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Updated: May 20, 2025

Multiplexed Analysis of Retinal Gene Expression and Chromatin Accessibility Using scRNA-Seq and scATAC-Seq
Published on: March 12, 2021
Paired DNA and RNA sequencing uncovers common and rare genetic variants regulating gene expression in the human
Jacob Sampson1, Ayellet V Segrè2,3,4, Kinga M Bujakowska2,3
1Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Abstract:
Genetic disorders impacting vision affect millions of individuals worldwide, including age-related macular degeneration (common) and inherited retinal disorders (rare). There is incomplete understanding of the impact of genetic variation on gene expression in the human retina, and its role in genetic disorders. Through the generation of whole genome sequencing and bulk RNA-sequencing of neurosensory retina (NSR) and retinal pigment epithelium (RPE) from 201 post-mortem eyes, we uncovered common and rare genetic variants shaping retinal expression profiles. This includes 1,483,595 significant cis-expression quantitative trait loci (eQTLs) impacting 9,959 and 3,699 genes in NSR and RPE, respectively, with associated genetic variants enriched to cis-candidate regulatory elements and notable shared eGenes between NSR and RPE. We also detected 1051 expression outliers and prioritised 299 rare non-coding single-nucleotide, structural variants or copy number variants as plausible drivers for 28% of outlier events. This study increases understanding of gene expression regulation in the human retina.
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