Functional assays in <i>Drosophila</i> facilitate classification of variants of uncertain significance associated with rare diseases.

ABSTRACT: Individuals living with rare diseases often undergo a frustrating and expensive diagnostic odyssey. Clinical geneticists who analyze exome or genome sequencing data from rare disease patients often encounter a list of variants of uncertain significance (VUS) in known disease-causing genes or rare variants in genes of uncertain significance (GUS) that are difficult to interpret, even with the integration of the latest bioinformatic tools. In this Perspective, we review how studies using the fruit fly Drosophila melanogaster have facilitated rare disease diagnosis by uncovering the clinical relevance of GUS and classifying rare variants into specific allelic categories (loss-of-function or gain-of-function, Muller's morphs). We showcase how fly researchers have been collaboratively st

SUBMITTER: Mok JW 

PROVIDER: S-EPMC12212082 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature