Chromosomal Abnormalities Flashcards
What are the 2 major types of numerical cytogenic abnormalities?
- Aneuploidy
- Polyploidy
What is aneuploidy?
Abnormal number of chromosomes in a cell due to loss/gain of whole chromosomes.
What are the 2 types of aneuploidy? Give clinical examples of each.
Trisomies
- Down syndrome (21)
- Edwards syndrome (18)
- Patau syndrome (13)
Monosomies
- Turner syndrome (45,X) - only full monosomy syndrome to be viable.
What are the effects of meiotic non-disjunction for zygotes?
Non-disjunction in meiosis I (100% screwed)
- 2 trisomic zygotes
- 2 monosomic zygotes
Non-disjunction in meiosis II (50% screwed)
- 2 OK zygotes
- 1 trisomic zygote
- 1 monosomic zygote
Suggest a cause for meiotic non-disjunction.
- Anaphase lag = chromosome can be “left-behind” at cell division because of defects in spindle function or attachment to chromosomes.
What is the result of mitotic non-disjunction during cell division in the zygote?
Mosaicism
What is polyploidy, and what is its most common cause?
- Gain of a whole haploid set of chromosomes, i.e. Triploidy 3n (69,XXX).
- Polyspermy.
Name 4 examples of cytogenic structural abnormalities.
- Translocations
- Deletions
- Duplications
- Inversions
What is the cause of chromosomal deletions and duplications?
Arise through uneven pairing and recombination.
- 2 gametes OK
- 1 gamete with duplication
- 1 gamete with deletion
What is the difference between balanced and unbalanced chromosomal rearrangements?
- Balanced = no loss of genetic information (e.g. In many inversions)
- Unbalanced = loss of genetic information
What are the 2 types of translocation?
- Reciprocal translocation
2. Robertsonian translocation
What are the causes for reciprocal and robertsonian translocations?
Reciprocal
- 2 break rearrangement (involving 2 chromosome ends breaking and switching)
Robertsonian
- q arms of 2 acrocentric chromosomes fuse together (loss of p arms)
- can involve homologous or heterologous fusion
What structure do reciprocal translocations form at meiosis 1 metaphase?
Quadrivalent (instead of bivalent)
Describe the types of segregation occurring in meiosis 1 of reciprocally translocated chromosomes.
- Alternate
- 1 normal balanced gamete
- 1 translocated balanced gamete - Adjacent 1 (non-homologous centromeres)
- 2 unbalanced gametes - Adjacent 2 (homologous centromeres)
- 2 unbalanced gametes
Is adjacent 1 or 2 segregation more likely to occur in reciprocal translocations?
- Adjacent 1.
- Adjacent 2 is very rare - causes large degree of imbalance.
What kind of structure is formed in metaphase of meiosis 1 in robertsonian translocations?
Trivalent (instead of divalent)
What kind of gametes are formed from a homologous fusion resulting in Robertsonian translocation?
Always results in trisomies as:
- 1 gamete gets the 2 fused homologs
- 1 gamete gets nothing - non-viable
What kind of gametes are formed from a heterologous fusion resulting in Robertsonian translocation?
Gametes will either contain
- 2 normal chromosomes: balanced
- fused chromosomes: balanced
- fused chromosome + 1 normal: unbalanced
- just normal chromosome: non-viable
What are uniparental disomies?
Presence of chromosomes from 1 parent only.
What are the different types of UPDs?
- Isodisomy: 2 identical chromosomes from 1 parent (error in meiosis II)
- Heterodisomy: 2 homologous chromosomes from 1 parent (error in meiosis I)
- Segmental UPD: only part of chromosome involved
- Acquired UPD: solid tumours and leukaemias
Why does UPD matter?
- Because of genomic imprinting: in some genes, only 1 allele is active depending on parent of origin (determined via epigenetics/methylation).
- Most genes aren’t imprinted so most UPDs have no effect. But a person with UPD may lack any active copy of a gene undergoing genomic imprinting - loss of gene function.
- Can lead to delayed development, intellectual disability, etc.
Give 3 examples of UPD syndromes.
- Prader-Willi syndrome
- uncontrolled eating and obesity
- UPD on chromosome 15 (loss of paternal chromo) - Angelman syndrome
- intellectual disability and impaired speech
- UPD on chromosome 15 (loss of maternal chromo) - Beckwith-Widemann syndrome
- accelerated growth and increased risk of cancerous tumours
- UPD on chromosome 11
Which 4 main mechanisms can generate UPD? Which is the most common?
- Trisomic rescue (most common)
- Gamete complementation
- Monosomic rescue (+ endoduplication)
- Postfertilisation error (+ endoduplication)
How likely is trisomic rescue to lead to UPD?
1/3
