Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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Recent progress in using Drosophila as a platform for human genetic disease research

  • Wan Hee Yoon (Aging and Metabolism Research Program, Oklahoma Medical Research Foundation)
  • Received : 2023.11.19
  • Accepted : 2023.12.04
  • Published : 2023.12.31
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Abstract

As advanced sequencing technologies continue to uncover an increasing number of variants in genes associated with human genetic diseases, there is a growing demand for systematic approaches to assess the impact of these variants on human development, health, and disease. While in silico analyses have provided valuable insights, it is essential to complement these findings with model organism studies to determine the functional consequences of genetic variants in vivo. Drosophila melanogaster is an excellent genetic model for such functional studies due to its efficient genetic technologies, high gene conservation with humans, accessibility to mutant fly resources, short life cycles, and cost-effectiveness. The traditional GAL4-UAS system, allowing precise control of gene expression through binary regulation, is frequently employed to assess the effects of monoallelic variants. Recombinase medicated cassette exchange or CRISPR-Cas9-mediated GAL4 insertion within coding introns or substitution of gene body with Kozak-Gal4 result in the loss-of-function of the target gene. This GAL4 insertion strategy also enables the expression of reference complementary DNA (cDNA) or cDNA carrying genetic variants under the control of endogenous regulatory cis elements. Furthermore, the CRISPR-Cas9-directed tissue-specific knockout and cDNA rescue system provides the flexibility to investigate candidate variants in a tissue-specific and/or developmental-timing dependent manner. In this review, we will delve into the diverse genetic techniques available in Drosophila and their applications in diagnosing and studying numerous undiagnosed diseases over the past decade.

Keywords

Acknowledgement

W.H.Y. is supported by Oklahoma Medical Research Foundation (OMRF), the National Institute of Neurological Disorders and Stroke (5R01 NS121298-03) of the National Institutes of Health (NIH), and Oklahoma Center for Adult Stem Cell Research (241006).

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