Annual Report 2004/2005
Annual Report 2002/2003
Hess B. and Diane Finestone Laboratory in Memory of Jacob and Jenny Finestone
was established to promote the field of medical genetics at
Dr. Thomas Hudson and his laboratory continued its asthma, diabetes and other complex trait mapping projects. Work in 2004-2005 led to the discovery of links between vitamin D related genes and asthma, and a detailed map of transplantation antigens and their role in multiple sclerosis (soon to be published in Nature Genetics).
Dr. Patricia Tonin was awarded the 2004 Merck Frosst Award for
Excellence in Research, by the Department of Medicine,
Dr. Mary Ann Thomas completed her final year of Medical Genetics
residency and her first year in the cytogenetics program of the CCMG. Dr.
Chantal Morel has completed her RV year in Medical Genetics. Both Dr. Thomas and Dr. Morel successfully
completed the examination of the
After more than four years, clinical services for medical genetics within the McGill University Health Centre (MUHC) are still in the process of being restructured. The administration of the MUHC has started to put together a committee to search for a Program Director for medical genetics.
have been successful in recruiting Marc Tischkowitz, M.B., Ph.D. from the
Research Interests and Accomplishments of Individual Members:
Ken Dewar and his laboratory have
entered the 2nd year of a 4 yr NIH project to develop SNP-based genetic mapping
tools for the vervet monkey. Of note,
their analysis of using rhesus and human genome data to predict SNP locations
in vervet sequence was the focal points of presentations given at the
Dr. Eleanor Elstein continues her interest in caridovascular genetics, with particular emphasis on genetic factors modulating the development of obstructive vasculopathy in cardiac allographs, and on the levels of aminothiols in heart transplantation.
Dr. Brian Gilfix follows a cohort of patients with homocystinuria in the adult genetics clininc. He is using this opportunity to explore new treatments for this disease and to investigate the effect of elevated homocysteine on other risk factors for cardiovascular disease. He also is developing and implementing assays based on hybridization probes to replace molecular diagnostic assays based on restriction length polymorphisms. The benefit of this is decreased net cost and faster turn around times.
Dr. William Foulkes’ main research accomplishment this year was the publication of several papers further describing the clinico-pathological features of hereditary breast cancer. In particular, he has helped to define the basal pehnotype of BRCA1-related breast cancer. He co-ordinated the publication of the largest allelic association study of prostate cancer to date. Finally, with Dr. Steven Narod, he co-authored a 10-year anniversary review of BRCA1/2.
Mary Fujiwara studies the
distribution and maintenance of genetic variability, including deleterious
alleles in well-defined populations, in particular, the Hutterite population of
Thomas Hudson directs the rapidly
Kenneth Morgan has research
interests in the areas of population genetics, pedigree analysis, and genetic
modelling. He lead a Genetic Analysis
Group that participates in two Networks of Centres of Excellence programs: the
Canadian Genetic Diseases Network (CGDN) and the Mathematics of Information
Technology and Complex Systems. His
group is involved in the genetic analysis of Mendelian and complex traits in
humans and mice. He is also an
investigator in the
Collaborations with researchers in
In a continuing collaboration with Dr. Danielle Malo on the genetic architecture of host response to Salmonella persistence in mice, significant interactions have been detected.
Postdoctoral fellow, Dr. Loredo-Osti developed methodology for segregation analysis of a quantitative trait in sibships to find evidence for a major gene for urine calcium excretion in families ascertained for kidney stones, a collaboration with Alain Bonnardeaux, Hôpital Maisonneuve-Rosemont.
David Rosenblatt and his laboratory
continue to be the major international referral source for the diagnosis of
patients with inherited disorders of folate and vitamin B12. They are involved
in studying the molecular bases of these diseases. Dr. Lisa Worgan, a medical geneticist from
Dr. Patricia Tonin and her laboratory have two principal areas of research. The first involves the identification of genetic factors that are implicated in the development and/or progression of human epithelial ovarian cancer. The second involves the study of genetic factors that predispose to hereditary forms of breast cancer.
A. The Molecular study of Human Epithelial Ovarian Cancer
Our knowledge of the molecular events associated with the development and progression of epithelial ovarian cancer has been limited by the lack of a suitable model system. Also, since the disease is often diagnosed at a late stage when numerous complex chromosomal changes have already taken place, the early molecular events remain largely unknown. Deletions of chromosome 3p and 17q (distinct from the BRCA1 locus) are frequent events in ovarian tumours of epithelial origin. Dr. Tonin has shown deletions in low grade, early stage tumours and therefore has hypothesized that these chromosomal regions harbour tumour suppressor genes whose function is lost early in the development and/or progression of ovarian cancer. The goals of a CIHR funded projects, are to refine the localization and then clone the putative chromosome 3p and 17q tumour suppressor genes. Previously, she published a deletion map of chromosome 3p deletions observed in a large series of epithelial ovarian tumours. In addition she is applying a candidate gene approach and have excluded known candidates, such as TGF-ß-RII. Shedescribed a chromosome 3 transcriptome based on the comparison of expression profiles of ovarian cancer cell lines with normal surface epithelial cells using high through put oligonucleotide expression microarrays. In this study she was able to establish the sensitivity of detection and show that subtle changes in gene copy number are detectable by microarray analysis. In an effort to characterize the putative TSG on chromosome 3p implicated in ovarian tumourigensis, she established the relationship between chromosome losses frequently associated with specific regions of the human genome (BRCA2 and 13q, TP53 and 17p, BRCA1 and 17q, and Xp11), and that of 3p regions lost in ovarian cancer. She established chromosome 3p loss occurs independently from TP53 mutagenesis. Most recently she reported a comprehensive analysis addressing the fidelity of expression microarrays, such as Affymetrix GeneChips, showing that rigorous investigation of target sequences representing genes on these microarrays should be pursued prior to engaging in experiments of target genes.
B. Breast Cancer Susceptibility Genes: BRCA1 and BRCA2
Hereditary breast cancer accounts for
approximately 5% to 10% of all breast cancers and large majority of hereditary
cancer families are attributed to germline mutations in BRCA1 and BRCA2, which
confer an increased susceptibility to both breast and ovarian cancer. Dr. Tonin
and her laboratory are continuing to further define the spectrum of mutations
in the BRCA1 and BRCA2 cancer susceptibility genes in the French Canadian
© 2005 Finestone Laboratory