Genetics in pregnancy Flashcards
What are the different methods of sampling for genetic testing in antenatal care and when during the pregnancy can they be done ?
- CVS - 11.5 to 14wks
- Amniocentesis - from 16wks +
- Fetal blood sampling - from 18+wks
- Fetal DNA from maternal blood (NIPT) - 8+ wks
What is the main problem associated with CVS ?
Confined placental mosaicisim
What is the problem with amniocentesis ?
Poor tissue avaliability
Is fetal blood sampling used often ?
No it is rarley used
What is the problem with NIPT ?
Only limited analyses avaliable
Define what a chromosome is
A package containing a chunk of a genome - that is it contains some of the organisms genes (hence why you have 46 to make up together all the genome)
Define what the genome is
It is the whole of the genetic info of an organism i.e. all its genes
Define what a gene is
It is a segment of DNA on a chromosome that describes how to make a certain protein
What is the main test used to test the whole genome in genetics and give an example of the sort of mutation it is used to find
Array CGH - used to find bigger mutations such as chromosome changes e.g. DS, can be used for smaller mutations but not for things as small as point mutations
What is the main genetic test used for very small mutations such as point mutations ?
FISH
What is the problem with whole genome testing ?
You find millions of polymorphisms so need to distinguish these from the disease causing mutation
Define a mutation
A genetic change which causes disease
Define a polymorphism
A genetic variation that is not disease causing
What factors would help indicate a genetic change is a mutation?
- Its de-novo
- Affects the known gene involved in the disease
- Previously reported in same phenotype
What factors would help indicate a genetic change is a polymorphism?
- Normal parent has it
- Found in ‘‘empty’’ genetic region
- Previously reported as a polymorphism
When would QF-PCR be used and why ?
If a baby is born and quick confirmation is needed to confirm they have a condition (this is a whole genome test so needs to be big mutations) e.g. to quickly confirm DS on birth in clinically suspected baby
When do you do Array-CGH or chromsome analysis ?
- When high risk of DS on screening
- If fetal abnormality seen on screening
- Parent has a balanced chromsomal rearrangement
What is NIPT currently used for ?
- Sex determination
- Trisomy screening
Mrs Pink comes to see you. She is 10 weeks pregnant. She has a son who is affected with Duchenne muscular dystrophy.
What genetic test would you offer ?
NIPT as can determine sex and ==> if any more testing needed
If male then CVS would be the next test due to date of pregnancy
If female no test needed as mutation is X-linked
Mrs Blue comes to see you. She is 18 weeks pregnant. A detailed scan has shown that her baby has a cardiac defect: an AtrioVentricular Septal Defect (AVSD) that is commonly seen in Down syndrome
- Reassurance
- Serum Screening
- Chorionic Villus Biopsy
- Amniocentesis
- Non-Invasive Prenatal testing
4 - Amniocentesis
Mrs Blue comes to see you. She is 18 weeks pregnant. A detailed scan has shown that her baby has a cardiac defect: an AtrioVentricular Septal Defect (AVSD) that is commonly seen in Down syndrome.
- Array CGH
- Karyotype
- Chromosome analysis
- FISH for 21
- DNA testing for a point mutation
1 - array-CGH
What can array-CGH not detect?
Balanced chromsome abnormalities
What does FISH detect ?
The presence or absence of specific DNA sequences on chromosomes
Define a robertsonian translocation
2 acrocentric chromsomes stuck end to end
Define what a reciprocal translocation is
Chromosome rearrangement invovlving exchange of chromosome segements between 2 chromosomes that do not belong to the same pair of chromosomes as eachother
What will conception in parents with translocations result in ?
50% of conception will have either normal chromosomes or balanced translocation.
Unbalanced products result in miscarriage, dysmorphic delayed child etc
Mrs Roberts comes to see you. She is 10 weeks pregnant. She has a balanced reciprocal translocation between chromosome 4 and chromosome 9, that has a high risk of causing a liveborn child with multiple malformations.
- Reassurance
- Serum Screening
- Chorionic Villus Biopsy
- Amniocentesis
- Fetal Blood Sampling
3 - CVS
What is the risk of inheriting an x-linked disorder ?
It is 25%, unless the fetus is known to be male then it is 50%
What is the risk of inheriting an autosomal dominant disorder?
50%
What is the risk of inheriting an autosomal recessive disorder ?
25%
What is pre-implantation genetic diagnosis (PGD) and who is it done for?
This is an IVF like technique which involves performing a genetic test on an embryo before re-implanting one with the ‘correct’ genotype
The couple must be at risk of having a child with a serious genetic condition
For what genetic conditions is PGD carried out for ?
Chomromosal abnormalities - mainly reciprocal & robertsonian translocations
Single gene testing:
- Autosomal recessive disorders - CF, beta-thalassaemia, sickle cell, spinal muscular dystrophy
- Autosomal dominant disorders - myotonic dystrophy, huntingtons disease
- X-linked diseases - fragile X-syndrome, haemophilia A, duchenne muscular dystrophy
