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Mammalian Genome

, Volume 17, Issue 6, pp 598–614 | Cite as

Gene expression analysis of mouse chromosome substitution strains

  • Keith R. Shockley
  • Gary A. ChurchillEmail author
Article

Abstract

An analysis of transcriptional variation in the liver using a panel of B.A chromosome substitution strains identified 4209 transcripts that are differentially expressed relative to the C57BL/6J background and 1010 transcripts that are differentially expressed between C57BL/6J and A/J strains. A subset of these strains (substituting Chromosomes 1, 6, and 15) was used to identify 386 additional differentially expressed transcripts in the kidney. Approximately 15% of differentially expressed transcripts are located on the substituted chromosome. These cis-QTL are codirectionally expressed with the donor strain A/J. By comparison, trans-regulated loci comprise 85% of differentially expressed transcripts, often show opposite direction of change compared with A/J, and can be regulated by multiple chromosome substitutions. Gene expression differences in this study provide evidence for transgressive segregation: Only 438 of 4209 QTL in liver were inside the parental range. By combining QTL data with known biological functions, we were able to identify physiologic pathways altered in multiple strains. In many cases the same pathways were altered by multiple distinct chromosome substitutions. Taken together, these results suggest that widespread epistatic background effects may result in complex and overlapping transcriptional relationships among different chromosome substitution strains. Transcriptional profiling of chromosome substitution strains reveals a complex genetic architecture of transcriptional regulation.

Keywords

Quantitative Trait Locus Parental Strain Transgressive Segregation Single Nucleotide Polymorphism Data Limb Girdle Muscular Dystrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by the National Institutes of Health (NIH) grants HLB55001, GM070683, and HLB66611. The authors thank Jason Affourtit, Greg MacKenzie, and Yong H. Wu for their contributions to this study.

Supplementary material

supp.pdf (3.9 mb)

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.The Jackson LaboratoryBar HarborUSA

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