20.01.17 Segregation of Structural Abnormalities Flashcards
What percentage of pregnancies miscarry
15-20%
Proportion of miscarriages with a chromosomal abnormally
50%
Percentage of women with 2+ miscarriages
2-5%
Common autosomal trisomies in miscarriages:
- 13 (95% will miscarry)
- 18 (95% miscarry)
- 21 (80% miscarry)
What is the recurrence risk following autosomal trisomy
1%. If there is recurrence, then likely due to gonadal mosaicism
5% of couples with recurrent miscarriage have
balanced rearrangements
Types of balanced rearrangements
- Translocations
- Inversions
- Insertions
What is a reciprocal translocation
- When 2 nonhomologous chromosomes exchange segments. Balanced if there is no loss or gain
- 1:500 frequency in general population
WHat happens to a reciprocal translocation during cell cycle
- At meiosis 1, a quadrivalent forms to achieve maximum homology, called a pachytene cross
- Distribution of 4 homologues to two daughter cell is determined by segregation
How many outcomes of segregation are there for reciprocal translocations
- 16 outcomes
- 2:2 segregation (6 outcomes)
- 3:1 segregation (8 outcomes)
- 4:0 (2 outcomes)
What are the different types of 2:2 segregation in reciprocal translocations
- Alternate: only mode leading to balanced or normal gametes
- Adjacent 1: non homologous centromeres travel together
- Adjacent 2: homologous centromeres travel together
What are the different types of 3:1 segregation in reciprocal translocations
- Tertiary trisomy: 2 normal, 1 derivative
- Interchange trisomy: 2 derivatives, 1 normal
In reciprocal translocations, when is 2:2 adjacent 1 more likely
When translocated segments are shorter than centric ones.
In reciprocal translocations, when is 3:1 adjacent 1 more likely
-When one of the derivative chromosomes is small
What is haploid autosomal length (HAL)
-Correlation of quantitative chromatin imbalance with risk of an abnormal live-born child
How do you calculate HAL (haploid autosomal length)
- Measure length of chromosome (mm)
- Measure length of imbalanced segment (mm).
- Determine % of imbalance for the chromosome
- Bear in mind chromosome dependent. Imbalances are less tolerated in G-band negative regions.
What is a Robertsonian translocation
- When 2 acrocentric chromosomes fuse at centromere
- Acrocentric chromosomes= 13, 14, 15, 21, 22.