Chromosomes 03.10.22 Flashcards
How cell types do we look at for genetic testing?
- blood
- skin
- bone marrow
- solid tumour
- amniotic fluid
How do we create a karyotype from a cell culture?
- start with our sample e.g. blood and add it to a culture medium containing PHA which stimulates cell division.
- sample then proliferates at a continuous temp of 37 degrees for 2-3 days
- then colcemid is added, this inhibits spindle fibre formation, which causes the cycle to stop
- then hypotonic solution is added, causing cells to swell
- then the cells are dropped onto a slide and they are fixed to spread nicely
- glass slides then stained which creates characteristic banding pattern
- then analysed on a software on a computer.
What are some examples of chromosome abnormalities?
Numerical:
- Trisomy (47, XX, +21) extra chromosome
- Monosomy (45, X) turner syndrome
- Polyploidy (69, XXY)
Structural
- Translocation t(1;2)(q24;p12) bits of chromosome swapped over
- Inversion inv(7)(q11q21) chromosome broken turned 180 degrees and fitted back in
- Duplication dup(11)(p14p15) tolerated better than deletion
- Deletion del(22)(q11q12) associated with learning difficulties and is the most common.
How frequent are chromosome abnormalities?
overall 1 in 200
What is Edwards Syndrome?
Trisomy 18. Extra 18 chromosome. Babies don’t leave hospital with it. Nothing distinctive in appearance
What is Patau syndrome?
Trisomy 13. Extra 13 chromosome. A lot of facial problems. Brain doesn’t separate into separate spheres. Normally have a single eye and single open nostril. Baby normally non-survivable in utero or short time after birth
What is Klinefelter syndrome?
47, XXY. Affects male with an extra X chromosome and they don’t go through puberty. No sperm so infertile. Tend to be tall and thin. No learning problems
What is turner syndrome?
45, X. Heart failure. Learning difficulties sometimes. Gynaecological issues
What is a reciprocal translocation?
When one bit of a chromosome sticks onto another chromosome. It is normally balanced so no loss in genetic material so the patient should not have any complications unless at fertilisation there is an unbalanced segregation; which would result in miscarriage and karyotype would be trisomy or monosomy.
What is robertsonian translocation?
Balanced nonhomologous is when an entire (for example) 21 chromosome attaches to the 14. So it is balanced as no loss in genetic material and it is nonhomologous as it is not between a homologous pair of chromosomes. Write it as 45 as there technically is a loss of a chromosome. The person is clinically well but high chance their children won’t be.
What is unbalanced rearrangements?
When there is a deletion. It is a survivable.
E.g. Deletion of 5p called cri du chat. Baby has unusually high cry.
E.g. deletion of 15q called Prader Willi (morbidly obese and learning difficulties) / Angelman syndrome (small, don’t learn to speak, severe seizures). Depends if the deletion is on the paternal (PW) or maternal (AS) copy. Known as imprinting.
How do we study chromosome deletions?
- F.I.S.H
- Fluorescence in situ hybridisation
- We use DNA probes labelled with fluorophores which we know will bind to a specific section of DNA due to complementary base pairings
- Label it with a coloured dye
- Can use it to check the dosage in a patient’s sample so if there is a deletion, no dot, or duplication there is 2
- not fullproof as we do not necessarily know what we are looking for and we have to count them so human error and interpretation.
What are microarrays?
- new technology
- improves the resolution for detection of abnormalities (deletions)
- You have a test card. Probes for every bit of genome added, dye then added, DNA added onto slide, if patient DNA doesn’t bind know u have a deletion, computer analysis
What are constitutional and acquired abnormalities?
Constitutional:
- occur at gametogenesis and affects all the cells of the body and it is heritable
Acquired:
- restricted to cancer and malignant tissue, not heritable. Can see if the cancer will be vulnerable to certain chemotherapies or other treatments
How can translocation lead to cancer?
sometimes a translocation can activate a gene which drives the formation of cancer
E.g. ABL gene on 9q & BCR gene on 22q drives leukaemia
