The spectrum of copy number variation in the Pan-Canadian HostSeq databank
13 affiliations
- 1Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada
- 2Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada
- 3The Centre for Applied Genomics and the Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
- 4University of Toronto, Toronto, Ontario, Canada
- 5Unity Health Toronto, Toronto, Ontario, Canada
- 6William Osler Health System, Brampton, Ontario, Canada
- 7Schwartz/Reisman Emergency Medicine Institute, Sinai Health, Toronto, Ontario, Canada
- 8University Health Network, Toronto, Ontario, Canada
- 9Women’s College Hospital, Toronto, Ontario, Canada
- 10Dynacare Medical Laboratories, Brampton, Ontario, Canada
- 11Mackenzie Health, Richmond Hill, Ontario, Canada
- 12Ontario Institute for Cancer Research, Toronto, Ontario, Canada
- 13McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
Abstract
The integration of copy number variant (CNV) workflows into genome sequencing (GS) analysis pipelines allows for the identification of CNVs implicated in disease. Here, we generated a novel resource of CNVs identified in the HostSeq population cohort from Canada, identified the prevalence of recurrent CNVs associated with neurodevelopmental disorders, and determined CNVs of potential clinical relevance for reproductive planning and personal disease risk. GS data and CNV calls were generated for 10,488 participants from across Canada as part of the HostSeq initiative. The CNV calls were filtered to generate a rare dataset, which was further filtered into the OMIM morbid, ClinGen dosage, and DECIPHER datasets. CNV deletions were stratified into either Tier 1, 2, or 3 based on the inheritance pattern of the genes involved. A putatively pathogenic dataset was generated by identifying CNVs in the ClinGen dosage and DECIPHER datasets with at least 80% overlap with previously identified pathogenic CNVs. A total of 8,543,334 CNV calls were generated. Filtering for rare variants yielded 36,631 CNVs, of which 9,922 (27.08%) encompassed at least one OMIM gene, 728 (1.99%) had at least 10% overlap with a DECIPHER region, and 1,136 (3.10%) encompassed at least one ClinGen dosage-sensitive gene. CNV deletions were stratified into 1,833 Tier 1 deletions, 32 Tier 2 deletions, and 184 Tier 3 deletions. There were 82 CNVs identified in regions associated with neurodevelopmental disorders. Of the genes with either a ClinGen dosage sensitivity score or overlap with a DECIPHER region, 206 CNVs were deemed as putatively pathogenic. We were able to detect a wide range of CNVs, highlighting the use of integrating CNV workflows into the analysis pipeline, and generated a data resource for medical genomics for the Canadian population encompassing the full spectrum of CNVs.
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BibTeX
@article{aujla2026spectrum,
title = {{The spectrum of copy number variation in the Pan-Canadian HostSeq databank}},
author = {Navneet Aujla and Bhooma Thiruvahindrapuram and Selina Casalino and Erika Frangione and Radhika Mahajan and David Di Iorio and Chun Yiu Jordan Fung and Lochana Jayachandran and Georgia MacDonald and Gregory Morgan and Dawit Wolday and Juliet Young and Maahil Arshad and Marc Clausen and Saranya Arnoldo and Alexandra Binnie and Bjug Borgundvaag and Sunakshi Chowdhary and Marc Dagher and Luke Devine and Steven Marc Friedman and Anne-Claude Gingras and Lee W. Goneau and Zeeshan Khan and Elisa Lapadula and Tony Mazzulli and Allison McGeer and Shelley McLeod and Chloe Mighton and Trevor J. Pugh and David Richardson and Jared Simpson and Seth Stern and Ahmed Taher and Lisa Strug and Yvonne Bombard and Hanna Faghfoury and Elena Greenfeld and CGEn HostSeq Initiative and Stephen W. Scherer and Jennifer Taher and Abdul Noor and Jordan Lerner-Ellis},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0359210},
url = {https://doi.org/10.1371/journal.pone.0359210},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The spectrum of copy number variation in the Pan-Canadian HostSeq databank
AU - Navneet Aujla
AU - Bhooma Thiruvahindrapuram
AU - Selina Casalino
AU - Erika Frangione
AU - Radhika Mahajan
AU - David Di Iorio
AU - Chun Yiu Jordan Fung
AU - Lochana Jayachandran
AU - Georgia MacDonald
AU - Gregory Morgan
AU - Dawit Wolday
AU - Juliet Young
AU - Maahil Arshad
AU - Marc Clausen
AU - Saranya Arnoldo
AU - Alexandra Binnie
AU - Bjug Borgundvaag
AU - Sunakshi Chowdhary
AU - Marc Dagher
AU - Luke Devine
AU - Steven Marc Friedman
AU - Anne-Claude Gingras
AU - Lee W. Goneau
AU - Zeeshan Khan
AU - Elisa Lapadula
AU - Tony Mazzulli
AU - Allison McGeer
AU - Shelley McLeod
AU - Chloe Mighton
AU - Trevor J. Pugh
AU - David Richardson
AU - Jared Simpson
AU - Seth Stern
AU - Ahmed Taher
AU - Lisa Strug
AU - Yvonne Bombard
AU - Hanna Faghfoury
AU - Elena Greenfeld
AU - CGEn HostSeq Initiative
AU - Stephen W. Scherer
AU - Jennifer Taher
AU - Abdul Noor
AU - Jordan Lerner-Ellis
PY - 2026
DA - 2026/09/25
JO - PLOS One
DO - 10.1371/journal.pone.0359210
UR - https://doi.org/10.1371/journal.pone.0359210
AB - The integration of copy number variant (CNV) workflows into genome sequencing (GS) analysis pipelines allows for the identification of CNVs implicated in disease. Here, we generated a novel resource of CNVs identified in the HostSeq population cohort from Canada, identified the prevalence of recurrent CNVs associated with neurodevelopmental disorders, and determined CNVs of potential clinical relevance for reproductive planning and personal disease risk. GS data and CNV calls were generated for 10,488 participants from across Canada as part of the HostSeq initiative. The CNV calls were filtered to generate a rare dataset, which was further filtered into the OMIM morbid, ClinGen dosage, and DECIPHER datasets. CNV deletions were stratified into either Tier 1, 2, or 3 based on the inheritance pattern of the genes involved. A putatively pathogenic dataset was generated by identifying CNVs in the ClinGen dosage and DECIPHER datasets with at least 80% overlap with previously identified pathogenic CNVs. A total of 8,543,334 CNV calls were generated. Filtering for rare variants yielded 36,631 CNVs, of which 9,922 (27.08%) encompassed at least one OMIM gene, 728 (1.99%) had at least 10% overlap with a DECIPHER region, and 1,136 (3.10%) encompassed at least one ClinGen dosage-sensitive gene. CNV deletions were stratified into 1,833 Tier 1 deletions, 32 Tier 2 deletions, and 184 Tier 3 deletions. There were 82 CNVs identified in regions associated with neurodevelopmental disorders. Of the genes with either a ClinGen dosage sensitivity score or overlap with a DECIPHER region, 206 CNVs were deemed as putatively pathogenic. We were able to detect a wide range of CNVs, highlighting the use of integrating CNV workflows into the analysis pipeline, and generated a data resource for medical genomics for the Canadian population encompassing the full spectrum of CNVs.
SN - 1932-6203
ER -