Recent progress in using Drosophila as a platform for human genetic disease research

• 영문명: Recent progress in using Drosophila as a platform for human genetic disease research
• 발행기관: 대한의학유전학회
• 저자명: Wan Hee Yoon
• 간행물 정보: 『대한의학유전학회지』제20권 제2호, 39~45쪽, 전체 7쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2023.12.31

영문 초록

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.

목차

Introduction

Advantages of Using Drosophila As a Genetic Model for Studying Human Diseases

Determine the Impact of Monoallelic Variants Using GAL4-UAS System

Use of Null Alleles Created by Chemical and Transposable Element-Mediated Mutagenesis

Combination of RNA Interference with UASHuman cDNA Strategy

Generation of T2A-Gal4 Null Mutant Allele Using Recombinase Medicated Cassette Exchange (RMCE)

Generation of T2A-Gal4 Alleles Using CRIMIC

Kozak-Gal4 Null Mutant Generation via CRISPR-Cas9 Editing

CRISPR/Cas9-Mediated Tissue-Specific Knockout and cDNA Rescue

Conclusion

Acknowledgements

Funding

References

키워드

Genetic variation Genetic diseases Drosophila melanogaster Genetic techniques Gene editing Clustered regularly interspaced short palindromic repeats