Format

Send to

Choose Destination
Cell Stem Cell. 2017 Apr 6;20(4):533-546.e7. doi: 10.1016/j.stem.2017.03.009.

Large-Scale Profiling Reveals the Influence of Genetic Variation on Gene Expression in Human Induced Pluripotent Stem Cells.

Author information

1
Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093-0419, USA.
2
Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093-0419, USA.
3
Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093-0419, USA; Department of Biomedical Informatics, University of California, San Diego, La Jolla, CA 92093-0419, USA.
4
Department of Pediatrics and Rady Children's Hospital, University of California, San Diego, La Jolla, CA 92093-0419, USA.
5
Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0419, USA; Division of Biological Sciences, Section of Molecular Biology, University of California, San Diego, La Jolla, CA 92093-0419, USA.
6
Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093-0419, USA; Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
7
Human Longevity, San Diego, CA 92121, USA.
8
Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093-0419, USA; Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0419, USA.
9
Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0419, USA; Division of Biological Sciences, Section of Molecular Biology, University of California, San Diego, La Jolla, CA 92093-0419, USA. Electronic address: efarley@ucsd.edu.
10
Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093-0419, USA; Department of Pediatrics and Rady Children's Hospital, University of California, San Diego, La Jolla, CA 92093-0419, USA. Electronic address: kafrazer@ucsd.edu.

Abstract

In this study, we used whole-genome sequencing and gene expression profiling of 215 human induced pluripotent stem cell (iPSC) lines from different donors to identify genetic variants associated with RNA expression for 5,746 genes. We were able to predict causal variants for these expression quantitative trait loci (eQTLs) that disrupt transcription factor binding and validated a subset of them experimentally. We also identified copy-number variant (CNV) eQTLs, including some that appear to affect gene expression by altering the copy number of intergenic regulatory regions. In addition, we were able to identify effects on gene expression of rare genic CNVs and regulatory single-nucleotide variants and found that reactivation of gene expression on the X chromosome depends on gene chromosomal position. Our work highlights the value of iPSCs for genetic association analyses and provides a unique resource for investigating the genetic regulation of gene expression in pluripotent cells.

KEYWORDS:

eQTL; expression quantitative trait loci; gene expression; regulation of gene expression; stem cell gene expression; stem cell genetics

PMID:
28388430
PMCID:
PMC5444918
DOI:
10.1016/j.stem.2017.03.009
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center