Mechanisms of Chromosomal Abnormality ✅ Flashcards
What is mitosis?
The process by which most cells replicate
What does mitosis result in?
The production of 2 identical daughter cells
What does each of the daughter cells from mitosis contain?
A diploid genome (46 chromosomes)
What is meiosis?
The process by which gametes are formed
What does meiosis involve?
2 successive cell divisions
What do the cells produced in meiosis contain?
Haploid genome (23 chromosomes)
Is cell division perfect?
No, errors do arise
What are the mechanisms of chromosomal abnormality?
- Non-disjunction
- Anaphase lag
- Mosaicism
- Chromosome translocations
- Reciprocal chromosome translocations
- Robertsonian translocations
Why do numerical chromosome abnormalities occur?
Generally because of non-disjunction during meiosis
What is non-disjunction?
When two paired chromosomes (in meiosis I) or two sister chromatids (in meiosis II) fail to separate and segregate into separate cells
What is the result of non-disjunction in meiosis?
The gametes will have either too many (24) or too few (22) chromosomes
What happens following fertilisation in a gamete with too many or too few chromosomes?
The zygote is either trisomic or monosomic for the relevant chromosome
Can an embryo be trisomic for every chromosome?
Yes
What happens if an embryo is trisomic for every chromosome?
Most will spontaneously abort
Does non-disjunction occur in men or women?
It can occur in either
What do most cases of trisomy seem to take place because of, in terms of non-disjunction?
Non-disjunction at meiosis I in the mother
Why do most cases of trisomy take place because of non-disjunction at meiosis I in the mother?
Due to this stage being very long in women - starting before birth, and ending at ovulation
What happens to the risk of Down syndrome with maternal age?
Increases, obviously.
1 in 1500 for 20 year old woman
1 in 30 for 45 year old woman
Are all aneuplodies affected by age?
Similar age-dependence for all aneuplodies except Turner’s syndrome
What is an aneuploidy?
The presence of abnormal number of chromosomes in a cell
By what mechanism does Turner’s syndrome occur?
Anaphase lag
What happens in anaphase lag?
One of the sex chromosomes (X or Y) moves too slowly to the pole of the daughter cell during cell division. It therefore ends up outside the nucleus, and is broken down
When can anaphase lag occur?
During meiosis, or during early mitotic divisions of the embryo
What does chromosomal mosaicism refer to?
The presence of two cell lines, with differing numbers of chromosomes in each, usually one normal and one abnormal
Give 2 examples of mosaic chromosomal disorders
- Mosaic Down’s syndrome (46 XX/47 XX+21)
- Mosaic Turner’s syndrome (45,X/46, XX)
What does mosaicism usually result in?
Milder phenotypes
How can mosaicism occur?
When the abnormal cell line arises post-zygotically
- When aneuploidy is present from conception, but some cells revert to normal karyocyte
Give an example of how aneuploidy can be present from conception, but some cells revert to normal karyotype?
Losing a copy of a trisomic chromosome - called trisomy rescue
When is a chromosomal translocation described as ‘balanced’?
When there is no net loss or gain of genetic material
When is a chromosomal translocation described as unbalanced?
If there is deletion or duplication of genetic material
Why are balanced translocations important to recognise?
They can result in transmission of an unbalanced chromosome translocation to the offspring
Can balanced translocations cause disease?
Occasionally
When can balanced translocations cause disease?
If a translocation breakpoint disrupts a disease gene
When do reciprocal chromosome translocations arise?
When any two chromosomes swap non-homologous segments
What might happen in a carrier of a reciprocal translocation?
They may potentially have offspring with trisomy of one of the translocated segments and monosomy of the other
What are Robertsonian translocations?
Translocations involving the ‘acrocentric’ chromosomes
Which chromosomes are acrocentric?
13 14 15 21 22 Y
What is an acrocentric chromosome?
One that has it’s centromeres close to one end
What happens in a Robertsonian translocation?
Inappropriate non-homologous recombination means that 2 acrocentric chromosomes join to form a single fusion chromosome with breakpoints on the short arm, just above the centromere
Why are balanced Robertsonian translocations important to recognise?
Because they may cause transmission of an unbalanced chromosome complement to offspring.
What happens if a child inherits an unbalanced Robertsonian translocation?
It causes trisomy or monosomy for the affected chromosome
What do the most frequently encountered Robertsonian translocations involve?
Chromosome 21
