Laboratories of Human Molecular Genetics and Genomic Disorders

Schools of Medicine and Dentistry , University of Western Ontario

Welcome to the Laboratories of Human Molecular Genetics and Genomic Disorders, where we investigate the causes of inherited genetic disease and cancer using original genomic and bioinformatic approaches.

The links below describe some of our research interests and point to educational materials. Please note that our Facebook page is updated with greater regularity.

Employment Opportunities and Graduate Study

Staff include technologists, postdoctoral scientists, graduate and undergraduate students. We are seeking applications from qualified graduate students and undergraduates, especially those with a background in genomics, bioinformatics, or software development. Please contact us for more information about potential opportunities from qualified candidates.

Ongoing Research topics

Splice site and transcription factor binding site analysis using Information Theory
Single Copy Technology: scFISH, solution capture, and array comparative hybridization
(these products are available through Cytognomix Inc.)
Cancer Genetics
Uniparental inheritance
Molecular Cytogenetics and Medical Genetics
Molecular Biology and Genetics at Zoo de Thoiry

Teaching and Education

Biochemistry 4435a: Field Guide to the Human Genome
Course materials and lecture notes
Paper: Predicting severity of haemophilia A and B splicing mutations by information analysis. Haemophilia, 12: 258-262, 2006. PDF
Paper: Determination of Genomic Copy Number by Quantitative microsphere Hybridization. Hum Mut 27:376-386, 2006. PDF
Paper: Distortion of Quantitative Genomic and Expression Hybridization by Cot-1 DNA: Mitigation of This Effect, Nucl.Acids Res. 33(22): e191, 2005. PDF
Website: Automated splice site analyses: Detection of mutations and polymorphisms. Publication: Hum. Mut. 25:334-342, 2005.
US Patent #6,828,097: Single copy genomic probes and methods of generating same.
US Patent #7,014,997: Chromosome structural abnormality localization with single copy probes.

Current Projects

Splice Site Analyses


Our goal is to predict the effects of sequence changes that alter mRNA splicing in human diseases. We are designing a system to evaluate changes in splice site strength based on information theory-based models of donor and acceptor splice sites. The predicted molecular phenotypes of these mutations can be related to models of exon recognition and ultimately, the severity of disease in patients harboring these mutations.

We are compiling mutation data for genetic disorders from a wide variety of peer-reviewed sources. These sources include HUGO approved mutation designation in published literature and non-standard mutation description in locus specific databases.

Principal Investigator's contact information: Click here.

Our peer reviewed publications - Information theory based analyses of splicing mutations
Precomputed automated splice site analyses of Locus-Specific and Federated Mutation Databases [ Documentation -- password required].
Registered server for automated splice site analyses - User-defined mutation analyses (this will be moving to
Total Exon information analyses - Predicting cryptic sites.
Information Theory: read about the applications of information theory to molecular biology on Dr. Tom Schneider's pages.
Patent: US Ser. No. 5,867,402: Computational analysis of nucleic acid information defines binding sites

Transcription Factor Binding site recognition

To CONTACT the Principal Investigators at our NEW EMAIL Addresses: click here.

Genome wide analysis

Delila-Genome - A software tool for complete genome scanning for and display of protein binding sites
Genome-wide prediction, display and refinement of binding sites with information theory-based models Gadiraju S, Vyhlidal CA, Leeder JS, Rogan PK. BMC Bioinformatics, 4:38, 2003.
Tandem machine learning for the identification of genes regulated by transcription factors Deendayal Dinakarpandian, Venetia Raheja, Saumil Mehta, Erin G. Schuetz, Peter K Rogan. BMC Bioinformatics, 6: 204, 2005.
Definition of cis-recognition elements
Development and refinement of pregnane X receptor DNA binding site model using information theory: Insights into PXR mediated gene regulation Carrie A. Vyhlidal, Peter K. Rogan, and J. Steven Leeder, J. Biol. Chem., Vol. 279, Issue 45, 46779-46786, November 5, 2004.

BIPAD: A Web Server for Modeling Bipartite Sequence Elements C Bi and Peter K. Rogan, BMC Bioinformatics 7:76 (2006).

Bipartite Pattern Discovery by Entropy Minimization-Based Multiple Local Alignment C Bi and Peter K. Rogan, Nucleic Acids Research, 32:4979-4991(2004).

Determining Thresholds of Binding Site Sequence Models Using Information Theory C Bi and Peter K. Rogan, Proceedings of the JCIS/6th International Symposium on Computational Biology and Genome Informatics, July 21-26, 2005, Salt Lake City UT.

Defining sequence elements that regulate CYP450 gene expression Peter K. Rogan, Proceedings of the 14th Intl. Conf. on Cytochromes P450, Dallas TX, 5/31-6/5/2005 (in press).


US Ser. No. 5,867,402: Computational analysis of nucleic acid information defines binding sites. Thomas D. Schneider and Peter K. Rogan, 1998.

Species Identification


Method for rapid identification of prokaryotic and eukaryotic organisms Peter K. Rogan, US Ser. # 5,849,492

Published papers

Visual Display of Sequence Conservation as an Aid to Taxonomic Classification Using PCR Amplification Peter K. Rogan, Joseph J. Salvo, R. Michael Stephens, and Thomas D. Schneider, in Visualizing Biological Information, (ed. C.A. Pickover) pp. 21-32, World Scientific, River Edge NJ. 1995

Phylogenetic Inference based on Information Theory-based PCR Amplification P.W. Tooley, J.J. Salvo, T.D. Schneider, and P.K. Rogan, J. Phytopathology 146:427-430, 1998

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: click here.

2006 Modern Marvels Invent Now! Challenge recognizes and honors the invention of Single Copy Technology.
US Patent #7,014,997, Chromosome structural abnormality localization with single copy probes
US Patent #6,828,097, Single copy genomic probes and method of generating same (press release).
New applications of sc technology.

High throughput copy number determination with single copy technology by flow cytometry (Patent pending). Presented at the American Society of Human Genetics annual meeting, Oct. 28, 2005. A manuscript has been published in Human Mutation 27, 376-386, 2006. PDF Supplementary Material
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
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
Brief introductory presentation on single copy FISH technology
Published articles about scFISH techniques and applications

Table of scFISH probes used in detecting the cytogenetic abnormalities (hyperlinked to Ensembl browser; from Knoll and Rogan, AJMG, 2003) DOC PDF
Genome Research (Rogan, Cazcarro, Knoll 2001) manuscript on development of sc probes and potential for genome wide utility PDF
American Journal of Medical Genetics (Knoll, Rogan; 2003) manuscript validating sc probes for >40 genetic disorders and leukemias PDF
IEEE Conference on Biomedical Imaging (Rogan, Knoll 2004) manuscript: computational selection of probes PDF
Discovery Medicine (Rogan & Knoll 2004) manuscript - a short review PDF
"Single Copy FISH Probes the Genome" (R. Lewis, Biophotonics International, Sept. 2003). Trade magazine article PDF
Published Patents and Patent Applications:

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

Cytognomix ... whose goal is to make scFISH probes widely available for research and clinical applications
Gallery of images of genomic disorders detected with scFISH


Relevant publications by Peter K. Rogan and Joan H. M. Knoll.

Rogan PK, Close P, Bloudin J-L, Seip JR, Ladda RL, Antonarkis SE. Duplication and loss of Chromosome 21 in two children with Down syndrome and leukemia. 1995, Amer J Med Genet 59: 174-181. This article can be downloaded here. (Note: This download is rather large and may take a few minutes).

Hahn WC, Stewart SA, Brooks MW, York SG, Eaton E, Kurachi A, Beijersbergen RL, Knoll JHM, Meyerson M, Weinberg RA. Inhibition of telomerase limits the growth of human cancer cells. Nature Medicine 5:1164-1170, 1999. This article can be downloaded here.

Kim AC, Peters LL, Knoll JHM, Van Huffel C, Ciciotte SL, Kleyn PW, Chishti AH. Limatin (LIMAB1), an Actin-Binding LIM Protein, Maps to Mouse Chromosome 19 and Human Chromosome 10q25, a Region Frequently Deleted in Human Cancers. Genomics 46:291-293, 1997. This article can be downloaded here.

Ott G, Katzenberger T, Siebert R, DeCoteau JF, Fletcher JA, Knoll JHM, Kalla J, Rosenwald A, Ott MM, Weber-Matthiesen K, Kadin ME, Muller-Hermelink HK. Chromosomal Abnormalities in Nodal and Extranodal CD30+ Anaplastic Large Cell Lymphomas: Infrequent Detection of the t(2;5) in Extranodal Lymphomas. Genes, Chromosomes, Cancer 22:114-121, 1998. This article can be downloaded here.

Peters K, Knoll JHM, Kadin ME. Cytogenetic Findings in Regressing Skin Lesions of Lymphomatoid Papulosis. Cancer Genet Cytogenet 80:13-16, 1995. This article can be downloaded here.

Sterpetti P, Hack AA, Bashar MP, Park B, Cheng SD, Knoll JHM, Urano T, Feig LA, Toksoz D. Activation of the Lbc Rho Exchange Factor Proto-Oncogene by Truncation of an Extended C Terminus That Regulates Transformation and Targeting. Molecular & Cellular Biology 19:1334-1345, 1999. This article can be downloaded here.

Belchis DA, Meece CA, Benko FA, Rogan PK, Williams RA, Gocke CD. Loss of Heterozygosity and Microsatellite Instability at the Retinoblastoma Locus in Osteosarcomas. Diagnostic Molecular Pathology 5:214-219, 1996. This article can be downloaded here.

Molecular Cytogenetics Resources

Over the past 40 years, cytogenetics has become the gold standard for chromosome analysis in clinical and research laboratories. Giemsa and other types of chromosome banding techniques are used to definitively diagnose inherited and acquired genetic disorders. Molecular cytogenetics, a relatively recent development, permits detection of chromosome abnormalities at single or multigene resolution.
Publications from the Laboratories of Human Molecular Genetics and Genomic Disorders here.
Our published FISH protocol: J. Knoll and P. Lichter, Unit 4.3, Current Protocols in Human Genetics, Wiley NY
Integrated Automated Molecular Cytogenetic System here
Lecture: Introduction to Cytogenetics here.
Lecture: Telomeres and disease here.
Lecture: Genetic chimerism in humans here.
Links to other websites

Protocols in Molecular Cytogenetics here.

Recent review on Molecular Cytogenetics applications here.

Cytogenetics Resources Links page at KUMC (Many sites, mostly educational) here.

Multiple Congenital Anomaly/Mental Retardation Syndrome Database at National Library of Medicine here.

Online Mendelian Inheritance of Man here.


Relevant publications by Peter K. Rogan and Joan H. M. Knoll.

Krizkova L, Sakthivel R, Olowe SA, Rogan PK, Floros J. Human SP-A: genotype and single-strand conformation polymorphism analysis. Am J Physiol 266:L519-L527 1994. This article can be downloaded here. .

Mottez E, Rogan PK, Manuelidis L. Conservation in the 5' region of the long interspersed mouse L1 repeat: implications of comparative sequence analysis. Nucleic Acids Research 14:3119-3136, 1986. This article can be downloaded here.

Rogan PK, Salvo JJ. High-Fidelity Amplification of Ribosomal Gene Sequences from South American Mummies. Chapter 12 in Ancient DNA; Herrman & Hummel eds; Springer-Verlang NY 1994. This article can be downloaded here.

Rogan PK, Lentz SE. Molecular genetic evidence suggesting treponematosis in pre-Columbian, Chilean mummies. Abstract of presentation to American Association of Physical Anthropologists. This article can be downloaded here.

Rogan PK, Salvo JJ. Molecular Genetics of Pre-Columbian South American Mummies. Pp 223-234 in Molecular Evolution; Allan R. Liss, Inc. 1990. This article can be downloaded here.

Rogan PK, Salvo JJ. Study of Nucleic Acids Isolated From Ancient Remains. Yrbk Phys Anthropol 33:195-214, 1990. This article can be downloaded here.

Rogan PK, Pan J, Weissman SJ. L1 Repeat Elements in the Human Î-G-g-Globin Gene Intergenic Region: Sequence Analysis and Concerted Evolution within This Family. Mol Biol Evol 4:327-342, 1987. This article can be downloaded here.

Rogan PK. Restriction mapping by preferential ligation of adjacent digestion fragments. Nucleic Acids Research 14:9219, 1986. This article can be downloaded here.

Floros J, DiAngelo S, Koptides M, Karinch AM, Rogan PK, Nielsen H, Spragg RG, Watterberg K, Deiter G. Human SP-A Locus: Allele Frequencies and Linkage Disequilibrium between the Two Surfactant Protein A Genes. American Journal Respir. Cell Mol. Biol. 15:489-498, 1996. This article can be downloaded here.

Lemkin PF, Rogan PK. Automatic detection of noisy spots in two-dimensional Southern blots. (International Electrophoresis Society Meeting, Washington DC, March 16-19, 1991). Applied and Theoretical Electrophoresis 2:141-149, 1991. This article can be downloaded here.

Rogan PK, Salvo JJ. Study of Nucleic Acids Isolated from Ancient Remains. Yearbook of Physical Anthropology 33:195-214, 1990. This article can be downloaded here.

Rogan PK, Williams GJB. The Structure of the Dihydrofolate Reductase Inhibitor 2,4,6-Triamino-5-chloroquinazoline. Acta Cryst. B36:2358-2362, 1980. This article can be downloaded here.

Rogan PK, Zaccai G. Hydration in Purple Membrane as a Function of Relative Humidity. Journal of Molecular Biology 145:281-283, 1981. This article can be downloaded here.

Rogan PK, Lemkin PL, Klar AJS, Singh J, Strathern JN. Two-Dimensional Agarose Gel Electrophoresis of Restriction-Digested Genomic DNA. Methods Companion 3:91-97, 1991. This article can be downloaded here.

Rogan PK, Salvo JJ, Stephens RM, Schneider TD. Visual Display of Sequence Conservation as an Aid to Taxonomic Classification Using PCR Amplification. Visual Biological Information (C. Pickover, ed), World Scientific, River Edge NJ, 1995. This article can be downloaded here.

Tooley PW, Salvo JJ, Schneider TD, Rogan PK. Phylogenetic Inference Based on Information Theory-Based PCR Amplification. Journal of Phytopathology 146:427-430, 1998. This article can be downloaded here.

Veletza SV, Rogan PK, TenHave T, Olowe SA, Floros J. Racial differences in allelic distribution at the Human Pulmonary Surfactant Protein B gene locus (SP-B). Experimental Lung Research 22:489-494, 1996. This article can be downloaded here.


Biochemistry 4435B


Students will learn how to use internet-based resources to explore human genomic sequences and associated data. Topics covered include: how the genome is organized and annotated; genetic variation among individuals, particularly relating to congenital and acquired genetic diseases; recognizing DNA elements that affect gene expression; and identifying protein interaction networks by analysis of microarray and proteomics databases. Skills acquired in the course will be applicable to many disciplines in the biomedical sciences.


TUESDAY & THURSDAY 11:30 am - 12:20 pm
LAB: Wednesday 5:30 -7:30


Biochemistry 3381a
Recommended: Biochemistry 3382B.


Course Manager
Dr. Peter Rogan MSB 388 519-661-4255
Dr. Joan Knoll HSA H424 519-661-2111 x86407
Dr. Gary Shaw MSB 306 519-661-4021
Biweekly reports (5 page, total of 5) summarizing analyses of topics covered in class during in the previous two week interval. Each student will be assigned a distinct gene(s) and/or genetic disorders to research in their report. Reports will contain results of genomic, bioinformatic and proteomic analysis, supported by relevant literature citations. Taylor Library professional staff have agreed to be available to assist students in seaching literature during scheduled computer laboratories, however students will be solely responsible for interpreting and assessing the relevance of published research papers for their assignments.

After a student initially submits their report, the report will be graded by the instructor. However, reports will also be available for peer review through WebCT to all class members for a limited time. Other class members who contribute novel insights related to their classmate's assigned gene(s) and/or genetic disorders through this peer review process may be eligible for additional credit towards their own report. The amount of extra credit that may be awarded will be limited and subject to the instructor's discretion.

All enrolled students must agree to abide by the University's policy on plagiarism. Reports will be due (via WebCT) one week after laboratory. The peer review option will be enabled for 3 days after all reports for a particular week have been graded. Each report will comprise 10% of the student’s grade.


FINAL EXAM Final examination will be comprehensive for the entire course and will comprise 50% of the student’s grade. Students should not assume that a makeup exam will be scheduled.

Notes: (1) If you have any conflicts with the examination dates, or If you are sick and cannot write a test, you must obtain a student medical certificate and have it approved by a Faculty of Science Counsellor. (3) Requests for an alternate date for the final examination should be submitted to the Office of the Dean of Science within a week after the final examination timetable is posted.

Statement on Use of Electronic Devices Unless specified otherwise, electronic devices (including cell phones and MP3 players) will not be permitted in exams.


No textbook required. This course is not textbook based, however human genetic and genomic texts may be helpful for background. This course will utilize publicly available software and databases assigned by the instructor. Other course materials will be posted on the course WebCT site. To the extent possible, stable bioinformatic resources will be selected, however students are encouraged to use additional public software and databases which have been peer-reviewed in relevant scientific journals. There is no guaranty that these websites will always be available. This may necessitate students accessing these resources outside of the regular class schedule.

Scholastic Discipline
Statement on Academic Offences
University Policy for Plagiarism
Absences from course commitments
Support Services
Revised July 25, 2011 by Melita Hayes

Return to Western's home page

Schulich School of Medicine & Dentistry
Department of Biochemistry
Medical Sciences Building 342, Western University
London, Ontario, Canada, N6A 5C1
Tel: (519) 661-3074 Fax:(519) 661-3175
See our policies on Privacy and Web Standards.

Course Materials and Lecture Notes

Editorials and Letters to the Editor

Kansas City Star 2000: The Promise the Human Genome Project here.
Kansas City Star 2001: Peer review needed in Human Cloning Studies here.
The Scientist 2005: Fluorescence in situ hybridization beats molecular karyotyping here.
Medical Laboratory Observer 2005: Fluorescence in situ hybridization vs. aCGH here.