Genetics

Question 1

How can placental tissue be obtained for genetic testing?

Answer 1

Chorionic villus biopsy from 11.5 weeks gestation

Testing with FISH or PCR for chromosome abnormality

Question 2

How can skin/urine cells of a foetus be obtained for genetic testing?

Answer 2

Amniocentesis from 16 weeks gestation

Question 3

How can blood of a foetus be obtained for genetic testing?

Answer 3

Foetal blood sampling from 18 weeks gestation

Question 4

How can foetal DNA be obtained for genetic testing?

Answer 4

Maternal serum from 8 weeks gestation

Question 5

Rank chorionic villus biopsy, amniocentesis, foetal blood sampling and maternal serum in order of greatest to smallest risk of miscarriage

Answer 5

Chorionic villus biopsy
Foetal blood sampling
Amniocentesis
Maternal serum (no risk)

Question 6

Rank chorionic villus biopsy, amniocentesis, foetal blood sampling and maternal serum in order of most viable to least viable tissue

Answer 6

Chorionic villus biopsy
Foetal blood sampling
Maternal serum
Amniocentesis

Question 7

What is confined placental mosaicism? Which method of genetic testing is it most associated with?

Answer 7

Discrepancy between chromosomal makeup of placental cells and cells in the baby
Chorionic villus biopsy

Question 8

List the indications for chromosomal analysis in pregnancy

Answer 8

Raised maternal age
Increased risk on screening: nuchal thickness, serum, DNA
Abnormality on ultrasound
Known parental abnormality

Question 9

What does array CGH analyse?

Answer 9

Changes in the number of copies of a particular gene in a diseased state
Basically looks at chromosome makeup

Question 10

List the 4 main genetic tests used for chromosome analysis and state whether these tests assess the whole genome or are targeted

Answer 10

Array CGH (whole genome)
Standard karyotype (whole genome)
FISH (targeted)
QF-PCR (targeted)

Question 11

What is the earliest stage of pregnancy where nuchal thickness can be assessed via ultrasound?

Answer 11

12 weeks

Question 12

List indications for obtaining free fetal DNA

Answer 12

Antenatal screening for down’s syndrome
Fetal sexing for X-linked disorders
Monogenic disorders

Question 13

Distinguish a mutation from a polymorphism

Answer 13

Genetic change that causes disease

Genetic variation that is not disease-causing

Question 14

List the most common types of chromosomal abnormalities

Answer 14

Aneuploidy (abnormal no. of chromosomes in a cell)
Rearrangements (translocations, inversions)
Deletions/ duplications

Question 15

List the main types of chromosomal translocations

Answer 15

Robertsonian (two acrocentric chromosomes end-end)
Balanced (all chromosome material present)
Unbalanced (extra or missing chromosome material)

Question 16

Which type of chromosomal translocation is the most common reproductive risk?

Answer 16

Unbalanced chromosomal translocation

Question 17

Large segments of unbalanced chromosomal translocation causes…

Answer 17

Miscarriage

Question 18

Small segments of unbalanced chromosomal translocation causes…

Answer 18

Dysmorphic delayed child

Question 19

What does pre-implantation genetic diagnosis (PGD) involve?

Answer 19

Perform a genetic test on an embryo before re-implanting it with “correct” genotype, using IVF

Question 20

What method is used to implant genetic info in PGD?

Answer 20

Intra-cytoplasmic sperm injection (ICSI)

Question 21

How old is the embryo when it is biopsied in PGD?

Answer 21

3 days

Question 22

List types of DNA analysis commonly used and their relative indication in pregnancy

Answer 22

aCGH for deletions/duplications in small sequences
Chromosome analysis for balanced rearrangements
NGS for large sequences
Non-invasive prenatal testing for large sequences

Question 23

What type of mutational change would produce an abnormal or absent protein?

Answer 23

Splice consensus altered

Question 24

What type of mutational change would make a short or absent protein?

Answer 24

Base change makes new stop

Question 25

What type of mutational change would make a different or non-functioning protein?

Answer 25

Base change alters amino acid sequence

Question 26

What is the main disadvantage of NGS in pre-natal testing?

Answer 26

It detects lots of polymorphisms

Question 27

When can fetal anomalies be identified during pregnancy on US scan?

Answer 27

Booking scan (10-12 weeks) 
Detailed scan (20 weeks)

Question 28

What is the pattern of inheritance for Duchenne muscular dystrophy?

Answer 28

X-linked recessive

Gene that can carry a DMD-causing mutation is on the X chromosome which passes from mother to son

Question 29

What is the risk of a child being affected by DMD?

Answer 29

1 in 4

1 in 2 if you know the child is male

Question 30

What is the risk of a child being affected by an autosomal dominant condition?

Answer 30

1 in 2 risk if parent is affected

Question 31

What is the risk of a child being affected by an autosomal recessive condition?

Answer 31

1 in 4 risk of affected child if parents are carriers

Question 32

What factors influence risk estimation of a child?

Answer 32

Family history
Obstetric history
Maternal history
Scan findings
Genetic tests

Question 33

What is the best genetic management if DNA testing in pregnancy indicates risk of inheritance?

Answer 33

Non-invasive fetal sexing

Chorionic villus biopsy if male

Question 34

List indications for consideration of PGD in pregnancy

Answer 34

Parental chromosomal abnormality (robertsonian translocation, reciprocal translocation)
X-linked disorders (reimplantation of female embryo)
Other single gene disorders (spinal muscular atrophy, cystic fibrosis, huntingdon’s disease)

Question 35

What is a Robertsonian translocation?

Answer 35

Chromosomes break at their centromeres and the long arms fuse to form a single, large chromosome with a single centromere

Question 36

What is a reciprocal translocation?

Answer 36

Chromosome abnormality caused by rearrangement of parts between non-homologous chromosomes