Structural Chromosomal Abnormalities Flashcards
What are some examples of structural abnormalities?
Translocation Inversion Deletion Duplication Rings Robertsonian
What are the two types of translocational abnormalities?
Reciprocal and robertsonian
What is translocation?
Exchange of two segments between non homologous chromosomes
What is the main reason translocation takes place?
Inappropriate non-homologous end joining
What is non-homologous end joining?
DNA repair mechanism that repairs double stranded breaks by literally just sticking them back together
How is a derivative chromosome created?
Broken bits of chromosome being stuck back on the wrong chromosome
What is balanced translocation?
There is non-homologous end joining but because the net amount of DNA in a cell hasn’t changed, it doesnt matter
What is the philadelphia chromosome?
Derivative chromosome 22
What does the philadelphia chromosome cause?
The activation of the oncogene nature of the gene
Leads to types of leukaemia and myeloma
What is the philadelphia chromosome formed from?
Non-homologous end joining between a proto-onco gene on chromosome 9 and a gene on chromosome 22
How are unbalanced individuals produced?
Tetravalent structure formed instead of a bivalent structure
What is a tetravalent structure formed from?
Two normal chromosomes and two chromosomes that have undergone inappropriate non-homologous end joining
What do unbalanced individuals cause?
Essentially trisomic for one end of the chromosome and monosomic at the other end
What are the results of unbalanced reciprocal translocation?
May lead to miscarriage
Learning difficulties/physical difficulties
Very person-specific so clinical features vary
Where is the only place robertsonian translocation can happen?
With acrocentric chromosomes that carry specific sets of copies of rRNA
What happens if you loose chromosomes in robertsonian translocation?
Nothing
What is a robertsonian chromosome?
Two chromosomes that can stick together with a single centromere
How many chromosomes does a balanced carrier have?
45
What has happened if there are 46 chromosomes including a robertsonian?
Unbalanced carrier
What are the products of normal mitosis, reciprocal and robersonian?
Normal - two bivalents
Reciprocal - quadrivalent
Robertsonian - trivalent
What is a terminal deletion?
Loss of tetrameric chunks
What is an interstitial deletion?
Loss of a chunk of chromosome in the middle of an arm
What are some examples of interstitial deletions?
Prader-willi
Digeorge syndrome
Cri du chat
What do deletions cause?
A region of monosomy
How can we see gross deletions?
Metaphase spread on G-banded karyotype
Why do deletion/duplication events generally happen?
Unequal crossing over
What are the steps of chromosome staining?
Blood sample taken Add phytohaemagglutinin and culture medium Culture at 37 deg celcius for 3 days Add colchicine and hypotonic saline Cells fixed Spread cells onto slide by dropping Digest with trypsin and stain with giemsa Analyse and karyotype
What are the steps in fluorescent in situ hybridisation (FISH)?
Culture cells and metaphase spread Add fluorescent probe Denature probe and target DNA Mix probe and target DNA Probe binds to target
What are the components of PCR?
Template Primers Polymerase Nucleotides Buffer MgCl2
What is non-invasive prenatal testing?
Taking fetal DNA from maternal blood
