Fine-mapping within eQTL credible intervals by expression CROP-seq

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dc.contributor.authorPan, Yidan
dc.contributor.authorTian, Ruoyu
dc.contributor.authorLee, Ciaran M.
dc.contributor.authorBao, Gang
dc.contributor.authorGibson, Greg
dc.contributor.funderNational Institutes of Healthen
dc.date.accessioned2021-01-15T11:47:53Z
dc.date.available2021-01-15T11:47:53Z
dc.date.issued2020-03-28
dc.date.updated2021-01-15T11:36:45Z
dc.description.abstractThe majority of genome-wide association study (GWAS)-identified SNPs are located in noncoding regions of genes and are likely to influence disease risk and phenotypes by affecting gene expression. Since credible intervals responsible for genome-wide associations typically consist of ≥100 variants with similar statistical support, experimental methods are needed to fine map causal variants. We report here a moderate-throughput approach to identifying regulatory GWAS variants, expression CROP-seq, which consists of multiplex CRISPR-Cas9 genome editing combined with single-cell RNAseq to measure perturbation in transcript abundance. Mutations were induced in the HL60/S4 myeloid cell line nearby 57 SNPs in three genes, two of which, rs2251039 and rs35675666, significantly altered CISD1 and PARK7 expression, respectively, with strong replication and validation in single-cell clones. The sites overlap with chromatin accessibility peaks and define causal variants for inflammatory bowel disease at the two loci. This relatively inexpensive approach should be scalable for broad surveys and is also implementable for the fine mapping of individual genes.en
dc.description.sponsorshipNational Institutes of Health (1-R01-HG008146)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleidbpaa008en
dc.identifier.citationPan, Y., Tian, R., Lee, C., Bao, G. and Gibson, G. (2020) 'Fine-mapping within eQTL credible intervals by expression CROP-seq', Biology Methods and Protocols, 5(1), bpaa008 (8pp). doi: 10.1093/biomethods/bpaa008en
dc.identifier.doi10.1093/biomethods/bpaa008en
dc.identifier.endpage8en
dc.identifier.issn2396-8923
dc.identifier.issued1en
dc.identifier.journaltitleBiology Methods and Protocolsen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/10923
dc.identifier.volume5en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.rights© 2020, The Author(s). Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectRegulatory GWAS variantsen
dc.subjectExpression CROP-seqen
dc.subjectCRISPR-Cas9en
dc.subjectGenome editingen
dc.subjectSingle-cell RNAseqen
dc.titleFine-mapping within eQTL credible intervals by expression CROP-seqen
dc.typeArticle (peer-reviewed)en
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