Cytogenetic abnormalities Flashcards
What numerical chromosome abnormalities are there?
- Aneuploidy= gain (trisomy) or loss (monosomy)
- Polyploidy= gain whole sets (triploidy or tetraploidy)
- Mosaicism= diploidy& aneuploidy
What are the origins of numerical abnormalities?
- Gametogenesis
- Fertilisation
- Early cleavage
Describe errors occur at gametogenesis
- inc maternal age= inc aneuploidy
- inc paternal age= no significant risk
What is non-disjunction and when does it occur?
- Failure of chromosome or chromatid separation
- Meiosis 1 =80-90% chromosome non-disjunction
- Meiosis 2= chromatid non-disjunction
- common aneuploidies are often a result of this
What are the origins of triploidy?
- 1dad + 2mum =Digyny
- 2dad + 1mum=Diplospermy
- 2 separate sperm + 1mum= Dispermy
What errors can occur at fertilisation?
- Polyploidy (usually triploidy)
- Molar pregnancy (double paternal no maternal)
What are types of balanced rearrangement?
- Translocation (Reciprocal, Robertsonian)
- Inversion (Pericentric, Paracentric)
- Insertion
What is reciprocal translocation?
- Part of one gene is broken and exchanged for part of another gene
- reproductive risk
- small phenotype risk
When would you:
- Gain/loose a single chromosome
- Gain/loose a whole chromosome set
- Gain/loose during mitosis
- Single= Meiosis
- Set= Fertilisation
- Mitosis= Post-fertilisation
What is a molar pregnancy and its consequences?
1dad+ 0mum= haploid zygote
- copies itself to form diploid zygote= double paternal genome
- Massive cystic placenta no foetus
What errors can occur at early cleavage?
-Mosaicism-mitotic non-disjunction
Chromosomes 21 and 22 are examples of _______ chromosomes?
Acrocentric
How is autosomal aneuploidy linked to maternal age?
- Age-dependant deterioration of meiotic structures (hormonal imbalance, oral contraceptives)
- Unfavourable chiasmata distribution
Describe sex chromosome aneuploidy
- No age related risk
- Phenotype less severe than autosomal
- Turner’s syndrome (45X)
- Klinefelter’s syndrome (47XXY)
What outcomes occur from double paternal or maternal? What can we conclude from this?
- DP= large placenta, some growth delay
- MP=tiny placenta, signif growth delay, head-saving macrocephaly
- Maternal genome for foetus -Paternal genome for placenta
What is inversion?
- 2 breaks then rotation and rejoining
- small phenotype risk
- reproductive risk
- Pericentric= swap to opposite sides of centre
- Paracentric= swap on the same side of the centre
What are unbalanced rearrangements?
- Deletions& duplications
- copy number variation
- several genes
- mostly sporadic
What is robertsonian?
- Whole arm fusion
- Acrocentrics
- Reproductive risk
- No phenotype risk
What are consequences of mosaicism?
- Variable phenotype
- Variable lethality foetus
- Non-identical twin
- Tissue-specificity=lateral asymmetry
- May generate uniparental disomy
- Recurrence risk
What types of deletions are there?
- Interstitial deletion= within the chromosome
- Terminal deletion= at end of a chromosome
