, are expressed in these tissues. Both enhancers and non-coding RNAs have roles in regulating gene expression. They hypothesize that disruption of one or more of these regulatory elements are an underlying contributor to macular telangiectasia type 2. The immediate goal of Dr. Cherry’s lab is to characterize these enhancers and RNAs to understand how they regulate gene expression that may be critical for the maintenance of retinal, retinal pigment or vascular cells in the human eye. This work will focus the search for MacTel-associated genetic variants on non-coding regulatory elements, facilitate the interpretation of these variants, and shed light on the underlying biology of MacTel.
More information about Dr. Cherry’s research can be found at his laboratory website.