Chromosomal abnormalities II Flashcards
(46 cards)
Structural abnormalities - list 7 types
Translocations - Reciprocal - Robertsonian Inversion Deletion Duplication Rings Isochromosomes Microdeletions/Microduplications
Describe formation of structural abnormalities
Double strand DNA breaks
Occur throughout cell cycle
Generally repaired through DNA repair pathways
Mis-repair leads to structural abnormalities
Reciprocal Translocations - define
Exchange of two segments between non-homologous chromosomes
So mechanism is called Non-Homologous End Joining (NHEJ)
Reciprocal Translocations - reason for its name = “non-homologous end joining”
The DNA repair mechanism is called “non-homologous end joining”: end joining because it’s joining together two ends and non-homologous because it’s irrespective of the DNA sequence joined together
These are also known as balanced translocations
Reciprocal Translocations - when
It’s thought that they form spontaneously during meiosis
Reciprocal Translocations - key characteristic
The key characteristic is that there is no net gain or loss of genetic material – it’s all there, just in a different place.
Reciprocal Translocations - which chromosomes involved
They can involve any chromosome and the fragments can be of any size
Reciprocal Translocations - incidence
They are relatively common – estimates suggest that they occur in 1 in 930 people
Balanced vs Unbalanced translocations
Balanced = have the right amount of each chromosome just maybe not in the expected place!
Unbalanced = too much or too little of a particular chromosome
Effect on carriers of balanced translocation - example
Philadelphia chr = abnormal chr22
Leads to Chronic myeloid leukaemia (CML)
ABL fuses w/BCR
BCR=breakpoint cluster region (Function of normal protein product not known)
ABL=protooncogene
Fusion of genes leads to an activated oncogene
Balanced translocation - define
Balanced translocation – no net gain or loss of material
Reciprocal Translocations - define
Exchange of two segments between non-homologous chromosomes
no loss or gain of material
Reciprocal Translocations - effect on phenotype
Usually no deleterious phenotype unless breakpoint affects regulation of a gene
Reciprocal Translocations - effect on carriers
Carrier of balanced translocation at risk of producing unbalanced offspring
Unbalanced individuals at significant risk of chromosomal disorder
How are unbalanced individuals produced?
Balanced carrier to unbalanced zygote
Consequences of reciprocal translocations
in meiosis
Chromosomes pair up before separating, form = pachytene quadrivalent = CS A + B with C + D (example)
CS separate along horizontal line, = one cell having a gain in A/B CS and a loss of the end of C/D CS;
the other daughter cell has a loss of the end of the A/B CS and gain of C/D
OR CS could separate along this vertical line
= an unbalance arrangement where, in each daughter cell, there is loss of one end of a chromosome and gain of the end of the other chromosome.
The exact consequences of inheriting a unbalanced rearrangement depend on what
The exact consequences of inheriting a unbalanced rearrangement depend on the particular chromosomes involved and the size of the translocated material.
Clinical result 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
Tend to be specific to each individual so exact risks and clinical features vary
Robertsonian translocation - define
When two acrocentric chromosomes break at or near their centromeres, when 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.
Robertsonian translocation - resulting number of CS
45
Robertsonian translocation - what is lost
The only genetic material we’ve lost are these satellites and the cell can do without those and so this isn’t a problem for the cell.
Robertsonian translocation - which CS effected
Only affect acrocentric chromosomes – ie. Those which have the centromere near the chromosome tip. These are chromosomes 13, 14, 15, 21 & 22
Robertsonian translocation - most common type + its result
Most common Robertsonian translocation involves chromosomes 13 and 14, which accounts for approximately 1/3 of all Robertsonian translocations
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
What’s the centromere?
It’s the part of the chromosome which attaches to the spindle during cell division.
