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Nat Genet. 2015 Apr;47(4):353-60. doi: 10.1038/ng.3222. Epub 2015 Mar 2.

Analyses of allele-specific gene expression in highly divergent mouse crosses identifies pervasive allelic imbalance.

Author information

1
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
2
1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [2] Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
3
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
4
1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [3] Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
5
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
6
1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
7
Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, College Station, Texas, USA.
8
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
9
1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [2] Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [3] Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [4] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Abstract

Complex human traits are influenced by variation in regulatory DNA through mechanisms that are not fully understood. Because regulatory elements are conserved between humans and mice, a thorough annotation of cis regulatory variants in mice could aid in further characterizing these mechanisms. Here we provide a detailed portrait of mouse gene expression across multiple tissues in a three-way diallel. Greater than 80% of mouse genes have cis regulatory variation. Effects from these variants influence complex traits and usually extend to the human ortholog. Further, we estimate that at least one in every thousand SNPs creates a cis regulatory effect. We also observe two types of parent-of-origin effects, including classical imprinting and a new global allelic imbalance in expression favoring the paternal allele. We conclude that, as with humans, pervasive regulatory variation influences complex genetic traits in mice and provide a new resource toward understanding the genetic control of transcription in mammals.

PMID:
25730764
PMCID:
PMC4380817
DOI:
10.1038/ng.3222
[Indexed for MEDLINE]
Free PMC Article

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