Chromosome Pathology Flashcards
How do chromosomal changes produce an abnormal phenotype? From commonest to rarest
- Dosage effect
- Disruption of a gene at a breakpoint
- Position effect
- Unmasking of a recessive disorder
What is ‘dosage effect’?
The number of copies of a particular gene present in a genome –> loss is usually worse than gain
What is ‘position effect’?
The effect on the expression of a gene when its location in a chromosome is changed, often by translocation
What is copy number variation?
When the number of copies of a particular gene varies from one individual to the next. There is a huge spectrum of sizes that can be lost or gained: - A whole chromosome (100 million base pairs) - All the way down to 1 base pair
![](https://s3.amazonaws.com/brainscape-prod/system/cm/323/429/154/a_image_thumb.png?1602246502)
Techniques used to detect different types of copy number variations:
Ranges from G-banding (larger additions/losses) down to Sanger sequencing (smaller additions/losses)
![](https://s3.amazonaws.com/brainscape-prod/system/cm/323/429/164/a_image_thumb.png?1602246610)
What are the types of CNV?
- Chromosome number
- Aneuploidy
- Polyploidy
- Chromosome structure
- Deletion
- Duplication
- Mosaicism
What is aneuploidy?
The presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes
What is the most common type of aneuploidy?
Trisomy - there is an extra chromosome.
Examples:
- Trisomy 21 (Down syndrome)
- Trisomy 13 (Patau syndrome)
- Trisomy 18 (Edwards syndrome)
What is monosomy?
Another type of aneuploidy in which there is a missing chromosome.
Example:
- Turner syndrome - a female has a missing or damaged X chromosome.
What is polyploidy?
Polyploidy is a chromosomal mutation in which a cell has entire extra sets of chromosomes (the cells of an organism have more than two paired sets of chromosomes)
LETHAL
What is mosaicism?
Mosaicism is when a person has 2 or more genetically different sets of cells in his or her body. A person with mosaicism may have some cells in his or her body with 46 chromosomes. But other cells have 47 chromosomes.
How does maternal/paternal age affect aneuploidy?
Aneuploidy dramatically increases as women age (higher risk of having Down Syndrome baby the older you get)
Little or no paternal age effect
How does aneuploidy arise?
Errors in meiosis –> non-disjunction
What is non-disjunction?
Failure of homologous chromosomes or sister chromatids to separate during cell division (meiosis), so that both chromosomes go to one daughter cell and none go to the other.
- This can arise from meiosis I (80-90%) or meiosis II (10-20%)
![](https://s3.amazonaws.com/brainscape-prod/system/cm/323/430/305/a_image_thumb.png?1602248184)
How does non-disjunction in meosis I differ from meosis II?
Meiosis I: failure of separation of homologous chromosomes
Meisosis II: failure of separation of sister chromatids
Nondisjunction results in daughter cells with abnormal chromosome numbers (aneuploidy)
![](https://s3.amazonaws.com/brainscape-prod/system/cm/323/430/691/a_image_thumb.png?1602248770)
Results of non-disjunction:
Disomic + normal –> fetal trisomy (may be viable)
Monosomic + normal –> fetal monosomy (lethal)
![](https://s3.amazonaws.com/brainscape-prod/system/cm/323/431/360/a_image_thumb.png?1602248877)
Presentations of Trisomy 21?
Down syndrome
Heart malformations
Learning difficulties
Gut atresias
Early dementia
Leukaemia
1/700
Presentations of Trisomy 13?
Patau Syndrome
Microcephaly
Holoprosencephaly
Clefting
Polydactyly
1/5000
Presentations of Trisomy 18?
Edwards syndrome
Microcephaly
Growth retardation
Rocker-bottom feet
Clenched hands
Cardiac anomalies
1/5000
What are the only viable aneuploidies?
13, 18, 21