Abstract
This chapter presents a broader view of the state of human disease modeling in Drosophila melanogaster and discusses new directions in the study of the genetic basis of human disorders in flies. The Drosophila classical genetics powerhouse, in combination with rapidly developing genomic and postgenomic tools, accelerates the identification and characterization of gene networks. Because the molecular mechanisms controlling a variety of physiological pathways are largely conserved between flies and humans, flies are quite useful in modeling a variety of human diseases. These include nervous system disorders, cancer, immune responses, elements of the cardiovascular system, and many more. Possibly the most successful area of human neurological disease modeling in Drosophila is the models of polyglutamine tract repeat disorders. The fly eye is an excellent readout for polyglutamine tract repeat disorders, like such as Huntington's disease and the spinocerebellar ataxias. In both conditions, there is a critical threshold of polyglutamine repeats that must be reached before a clinical presentation is observed. In flies, the expression of the human Huntingtin protein or the SCA3/MJD protein, containing the clinically relevant number of repeats, leads to the degeneration of photoreceptor neurons.
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