Chromosome Abnormalities Flashcards
How long does it take the cell cycle to complete?
24 hours
What is used to culture t-lymphocytes?
Blood
Explain the endothelial cell culture process
Add the sample to culture medium which contains PHA (phytohaemagglutinin)
Leave the sample proliferate at 37°c for 48-72 hours
Then add colcemid ( drug that inhibits spindle formation in metaphase causing the cell cycle to arrest to get the maximum number of cells in metaphase )
Hypotonic solution is then added which causes the cells to swell
Cells are then dropped and fixed on a slide to allow the chromosomes to spread nicely
Slides are then treated by trypsin ( an enzyme that breaks down peptones into smaller peptides )
The trypsin digests the proteins and dyes them producing the characteristic banding patterns
The slides are then scanned and analysed on a software using computer technology ( karyotyping )
What is phytohaemagglutinin?
A plant derived alkaloid that stimulates t-lymphocytes to divide in the test tube
Chromosomal abnormality numerical (trisomy)
47, xx, +21
Chromosomal abnormality numerical (monosomy)
45,x
Chromosomal abnormality numerical (polyploidy)
69,xxy
Frequency of chromosome abnormalities (overall)
1 in 200
Frequency of chromosome abnormalities (trisomy 21)
1 in 700
Frequency of chromosome abnormalities (trisomy 18)
1 in 3000
Frequency of chromosome abnormalities (trisomy 13)
1 in 5000
What is nondisjunction?
A condition in which pairs of homologous chromosomes fail to separate during meiosis or a chromosome fails to divide at anaphase of mitosis or meiosis resulting in a cell with an abnormal number of chromosomes
How many births does down syndrome affect?
1/1000 births
Features of Down syndrome in childhood
Hypotonia
Developmental delay
Learning difficulties
Heart problems
Digestive problems
Distinctive facial features ( flat facial features, small head & ears, short neck, bulging tongue, epicanthic neck folds, atypically shaped ears )
Single palmar crease
Features of down syndrome in adulthood
Cataracts
Leukaemia
Obesity
Life expectancy ~ 60
What is F.I.S.H?
Label the probe with fluorochrome
Separate DNA to single stranded
Hybridise these probes onto the target DNA
Use a fluorescent microscope to light probe, we can count chromosomes in the nuclei and look for submicroscopic deletion using loci specific probes which we can identify abnormalities more clearly and look for specific rearrangements such as gene fusions in acquired abnormalities
What are constitutional abnormalities?
Occur at gametogenesis
Usually affect all cells in the body
Can be heritable
What a acquired abnormalities?
Change during a patients lifetime
Associated malignant changes generally restricted to malignant tissues
Not heritable
What is the role of cytogenetics in acquired abnormalities?
Confirmation of malignancy
Classification of a disease type
Prognosis
Monitoring
What is reciprocal translocation?
Occurs when part of one chromosome is exchanged with another
What can translocation cause?
Can disrupt functional parts of the genome and have implications for protein production with phenotypic consequences
What is robertsonian translocation?
The whole of a chromosome is joined end to end with another
What chromosomes are involved with robertsonian translocation, and why?
13,14, 15, 21 and 22
Because the ends of their short arms have similar repetitive DNA sequences that predispose to their fusion
What is Edward’s syndrome/Trisomy 18?
When babies have more of chromosome 18 in some or all of the cells in their body
What is Patau’s syndrome/Trisomy 13?
An additional copy of chromosome 13
What do cytogenetics do?
They look for constitutional abnormalities
What do micro arrays do?
They investigate the genome at a higher resolution than possible by microscopy
Which of the following most accurately describes an individual with the karyotype: “45,X”
Female with Turner syndrome
