Chromosomes Flashcards
Which of the following most accurately describes an individual with the karyotype: “45,X”
Female with Turner syndrome
What type of tissues types can be cultured?
– Blood – T-lymphocytes
– Skin / Umbilical cord / Placenta
– Bone marrow
– Solid tumour
– Amniotic fluid / Chorionic villus
Chromosome abnormalities
Numerical
Structural
Numerical
– 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
Structural
– Translocation t(1;2)(q24;p12)
– Inversion inv(7)(q11q21)
– Duplication dup(11)(p14p15)
– Deletions del(22)(q11q12)
Frequency of chromosome abnormalities
• 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
Sex chromosome abnormalities
47, XXY Klinefelter
47, XXX Triple X
47, XYY
48, XXYY or 48, XXXY
45, X Turner
Karyotype
‘Normal’ karyptype: 46, XX or 46,XY
Structural
Reciprocal translocation
Segregation of a 2/18 translocation
Roberstonian translocation
Unbalanced rearrangements- deletion 5p “Cri Du Chat”
Deletion 15q- Prader Willi/Angelman syndrome
F.I.S.H
Fluorescence
In
Situ
Hybridisation
What are fluorophores used for
Added to DNA
They are hybridised directly to the chromosome preparation or interphase nuclei
FISH and cytogenetics
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
Microarrays
• 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)
Microarrays
• As patients are screened by microarrays we are contributing to a database of cytogenetic and phenotypic abnormalities
• “New” microdeletion/duplication syndromes are being proposed
Constitutional
Occur at gametogenesis
Affects all cells of the body
Heritable
Acquired
changes occur during lifetime
restricted to malignant tissue
not heritable
Role of Cytogenetics
• Confirmation of malignancy
• Classification of a disease type
• Prognosis
• Monitoring
Non random changes
• Close association with disease sub-type
• Association with clinical feature
• Association with lineage
• No specific association
• Apparent multiple association
Fusion genes/ hybrid genes
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)
Deregulation
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)
Chronic Myeloid Leukaemia
> 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
SUMMARY
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.
