RT Journal Article
SR Electronic
T1 Sorting & Sequencing Flies by Size: Identification of novel TOR regulators and Parameters for Successful Sorting
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 119719
DO 10.1101/119719
A1 Katrin Strassburger
A1 Tanja Zöller
A1 Thomas Sandmann
A1 Svenja Leible
A1 Grainne Kerr
A1 Michael Boutros
A1 Aurelio A. Teleman
YR 2017
UL http://biorxiv.org/content/early/2017/03/23/119719.abstract
AB As DNA sequencing throughput increases, novel strategies for discovering genes that affect traits of interest become available. One strategy starts with a population of animals and selects individuals over multiple generations for a particular trait. Subsequent whole genome sequencing should identify loci affecting this trait. We apply this strategy by sorting flies for wing length over 18 generations, obtaining two populations that differ in wing length by 20%. Flies with longer wings had increased overall body sizes and elevated TOR activity, suggesting that genetic variation targets TOR signaling to influence body size. High-throughput sequencing of big and small flies identified thousands of single nucleotide polymorphisms that differed between the two populations, leading us to identify five novel regulators of TOR signaling. Surprisingly, stochastic simulations of the process show that large fractions of the genetic differences between the big and small flies are probably biological false positives, selected by chance by random drift. We employ these computer simulations to identify experimental setup parameters to improve the signal-to-noise ratio for successfully running sort-and-sequence experiments – a resource which will hopefully be useful for the community.