Annual Report 2006/2007
Annual Report 2006/2007
Hess B. and Diane Finestone Laboratory in Memory of
Jacob and Jenny Finestone exists
in order to promote the field of medical genetics at
Dr. William Foulkes and Dr. Marc Tischkowitz demonstrated the involvement of PALB2/FANCN in hereditary breast cancer families.
David Rosenblatt and his
collaborators have shown that mutations in the MCEE gene can result in elevated methylmalonic
acid excretion. With colleagues in the
Dr. Patricia Tonin developed a derivative ovarian cancer cell line though the transfer of chromosome 3 fragments, using a novel modification of an established technique involving whole chromosome transfer. This cell line is now being used to identify the underlying chromosome 3p gene(s) involved in tumour suppression. A positive outcome has been the modulation of transcriptome networks, which will enable them to prioritize gene candidates for an independent project aimed at elucidating genes involved in ovarian tumourigenesis.
Dr. William Foulkes was awarded a highly competitive Chercheur Nationaux Award from the FRSQ.
Dr. Marc Tischkowitz was awarded a Chercheur Clinicien Award from the FRSQ.
Dr. Nicholas AhMew completed the RV year of his training program and
successfully passed the examinations of the
After more than five years, a Department of Medical Genetics was
finally established at the MUHC. Dr.
Teresa Costa has been appointed the first Chief of this hospital department.
Dr. Costa has held positions in the past in
In keeping with the new RUIS structure mandated by the Government
Suzanne Dufrasne, M.Ps, Psychologist:
· Number of new patients seen: 16
· Number of sessions in person: 28
· Number of counselling phone calls with patients (pre-session, follow-up): 48
· Number of counselling phone calls with health professionals: 20
· Total number of interventions with patients: 76
Other Diseases (Creutzfeldt-Jakob, Familial adenomatous polyposis)
· Number of patients seen: 2
· Number of new patients seen: 75
· Number of follow-up patients seen: 80
· Total cases seen: 155
Total Patients Seen at MUHC
· 2003-2004: 377
· 2004-2005: 376
· 2005-2006: 456
· 2006-2007: 451 (~20% increase since 2004-2005)
NOTES FOR LEGEND:
· Fiscal periods are calculated from April 1st- March 31st.
· Totals for KASL (Lidia Kasprzak) take into account all patients seen by KASL and/or her replacements (SFOX [Stephanie Fox], MLAL [Maria Lalous], LROB [Laura Robb]) over each financial period.
For 2005-2006 fiscal period, PALL (Laura
Palma) totals are calculated from time of start date
· Stats for RES include the total number of patients seen by either genetics residents and/or FITZJ (Jennifer Fitzpatrick)
Dr. Eleanor Elstein has an active clinic in the area of cardiovascular genetics, which evaluates inherited cardiac diseases as well as systemic genetic diseases that have cardiac manifestations.
Dr. Ken Dewar and his laboratory are using genomics and bioinformatics technologies to study genome structure and variation. One focus of the lab is to develop genetic mapping tools for investigating complex trait mapping in a nonhuman primate, the vervet monkey. Using comparative genomics approaches they have leveraged other genome projects (human, chimpanzee, rhesus monkey) to streamline the discovery of markers of genetic variation (SNPs). They have also embarked upon the generation of corresponding genome wide physical map, entailing the paired-end sequencing and genome alignments for >200,000 BAC clones. The vervet BAC map is being used to delineate chromosomal breakpoints and to identify vervet BAC clones associated with evolutionary recently derived centromeres and pericentromeric regions.
His group is also interested
in understanding genome structure and virulence factors in the human bacterial
pathogen Clostridium difficile. C. difficile remains a serious health risk in
Dr. William Foulkes and colleagues have been characterizing mutations in the new breast cancer gene PALB2. In addition, he has worked with BRCA1-mutated cell lines to try to develop novel treatments. With George Chong, he has described several novel mutations in genes associated with hereditary colorectal cancer. As mentioned above, in recognition of the excellence of his work, he has been awarded a Chercheur Nationaux award from the FRSQ.
Mary Fujiwara studies the distribution and maintenance of genetic variability,
including deleterious alleles, in populations.
During the current reporting period, she continued collaborations on the
Hutterite population of
She also collaborate with Daniel Bichet (Hôpital Sacré-Coeur de Montréal) on the genetics of nephrogenic and neurohypophyseal diabetes insipidus. The study of mutations in three different genes has shown that the mode of inheritance can differ based on the particular mutation. They maintain locus specific mutation databases for these genes which encode the hormone arginine vasopressin, its receptor, and a water channel (AVP, AVPR2, and AQP2, respectively).
Dr. Brian Gilfix focuses on two main areas of research: 1) Homocysteine and its Metabolism/Inborn Errors of Metabolism (Homocystinuria)-they have a large cohort of patients in the Adult Genetics Clinic with homocystinuria. He is using this opportunity to explore new treatments of homocystinuria and investigate the effect of elevated homocysteine on other risk factors for cardiovascular disease; 2) Development of Laboratory Methods in Molecular Diagnostics and HPLC-he is developing and implementing assays based on hybridization probes to replace standard assays based on restriction fragment length polymorphism used to genotype single nucleotide polymorphisms in the clinical laboratory. The benefit of this is decreased net cost and faster turnaround time.
Dr. Ken Morgan has a major interest in human population genetics and genetic epidemiology. He is involved in the genetic analysis of Mendelian and complex traits in humans and mice. Accomplishments related to human genetics include mapping rare Mendelian diseases. Ongoing collaborations include segregation and linkage analysis of intermediate phenotypes contributing to calcium kidney stone formation; genetic susceptibility to inflammatory bowel disease in children; and reducing the complexity of pedigrees in founder populations such that statistical analysis is computationally feasible.
He is a member of the CIHR
Institute of Genetics Priorities and Planning committee for genetic
epidemiology and statistical genetics and was on the organizing committee of
the “Second Annual Canadian Genetic Epidemiology and Statistical Genetics
Meeting”, held in
Dr. 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 biochemical and molecular bases of these
diseases. This year they have expanded mutation
analysis among patients with combined homocystinuria
and methylmalonic aciduria
due to mutations in MMACHC. They have
also shown that mutations in the MCEE gene can result in elevated methylmalonic acid excretion. With colleagues in the
Dr Marc Tischkowitz has been establishing a research program at the Segal Centre, Jewish General Hospital to undertake innovative and effective research in the field of hereditary predisposition to cancer, with a focus on the genetic links between breast cancer and Fanconi Anemia. He was part of an international collaboration that identified PALB2/FANCN as a new Fanconi Anemia gene and together with Dr Foulkes he helped to establish that PALB2 is a breast cancer predisposition gene.
Patricia Tonin works in two principal areas of research; these are described on the web site: www.toninlab.mcgill.ca.
A. The Molecular study of Human Epithelial Ovarian Cancer
More than 70% of women diagnosed with ovarian cancer die of the disease. 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. Research in the lab is focused on the identification of tumour suppressor genes, particularly those physically associated with chromosomes 3p and 17q. Various molecular genetic techniques are used to identify them, which include, allelic content analysis such loss of heterozygosity studies and single nucleotide (SNP) polymorphism analyses, large-scale gene expression assays (Affymetrix platform), and more recently functional approaches based on chromosome transfer fragment and gene complementation. A major accomplishment of the last year was development of a derivative ovarian cancer cell line though the transfer of chromosome 3 fragments. This cell line was developed using a novel modification of an established technique involving whole chromosome transfer. This cell line is now being used to identify the underlying chromosome 3p gene(s) involved in tumour suppression. A positive outcome has been the modulation of transcriptome networks, which will enable them to prioritize gene candidates for an independent project aimed at elucidating genes involved in ovarian tumourigenesis. [See News item at www.toninlab.mcgill.ca for Press Release.]
In collaboration with colleagues at the CHUM-Notre Dame, they investigate gene expression profiles of ovarian cancer samples with the aim of identifying signature patterns of gene expression in order to elucidate molecular pathways important in ovarian tumourigenesis.
B. Breast and Ovarian Cancer Susceptibility Genes
Hereditary breast and
ovarian cancer accounts for approximately 5-10% of all breast and ovarian
cancers. A large majority of cancer
families are attributed to germline mutations in
BRCA1 and BRCA2. However, about 40% of cancer families are negative for
mutations in these known genes. Dr. Tonin’s
group is also focused on determining the contribution of known and unknown
cancer susceptibility genes to inherited predispositon
to breast and ovarian cancer. They focus on the founder French Canadian
© 2007 Finestone Laboratory