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

Yehudit Hasin-Brumshtein; Arshad H Khan; Farhad Hormozdiari; Calvin Pan; Brian W Parks; Vladislav A Petyuk; Paul D Piehowski; Anneke Brümmer; Matteo Pellegrini; Xinshu Xiao; Eleazar Eskin; Richard D Smith; Aldons J Lusis; Desmond J Smith

doi:10.7554/eLife.15614

eLife (Sep 2016)

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

Yehudit Hasin-Brumshtein,
Arshad H Khan,
Farhad Hormozdiari,
Calvin Pan,
Brian W Parks,
Vladislav A Petyuk,
Paul D Piehowski,
Anneke Brümmer,
Matteo Pellegrini,
Xinshu Xiao,
Eleazar Eskin,
Richard D Smith,
Aldons J Lusis,
Desmond J Smith

Affiliations

Yehudit Hasin-Brumshtein: ORCiD; Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Department of Microbiology, University of California, Los Angeles, Los Angeles, United states; Department of Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Arshad H Khan: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States
Farhad Hormozdiari: Department of Computer Science, University of California, Los Angeles, Los Angeles, United States
Calvin Pan: Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Brian W Parks: Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Department of Microbiology, University of California, Los Angeles, Los Angeles, United states; Department of Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Vladislav A Petyuk: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States
Paul D Piehowski: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States
Anneke Brümmer: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States
Matteo Pellegrini: Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Xinshu Xiao: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States
Eleazar Eskin: Department of Computer Science, University of California, Los Angeles, Los Angeles, United States
Richard D Smith: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States
Aldons J Lusis: Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Department of Microbiology, University of California, Los Angeles, Los Angeles, United states; Department of Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Desmond J Smith: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States

DOI: https://doi.org/10.7554/eLife.15614
Journal volume & issue: Vol. 5

Abstract

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Previous studies had shown that the 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 provide a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation.

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

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