Large-scale identification of chemically induced mutations in Drosophila melanogaster

Nele A. Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J.T. Venken, Shinya Yamamoto, Rui Chen, Hugo J. Bellen

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Forward genetic screens using chemical mutagens have been successful in defining the function of thousands of genes in eukaryotic model organisms. The main drawback of this strategy is the time-consuming identification of the molecular lesions causative of the phenotypes of interest. With whole-genome sequencing (WGS), it is now possible to sequence hundreds of strains, but determining which mutations are causative among thousands of polymorphisms remains challenging. We have sequenced 394 mutant strains, generated in a chemical mutagenesis screen, for essential genes on the Drosophila X chromosome and describe strategies to reduce the number of candidate mutations from an average of ~3500 to 35 single-nucleotide variants per chromosome. By combining WGS with a rough mapping method based on large duplications, we were able to map 274 (~70%) mutations. We show that these mutations are causative, using small 80-kb duplications that rescue lethality. Hence, our findings demonstrate that combining rough mapping with WGS dramatically expands the toolkit necessary for assigning function to genes.

Original languageEnglish (US)
Pages (from-to)1707-1718
Number of pages12
JournalGenome Research
Volume24
Issue number10
DOIs
StatePublished - Oct 1 2014

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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