Testing for genetic abnormalities Flashcards
Copy number variants
Large number of duplications/deletions
Chromosomal aneuploidy
Loss of chromosome
What is a de novo mutation
Occurs spontaneously
Syndromic presentation
Collection of findings, suggesting underlying known cause
Non-syndromic presentation
No recognised underlying syndrome
What is light microscopy good for?
When chromosomes are replicating and condense, they become visible - detects aneuploidy, trisomy 21, turners etc
G banded karyotype
Dye chromosome with particular stain so resolution is higher - shows bands on loci
Microarray
factory produced DNA binds to specific sections of the gene - this causes it to fluoresce - no light indicates deletions. This is useful if you know what you are looking for
Antenatal screening
- Combined test: 10-14 weeks, blood test for PAPP-A and B HCG + nuchal translucency
- Quadruple test offered when: NT measurement not obtained/CRL >84mm/too late in pregnancy
- Quadruple test: 14-20 weeks, AFP, B HCG and inhibin levels
- 20 week screening: USS 18-21 weeks for:
NIPT
non-invasive prenatal testing, detects foetal DNA in mother’s bloodstream - offered if combined or quadruple are high risk
Pros karyotype analysis
Cheap
Visualise aneuploidy
large structural changes
Cons to karyotyping
Limite information
Miss subtle abnormalities
Pros micro-array
Answer specific questions
Cheap
Cons micro-array
Miss small/rare mutations
Only specific pathologies tested
Pros exam sequencing
Analyse thousands of genes
Cheaper than whole genome
Cons exome sequencing
Expensive
Miss introns
Limited availability
Pros whole genome sequencing
Analyse whole genome
Phenotypically unbiased
High diagnostic rate
Cons whole genome sequencing
Higher data burden
Expensive
Mutations of unknown significance
