Downs and XXY
Transcript of Downs and XXY
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Downs Syndrome
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What is it?
Downs Syndrome is ananeuploidal, genetic disease
caused by 3 copies ofchromosome 21 in each cell.
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What are the
symptoms? Mental retardation
Stunted growth
Low muscle tone
Abnormal, juvenileproportions
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How does it
arise?Aneuploidy disorders happen
due to nondisjunction ofchromosomes in meiosis 1.
Once the gametes with (n+1)number of chromosomes fuse
with a gamete of nchromosomes, a zygote with
2n+1 chromosomes isformed.
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What makes Downs
so serious? The presence of an extra chromosome
means the presence of extra genes
These genes are then over-transcribedand subsequently over-translated intoproteins.
This leads to 1.5x the normal levels ofproteins on chromosome 21.
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Why are excess
proteins so bad? Not all of the proteins are detrimental.
The most important proteins areDSCR1 and DYRK1A DSCR1 affects the signalling pathways
for gene transcription by interacting withCalcineurin-A which stops critical genesneeded for growth being expressed.
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Why are there no
cures? Downs is difficult to treat because in
order to remove the symptoms, achromosome must be effectivelyremoved from every cell in the body.
Drugs that interfere with cell signallingpathways normally cause more harmthan good.
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47, XXY( Klinefelters
Syndrome)
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XXY is anotheraneuploidal disorder,but to do with the X sex
chromosome. Almost 1in 1000 men are XXY.
Once again, theproblem arises in
Meiosis stage 1 whereboth X chromosomes ina pair move into one
cell.
What is XXY?
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Symptoms of XXY
Sufferers of XXY have normal IQ andnormal growth
In a few cases, slight language difficultyhas been seen
Nearly all Klinefelters sufferers areinfertile.
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Why does Downs
present with so many
symptoms, butalmost none for
XXY?
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X Inactivation In every X chromosome is
a gene call Xistin a regionknow as Xic
When Xistis transcribed, itproduces ncRNA
This ncRNA wrapsaround the X
chromosome making itunreadable bytranscription enzymes.
The inactivated Xchromosome then staysinactivated after replication
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A possible way to
treat aneuploidy? Current research that if the Xistgene is placed on
another chromosome, that chromosome will become
inactivated.
If transplanted on to chromosome 21 by genetherapy, the extra chromosome may be inactivated,leading to normal gene expression
The main problem with this is that gene therapy isunreliable and as yet relatively ineffective, althoughthis is rapidly changing.