Clinical genetics in pregnancy

Question 1

List the DNA analysis methods from least to most specific

Answer 1

• Chromosome analysis
• aCGH
• Polymerase chain reaction and sanger sequencing
• next generation sequencing

Question 2

What is aCGH for?

Answer 2

For chromosome deletions/duplications

(chromosome analysis for balanced rearrangements)

Question 3

What are the non coding regions called?

Answer 3

Intron

Question 4

What does NGS do?

Answer 4

Sequence whole genome or just all known exons

Question 5

When do antenatal USS take place?

Answer 5

Booking scan- usually 10-12 weeks

Detailed scan at 20 weeks

To detect specific anomalies ;

• cardiac (12-20 weeks)
• • microcephaly (usually after 22 weeks)*
• • short limbs (usually after 22 weeks)*
• • brain malformations*

Question 6

What contributes to diagnosis and risk estimation?

Answer 6

• family history
• pregnancy history
• maternal history
• scan findings
• clever tests

Question 7

What happens after genetic diagnosis is made?

Answer 7

Recurrence risk calculated

Treatment?

Prognosis

Genetic tests

Question 8

What are the options for DNA testing during pregnancy?

Answer 8

• usually PCR based results in 2-3 days
• ocassionaly southern blotting may take 2-3 weeks
• chorionic villus biopsy at 11.5+ weeks
• amniocentesis at 16 + weeks

Question 9

What is southern blotting?

Answer 9

• used to detect a specific DNA sequence in a blood or tissue sample
• restriction enzyme is used to cut a sample of DNA into fragments that are separated using gel electrophoresis
• The DNA fragments are transferred out of the gel to the surface of a membrane
• The membrane is exposed to a DNA probe labeled with a radioactive or chemical tag
• If the probe binds to the membrane, then the probe sequence is present in the sample

Question 10

What is PGD?

Answer 10

Pre-implantation genetic disgnosis

Perform a genetic test on an embryo before re-implanting one with the ‘correct’ genotype

Question 11

What are the down-sides of PGD?

Answer 11

• requires IVF- like procedure
  
  • expensive
  • invasive
• overall 30% take home baby rate per cycle
  
  • emotional rollercoaster
• less reliable than prenatal testing- analysing a single cell
• multiple pregnancy risk

Question 12

What are the advantages of PGD?

Answer 12

Pregnancy less likely to be affected from outset

Lower likelihood of requiring TOP

Question 13

When might PGD be considered?

Answer 13

• Parental chromosome abnormality
  
  • robertsonian translocation
  • reciprocal translocation
• X-linked disorders
  
  • re-implantation of female embryos
• Other single gene disorders
  
  • SMA
  • C.F
  • Huntingtons