2021 Digital Edition of the ACMG Foundational Specialty Training in Cytogenetics and Genomics and Molecular Genetics and Genomics (Not accredited)

Location: Held online via the ACMG Genetics Academy

Dates of sessions: July 19 – 22, 2021

Due to the format, the digital edition version does not offer educational credits, nor does it meet the live component requirement associated with the ABMGG Alternative Pathway to Board Certification in Laboratory Genetics and Genomics.

Expiration Date: December 1, 2023

Credits offered: No credits for this course

This course contains:

• 19 presentations (14 presentations recorded during the live 2019 course and 5 updated 2021 presentations)
• 4 recorded Q&A webinars

Target Audience:

This course is for those interesting in the ABMGG specialty of Laboratory Genetics and Genomics. Those in cytogenetics and genomics and molecular genetics and genomics will be able to cross-learn specialties.

Learning Objectives

At the conclusion of this session, participants should be able to:

1. Upon completion of participating in this activity, you should be able to:
2. Review new content areas in cytogenetics and genomics specialty
3. Review new content areas in molecular genetics and genomics specialty

Pathway Learning Objectives:

Cytogenetics and Genomics (CGG) Pathway

Mitosis/Meiosis, Nondisjunction/Aneuploidy, Chromosome Structure

• Describe the cell cycle, mitosis, and meiosis
• Describe chromosome structure and banding
• Describe the consequences of meiotic/mitotic errors
• Differentiate between polymorphisms and pathogenic structural variants

Chromosome Analysis and Cytogenetic Nomenclature

• Describe the basic principles of cell culture (general and selective, stimulated and unstimulated, in situ and suspension
• Describe the principles of cell culture harvest, slide preparation and staining/banding
• Describe the basics concepts of cytogenetics nomenclature
• Differentiate between polymorphisms and pathogenic structural variants

Structural Abnormalities-translocation, inversion, del/dup, abnormal segregation

• Describe structural abnormalities and nomenclature
• Describe meiotic segregation patterns and risks of miscarriage and abnormal offspring
• Describe mosaicism, particularly in the context of ring/markers, as well as considerations for testing in such situations (skin etc.)

Sex Chromosomes Abnormalities, X-Inactivation

• Describe the structure and important regions of the X and Y chromosome, dosage
• Explain the principles of X-inactivation and functional disomy
• Recognize the different sex chromosome aneuploidies and variants (Turner syndrome and variants, etc.)

Congenital FISH and microarray testing, including UPD

• Explain the basic fundamentals of FISH and chromosomal microarray
• Describe the various microdeletion/microduplication syndromes and mechanisms (segmental dup mediated and non-seg dup mediated)
• Discuss the detection of uniparental disomy (UPD) and consanguinity using SNP microarray, as well as consanguinity

HEME I: Introduction to Technology

• Explain FISH probe basics and validation
• Demonstrate competence in FISH probe strategies and nomenclature
• Explain FISH probe patterns (both normal and abnormal)

Heme II: Myeloid Neoplasms

• Describe the process of myelopoeisis
• Describe the different myeloid neoplasms (MPN, MDS, AML)
• Define the common cytogenetic abnormalities and what testing is recommended for various myeloid malignancies

Heme III: Lymphoid Neoplasms

• Describe the process of lymphopoeisis
• Describe the different lymphoid neoplasms (B leukemia/lymphoma, T leukemia/lymphoma, CLL, myeloma)
• Define the common cytogenetic abnormalities and what testing is recommended for various lymphoid neoplasms

Solid Tumors [Breast and HER2 amp; Lung (ALK/ROS/RET)]

• Describe genetic mechanisms of oncogenesis and tumor suppression
• Explain the relevance of structural, numerical, and ploidy changes
• Define appropriate assays (and limitations) to detect specific types of aberrations
• Define pathognomonic cytogenetic/genomic aberrations for key solid tumors

Molecular Genetics and Genomics (MGG) Pathway Course

Normal Structure/Nomenclature/Types of Variation

• Describe genetic variation, and define mutation, polymorphism, locus, allele, genotype phenotype and copy number
• Define the different type of mutation: missense, nonsense, synonymous, null, and frameshift
• Use nomenclature as standardized by the Human Genome Variation Society

Common Disorders/Screening (CF, Hemophilia, Hemoglobin Disorders, Venous Thromboembolism)

• Differentiate diagnostic vs. carrier screening
• Calculate residual risk
• Describe the pathogenesis of each disorder
• Explain the methodology used in screening for each disorder
• Evaluate the test performance
• Interpret test results

Neurogenetic Disorders – (DMD, SMA, CMT, NF1)

• Explain the methodology used in each disorder; exon-level CNV (del/dup), cis/trans
• Evaluate the test performance
• Interpret test results
• Define germline and somatic mosaicism and testing limitations

Triplet Repeat Disorders (FX, MD, HD)

• Describe the specific repeats, inheritance, anticipation, pathogenesis of each disorder
• Evaluate the test performance
• Interpret test results
• Explain parental differences in transmissions

Non-mendelian and Identity (Imprinting, Mitochondrial, Identity, MCC)

• Describe the pathogenesis of each disorder
• Explain the methodology used in each disorder
• Methylation, STR, contamination, UPD Evaluate test performance
• Interpret the test results
• Define clinical significance of heteroplasmy

Introduction to Next-Generation Sequencing (NGS)

• Review the technical details of next-generation sequencing – limitations and advantages of different methods of library preparation and sequencing.
• Review the assay design process, including selecting capture for hybridization
• Explain the refinement steps of assay design to optimize data generation at difficult genomic regions, e.g., at repetitive sequences or GC-rich sequences.
• Discuss the limitations of sequence depth coverage and implications for diagnostic testing.
• Use software for NGS read alignment, variant calling and confirmation

Somatic (FLT3, JAK2, BCR-ABL1, RAS, EGFR) Interpretation of Sequence Variants

• Describe the pathogenesis of each disorder
• Explain the methodology used in each disorder; somatic vs germline interpretation
• Evaluate the test performance
• Interpret the test results

Inherited Cancers and Predisposition screening (Lynch, FAP, BRCA, MEN2)

• Describe the pathogenesis of each disorder
• Discuss predisposition screening in the NGS setting
• Interpret test results; microsatellite instability, penetrance, tumor suppressor, oncogene, repair gene, loss of heterozygosity, lifetime cancer risk

Constitutional NGS (including NIPT); Interpretation of Sequence Variants

• Use software for NGS read alignment, depth of coverage, variant calling and confirmation
• Explain the analysis of NGS data and the biostatistical components
• Evaluate the test performance
• Interpret the test results
• Recognize secondary findings

Presentations

Cytogenetics and Genomics

1. Mitosis/Meiosis, Nondisjunction/Aneuploidy, Chromosome Structure - Catherine Rehder, PhD, FACMG
2. Chromosome Analysis and Cytogenetic Nomenclature - Julie Gastier-Foster, PhD, FACMG
3. Structural Abnormalities-translocation, inversion, del/dup, abnormal segregation - Catherine Rehder, PhD, FACMG
4. Sex Chromosomes Abnormalities, X-Inactivation - Julie Gastier-Foster, PhD, FACMG
5. Congenital FISH and microarray testing, including UPD - Julie Gastier-Foster, PhD, FACMG
6. HEME I: Introduction to Technology (New 2021) – Jennelle Hodge, PhD, FACMG
7. Heme II: Myeloid Neoplasms (New 2021) – Jennelle Hodge, PhD, FACMG
8. Heme III: Lymphoid Neoplasms - Catherine Rehder, PhD, FACMG
9. Solid Tumors [Breast and HER2 amp; Lung (ALK/ROS/RET)] (New 2021) – Jennelle Hodge, PhD, FACMG

Molecular Genetics and Genomics

1. Normal Structure/Nomenclature/Types of Variation - Elaine Lyon, PhD, FACMG
2. Common Disorders/Screening (CF, Hemophilia, Hemoglobin Disorders, Venous Thromboembolism) (New 2021) – Thomas Prior, PhD, FACMG
3. Neurogenetic Disorders – (DMD, SMA, CMT, NF1) (New 2021) – Thomas Prior, PhD, FACMG
4. Triplet Repeat Disorders (FX, MD, HD) Cindy Vnencak-Jones, PhD, FACMG
5. Non-mendelian and Identity (Imprinting, Mitochondrial, Identity, MCC) - Gerald Feldman, MD, PhD, FACMG
6. Introduction to Next-Generation Sequencing (NGS) - Elaine Lyon, PhD, FACMG
7. Somatic (FLT3, JAK2, BCR-ABL1, RAS, EGFR) Interpretation of Sequence Variants – Part 1 - Cindy Vnencak-Jones, PhD, FACMG
8. Somatic (FLT3, JAK2, BCR-ABL1, RAS, EGFR) Interpretation of Sequence Variants – Part 2 - Cindy Vnencak-Jones, PhD, FACMG
9. Inherited Cancers and Predisposition screening (Lynch, FAP, BRCA, MEN2) - Julie Gastier-Foster, PhD, FACMG
10. Constitutional NGS (including NIPT); Interpretation of Sequence Variants - Elaine Lyon, PhD, FACMG

Meet the Q&A Panelists

Julie M. Gastier-Foster, PhD, FACMG

Director, Laboratory and Pathology, Global Hematology/Oncology Pediatric Excellence (HOPE)

Professor, Department of Pediatrics, Section of Hematology/Oncology, Baylor College of Medicine

Texas Medical Center

jxgastie@texaschildrens.org

Jennelle Hodge, PhD, FACMG

Associate Professor, Medical & Molecular Genetics

Co-Director, Clinical, Cytogenetics Laboratory

Associate Director, Molecular Genetics Diagnostic Laboratory

Indiana University School of Medicine

jhodge1@iu.edu

Catherine Rehder, PhD, FACMG

Associate Professor, Department of Pathology

Director, Clinical Cytogenetics Laboratory

Associate Director, Molecular Diagnostics Laboratory

Duke University Health System Clinical Laboratories

catherine.rehder@duke.edu

Robert Hufnagel, MD, PhD, FACMG

Chief, Medical Genetics and Ophthalmic Genomics Unit

Chief, Ophthalmic Genomics Laboratory

NIH: National Eye Institute

robert.hufnagel@nih.gov

Thomas William Prior, PhD, FACMG

Professor of Pathology and Director of the Molecular Genetics Laboratory

Case Western Reserve University

Thomas.Prior@UHhospitals.org

Cindy L. Vnencak-Jones, PhD, FACMG

Professor, Departments of Pathology, Microbiology & Immunology and Pediatrics

Medical Director, Molecular Diagnostics Lab

Vanderbilt University Medical Center

cindy.vnencak-jones@vumc.org

Financial Disclosures

Disclosure Statement

It is the policy of the American College of Medical Genetics and Genomics to plan and implement all of its educational activities in accordance with the ACCME Essentials and Areas and ACCME® Policies to ensure balance, independence, objectivity and scientific rigor. In accordance with the ACCME® Standards for Commercial Support, everyone (speakers, moderators, committee members and staff) who is in a position to control the content of an educational activity certified for AMA PRA Category 1 Credit™ is required to disclose all financial relationships with any commercial interests (see definition below) within the past 12 months that creates a real or apparent conflict of interest. Individuals who do not disclose will be disqualified from participating in a CME activity.

This disclosure pertains to relationships with ACCME-defined commercial interests whose products or services may be related to the subject matter of the presentation topic. Any real or apparent conflicts of interest related to the content of the presentations must be managed prior to the educational activity. ACMG will identify, review and resolve all conflicts of interests prior to an educational activity being delivered to learners.

NOTE:

• ACMG will follow the ACCME’s expectation that no employees or owners of commercial interests will be involved as planners/faculty/presenters of a CME accredited activity.
• The ACCME definition of a commercial interest is any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients.
• The ACCME does not consider providers of clinical service directly to patients to be commercial interests - unless the provider of clinical service is owned, or controlled by, an ACCME-defined commercial interest.
• Diagnostic laboratories are not considered commercial interests unless they are owned by or have a sister organization which is a commercial interest.

The following have not relevant financial relationships to disclose:

Gerald (Jerry) Feldman, MD, PhD, FACMG

Robert Hufnagel, MD, PhD

Thomas Prior, PhD, FACMG

Cindy L. Vnencak-Jones, PhD, FACMG

Julie M. Gastier-Foster, PhD, FACMG

Jennelle Hodge, PhD, FACMG

It is determined that participation does not relate to members relationship with commercial interests

Elaine Lyon, PhD, FACMG discloses that she is a consult for Genoox.

Catherine Weaver Rehder, PhD, FACMG discloses that she is a consultant for Illumina.

HIPAA Compliance

The ACMG supports medical information privacy.  While the ACMG is not a “covered entity” under HIPAA 1996 and therefore is not required to meet these standards, ACMG wishes to take reasonable steps to ensure that the presentation of individually identifiable health information at ACMG-sponsored events has been properly authorized.  All presenters have completed a form indicating whether they intend to present any form of individually identifiable healthcare information.  If so, they were asked either to attest that a HIPAA-compliant consent form is on file at their institution, or to send ACMG a copy of the ACMG HIPAA compliance form. This information is on record at the ACMG Administrative Office and will be made available on request.

Content Validation

ACMG follows the ACCME policy on Content Validation for CME activities, which requires:

Content Validation and Fair Balance

1. ACMG follows the ACCME policy on Content Validation for CME activities, which requires:

1. All recommendations involving clinical medicine must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients.
2. All scientific research referred to, reported or used in CME in support or justification of patient care recommendations must conform to the generally accepted standards of experimental design, data collection and analysis.

2. Activities that fall outside the definition of CME/CE; “Educational activities that serve to maintain, develop, or increase the knowledge, skills, and professional performance and relationships that a physician uses to provide services for patients, the public, or the profession” (source: ACCME and AMA) will not be certified for credit. CME activities that promote recommendations, treatment, or manners of practicing medicine or pharmacy that are not within the definition of CME/CE or, are known to have risks or dangers that outweigh the benefits or, are known to be ineffective in the treatment of patients.
3. Presentations and CME/CE activity materials must give a balanced view of therapeutic options; use of generic names will contribute to this impartiality.  If the CME/CE educational materials or content includes trade names, where available, trade names from several companies must be used.

Off-label Uses of Products

When an off-label use of a product, or an investigational use not yet approved for any purpose, is discussed during an educational activity, the accredited sponsor shall require the speaker to disclose that the product is not labeled for the use under discussion, or that the product is still investigational. Discussions of such uses shall focus on those uses that have been subject of objective investigation.