Genome Bioinformatics and Genomic Disorders
Schulich School of Medicine, The University of Western Ontario
Single Copy Genomic Technology:
Fluorescent In Situ
Hybridization (FISH) and Quantitative Microsphere Hybridization
Single copy (sc) technology uses computationally determined unique sequences in the human and other
eukaryotic genomes for nucleic acid probe design and synthesis. We are currently developing diagnostic
applications of sc technology. FISH is an
increasingly requested procedure that uses DNA probes to distinguish
chromosomal abnormalities in neoplastic and congenital disorders not evident by routine chromosome
banding. ScFISH is similar to FISH, except that probes are more precisely
defined and more densely arrayed along chromosomes.
Abnormalities can be detected for specific loci at much
higher resolution and genomic density than commercially available DNA probes.
We have used the human genome sequence to
develop 0.1 - 10 kb single copy hybridization probes (Rogan et.
al 2001; Newkirk et al. 2006). These probes have also been attached to fluorescent microspheres and hybridized to patient-derived genomic DNA and cDNA. The copy number of different sequences in these samples can simultaneously be determined by flow cytometry.
To CONTACT the Principal Investigators at
our NEW EMAIL Addresses:
New applications of sc technology.
H.L. Newkirk, J.H.M. Knoll, and P.K. Rogan.
Distortion of Quantitative Genomic and Expression Hybridization by Cot-1 DNA: Mitigation of This Effect,
Nucleic Acids Research, 2005. PDF
about scFISH techniques and applications
J.R. Mora, J.H.M. Knoll, P.K. Rogan, R.C. Getts, and G.S. Wilson.
Dendrimer FISH detection of single-copy intervals in acute promyelocytic leukemia.
Molecular and Cellular Probes 20,114-120, 2006. PDF
- Table of scFISH probes used in detecting the cytogenetic
abnormalities (hyperlinked to Ensembl browser; from Knoll and Rogan, AJMG, 2003) DOC PDF
Research (Rogan, Cazcarro, Knoll 2001) manuscript on development of sc probes and potential for genome wide utility
Journal of Medical Genetics (Knoll, Rogan; 2003) manuscript validating sc probes for >40 genetic disorders and leukemias
Conference on Biomedical Imaging (Rogan, Knoll 2004) manuscript: computational selection of probes
- Discovery Medicine
(Rogan & Knoll 2004) manuscript - a short review
Published Patents and Patent Applications:
Copy FISH Probes the Genome" (R. Lewis, Biophotonics International, Sept. 2003). Trade magazine article
US Patent #7,014,997
US Patent #6,828,097
US Patent Application 09/854,867
US Patent Application 10/786,970
US Patent Application 10/676,248
International Patent Application WO 01/088089
International Patent Application WO 2004/029283
International Patent Application WO 2005/094291
Links to related sites
... whose goal is to make scFISH probes widely available for research and clinical applications
Gallery of images of genomic disorders detected with scFISH