Analyses of allele-specific gene expression in highly divergent mouse crosses identifies pervasive allelic imbalance.
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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.
Crowley, J. J., Zhabotynsky, V., Sun, W., Huang, S., Pakatci, I. K., Kim, Y., ... Pardo-Manuel de Villena, F.
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Crowley, James J||Zhabotynsky, Vasyl||Sun, Wei||Huang, Shunping||Pakatci, Isa Kemal||Kim, Yunjung||Wang, Jeremy R||Morgan, Andrew P||Calaway, John D||Aylor, David L||Yun, Zaining||Bell, Timothy A||Buus, Ryan J||Calaway, Mark E||Didion, John P||Gooch, Terry J||Hansen, Stephanie D||Robinson, Nashiya N||Shaw, Ginger D||Spence, Jason S||Quackenbush, Corey R||Barrick, Cordelia J||Nonneman, Randal J||Kim, Kyungsu||Xenakis, James||Xie, Yuying||Valdar, William||Lenarcic, Alan B||Wang, Wei||Welsh, Catherine E||Fu, Chen-Ping||Zhang, Zhaojun||Holt, James||Guo, Zhishan||Threadgill, David W||Tarantino, Lisa M||Miller, Darla R||Zou, Fei||McMillan, Leonard||Sullivan, Patrick F||Pardo-Manuel de Villena, Fernando
