Gary Churchill

Domains and Networks of Correlated Gene Expression

 

Transcriptional regulation of gene expression, its timing, tissue distribution and response to both internal and environmental inputs, is a key link between the genome and phenotype. Variation in expression patterns across cell types is a primary determinant of tissue identity and function. Individual genetic variation in gene expression determines both our susceptibility to disease and provides the substrate for evolutionary adaptation. An integrated view of genome dynamics requires understanding these relationships in terms of genome organization.

Towards this goal we are:

  1. Analyzing publicly available gene expression data resources for physical correlates of tissue-specific gene expression patterns and for clustering of co-expression in linkage disequilibrium domains and networks.

  2. Surveying gene expression in 16 mouse strains using microarrays. The selected strains include 'classical' inbred strains, inbred strains derived from M.m. musculus, M.m. domesticus, and M.m. castaneus origin, and inbred strains derived from hybrid origins. We will examine four tissues in mice of both sexes and relate our findings to genome organization and functional variation.

  3. Developing statistical methods and software for these analyses.

Center related publications

Genetic analysis of complex traits in the emerging collaborative cross
Aylor DL, Valdar W, Foulds-Mathes W, Buus RJ, Verdugo RA, Baric RS, Ferris MT, Frelinger JA, Heise M, Frieman MB, Gralinski LE, Bell TA, Didion JD, Hua K, Nehrenberg DL, Powell CL, Steigerwalt J, Xie Y, Kelada SN, Collins FS, Yang IV, Schwartz DA, Branstetter LA, Chesler EJ, Miller DR, Spence J, Liu EY, McMillan L, Sarkar A, Wang J, Wang W, Zhang Q, Broman KW, Korstanje R, Durrant C, Mott R, Iraqi FA, Pomp D, Threadgill D, Pardo-Manuel de Villena F, Churchill GA.
Genome Res. 2011 Aug;21(8):1223-38. PMCID: PMC3149489 [ Full Text ] [ Highlight in Nature Reviews Genetics ] [ datasets ]

A Bayesian Framework for Inference of the Genotype-Phenotype Map for Segregating Populations
Hageman RS, Leduc MS, Korstanje R, Paigen B, Churchill GA.
Genetics. 2011 Apr;187(4):1163-70. PMCID: PMC3070524 [ Full Text ] [ datasets 1 ] [ datasets 2 ]

Architecture of energy balance traits in emerging lines of the Collaborative Cross
Mathes WF, Aylor DL, Miller DR, Churchill GA, Chesler EJ, de Villena FP, Threadgill DW, Pomp D.
Am J Physiol Endocrinol Metab. 2011 Jun;300(6):E1124-34. PMCID: PMC3118585 [ Full Text ] [ datasets ]

Genetic analysis in the Collaborative Cross breeding population
Philip VM, Sokoloff G, Ackert-Bicknell CL, Striz M, Branstetter L, Beckmann MA, Spence JS, Jackson BL, Galloway LD, Barker P, Wymore AM, Hunsicker PR, Durtschi DC, Shaw GS, Shinpock S, Manly KF, Miller DR, Donohue KD, Culiat CT, Churchill GA, Lariviere WR, Palmer AA, O'Hara BF, Voy BH, Chesler EJ.
Genome Res. 2011 Aug;21(8):1223-38. PMCID: PMC3149490 [ Full Text ]

Stochastic Variation of Transcript Abundance in C57BL/6J mice
Vedell PT, Svenson KL, Churchill GA.
BMC Genomics. 2011 Mar 30;12(1):167. PMCID: PMC3082245 [ Full Text ] [ datasets ]

Subspecific origin and haplotype diversity in the laboratory mouse
Yang H, Wang JR, Didion JP, Buus RJ, Bell TA, Welsh CE, Bonhomme F, Yu AH, Nachman MW, Pialek J, Tucker P, Boursot P, McMillan L, Churchill GA, de Villena FP.
Nat Genet. 2011 May 29;43(7):648-55. PMCID: PMC3125408 [ Full Text ] [ News Article ] [ datasets ]

High-fat diet leads to tissue-specific changes reflecting risk factors for diseases in DBA/2J mice
Hageman RS, Wagener A, Hantschel C, Svenson KL, Churchill GA, Brockmann GA.
Physiol Genomics. 2010 Jun;42(1):55-66. PMCID: PMC2888560 [ Full Text ] [ datasets ]

CGDSNPdb: a database resource for error-checked and imputed mouse SNPs
Hutchins LN, Ding Y, Szatkiewicz JP, Smith RV, Yang H, de Villena FP, Churchill GA, Graber JH.
Database (Oxford). 2010 Jul 6;2010:baq008. Print 2010. PMCID: PMC2911843. [ Full Text ] [ datasets 1 ] [ datasets 2 ]

Epistasis contributes to the genetic buffering of plasma HDL cholesterol in mice
Li RH, Churchill GA.
Physiol Genomics. 2010 Nov 29;42A(4):228-34. PMCID: PMC3008368 [ Full Text ] [ datasets ]

Critical reasoning on causal inference in genome-wide linkage and association studies
Li Y, Tesson BM, Churchill GA, Jansen RC.
Trends Genet. 2010 Dec;26(12):493-8. PMCID: PMC2991400 [ Full Text ]

Coordinated expression domains in mammalian genomes
Woo YH, Walker M, Churchill GA.
PLoS One. 2010 Aug 18;5(8):e12158. PMCID: PMC2923606. [ Full Text ] [ datasets ]

Genetic factors contributing to obesity and body weight can act through mechanisms affecting muscle weight, fat weight, or both
Brockmann GA, Tsaih SW, Neuschl C, Churchill GA, Li R.
Physiol Genomics 2009 Jan 8;36(2):114-126. PMCID: PMC2636925. [ Full Text ] [ datasets 1 ] [ datasets 2 ]

A New Standard Genetic Map for the Mouse
Cox A, Ackert-Bicknell C, Dumont BL, Ding Y, Tzenova Bell J, Brockmann GA, Wergedal JE, Bult C, Paigen B, Flint J, Tsaih SW, Churchill GA, Broman KW.
Genetics. 2009 Aug;182(4):1335-44. PMCID: PMC2728870. [ Full Text ]

PPARgamma2 nuclear receptor controls multiple regulatory pathways of osteoblast differentiation from marrow mesenchymal stem cells
Shockley KR, Lazarenko OP, Czernik PJ, Rosen CJ, Churchill GA, Lecka-Czernik B.
J Cell Biochem. 2009 Feb 1;106(2):232-46. PMCID: PMC2745312. [ Full Text ] [ datasets ]

The Effects of Atherogenic Diet on Hepatic Gene Expression Across Mouse Strains
Shockley KR, Witmer D, Burgess-Herbert SL, Paigen B, Churchill GA.
Physiol Genomics. 2009 Nov 6;39(3):172-82. PMCID: PMC2789673. [ Full Text ] [ datasets ]

Importance of randomization in microarray experimental designs with Illumina platforms
Verdugo RA, Deschepper CF, Muñoz G, Pomp D, Churchill GA.
Nucleic Acids Res. 2009 Sep;37(17):5610-8. PMCID: PMC2761262. [ Full Text ] [ datasets ]

A customized and versatile high-density genotyping array for the mouse
Yang H, Ding Y, Hutchins LN, Szatkiewicz J, Bell TA, Paigen BJ, Graber JH, de Villena FP, Churchill GA.
Nat Methods. 2009 Sep;6(9):663-6. PMCID: PMC2735580. [ Full Text ] [ datasets ]

The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics
Chesler EJ, Miller DR, Branstetter LR, Galloway LD, Jackson BL, Philip VM, Voy BH, Culiat CT, Threadgill DW, Williams RW, Churchill GA, Johnson DK, Manly KF.
Mamm Genome. 2008 Jun;19(6):382-9. PMCID: PMC2745091. [ Full Text ]

Relationships of dietary fat, body composition, and bone mineral density in inbred mouse strain panels
Li R, Svenson KL, Donahue LR, Peters LL, Churchill GA.
Physiol Genomics. 2008 Mar 14;33(1):26-32. [ Full Text ] [ datasets ]

An imputed genotype resource for the laboratory mouse
Szatkiewicz JP, Beane GL, Ding Y, Hutchins L, Pardo-Manuel de Villena F, Churchill GA.
Mamm Genome. 2008 Mar;19(3):199-208. PMCID: PMC2725522. [ Full Text ] [ datasets ]

Randomization in laboratory procedure is key to obtaining reproducible microarray results
Yang H, Harrington CA, Vartanian K, Coldren CD, Hall R, Churchill GA.
PLoS ONE. 2008;3(11):e3724. PMCID: PMC2579585 [ Full Text ]

Recombinant inbred strain panels: a tool for systems genetics
Churchill GA.
Physiol Genomics. 2007 Oct 22;31(2):174-5. [ Full Text ]

The mouse as a model for human biology: a resource guide for complex trait analysis
Peters LL, Robledo RF, Bult CJ, Churchill GA, Paigen BJ, Svenson KL.
Nat Rev Genet. 2007 Jan;8(1):58-69.

Evidence of a large-scale functional organization of mammalian chromosomes
Petkov PM, Graber JH, Churchill GA, DiPetrillo K, King BL, Paigen K.
PLoS Biol. 2007 May;5(5):e127; author reply e128. PMCID: PMC1868061 [ Full Text ]

PPARgamma2 Regulates a Molecular Signature of Marrow Mesenchymal Stem Cells
Shockley KR, Rosen CJ, Churchill GA, Lecka-Czernik B.
PPAR Res. 2007;2007:81219. PMCID: PMC2234088. [ Full Text ] [ datasets ]

Multiple trait measurements in 43 inbred mouse strains capture the phenotypic diversity characteristic of human populations
Svenson KL, Von Smith R, Magnani PA, Suetin HR, Paigen B, Naggert JK, Li R, Churchill GA, Peters LL.
J Appl Physiol. 2007 Jun;102(6):2369-78. [ Full Text ] [ datasets ]

Estimating p-values in small microarray experiments
Yang H, Churchill G.
Bioinformatics. 2007 Jan 1;23(1):38-43. [ Full Text ] [ datasets ]

On the subspecific origin of the laboratory mouse
Yang H, Bell TA, Churchill GA, Pardo-Manuel de Villena F.
Nat Genet. 2007 Sep;39(9):1100-7.

The genetics of gene expression
Churchill GA.
Mamm Genome. 2006 Jun;17(6):465.

Patterns and mechanisms of genome organization in the mouse
Graber JH, Churchill GA, Dipetrillo KJ, King BL, Petkov PM, Paigen K.
J Exp Zoolog A Comp Exp Biol. 2006 Sep 1;305(9):683-8.

Structural model analysis of multiple quantitative traits
Li R, Tsaih SW, Shockley K, Stylianou IM, Wergedal J, Paigen B, Churchill GA.
PLoS Genet. 2006 Jul;2(7):e114. PMCID: PMC1513264 [ Full Text ] [ datasets ]

 

Gary Churchill

 

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