Neurological genetics

Details

Title

Neurological genetics

Type

Stage Two

Module code

HLS423

Requirement

Compulsory

Module objective

By the end of the training period trainees will, in respect of neurological genetics, understand the rationale of genetics screening and testing for neurology (neurological /neuromuscular disorders) excluding cancer and be able to

• analyse, synthesise, evaluate and apply knowledge
• perform adapt and master a range of scientific and clinical skills and procedures understand the technical principles and processes underpinning these skills
• demonstrate the attitudes and behaviours necessary for professional practice as a consultant clinical scientist dealing with the complexities, uncertainties and tensions of professional practice at this level.

Knowledge and understanding

1. Selection and validation of appropriate screening protocols 
2. Selection and validation of appropriate tests 
3. Selection and use of appropriate samples 
4. Timeliness of tests 
5. Scientific quality assurance of test procedures 
6. Validity and reliability of test results and their application
7. Costs of tests

By the end of the training period the trainee will be able to demonstrate the ability to analyse, evaluate and synthesise relevant knowledge and its application to their professional practice in relation to:

Selection and validation of appropriate screening protocols

• selection criteria for neurogenetic testing:
  • clinical features
  • results of other pathology testing (neurological function, immunoanalysis, biochemical tests)
  • family history
  • care pathways

Selection and validation of appropriate tests

• selection and validation of appropriate genetic tests including their basis:
  • whole genome sequencing/exome sequencing/mitochondrial genome sequencing
  • sequencing gene panel (e.g. LGMD)
  • sequencing single gene (e.g. DMD)
  • targeted tests (sequencing, MLPA, PCR fragment analysis, Southern blotting)
  • linkage analysis using microsatellite markers

Selection and use of appropriate samples

• selection and use of appropriate samples:
  • sample types
  • sample volumes
  • transportation/storage issues

Timeliness of tests

• understanding of the timeliness of tests in the context of neurological/neuromuscular disorders

Scientific quality assurance of test procedures

• scientific quality assurance of test procedures:
  • test validation
  • quality control measures
  • internal/external quality assurance

Validity and reliability of test results and their application

• validity and reliability of test results and their application:
  • document control/process records
  • audit
  • value of user feedback and interaction

Costs of tests

• costs of tests (equipment, consumables and associated staffing costs).

Technical and clinical skills

By the end of the training period the trainee will be able to demonstrate a critical understanding of current relevant research, theory and knowledge and its application to the performance, adaptation and mastery of the following technical procedures and laboratory skills:

• laboratory techniques relevant to the test repertoire
  • whole nuclear/mitochondrial genome (DNA sequencing)
  • gene panel (DNA sequencing)
  • single gene (DNA sequencing)
  • targeted tests (DNA sequencing, MLPA, PCR fragment analysis for trinucleotide expansions, southern blotting)
  • linkage analysis using microsatellite markers
• systems for ensuring the quality of test procedures and reagents
  • use of appropriate internal controls and monitoring assay performance
  • internal quality assurance
  • external quality assurance
• Validity and reliability of test results and their application
  • using available IT systems/laboratory database to produce timely, accurate and relevant laboratory reports with appropriate interpretative comments
  • use of bioinformatics resources to assess pathogenicity
  • calculation of recurrence risks
  • calculation of risks to relatives

By the end of the training period the trainee will be able to apply knowledge of neurological genetics to perform, adapt and master the clinical skills necessary to manage the:

• biological and clinical context in which tests are offered
• socio-economic context in which tests are offered
• ethical issues raised by testing in neurogenetic conditions (for example presymptomatic testing in Huntington disease)
• best practice guidelines and disease-specific databases in interpretation and reporting of results
• genetic tests required to investigate the risk to a patient as a result of:
  • a particular family history
  • a particular clinical phenotype
• interpretation of results and any further follow-up testing.