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

Simple item page
dc.citation.articleNumberbpaa008
dc.citation.issueNumber1
dc.citation.journalTitleBiology Methods and Protocols
dc.citation.volumeNumber5
dc.contributor.authorPan, Yidan
dc.contributor.authorTian, Ruoyu
dc.contributor.authorLee, Ciaran
dc.contributor.authorBao, Gang
dc.contributor.authorGibson, Greg
dc.date.accessioned2021-02-24T19:15:49Z
dc.date.available2021-02-24T19:15:49Z
dc.date.issued2020
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.
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.
dc.identifier.digitalbpaa008
dc.identifier.doihttps://doi.org/10.1093/biomethods/bpaa008
dc.identifier.urihttps://hdl.handle.net/1911/110091
dc.language.isoeng
dc.publisherOxford University Press
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.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/),
dc.titleFine-mapping within eQTL credible intervals by expression CROP-seq
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
bpaa008.pdf
Size:
503.78 KB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
Bioengineering Publications