Transcriptome Atlases of Mouse Brain Reveals Differential Expression Across Brain Regions and Genetic Backgrounds

G3: Genes, Genomes, Genetics

Fred A. Wright²  Zaining Yun⁴  Vasyl Zhabotynsky⁴  Fernando Pardo-Manuel de Villena¹  Wei Sun⁵  Darla R. Miller⁴  Ryan J. Buus⁴  Fei Zou²  James J. Crowley⁴  Patrick F. Sullivan⁴  Jeremy Wang³  Leonard McMillan³  Seunggeun Lee² 

[1] Department of GeneticsLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599Department of GeneticsDepartment of GeneticsLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599Department of GeneticsLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599;Department of BiostatisticsDepartment of BiostatisticsDepartment of Biostatistics;Department of Computer SciencesDepartment of Computer SciencesDepartment of Computer Sciences;Department of GeneticsDepartment of GeneticsDepartment of Genetics;Department of GeneticsDepartment of BiostatisticsDepartment of GeneticsDepartment of GeneticsDepartment of BiostatisticsDepartment of BiostatisticsDepartment of GeneticsDepartment of Biostatistics

关键词: Mouse Genetic Resource;    Mouse Collaborative Cross;    mouse;    gene expression;    whole brain;    forebrain;    hindbrain;    sequence variation;   

DOI  :  10.1534/g3.111.001602

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

Mouse models play a crucial role in the study of human behavioral traits and diseases. Variation of gene expression in brain may play a critical role in behavioral phenotypes, and thus it is of great importance to understand regulation of transcription in mouse brain. In this study, we analyzed the role of two important factors influencing steady-state transcriptional variation in mouse brain. First we considered the effect of assessing whole brain vs. discrete regions of the brain. Second, we investigated the genetic basis of strain effects on gene expression. We examined the transcriptome of three brain regions using Affymetrix expression arrays: whole brain, forebrain, and hindbrain in adult mice from two common inbred strains (C57BL/6J vs. NOD/ShiLtJ) with eight replicates for each brain region and strain combination. We observed significant differences between the transcriptomes of forebrain and hindbrain. In contrast, the transcriptomes of whole brain and forebrain were very similar. Using 4.3 million single-nucleotide polymorphisms identified through whole-genome sequencing of C57BL/6J and NOD/ShiLtJ strains, we investigated the relationship between strain effect in gene expression and DNA sequence similarity. We found that cis-regulatory effects play an important role in gene expression differences between strains and that the cis-regulatory elements are more often located in 5′ and/or 3′ transcript boundaries, with no apparent preference on either 5′ or 3′ ends.

【 授权许可】

Unknown