Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes

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Abstract

Previous studies had shown that integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP), a reference resource population for cardiovascular and metabolic traits. We report numerous novel transcripts supported by proteomic analyses, as well as novel non coding RNAs. High resolution genetic mapping of transcript levels in HMDP, reveals both local and trans expression Quantitative Trait Loci (eQTLs) demonstrating 2 trans eQTL 'hotspots' associated with expression of hundreds of genes. We also report thousands of alternative splicing events regulated by genetic variants. Finally, comparison with about 150 metabolic and cardiovascular traits revealed many highly significant associations. Our data provides a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation.

Data availability

The following data sets were generated

(2016) Hypothalamic transcriptome of male mice on high fat diet, from 99 strains
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE79551).

http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE79551
1. Hasin-Brumshtein Y et al.
(2016) Data from: Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes
Available at Dryad Digital Repository under a CC0 Public Domain Dedication.

http://dx.doi.org/10.5061/dryad.vm525

Article and author information

Author details

Yehudit Hasin-Brumshtein

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States

For correspondence
yehudit.hasin@gmail.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7528-603X
Arshad H Khan

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Farhad Hormozdiari

Department of Computer Science, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Calvin Pan

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Brian W Parks

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Vladislav A Petyuk

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States

Competing interests
The authors declare that no competing interests exist.
Paul D Piehowski

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States

Competing interests
The authors declare that no competing interests exist.
Anneke Bruemmer

Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Matteo Pellegrini

Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Xinshu Xiao

Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Eleazar Eskin

Department of Computer Science, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Richard D Smith

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States

Competing interests
The authors declare that no competing interests exist.
Aldons J Lusis

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Desmond J Smith

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.

Funding

National Institutes of Health (R01HG006264)

Xinshu Xiao

National Institutes of Health (R01GM098273)

Yehudit Hasin-Brumshtein
Arshad H Khan
Calvin Pan
Vladislav A Petyuk
Paul D Piehowski
Richard D Smith
Aldons J Lusis
Desmond J Smith

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The animal protocol for the study was approved by the Institutional Animal Care and Use Committee (IACUC) at University of California, Los Angeles.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.