RT Journal Article
SR Electronic
T1 Accelerating gene discovery by phenotyping whole-genome sequenced multi-mutation strains and using the sequence kernel association test (SKAT)
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 027540
DO 10.1101/027540
A1 Tiffany A. Timbers
A1 Stephanie J. Garland
A1 Swetha Mohan
A1 Stephane Flibotte
A1 Mark Edgley
A1 Quintin Muncaster
A1 Donald G. Moerman
A1 Michel R. Leroux
YR 2015
UL http://biorxiv.org/content/early/2015/10/22/027540.abstract
AB Forward and reverse genetic screens represent powerful methods to uncover new components for any biological process, but suffer from gene cloning or throughput bottleneck issues, respectively. Here, we employ an innovative approach to gene discovery: we screened a C. elegans whole-genome sequenced multi-mutation library for our phenotype of interest, namely defective ciliated sensory neuron development, and performed the Sequence Kernel Association Test (SKAT) to rapidly identify genes exhibiting this phenotype. Our approach unveiled a novel gene, bgnt-1.1, that influences cilia length. Notably, the human orthologue B3GNT1/B4GAT1 is associated with Walker-Warburg syndrome, a suspected ciliary disorder.