Structural Chromosomal Abnormalities*

Question 1

What are some examples of structural abnormalities?

Answer 1

• Translocation
• Inversion
• Deletion
• Duplication
• Rings

Question 2

What are the two types of translocational abnormalities?

Answer 2

• Reciprocal and robertsonian

Question 3

What is translocation?

Answer 3

• Exchange of two segments between non homologous chromosomes

Question 4

What is the main reason translocation takes place?

Answer 4

Inappropriate non-homologous end joining (NHEJ)

Question 5

What is non-homologous end joining?

Answer 5

• DNA repair mechanism that repairs double stranded breaks by literally just sticking them back together

Question 6

How is a derivative chromosome created?

Answer 6

Broken bits of chromosome being stuck back on the wrong chromosome

Question 7

What is balanced translocation?

Answer 7

There is non-homologous end joining but because the net amount of DNA in a cell hasn’t changed, it doesnt matter

Question 8

What is the philadelphia chromosome?

Answer 8

Philadelphia chromosome is an exchange between Cr9 and Cr22

Question 9

What does the philadelphia chromosome cause?

Answer 9

• The activation of the oncogene nature of the gene

→ Leads to types of leukaemia and myeloma

Question 10

What is the philadelphia chromosome formed from?

Answer 10

Non-homologous end joining between a proto-onco gene on chromosome 9 and a gene on chromosome 22

Question 11

How are unbalanced individuals produced?

Answer 11

Tetravalent structure formed instead of a bivalent structure

Question 12

What is a tetravalent structure formed from?

Answer 12

Two normal chromosomes and two chromosomes that have undergone inappropriate non-homologous end joining

Question 13

What do unbalanced individuals cause?

Answer 13

Essentially trisomic for one end of the chromosome and monosomic at the other end

Question 14

What are the results of unbalanced reciprocal translocation?

Answer 14

• May lead to miscarriage
• Learning difficulties/physical difficulties

Very person-specific so clinical features vary

Question 15

Where is the only place robertsonian translocation can happen?

Answer 15

With acrocentric chromosomes that carry specific sets of copies of rRNA

Question 16

What happens if you loose chromosomes in robertsonian translocation?

Answer 16

Nothing

Question 17

What is a robertsonian chromosome?

Answer 17

Two chromosomes that can stick together with a single centromere

Question 18

How many chromosomes does a balanced carrier have?

Answer 18

45

Question 19

What has happened if there are 46 chromosomes including a robertsonian?

Answer 19

Unbalanced carrier

Question 20

What are the products of normal mitosis, reciprocal and robersonian?

Answer 20

• Normal - two bivalents
• Reciprocal - quadrivalent
• Robertsonian - trivalent

Question 21

What is a terminal deletion?

Answer 21

Loss of tetrameric chunks

Question 22

What is an interstitial deletion?

Answer 22

Loss of a chunk of chromosome in the middle of an arm

Question 23

What are some examples of interstitial deletions?

Answer 23

Prader-willi
Digeorge syndrome
Cri du chat

Question 24

What do deletions cause?

Answer 24

A region of monosomy

Question 25

Where are gross deletions seen?

Answer 25

Metaphase spread on G-banded karyotype

Question 26

Why do deletion/duplication events generally happen?

Answer 26

Unequal crossing over

Question 27

What are the steps of chromosome staining?

Answer 27

Blood sample taken Add phytohaemagglutinin and culture medium Culture at 37 deg celcius for 3 days Add colchicine and hypotonic saline Cells fixed Spread cells onto slide by dropping Digest with trypsin and stain with giemsa Analyse and karyotype

Question 28

What are the steps in fluorescent in situ hybridisation (FISH)?

Answer 28

Culture cells and metaphase spread Add fluorescent probe Denature probe and target DNA Mix probe and target DNA Probe binds to target

Question 29

What are the components of PCR?

Answer 29

Template Primers Polymerase Nucleotides Buffer MgCl2

Question 30

What is non-invasive prenatal testing?

Answer 30

Taking fetal DNA from maternal blood