9: Genetics I

Question 1

If there is a family history of inherited disease or dodgy genetic/ultrasound results in pregnancy, who should a mother be referred to?

Answer 1

Clinical geneticist

Question 2

Which genetic sampling techniques for pregnancy use samples from the

a) placenta

b) amniotic fluid

c) blood?

Answer 2

a) Chorionic villus biopsy

b) Amniocentesis

c) Foetal / maternal blood sampling

Question 3

Which tissues are sampled by

a) chorionic villus biopsy
b) amniocentesis
c) maternal blood sampling?

Answer 3

a) Placenta

b) Amniotic fluid

c) Maternal AND foetal blood

Question 4

At what point in gestation can you do a

a) chorionic villus biopsy
b) amniocentesis
c) maternal blood sample for foetal DNA?

Answer 4

a) Around 11 weeks

b) 16+ weeks

c) 8+ weeks

Question 5

What type of genetic sample is also known as non-invasive pre-natal testing?

Answer 5

Maternal blood sample for foetal DNA

Question 6

When is the earliest point in gestation at non-invasive pre-natal testing can be carried out?

Answer 6

8 weeks

Making it very useful compared to chorionic villus biopsy and amniocentesis, which are both invasive and can only be done later in gestation

Question 7

What is the risk involved in chorionic villus biopsy?

Answer 7

Miscarriage

1-2% miscarriage rate

Question 8

Cells obtained from a chorionic villus biopsy may show different genotypes from one another.

Why?

Answer 8

Placental mosaicism

Question 9

Which genetic sampling method can be carried out from around 11 weeks gestation?

Answer 9

Chorionic villus biopsy

Question 10

Which genetic sampling method can be carried out from 16 weeks gestation?

Answer 10

Amniocentesis

Question 11

What is the problem with amniocentesis as a genetic sampling method?

Answer 11

Tissue quality can be poor

Question 12

Which genetic sampling method can be carried out from 8 weeks gestation, making it the earliest sample which can be done?

Answer 12

Maternal blood sample for foetal DNA

Question 13

Taking maternal blood for foetal DNA, or non-invasive pre-natal testing, is one of the earliest and most effective tests you can do.

What’s the problem with it at the moment?

Answer 13

Can only test for a limited number of genetic disorders

Question 14

Which percentage of embryos have chromosomal abnormalities?

Answer 14

40%

But 40% of embryos don’t result in miscarriage, so repair mechanisms must exist

Question 15

Which whole genome tests are commonly used pre-natally?

Answer 15

Array CGH

Foetal DNA from maternal blood

Next generation sequencing (NGS)

Question 16

Array CGH is a whole genome test used to detect (balanced / unbalanced) chromosome mutations.

Answer 16

unbalanced mutations

Question 17

Which targeted tests are commonly used pre-natally?

Answer 17

Point mutation testing

Quantitative fluorescent PCR (QF-PCR)

Question 18

What is the definition of a mutation?

Answer 18

Genetic change which causes disease

Question 19

What is the definition of polymorphism?

Answer 19

Genetic change which doesn’t cause disease on its own

Question 20

How many polymorphisms does a person have on average?

Answer 20

3 million

Question 21

Apart from genetic testing, how else can foetal abnormalities be discovered before birth?

Answer 21

Ultrasound scan

Question 22

When are foetal ultrasound scans typically carried out?

Answer 22

12 weeks

20 weeks

To check for structural abnormalities suggestive of congenital disease

Question 23

What measurement, made on foetal ultrasound, indicates whether or not a child has Down’s syndrome?

Answer 23

Nuchal thickness

Question 24

What is nuchal thickness?

Which disease is it used to diagnose?

Answer 24

Thickness of the skin on the back of a foetus’s neck

Seen during foetal ultrasound

Down’s syndrome

Question 25

After seeing clear **nuchal thickening** on **foetal ultrasound**, which genetic test would you use to diagnose **Down's syndrome?**

Answer 25

**Array CGH** Remember it detects **extra or missing chromosomes** - trisomy 21

Question 26

Apart from **array CGH**, what other genetic test could you use to diagnose Down's syndrome?

Answer 26

**Maternal blood for foetal DNA** **=\> Karyotype** (trisomy 21)

Question 27

What is **NIPT**?

Answer 27

**Non-invasive pre-natal testing** The use of foetal DNA from a maternal blood sample to diagnose genetic disorders

Question 28

What **percentage of maternal blood** contains some **foetal DNA?**

Answer 28

**10%** So not a huge amount to sample

Question 29

What is an **advantage of chorionic villus biopsy or amniocentesis** over NIPT?

Answer 29

**Can test for a greater number of disorders** **NIPT is currently limited to Down's syndrome**

Question 30

Which **genetic disorder** is commonly diagnosed using **NIPT?**

Answer 30

**Down's syndrome** Occasionally you can use it for other stuff like DMD

Question 31

Apart from diagnosing **genetic disorders**, what else can you use NIPT for?

Answer 31

**Sex determination** Is it a boy or a girl?

Question 32

\_\_\_ chromosome translocations are better than ___ ones.

Answer 32

**Balanced** is better than **unbalanced**

Question 33

In which case is an **unbalanced translocation** not as bad?

Answer 33

If it affects **sex chromosomes** e.g Turner's 45 XO, Klinefelter's 47 XXY These children are definitely symptomatic but not devastatingly so

Question 34

What is a **Robertsonian** **translocation**?

Answer 34

Some chromosomes are **acrocentric** i.e they only have one side, nothing after the centrosome In a Robertsonian translocation, an **acrocentric chromosome binds to the end of a normal chromosome** Producing an **unbalanced translocation**

Question 35

**Robertsonian translocations** increase your chances of inheriting what type of genetic disorder?

Answer 35

**Trisomy** Three copies of the same chromosome (even with an acrocentric chromosome stuck on the end) This is bad

Question 36

What does **aneuploidy** mean?

Answer 36

**Too few chromosomes** **Too many chromosomes**

Question 37

How would **array CGH** appear in a patient with a **balanced translocation?**

Answer 37

**Normal** Array CGH only detects unbalanced translocations

Question 38

What do **a) large** **b) small** **unbalanced translocations** cause in a foetus?

Answer 38

**a) Miscarriage** **b) Developmental delay** (severity ranging from mild to severe)