SPR L6 Ethical Aspects of Clinical Genetics Flashcards Preview

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Flashcards in SPR L6 Ethical Aspects of Clinical Genetics Deck (18):

Learning Objectives

  • Be able to explain the ‘special nature’ of DNA testing when compared to other medical tests
  • Be able to describe the ethical issues involved in the use of predictive or presymptomatic testing for untreatable genetic diseases
  • Know why it is important to consider the ethical reasons for testing (or not testing) children for genetic diseases
  • Discuss the implications of genetic screening and the potential misuse by insurance companies and employers
  • Appreciate the power and also limitations of screening in forensic genetics such as paternity testing 


What is genetic information?

  • DNA based test
  • Detection of product of mutated gene e.g. renal cysts
  • Family history e.g. Huntington disease
  • Complex family history e.g. heart disease
  • Gender may be genetic information
  • Age may be genetic information 


Define a genetic test?

A test to detect the presence or absence of, or alteration in, a particular gene, chromosome or a gene product, in relation to a genetic disorder. 


  1. Give examples of paternity testing + ethical issues
  2. What has been a result of this?
  3. What are the legal implications?


  • Filed for maintenance
  • Putative father asked for saliva sample
  • Sample confirms paternity 

2. Unlawful DNA theft is an offence (2004)

3. Incorporated into 2005 Human Tissue Act 


Obtaining and handling personal genetic information 

  1. Give examples of primary general principles
  2. Give examples of seconary general principles
  3. What legalities currently cover this?

  1. Genetic solidarity and altruism, & respect for persons 

  2. – Confidentiality

    – Privacy
    – Consent
    – Non-discrimination 

  3. – Data Protection Act, Human Tissue Act 


Testing Children

  1. What is an important prerequisite?
  2. When are they usually tested for a late onset disorder?
  3. What implications can there be?
  4. What else is important to consider?

  1. Need to have an effective treatment e.g. childhood cancers (MEN-2, FAP) 

  2. Usually test at ~18 years or over if a ‘late onset disorder’ 

  3. Insurance implications

  4. Does the child want to know (eg. if they have an incurable condition? 

    Don’t test just because the parents want



  1. What is MEN-2?
  2. Outline it's pathology
  3. When is diagnosis often made?
  4. What is curative of this condition?
  5. Give an example of this case

  1. Multiple Endocrine Neoplasia type II
  2. Medullary thyroid cancer

    • C-cell hyperplasia

  3. Often diagnosis in childhood

  4. Thyroidectomy

  5. PJM asked to investigate the family and present research findings at the 1988 international MEN meeting in Heidelberg, Germany. Mayo Clinic. Edis discovers the 3 brothers are relatives of the 2 N.Ireland sibs 

    1. PJM asked to find the gene – which we localised to chromosome 10 in 1990 – later exon 10 CysTyr mutation identified in Ret 



  1. Which gene is affected?
  2. What can the clinical findings be?
  3. Outline the process of testing in the sisters from the case mentioned before

  1. later exon 10 CysTyr mutation identified in Ret 

  2. Medullary ca thyroid, Phaeochromocytoma & parathyroid adenoma. 

  3. Tested for Cys to Tyr change at codon 634 in exon 10

    • Both gene carriers aged 10 and 8

    • No abnormal clinical or lab or screening investigations

    • Surgery planned on basis of gene test

    • Sister 1 – 9mm focus of MTC

    • Sister 2 - 5mm focus of c-cell hyperplasia

    • Correct diagnosis and correct to operate

    • Established the concept of preventative surgery 


Familial Adenomatous Polyposis Coli 

  1. What is it's incidence?
  2. What is the mode of inheritance?
  3. What is it characterised by?
  4. By age 15, >50% of affected individuals will have multiple polyps, what does this mean about the condition?

  5. Where do the mutations lie?

  1. ~1/10,000

  2. Autosomal Dominant

  3. Thousands of polyps

  4. High Penetrance

  5. Mutations in APC gene (Chromosome 5) 


Huntington Disease 

  1. What are the clinical features?
  2. When is the average onset?

  1. Chorea

    Cognitive dysfunction

    Psychiatric illness                                                        Relatively selective loss of cells in neurodegeneration

  2. Average onset early middle life (35 -45 yrs) 


Huntington Disease 

  1. What is the mode of inheritance?
  2. What is the prevalence of this condition?
  3. What is the underlying genetic cause?
    1. What is the abnormal range for these repeats?
    2. What else is clinical significant about the repeats?

  1. Autosomal Dominant
  2. 10-12/100,000 

  3. Triplet repeat expansion

    CAG(n)- normal up to 35 repeats 

    1. >35 repeats 

    2. Greater the expansion, generally worse prognosis and earlier onset of the disease 


Huntington Disease

  1. What locus is affected?
  2. On which gene?
  3. What is the gene product?
  4. What is the effect of the mutation?
  5. What is the treatment?
  6. What testing is available?

  1. Locus: 4p16
  2. Gene IT15
  3. Gene product: huntingtin
  4. Effect of mutation: toxic gain of function
  5. No treatment at present
  6. Presymptomatic gene testing is available 


HD - Genetic Testing

  1. What will the diagnostic test confirm?
  2. Outline the Presymptomatic or predictive test
    1. What should occur before this type of testing?

  1. confirms diagnosis in symptomatic patient 

  2. testing an at risk asymptomatic person – set protocol for assessing attitudes to, knowledge of, and experience of HD 

    1. At least 2 sessions with a geneticist or genetic counsellor before testing 


Pre-implantation diagnosis 

  1. How is this carried out?
    1. What is needed?
  2. Why is this carried out?
  3. What are the drawbacks?

  1. 8 cell embryo - Remove 1 cell - test DNA for single gene and chromosomal disorders

    If abnormal, do not implant egg, If normal then implantation

    20-30% “take home baby rate” 

    1. each disorder needs a licence from the HFEA

  2. Parental choice

    May avoid termination of pregnancy for serious abnormalities

  3. Drawbacks – cost, error, stress, travelling 



​Outline the issues

• Should employers have the results of genetic tests?

• Should insurers have the results of genetic tests

• Better that employer makes the workplace safe than demanding a genetic test 


Insurance Moratorium 

Outline this

  • Government moratorium currently in place
  • Life insurance: no use to be made of genetic test results on policies up to £500,000
  • Long-term care insurance, critical cover: No use to be made on policies up to £300,000
  • Only one test approved at present – HD gene 


Give examples of the personal genome


Example of testing (don't learn)