Genetic Testing Flashcards
- What is the main method for prenatal diagnosis of foetal abnormalities?
- Why might a Normal Nuchal scan be taken and when are they taken?
Ultrasound, one scan at 11-14 weeks and one at 20-22 weeks
To read the thickness of the fluid at the back of the neck At 12 weeks and 20 weeks
- What is the aim of the 12 week scan?
To date the pregnancy accurately
To diagnose multiple pregnancies To diagnose major foetal abnormalities To diagnose early miscarriage To assess the risk of Down Syndrome and other chromosomal abnormalities
- A thickness of fluid at the back of fetal neck of above 3mm can indicate what?
Chromosome abnormalities eg downs, turners
Birth defects - Cardiac anomalies - Pulmonary defects - Renal defects - Abdominal wall defects Skeletal dysplasias
- Is Nuchal Translucency a screening test or a diagnostic?
- When is prenatal testing arranged?
Screening test
Following abnormal findings at nuchal scan or mid-trimester scan Following results of combined test which give an increased risk of Down Syndrome If previous pregnancy affected with a condition If parent is a carrier of chromosome rearrangement or genetic condition Family history of genetic condition
- What are the aims of prenatal testing?
To inform and prepare parents for the birth of an affected baby
To allow in utero treatment Manage remainder of pregnancy To be prepared for complication at or after birth To allow termination of an affected fetus
- Why is a Fetal MRI needed?
- Why is a fetal cardiac scan needed?
For more detailed scan to see organs more clearly
To look at flow of blood through body's heart to diagnose cardiac conditions
- What is cffDNA?
- When can cffDNA be detected?
Cell-free fetal DNA
Short DNA fragments of baby
Floats around in mother’s blood from placenta & composed of baby’s DNA
First 4-5 weeks of gestation but cannot accurately be detected on testing until 9 weeks
- What is NIPD?
- For which genetic conditions is NIPD free for?
Non-invasive prenatal diagnosis, analyses fragments of DNA present in maternal plasma during pregnancy (cell free DNA)
Maternal blood test at around 9 weeks of pregnancy
Achondroplasia Thanatophoric dysplasia Apert syndrome
- What gene is detected to determine the sex of the fetus?
- How does this diagnose an X linked condition in the family?
SRY gene on the Y chromosome
If male - go on to prenatal test
If female- no invasive testing is required
- For Cystic Fibrosis, what test is used to detect both maternal and paternal mutation in the fetal DNA?
Haplotyping
- What are the limitations of NIPD and NIPT?
Not possible in multiple pregnancies to tell which DNA came from which fetus
Relative proportion of cffDNA is reduced in women with high BMI so 2nd sample may be needed after 9 weeks Women may not be as prepared for the result as they would be for an invasive test Invasive test may still be required to confirm an abnormal result
- What are the benefits of NIPT and NIPD?
Number of invasive tests carried out is likely to reduce as a result
No increased risk of miscarriage Less expertise required to perform blood test than invasive test NIPD/NIPT can be offered earlier than traditional invasive testing, so result given earlier
- What is CVS?
- How long until CVS can be carried out?
Sample of chorionic villi (part of developing placenta with same DNA as fetus) is taken transabdominally or transvaginally
Allowing patient to have result earlier than amniocentesis
11-14 weeks
- How long until Amniocentesis can be carried out?
- What is Amniocentesis?
- What are the risks of Amniocentesis?
16 weeks
Sample of amniotic fluid which contains fetal cells is taken Up to 1% risk of miscarriage Infection Rh Sensitisation
- What tests are done with a DNA sample?
Test for genetic disorder in question
Karyotype if chromosome abnormality is present in the family history QF-PCR for all - Looks for trisomy 13, 18 and 21
- What is CGH array?
- If something is found on the array, what happens next?
If there are concerns on 20 week scan, the gold standard is to offer CGH array
Look for small/large imbalances in chromosomes (microdeletions and duplications) Standardly test parents to see if either is a carrier to help with interpretation
- What are the 4 steps in carrying out a CGH array?
Extract DNA from test and from control sample and Label one with a red dye and the other with a green dye
Mix and Hybridise (bind) to a microassay with thousands of oligonucleotide probes, then wash
detect red and green signals with a fluorescent scanner
Analyse Data- compute and report gains/ losses of test DNA using software
- What does a Trio Exome allow?
- What is an Exome?
- What is a Trio Exome?
Efficient diagnosis of genetic condition in utero
The coded region of DNA Exome is taken from the baby and parents
full genetic sequencing. offered where previous pregnancies have had significant anomalies
- What is a reason why are there fewer egg and sperm donors?
- What are the 2 stages that must be gone through when a couple want to adopt?
Donations are no longer anonymous and children conceived have the right to contact the donor when 18
Registration and checks- references, criminal checks Assessment and approval- social worker visits home, a panel review couple
- What is Pre-implantation Genetic Diagnosis?
- Who is PGD particularly used by?
PGD uses IVF with an additional step to genetically test the embryo before implantation
People who do not want TOP (termination of pregnancy)
- Describe the process of PGD?
Stimulation of ovaries- hyperstimulation so many eggs removed
Egg collection Insemination - intracytoplasmic sperm injection (ICSI) of only a single sperm to reduce contamination from more sperm cells Fertilisation Embryo biopsy- at the 8 cell stage Embryo testing - at blastocyst stage Embryo transfer - of those that did not inherit the genetic condition into the womb Pregnancy test
- For which disorders is PGD used for?
Used for conditions caused by single faulty gene to reduce the amount of non embryo DNA (incl sperm DNA) which could make the risk of a wrong diagnosis higher
Translocation carriers
Huntingdons disease
Duchenne Muscular Dystrophy - only implant female embryos
Cystic Fibrosis
