Chromosomes

Question 1

Which of the following most accurately describes an individual with the karyotype: “45,X”

Answer 1

Female with Turner syndrome

Question 2

What type of tissues types can be cultured?

Answer 2

– Blood – T-lymphocytes
– Skin / Umbilical cord / Placenta
– Bone marrow
– Solid tumour
– Amniotic fluid / Chorionic villus

Question 3

Chromosome abnormalities

Answer 3

Numerical

Structural

Question 4

Numerical

Answer 4

– Trisomy: a condition in which an extra copy of a chromosome is present in the cell nuclei, causing developmental abnormalities.
-47,XX,+21 (down syndrome)
–47, XX, +18 (Edwards syndrome)
- 47, XX, +13 (Patau syndrome)

– Monosomy: the absence of one member of a pair of chromosomes
-45,X

–Polyploidy: have more than one pair of chromosomes -69,XXY

Question 5

Structural

Answer 5

– Translocation t(1;2)(q24;p12)
– Inversion inv(7)(q11q21)
– Duplication dup(11)(p14p15)
– Deletions del(22)(q11q12)

Question 6

Frequency of chromosome abnormalities

Answer 6

• Overall : 1 in 200
• Trisomy 21: 1 in 700
• Trisomy 18: 1 in 3000
• Trisomy 13:
• 47,XXY:
• 47,XXX:
• 45,X:
1 in 5000
1 in 1000 male births
1 in 1000 female births
1 in 2500
• Balanced translocation: 1 in 500
• Unbalanced (products, deletion etc):1 in 2000
• Inversion: 1 in 1000

Question 7

Sex chromosome abnormalities

Answer 7

47, XXY Klinefelter

47, XXX Triple X

47, XYY

48, XXYY or 48, XXXY

45, X Turner

Question 8

Karyotype

Answer 8

‘Normal’ karyptype: 46, XX or 46,XY

Question 9

Structural

Answer 9

Reciprocal translocation
Segregation of a 2/18 translocation
Roberstonian translocation
Unbalanced rearrangements- deletion 5p “Cri Du Chat”
Deletion 15q- Prader Willi/Angelman syndrome

Question 10

F.I.S.H

Answer 10

Fluorescence

In

Situ

Hybridisation

Question 11

What are fluorophores used for

Answer 11

Added to DNA

They are hybridised directly to the chromosome preparation or interphase nuclei

Question 12

FISH and cytogenetics

Answer 12

We can “count” chromosomes in interphase nuclei

• We can look for submicroscopic deletions using locus specific probes

• We can interprete abnormalities more clearly

• We can look for specific rearrangements such as gene fusions etc in acquired abnormalities

Question 13

Microarrays

Answer 13

• A new technology

• Improves the resolution for detection of cytogenetic abnormalities

• G-band resolution 5-10Mb

• But microdeletions can be ~3Mb

• Arrays - there are different types but resolution is <1Mb (~200kb)

Question 14

Microarrays

Answer 14

• As patients are screened by microarrays we are contributing to a database of cytogenetic and phenotypic abnormalities

• “New” microdeletion/duplication syndromes are being proposed

Question 15

Constitutional

Answer 15

Occur at gametogenesis

Affects all cells of the body

Heritable

Question 16

Acquired

Answer 16

changes occur during lifetime

restricted to malignant tissue

not heritable

Question 17

Role of Cytogenetics

Answer 17

• Confirmation of malignancy

• Classification of a disease type

• Prognosis

• Monitoring

Question 18

Non random changes

Answer 18

• Close association with disease sub-type
• Association with clinical feature
• Association with lineage
• No specific association
• Apparent multiple association

Question 19

Fusion genes/ hybrid genes

Answer 19

breakpoints occur within the two genes involved.

Fusion creates a hybrid gene which gives rise to a chimaeric protein.
eg t(9;22)(q34;q11)

Question 20

Deregulation

Answer 20

juxtaposition of gene to a regulating gene (eg IgH).

Altered regulation can result in increased transcription and neoplastic growth (cells divifing more than they should).
eg t(8;14)(q24;q32)

Question 21

Chronic Myeloid Leukaemia

Answer 21

> 90% of patients show: t(9;22)(q34;q11)
ABL gene on 9q & BCR gene on 22q

• 5% of patients have rearrangement of BCR/ABL not seen cytogenetically, but detectable by FISH

Question 22

SUMMARY

Answer 22

Cytogenetics can look for constitutional abnormalities

• These can be prenatal and postnatal, numerical or structural, balanced or unbalanced

• Cytogenetics can look for acquired abnormalities for confirmation and diagnosis of malignancy

• FISH is routine and can provide quick results without the need to look at chromosomes or provides more “detailed” information

• Arrays investigate the genome at a higher resolution than possible by microscopy.