All test orders will be reviewed by a SickKids or CHEO genetic counsellor to ensure that the Genome-Wide Sequencing (GWS) application requirements and clinical eligibility criteria are met.

Application requirements

  • All patients for whom GWS is ordered must meet the Ontario Health patient eligibility criteria for funding as outlined in the requisition.
  • The ordering provider must have sufficient genetics expertise and/or clinic support to provide pre and post-test counselling, and safely manage results .
  • All efforts have been made to provide trio genetic samples (i.e., both biological parents and proband) 
  • The application should outline the results of prior genetic testing and relevant investigations.
  • Incomplete applications may delay review and adjudication of test approval, as well as turnaround time. Test orders with incomplete information will not be processed; the laboratory will store the sample and request additional information prior to initiating testing.

Clinical eligibility criteria

  • If you have a patient for which you would like to order GWS, but you are unsure if they meet the current clinical eligibility criteria, please reach out the laboratory genetic counsellors at gso@cheo.on.ca (CHEO) or gso.requests@sickkids.ca (SickKids).
  • All test orders will be reviewed by a SickKids or CHEO genetic counsellor.
  • Clinical eligibility criteria are outlined on the requisition. Additional details relating to eligibility and investigations are outlined in the PGP expert group guidance documents. Notably, 
    • A diagnosis that explains all or most of the patient’s phenotype must not have been confirmed by previous genetic testing (including previous GWS).
    • GWS must be considered the standard of care in the specified clinical situation and should not be ordered for research purposes or gene discovery.

Review process

When specimens and required documents are received at the GSO laboratory, the request is reviewed by the laboratory staff.

  • If documentation is incomplete, the ordering provider will be informed of the incomplete order.
  • If documentation is complete and the patient meets the clinical criteria for testing, testing will proceed.
  • If additional information is needed to confirm eligibility or guide the analysis, the GSO laboratory will contact the referring provider. Testing will proceed once the additional information is obtained.

Analysis strategy

Testing should be completed on the affected individual. Additional affected relatives or unaffected parents, when available, can be analyzed concurrently to facilitate and improve variant interpretation:

  • Trios (proband and both biological parents) are the preferred GWS analysis strategy for all undiagnosed patients, with a few exceptions.
    • All efforts must be made to provide trio genetic samples.
    • Parental samples when possible, should be submitted alongside the proband sample to allow concurrent analysis.
    • If parents are not available for concurrent analysis, other sequencing strategies can be considered and samples from alternate family members may be submitted for concurrent analysis. Please contact the lab to discuss possible test strategies.
  • If autosomal recessive inheritance is suspected, including in the context of consanguineous families, samples from additional affected individuals (e.g., sibling) may be submitted for concurrent analysis in addition to the parents.
  • If X‐linked inheritance is suspected, both parents should still be included for trio analysis when possible. If a better suited targeted X-linked panel is available, the panel approach should be prioritized. In very rare instances of clear X-linked inheritance, samples from other family members may be submitted for comparative analysis, after discussion with the diagnostic laboratory.
  • In instances of very clear autosomal dominant inheritance, samples from different family members may be helpful in the analysis and can be submitted for comparative analysis after discussion with the diagnostic laboratory.
  • Please note, a separate analysis is not performed on samples from family members; they are used for the purposes of interpreting the proband’s results.

Additional genetic testing must be considered (concurrently if indicated) for conditions not detected by exome sequencing (i.e., disorder of copy number variation, imprinting, nucleotide repeat expansion, or mitochondrial DNA-encoded)   

  • If a disorder associated with variants in the mitochondrial genome is suspected, a targeted clinical test designed to assess the mitochondrial genome should be performed.
  • If the patient has a phenotype highly specific to a known genetic condition for which an optimized genetic panel exists, or for which all known gene‐disease associations can be assessed, a targeted gene panel should be given priority assuming it is more sensitive (e.g., Noonan spectrum disorders).