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Perspective: Functional assays in Drosophila facilitate classification of variants of uncertain significance associated with rare diseases
- Jung-Wan Mok,
- Shelley B. Gibson,
- Haley A. Dostalik,
- and Shinya Yamamoto
Genome Res. July 2025 35: 1473-1484; Published in Advance June 4, 2025, doi:10.1101/gr.278291.123
...and functional classification of VUS. To compile a list of papers published using Drosophila melanogaster as a model organism to study rare disease genes and variants between January 2020 and April 2024, we first performed manual inspections of all abstracts published in the following journals where many new...
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Research: Oxygen-induced stress reveals context-specific gene regulatory effects in human brain organoids
- Benjamin D. Umans and
- Yoav Gilad
Genome Res. August 2025 35: 1689-1700; Published in Advance June 2, 2025, doi:10.1101/gr.280219.124
...-state conditions.Gene regulatory catalogs like the Genotype-Tissue Expression (GTEx) project (The GTEx Consortium 2020) provide valuable insights into how genetic variants affect gene expression across various tissues in steady-state conditions. However, the majority of disease-associated loci remain unexplained...
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Research: Transcriptional programs mediating neuronal toxicity and altered glial–neuronal signaling in a Drosophila knock-in tauopathy model
- Hassan Bukhari,
- Vanitha Nithianandam,
- Rachel A. Battaglia,
- Anthony Cicalo,
- Souvarish Sarkar,
- Aram Comjean,
- Yanhui Hu,
- Matthew J. Leventhal,
- Xianjun Dong,
- and Mel B. Feany
Genome Res. April 2024 34: 590-605; Published in Advance April 10, 2024, doi:10.1101/gr.278576.123
....ResultsPhenotypic analysis of a Drosophila knock-in model of frontotemporal dementiaWe used CRISPR-Cas9 gene editing to recapitulate the genetic basis of human frontotemporal dementia in the powerful genetic experimental organism Drosophila by modeling the disease-causing proline 301 to leucine in fly Tau. Protein sequence...
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Method: A best-match approach for gene set analyses in embedding spaces
- Lechuan Li,
- Ruth Dannenfelser,
- Charlie Cruz,
- and Vicky Yao
Genome Res. September 2024 34: 1421-1433; Published in Advance September 4, 2024, doi:10.1101/gr.279141.124
...to study directly. Thus, improving functional knowledge transfer increases the potential impact of model system study.To determine if ANDES can aid in functional knowledge transfer, we use ETNA to build three pairwise joint gene embeddings between humans and three model organisms: Mus musculus, Drosophila...
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Research: Circadian gene variants and the skeletal muscle circadian clock contribute to the evolutionary divergence in longevity across Drosophila populations
- Liam C. Hunt,
- Jianqin Jiao,
- Yong-Dong Wang,
- David Finkelstein,
- Deepti Rao,
- Michelle Curley,
- Maricela Robles-Murguia,
- Abbas Shirinifard,
- Vishwajeeth R. Pagala,
- Junmin Peng,
- Yiping Fan,
- and Fabio Demontis
Genome Res. August 2019 29: 1262-1276; Published in Advance June 27, 2019, doi:10.1101/gr.246884.118
...the s of Drosophila melanogaster strains with exceptional longevity that were obtained via multiple rounds of selection from a parental strain. Comparison of genomic, transcriptomic, and proteomic data revealed that changes in gene expression due to intergenic polymorphisms are associated with longevity...
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Resource: Natural variation in genome architecture among 205 Drosophila melanogaster Genetic Reference Panel lines
- Wen Huang,
- Andreas Massouras,
- Yutaka Inoue,
- Jason Peiffer,
- Miquel Ràmia,
- Aaron M. Tarone,
- Lavanya Turlapati,
- Thomas Zichner,
- Dianhui Zhu,
- Richard F. Lyman,
- Michael M. Magwire,
- Kerstin Blankenburg,
- Mary Anna Carbone,
- Kyle Chang,
- Lisa L. Ellis,
- Sonia Fernandez,
- Yi Han,
- Gareth Highnam,
- Carl E. Hjelmen,
- John R. Jack,
- Mehwish Javaid,
- Joy Jayaseelan,
- Divya Kalra,
- Sandy Lee,
- Lora Lewis,
- Mala Munidasa,
- Fiona Ongeri,
- Shohba Patel,
- Lora Perales,
- Agapito Perez,
- LingLing Pu,
- Stephanie M. Rollmann,
- Robert Ruth,
- Nehad Saada,
- Crystal Warner,
- Aneisa Williams,
- Yuan-Qing Wu,
- Akihiko Yamamoto,
- Yiqing Zhang,
- Yiming Zhu,
- Robert R.H. Anholt,
- Jan O. Korbel,
- David Mittelman,
- Donna M. Muzny,
- Richard A. Gibbs,
- Antonio Barbadilla,
- J. Spencer Johnston,
- Eric A. Stone,
- Stephen Richards,
- Bart Deplancke,
- and Trudy F.C. Mackay
Genome Res. July 2014 24: 1193-1208; Published in Advance April 8, 2014, doi:10.1101/gr.171546.113
...insertions of Wolbachia sequences, but effects of Wolbachia infection on quantitative traits are rarely significant. The DGRP complements ongoing efforts to functionally annotate the Drosophila genome. Indeed, 15% of all D. melanogaster genes segregate for potentially damaged proteins in the DGRP...
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Resource: Systematic detection of brain protein-coding genes under positive selection during primate evolution and their roles in cognition
- Guillaume Dumas,
- Simon Malesys,
- and Thomas Bourgeron
Genome Res. March 2021 31: 484-496; Published in Advance January 13, 2021, doi:10.1101/gr.262113.120
...are openly available on the companion website and allow checking at the variant level which amino acids changed.PerspectivesOur systematic analysis of protein sequence diversity confirmed that protein-coding genes relating to brain function are among the most highly conserved in the human . The set of PSGs...
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Research: Chromatin conformation and transcriptional activity are permissive regulators of DNA replication initiation in Drosophila
- Robin L. Armstrong,
- Taylor J.R. Penke,
- Brian D. Strahl,
- A. Gregory Matera,
- Daniel J. McKay,
- David M. MacAlpine,
- and Robert J. Duronio
Genome Res. November 2018 28: 1688-1700; Published in Advance October 2, 2018, doi:10.1101/gr.239913.118
...-poor, inaccessible heterochromatin, a causal relationship between chromatin structure and replication initiation remains elusive. Here, we combined histone gene engineering and whole- sequencing in Drosophila to determine how perturbing chromatin structure affects replication initiation. We found that most...
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Research: Intragenic repeat expansion in the cell wall protein gene HPF1 controls yeast chronological aging
- Benjamin P. Barré,
- Johan Hallin,
- Jia-Xing Yue,
- Karl Persson,
- Ekaterina Mikhalev,
- Agurtzane Irizar,
- Sylvester Holt,
- Dawn Thompson,
- Mikael Molin,
- Jonas Warringer,
- and Gianni Liti
Genome Res. May 2020 30: 697-710; Published in Advance April 10, 2020, doi:10.1101/gr.253351.119
...) in HPF1 for NA and WA alleles. Hatched rectangle: a HPF1 internal unique region with high sequence variation between NA and WA alleles. Right: repeat motif units. Amino acids are colored according to the RasMol nomenclature. Numbers = motif size (amino acids). (B) Size variation of genes containing long...
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ARTICLE: Novel Protein Domains and Repeats in Drosophila melanogaster: Insights into Structure, Function, and Evolution
- Chris P. Ponting,
- Richard Mott,
- Peer Bork,
- and Richard R. Copley
Genome Res. December 1, 2001 11: 1996-2008; Published in Advance November 12, 2001, doi:10.1101/gr.198701
...of sequence similarities among single regions of proteins. Searches of whole databases however, are not optimized to detect multiple homologous regions within a single polypeptide. Here we have used the prospero algorithm to perform self-comparisons of all predicted Drosophila melanogaster gene products...

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