Gary Churchill

Research Interests

Statistical Genetics

Genetics of Complex Traits

Understanding the genetic determination of complex, disease-related traits is a long-standing focus of research in our laboratory. This year we have published a proposal for the development of a novel genetic resource—the collaborative cross—that will provide new approaches to the analysis of complex systems. We have continued to apply the methods of complex trait analysis to phenotypes related to osteoporosis, hypertension, heart disease, anemia, and depression. We have developed novel experimental designs to improve the efficiency of mapping gene expression traits assayed using microarray technology.

Gene Expression Microarrays

ANOVA methods for microarrays were first proposed by our group in 2000 and have now gained wide acceptance within the microarray user community. This year presented an opportunity to write a review article summarizing our achievements in this area over the past five years. We have also carried out and published a comparative analysis of different microarray platforms in order to investigate the accuracy and precision of these technologies.

Selected Publications

  • Ackerman KG, Huang H, Grasemann H, Puma C, Singer JB, Hill AE, Lander E, Nadeau JH, Churchill GA, Drazen JM, Beier DR. 2005. Interacting Genetic Loci Cause Airway Hyperresponsiveness. Physiol Genomics 21:105-111.
  • Ahmadiyeh N, Churchill GA, Solberg LC, Baum AE, Shimomura K, Takahashi JS, Redei EE. 2005. Lineage is an Epigenetic Modifier of QTL Influencing Behavioral Coping with Stress. Behav Genet 35(2):189-198.
  • Cui XQ, Hwang JT, Qiu J, Blades NJ, Churchill GA. 2005. Improved statistical tests for differential gene expression by shrinking variance components. Biostatistics 6:59-75.
  • Petkov PM, Graber JH, Churchill GA, Dipetrillo K, King BL, Paigen K. 2005. Evidence of a Large-Scale Functional Organization of Mammalian Chromosomes. PLos Genet 1(3):e33.
  • Sen S, Satagopan JM, Churchill GA. 2005. Quantative trait locus study design from an information perspective. Genetics 170:447-464.
  • Tsaih SW, Lu L, Airey DC, Williams RW, Churchill GA. 2005. Quantitative trait mapping in a diallel cross of recombinant inbred lines. Mamm Genome 16(5):344-355.
  • Wittenburg H, Lyons MA, Li R, Kurtz U, Mossner J, Churchill GA, Carey MC, Paigen B. 2005. Association of a lithogenic Abcg5/Abcg8 allele on Chromosome 17 (Lith9) with cholesterol gallstone formation in PERA/EiJ mice. Mamm Genome 16(7):495-504.
  • Yi N, Yandell BS, Churchill GA, Allison DB, Eisen EJ, Pomp D. 2005. Bayesian model selection for genome-wide epistatic quantitative trait Loci analysis. Genetics 170(3):1333-1344.
  • Peters LL, Zhang W, Lambert AJ, Brugnara C, Churchill GA, Platt OS. 2005. Quantitative trait loci for baseline white blood cell count, platelet count, and mean platelet volume. Mamm Genome 16:749-763.
  • Churchill GA. 2004. Using ANOVA to analyze microarray data. Biotechniques 37(2):173-175.
  • Complex Trait Consortium. 2004. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet 36(11):1133-1137.
  • Ishimori N, Li R, Kelmenson PM, Korstanje R, Walsh KA, Churchill GA, Forsman-Semb K, Paigen B. 2004. Quantitative trait loci analysis for plasma HDL-cholesterol concentrations and atherosclerosis susceptibility between inbred mouse strains C57BL/6J and 129S1/SvImJ. Arterioscler Thromb Vasc Biol 24:161-166.
  • Korstanje R, Albers JJ, Wolfbauer G, Li R, Tu A-Y, Churchill GA, Paigen BJ. 2004. Quantitative trait locus mapping of genes that regulate phospholipids transfer activity in SM/J and NZB/BINJ inbred mice. Arterioscler Thromb Vasc Biol 24:155-160.
  • Korstanje R, Li R, Howard T, Kelmenson P, Marshall J, Paigen BJ, Churchill GA. 2004. Influence of sex and diet on quantitative trait loci for HDL cholesterol levels in an SM/J by NZB/BINJ intercross population. J Lipid Res 45:881-888.
  • Lyons MA, Wittenburg H, Li R, Walsh KA, Korstanje R, Churchill GA, Carey MC, Paigen BJ. 2004. Quantitative trait loci that determine lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and CASTE/Ei inbred mice. Physiol Genomics 17:60-68.
  • Peters LL, Swearingen RA, Andersen SG, Gwynn B, Lambert AJ, Li R, Lux SE, Churchill GA. 2004. Identification of quantitative trait loci that modify the severity of hereditary spherocytosis in wan a new mouse model of band-3 deficiency. Blood 103(8):3233-3240.
  • Solberg LC, Baum AE, Ahmadiyeh N, Shimomura K, Li R, Turek FW, Churchill GA, Takahashi JS, Redei EE. 2004. Sex-and lineage-specific inheritance of depression-like behavior in the rat. Mamm Genome 15(8):648-662.
  • Woo Y, Affourtit J, Daigle S, Viale A, Johnson K, Naggert J, Churchill GA. 2004. A comparison of cDNA oligonucleotide, and affymetrix genechip gene expression microarray platforms. J Biomol Tech 15(4):276-284.
  • Ahmadiyeh N, Churchill GA, Shimomura K, Solberg LC, Takahashi JS, Redei EE. 2003. X-Linked and lineage dependent inheritance of coping response to stress. Mamm Genome 14:748-757.
  • Brich J, Shie F-S, Howell BW, Li R, Tus K, Wakeland EK, Jin L-W, Mumby M, Churchill GA, Herz J, Cooper JA. 2003. Genetic modulation of tau phosphorylation in the mouse. J Neurosci 23(1):187-192.
  • Broman KW, Wu H, Sen S, Churchill GA. 2003. R/qtl: QTL mapping in experimental crosses. Bioinformatics 19(7):889-890.
  • Cui XQ, Churchill GA. 2003. Statistical tests for differential expression in cDNA microarray experiments. Genome Biology 4:210.1-210.9.
  • Cui XQ, Kerr MK, Churchill GA. 2003. Transformations for cDNA microarray data. Statistical Applications in Genetics and Molecular Biology, volume 2, article 4.
  • Flaherty L, et al. 2003. The nature and identification of quantitative trait loci: a community’s view. Nat Rev Genet 4:911-916.
  • Lyons MA, Wittenburg H, Li R, Walsh KA, Churchill GA, Carey MC, Paigen B. 2003. Quantitative trait loci that determine lipoprotein cholesterol levels in DBA/2J and CAST/Ei inbred mice. J Lipid Res 44:953-967.
  • Lyons MA, Wittenburg H, Li R, Walsh KA, Leonard MR, Churchill GA, Carey MC, Paigen BJ. 2003. New quantitative trait loci that contribute to cholesterol gallstone formation detected in an intercross of CAST/Ei and 129S1/SvImJ inbred mice. Physiol Genomics 14:225-239.
  • Lyons MA, Wittenburg H, Li R, Walsh KA, Leonard MR, Korstanje R, Churchill GA, Carey MC, Paigen BJ. 2003. Lith6: a new QTL for cholesterol gallstones from an intercross of CAST/Ei and DBA/2J inbred mouse strains. J Lipid Res 44:1763-1771.
  • Mathews CE, Graser RT, Bagley RJ, Caldwell JW, Li R, Churchill GA, Serreze DV, Leiter EH. 2003. Genetic analysis of resistance to type I diabetes in ALR/Lt Mice, a NOD related strain with defenses against autoimmune-mediated diabetogenic stress. Immunogenetics 55(7):491-496.
  • Nadeau JH, Burrage LC, Restivo J, Pao Y-H, Churchill GA, Hoit BD. 2003. Pleiotropy, homeostasis, and functional networks based on assays of cardiovascular traits in genetically randomized populations. Gen Res 13:2082-2091.
  • Sundberg JP, Boggess D, Silva K, McElwee KJ, King LE, Li R, Churchill GA, Cox GA. 2003. Major locus on mouse chromosome 17 and minor locus on chromosome 9 are linked with alopecia areata in C3H/HeJ mice. J Investigative Dermatology 120:1-5.
  • Wang X, Le Roy I, Nicodeme E, Li R, Wagner R, Petros C, Churchill GA, Harris S, Darvasi A, Kirilovsky J, Roubertoux PL, Paigen BJ. 2003. QTL analysis of HDL cholesterol concentrations using an advanced intercross between inbred mouse strains C57Bl/6J and NZB/B1NJ. Genome Research 13(7):1654-1664.
  • Wittenburg H, Lyons MA, Li R, Churchill GA, Carey MC, Paigen BJ. 2003. FXR and ABCG5/ABCG8 as determinants of cholesterol gallstone formation from quantitative trait locus mapping in mice. Gastroenterology 125:868-881.
  • Wu H, Kerr MK, Cui XQ, 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, Garret ES, Irizarry RA, Zeger SL, [eds], Springer, N.Y.
  • Wu H, Kerr MK, Cui XQ, 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, Garret ES, Irizarry RA, Zeger SL, [eds], Springer, N.Y.
  • Cui XQ, Churchill GA. 2003. How many mice and how many arrays? Replication in mouse cDNA microarray experiments in Methods of Microarray Data Analysis III, Kimberly F. Johnson and Simon M. Lin (eds). Kluwer Academic Publishers, Norwell, MA. 139-154.
  • Adamo ML, Powell DR, Turner RT, Muller R, Beamer WG. 2002. Generation of a new congenic mouse strain to test the relationships among serum IGF1, bone mineral density and skeletal morphology in vivo. J Bone and Mineral Research 17:570-579.
  • Broman KW, Rowe LB, Churchill GA, Paigen K. 2002. Crossover interference in the mouse. Genetics 160:1123-1131.
  • Churchill GA. 2002. Fundamentals of experimental design for cDNA microarrays. Nat Gen Supp 32: 490-496.
  • Mahler M, Most C, Schmidttke S, Sundberg JP, Li R, Hedrich H, Churchill GA. 2002.
  • Oleksiak M, Churchill GA, Crawford DL. 2002. Natural variation in gene expression. Nat Gen 32:261-266.
  • Sampson SS, Harris S, Paigen B. 2002. Quantitative trait locus mapping of genes that regulate HDL cholesterol in SM/J and NZB/B1NJ inbred mice. Physiol Genomics 9:93-102.
  • Volaufova J, Zuberi A, York B. 2002. Quantitative trait analysis of self-selected macronutrient diet intake: Fat, carbohydrate and total kilocalories. Physiol Genomics 11:205-217.
  • Sugiyama F, Churchill GA, Li R, Libby LJM, Carver T, Yagami K, John SWM, Paigen BP. 2002. QTL associated with blood pressure, heart rate, and heart weight in CBA/CaJ and BALB/cJ mice. Physiol Genomics10:5-12.
  • Williams RW, Broman KW, Chevrud JM, Churchill GA, Hitzeman RW, Hunter KW, Mountz J, Pomp D, Reeves RH, Schalkwyk LC, Threadgill DW. 2002. Complex Trait Consortium 1st workshop report: A collaborative cross for high-precision complex trait analysis.
  • Wittenburg H, Lammert F, Wang DQ-H, Churchill GA, Li R, Bouchard B, Carey MC, Paigen B. 2002. Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice. Physiol Genomics 8:67-77.
  • Kerr MK, Leiter EH, Picard L, Churchill GA. 2002. Sources of Variation in Microarray Experiments. In: Computational and Statistical Approaches to Genomics Wei Zhang and Ilya Shmulevich (eds). Kluwer Academic Publishers 41-51.