Exome Sequencing

Exome Sequencing at OHSU Knight Diagnostic Laboratories (KDL) is designed to detect germline mutations in the coding regions within the entire exome with additional coverage in genes that are known to be associated with inherited disease. These protein coding regions, called exons, are captured and sequenced using next-generation sequencing (NGS) techniques. Unlike conventional sequencing techniques, which only test for single or small groups of genes, Exome Sequencing involves testing and analyzing thousands of genes.

To provide comprehensive germline mutation spectrum analysis, KDL also offers Exome Exon-centric Deletion/Duplication analysis. The deletion/duplication analysis is designed to identify single exon deletions and duplications. This one million probe array provides complete coverage of over 4600 disease-associated genes, which are missed on whole exome sequencing platforms. If a trio with deletion/duplication is ordered, only the proband will receive this component of the analysis.

Exome Sequencing has proved to be valuable in diagnosing rare hereditary diseases, especially when the patient’s physical exam and medical history strongly suggest a genetic etiology. Ordering Exome Sequencing can occur early in the proband’s evaluation or following extensive negative genetic or metabolic testing.

For more information about Exome Sequencing and Exome Exon-centric Deletion/Duplication analysis: Please read our Exome Sequencing Booklet

Exome Testing Options
KDL offers different Whole Exome Sequencing options. Physicians may decide to order exome sequencing and exon-centric deletion/duplication analysis, exome sequencing only, and exon-centric deletion/duplication analysis only. In addition, KDL can test the proband only or patients as a trio
  • Exome Sequencing &
    Del/Dup*
    icon-infographic-01 Trio Testing Read More
    *Del/Dup analysis
    provided for Proband only
  • Exome
    Sequencing only
    icon-infographic-01 Trio Testing Read More
  • ​Exome
    Del/Dup only
    icon-infographic-02 Not Offered
  • Exome Sequencing &
    Del/Dup*
    icon-infographic-03 Proband Only Testing Read More
  • Exome
    Sequencing only
    icon-infographic-03 Proband Only Testing Read More
  • ​Exome
    Del/Dup only
    icon-infographic-03 Proband Only Testing Read More

Exome Sequencing
The Exome Sequencing test will analyze the exons or coding regions of thousands of genes simultaneously using Illumina NextSeq 500 technology and preparing samples using hybridization probes to enrich exonic regions. In addition, extra probes are added to enrich clinically relevant genes.

Exon-centric Deletion/Duplication Analysis
The Exome Exon-centric ​Deletion/Duplication analysis uses CytoSure Medical Research Exome Array (Oxford Gene Technology) to detect deletions and duplications. The targeted array has 1,000,000 probes targeted to the exonic regions of 4,645 medically relevant genes. The arrays will be run using Agilent SureScan technology. This array is an ideal complement to an exome sequencing approach to provide a comprehensive mutation spectrum analysis in rare disease.

Proband vs. Trio
Trio testing compares the proband and both parents to identify de novo, biallelic, and hemizyogous changes that may explain the patient’s phenotype. We recommend trio testing because comparing the patient’s sequencing data to the parents allows for better interpretation of results. Trio testing is appropriate for NextGen Sequencing and if both parents are available for testing. When trio testing is not possible, KDL also offers proband only testing.

Target variant testing can also be carried out on other family members if needed.

Deciding What Test To Order
The table below is designed to help with the test selection process. When deciding which test to order, it’s important to consider if both parents are available for trio testing and if deletion and duplication analysis is desired.

KDL Code

Test Name

Considerations for Test Selection

2850

Trio Sequencing + Proband Del/Dup

Both parents are available and de novo, biallelic, and hemizygous variant reporting is desired. The risk of ambiguous results is decreased with trio testing. Adding deletion/duplication provides exon-level copy number changes undetectable in sequencing only. Reasons for referral often include diagnostic testing for symptomatic patients without a definite diagnosis, presentation of multiple and unexplained phenotypes, or reflex testing for patients who have already undergone testing for single genes or gene panels with negative findings.

2825

Proband Sequencing + Del/Dup

Both parents are not available. Adding deletion/duplication provides exon-level copy number changes undetectable in sequencing only. Reasons for referral often include diagnostic testing for symptomatic patients without a definite diagnosis, presentation of multiple and unexplained phenotypes, or reflex testing for patients who have already undergone testing for single genes or gene panels with negative findings.

2890

Trio Sequencing only

Both parents are available and de novo, biallelic, and hemizygous variant reporting is desired. The risk of ambiguous results is decreased with trio testing. This test is unable to detect exon-level deletion/duplications. Reasons for referral often include diagnostic testing for symptomatic patients without a definite diagnosis, presentation of multiple and unexplained phenotypes, or reflex testing for patients who have already undergone testing for single genes or gene panels with negative findings.

2800

Proband Sequencing only

Both parents are not available. This test is unable to detect exon-level deletion/duplications. Reasons for referral often include diagnostic testing for symptomatic patients without a definite diagnosis, presentation of multiple and unexplained phenotypes, or reflex testing for patients who have already undergone testing for single genes or gene panels with negative findings.

2875

Proband Del/Dup only

Reasons for referral often include only a single pathogenic variant or VUS is identified in a patient with an autosomal recessive disorder, no pathogenic variants or VUS were identified on prior exome-sequencing, and the suspected condition(s) have a high incidence of causative deletions/duplications.


Ordering Process

  1. Patient will read and sign the consent form (located in the same PDF as the requisition form)
    • The proband only or trio consent forms should be used based on the test ordered
  2. Requisition form is completed by physician
    • Complete clinical/phenotypic information must  be included (included as part of the requisition form)
  3. Patient provides a blood sample
  4. Sample, consent form, and requisition form are shipped to: 2525 SW 3rd Ave, Ste 350, Portland, OR 97201 

The phenotypic history and consent forms are attached to the requisition forms:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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