RT Journal
A1 Haelterman, Nele A.
A1 Jiang, Lichun
A1 Li, Yumei
A1 Bayat, Vafa
A1 Sandoval, Hector
A1 Ugur, Berrak
A1 Tan, Kai Li
A1 Zhang, Ke
A1 Bei, Danqing
A1 Xiong, Bo
A1 Charng, Wu-Lin
A1 Busby, Theodore
A1 Jawaid, Adeel
A1 David, Gabriela
A1 Jaiswal, Manish
A1 Venken, Koen J.T.
A1 Yamamoto, Shinya
A1 Chen, Rui
A1 Bellen, Hugo J.
T1 Large-scale identification of chemically induced mutations in Drosophila melanogaster
JF Genome Research 
JO Genome Research 
YR 2014 
FD October 01 
VO 24 
IS 10 
SP 1707 
OP 1718 
DO 10.1101/gr.174615.114 
UL http://genome.cshlp.org/content/24/10/1707.abstract 
AB 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.