Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct 25;193(42):E1626-E1629.
doi: 10.1503/cmaj.210549.

Genome sequencing as a diagnostic test

Gregory Costain  1 , Ronald D Cohn  2 , Stephen W Scherer  2 , Christian R Marshall  2
Affiliations

Genome sequencing as a diagnostic test

Gregory Costain et al. CMAJ. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Competing interests: Stephen Scherer reports royalties from Athena Diagnostics, Lineagen and Population Bio, and consulting fees from Population Bio and Deep Genomics. No other competing interests were declared.

Figures

Figure 1:
Figure 1:
Genome sequencing process. Middle panel was adapted from “Whole Genome Sequencing” by BioRender.com (2021); retrieved from https://app.biorender.com/biorender-templates. Note: Variants in the KDM6A gene are linked to Kabuki syndrome. After appropriate pretest counselling, including review of possible results, a DNA sample is obtained from the patient, usually via a blood draw. Samples from biological parents are often sequenced at the same time to give additional context regarding inheritance. DNA is fragmented into small pieces and run on a high-throughput sequencing machine to generate millions of “nucleotide reads.” Reads are aligned to a reference genome, like puzzle pieces being assembled by looking at the image pictured on the box. The average number of reads covering a given genomic position (the “read depth”) is typically 30–40. Variants (differences) from that reference are annotated using sophisticated bioinformatics tools and large-scale databases of genomic variation. These variants are filtered and reviewed by a genome analyst to identify 1 or more that might be causal for the observed clinical presentation.
See this image and copyright information in PMC

References

    1. Clark MM, Stark Z, Farnaes L, et al. . Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases. NPJ Genom Med 2018;3:16. - PMC - PubMed
    1. Bick D, Jones M, Taylor SL, et al. . Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases. J Med Genet 2019;56: 783–91. - PMC - PubMed
    1. Manickam K, McClain MR, Demmer LA, et al. ACMG Board of Directors. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2021. July 1 [Epub ahead of print]. doi: 10.1038/s41436-021-01242-6. - DOI - PubMed
    1. Dimmock DP, Clark MM, Gaughran M, et al. RCIGM Investigators. An RCT of rapid genomic sequencing among seriously ill infants results in high clinical utility, changes in management, and low perceived harm. Am J Hum Genet 2020;107: 942–52. - PMC - PubMed
    1. Turro E, Astle WJ, Megy K, et al. . Whole-genome sequencing of patients with rare diseases in a national health system. Nature 2020;583:96–102. - PMC - PubMed

Publication types

Grants and funding