L15 - Structural Chromosomal Abnormalities

Question 1

State 3 types of structural chromosomal abnormalities?

Answer 1

• Translocations
• deletions
• Duplications

Question 2

What is a translocation?

Answer 2

Exchange of 2 segments between non - homologous chromosomes

Question 3

How can translocation occur?

Answer 3

Inappropriate non-homologous end joining
Sometimes, when parts of chromosomes break off, a a DNA repair mechanism called end joining joins them back together.
However sometimes this goes wrong, and the mechanism instead attaches the chromosome onto another chromosome. This forms derivatives

Question 4

What is the result of unbalanced reciprocal translocation?

Answer 4

• miscarriage
• learning difficulties
• physical disabilities

Question 5

What are the 2 types of translocation?

Answer 5

reciprocal

robertsonian

Question 6

What is Robertsonian translocations?

Answer 6

They involve just the acrocentric chromosomes.
Sometimes the little p arms are cut off from 2 chromosomes and then the q arms of the acrocentric chromosomes are stuck together.
Balanced carrier has 45 chromosomes and is healthy
Unbalanced carrier has 46 chromosomes

Question 7

What is the difference between a terminal deletion and an interstitial deletion?

Answer 7

terminal deletion is the loss of a telomeric chunk at the end of a chromosome, whereas interstitial deletion is the loss of a chunk in the middle of a chromosome

Question 8

What is a microdeletion?

Answer 8

deletion of small region of DNA on chromosome

many patients have no abnormality visible on the metaphase spread

Question 9

How do deletions occur?

Answer 9

Due to unequal crossing over.

Exchange of genetic material between chromosomes, but the chromosomes have not aligned properly

Question 10

What are some prenatal sources where a sample can be taken from?

Answer 10

• amniocentesis
• chorionic villus sampling
• cell free fetal DNA

Question 11

What are some postnatal sources where a sample can be taken from?

Answer 11

• blood

- saliva

Question 12

What is G-banding?

Answer 12

The most common type of chromosomal staining

G = a chemical called Giemsa

Question 13

Why are bands shown in chromosomal staining like G-banding?

Answer 13

Bands are due to the different types of chromatin present
Euchromatin is lossely packed and stains light
Heterochromatin is tightly-packed and stains darker

Question 14

How is blood used to karyotype?

Answer 14

sample of venous blood is taken
phytohemagglutinin and culture medium is added.
it is cultured at 37 degrees for 3 days
Then colchicine and hypotonic saline are added.
Cells are stopped in the metaphase stage and fixed
cells are spread onto the slides by dropping
They are then digested with trypsin and stained with giemsa
Metaphase spread is then analysed and karyotyped

Question 15

What is G-banding used for?

Answer 15

only detects aneuploides, translocations or large deletions - cannot detect small abnormalities.

Question 16

What is FISH used for?

Answer 16

only detects aneuploides, translocations or large deletions - cannot detect small abnormalities.

Question 17

What technique can be used to detect small chromosomal abnormalities?

Answer 17

Array comparative genomic hybridisation

Question 18

How is Array comparative genomic hybridisation performed?

Answer 18

patient DNA labelled green and control DNA labelled red and they are applied to the microarray
the 2 DNAs compete to attach to the microarray
the microarray scanner measures the fluorescent signals
The computer software then analyses the data and generates a plot

Question 19

What is QF-PCR and what is it used for

Answer 19

Quantitative fluorescence PCR
used to detect trisomies 13, 18, 21
uses primers for microsatellites that are known to be on chromosome
data shown in peaks where the X axis is the size of DNA and the Y axis shows the fluorescence intensity.
2 peaks = disomic
3 peaks = trisomic

Question 20

What is NIPT?

Answer 20

Non invasive pre-natal testing 
takes fetal DNA from maternal blood sample
cell free fetal DNA 
allows for trisomy testing
screening not diagnostic