Applied Genetics and Genomics in Clinical Care

Module details

Title

Applied Genetics and Genomics in Clinical Care

Type

Specialist

Module code

S-GC-S2

Credits

10

Phase

2

Requirement

Compulsory

Aim of this module

This module will provide the trainee with a knowledge base across a breadth of commonly encountered genetic and genomic conditions. It will equip students with the skills to apply knowledge as they work in partnership with patients, their families and clinical colleagues and will help them consider the genetic and genomic counselling service from a patient perspective.

Training activities

Assessments

Complete 2 Case-Based Discussions

Complete 2 DOPS or OCEs

Direct Observation of Practical Skills Titles

• Arrange primary or secondary preventative strategies for an individual where screening or prophylatic treatment has been proven to reduce risk of disease.
• Produce a summary letter using appropriate language to communicate the clinical and psychosocial aspects, and recurrence risks.
• Present a case at a clinical meeting and seek advice to resolve an issue extending beyond your scope of practice as a trainee.

Observed Clinical Event Titles

• Complete a risk assessment for a Mendelian condition and communicate risk information to a patient.
• Plan and deliver predictive testing in a genetic counselling consultation, under supervision.
• Present information on a research study to the patient including the risks, benefits and limitations of the study.
• Explain a genetic test to a patient and gain informed consent.

Learning outcomes

Activities

1. Observe triage for a range of referrals to appreciate the decision-making process for care.
2. Read post-clinical summary letters/leaflets for a range of consultations/situations to appreciate the differing styles and constancy of the clarity of the message and the language and tone.
3. Observe clinics, interventions and multidisciplinary teams for a range of clinical specialties not previously observed for example breast, bowel, gynaecology, oncology, cardiology, neurology, reproductive medicine, fetal medicine and termination of pregnancy.

Learning outcomes

On successful completion of this module the trainee will be able to:

1. Critically evaluate a range of current genomic testing strategies and their application.
2. Explain the way genomic results are generated and how data is filtered using bioinformatic pipelines.
3. Evaluate and use approaches for the interpretation of genomic results and the use of genotype and phenotype data in establishing pathogenicity.
4. Critically appraise the use of genomic results in personalised/precision medicine, pharmacogenetics and emerging therapeutics.
5. Critically appraise the broader use of genomic screening for disease risk prediction.
6. Describe the role of the Genetic Counsellor in the partnership of genetics with other clinical specialisms in the diagnosis of genetic disorders.
7. Critically evaluate theories and approaches to adult education and how to apply these to genetics and genomics.

Indicative content

• Advanced Genomic Counselling
• Pre-conception and    reproductive    genetic    counselling   that    use    genomic technologies, including prenatal diagnostic support
• Genomics in the fetal medicine clinic
  • Diagnostic challenges of antenatal scanning
  • NIPT
  • RCPath guidance on the sharing of incidental findings picked up in pregnancy
• The diagnostic odyssey and the specific benefits and challenges of genomics in a range of settings
• The use of sources for researching the natural history of rare diseases including:
  • OMIM
  • Orphanet
  • Gene Review
  • Pubmed
  • Eurogentest
  • Support groups, such as Unique
• Genomic testing strategies
• Genomic testing strategies such as: gene focused, multiple genes or whole genome or exome and for detection of sequence, copy number or rearrangements, including when these might be applied by laboratory clinical scientists
• How laboratory clinical scientists determine the analytical sensitivity and specificity of genomic tests
• The health economic limitations of testing in a publicly funded health service
• Have an appreciation of the necessary interplay between genomics delivered via clinical services and subsequently research services (when the limits of what can be offered clinically have been reached)
• Bioinformatic pipelines
• Principles applied to quality control of sequencing data, alignment of sequence to the reference genome, calling and annotating sequence variants and filtering strategies to identify pathogenic mutations in sequencing data
• Use of multiple database sources, in silico tools and literature for pathogenicity evaluation and familiarity with the statistical programmes to support this (e.g. EVS, dbSNP and polyphen)
• Principles of integration of laboratory and clinical information, including knowledge of best practice guidelines for indicating the clinical significance of results
• Evaluating pathogenicity
• Approaches to the evaluation of pathogenicity of variants in the context of an NHS clinical report
• The value and importance of phenotype and inheritance information alongside sequence analysis to determine diagnosis and pathogenicity [phenotype to genotype]
• Prediction of phenotype from variants obtained from a hypothesis free whole exome/genome analysis [genotype to phenotype] in established genetic conditions
• Analytical challenges in genomics as applied to rare inherited diseases including:
  • The benefits and potential risks of sharing, integrating and aggregating clinical data and information
  • The potential of electronic health records to enrich patient data
  • Importance of phenotyping and use of databases such as ClinVar, OMIM and Decipher
  • Use of large population datasets, e.g. ExAC
  • Sharing information, e.g. Human Variome Project
• The role of the Genetic Counsellor in the multidisciplinary team
• Interpreting variant data in the clinic: the role of a Genetic Counsellor in the multidisciplinary team to discuss pathogenicity of possible variants linked to a specific phenotype
• The role of the Genetic Counsellor and other members of the multidisciplinary team in communicating uncertain information, variants of uncertain significance and incidental findings and counselling approaches to this
• Approaches to the management of incidental findings and the difference between this and opportunistic genomic screening
• The role of the Genetic Counsellor in facilitating supporting investigations including segregation analysis
• Approaches to and implications of the release of differing extents of genomic information
• Use of genomic diagnosis
• Examples of the use of a genomic diagnosis in establishing treatment strategies and personalised medicine, including in oncology, adult medicine, paediatrics and prenatal settings
• Non-invasive prenatal diagnosis
• Preimplantation genetic diagnosis
• Current uses of pharmacogenetics
• The role of genomics and other omics technologies in the development of new therapeutics, including gene therapy
• Genomic screening for risk prediction
• Existing population screening programmes in adult settings (familial hypercholesterolaeimia, breast, cervical and bowel cancer)
• Emerging strategies of genomic screening for disease risk prediction in reproductive (e.g. panels for carrier testing) and adult settings (e.g. cancer and neuropsychiatric), including application in specific ethnic groups
• Approaches to opportunistic genomic screening internationally and the risks and merits of these approaches
• How to take ‘broad consent’, together with the pros and cons of this approach
• The challenges of genomic screening for risk prediction in multifactorial disease and evaluate current approaches to combining risk factors
• The evidence on how patients manage their behaviour in light of risk stratification information
• The differing impact of genomic screening within private healthcare and in the direct-to-consumer market, including the impact of such testing on the NHS