Project description:Prostate cancer (PCa) associated risk SNPs are enriched in cis-regulatory elements (CREs). In this study, we screened 260 CREs that contain at least one PCa risk SNP for essentiality in V16A, 22Rv1 and A549 cells. We tiled the CREs and 14 control regions using 5,873 sgRNAs.
Project description:Genome-wide association studies implicate multiple loci in risk for systemic lupus erythematosus (SLE), but few contain exonic variants, rendering systematic identification of non-coding variants essential to decoding SLE genetics. We utilized SNP-seq and bioinformatic enrichment to interrogate 2180 single-nucleotide polymorphisms (SNPs) from 87 SLE risk loci for potential binding of transcription factors and related proteins from B cells. 52 SNPs that passed initial screening were tested by electrophoretic mobility shift (EMSA) and luciferase reporter assays. To identify binding of transcription factors and/or other nuclear proteins in an allele-determined manner, we employed pulldown using nuclear extract from Daudi cells and silver staining in SNPs that had exhibited allele-specific differential binding by EMSA. Each pulldown product for each allele of the five high-probability SNPs (rs2297550 C/G, rs13213604 C/G, rs276461 T/C, rs9907955 C/T, rs7302634 T/C) was evaluated by mass spectrometry (MS) to identify binding nuclear proteins, yielding a set of candidate proteins for each.
Project description:Prostate cancer (PCa) associated risk SNPs are enriched in cis-regulatory elements (CREs). In this study, we screened 260 CREs that contain at least one PCa risk SNP for essentiality in V16A, 22Rv1 and A549 cells. We tiled the CREs and 14 control regions using 5,873 sgRNAs.
Project description:Prostate cancer (PCa) associated risk SNPs are enriched in cis-regulatory elements (CREs). In this study, we screened 260 CREs that contain at least one PCa risk SNP for essentiality in V16A, 22Rv1 and A549 cells. We tiled the CREs and 14 control regions using 5,873 sgRNAs.
Project description:Prostate cancer (PCa) associated risk SNPs are enriched in cis-regulatory elements (CREs). In this study, we screened 260 CREs that contain at least one PCa risk SNP for essentiality in V16A, 22Rv1 and A549 cells. We tiled the CREs and 14 control regions using 5,873 sgRNAs.
Project description:Using Massively Parallel Reporter Assays (MPRAs), we functionally screened over 1,000 SNPs, prioritized from 39 neuropsychiatric trait/disease GWAS loci based on overlap with predicted regulatory features—including expression quantitative trait loci (eQTL) and histone marks—from human brains and cell cultures. Using mouse neuroblastoma Neuro2a (N2a) cells, we identify over 100 SNPs with allelic effects on expression. Functional SNPs were enriched for binding sequences of retinoic acid-receptive transcription factors (TFs); with additional allelic differences unmasked in cells treated with all-trans retinoic acid (ATRA). Motifs overrepresented at functional SNPs corresponded to a set of TFs highly specific to serotonergic neurons and collectively downregulated in schizophrenia. Our application of MPRAs to screen MDD-associated SNPs suggested a shared transcriptional regulatory program across loci, a subset of which are unmasked by retinoids. Additional code and results corresponding to this GEO submission can be found at https://bitbucket.org/jdlabteam/n2a_atra_mdd_mpra_paper/src
2021-06-30 | GSE167517 | GEO
Project description:Sequencing datas for Rhododendron cyanocarpum using ddRAD-seq
Project description:Most type 1 diabets (T1D) associated SNPs are located in non-coding regions, making it hard to understand their functional impact. We performed epigenomic profiling of two enhancer marks, H3K4me1 and H3K27ac, using primary TH1 and TREG cells from healthy and T1D subjects. By integrating enhancers predicted using these ChIP-Seq data, T1D associated SNPs and additional supporting data, we found and validated several novel risk SNPs for T1D.
