Whole-organism eQTL mapping at cellular resolution with single-cell sequencing

eLife

Leonid Kruglyak¹  Joshua S Bloom¹  James Boocock¹  Stefan Zdraljevic¹  Longhua Guo¹  Eyal Ben-David² 

[1] Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States;Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States;Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, The Hebrew University School of Medicine, Jerusalem, Israel;

关键词: eqtl;    single-cell;    cell-types;    rna-seq;    mapping;    C. elegans;   

DOI  :  10.7554/eLife.65857

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Genetic regulation of gene expression underlies variation in disease risk and other complex traits. The effect of expression quantitative trait loci (eQTLs) varies across cell types; however, the complexity of mammalian tissues makes studying cell-type eQTLs highly challenging. We developed a novel approach in the model nematode Caenorhabditis elegans that uses single-cell RNA sequencing to map eQTLs at cellular resolution in a single one-pot experiment. We mapped eQTLs across cell types in an extremely large population of genetically distinct C. elegans individuals. We found cell-type-specific trans eQTL hotspots that affect the expression of core pathways in the relevant cell types. Finally, we found single-cell-specific eQTL effects in the nervous system, including an eQTL with opposite effects in two individual neurons. Our results show that eQTL effects can be specific down to the level of single cells.

【 授权许可】

CC BY