Genetics - Genetic Testing Flashcards
What happens at 10-14 weeks into the pregnancy?
Nuchal scan
What is involved in a nuchal scan?
Variety of blood tests and nuchal translucency tests
What do we assess the risk of with a nuchal translucency?
Downs
What is the main purpose of a nuchal scan?
Detects for multiple pregnancy Dates the pregnancy Detects for early miscarriage Detects for major foetal abnormalities Detects for Downs
When is the next scan after the nuchal scan?
Mid trimester - 20-22 weeks
What is the purpose of a mid trimester anomaly scan?
More detailed normal scan - looks at brain, spinal cord, bones, heart face, kindeys
How many conditions do we look for with a mid trimester anomaly scan?
11
How do we gauge the risk for Down’s in an NT?
Increased thickness of back of neck (above 3mm)
What are we measuring in an NT?
Thickness at back of neck
What is NT not used for?
Not diagnostic - screening purposes only
When do we arrange pre natal testing?
Following abnormalities on normal scans
Combined risk of Downs
Parents have good reason to arrange e.g. family history
What are the main aims of prenatal testing?
Inform parents of affected baby
Prepare for complications before or after birth
What does prenatal testing allow for?
Termination of foetus
Management of pregnancy around the disease
What can a foetal MRI be used for?
Further testing or clarification
What can we use to diagnose any cardiac conditions?
Foetal cardiac scan
Aside from NT, what else can we use to detect for the risk of trisomy 21/18 or neural tube defects
Maternal serum testing markers in then blood
What is the neural tube
Precursor to CNS
What are the two non invasive methods of prenatal testing?
Maternal blood tests
cell free foetal DNA (cffDNA)
What is cell free foetal DNA?
Where fragments of foetal DNA are shed from the placenta and enter the mother’s blood stream
When is the earliest that cffDNA can be detected in the blood
4-5 weeks
Why do we not test for cffDNA at its earliest point that it appears?
Cannot be tested until around 9 weeks when results are most accurate.
What is NIPD?
Non invasive prenatal diagnosis
What NIPDs can we get from cffDNA?
Achondroplasia
Thanatophoric dysplasia
Apert syndrome
What non disease can we use NIPD for?
Sexing - SRY gene on the Y chromosome of boys can be detected
How much do NIPD cost?
Free on NHS
Can we diagnose with NIPT?
No
What do we do if we find anomalies with NIPT?
Arrange invasive testing
How are multiple pregnancies a limitation with NIPT/D?
We do not know which child is affected or whether both are affected
How is women with a high BMI a limitation with NIPT/D?
They will have overall more of their own cell free DNA in the blood
What are some of the benefits of NIPT/D?
Non invasive
No risk of miscarriage
No specialist required
Can be offered earlier than most invasive tests
When is invasive testing offered?
When there is a known risk of a disease or there is abnormal results from normal scans/ NIPT
What are the two main invasive testing methods?
Chorionic Villus Sampling
Amniocentesis
What do invasive tests include?
Include molecules, cytogenic and biochemical tests
How is invasive testing offered?
Outpatient bases
When is CVS carried out?
11-14 weeks
What is the risk of a miscarriage with CVS?
1-2%
How is a CVS sample taken?
Sample of chorionic villus is taken via the transvaginal or trans abdominal route
What is the main benefit of CVS?
Allows the patient to get earlier results than amniocentesis - important for ToP decisions.
What is amniocentesis?
Insertion of a needle into amniotic sac and taking a sample of the fluid
When is amniocentesis carried out?
15-16 weeks
What is the miscarriage risk of amniocentesis?
up to 1%
What is another risk of amniocentesis?
Risk of infection or Rh sensitisation
What tests do we carry out with an obtained DNA sample?
- Testing for the disorder in question
- Karyotyping
- QF-PCR
What is the purpose of testing for the disorder in question?
We want to see if the foetus is a carrier or whether they are affected/unaffected
What is the purpose of karyotyping?
If parents are affected by translocation, there is a chance that the foetus will also be affected
What is the purpose of QF-PCR
Carried out for all - looks for trisomy of 13, 18 and 21
What is a CGH array?
Detects imbalances on all of the chromosomes and will be able to detect for micro deletions or duplications
When is a CGH array offered?
After anomalies on 20 week scan
What happens if abnormalities are shown on a CGH array?
We will test the parents to see if the abnormality is inherited or if the foetus is the first affected family member.
What is trio-exome?
Prenatal exome testing
What is the exome?
Coding region of a genome
What does trio-exome allow us to do?
allows us to look at the baby’s exome if there are significant abnormalities
What do we sequence in tiro-exome?
Exons not introns
When there is a known reproductive risk, what options do parents have?
Conceive naturally Use egg/sperm donor Adoption Choose not to have children PGD
What is PGD?
Pre-implantation genetic diagnosis (IVF with additional step to test embryo before implantation)
What is step 1 of PGD?
Stimulation of ovaries
What is step 2 of PGD?
Egg collection
What is step 3 of PGD?
Insemination in lab
What is step 4 of PGD?
Fertilisation
What is step 5 of PGD?
Embryo biopsy
What is step 6 of PGD?
Embryo testing
What is step 7 of PGD?
Embryo transfer (if embryo test is ok)
What is step 8 of PGD?
Pregnancy test
What is ICSI?
Intracytoplasmic Sperm Injection - avoid complications generate by letting sperm compete for the egg
When do we use PGD?
Used for genetic conditions e.g. Huntington’s DMD susceptibility.
What are some of the criteria for PGD?
Non smokers
Stable relationship
Mother is maximum 39 years old
What may decision making depend upon?
Previous experience
Family situation
Personal/cultural beliefs
