In July 2010, Genome Canada launched the Advancing Technology Innovation through Discovery (ATID) Program. This joint collaborative program was developed by Genome Canada and the Canadian Institutes of Health Research (CIHR) to bring together Genome Canada-funded Science and Technology Innovation Centres with Canadian researchers to focus on applying the latest genomics technologies to identify the genetic causes of childhood diseases. This funding opportunity will specifically focus on diseases where such identification can be achieved rapidly with the potential for important novel biological, clinical and commercial discoveries.
Results were announced on February 22, 2011. Two (2) research teams were supported for a total budget of $6,497,354 over two years with a maximum of $2 million from Genome Canada, $2.5 million from the Canadian Institutes of Health Research, $600,000 from Genome British Columbia and $500,000 from Genome Quebec. Researchers from the two teams are based in British Columbia, Ontario, Quebec and Nova Scotia.
- Finding of Rare Disease Genes in Canada (FORGE Canada)
- The Canadian Pediatric Cancer Genome Consortium
Project Leaders: Kym Boycott, Jan Friedman, Jacques Michaud, Centre CHU Sainte-Justine
Institutions: Children’s Hospital of Eastern Ontario Research Institute, the University of British Columbia, the Université de Montréal
Genome Centres: Ontario Genomics, Genome British Columbia, Génome Québec
Genetic disorders of children are individually rare but collectively frequent, affecting the lives of approximately 500,000 children in Canada. These disorders cause a variety of medical problems including birth defects, intellectual disability, difficulty with growth and organ failure.
Most genes that cause these conditions have not yet been found, mainly because gene-discovery studies are difficult to perform when DNA from only a small number of affected children is available. Recently a new technology (called Next Generation Sequencing) has been developed which allows a person’s entire genetic code (about 22,000 genes) to be analyzed within a few days at reasonable cost. This new type of DNA sequencing has revolutionized the study of rare genetic diseases because it is now possible to find disease-causing genes using a relatively small number of patients.
The team has created a large network of Canadian doctors and scientists who will now have access to this powerful technology for their patients. Through this national collaboration they will be able to rapidly identify many genes responsible for genetic disorders that affect children in this country and throughout the world. The Canadian Pediatric Genetic Disorders Sequencing (CPGDS) Consortium (www.cpgdsconsortium.com) has 150 members and will ensure that Canada becomes a world leader in this exciting field. The Consortium brings together doctors from all genetics centres across Canada, internationally-recognized Canadian scientists with expertise in finding genes, and teams from the three Genome Canada Science and Technology (GC S&T) Innovation Centres (Montreal, Toronto, Vancouver), which have already set up the new sequencing technology.
The CPGDS Consortium will:
- Assist doctors to identify patients with rare childhood diseases. Because the Consortium has members from all the medical genetic clinics in the country, for any given disorder they will be able to enroll children and families from across Canada. Therefore, even for very rare conditions, disease-causing genes will be able to be found. So far, over 100 genetic disorders that affect Canadian children have been submitted for study.
- Sequence the genomes of patients to identify disease-causing genetic changes.
- Set up a national data coordination centre to streamline and improve existing large-scale sequence analysis tools. This will improve their ability to distinguish genetic changes that cause disease from ones that are normal variants contributing to human diversity.
- Create national ethical guidelines for analyzing sequence data from entire genomes and for sharing results with families.
The consortium will allow for rapid gene discovery of rare childhood-onset disorders, with immediate and long-term health benefits for Canadian families. Their discoveries will lead to genetic tests that will allow earlier and more precise diagnoses. Better diagnoses will allow Canadian health care teams to reduce or prevent patient complications, to develop tailored treatments, and to provide more accurate reproductive counselling to families. In the long term, identification of disease genes is an essential step toward the development of drugs that will one day improve the lives of affected children. Finally, successful completion of this proposal’s activities will firmly establish a sustainable National Gene Discovery Consortium.
Project Leaders: Poul Sorensen, Conrad Fernandez, Cynthia Hawkins, Annie Huang, Nada Jabado, David Malkin
Institutions: the University of British Columbia, Dalhousie University, the Hospital for Sick Children, McGill University
Genome Centres: Genome British Columbia, Génome Québec, Ontario Genomics
Cancer is the most common cause of non-accidental death in children from infancy to young adulthood. In Canada, ~1,400 children (0-18 years of age) will be diagnosed with cancer every year. Approximately 200 will die and many more will live with life-long complications of their disease and treatments. Thus, cancer and cancer-related illness remains an unacceptable social and economic burden for Canada and Canadian families.
Although overall survival for children with cancer has improved substantially over the last three decades, significant challenges remain. A considerable proportion of childhood cancers remain incurable, or can only be cured with treatments that leave a child with life-long mental or physical disabilities. Furthermore, for children with tumours that recur or that spread to other parts of the body, current therapies are largely unsuccessful. To further improve survival, the quality of life of children surviving their cancer, and alleviate the socio-economic burden on their families, it is important to understand why specific types of tumours spread or come back, and why some of the most aggressive tumours are so resistant to therapy.
To this end, a group of highly accomplished Canadian researchers and clinicians, who are experts in childhood cancer and novel DNA sequencing technologies, have joined forces to use one of the most powerful gene sequencing technologies ever developed, to probe the genomes (DNA) of four of the most challenging childhood cancers known. The ultimate aim of this comprehensive project is to use the newly discovered genetic information about these cancers that they uncover, to gain insight into targets and new therapies that may be developed for these devastating diseases.
The researchers will use this powerful, leading edge “next generation sequencing” technology to rapidly scan the DNA of the entire human genome that is contained in tumour cells. They will examine and directly compare the genetic signature of primary tumour cells and tumour cells that have spread (metastasized) or relapsed in childhood medulloblastoma (brain cancer), metastatic osteosarcoma (bone cancer) and recurrent leukemia (cancer of white blood cells), to uncover genetic abnormalities that direct tumour cells to spread or become resistant to treatment. In addition, they will determine the gene signatures of three highly lethal childhood brain tumours to uncover new genes that may be targets for new drug therapies. The studies will generate an unprecedented view of the tumour genomes in these diseases. This will not only provide short-term potential for improving tailored therapies for children with these lethal cancers, but in the longer term will enable the development of new drugs for patients who otherwise have limited options for treatment.
This project also provides the opportunity to study the many ethical issues that arise in deciding when and how best to provide the results from genetic studies on childhood cancers back to the patients and their families. In the short-term, this multi-disciplinary, cross-Canada national study will redefine the genetic basis of aggressive childhood cancers, which they expect will lead to a better understanding of the potential role for novel ‘targeted’ therapies for this group of diseases. In the longer term, the results will lead to improved survival and reduced long-term consequences for children with cancer.