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

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.

journal_name

Elife

journal_title

eLife

authors

Hasin-Brumshtein Y,Khan AH,Hormozdiari F,Pan C,Parks BW,Petyuk VA,Piehowski PD,Brümmer A,Pellegrini M,Xiao X,Eskin E,Smith RD,Lusis AJ,Smith DJ

doi

10.7554/eLife.15614

subject

Has Abstract

pub_date

2016-09-13 00:00:00

issn

2050-084X

journal_volume

5

pub_type

杂志文章

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