Sessions Descriptions

Sessions

Closing the Gap: The Diagnostic Power of High Resolution CNV detection by NGS - Dr. Jennifer Schleit

At the end of the session, the participants will be able to:

  • Review different CNV detection methods and their limitations
  • Describe in detail, the recently developed NGS-based CNV detection methods
  • Present case examples demonstrating the effectiveness of performing sequencing and CNV analysis at the same time in a patient

Description:

Copy number variants (CNVs) were historically felt to play a small but important part in molecular diagnostics. However, recent studies suggest that up to 35% of patients in certain clinical specialties may have a disease-causing CNV. As detection capabilities improve CNVs are playing a larger role than previously anticipated. This seminar will review the capabilities and limitations of different CNV detection methods, with an emphasis on the newly-developed NGS-based CNV detection methods. We will use case examples to highlight the diagnostic power of combining both CNV detection and sequence analysis in a single testing method.

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Inter-generational Communication – Bridging the Gap - Jennifer MacKenzie

At the end of the session, the participants will be able to:

  • Identify personal perspectives on teaching and learning based on the characteristic values of different generations.
  • Distinguish the gap in expectations typical for different generations.
  • Analyse how differences in communication can lead to misunderstanding and tension.
  • Reflect on how to adjust teaching style, feedback, mentoring, and learning, to align with current learners.
  • Assess how CBME aligns with values of the millennial generation.

Description:

In North America, health care providers continue to work past traditional retirement ages, while the younger generation, including Millennials and Generation Z, account for nearly all residents, resulting in multiple generations in medical schools and clinical practice. Generational differences contribute to expectations, educational philosophy, and learning preferences. Millennials, notwithstanding diverse backgrounds and personalities, are typically characterized as highly motivated to achieve, technologically advanced, less self-reliant needing more support and structure, optimistic and confident, mindful of their own wellness, and committed improve society. These traits contrast with those of other generations increasing the risk of misunderstanding, and conflict. Therefore, an understanding of the diversity in values between generations by educators and learners has the potential to improve educational outcomes as both have the potential to learn from each other. Considerations when developing educational sessions include the use of self-directed learning, digital resources, experiential learning, and attention to wellness in the context of explicit relevance, ongoing support, and clear expectations.

Competency based medical education (CBME), including milestones and entrustable professional activities, focuses on transparency, personalized learning, and frequent formative assessment, which aligns with the typical learning preferences of Millennials. CBME also provides a framework for remediation due to frequent assessments and feedback.

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Clinical utility assessment of BRCA1/2 tumour testing in a cohort of patients with high grade serous ovarian cancer (HGSOC) in the greater Hamilton area - Darci Butcher Tracy Stockley

Description:

Recently new cancer drugs have been approved in Canada that are active in cancer patients with either somatic (acquired) or germline (inherited) BRCA variants. One effective approach to capturing all BRCA-positive patients who may benefit from such treatment is to test the tumor tissue first, as this will identify both somatic and germline BRCA mutations. However this new approach also provides challenges, such as the best methods for tumor testing, how to investigate and report the significance of variants identified in tumor tissue, and how to include clinical genetics in the confirmation of germline variants and subsequent management of patients with inherited variants. This workshop will use interactive case examples to discuss the current issues in tumor-first testing for somatic and germline cancers.

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Immunogenetics of B-cell related diseases - Dr. Eyal Grunebaum

At the end of the session, the participants will be able to:

  • Describe an approach to the diagnosis and management of B-cell related diseases.
  • Discuss the role of immunogenetics in the management of B-cell related disease.
  • Appreciate the importance of immunogenetics in understanding the interactions between B-cell related diseases and other primary immune defects.

Description:

Dr. Grunebaum will describe an approach to the diagnosis and management of inherited B-cell defects, including the role of immunogenetics in the understanding and management of these conditions. Dr. Grunebaum will also talk about B-cell disorders in a variety of other primary immune defects.

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Education: Teaching in the 21st Century Symposium 2 - Linlea Armstrong

At the end of the session, the participants will be able to:

  • Describe and discuss 'Competence by Design' (CBD), a Canadian version of Competency based medical education (CBME)
  • Discuss how CBME is impacting Medical Genetics and Genomics in undergraduate and postgraduate medical education, and continuing professional development
  • Reflect on opportunities and challenges for CCMG programs in adopting CBD
  • Assess how CBME aligns with values of the millennial generation.

Description:

Competency based education (CBE) was developed in the 1920s by industry researchers wanting ways to achieve production of a product in a standardized way. Concepts relatd to use of explicit specification of standards and milestones in competency development are now being revisited by medical educators around the world. Competency based medical education has a culture of continuous learning across the career trajectory, and is visioned as our way of putting the patient back at the center, and achieving social responsibility. The Royal College has now rolled out Canada’s version, 'Competence by Design' (CBD), across some specialties. The Medical Genetic and Genomics committee will start our two-years transition process this spring. This session orients participants to competency based approaches to education, with attention to aspects relevant to medical genetics and genomics residency training programs as well as laboratory training programs.

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Variable outcome in patients with glutaric aciduria type 1 identified by expanded newborn screening: The Calgary Metabolic Clinic experience - Eliza Phillips Forough Noohi

Description:

Today, more than ever, the progress of scientific technologies continues to push legal and ethical boundaries. At the centre of the controversy surrounding the regulation of scientific advancements is human genome editing—more specifically, the manipulation of human embryos and the human germline. Mitochondrial Replacement Therapy (MRT) is a new type of in vitro fertilization that aims to prevent the transmission of mitochondrial diseases (matrilineal transmission) by replacing mutated mitochondrial DNA in unfertilized oocytes or zygotes with normal mitochondria from a healthy donor. Since as a result of MRT, permanent changes are made to the germline that would be transmitted through generations, this controversially so-called “three-parent IVF” is considered as a means of genetic modification. Besides the UK, which became the first country to approve MRT in 2015, only a few countries have addressed this controversial technique through public policy…

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Intergenerational Communication - Bridging the Gap in Healthcare Education - Dr. Jennifer MacKenzie

At the end of the session, the participants will be able to:

  • Identify personal perspectives on teaching and learning based on the characteristic values of different generations.
  • Distinguish the gap in expectations typical for different generations.
  • Analyse how differences in communication can lead to misunderstanding and tension.
  • Reflect on how to adjust teaching style, feedback, mentoring, and learning, to align with current learners
  • Assess how CBME aligns with values of the millennial generation.

Description:

In North America, health care providers continue to work past traditional retirement ages, while the younger generation, including Millennials and Generation Z, account for nearly all residents, resulting in multiple generations in medical schools and clinical practice. Generational differences contribute to expectations, educational philosophy, and learning preferences. Millennials, notwithstanding diverse backgrounds and personalities, are typically characterized as highly motivated to achieve, technologically advanced, less self-reliant needing more support and structure, optimistic and confident, mindful of their own wellness, and committed improve society. These traits contrast with those of other generations increasing the risk of misunderstanding, and conflict. Therefore, an understanding of the diversity in values between generations by educators and learners has the potential to improve educational outcomes as both have the potential to learn from each other. Considerations when developing educational sessions include the use of self-directed learning, digital resources, experiential learning, and attention to wellness in the context of explicit relevance, ongoing support, and clear expectations. Competency based medical education (CBME), including milestones and entrustable professional activities, focuses on transparency, personalized learning, and frequent formative assessment, which aligns with the typical learning preferences of Millennials. CBME also provides a framework for remediation due to frequent assessments and feedback.

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Human pathology revisited through clinical genomics - Fowzan Sami Alkuraya

At the end of the session, the participants will be able to:

  • Describe how clinical genomics can reveal novel pathological mechanisms of known human diseases.
  • Associate how the discovery of novel disease genes and syndromes will provide novel insights into the structure and function of the human body.
  • Restate how clinical genomics can define the “druggable” genome to accelerate the development of novel therapeutics for human diseases. 

Description:

Understanding mechanisms of diseases is at the core of the discipline of pathology. Although studying diseases at the molecular level has been carried out for decades, the ability to link diseases to their underlying molecular etiology in an unbiased fashion represents a very recent trend that forms the foundation of clinical genomics. Such an unbiased approach has lived up to its promise of revealing novel pathologies that defy predictions based on prior knowledge, thus expanding the horizons of human pathology at an unprecedented pace. This revolution in our understanding of the molecular underpinning of human physiology and pathology through clinical genomics also promises to revolutionize our approach to therapeutics with the druggable genome being the latest trend in target discovery and validation. Importantly, the implications of such developments are far from limited to Mendelian diseases. Indeed, the concept of druggable genome is primarily conceived for the treatment of common disorders.

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Tumor-First Testing Workshop: Somatic and Germline Cancers - Tracy Stockley

At the end of the session, the participants will be able to:

Recently new cancer drugs have been approved in Canada that are active in cancer patients with either somatic (acquired) or germline (inherited) BRCA variants. One effective approach to capturing all BRCA-positive patients who may benefit from such treatment is to test the tumor tissue first, as this will identify both somatic and germline BRCA mutations. However this new approach also provides challenges, such as the best methods for tumor testing, how to investigate and report the significance of variants identified in tumor tissue, and how to include clinical genetics in the confirmation of germline variants and subsequent management of patients with inherited variants. This workshop will use interactive case examples to discuss the current issues in tumor-first testing for somatic and germline cancers.

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Coding Variants Without Coding: The Clinical Geneticist and the .vcf file - William Gibson

At the end of the session, the participants will be able to:

  • Understand the different components of a Variant Call Format (VCF) file, along with some of the common variant annotations in use
  • Use variant annotations, case-specific phenotype information and inheritance patterns to prioritize variants
  • List at least 3 limitations associated with NGS data and current variant prioritization methods
  • Explain the benefits and limitations of using HPO terms to describe phenotypes
  • Describe (in general terms) the methods used by commercial labs to identify, prioritize and annotate rare variant lists in humans, including the limitations of these protocols Enumerate the advantages of “exome rounds,” even in the absence of raw exome data
  • List 3 approaches to validate or refute “plausibly pathogenic” variants in candidate genes
  • Distinguish between actionable and non-actionable results
  • List at least 3 limitations and at least 3 benefits of commercial software for variant analysis, compared to publicly-available software
  • Estimate "residual uncertainty" after NGS testing has returned a non-diagnostic result.
  • List at least 3 types of non-coding variants in which likely-pathogenic or pathogenic variants have been identified.
  • Use the web-based NeuroSeq interface to find variants of interest, VCF files, and families annotated in the NeuroSeq database.

Description:

As the number of patients who remain unsolved after NGS panels and exomes increases, clinical geneticists and diagnostic laboratories face a challenge in managing data generated on their patients by external service providers. In theory, best practice would be to request, store and reanalyze variant files when novel diagnoses appear in the literature and/or candidates emerge via GeneMatcher. However, resources to do this in a systematic way are not ubiquitous. This workshop will address these challenges and will provide worked examples of how to analyze .vcf files using tools available on the web. Facility with Linux and command-line code not required.

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Mitochondrial Diseases: Genetics, Diagnostics and Ethics.
Chair: Mark Tarnopolsky

Neal Sandheimer (40 mintues):  Mitochondrial cytopathies—overview and treatment options. 

At the end of the session, participants will be able to:

1. Describe mitochondrial biology and pathophysiology.
2. Develop a clinical approach to the diagnosis of mitochondrial disease.
3. Choose treatment options for patients.

Description:

Mitochondrial medicine is an emerging field that is complicated by the significant variability of clinical presentations and limitations in medical evidence for commonly used therapies. The availability and efficacy of medications are often uncertain. In this session, we will discuss the best available evidence for mitochondrial therapies in a variety of situations and consider best practices in managing patients with mitochondrial disease and their families.

Lauren MacNeil (20 Minutes):  Biochemical enzyme testing for mitochondrial diseases in the era of molecular testing.

At the end of this session, participants will be able to:

  1. Relate ro currently available biochemical laboratory tests to mitochondrial function
  2. Identify how molecular genetic analysis has changed the ordering of biochemical testing
  3. Describe limitations to the expansion of biochemical testing for mitochondrial disease

Description:

This presentation will review the current biochemical testing options for disorders affecting mitochondrial pyruvate metabolism and oxidative phosphorylation available at The Hospital for Sick Children. For decades tissue biopsy enzyme testing has been considered the “Gold standard” for diagnosis of mitochondrial disease. Multiple inheritance patterns, multiple sources of DNA, tissue heteroplasmy, large number of mitochondrial proteins, cost, etc. originally made genetic diagnosis challenging; however, advancements in molecular technologies, reduction of cost and a less invasive procedure have resulted in a shift in early clinical testing strategies. Biochemical testing continues to be an important component of an accurate diagnosis as it confirms altered functional capacity associated with known pathogenic variants as well as assessing impact of variants of uncertain significance. This session will be of value to genetic counsellors and clinical geneticists involved in cases of suspected mitochondrial disease.


Stacey Hume (20 Minutes): The science behind diagnosing and preventing mitochondrial disorders.

At the end of the session, participants will be able to:

1. Contrast the molecular analysis of a gene encoded by the nucleus vs. the mitochondria.
2. Classify mitochondrial genome variants.
3. Describe the mitochondrial replacement techniques available and review the technical challenges that have been reported

Forough Noohi (20 mintues): Mitochondrial Diseases: Genetics, Diagnostics and Ethics

At the end of the session, participants will be able to:

  1. Analyze the most important controversies surrounding Mitochondrial Replacement Therapy (MRT) (in both research and clinical context)
  2. Describe the most cited challenges in the literature for clinical translation of MRT
  3. Contrast MRT’s ethical, policy, and legal frameworks of Canada vs. the UK and the US  

Description

Today, more than ever, the progress of scientific technologies continues to push legal and ethical boundaries. At the centre of the controversy surrounding the regulation of scientific advancements is human genome editing—more specifically, the manipulation of human embryos and the human germline. Mitochondrial Replacement Therapy (MRT) is a new type of in vitro fertilization that aims to prevent the transmission of mitochondrial diseases (matrilineal transmission) by replacing mutated mitochondrial DNA in unfertilized oocytes or zygotes with normal mitochondria from a healthy donor. Since as a result of MRT, permanent changes are made to the germline that would be transmitted through generations, this controversially so-called “three-parent IVF” is considered as a means of genetic modification. Besides the UK, which became the first country to approve MRT in 2015, only a few countries have addressed this controversial technique through public policy.

 

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Competence by Design: Philosophy, Principles and Practice - Jonathan Sherbino

At the end of this session, participants will be able to:

  1. Define competency-based education
  2. List key arguments for a transition to CBME
  3. Describe supporting principles and philosophies of CBME

Description:

The transition to competency-based medical education is the most dramatic change in residency education in more than a century. The term CBME seems to be everywhere in medical education. But do we have a shared understand of what it means? Do we understand the rationale for this significant and resource intensive transition? This interactive large group session provides a rationale for this change with an emphasis on the key principles and practices that inform CBME.

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Giving Feedback - Denyse Richardson

At the end of the session, the participants will be able to:

·        Define Coaching in a Competence Based Education context

·        Differentiate Coaching in the Moment and Coaching over Time

·       Describe a Coaching process approach for a clinical learning and progressive development of competence.

Description:

Inherent in the new Competence by Design (CBD) model is a philosophical shift from “assessment of learning” to “assessment for learning”.  In CBD, learning is individualized and it is guided by regular, work-based, quality coaching and assessment of the resident. This philosophical shift demands a purposeful reconsideration of the traditional role of a Clinical Supervisor.  Of course, clinical supervision will always be necessary but, no longer is supervision of work sufficient.  All Clinical Teachers need to incorporate, into their daily work, an increased proportion of observation of each Resident’s day to day work, with planned and deliberate coaching for improvement – “Coaching in the Moment” 

In CBD, residents will receive many types, and a far greater volume, of assessment data.  PD’s and Competence Committee (CC)  members and/or Faculty Academic Advisors need to be able to give residents guidance and input on how to synthesize the assessment data that they get from a variety of sources, in order to adjust their behaviours and performance – “Coaching over Time”

In this session coaching will be defined in a Competency Based Education context and Coaching in the Moment will be differentiated from Coaching over time.  A practical coaching process for daily use will be shared.

 

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How to Apply CBC to Dysmorphology and Genetic Counselling - Linlea Armstrong

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Competency by Design in Laboratory Education - Sherry Taylor

At the end of the session, the participants will be able to:

  1. Describe the components of a competency by design approach to laboratory training programmes
  2. Discuss suggestions for changes to in-training evaluation and examination of laboratory trainees
  3. Encourage leadership by example and being transformational

Description:
The purpose of this presentation is to raise points with respect to laboratory training programmes for future consideration and discussion by the CCMG membership.
The main points will be to discuss a move to a competency based program of laboratory training, to have more robust in training evaluations which contribute to the overall final evaluation of trainees and to encourage those who train to exemplify the principles they are teaching and to encourage ongoing transformation throughout one’s career.

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Forensic Genetics using Kinship Analysis and Ancestry Searching: The Intersection of Science, Law, and Policy - Frederick R. Bieber

At the end of the session, the participants will be able to:

  1. Explain the concepts of kinship analysis and the role of STR and SNP analysis for reconstruction of kindreds,
  2. Summarize the successes of DNA-based kinship testing in identification of missing persons and in resolving serious crimes, and
  3. Describe the policy choices and privacy debates surrounding collection and storage of DNA profiles from convicted offenders and the general public.

Description:
This presentation will focus on the technical, procedural, and policy aspects of genetic kinship analysis for human identification using STR and SNP profiling for investigation of serious crimes, identification of missing persons, human trafficking and reunification of recovered remains after war, genocide, and natural disasters. Advances in SNP profiling and ancestry searching offer new opportunities for success in each of these areas and also raise legal and policy questions surrounding implementation of law enforcement uses of data mining and genealogy to investigate serious crimes.

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DNA Testing in Support of Criminal and Other Investigations at Ontario's Centre of Forensic Sciences - Jack Laird

At the end of the session, the participants will be able to:

  1. Discuss how DNA testing is employed in support of investigations and judicial proceedings across Ontario,
  2. Identify the core and emerging technologies that underpin forensic DNA analysis today and into the future, including phenotypic testing, and
  3. Compare and contrast permissible forensic uses of Canada’s National DNA Data Bank relative to those in other jurisdictions, and explain how DNA profiles generated at the Centre of Forensic Sciences may be searched against this Data Bank.

Description:
Forensic DNA testing has been established as a critical tool in support of criminal investigations and judicial proceedings for close to 30 years.
In that time, a number of key developments have expanded the value of DNA testing to identify perpetrators and victims of crime. These include the advent of Canada's National DNA Data Bank in 2000, the development of ever more sensitive and discriminating DNA typing systems and, more recently, the rapid expansion of Single Nucleotide Polymorphism (SNP) databases which permit inferences regarding a range of investigatively significant data, such as biogeographic ancestry, various externally visible characteristics, and highly sensitive determinations of relatedness.
This presentation will address the DNA testing services available to investigators through Ontario's Centre of Forensic Sciences and will offer an overview of how forensic DNA testing is used to support investigations and judicial proceedings in criminal and other cases, from high volume property crimes through to homicides.
Finally, the presentation will briefly address how forensic biology/DNA results can be used when the identity of the donor is not contested, and instead the key question in the case is how or when a DNA sample came to be deposited.

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Panel Discussion -

Frederick R. Bieber
Patricia Kosseim
Jack Laird
At the end of the session, the participants will be able to:

  1. List a minimum of 3 emerging uses of DNA and/or databases of genetic information in forensic identification procedures.
  2. Describe the different types of "hits" that a forensic sample can generate when queried against a DNA database (e.g. Crime Scene to Crime Scene, Crime Scene to Offender, Volunteer Sample to Relative),with the privacy implications of each.
  3. Describe current controversies regarding the appropriate boundaries between an individual's privacy-based right to protection against unreasonable search or seizure, and recognition that the state’s interest in enforcing its laws will sometimes require some level of intrusion into the private sphere.

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Immunogenetics / Cancer David Chitayat

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The genetic landscape of severe combined immune deficiency in the era of newborn screening and high throughput genomic analysis - Dr. Luigi D. Notarangelo

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Immunogenetics of B-cell related diseases - Dr. Eyal Grunebaum

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Immunogenetics / Cancer Tuberculosis : a genetic disorder - Dr. Stephanie Boisson-Dupuis

Description:

About a quarter of the world’s population is infected with Mycobacterium tuberculosis, resulting in ∼10 million new cases of tuberculosis (TB) and 1.6 million deaths worldwide in 2017. Nevertheless, only ∼5% of infected individuals develop active TB in their lifetime, suggesting the existence of a genetic component of TB in humans. However, its molecular architecture has long remained elusive. From 1996 onward, single-gene inborn errors of IFN-γ immunity have been found to underlie Mendelian susceptibility to mycobacterial disease (MSMD), which is characterized by severe disease caused by poorly virulent mycobacteria (bacillus Calmette–Guérin vaccines and environmental mycobacteria). The clinical penetrance for MSMD depends on the genetic etiology and is inversely correlated with the levels of residual IFN-γ immunity. From 2001 onward, autosomal recessive interleukin-12 receptor β1 (IL-12Rβ1) and tyrosine kinase 2 (TYK2) deficiencies have also been identified in children with severe TB and without MSMD. These two deficiencies impair both the IL-12– and IL-23–dependent production of IFN-γ. They are caused by very rare (minor allele frequency, MAF

At the end of the session, the participants will be able to:

  • Describe what causes MSMD and tuberculosis
  • Describe the important cellular factors during mycobacterial infections
  • List one genetic cause of MSMD and tuberculosis
  • Explain the benefits of genetic studies
  • Recognize cases of familial mycobacterial disease

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Tumor-First Testing Workshop: Somatic and Germline Cancers - Tracy Stockley

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Forensics Symposium
Forensic DNA Analysis and Data Curation in North America - Chair: William Gibson

At the end of the session, the participants will be able to:

  • List a minimum of 3 emerging uses of DNA and/or databases of genetic information in forensic identification procedures.
  • Associate how the discovery of novel disease genes and syndromes will provide novel insights into the structure and function of the human body.
  • Describe current controversies regarding the appropriate boundaries between an individual's privacy-based right to protection against unreasonable search or seizure, and recognition that the state’s interest in enforcing its laws will sometimes require some level of intrusion into the private sphere.

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Legal, Ethical and Social Implications of Expanding Canada’s National DNA Databank - Patricia Kosseim

At the end of the session, the participants will be able to:

  • Explain the legal history and evolution of Canada’s National DNA Databank.
  • Describe the underlying policy tension between the individual’s right to privacy and the public interest in ensuring public safety.
  • Discuss the broader legal, ethical and social implications of some of the emerging technologies and future directions being contemplated.

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Clinical/Biochemical breakout - David Chitiyat

At the end of the session, the participants will be able to:

  • Recognize rare clinical disorders of difficult diagnosis
  • Evaluate the utility of new diagnostic techniques in the assessment of patients with rare disorders including whole exome and whole genome sequencing.
  • Review the value of a complete phenotypic assessment and integration of genotype and phenotype data.
  • Review strategies for follow-up of abnormal biochemical investigations.

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Molecular/Cytogenetics Breakout - Dennis Bulman

At the end of the session, the participants will be able to:

  • Identify potential technical and interpretive issues in the molecular/cyto labs
  • Assess technical issues which are presented to some of our colleagues
  • Collaboration with fellow laboratorians to inform and educate ourselves and our peers
  • To identify and discuss issues which may be unique to our respective field

Description:
The Molecular/Cytogenetics Breakout Session is an opportunity to present unique cases, findings, unusual results in the context of the molecular or cytogenetics laboratories. Short 5-10 minutes presentations are delivered by members of our community, which they identify as important and informative. The purpose is to educate and inform. Presentations are encouraged from lab staff and their trainees and participation is open to all.

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