Topic: Genome Sequencing
Fragile X Syndrome is the single greatest genetic cause
of mental retardation in humans. You are a molecular neurologist hoping
to understand the nature of the disease in order to effect its ultimate
cure. The protein responsible for Fragile X Syndrome has long been known.
FMRP is a protein that affects the translation of 100's of mRNAs. You'd
like to know if there is one mRNA or perhaps a small subset of them that
is responsible for the disease symptoms.
One approach is to systematically disrupt the genes encoding the affected mRNAs. Such experiments with humans are currently frowned upon, so you have turned to mice. Unfortunately, FMRP-deficient mice turn out not to be the ideal system in which to study the basis of mental retardation. Mice are only subtly affected by the loss of the protein, and experiments are not easy to perform. Things are not going well.
Then one morning, you wake up and think Flies. Yes… flies. Fruit flies. People have been using the fruit-fly Drosophila as a model system for a hundred years. It is easy to do genetic manipulations and a great deal is known about the behavior and development of Drosophila. True, it might be difficult to detect mental retardation in a fruit-fly, but that question shows a certain want of feeling. You decide to go for it.
You obtain the FMRP sequence, use it to scan the Drosophila genome for a gene that encodes a similar protein, find it, clone it, mutate it, put the modified gene back into Drosophila, gain deep insight into the causes of mental retardation, and book a flight to Stockholm to pick up your Nobel Prize.
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The key point in this little tale is contained in this fragment "… scan the Drosophila genome for a gene that encodes a similar protein…". Having in hand the genome of Drosophila and hundreds of other organisms has made possible lines of inquiry that were unthinkable just a several years ago. Our goal today is to understand how genomic sequences are obtained and how they may be put to good use. First we'll search the Drosophila genome (as did the hero of our tale) for a gene encoding an FMRP-like protein. Then we'll examine the process of sequencing of the Drosophila genome. Understanding how the genome sequence was deduced may illuminate both the power and the limitations of the resource we have at our disposal.