RT Journal
A1 Leshchiner, Ignat
A1 Alexa, Kristen
A1 Kelsey, Peter
A1 Adzhubei, Ivan
A1 Austin, Christina
A1 Cooney, Jeffrey
A1 Anderson, Heidi
A1 King, Matthew
A1 Stottmann, Rolf W
A1 Ha, Seungshin
A1 Drummond, Ian
A1 Paw, Barry H.
A1 North, Trista
A1 Beier, David
A1 Goessling, Wolfram
A1 Sunyaev, Shamil
T1 Mutation mapping and identification by whole genome sequencing
JF Genome Research 
JO Genome Research 
YR 2012 
FD May 03 
DO 10.1101/gr.135541.111 
SP gr.135541.111 
UL http://genome.cshlp.org/content/early/2012/06/14/gr.135541.111.abstract 
AB Genetic mapping of mutations in model systems has facilitated the identification of genes contributing to fundamental biological processes, including human diseases. However, this approach has historically required the prior characterization of informative markers. Here, we report a fast and cost-effective method for genetic mapping using Next Generation Sequencing that combines single nucleotide polymorphism discovery, mutation localization, and potential identification of causal sequence variants. In contrast to prior approaches, we have developed a Hidden Markov Model to narrowly define the mutation area by inferring recombination breakpoints of chromosomes in the mutant pool. In addition, we created an interactive online software resource to facilitate automated analysis of sequencing data and demonstrate its utility in the zebrafish and mouse models. Our novel methodology and online tools will make Next Generation Sequencing an easily applicable resource for mutation mapping in all model systems.