title: Sex-specific gene expression in the BXD mouse liver.
abstract: Differences in clinical phenotypes between the sexes are well documented and have their roots in differential gene expression. While sex has a major effect on gene expression, transcription is also influenced by complex interactions between individual genetic variation and environmental stimuli. In this study, we sought to understand how genetic variation affects sex-related differences in liver gene expression by performing genetic mapping of genomewide liver mRNA expression data in a genetically defined population of naive male and female mice from C57BL/6J, DBA/2J, B6D2F1, and 37 C57BL/6J x DBA/2J (BXD) recombinant inbred strains. As expected, we found that many genes important to xenobiotic metabolism and other important pathways exhibit sexually dimorphic expression. We also performed gene expression quantitative trait locus mapping in this panel and report that the most significant loci that appear to regulate a larger number of genes than expected by chance are largely sex independent. Importantly, we found that the degree of correlation within gene expression networks differs substantially between the sexes. Finally, we compare our results to a recently released human liver gene expression data set and report on important similarities in sexually dimorphic liver gene expression between mouse and human. This study enhances our understanding of sex differences at the genome level and between species, as well as increasing our knowledge of the molecular underpinnings of sex differences in responses to xenobiotics.
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Gatti
authors.forename: Ni
authors.initials: N
authors.lastname: Zhao
authors.forename: Elissa J
authors.initials: EJ
authors.lastname: Chesler
authors.forename: Blair U
authors.initials: BU
authors.lastname: Bradford
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Shabalin
authors.forename: Roumyana
authors.initials: R
authors.lastname: Yordanova
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Ivan
authors.initials: I
authors.lastname: Rusyn
mesh_terms: D000818:Animals; D002678:Chimera / Q000235:genetics* / Q000378:metabolism; D003433:Crosses, Genetic; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D020411:Oligonucleotide Array Sequence Analysis; D012737:Sex Factors