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Elife. 2016 Sep 13;5. pii: e15614. doi: 10.7554/eLife.15614.

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

Author information

1
Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States.
2
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States.
3
Department of Microbiology, University of California, Los Angeles, Los Angeles, United states.
4
Department of Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States.
5
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States.
6
Department of Computer Science, University of California, Los Angeles, Los Angeles, United States.
7
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States.
8
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States.
9
Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.

Abstract

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.

KEYWORDS:

RNA-Seq; eQTL; evolutionary biology; genomics; high fat diet; hypothalamus; mouse; neuroscience; obesity; trans-eQTL

PMID:
27623010
PMCID:
PMC5053804
DOI:
10.7554/eLife.15614
[Indexed for MEDLINE]
Free PMC Article

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