Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Children's Hospital Research Institute of Manitoba (CHRIM), University of Manitoba, Winnipeg, MB, Canada.
Genome. 2024 Jun 1;67(6):158-167. doi: 10.1139/gen-2023-0135. Epub 2024 Feb 27.
The last decade has been highlighted by the increased use of next-generation DNA sequencing technology to identify novel human disease genes. A critical downstream part of this process is assigning function to a candidate gene variant. Functional studies in , the common fruit fly, have made a prominent contribution in annotating variant impact in an in vivo system. The use of patient-derived knock-in flies or rescue-based, "humanization", approaches are novel and valuable strategies in variant testing but have been recently widely reviewed. An often-overlooked strategy for determining variant impact has been GAL4/upstream activation sequence-mediated tissue-defined overexpression in . This mini-review will summarize the recent contribution of ectopic overexpression of human reference and variant cDNA in to assess variant function, interpret the consequence of the variant, and in some cases infer biological mechanisms.
过去十年，人们越来越多地使用下一代 DNA 测序技术来鉴定新的人类疾病基因。该过程的一个关键下游部分是为候选基因变异赋予功能。在模式生物 中进行的功能研究，在体内系统中注释变异影响方面做出了突出贡献。利用患者来源的基因敲入苍蝇或基于拯救的“人源化”方法，是变异检测中的新颖且有价值的策略，但最近已被广泛综述。另一种常常被忽视的确定变异影响的策略是在 中通过 GAL4/上游激活序列介导的组织特异性过表达。本综述将总结最近在 中异位过表达人类参考和变异 cDNA 来评估变异功能、解释变异后果的研究进展，并在某些情况下推断生物学机制。
