RT Journal Article
SR Electronic
T1 Mapping challenging mutations by whole-genome sequencing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 036046
DO 10.1101/036046
A1 Harold E. Smith
A1 Amy S. Fabritius
A1 Aimee Jaramillo-Lambert
A1 Andy Golden
YR 2016
UL http://biorxiv.org/content/early/2016/01/05/036046.abstract
AB Whole-genome sequencing provides a rapid and powerful method for identifying mutations on a global scale, and has spurred a renewed enthusiasm for classical genetic screens in model organisms. The most commonly characterized category of mutation consists of monogenic, recessive traits, due to their genetic tractability. Therefore, most of the mapping methods for mutation identification by whole-genome sequencing are directed toward alleles that fulfill those criteria (i.e., single-gene, homozygous variants). However, such approaches are not entirely suitable for the characterization of a variety of more challenging mutations, such as dominant and semi-dominant alleles or multigenic traits. Therefore, we have developed strategies for the identification of those classes of mutations, using polymorphism mapping in Caenorhabditis elegans as our model for validation. We also report an alternative approach for mutation identification from traditional recombinant crosses, and a solution to the technical challenge of sequencing sterile or terminally arrested strains where population size is limiting. The methods described herein extend the applicability of whole-genome sequencing to a broader spectrum of mutations, including classes that are difficult to map by traditional means.