|
|
Annual Report 2006/2007 Annual Report |
Annual
Report
2007/2008
The
Hess B. and Diane Finestone Laboratory in Memory of Jacob and Jenny Finestone
exists in order to promote the field of medical genetics at
Highlights:
Research
Dr. David Rosenblatt and his collaborators have also shown that mutations in the MMADHC gene are responsible for the cblD inborn error of vitamin B12 metabolism. These findings were published in the New England Journal of Medicine.
Dr. William Foulkes and Dr. Marc Tischkowitz have continued to explore the role of PALB2 in breast cancer. They identified and characterized a novel founder mutation, Q775X, in PALB2, that accounts for a small fraction of breast cancer occurring in French Canadian women. The work was published in Breast Cancer Research (doi:10.1186/bcr1828). Studies to understand the function of this and other mutations are underway.
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 being used to identify
the underlying chromosome 3p gene(s) involved in tumour suppression.
Highlights:
Awards
Dr. Ken Dewar has been appointed Acting
Director of the McGill University-Genome Quebec Innovation Centre and promoted
to the rank of Associate Professor with tenure at McGill.
Dr. William Foulkes continues to hold a highly competitive Chercheur
National Award from the FRSQ.
Dr. Marc Tischkowitz holds a Chercheur Clinicien Award from the FRSQ.
Highlights: Teaching
In the area of professional training, the Department of Human Genetics at McGill has the responsibility for the teaching of Medical Genetics to undergraduate medical students and for residency training in Medical Genetics. McGill has training programs that are certified by the Royal College of Physicians and Surgeons of Canada (RCPSC) and by the Canadian College of Medical Geneticists (CCMG). The M.Sc. program in Genetic Counselling achieved re-certification by the American Board of Genetic Counsellors (ABGC). It should be noted that much of the teaching in the professional programs is done by faculty members, who are primary employees of the teaching hospitals, or by physicians with heavy clinical responsibilities. They give generously of their time and energy to ensure the high quality of these programs.
There are 8 medical genetics residents in the RCPSC training program, 1 in the CCMG molecular training program and 1 in the CCMG clinical genetics-training program (see page 15). In the past year, Dr. Phillipe Campeau has successfully passed the examination in Medical Genetics of the Royal College and Physicians of Canada. In September 2008, he plans to continue fellowship training at Baylor College in Houston. Dr. Nicholas Ah Mew has spent the last academic year in China and will be continuing fellowship training at the National Children’s Hospital in Washington. There are 8 M.Sc. Genetic Counselling students in the ABGC accredited M.Sc. in Genetic Counselling training program.
WILLIAM FOULKES
516 – 614B Environmental Carcinogenesis
Department: Medicine (Div. Experimental Medicine)
Format: Lecture
Title: Cancer Genetics/Prevention
Role: Lecturer
Level: MSc program
Time (hr/yr): One two-hour session
516–0635D Experimental and Clinical Oncology
Format: Lecture
Title: Cancer Genetics
Role: Lecturer
Level: MSc program
Time (hr/yr): 1.5-hour seminar
521-690B Inherited
Cancer Syndromes
Department: Department of Human Genetics
Format: Lecture
Title: Cancer Genetics
Role: Lecturer
Level: MSc program
Time (hr/yr): Four two-hour sessions
Unit 8 small
group teaching in medical genetics
Role: Lecturer
Level: Medical students
Format: One 2 hour lecture and 4 small groups sessions, 2 hours each
DAVID ROSENBLATT
Biology 575
Department: Biology/Human Genetics
Format: Lecture
Title: Inborn Errors of Folate and Cobalamin Transport and Metabolism
Role: Lecturer and Course Co-ordinator
Level: Undergraduate/Graduate
Time: 6 hours
Department: Human Genetics
Format: Lecture and Small Group Teaching
Role: Lecturer-2 sessions; Small Group Leader
Title: Introduction
to Medical Genetics Huntington Disease
Level: Medical Students
Time: 2 lectures plus 5 2-hour sessions, twelve hours in total
MARC TISCHKOWITZ
HGEN 690
Department: Human Genetics
Format: Lecture and student presentations
Title: Cancer Genetics
Role: Lecturer
Level: MSc program
Time: 2 x three-hour sessions
HGEN 692
Department: Human Genetics
Format: Lecture
Title: DNA repair and pediatric
cancer syndromes Adult cancer predisposition syndromes
Role: Lecturer
Level: MSc program
Time: 2 x two-hour sessions
516 – 614B Environmental Carcinogenesis
Department: Medicine (Div. Experimental Medicine)
Format: Lecture
Title: It's a dangerous world out there: DNA repair and environmental
toxins
Role: Lecturer
Level: MSc program
Time: One two-hour session
516–0635D Experimental and Clinical Oncology
Format: Lecture
Title: Clinical Issues in Hereditary Cancer Genetics
Role: Lecturer
Level: MSc program
Time: 1.5-hour seminar
Unit 8
Department: Human Genetics
Format: Lecture and Small Group Teaching
Role: Lecturer-2 sessions:
Titles: Cancer, Prenatal, Ethics,
Screening Developmental Delay
Level: Medical Students
Time: 5 x Two hour sessions, ten hours in total
Department: Human Genetics, Oncology
Format: Lecture and Small Group Teaching
Role: Lecturer
Titles: Using Pathology in Cancer
Genetics
Level: Genetic Counselling MSc Course
Time: 1.5
hours
Highlights:
Clinical
The McGill University Health Centre created a hospital Department of Medical Genetics in 2007 and recruited Dr. Teresa Costa to be its first head. It is hoped that the creation of this department will lead to major role for Medical Genetics within the anticipated new MUHC hospital complex. The creation of the MUHC Department was not easy and took many years to accomplish. The first year since its creation has not been an easy one because to date, the MUHC has not clarified the administrative structure, nor infused sufficient resources to assure that it will be a success. Nonetheless, its creation was an important first and necessary step.
The Department of
Medical Genetics at the Jewish General Hospital, under the directorship of Dr.
David Rosenblatt, has defined its major areas as those of cancer genetics and
prenatal diagnosis. In this regard, the
Cancer Genetics Program, jointly based at the Jewish General Hospital and the
MUHC and also housed jointly in the McGill Departments of Human Genetics and
Oncology, received the highest rating by the Quebec Program in the Fight
against Cancer - the only cancer genetics program in the province to earn this
rating. This program is headed by Dr. William Foulkes and consists of Dr. Marc
Tischkowitz, genetic counselors Nora Wong and Sonya Zaor at the JGH, and Lidia
Kasprzak and Laura Palma at the MUHC.
In keeping with the new
RUIS structure mandated by the Government of Quebec, a provincial committee and
a local McGill committee have been established to examine how to best serve the
interest of the Quebec population in the area of Medical Genetics. These two committees have begun to address
issues such as manpower for health services in genetics, screening for Down
Syndrome, newborn screening, and the availability of genetic testing.
Clinical Statistics:
At the MUHC site, the
total number of cancer genetics patients seen in 2007-2008 was 482, which is a
small increase over the 456 seen the previous year.
Research Interests and Accomplishments of Individual
Members:
Dr. Eleanor Elstein 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 Quebec, North America, and Europe, in part due to an epidemic strain of increased virulence, which has emerged in the last several years. The laboratory has performed the sequencing of the entire 4 Mb genome of a virulent strain from Montreal, and is now generating the genome sequences of other isolates with important clinical phenotypes. Cross-genome comparisons of gene content and organization will be used to identify additional candidate genes involved in pathogenicity.
Dr. William Foulkes and colleagues have been characterizing mutations in the
new breast cancer gene PALB2, as indicated above. 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 families
with colorectal cancer. As mentioned above, in recognition of the excellence of
his work, he has been awarded a Chercheur Nationaux award from the FRSQ. Please
see www.mcgill.ca/cancergenetics for more information about
the Program in Cancer Genetics.
Mary Fujiwara is interested in the distribution and maintenance of genetic variability, including deleterious alleles, in human populations. She studies the Hutterite population of North America, an inbred population isolate, to map and further delineate the clinical variability of a Joubert-related cerebello-oculo-renal syndrome. She also collaborates 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.
Dr. Brian Gilfix has a large cohort of patients in the
Adult Genetics Clinical with homocystinuria. He is exploring new treatments of
for homocystinuria and investigating the effect of elevated homocysteine on
other risk factors for cardiovascular disease.
He also works on developing new laboratory methods in molecular
diagnostics in order to decrease net cost and to allow for a faster
turn-around-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. 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. 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.
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, along
with collaborators in Switzerland and the United Kingdom, have described the
gene responsible for the cblD inborn error of cobalamin metabolism. They have also shown that with newborn
screening of infants, it is also possible to diagnose non-genetic disease
involving vitamin B12 in their mothers. Dr. Rosenblatt continues to serve as
Chairman of the Department of Human Genetics at McGill.
Dr. Marc Tischkowitz has established a research
program at the Segal Centre, Jewish General Hospital, where he is undertaking
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. Over the past year he has continued to explore the
role of the Fanconi Anemia gene PALB2 in breast cancer predisposition.
He aims
to deliver high-quality patient-focused research results, as shown by several
of his recent papers (PMID: 18285836, 17650314). He has also fostered
collaborations with researchers working on gastric cancer – this work was
published in JAMA (PMID: 17545690). In his capacity of Attending Staff at the
Jewish General Hospital, he is responsible for providing services for Cancer
Genetics, Prenatal Diagnosis and General Genetics. In addition, he has clinical
responsibilities at Hôpital Charles LeMoyne, where he advises and assists the
local Genetic Counsellor and holds a genetics clinic once every other month.
Dr. 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. 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. In collaboration with her colleagues at the CHUM-Notre Dame, Dr. Tonin investigates 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 the determining the contribution of known and unknown
cancer susceptibility genes to inherited predisposition to breast and ovarian
cancer. Recent accomplishments include the analysis of high-risk families for
germ line TP53 mutations and further characterization of the contribution of
BRCA1/2 to hereditary breast and ovarian cancer families of French Canadian
descent.
Members | Report | Meetings
Publications | Funds | Financial
©
2008 Finestone Laboratory