Structural Chromosomal Abnormalities Flashcards
Reciprocal Translocation:
What causes it?
What occurs when it’s Balanced?
What is its occurs when it’s Unbalanced?
What can an Unbalanced translocation lead to?
- Due to inappropriate non-homologous end-joining - type of DNA repair mechanism where chromosome “breaks” and separates for a non-homologous chromosome to attach (homologous one is meant to attach)
- Sections of 2 chromosomes have switched places
- If either parent carries a balanced translocation, their child can inherit an unbalanced translocation in which there is an extra piece of one chromosome and/or a missing piece of another chromosome.
- Miscarriage, Learning/Physical disabilities, and tend to be specific to each individual
Robertsonian Translocation:
What causes it?
How many chromosomes will they have if they’re a balanced carrier of this?
How many chromosomes will they have if they’re an UNbalanced carrier of this?
- 2 Acrocentric chromosomes join at centromere with loss of p arms
- 45 chromosomes
- 46 chromosomes
Types of Deletion?
What does a deletion cause?
How are Microdeletions detected?
Cause for deletions?
- Terminal or Interstitial
- Region of monosomy = Haploinsufficiency in some genes
- High-resolution banding, FISH and CGH, but not detectable on Metaphase spread
- Due to unequal crossing over; exchange of genetic material but the homologous pairs aren’t aligned
Anueploidies:
What is DiGeorge syndrome? Features?
What is William’s syndrome? Features?
- 22q11
• Cardiac abnormalities, Cleft palate, Hypocalcemia, Immune deficiency, Developmental delay, Intellectual disability - 7q11
• Supravalvular aortic stenosis, Intellectual disability, Hypercalcemia
What are the 2 sources of sampling for chromosomal analysis? Examples
Chromosome Staining:
What is it?
Which chromosomes does it use? Why?
What is this used to look for?
Why does it take several days to get results?
- • Prenatal; Amniocentesis, Chorionic Villus sampling,
• Postnatal; Blood, Saliva - Most common is G(Giemsa)-banding, where differing bands Euchromatin and Heterochromatin form
- Metaphase chromosomes as they’re tightly condensed and easy to see
- Aneuploidies, Translocations, Large deletions
- Blood has to be cultured
FISH:
What does it stand for?
How does the Hybridisation work?
What does it require?
What is the Flourescent Probe?
How does it work?
What is this used to look for?
- Fluorescent In Situ Hybridisation
- Single-stranded nucleic acid binds to a new single-stranded nucleic acid strand e.g. DNA→DNA or DNA→RNA
- Metaphase spread, Fluorescent probe
- Single-stranded DNA/RNA tagged with a fluorescent molecule
- Denature probe and target DNA (double to single strand), then mix both together for probe to bind to its SPECIFIC DNA SEQUENCE
- Aneuploidies, Translocations, Large deletions
aCGH:
What does it stand for?
How does it work?
What is it used to look for?
- Array Comparative Genomic Hybridisation
- Patient and Control DNA are labelled with fluorescent dyes and put in a microarray
- Both DNA’s compete to hybridise/attach to the microarray
- Microarray scanner measures fluorescent signals
- Patient and Control DNA are labelled with fluorescent dyes and put in a microarray
- Microdeletions, Microduplications
qf-PCR:
What does it stand for?
What is it used to diagnose?
What does it use? How are they detected?
Result if homozygous?
Result if heterozygous?
- Quantitative Fluorescence PCR
- Trisomy’s 13, 18, 21
- • Microsatellites on specific chromosomes; Short repeated sequences
• DNA is isolated, primers are formed, PCR used to amplify and gel electrophoresis carried out - 1 high signal peak
- 2 lower signal peaks
Antenatal Testing:
When during pregnancy is it carried out?
What else can be offered if patient is at high risk?
NIPT:
What does it stand for?
What sample is used?
What does it test for?
- First Trimester (just screening, no diagnosis)
- Invasive test (Chorionic Villus Sampling/Amniocentesis) or Non-Invasive test (NIPT)
- Non-invasive Pre-natal Testing
- Cell-free fetal DNA from a maternal blood sample
- Trisomy
