downs and xxy

8/2/2019 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.

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