Construction of a 2-Mb resolution BAC microarray for CGH analysis of canine tumors

  1. Rachael Thomas1,
  2. Allyson Scott1,
  3. Cordelia F. Langford2,
  4. Susan P. Fosmire3,
  5. Cristan M. Jubala3,
  6. Travis D. Lorentzen4,
  7. Christophe Hitte5,
  8. Elinor K. Karlsson6,7,
  9. Ewen Kirkness8,
  10. Elaine A. Ostrander4,9,
  11. Francis Galibert5,
  12. Kerstin Lindblad-Toh6,
  13. Jaime F. Modiano3,10, and
  14. Matthew Breen1,11
  1. 1 Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA
  2. 2 Microarray Facility, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom
  3. 3 Integrated Department of Immunology and AMC Cancer Center, University of Colorado Health Sciences Center, Colorado 80214, USA
  4. 4 Clinical Research and Human Biology Divisions, Fred Hutchinson Cancer Research Center, Seattle Washington 98109-1024, USA
  5. 5 UMR 6061 CNRS, Génétique et Développement, Faculté de Médecine, 35043 Rennes Cédex, France
  6. 6 Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02141 USA
  7. 7 Bioinformatics Program, Boston University, Boston, Massachusetts 02215, USA
  8. 8 The Institute for Genomic Research, Rockville, Maryland 20850, USA
  9. 9 National Human Genome Research Institute/National Institutes of Health (NHGRI/NIH), Bethesda, Maryland 20892-8000, USA
  10. 10 University of Colorado Cancer Center, Denver, Colorado 80214, USA

Abstract

Recognition of the domestic dog as a model for the comparative study of human genetic traits has led to major advances in canine genomics. The pathophysiological similarities shared between many human and dog diseases extend to a range of cancers. Human tumors frequently display recurrent chromosome aberrations, many of which are hallmarks of particular tumor subtypes. Using a range of molecular cytogenetic techniques we have generated evidence indicating that this is also true of canine tumors. Detailed knowledge of these genomic abnormalities has the potential to aid diagnosis, prognosis, and the selection of appropriate therapy in both species. We recently improved the efficiency and resolution of canine cancer cytogenetics studies by developing a small-scale genomic microarray comprising a panel of canine BAC clones representing subgenomic regions of particular interest. We have now extended these studies to generate a comprehensive canine comparative genomic hybridization (CGH) array that comprises 1158 canine BAC clones ordered throughout the genome with an average interval of 2 Mb. Most of the clones (84.3%) have been assigned to a precise cytogenetic location by fluorescence in situ hybridization (FISH), and 98.5% are also directly anchored within the current canine genome assembly, permitting direct translation from cytogenetic aberration to DNA sequence. We are now using this resource routinely for high-throughput array CGH and single-locus probe analysis of a range of canine cancers. Here we provide examples of the varied applications of this resource to tumor cytogenetics, in combination with other molecular cytogenetic techniques.

Footnotes

  • [Supplemental material is available online at www.genome.org and http://www.cvm.ncsu.edu/mbs/breen_matthew.htm.]

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.3825705.

  • ↵11 Corresponding author. E-mail Matthew_Breen{at}ncsu.edu; fax (919) 513-7301.

    • Accepted May 4, 2005.
    • Received February 13, 2005.
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  1. doi: 10.1101/gr.3825705 Genome Res. 15: 1831-1837 Cold Spring Harbor Laboratory Press

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