Genetic regulation of sex-specific gene expression in mouse liver.

摘要

Sexual dimorphism in the expression of many genes is thought to play an important role in disease susceptibility, drug metabolism, and xenobiotic response in both humans and other species. While previous research has explored the relationship between phenotypes and sex-dependent differences in expression of individual genes, this study dissected the genetic underpinnings that control sex-specific gene expression in mouse liver. We performed genetic mapping of genome-wide liver mRNA expression data in naive male and female mice from C57BL/6J, DBA/2J, B6D2F1, and 37 BXD strains. Thousands of liver transcripts exhibited considerable differences in expression between females and males. An array permutation based functional analysis identified several xenobiotic metabolism pathways, which are strongly dependent on subject's sex. Furthermore, expression quantitative trait locus (eQTL) mapping identified several eQTLs that are major sex-specific regulators of gene expression in mouse liver and the candidate genes that are likely to be the regulators for these loci were revealed. Co-expressed genes were shown to be more likely to be involved in similar functions, supporting the hypothesis of "guilt by association". Conclusion. This study provided more evidence in the sexually dimorphic gene expression in the liver, which can convey important implications to toxicological and pharmaceutical studies.