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An ideal organism might be Drosophila melanogaster, which is well understood,
has a short generation cycle and is very inexpensive and easy to work with. To find
out if there is a Drosophila melanogaster gene product similar to the Huntington
Disease gene product found in Humans, we can use the TaxPlot tool.
- Go to the TaxPlot site (http://www.ncbi.nlm.nih.gov/sutils/taxik2.cgi) and configure the
tool to compare the Homo sapiens genome proteins against the Drosophila
melanogaster and Mus musculus genome proteins.
- Enter the name of the Huntingtons Disease gene product, huntingtin, into the QUERY
box and click on the COMPARE button.
- Note that the result is 25 hits, or potential candidates. These are indicated by red
diamonds in the page scatter plot diagram (see FIG 8A).
- Scroll down the list of potential hits and note the huntington homologue listed (see
FIG 8B)
- Click on the Blast2Seq link at the right of the Drosophila listing to see the direct
comparison between the Human and Drosophila proteins.
- Similarly, click on the Blast2Seq for the Mouse protein.
- Note what is missing in the Drosophila product…there is no N-terminus Poly Q stretch
in the Drosophila protein. The poly Q is the region now known to cause the effects
seen in Huntingtons Disease
 FIG 8A: TaxPlot configured to search for Huntingtons Disease homologs in Drosophila
FIG 8B: Blast2Seq showing regions of similarity to Human huntingtin in Drosophila
FIG 8C: Blast2Seq showing regions of similarity to Human huntingtin in Mouse
The near identity of the Drosophila sequence to the Human sequence, except for
The N-terminus Poly Q region, suggests that it might be an ideal tool to test the role
of glutamine stretches in huntingtin by using molecular genetic techniques to add
Poly Q cassets into the gene and determine the effects in transfected Fruit Flys…
Drosophila as a model system for studying the role of huntingtin in neural degeneration
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