The Exome and Whole Exome Sequencing

Learning Objectives and CME/Disclosure Information

This activity is intended for healthcare providers delivering care to women and their families.

After completing this activity, the participant should be better able to:

1. Contrast ‘the exome’ with ‘whole exome sequencing’
2. Recall what constitutes a VUS

Estimated time to complete activity: 0.25 hours

Faculty:

Susan J. Gross, MD, FRCSC, FACOG, FACMG
President and CEO, The ObG Project

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires instructors, planners, managers and other individuals who are in a position to control the content of this activity to disclose any real or apparent conflict of interest (COI) they may have as related to the content of this activity. All identified COI are thoroughly vetted and resolved according to PIM policy. PIM is committed to providing its learners with high quality CME activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest.

Faculty: Susan J. Gross, MD, receives consulting fees from Genoox, Inc., and has financial interest in The ObG Project, Inc.

Planners and Managers: The PIM planners and managers, Trace Hutchison, PharmD, Samantha Mattiucci, PharmD, CHCP, Judi Smelker-Mitchek, MBA, MSN, RN, and Jan Schultz, MSN, RN, CHCP have nothing to disclose.

Method of Participation and Request for Credit

Fees for participating and receiving CME credit for this activity are as posted on The ObG Project website. During the period from Dec 31 2017 through Dec 31 2019, participants must read the learning objectives and faculty disclosures and study the educational activity.

If you wish to receive acknowledgment for completing this activity, please complete the post-test and evaluation. Upon registering and successfully completing the post-test with a score of 100% and the activity evaluation, your certificate will be made available immediately.

For Pharmacists: Upon successfully completing the post-test with a score of 100% and the activity evaluation form, transcript information will be sent to the NABP CPE Monitor Service within 4 weeks.

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education

Postgraduate Institute for Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Continuing Nursing Education

The maximum number of hours awarded for this Continuing Nursing Education activity is 0.2 contact hours.

Read Disclaimer & Fine Print

WHAT IS IT?

The exome refers to the expressed regions of the genome, or the exons, which code for proteins
- The exome constitutes about 2%-3% of the genome
- There are about 180,000 exons in the over 20,000 genes in the human genome

DNA sequence analysis of all of the expressed genes in the genome is referred to as Whole Exome Sequencing (WES or WXS)

WES generally allows for simultaneous analysis of all exons in one test
- WES will analyze close to 95% of the exons
WES is usually considered for individuals with rare diseases or syndrome for whom testing of specific potentially disease causing genes have not identified any disease causing gene mutations
WES will not detect all types of genetic changes in the exome, so there are limitations
Costs tend to be lower than whole genome sequencing (WGS)
Currently, the use of WES in the prenatal period is considered investigational
- WES should not be done routinely in pregnancy
- There may be specific circumstances where WES may be considered with appropriate counseling and informed consent (see ISPD/SMFM/PQF recommendations below in ‘Related ObG Topics’)

KEY POINTS:

WES analysis will generally require a blood sample
- Requirements will vary by laboratory
Results from WES will not always yield definitive, actionable results that confirm a diagnosis
- Findings may indicate a Variant of Uncertain Significance (VUS) that may be tracked over time to determine if the variant is ultimately benign or pathogenic
- WES testing may often be most informative when an individual’s family members are also tested or willing to be tested to clarify result interpretation
Genetic counseling is recommended pre and post WES analysis
Thorough informed consent process is imperative given the potential for results that may or may not be definitive