Chromosomal abnormalities 2 Flashcards
(39 cards)
Examples of structural abnormalities of chromosomes
-Translocations
-Reciprocal
-Robertsonian
-Inversion
-Deletion
-Duplication
Rings
Isochromosomes
-Microdeletions/
Microduplications
Steps involved in structural abnormalities arising in chromosomes
- Double strand DNA breaks
- Occur throughout cell cycle
- Generally repaired through DNA repair pathways
- Mis-repair leads to structural abnormalities
What is reciprocal translocation?
Exchange of two segments between non-homologous chromosomes
What is non homologous end joining(NHEJ) and how does it arise?
If there is a double stranded break, sometimes instead of being stuck back together appropriately, it finds another free end and sticks there
- Stuck to the wrong chromosome - Physical exchange between two non-homologous chromosomes - Happens if they are physically close to one another
What is translocation?
Translocation is where we happen to have two double strands breaks
What are translocation due to inappropriate NHEJ also known as?
Also known as balanced translocations
What is the key characteristic of balanced translocations?
The key characteristic is that there is no net gain or loss of genetic material – it’s all there, just in a different place
What chromosome is balanced translocation an example of?
Philadelphia chromosome
What is the Philadelphia chromosome involved in?
Involved in causing chronic myeloid leukaemia
Formation of balanced translocation in philadelphia chromosome
- Chr 9 has ABL proto-oncogene and Chr22 has BCR
- BCR has tendency for double stranded breaks
- Double stranded break causing exchange of material between 9 and 22
- Causes a fusion gene and results in ABL going from being proto-oncogenic to oncogenic
What is unbalanced translocation?
too much or too little of a particular chromosome
What are reciprocal translocations?
Exchange of two segments between non-homologous chromosomes
When is there deleterious phenotypes in reciprocal translocations?
deleterious phenotype if breakpoint affects regulation of a gene
What are carriers of balanced translocations at risk of?
Carrier of balanced translocation at risk of producing unbalanced offspring
What are individuals with unbalanced translocations at significant risk of?
Unbalanced individuals at significant risk of chromosomal disorder
How do you go from a balanced carrier to an unbalanced zygote?
Problems arise when gamete has one intact chromosome and one derivative chromosome
- Zygote will then have an extra copy of one part of the intact chromosome
- Becomes partially trisomic and partially monosomic
What is reciprocal translocations?
no loss or gain of material and so there’s often little consequence to the cell of carrying a reciprocal translocation
Steps involved in reciprocal translocation
SEE NOTES AND DIAGRAM
What is the clinical results of unbalanced reciprocal translocation?
- Many lead to miscarriage (hence why a woman with a high number of unexplained miscarriages should be screened for a balanced translocation)
- Learning difficulties, physical disabilities
What chromosomes do Robertsonian translocations involve?
Involve acrocentric chromosomes
-13, 14, 15, 21, 22
What is a robertsonian translocation
?
Two acrocentric chromosomes break at or near their centromeres
-The fragments are joined together again it’s possible for just the two sets of long arms to be brought together and there’s loss of the satellites
What is the most common robertsonian translocation?
Most common Robertsonian translocation involves chromosomes 13 and 14
What does the robertsonian translocation of chromosomes 13 and 14 result in and what does the resultant chromosome contain?
Results in loss of two short arms and fusion of the two long arms, with either one or two centromeres
-The resultant chromosome usually contains the long arms of different chromosomes
How many chromosomes does an individual who’s a balanced carrier involving a robertsonian translocation?
Balanced carrier has 45 chromosomes
