Genetic Tests And Technologies Flashcards
(31 cards)
What are 3 reasons for a genetic test?
- testing for genetic conditions
- testing to clarify familial relationships
- genetic testing to determine identity (forensics)
Why do we carry out genetic tests on the NHS? (7 reasons)
- confirm clinical diagnosis
- determine prognosis
- inform disease management
- allow predictive testing in close relatives
- carrier testing
- determine récurrence risks
- prenatal diagnosis
What is important to obtain before carrying out a genetic test?
Full and informed consent.
Why is obtaining consent so important before a genetic test?
- may discover unwanted and unexpected secondary findings
- implications for insurance / employment if secondary findings indicate increased risk of cancer, etc.
What can chromosome analysis show?
- abnormalities of chromosome number
- abnormalities of (gross) chromosome structure
What can chromosomal microarray analysis show?
Chromosome microdeletions / duplications
What can fluorescence in situ hybridisation show?
- Chromosome microdeletions / duplications
- whole or partial gene deletions and duplications
What can single gene sequencing show?
Single nucleotide changes in the gene.
What can deletion / duplication analysis show?
- whole or partial gene deletions and duplications
- chromosome microdeletions / duplications
What can targeted mutation analysis show?
How does it work?
- single nucleotide changes
- whole or partial gene deletions and duplications
Picks up a limited range of known gene mutations.
What is a multi-gene panel?
What can a multi-gene panel show?
Picks up mutations in several genes associated with a genetic disease.
- single nucleotide changes
- whole or partial gene deletions and duplications
- abnormalities of chromosome number
- abnormalities of chromosome structure
- chromosome microdeletions/ duplications
What can whole exome/genome sequencing show?
- single nucleotide changes
- whole or partial gene deletions and duplications
- abnormalities of chromosome number
- abnormalities of chromosome structure
- chromosome microdeletions/ duplications
How does chromosome microarray analysis work?
- Patient sample dyed green, control sample dyed red.
- samples are mixed and hybridised
- computer analysis determines the ratio of green to red, and therefore whether the patient has a chromosomal deletion or duplication
- location of deletion/duplication can be determined because complementary probes are used, which correspond to location of the deleted/duplicated region
What is Sanger sequencing?
- uses PCR to amplify DNA regions of interest
- PCR products are synthesised
- useful for single gene testing
What is next generation sequencing?
- massively parallel sequencing
- can sequence entire human genome in one day
- useful for multi-gene panels and whole exome/genome sequencing
What is meant by massively parallel sequencing?
Many genes can be sequenced at the same time.
What are some advantages/disadvantages of Sanger sequencing?
+ simple analysis
+ very accurate
+ greater depth of coverage
- high cost per gene
- time consuming
What are some advantages/disadvantages of NGS?
+ low cost per gene
+ fast
- huge amounts of raw data to analyse
- moderately accurate
- less depth of coverage
How is NGS analysed?
- millions of short DNA fragments generated
- these are filtered for quality and aligned to a reference sequence
- variants are identified and interpreted
How are variants identified and interpreted from DNA sequences?
- control database of normal human genomes is used to determine whether a variant is significant
- database consists mainly of white genomes so less reliable for BAME patients
What are the 3 ways in which a variant can be interpreted?
- pathogenic variant
- variant of unknown significance
- normal variation
How can computer programs help interpret a variant?
Computer programs can model the function of the protein produced as a result of a variant, to determine if it’s likely to be pathogenic.
What further means can be used to determine the significance of an unclassified variant?
- consider the severity of the amino acid substitution
- mRNA analysis
- analysis of affected and unaffected individuals in family studies
What are some advantages / disadvantages of multi-gene panels?
+ specific genes are sequenced so less raw data to analyse
+ more cost-effective
+ fewer variants of unknown significance
+ no secondary findings
+ greater depth of coverage
- panels need to be updated if more genes are discovered to be related to a condition
- not a comprehensive analysis of possible genetic causes of a disease
