9: Genetics I Flashcards
If there is a family history of inherited disease or dodgy genetic/ultrasound results in pregnancy, who should a mother be referred to?
Clinical geneticist
Which genetic sampling techniques for pregnancy use samples from the
a) placenta
b) amniotic fluid
c) blood?
a) Chorionic villus biopsy
b) Amniocentesis
c) Foetal / maternal blood sampling
Which tissues are sampled by
a) chorionic villus biopsy
b) amniocentesis
c) maternal blood sampling?
a) Placenta
b) Amniotic fluid
c) Maternal AND foetal blood
At what point in gestation can you do a
a) chorionic villus biopsy
b) amniocentesis
c) maternal blood sample for foetal DNA?
a) Around 11 weeks
b) 16+ weeks
c) 8+ weeks
What type of genetic sample is also known as non-invasive pre-natal testing?
Maternal blood sample for foetal DNA
When is the earliest point in gestation at non-invasive pre-natal testing can be carried out?
8 weeks
Making it very useful compared to chorionic villus biopsy and amniocentesis, which are both invasive and can only be done later in gestation
What is the risk involved in chorionic villus biopsy?
Miscarriage
1-2% miscarriage rate
Cells obtained from a chorionic villus biopsy may show different genotypes from one another.
Why?
Placental mosaicism
Which genetic sampling method can be carried out from around 11 weeks gestation?
Chorionic villus biopsy
Which genetic sampling method can be carried out from 16 weeks gestation?
Amniocentesis
What is the problem with amniocentesis as a genetic sampling method?
Tissue quality can be poor
Which genetic sampling method can be carried out from 8 weeks gestation, making it the earliest sample which can be done?
Maternal blood sample for foetal DNA
Taking maternal blood for foetal DNA, or non-invasive pre-natal testing, is one of the earliest and most effective tests you can do.
What’s the problem with it at the moment?
Can only test for a limited number of genetic disorders
Which percentage of embryos have chromosomal abnormalities?
40%
But 40% of embryos don’t result in miscarriage, so repair mechanisms must exist
Which whole genome tests are commonly used pre-natally?
Array CGH
Foetal DNA from maternal blood
Next generation sequencing (NGS)
Array CGH is a whole genome test used to detect (balanced / unbalanced) chromosome mutations.
unbalanced mutations
Which targeted tests are commonly used pre-natally?
Point mutation testing
Quantitative fluorescent PCR (QF-PCR)
What is the definition of a mutation?
Genetic change which causes disease
What is the definition of polymorphism?
Genetic change which doesn’t cause disease on its own
How many polymorphisms does a person have on average?
3 million
Apart from genetic testing, how else can foetal abnormalities be discovered before birth?
Ultrasound scan
When are foetal ultrasound scans typically carried out?
12 weeks
20 weeks
To check for structural abnormalities suggestive of congenital disease
What measurement, made on foetal ultrasound, indicates whether or not a child has Down’s syndrome?
Nuchal thickness
What is nuchal thickness?
Which disease is it used to diagnose?
Thickness of the skin on the back of a foetus’s neck
Seen during foetal ultrasound
Down’s syndrome
After seeing clear nuchal thickening on foetal ultrasound, which genetic test would you use to diagnose Down’s syndrome?
Array CGH
Remember it detects extra or missing chromosomes - trisomy 21
Apart from array CGH, what other genetic test could you use to diagnose Down’s syndrome?
Maternal blood for foetal DNA
=> Karyotype (trisomy 21)
What is NIPT?
Non-invasive pre-natal testing
The use of foetal DNA from a maternal blood sample to diagnose genetic disorders
What percentage of maternal blood contains some foetal DNA?
10%
So not a huge amount to sample
What is an advantage of chorionic villus biopsy or amniocentesis over NIPT?
Can test for a greater number of disorders
NIPT is currently limited to Down’s syndrome
Which genetic disorder is commonly diagnosed using NIPT?
Down’s syndrome
Occasionally you can use it for other stuff like DMD
Apart from diagnosing genetic disorders, what else can you use NIPT for?
Sex determination
Is it a boy or a girl?
___ chromosome translocations are better than ___ ones.
Balanced is better than unbalanced
In which case is an unbalanced translocation not as bad?
If it affects sex chromosomes
e.g Turner’s 45 XO, Klinefelter’s 47 XXY
These children are definitely symptomatic but not devastatingly so
What is a Robertsonian translocation?
Some chromosomes are acrocentric i.e they only have one side, nothing after the centrosome
In a Robertsonian translocation, an acrocentric chromosome binds to the end of a normal chromosome
Producing an unbalanced translocation
Robertsonian translocations increase your chances of inheriting what type of genetic disorder?
Trisomy
Three copies of the same chromosome (even with an acrocentric chromosome stuck on the end)
This is bad
What does aneuploidy mean?
Too few chromosomes
Too many chromosomes
How would array CGH appear in a patient with a balanced translocation?
Normal
Array CGH only detects unbalanced translocations
What do
a) large
b) small
unbalanced translocations cause in a foetus?
a) Miscarriage
b) Developmental delay (severity ranging from mild to severe)
