19. Chromosome Abnormalities Flashcards
What are the possible causes of cytogenic structural abnormalities?
Translocations, inversions, deletions, duplications, insertion, rings, marker chromosomes, isochromosomes.
How do reciprocal translocations occur?
A two break rearrangement - there’s a break in one chromosome and a break in another and the two segments swap over.
What gametes are a result of carriers of reciprocal translocations?
Either balanced or unbalanced (abnormal phenotype).
Decode the following karyotype: 46,XY,t(2;18)(q12;q22).
Male, with a translocation of break points on chromosome 2 and 18 respectively on their q/long arms.
What are the balanced and unbalanced segragation types of meiotic disjunction?
Balanced - alternate
Unbalanced - adjacent 1 (non homologous centromeres), adjacent 2 (homologous centromeres), 3:1 disjunction and 4:0 disjunction.
How are unbalanced segregant outcomes assessed?
The likely segregation is established. The imbalance is looked up to see if it’s been reported before in the literature. The risks are then quotes if they have been established.
What is Robertsonian translocation?
Two acrocentric chromosomes fused together. There is a chromosome count of 45 as an unstable trivalent is formed at meiosis. So there is an aneuploidy risk.
Of the following, which are viable and which are not?
Trisomy 14, trisomy 21, monosomy 14 and monosomy 21.
Viable - monosomy 14, monosomy 21 and trisomy 21
Non-viable - trisomy 14.
What causes deletions?
Uneven pairing and recombination in meiosis.
What is the difference between terminal and interstitial deletions?
Terminal deletions are at the ends of chromosomes but interstitial deletions are within the chromosome.
What is needed to confirm a micro deletion?
FISH technique.
How are abnormal results from karyotyping reported?
The correct ISCN is given and then the abnormality is described in words and related to a clinical problem. A parental or family sample is taken if required and they’re referred to clinical genetics. Appropriate literature is provided for the clinician if available.
What is Fluorescent in situ hybridisation?
A molecular cytogenic technique that allow very specific questions to be answered using probes for specific chromosomes or loci.
How is FISH performed?
The DNA probe and target material and added together then denatured and hybridised. It undergoes stringency and then goes to washing to remove unbound probes. The results can then be visualised.
What are the four FISH probe types?
For microdeletion syndromes:
Locus/gene specific probes - small dots on specific regions
Telomere probes - individual ones of the short and long arms.
For identification of the chromosome of origin:
Centromere probes - hybridise to the individual centromeres (not for acrocentric chromosomes)
Whole chromosome paints - to identify a chromosome in rearrangement.
When are centromere probes used in FISH?
In metaphase and interphase for copy number analysis.
What can whole chromosome paints be used for?
Identification of individual chromosomes even when they’re rearranged.
What are locus specific probes used for in FISH?
For microdeletion/duplication syndromes. Often used to rule out DiGeorge (immune problems) before surgery.
What do prenatal aneuploidy screenings do?
They test for common aneuploidies in 24-48 hours.
Why are prenatal aneuploidy screenings chosen over PND?
They take a lot less time - 1-2 days rather than up to 14 days.
How do Vysis Aneuvysion probes work?
There is one single microscope slide but two distinct areas with uncultured amniotic fluid. There is one probe for each area. 30 cells are scored by 2 blinded analysts.
What is microarray methodoloy?
Examining the whole genome at high resolution using the patients’ DNA rather than chromosomes. Only used for comparison of copy numbers.
How is microarray performed?
Equal amount of patient (green) and reference (red) DNA are mixed with COT-1. This is added to an array slide spotted with oligonucleotides and hybridised for 48 hours. The slide is then washed and scanned, the scanned images are put into an analysis software.
What do the results of microarrays suggest?
If it’s yellow, then it’s normal. If there are not equal amounts of red and green, then it’s abnormal. More red means deletion of test DNA and more green means duplication of test DNA.
