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The Personal Genome Project Canada: findings from whole genome sequences of the inaugural 56 participants

Miriam S. Reuter, Susan Walker, Bhooma Thiruvahindrapuram, Joe Whitney, Iris Cohn, Neal Sondheimer, Ryan K.C. Yuen, Brett Trost, Tara A. Paton, Sergio L. Pereira, Jo-Anne Herbrick, Richard F. Wintle, Daniele Merico, Jennifer Howe, Jeffrey R. MacDonald, Chao Lu, Thomas Nalpathamkalam, Wilson W.L. Sung, Zhuozhi Wang, Rohan V. Patel, Giovanna Pellecchia, John Wei, Lisa J. Strug, Sherilyn Bell, Barbara Kellam, Melanie M. Mahtani, Anne S. Bassett, Yvonne Bombard, Rosanna Weksberg, Cheryl Shuman, Ronald D. Cohn, Dimitri J. Stavropoulos, Sarah Bowdin, Matthew R. Hildebrandt, Wei Wei, Asli Romm, Peter Pasceri, James Ellis, Peter Ray, M. Stephen Meyn, Nasim Monfared, S. Mohsen Hosseini, Ann M. Joseph-George, Fred W. Keeley, Ryan A. Cook, Marc Fiume, Hin C. Lee, Christian R. Marshall, Jill Davies, Allison Hazell, Janet A. Buchanan, Michael J. Szego and Stephen W. Scherer
CMAJ February 05, 2018 190 (5) E126-E136; DOI: https://doi.org/10.1503/cmaj.171151
Miriam S. Reuter
The Centre for Applied Genomics (Reuter, Walker, Thiruvahindrapuram, Whitney, Yuen, Trost, Paton, Pereira, Herbrick, Wintle, Merico, Howe, MacDonald, Lu, Nalpathamkalam, Sung, Wang, Patel, Pellecchia, J. Wei, Strug, Bell, Kellam, Mahtani, Hosseini, Fiume, Marshall, Buchanan, Scherer); Divisions of Clinical Pharmacology and Toxicology (I. Cohn), or Clinical, and Metabolic Genetics (Sondheimer, Weksberg, Shuman, Bowdin, Meyn, Monfared), The Hospital for Sick Children; Departments of Paediatrics (Sondheimer, R. Cohn) and Molecular Genetics (Yuen, Weksberg, Shuman, R. Cohn, Ellis, Meyn), University of Toronto; Deep Genomics Inc. (Merico); Department of Psychiatry (Bassett), University Health Network and Centre for Addiction and Mental Health, University of Toronto; Li Ka Shing Knowledge Institute (Bombard), St. Michael’s Hospital; Institute of Health Policy, Management and Evaluation (Bombard), University of Toronto; Centre for Genetic Medicine (Stavropoulos, Bowdin, Ray, Monfared); Molecular Genetics Laboratory (Stavropoulos, Ray, Marshall), Division of Genome Diagnostics, Paediatric Laboratory Medicine; Developmental and Stem Cell Biology (Hildebrandt, W. Wei, Romm, Pasceri, Ellis); Ted Rogers Cardiac Genome Clinic (Hosseini); Cytogenetics Laboratory (Joseph-George), Division of Genome Diagnostics, Paediatric Laboratory Medicine, The Hospital for Sick Children; Departments of Biochemistry and Laboratory Medicine, and Pathobiology (Keeley), University of Toronto; DNAstack (Cook, Fiume); McLaughlin Centre (Lee, Scherer), University of Toronto; Medcan Health Management Inc. (Davies, Hazell); Dalla Lana School of Public Health (Szego), Department of Family and Community Medicine, and The Joint Centre for Bioethics, University of Toronto; Centre for Clinical Ethics (Szego), St. Joseph’s Health Centre, Toronto, Ont.
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Susan Walker
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Bhooma Thiruvahindrapuram
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Joe Whitney
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Iris Cohn
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Neal Sondheimer
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Ryan K.C. Yuen
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Brett Trost
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Tara A. Paton
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Richard F. Wintle
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Jeffrey R. MacDonald
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Chao Lu
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Thomas Nalpathamkalam
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Wilson W.L. Sung
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Ronald D. Cohn
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S. Mohsen Hosseini
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Michael J. Szego
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Stephen W. Scherer
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  • For correspondence: stephen.scherer@sickkids.ca
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  • RE: Genetic revolution revealing hundred-dollar genome: a health care cart before the genomic horse
    Shiva Singh
    Posted on: 20 February 2018
  • Posted on: (20 February 2018)
    RE: Genetic revolution revealing hundred-dollar genome: a health care cart before the genomic horse
    • Shiva Singh, Professor, The University of Western Ontario, London, Ontario

    The science of genetics is grounded in the principles of inheritance outlined over 150 years ago. Almost 100 years later, the physical bases for these principles were articulated in the DNA model published in 1953 by Watson and Crick. Together, they provided a framework to explain transmission of like begets like and accommodated incredible differences seen across life forms as well as across individuals within a species. In doing so, they provided the very foundation for the universality of evolution by natural selection and unified all life sciences.

    The next stepping stone in advancing genetic research came with the technological developments that allowed direct appraisal of DNA leading to the sequencing of the complete genomes and the current "omics" revolution. It is now possible to assess an individual for their complete set of DNA, RNA and proteins including some of the regulatory features. Finally, we are able to directly look at the genome and explore such fundamental questions as where does it come from, what does it do? how does it do it and what may go wrong? The secret of life is being divulged in increasing details.

    Probably the most important development in advancing genetic research came with making the DNA technologies affordable for individual researchers across the world. As an example, the human genome project that produced a composite of human genome sequence was completed at a cost of $2.7 billion in 1991 dollars. It followed...

    Show More

    The science of genetics is grounded in the principles of inheritance outlined over 150 years ago. Almost 100 years later, the physical bases for these principles were articulated in the DNA model published in 1953 by Watson and Crick. Together, they provided a framework to explain transmission of like begets like and accommodated incredible differences seen across life forms as well as across individuals within a species. In doing so, they provided the very foundation for the universality of evolution by natural selection and unified all life sciences.

    The next stepping stone in advancing genetic research came with the technological developments that allowed direct appraisal of DNA leading to the sequencing of the complete genomes and the current "omics" revolution. It is now possible to assess an individual for their complete set of DNA, RNA and proteins including some of the regulatory features. Finally, we are able to directly look at the genome and explore such fundamental questions as where does it come from, what does it do? how does it do it and what may go wrong? The secret of life is being divulged in increasing details.

    Probably the most important development in advancing genetic research came with making the DNA technologies affordable for individual researchers across the world. As an example, the human genome project that produced a composite of human genome sequence was completed at a cost of $2.7 billion in 1991 dollars. It followed assembly of the complete genome sequence of an individual human at the cost of $100 million dollars in the year 2007. Ten years later, an individual genome sequence is being assembled at a cost of $1000 and we are not done yet. Soon, it may cost $100 to sequence the complete genome of any human, new born, young and old. It will be a permanent and most comprehensive description of the individual. As it stands, the interpretation of the results will be most challenging. Yet, they will hold the key to the past, present and future. It just keeps on getting cheaper and better.

    This affordability and utmost resolution is allowing researchers to consider research that would have been unthinkable just a few years ago. It is not uncommon to use the complete genome sequence of patient(s) with a disease in relation to their unaffected relatives while assessing connection of gene mutation(s) causing the disease. Interestingly, this research has moved the genome sequence to include the variations in the general population. The projects on sequencing genomes of normally functioning individuals from the general population covers all DNA sequence differences or variants that may have positive, negative or no effect on our daily lives. Some of these effects are known while others are viewed as variants of unknown significance (VUS). More important, the genome sequence data could be stored, archived, reanalyzed at timely intervals using ever improving tools, technologies and understanding of human variations. We have moved in to a new era of prediction of health and wellbeing. The question is, are we ready for it?

    Comparisons of individual genomes representing the general population have begun to generate novel insights and opening new directions to questions that were beyond the bound of any inquiry just a year ago. For example, research on 56 individuals representing Personal Genome Project Canada published in CMAJ (February 5, 2018) reports that "most variants were of uncertain significance or likely benign", "most participants carried at least 1 disease-associated allele" and "in ~25% of individuals the whole genome sequencing can benefit their routine health care in the future". The implication and interpretation of such results will continue to be challenging.

    In the future, it is likely that individual genome sequences of individuals, young and old including new born babies will be generated. In some cases, it will be generated in order to guide health and wellbeing issues for life that may include early diagnosis and personalized medicine while for others it will represent a curiosity, not unlike what is available today through variety of ancestry-related commercial operations. The generation of genome sequences will be irresistible at a cost of $100. There is no doubt that it will be generated on a large scale because we can and with no obvious purpose. Yet, every personal genome sequence will carry with it a variety of health and societal implications. It will bring about novel ethical questions that could not be left to a single individual or group to identify and offer solutions. It deserves broad societal input.

    What is needed is for the health professionals as well as general public to become informed, interested and involved. The public must take full ownership of this issue. The $100 genome is here to stay. Like a driver's licence and health card, it will represent a critical piece of identity. More than the driver's licence and health card however, the sharing of this information with others must be protected. To this end, legislations like "The Genetic Non-Discrimination Act" of the Government of Canada will be needed and necessary. There is a plethora of insights in the $100 genome. Only the most careful application and sharing of this insight will assure its full value for the individual, his/her family and the society.

    Show Less
    Competing Interests: None declared.
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Canadian Medical Association Journal: 190 (5)
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The Personal Genome Project Canada: findings from whole genome sequences of the inaugural 56 participants
Miriam S. Reuter, Susan Walker, Bhooma Thiruvahindrapuram, Joe Whitney, Iris Cohn, Neal Sondheimer, Ryan K.C. Yuen, Brett Trost, Tara A. Paton, Sergio L. Pereira, Jo-Anne Herbrick, Richard F. Wintle, Daniele Merico, Jennifer Howe, Jeffrey R. MacDonald, Chao Lu, Thomas Nalpathamkalam, Wilson W.L. Sung, Zhuozhi Wang, Rohan V. Patel, Giovanna Pellecchia, John Wei, Lisa J. Strug, Sherilyn Bell, Barbara Kellam, Melanie M. Mahtani, Anne S. Bassett, Yvonne Bombard, Rosanna Weksberg, Cheryl Shuman, Ronald D. Cohn, Dimitri J. Stavropoulos, Sarah Bowdin, Matthew R. Hildebrandt, Wei Wei, Asli Romm, Peter Pasceri, James Ellis, Peter Ray, M. Stephen Meyn, Nasim Monfared, S. Mohsen Hosseini, Ann M. Joseph-George, Fred W. Keeley, Ryan A. Cook, Marc Fiume, Hin C. Lee, Christian R. Marshall, Jill Davies, Allison Hazell, Janet A. Buchanan, Michael J. Szego, Stephen W. Scherer
CMAJ Feb 2018, 190 (5) E126-E136; DOI: 10.1503/cmaj.171151

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The Personal Genome Project Canada: findings from whole genome sequences of the inaugural 56 participants
Miriam S. Reuter, Susan Walker, Bhooma Thiruvahindrapuram, Joe Whitney, Iris Cohn, Neal Sondheimer, Ryan K.C. Yuen, Brett Trost, Tara A. Paton, Sergio L. Pereira, Jo-Anne Herbrick, Richard F. Wintle, Daniele Merico, Jennifer Howe, Jeffrey R. MacDonald, Chao Lu, Thomas Nalpathamkalam, Wilson W.L. Sung, Zhuozhi Wang, Rohan V. Patel, Giovanna Pellecchia, John Wei, Lisa J. Strug, Sherilyn Bell, Barbara Kellam, Melanie M. Mahtani, Anne S. Bassett, Yvonne Bombard, Rosanna Weksberg, Cheryl Shuman, Ronald D. Cohn, Dimitri J. Stavropoulos, Sarah Bowdin, Matthew R. Hildebrandt, Wei Wei, Asli Romm, Peter Pasceri, James Ellis, Peter Ray, M. Stephen Meyn, Nasim Monfared, S. Mohsen Hosseini, Ann M. Joseph-George, Fred W. Keeley, Ryan A. Cook, Marc Fiume, Hin C. Lee, Christian R. Marshall, Jill Davies, Allison Hazell, Janet A. Buchanan, Michael J. Szego, Stephen W. Scherer
CMAJ Feb 2018, 190 (5) E126-E136; DOI: 10.1503/cmaj.171151
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