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

• Published in: Nature genetics Vol. 47; no. 4; pp. 353 - 360
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2015; Nature Publishing Group
• Subjects: 38/90; 45/91; 631/208/199; 631/208/212/2019; 64/60; Agriculture; Alleles; Allelic Imbalance - genetics; Allelomorphism; Animal Genetics and Genomics; Animals; Biomedicine; Cancer Research; Crosses, Genetic; Dosage Compensation, Genetic; Epigenetics; Female; Gene Expression; Gene Function; Genetic diversity; Genetic research; Genetic Speciation; Genetic variation; Genomes; Human Genetics; Humans; Identification and classification; Laboratories; Male; Medicin och hälsovetenskap; Mental health; Mice - genetics; Mice, Knockout; Phylogeny; Polymorphism, Single Nucleotide; Properties; Studies
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.3222

Fernando Pardo-Manuel de Villena and colleagues generate a 3 × 3 diallel cross of three inbred mouse lines and examine gene expression in multiple tissues. They identify allelic imbalance favoring the expression of the paternal allele across the genome. 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.