Drosophila melanogaster is a genetic model organism that has contributed to the discovery of numerous genes whose human homologues are associated with diseases. The development of sophisticated genetic tools to manipulate its genome accelerates the discovery of the genetic basis of undiagnosed human diseases and the elucidation of molecular pathogenic events of known and novel diseases. Here, we discuss various approaches used in flies to assess the function of the fly homologues of disease-associated genes. We highlight how systematic and combinatorial approaches based on recently established methods provide us with integrated tool sets that can be applied to the study of neurodevelopmental and neurodegenerative disorders.
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