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

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dc.citation.articleNumberbpaa008en_US
dc.citation.issueNumber1en_US
dc.citation.journalTitleBiology Methods and Protocolsen_US
dc.citation.volumeNumber5en_US
dc.contributor.authorPan, Yidanen_US
dc.contributor.authorTian, Ruoyuen_US
dc.contributor.authorLee, Ciaranen_US
dc.contributor.authorBao, Gangen_US
dc.contributor.authorGibson, Gregen_US
dc.contributor.orgBioengineeringen_US
dc.date.accessioned2021-02-24T19:15:49Zen_US
dc.date.available2021-02-24T19:15:49Zen_US
dc.date.issued2020en_US
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_US
dc.identifier.citationPan, Yidan, Tian, Ruoyu, Lee, Ciaran, et al.. "Fine-mapping within eQTL credible intervals by expression CROP-seq." <i>Biology Methods and Protocols,</i> 5, no. 1 (2020) Oxford University Press: https://doi.org/10.1093/biomethods/bpaa008.en_US
dc.identifier.digitalbpaa008en_US
dc.identifier.doihttps://doi.org/10.1093/biomethods/bpaa008en_US
dc.identifier.urihttps://hdl.handle.net/1911/110091en_US
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.rightsThis 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_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/),en_US
dc.titleFine-mapping within eQTL credible intervals by expression CROP-seqen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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