MCGB - Chromosome Abnormalities

Question 1

What is cytogenetics?

Answer 1

Study of the genetic constitution of cells through the visualisation and analysis of chromosomes

Question 2

Give some reasons for cytogenetic analysis to be carried out.

Answer 2

• accurate diagnosis/prognosis of clinical problems
• better clinical management
• assess future reproductive risks
• prenatal diagnosis

Question 3

What are “constitutional abnormalities”?

Answer 3

They are a reason for referral for cytogenetic analysis - includes prenatal diagnosis, birth defects, infertility etc

Question 4

What are “acquired abnormalities”?

Answer 4

Also referral reason for cytogenetic testing - include leukaemias, solid tumours etc

Question 5

Give two prenatal diagnosis methods.

Answer 5

• chorionic villus sampling (11-12 weeks, 1.2% miscarriage risk)
• amniocentesis (15+ weeks, 0.8% miscarriage risk)

Question 6

Give some examples of birth defects that can be identified by prenatal screening.

Answer 6

Dysmorphism, congenital malformations, mental retardation, developmental delay, specific syndromes (eg. Downs, Williams, DiGeorge)

Question 7

What is the name of this procedure?

Metaphase chromosomes are stained, paired up and grouped together. Abnormalities are identified and described.

Answer 7

Karyotyping

Question 8

Give an example of a disorder caused due to trisomy.

Answer 8

Down’s syndrome (+21), Patau syndrome (+13), Edwards syndrome (+18)

Question 9

Give a disorder caused by monosomy.

Answer 9

Turner syndrome (only one X)

Question 10

What is polyploidy?

Answer 10

Gain of a whole haploid set of chromosomes, like trisomy but for entire set of chromosomes. Usually spontaneously aborts during pregnancy.

Question 11

What is the most common cause of polyploidy?

Answer 11

Polyspermy - fertilisation of an egg by more than one sperm.

Question 12

What is it called when chromosomes are “left behind” at cell division due to defects in spindle function?

Answer 12

Anaphase lag

Question 13

What is Edwards syndrome?

Answer 13

Trisomy 18. Usually only live 5-15 days, symptoms are rocker bottom feet, low-set ears, overlapping fingers, small lower jaw.

Question 14

What does trisomy 13 cause?

Answer 14

Patau syndrome

Question 15

What is Turner syndrome?

Answer 15

Occurs when girls are born with one functioning X chromosome. Symptoms include puffy feet, redundant skin at back of neck, short stature

Question 16

What is mosaicism?

Answer 16

Presence of 2 or more cell lines in an individual, usually caused by mitotic non-disjunction.

Question 17

Give some examples of cytogenetic structural abnormalities.

Answer 17

• translocations
• inversions
• deletions
• duplications
• insertions

Question 18

What are reciprocal translocations?

Answer 18

Exchange of material between two chromosomes, eg part of chromosome 4 breaks off and is swapped with part of chromosome 18.

Question 19

What is a Robertsonian translocation?

Answer 19

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

Question 20

What is the benefit of using a whole chromosome paint?

Answer 20

Can identify individual chromosomes even when they are rearranged.

Question 21

What does microarray comparative genomic hybridisation do?

Answer 21

Examines the whole genome at high resolution, comparing normal control DNA to patient DNA.

Question 22

Give an anvantage and a disadvantage of array CGH.

Answer 22

+ examines entire genome
+ targeted against known genetic conditions

• more expensive than karyotyping
• does not detect balanced re-arrangements