Genetics

Question 1

What methods can be used for sampling metal tissue to test DNA?

Answer 1

• Chorionic villus biopsy - from placenta
• amniocentesis - skin/urine cells
• fetal blood sampling - from base of cord (needle accesses this through the placenta)
• Fetal DNA from maternal serum

Question 2

What method of sampling of foetal DNA for genetic testing can be used from 11/12 weeks gestation to 14 weeks gestation?

Answer 2

Chorionic villus biopsy

Question 3

What method of sampling of foetal DNA for genetic testing can be used from 15/16 weeks gestation?

Answer 3

Amniocentesis

Question 4

What method of sampling of foetal DNA for genetic testing can be used from 18 weeks gestation?

Answer 4

Fetal blood sampling

Question 5

What method of sampling of foetal DNA for genetic testing can be used from 8 weeks gestation?

Answer 5

Foetal DNA from maternal blood

Question 6

What is the miscarriage rate for:

a) chorionic villus biopsy
b) amniocentesis
c) foetal blood sampling

Answer 6

a) 1-2%
b) 0.5-1%
c) 1-2%

Question 7

What are the indications for an array-CGH or chromosome analysis?

Answer 7

High risk of chromosomal trisomy on screening
Fetal abnormality on scanning:
- small size, esp if symmetrical
- increased nuchal thickness
- structural malformation e.g. brain or heart
Parent has balanced chromosomal rearrangement

Question 8

Does Array CGH look at whole genome or targeted genes?

Answer 8

Whole genome

Question 9

What genetic tests are available to look at targeted genes?

Answer 9

• Point mutation testing
• FISH
• Quantitative fluorescent PCR (QF-PCR)

Question 10

What 2 types of polymorphisms are there?

Answer 10

Single nucleotide polymorphisms (single base changes)

Copy number variation (insertions or deletions of DNA segments)

Question 11

What prenatal screening tests are offered in Scotland?

Answer 11

12 weeks gestation: Dating Ultrasound scan with serum biochemistry (increased nuchal thickness may be detected at this point)
16 weeks gestation: maternal blood test to look for biochemical markers of Downs syndrome
20 weeks gestation: detailed scan to look for other foetal abnormalities

Question 12

What genetic tests can be done on non-invasive prenatal testing (free foetal DNA in maternal circulation)?

Answer 12

Sex determination
Trisomy testing
sometimes can test for chromosome deletions or single gene mutations

Question 13

Patient presents who is 10 weeks pregnant, and she has a son with Duchenne muscular dystrophy. How might you manage this patient?

Answer 13

Non-invasive prenatal testing (fetal DNA in maternal blood sampling) to determine sex of baby. If female, reassure patient; if male, offer chorionic villous sampling.

Question 14

How can non-invasive prenatal testing be used to detect for trisomy 21?

Answer 14

Do lots of next generation sequencing reads on DNA collected (it will be a mix of maternal and foetal DNA). If there are more reads from chromosome 21 than there should be, suggests trisomy 21 (ratio of 11:10)

Question 15

Patient who is 18 weeks pregnant has a detailed scan that shows her baby has an atrioventricular septal defect, which is commonly seen in Downs syndrome. What is the most appropriate
a) sampling technique
b) genetic test
for this patient’s management and why?

Answer 15

a) amniocentesis - 18 weeks gestation
b) array-CGH - cardiac deficit may be Downs syndrome but there are other genetic causes, and array CGH will detect small deletions that might be responsible

Question 16

What are the types of chromosomal abnormalities that cause disease?

Answer 16

Aneuploidy:
- too many chromosomes
- too few chromosomes
Rearrangement - translocations
- Robertsonian or reciprocal Balanced chromosome rearrangement - all the chromosomal material is present
- Unbalanced chromosome rearrangement - extra or missing chromosomal material (usually 1 or 3 copies of some of the genome)
Rearragement - Inversions
Deletions/duplications

Question 17

What aneuploidy genetic condition has neck webbing and oedema as clinical features?

Answer 17

Turner syndrome

Question 18

What is the outcome of Trisomy 14?

Answer 18

Miscarriage

Question 19

What is the chromosomal rearrangement associated with an increased risk of trisomy in a pregnancy?

Answer 19

Robertsonian Translocation - rearrangement where 2 chromosomes become stuck together. If balanced, patient will be phenotypically normal; if unbalanced will lead to trisomy of affected chromosome

Question 20

What would aCGH look like in a parent with a balanced translocation?

Answer 20

Normal - aCGH only detects imbalance