Mutation mapping and identification by whole-genome sequencing
Name
Leshchiner-2012-Mutation mapping and.pdf
Size
1.03 MB
Format
Adobe PDF
Checksum (MD5)
7018641a550624c41c1c179e9a15ac8c
Author(s)
Leshchiner, Ignaty
Alexa, Kristen
Kelsey, Peter
Adzhubey, Ivan
Austin-Tse, Christina A.
Cooney, Jeffrey D.
Anderson, Heidi
King, Matthew J.
Stottmann, Rolf W.
Garnaas, Maija K.
Date Issued
May 2012
Journal
Genome Research
Publisher
Cold Spring Harbor Laboratory Press
Citation
Leshchiner, I. et al. “Mutation Mapping and Identification by Whole-genome Sequencing.” Genome Research 22.8 (2012): 1541–1548. © 2012, Published by Cold Spring Harbor Laboratory Press
Version
Final published version
Abstract
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Creative Commons Attribution Non-Commercial
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1101/gr.135541.111
