TY  - JOUR
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
Y1  - 2014/10/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1707 
EP  - 1718 
DO  - 10.1101/gr.174615.114 
VL  - 24 
IS  - 10 
UR  - http://genome.cshlp.org/content/24/10/1707.abstract 
N2  - 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. 
ER  -