Analyses of allele-specific gene expression in highly divergent mouse crosses identifies pervasive allelic imbalance.
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.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
James J
JJ
Crowley
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Vasyl
V
Zhabotynsky
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.
Wei
W
Sun
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Shunping
S
Huang
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Isa Kemal
IK
Pakatci
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Yunjung
0000000190804739
Y
Kim
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Jeremy R
JR
Wang
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.
Andrew P
AP
Morgan
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.
John D
JD
Calaway
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
David L
DL
Aylor
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Zaining
Z
Yun
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.
Timothy A
TA
Bell
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.
Ryan J
RJ
Buus
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.
Mark E
ME
Calaway
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.
John P
JP
Didion
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.
Terry J
TJ
Gooch
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.
Stephanie D
SD
Hansen
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.
Nashiya N
NN
Robinson
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.
Ginger D
GD
Shaw
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Jason S
JS
Spence
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Corey R
CR
Quackenbush
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Cordelia J
CJ
Barrick
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Randal J
RJ
Nonneman
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Kyungsu
K
Kim
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
James
J
Xenakis
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Yuying
Y
Xie
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.
William
0000000224190430
W
Valdar
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Alan B
AB
Lenarcic
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Wei
W
Wang
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Catherine E
CE
Welsh
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Chen-Ping
CP
Fu
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Zhaojun
Z
Zhang
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
James
J
Holt
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Zhishan
Z
Guo
Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, College Station, Texas, USA.
David W
DW
Threadgill
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Lisa M
LM
Tarantino
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.
Darla R
DR
Miller
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Fei
F
Zou
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Leonard
L
McMillan
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.
Patrick F
000000026619873X
PF
Sullivan
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.
Fernando
F
Pardo-Manuel de Villena
D000483:Alleles; D022981:Allelic Imbalance / Q000235:genetics*; D000818:Animals; D003433:Crosses, Genetic; D004303:Dosage Compensation, Genetic; D005260:Female; D015870:Gene Expression; D049810:Genetic Speciation; D006801:Humans; D008297:Male; D051379:Mice / Q000235:genetics*; D018345:Mice, Knockout; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide