Genetic test and technologies

Question 1

What is a diagnostic test?

Answer 1

• patient has signs and symptoms suggesting a particular diagnosis
• molecular genetic test will confirm a diagnosis
• In this context a genetic test is being used to confirm a clinical diagnosis.
• Issues informed consent

Question 2

When is predictive testing used?

Answer 2

• Testing health at-risk family members for a previously identified familial variant – often dominant
• HD No intervention
• BRCA1/2 some intervention

Question 3

When is carrier testing used?

Answer 3

• Autosomal recessive and X-linked disorder
• Testing an individual in isolation not particularly helpful – couple testing
• Reproductive decision making

Question 4

What is a pre-natal test used for?

Answer 4

• Genetic test performed in pregnancy where there is a increased risk of a specific condition affecting the foetus
• Chorionic villous sample or amniocentesis
• Often chromosomal or DNA if specific variant in the family has been identified
  (Counselling issues)

Question 5

What is genetic screening used for?

Answer 5

• Target population, not high risk families
  E.g. Newborn screening for Cystic fibrosis
• It may be the same test but the context is different

Question 6

What is susceptibility testing?

Answer 6

Increased or decreased risk for a multifactorial condition
This issue is only just emerging

Question 7

What is the role of genetic testing?

Answer 7

• To confirm clinical diagnosis
• To give information about prognosis
• To inform management

Question 8

What is Sanger sequencing?

Answer 8

Uses PCR (polymerase chain reaction) to amplify regions of interest followed by sequencing of products
- Useful for single gene testing
(not used as much now as too time-consuming)

Question 9

What is Next generation sequencing?

Answer 9

• Can sequence whole human genome in one day
• Multi-gene panels, whole exome/genomes
  (preferred method)

Question 10

How is NGS data analysis used?

Answer 10

• generates millions of short DNA fragments that are quality filtered and aligned to a reference sequence
• identify variants which can then be interpreted

Question 11

What are incidental/secondary findings?

Answer 11

• additional findings that may or may not have health implications that are discovered and beyond the aims of the original test
• Need to consider wether to tell patient