Genetics Flashcards
What are the 3 types of foetal DNA sampling most commonly used in current practise?
- Non-invasive prenatal testing (NIPT)
- Chorionic villus sampling (CVS)
- Amniocentesis
What is non-invasive prenatal testing (NIPT)?
Foetal DNA is obtained through a blood sample from the mother
(as cells from the placenta are shed into the mother’s bloodstream)
What is chorionic villus sampling?
When chorionic villi are taken from the placenta for analysis of foetal DNA
What is amniocentesis?
An invasive procedure where a small sample of amniotic fluid is extracted from the uterus
(as amniotic fluid contains shed foetal cells)
At how many weeks gestation can... - NIPT - CVS - Amniocentesis ... be carried out?
NIPT: 10 weeks +
CVS: 11.5 weeks +
Amniocentesis: 15 weeks +
List these in order of highest to lowest miscarriage risk:
- NIPT
- CVS
- Amniocentesis
CVS > Amniocentesis > NIPT
Why does NIPT have the lowest miscarriage risk?
It is non-invasive
What are the pros and cons of NIPT?
Pros: Non-invasive so low miscarriage risk
Cons: Only 10% of the DNA comes from the foetus, the rest is maternal
What are the pros and cons of CVS?
Pros: Can be carried out earlier than amniocentesis so can detect foetal abnormalities earlier, higher foetal DNA content than NIPT
Con: Invasive + higher miscarriage risk than amniocentesis
What are the pros and cons of amniocentesis?
Pro: higher foetal DNA content than NIPT, can be used to confirm NIPT result
Con: invasive so increased miscarriage risk, carried out later than CVS
When is NIPT indicated? (2)
Testing for chromosomal abnormalities (e.g., trisomies)
Sex determination (for determining risk of inheriting sex-linked disorder)
When using NIPT for investigating a trisomy, what is a common reason for a false negative result?
Inadequate foetal fraction of DNA in the sample
When using NIPT for investigating a trisomy, what are 2 common reasons for a false positive result?
Confined placental mosaicism
Maternal malignancy
What is confined placental mosaicism?
When some cells in the placenta have a trisomy but the cells making up the foetus have a normal chromosome number
List 3 trisomies that may be picked up on foetal DNA sampling
Down’s syndrome (trisomy 21)
Edwards’ syndrome (trisomy 15)
Patau’s syndrome (trisomy 13)
If high levels of chromosome 21 are detected in maternal blood in NIPT, what is the risk of foetal Down’s syndrome?
99%+ (high sensitivity)
How is diagnosis confirmed once a high risk NIPT result is obtained?
Amniocentesis
When are invasive sampling tests (CVS/amniocentesis) indicated? (2)
For detecting chromosome abnormalities
For detecting single gene changes
What is chromosome microarray?
A technique which lights up microdeletions or microduplications in chromosomal DNA
aka ArrayCGH
What are the pros and cons of chromosome microarray (ArrayCGH)?
Pros: high resolution, quick, technically easier
Cons: also finds polymorphisms, can make incidental findings of other genetic abnormalities
When is chromosomal analysis by chromosome microarray (arrayCGH) indicated? (3)
- If NIPT screening is positive (high risk of chromosomal trisomy)
- If there is foetal abnormality on scanning
- If a parent has a balanced chromosomal rearrangement
List 3 foetal abnormalities that may be picked up on scanning
- Small size e.g., symmetrical growth failure
- Increased nuchal thickness (tissue at back of foetus’ neck)
- Structural malformation e.g., of brain or heart
PCR sequencing can be used to identify…
Specific single gene changes
What is a disadvantage of PCR?
You need to know the exact location of the gene you are looking for
Next generation sequencing can be used to…
Sequence the entire genome or exome to identify the causative single gene mutation
Parents are offered termination of pregnancy if their baby has a serious genetic abnormality. What method of TOP is offered at…
- <13 weeks
- 13 weeks +
- <13 weeks: medication or surgical termination
- 13 weeks +: labour induction TOP
TOP of usually not permitted after ? weeks gestation
24
In what cases can TOP be offered throughout the whole pregnancy (+24 weeks)? (2)
- If there is risk of serious abnormality in the child
- If there is serious risk to the mother’s health
Suggest 3 chromosomal/genetic abnormalities that can cause hypotonia (i.e., a ‘floppy baby’)
- Down’s syndrome
- Prader-Willi syndrome
- Spinal muscular atrophy
Hypotonia/floppy baby is caused by a defect in…
The communication pathway between the brain and muscles
so anywhere along the brain -> spinal cord -> nerves -> muscles pathway
What other clinical signs may be seen in a baby with hypotonia (a floppy baby?) (4)
- Weakness
- Decreased deep tendon reflexes (DTR’s)
- Fasciculations (muscle twitches) or seizures
- Reduced alertness
When would you carry out a creatine kinase test on a baby?
If concerned about a muscular disorder e.g., Duchenne muscular dystrophy
Why may a baby with hypotonia need respiratory or feeding support?
Lack of tone means they can struggle to increase work of breathing and to suck to feed
