Genome-wide sequencing pilot project helps Ontario families get answer


Ottawa and Toronto, Ontario — Tuesday April 26, 2022

Twelve-year-old Anna and her Ottawa family have been on a quest for diagnostic answers since she was six months old. Isla, 4, was a medical mystery from her first week of life. A pilot project from CHEO, a pediatric health care and research centre in Ottawa, and The Hospital for Sick Children (SickKids) in Toronto, aims to help ensure Ontarians with rare diseases have access to timely genetic diagnoses through genome-wide sequencing (GWS). 

Genome-wide Sequencing Ontario (GSO) is a pilot implementation and quality improvement project for rare disease diagnostics, designed to deliver timely clinical GWS to Ontario patients suspected of having a rare genetic condition. The pilot project, which has just completed the first year of its two-year mandate, is providing GWS in the form of exome sequencing and genome sequencing to approximately 2,000 Ontario families. Exome sequencing examines the very important one to two per cent of the genome that codes for proteins, while genome sequencing interrogates the entire genome. 

Although exome sequencing was already available for Ontario patients via labs outside of Canada, GSO will determine whether it’s feasible to provide increased access to, and faster results from, GWS while maintaining all data and samples in Ontario. Prior to the launch of GSO, patients and their families often waited six months or more for exome sequencing to be completed and little was known about the costs and quality of the testing or the outcomes of the testing, including the health systems impact and the percentage of Ontarians who receive a diagnosis.  

To date, GSO has sequenced the DNA of more than 1,800 patients and family members, and has returned almost all test results within three months of obtaining the samples. In addition, GSO has been able to provide a diagnosis for 32 per cent of participating families, which is in line with reported diagnostic rates for this technology worldwide.  

Long diagnostic odysseys can lead to stress, fragmented care for patients with rare diseases 

More than one-third of the estimated930,000 Ontarians with a rare disease lack a genetic diagnosis, despite lengthy and costly investigations, which was the case for most of Anna’s life.  

Anna had a childhood filled with regular injuries as a result of persistent muscle weakness, with hundreds of doctor’s visits. Her clinical team at CHEO completed dozens of tests, including muscle biopsies, metabolic testing and at least five different genetic tests, but no conclusive diagnosis was reached. 

Conventional genetic testing involves testing subsets of genes, often leading to multiple tests and investigations, which can present a complicated and time-consuming process for clinicians, patients and families. In contrast, GWS can search all known genes for variants that could be disease-causing, providing a much more comprehensive look at a patient’s genetic data. 

Isla had severe jaundice, skin rashes, extremely low energy, difficulty feeding and problems with growth associated with high levels of inflammation markers in her blood at just one week of age. She spent over a year in and out of SickKids with high fevers, infections, breathing issues and extreme acid reflux. Her clinical team addressed the symptoms while they searched to find the underlying cause, but tests to check her blood, bone marrow, immune system, DNA and more yielded nothing. 

Diagnoses provide clarity and open the door to treatment plans and relief for patients and their families 

A diagnosis can often be the first step to accessing targeted care and for families, it can provide emotional relief and improved access to support and resources. 

Isla was started on a biologic drug to reduce her inflammation levels with the hopes it would help address her other health issues. Still, her clinical team and her family wanted an explanation for all of Isla’s health concerns to help optimize treatment and prevent complications. Isla had exome sequencing as one of the last diagnostic options, which found aa new DNA change in a gene called CDC42, which is known to cause severe inflammation. Armed with this knowledge, Isla’s family and clinical team were confident that their treatment plan was the right one. 

Anna had genome sequencing as part of GSO’s quality improvement study to evaluate the benefit of interrogating the entire genome. GSO reported that she has a rare genetic condition because of two variants affecting a gene called SELENON. She inherited one variant from her mother and one from her father. Genome sequencing was critical to the identification of these variants in Anna as they were not detectable via the previous testing technologies and would not have been identified using exome sequencing. Although she is small for her age and her bone development is delayed, she takes swimming lessons, does her best to keep up with friends at recess, gets good grades and is an avid reader. Like any 12-year-old, she loves spending time on her tablet playing games. “More than I probably should,” Anna says.  

“It took 12 years to finally put a name to what Anna was experiencing every day sinceshe was an infant. When we got the genome sequencing results and diagnosis, it was the first time in 12 years that we were able to read something with a name on it and say, ‘That’s it! That’s what we’ve been dealing with,’” said Mallory Boileau, Anna’s mother. “It would be great for families to get this type of answer at the beginning of their journey. Twelve years is a long road not to have answers.” 

Now, Anna’s family and care team can keep an eye out for potential complications that are associated with her diagnosis. Mallory says, “The not knowing is sometimes more terrifying than anything. We’re no longer guessing all the time and can address things before they become an issue. It’s such a relief.” 

Isla’s family is thankful, too.   “After Isla started her treatment, you could tell how much better she was feeling. Isla started to have more energy and began smiling and even laughing,” says Miki Simmons, Isla’s mother. “At four years old, Isla’s keeping up with all her older siblings and I’m not sure where we would be if we didn’t have the treatment plan and diagnostic answers that we did when she was a baby.” 

GSO to investigate the cost and feasibility of genome sequencing compared to exome sequencing 

A subset of 650 families will form the basis of a quality improvement pilot, with half of those receiving genome sequencing rather than the current standard of care, exome sequencing. Exome sequencing focuses on the one to two per cent of DNA that encodes proteins, because genetic variants that alter the normal function of proteins are the most likely cause of severe disease.  Genome sequencing, while currently a costlier technology, determines almost the entire sequence of a person’s DNA. 

Through this quality improvement project, GSO will compare the results of each sequencing type and the findings will inform a robust assessment of diagnostic utility, cost effectiveness, and timeliness of exome sequencing and genome sequencing, which will hopefully inform provincial and cross-provincial policy related to genome-based diagnostics for rare diseases. 

GSO is funded by the Ontario Ministry of Health and Genome Canada, via Ontario Genomics.  

Genome Canada’s funding is part of its All for One precision health initiative that advances a new standard of health care for Canadians, expanding access to genome-wide sequencing for diagnosis and treatment of life-threatening genetic diseases. Now with pan-Canadian reach, and significant investment and strong partnership from provincial and regional health services authorities, All for One is deployed across six implementation projects serving nine provinces. 

More information and resources on GSO can be found at 

Partner quotations 

“Our government is proud to support this pilot with CHEO and SickKids, which is already helping Ontario families just one year into implementation. This promising project will improve patient outcomes by providing timely access to genetic diagnoses, which is another way Ontario is building a better connected health-care system, centred on the needs of patients.”
– Christine Elliott, Ontario’s Deputy Premier and Minister of Health 

“Early diagnosis of rare diseases at the molecular level is vital to shorten the diagnostic journey of rare disease patients, like Anna and Isla, and make sure they can access appropriate care as soon as possible. This partnership uses genomics tools to inform provincial and cross-provincial policies that improve rare disease diagnosis and quality of life.” 
– Dr. Bettina Hamelin, President and CEO, Ontario Genomics   

“For parents like Anna’s, there is an unbelievable and largely unseen stress that goes with not knowing what is causingtheir child’s condition. Along with this stress is a desperate desire to find answers and do the best thing for them. And having that uncertainty linger for years and years is such a burden. As clinicians, we want to providemore certainty to these families as soon as possible. We hope the findings from our project will bring that possibility closer to a reality.”
Dr. Kym Boycott, Chair, Department of Genetics, CHEO 

“Quick access to comprehensive genetic testing, like exome or genome sequencing, must be a cornerstone of health care for children and youth who have suspected, but undiagnosed, genetic conditions. With GSO, not only are we able to provide this testing, but we’re also preparing for the future when genome sequencing may become the new standard-of-care clinical test for these patients. This pilot is another step in the path to achieve SickKids’ vision of Precision Child Health, where every patient and family receives individualized care.”
– Dr. Martin Somerville, Division Head of Genome Diagnostics, SickKids 

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Media contact

Paddy Moore, CHEO
o. 613-737-7600, ext. 3536 | [email protected]

About CHEO

Dedicated to the best life for every child and youth, CHEO is a global leader in pediatric health care and research. Based in Ottawa, CHEO includes a hospital, children’s treatment centre, school and research institute, with satellite services located throughout Eastern Ontario. CHEO provides excellence in complex pediatric care, research and education. We are committed to partnering with families and the community to provide exceptional care — where, when and how it’s needed. CHEO is a partner of the Kids Come First Health Team, a network of partners in Eastern Ontario working to create a high quality, standardized and coordinated system for pediatric health care that is centred around children, youth and their families. Every year, CHEO helps more than 500,000 children and youth from Eastern Ontario, western Quebec, Nunavut and Northern Ontario.

About The Hospital for Sick Children (SickKids)  

The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally. Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is a founding member of Kids Health Alliance, a network of partners working to create a high quality, consistent and coordinated approach to paediatric health care that is centred around children, youth and their families. SickKids is proud of its vision for Healthier Children. A Better World. 

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