Autism is a severe neurodevelopmental disorder affecting thousands of Canadians. Although it is generally agreed that a strong genetic basis underlies the condition, the causes of autism are still unknown. Stephen Scherer at SickKids Hospital is project leader of the Autism Genome Project, an unprecedented initiative bringing together many of the leading geneticists, clinicians and genome scientists undertaking autism research in Canada, and linking to 170 other scientists from 10 other countries worldwide. This project screened the genomes from over 6000 members of 1600 families, to find where susceptibility genes reside along the chromosomes. The project, which identified 18 new candidate genes for autism spectrum disorder, and resulted in a publication in Nature, will incorporate genetic information about autism into health care delivery and policy development, and eventually lead to new and more accurate diagnostic tests.
Our work in the health sector:
Segmental duplications in neurodevelopmental, neurological and behavioral disorders
January 21, 2004There is individual variability in the genomic structure and the copy number of genes located at specific regions of the genome called segmental duplications or duplicons. These regions, which contain “molecular signatures” that facilitate rearrangements of genomic material on specific sites on chromosomal DNA, have been connected to neurological and behavioral disorders. Stephen Scherer and Xavier Estivill, and other Canadian and Spanish scientific research groups are studying these segmental duplications to accurately characterize them in large-scale DNA sequencing project for the first time, to gain further understanding on their role in neurodevelopmental, neurological, and behavioral disorder.
Stem cell genomics
July 20, 2001Stem cells have extraordinary potential to help in the treatment of some of our most intractable diseases—for example, diabetes, arthritis, stroke and neurological conditions such as Parkinson’s and Alzheimer’s. The full exploitation of their potential of stem cells requires greater understanding around the genetic factors of stem-cells. Michael Rudnicki and Ronald Worton determined which genes are active in stem cells using new methods of detection and analysis called DNA micro-arraying, Serial Analysis of Gene Expression and protein studies (proteomics). Their work created StemBase, the largest stem-cell gene-expression database in the world.
The Biomolecular Interaction Network Database (BIND)
July 20, 2001Human Genome Project researchers worldwide produce a huge amount of raw information about genes and proteins. This information must be turned into knowledge if it is to be useful for further studies and for practical applications. It must be organized into databases, analyzed in a great many ways and above all made available to researchers everywhere. In his team’s project, Christopher Hogue set up specialized databases used by genomic researchers around the world. This generated three main resources that contain crucial molecular-interaction data that are used by the worldwide biomedical research community: SeqHound, BIND, SMID databases for public use plus a large set of analytical software.
Mapping the genes influencing Cystic Fibrosis
July 20, 2001Due to the pioneering work in the 1980s of researchers at the Hospital for Sick Children, it is known that all Cystic Fibrosis patients are defective in a gene called CFTR, which instructs the cell to make a protein that moves ordinary chlorine ions into and out of cells. Yet, even in patients with the identical genetic change in CFTR, the severity of Cystic Fibrosis can be very different – pointing to other genes interacting with CFTR to alter the course of the disease. Peter Durie of The Hospital for Sick Children and Lap¬Chee Tsui of the University of Hong Kong used the most up-to-date genomic methods to find these other genes. This project created the world’s largest repository of family-based cell lines for clinical-genetic studies, and further identified genes that potentially affect the severity of Cystic Fibrosis.
Proteomics and functional genomics
July 20, 2001Brenda Andrews and Cheryl Arrowsmith of the University of Toronto used functional and chemical genomic approaches to establish a comprehensive description of the biology of the budding yeast Saccharomyces cerevisiae. They used a variety of cutting-edge functional genomics approaches to define gene function and to probe the mechanistic basis for drug action and the characterization of novel, unknown and microbial proteins. They then identified the biochemical function of these proteins and made hypotheses about their cellular role in microbial cells. This new information has greatly extended fundamental knowledge about microbial biology and created an experimental basis for the development of novel anti-microbial drugs and biotechnological processes by Canadian biotech industry.
Genetic determinants of human health and disease
July 20, 2001Katherine Siminovitch of The Lunenfeld-Tanenbaum Research Institute explored gene variants causing and/or modulating a number of common multigenic disorders, including Alzheimer’s, inflammatory bowel disease, cancer (breast, endometrial, prostate, ovarian, melanoma) and osteoporosis. In addition to knowledge relevant to the diagnosis and treatment of specific diseases, this program has provided new information and methods to improve technical platforms for genotyping, gene expression profiling and the computational management and statistical analyses of clinical and genetic datasets. Such tools are key to the exploitation of the human genome sequence for the purposes of disease gene discovery and, ultimately, for translation of genomic information to clinical and therapeutic applications.
Functional genomics of Type 1 Diabetes
July 20, 2001Type 1 Diabetes (T1D) is a complex, autoimmune-mediated disease caused by multiple genetic risk factors and currently unknown environmental factors. Canada has the third highest rate of T1D in the world, costing ~$13 billion annually in T1D-related health care, disability, lost work, and premature deaths. Jayne Danska, of SickKids, led a project to identify key genes conferring T1D risk to humans, and gain insight into the biological pathways that confer early stages in disease progression. Progress made under this project was essential to the formation of an expanded $15M, 4 year T1D research effort that recently began funding with support from Genome Canada/Ontario Genomics Institute, the National Institutes of Health, Celera Diagnostics, Inc., and several European funding agencies.
Fiber Optic Nucleic Acid (FONA) biosensor based gene profiling
July 20, 2001DNA and its close relative, RNA, carry the code of life in all of nature’s creatures, and their study enables scientists to learn a great deal about human genetic diseases, and disease-causing viruses and micro-organisms. For all of these studies, scientists need to measure very accurately the amount of nucleic acids in a sample, however, previous methods were defective, with major limitations. The goal of Alex MacKenzie, Paul Piunno and Ulrich Krull’s project was to develop a new kind of nucleic acid sensor (a “biosensor”) that is reusable, sturdy, rapid, accurate, selective, sensitive and cheap. The value of this new instrument was demonstrated by evaluating DNA associated with Spinal Muscular Atrophy, a very severe childhood genetic condition.
Functional genomics and proteomics of model organisms
April 4, 2001Janet Rossant of The Hospital for Sick Children and Brenda Andrews, Jack Greenblatt, Andrew Spence of the University of Toronto led the Functional Annotation of the Mouse Genome project, which generated mouse models for human conditions such as kidney disease and osteoporosis, developed new tools to help characterize Canada’s mutant mice, and established new mouse cell lines that are in high demand by academic and industrial investigators worldwide. Their approaches now promise to provide major insights into human pathologies and highlight effective targets for therapeutic development.