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

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...

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Main Authors:	Eyal Ben-David, James Boocock, Longhua Guo, Stefan Zdraljevic, Joshua S Bloom, Leonid Kruglyak
Format:	Article
Language:	English
Published:	eLife Sciences Publications Ltd 2021-03-01
Series:	eLife
Subjects:	eqtl single-cell cell-types rna-seq mapping
Online Access:	https://elifesciences.org/articles/65857

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spelling	doaj-0178ab02982d44659194f295d50931d72021-05-05T22:54:45ZengeLife Sciences Publications LtdeLife2050-084X2021-03-011010.7554/eLife.65857Whole-organism eQTL mapping at cellular resolution with single-cell sequencingEyal Ben-David0https://orcid.org/0000-0003-0514-0400James Boocock1Longhua Guo2Stefan Zdraljevic3Joshua S Bloom4https://orcid.org/0000-0002-7241-1648Leonid Kruglyak5https://orcid.org/0000-0002-8065-3057Department 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, IsraelDepartment of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United StatesDepartment of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United StatesDepartment of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United StatesDepartment of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United StatesDepartment of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United StatesGenetic 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.https://elifesciences.org/articles/65857eqtlsingle-cellcell-typesrna-seqmapping
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Eyal Ben-David James Boocock Longhua Guo Stefan Zdraljevic Joshua S Bloom Leonid Kruglyak
spellingShingle	Eyal Ben-David James Boocock Longhua Guo Stefan Zdraljevic Joshua S Bloom Leonid Kruglyak Whole-organism eQTL mapping at cellular resolution with single-cell sequencing eLife eqtl single-cell cell-types rna-seq mapping
author_facet	Eyal Ben-David James Boocock Longhua Guo Stefan Zdraljevic Joshua S Bloom Leonid Kruglyak
author_sort	Eyal Ben-David
title	Whole-organism eQTL mapping at cellular resolution with single-cell sequencing
title_short	Whole-organism eQTL mapping at cellular resolution with single-cell sequencing
title_full	Whole-organism eQTL mapping at cellular resolution with single-cell sequencing
title_fullStr	Whole-organism eQTL mapping at cellular resolution with single-cell sequencing
title_full_unstemmed	Whole-organism eQTL mapping at cellular resolution with single-cell sequencing
title_sort	whole-organism eqtl mapping at cellular resolution with single-cell sequencing
publisher	eLife Sciences Publications Ltd
series	eLife
issn	2050-084X
publishDate	2021-03-01
description	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.
topic	eqtl single-cell cell-types rna-seq mapping
url	https://elifesciences.org/articles/65857
work_keys_str_mv	AT eyalbendavid wholeorganismeqtlmappingatcellularresolutionwithsinglecellsequencing AT jamesboocock wholeorganismeqtlmappingatcellularresolutionwithsinglecellsequencing AT longhuaguo wholeorganismeqtlmappingatcellularresolutionwithsinglecellsequencing AT stefanzdraljevic wholeorganismeqtlmappingatcellularresolutionwithsinglecellsequencing AT joshuasbloom wholeorganismeqtlmappingatcellularresolutionwithsinglecellsequencing AT leonidkruglyak wholeorganismeqtlmappingatcellularresolutionwithsinglecellsequencing
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Whole-organism eQTL mapping at cellular resolution with single-cell sequencing

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