Biochemistry L08 - Chromosome Separation & Apoptosis Flashcards
What is nondisjunction and what are the consequences? Which are the three most common chromosomes to mess up?
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division.
Nondisjunction leads to aneuploidy.
Chromosomes 13, 18 and 21 are the ones most often messed up
What is aneuploidy?
Aneuploidy is where one or more chromosomes of a normal set of chromosomes are either missing or present in more than their usual number of copies. This typically alters an organism’s shape and proportions.
For example, monosomics have only one chromosome and trisomics have 3.
What is aberrant euploidy?
Aberrant euploidy is the gain of one or more ENTIRE SETS of chromosomes. It usually results in increased size, but the same basic shape and proportions.
The ratio of anyone gene to another is always 1:1.
What is monoploidy?
Monoploidy is the loss of an ENTIRE SET of chromosomes (i.e. the opposite of euploidy).
What is the gene-dosage effect?
The amount of transcript a gene makes is proportional to the number of copies of that gene in a cell. So, the more copies of the gene, the more transcripts and the more protein is translated.
In monosomics, the amount of transcript is only 50%, whereas in trisomics it is 150%.
Why are the effects of monosomics more extreme than trisomics?
In monosomics, one chromosome is missing. This results in extreme abnormality due to the expression of any deleterious recessive allelles on the monosomic chromosome.
What causes Down’s Syndrome?
DS is usually caused by an extra chromosome 21, and is sporadic. This is trisomy (an extra chromosome).
Rarer forms result from translocation events (usually exchange of material between nonhomologous chromosomes 21 and 14)
What is apoptosis and why would it be turned on?
Programmed, sequential cell death in response to cellular abnormalities
What are the sequences in apoptosis?
- Fragmentation of Chromosomes
- Organelle Disruption - Organelle structure is disrupted and cell loses its shape
- Fragmentation of cell – the cell breaks up into small bodies called apoptotic bodies and are phagocytosed. Scavenger cells also recyclable useable parts i.e. amino acids
What are caspases and what is their role in Apoptosis?
Caspases drive apoptosis. They are normally present in cell as inactive zymogen (pre-curser protein waiting to be activated).
Zymogen is activated by proteolysis (cleavage). The active caspases target other proteins for destruction. Caspases cleave target proteins, and these target proteins initiate fragmentation of DNA, organelle disruption etc.
What are Initiator and Executioner Caspases?
Initiator caspases are cleaved in response to an activation signal. They in turn cleave on of the executioner caspases, which in turn cleaves another until all are active (cascade). Executioner caspases also cleave target proteins in the cell, hence driving apoptosis.
