Genetics Flashcards
What do you need to do a DNA or chromosome test on a baby in utero?
Tissue with the same genetic make up
What are some examples of foetal testing?
Placenta- chorionic villus biopsy
Skin/Urine cells- amniocentesis
Blood- foetal blood sampling
Foetal DNA from maternal serum
When can CVS be carried out?
11.5 weeks
When can amniocentesis be carried out?
15 weeks +
What is the miscarriage risk of CVS?
1-2%
What is the miscarriage risk of amniocentesis?
0.5-1%
What is the miscarriage risk of foetal blood sampling?
1-2%
What is the miscarriage risk of foetal DNA from maternal blood?
None
When can foetal DNA from maternal blood be tested?
8 weeks +
When can foetal blood sampling be carried out?
18 weeks +
What viability of tissue is needed in CVS?
Good
What viability of tissue is needed in amniocentesis?
Poor
What viability of tissue is needed in foetal blood sampling?
Good
What viability of tissue is needed in foetal DNA from maternal blood testing?
Stable mother
What risks are there in CVS?
Miscarriage
Confined placental mosaicism
What limits are there in foetal DNA from maternal blood testing?
Limited analyses available
What whole genome analyses are available?
Standard karyotype- in metaphase
Array CGH (chromosomes)
Quantification of foetal DNA in maternal serum
Whole genome sequencing
What targeted analyses are available?
Point mutation testing
FISH
Quantitative Fluorescent PCR
What are copy number variations?
Insertions or deletions of DNA segments
How can you tell if a change is a copy number variation or mutation?
Mutation will be de-novo, polymorphism will be present in normal parent
Mutation will be bigger, affect known gene, and previously reported in same phenotype
When is FISH used?
When missing chromosome is too small to see
What is QF PCR used for?
Rapid counting of specific chromosomes- allows a dosage analysis of polymorphic repeat sequences at several loci on target chromosomes
When is aCGH or chromosome analysis used?
High risk of chromosomal trisomy on screening
Fetal abnormality on scanning-small size, especially if symmetrical growth failure, increased nuchal thickness, structural malformation e.g. brain, heart
Parent has balanced chromosomal rearrangement
When is serum screening carried out?
Week 16- look for biochemical markers of Down’s
When is a detailed scan to look for other fetal abnormalities carried out?
20 weeks
When may increased nuchal thickness be seen?
Dating USS at 12 weeks
What can be assessed through free fetal DNA in maternal circulation?
Sex determination
Trisomy testing
Chromosome deletions
Single gene
Why is free fetal DNA in maternal circulation a challenging test?
Only 10% of DNA comes from fetus
If a pregnant women who has 1 son with DMD, what test should be carried out?
NIPT through free fetal DNA to look for Y chromosome, if found do CVS
A pregnant women of 18 weeks has a detailed scan showing an AVSD, a common defect in Down’s, what testing should be done and why?
Amniocentesis/aCGH
18 weeks
Cardiac defect may have other causes
aCGH will detect small deletions such as 22q11
From initial 18 week scan and detection of AVSD on USS, when should amnio and aCGH be performed and results confirmed by?
+1-2 days: amniocentesis
+6 days: aCGH confirms result
What is a Robertsonian translocation?
Two acrocentric chromosomes stuck end to end (increased risk of trisomy)
What is aneuploidy?
Too many or too few chromosomes
What would aCGH look like in the parent with a balanced translocation ?
Normal- aCGH only detects imbalance
What reproductive risks are there in reciprocal translocations?
For most translocations, ~50% will have either normal chromosomes or balanced translocation
Unbalanced:
Miscarriage (large segments)
Dysmorphic delayed child (small segments)
A 10wks pregnant woman comes to see you, she has a balanced reciprocal translocation between Ch4 and Ch9, known to have a high risk of multiple malformations in a liveborn child, how do you manage?
CVB at 11.5 weeks
Direct Karyotype or Fish may be available at 11.5+3 days
At 13 weeks full karyotype complete
What is aCGH used for?
Chromosome deletions/duplications (analysis for balanced rearrangements)
What needs to be known to use FISH or DNA analysis?
Diagnosis
When can specific anomalies be detected?
Cardiac 12-20wks
Microcephaly after 22wks
Short Limbs after 22wks
Brain malformations
What is the best management to test for suspected DMD?
CVB
How can free fetal DNA in maternal serum help in diagnosing DMD?
At 8 weeks sexing on DNA, if boy proceed to invasive testing, if girl no concerns
What is Pre Implantation Genetic Diagnosis (PGD)?
Perform a genetic test on an embryo before re-implanting one with the ‘correct’ genotype
What is the process involved in PGD?
Down regulation Ovarian stimulation- FSH USS-follicular assessment Oocyte retrieval Fertilisation by ICSI Embryo biopsy day 3
When may PGD be considered?
Parental chromosome abnormality Robertsonian translocation Reciprocal translocation X-linked disorders Re-implantation of female embryos Other single gene disorders Increasing numbers of conditions Spinal Muscular Atrophy Cystic fibrosis Huntingtons disease
