Strictural Chromosomal Abnormalities Flashcards
What are the different types of structural abnormalities?
Translocations
- reciprocal
- robertsonian
Deletion
Duplication
What is translocation?
The exchange of two segments between non-homologous chromosomes
Reciprocal or robertsonian
Describe how translocation can occur due to inappropriate Non-homologous end joining.
During non homologous end joining is a dna repair mechanism
Can get double strand breaks in DNA in a chromosome - separating chromosomes
We get two chromosomes with a mixture - derivative chromosomes form - translocation
When can balanced translocation be a problem?
Depending on what genes they effect
Eg. Chromosome 9 and chromosome 12 translocation forms a Philadelphia gene to form - triggers the oncogenic potential and can cause types of leukaemia
How are unbalanced individuals produced?
When 4 chromosomes form a tetravalent structure.
End up with a individual whose trisomic and monosomic with respect to the particular chromosomes that are effected by the translocation
What is the result of unbalanced reciprocal translocation?
Many lead to miscarriage
Learning difficulties, physical disabilities
Tend to be specific to each individual so exact risks and clinical features vary.
What are Robertsonian translocation?
When Two acrosentric chromosomes join near centromere with loss of p arms
Balanced carrier of robertsonian has 45 chromosomes (healthy)
If 46 chromosomes present including robertsonian then it must be unbalanced - clinical problems
P arm encodes RNA
Robertsonian 13;14 and 14;21 relatively common.
21;21 leads 100% to Down syndrome in fetus
Describe why a balanced carrier of robertsonian will be healthy?
This is because they have only one Robertsonian chromosome (AB)
And 2 intact chromosomes A and B with intact p arms
You only need one p arm to survive and encode the RNA required
How can trisomy 21 arise due to a robertsonian translocation?
You will have your 2 normal 21 chromosomes. Then on chromosome 14, you would have a mixture of chromosome 14 and 21 in one arm. Therefore contain the genetic information of 3, 21 chromosomes.
What are the outcomes of translocations?
- very difficult to predict
- some unbalanced outcomes may lead to spontaneous abortion of conceptus so early that it’s not seen as a problem
- some unbalanced outcomes may lead to miscarriage later on
- some may result in live-born baby with various problems
- only have approximate probability of producing possible gametes
What occurs during terminal deletion?
The loss of a telomeric chunk
As long as there is a new telomere added then it will continue
But there could be a potential loss of genes in the region of the lost telomere
What occurs during interstitial deletion?
Loss of a chunk of chromosome in the middle and telomere then rejoins to its chromosome
But genes in deleted chunk have been lost
Eg. DiGeorge syndrome
What are the effects of deletions in chromosomes?
May be terminal or interstitial
Causes a region of monosomy
Haploid sufficiency of some genes
Phenotype is specific for size and place of deletion
What is meant by contiguous gene syndrome?
When multiple unrelated clinical features occur in a patient and it’s suspected that multiple genes have been effected by this mutation.
What are the effects of micro-deletions?
Many patients have no abnormalities visible on metaphase spread
High resolution banding, FISH and now CGH showed micro deletion
Only a few genes may be lost or gained
Eg. DiGeorge
