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North Carolina Macular Dystrophy Condition Linked to Enhancer Alterations

Investigators at Ghent University and other international centers consider the regulatory underpinnings of a rare, autosomal dominant macular development condition called North Carolina macular dystrophy (NCMD) for a paper in the American Journal of Human Genetics. The team began by bringing published chromatin immunoprecipitation sequencing, RNA sequence, ATAC-seq, and other genome-wide data generated for adult retinal tissue into the so-called RegRet database to understand the regulatory features of NCMD — a condition that has been linked to non-coding SNPs near PRDM13 and duplications in and around PRDM13 or IRX1. Following a series of chromosome conformation capture experiments and enhancer detection assays in cell lines and Xenopus tadpole models, the authors went on to characterize cis-regulatory element candidates with the help of single-cell RNA sequence data from retinal samples from embryonic and adult tissue samples, uncovering apparent gene enhancer shifts in NCMD. Together, they say, the results suggest that "altered PRDM13 or IRX1 expression impairs macula-specific synaptic interactions between amacrine and ganglion cells during retinogenesis." In addition, they note, "we have provided an integrated retinal multi-omics database, which advances the annotation of the genome in human retinal and represents a universal framework for the investigation of disease-associated loci implicated in rare as well as complex retinal diseases."