Video protocols published -- on bioinformatics and experimental approaches to using flies to study human gene variants

Wang J, Liu Z, Bellen HJ, Yamamoto S. Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information. J Vis Exp. 2019 Aug 15;(150). doi: 10.3791/59542. PubMed PMID: 31475990.

From the abstract: "Through whole-exome/genome sequencing, human geneticists identify rare variants that segregate with disease phenotypes. To assess if a specific variant is pathogenic, one must query many databases ... MARRVEL (Model organism Aggregated Resources for Rare Variant ExpLoration) is a one-stop data collection tool for human genes and variants and their orthologous genes in seven model organisms including in mouse, rat, zebrafish, fruit fly, nematode worm, fission yeast, and budding yeast. In this Protocol, we provide an overview of what MARRVEL can be used for and discuss how different datasets can be used to assess whether a variant of unknown significance (VUS) in a known disease-causing gene or a variant in a gene of uncertain significance (GUS) may be pathogenic. ... MARRVEL is an easily accessible open access website designed for both clinical and basic researchers and serves as a starting point to design experiments for functional studies."

Harnish JM, Deal SL, Chao HT, Wangler MF, Yamamoto S. In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila. J Vis Exp. 2019 Aug 20;(150). doi: 10.3791/59658. PubMed PMID: 31498321.

From the abstract: "... In the Undiagnosed Diseases Network (UDN) and other rare disease research consortia, model organisms (MO) including Drosophila, C. elegans, zebrafish, and mice are actively used to assess the function of putative human disease-causing variants. This protocol describes a method for the functional assessment of rare human variants ... The workflow begins with gathering human and MO information from multiple public databases, using the MARRVEL web resource ... Next, genetic tools ... are generated to assess the functions of variants of interest in Drosophila. ... This protocol allows rapid, in vivo assessments of putative human disease-causing variants of genes with known and unknown functions."