Week 3- genetics and embryology

Question 1

To be able to carry out genetic testing, you need some tissue to test on, which ways can you obtain these?

Answer 1

Placental tissue- chorionic villus sampling
Skin/urine cells-amniocentesis.
Blood- fetal blood sampling.

Question 2

What are the disadvantages of amniocentesis?

When can it be carried out?

Answer 2

Poor tissue viability due to essentially looking for tissues that have fallen off the baby
Can be carried out at 16+ weeks.

Question 3

What methods of obtaining genetic material provide good tissue viability?
When can these methods be carried out?
Do these methods have a higher miscarriage rate?

Answer 3

Chorionic villus sampling- 11.5 weeks
Fetal blood sampling- 18+ weeks

Yes- 1-2% as opposed to 0.5-1% as in amniocentesis.

Question 4

What other risk is associated (other than miscarriage) with chorionic villus sampling?

Answer 4

Confined placental mosiacism.

Question 5

What is confined placental mosaicism?

Answer 5

When the CVS result comes back with some abnormal cells and some normal cells. Comes from the placenta not matching the fetal karyotype, with the placenta being the abnormal karyotype and the foetus being the normal.

Question 6

What genetic modalities sample the whole genome?

Answer 6

Array CGH
Quantification of fetal DNA in maternal serum
Whole genome sequencing.

Question 7

What genetic modalities sample only specific parts of the genome to look for abnormalities?

Answer 7

Point mutation testing
Fluorescence in-situ hybridisation (FISH)
Quantitive fluorescent PCR (QF-PCR)

Question 8

How does array CGH work?

Answer 8

Essentially looks at whole chromosomes and counts them so you can look for big chromosomal imbalances.

Question 9

What is the issue with whole genome testing?

Answer 9

Can pick up polymorphisms as well as mutations. So the mutation may not actually be causing disease.

Question 10

What is the definition of a polymorphism?

Answer 10

Genetic variation that is not causing disease.

Question 11

What is a single nucleotide polymorphism?

Answer 11

A change in a single base.

Question 12

What is copy number variation polymorphisms?

Answer 12

Insertion or deletion of DNA segments.

Question 13

What features are likely to suggest that the genetic change is a polymorphism rather than a mutation?

Answer 13

Parent has the mutation- but is normal
Smaller
Previously been reported as a polymorphism.

Question 14

When would you use FISH?

Answer 14

When the missing bit of chromosome is too small for Array CGH

Question 15

When would you perform array CGH?

Answer 15

High risk of chromosomal trisomy on scanning.

Fetal abnormality on scanning- e.g. small size, increased nuchal thickness, structural malformation

Question 16

When is the first scan in pregnancy carried out? What tests are done alongside it?

Answer 16

Around 12 weeks

Serum biochemistry is also done.

Question 17

What tests are performed to test for down syndrome?

Answer 17

Serum screening at around 16 weeks.

Maternal blood test to look for markers.

Question 18

What non-invasive pre-natal testing can be done during pregnancy? How is it done?

Answer 18

Sex determination
Trisomy testing

(occasionally also chromosome depletions, single gene)

Done by looking at free fetal DNA in mothers circulation.

Question 19

What is the issue with looking for free fetal DNA in the mothers circulation?

Answer 19

Only 10% of the DNA is the foetus’s.

Question 20

Duschennes muscular dystrophy affects who?

Answer 20

Only males.

Question 21

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.
What is the best genetic test to do?

Answer 21

Array CGH of amniocentesis

• amniocentesis because she is 18 weeks pregnant, cardiac abnormalities may be due to other genetic disorders etc.

Question 22

What is meant by balanced chromosome rearrangement?

Answer 22

All the chromosomal material is present.

Question 23

What is meant by imbalanced chromosome rearrangement?

Answer 23

Extra or missing chromosomal DNA.

Question 24

What is a Robertsonian translocation?

What does this increase the risk of?

Answer 24

Two acrocentric chromosomes stuck end to end.

Trisomy 21.

Question 25

What would array CGH look like in a balanced translocation?

Answer 25

Normal- it only detects imbalance :(