Gene expression analysis of mouse chromosome substitution strains
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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.
KeywordsQuantitative Trait Locus Parental Strain Transgressive Segregation Single Nucleotide Polymorphism Data Limb Girdle Muscular Dystrophy
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.
- Ashburner M., Ball CA, Blake JA, Botstein D, Butler H, et al. 2002) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nature Genetics 25:25–29Google Scholar
- Silver LM (1995) Mouse Genetics (New York: Oxford University Press)Google Scholar
- Wu H, Kerr K, Churchill GA (2003) MAANOVA: A Software Package for the Analysis of Spotted cDNA Microarray Experiments. In The Analysis of Gene Expression Data: an Overview of Methods and Software, Parmigiani G, Garrett ES, Irizarry RA, Zeger AL (eds). (New York: Springer), pp 313–431Google Scholar
- Yang GM, Kitagawa K, Matsushita K, Mabuchi T, Yagita Y, et al. (1997) C57BL/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains: Selective neuronal death in the murine transient forebrain ischemia. Brain Res 752:209–218PubMedCrossRefGoogle Scholar