High resolution chromosome conformation capture from gene promoters at COVID-19, T1D, AS and RBC GWAS loci

Genome Wides Association Studies (GWAS) have identified tens of thousands of associations between human genetic variation and common disease. The majority of causative variants lie in regulatory elements that are located some distance from their target genes. High resolution chromosome conformation capture (3C) has proven useful for identifying enhancer-promoter interaction. We employed targeted Capture-C at loci with GWAS for severe COVID-19, Type-1 Diabetes (T1D), Ankylosing spondylitis (AS) and red blood cell traits (RBC) Overall design: To identify regulatory interactions, we performed high resolution chromatin conformation capture (3C) using NG CaptureC (Davies, NatMethods 2016) or NuTi Capture-C (Downes, NatComms 2020) targeting promoters near variants associated with COVID-19, T1D, AS and RBC. CaptureC was performed in triplicate for Day 10 differentiating erythroid (Ery) cells from three donors, human Embryonic Stem Cells (H1 hESC; WiCell), and Human Umbilical Vein Endothelial Cells (HUVEC; Lonza/Gibco/PromoCell), activated and non-activated CD4+ T-cells, and CD14+ monocytes. Capture was performed with 100-mer biotinylated oligonucleotides targeting sequences adjacent to DpnII sites.