Whole-organism EQTL Mapping at Cellular Resolution with Single-cell Sequencing

Overview

Journal Elife

Specialty Biology

Date 2021 Mar 18

PMID 33734084

Citations 17

Authors

Eyal Ben-David

James Boocock

Longhua Guo

Stefan Zdraljevic

Joshua S Bloom

Leonid Kruglyak

Affiliations

Soon will be listed here.

Abstract

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 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 individuals. We found cell-type-specific 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.

Citing Articles

Single-cell eQTL mapping in yeast reveals a tradeoff between growth and reproduction.

Boocock J, Alexander N, Alamo Tapia L, Walter-McNeill L, Patel S, Munugala C Elife. 2025; 13.

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Expansion microscopy reveals neural circuit organization in genetic animal models.

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Multimodal joint deconvolution and integrative signature selection in proteomics.

Pan Y, Wang X, Sun J, Liu C, Peng J, Li Q Commun Biol. 2024; 7(1):493.

PMID: 38658803 PMC: 11043077. DOI: 10.1038/s42003-024-06155-z.

The dynamic genetic determinants of increased transcriptional divergence in spermatids.

Panten J, Heinen T, Ernst C, Eling N, Wagner R, Satorius M Nat Commun. 2024; 15(1):1272.

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