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Mutation mapping and identification by whole-genome sequencing. 2012
Ignaty Leshchiner, and
Kristen Alexa, and
Peter Kelsey, and
Ivan Adzhubei, and
Christina A Austin-Tse, and
Jeffrey D Cooney, and
Heidi Anderson, and
Matthew J King, and
Rolf W Stottmann, and
Maija K Garnaas, and
Seungshin Ha, and
Iain A Drummond, and
Barry H Paw, and
Trista E North, and
David R Beier, and
Wolfram Goessling, and
Shamil R Sunyaev
Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
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.
Related Publications
Ignaty Leshchiner, and
Kristen Alexa, and
Peter Kelsey, and
Ivan Adzhubei, and
Christina A Austin-Tse, and
Jeffrey D Cooney, and
Heidi Anderson, and
Matthew J King, and
Rolf W Stottmann, and
Maija K Garnaas, and
Seungshin Ha, and
Iain A Drummond, and
Barry H Paw, and
Trista E North, and
David R Beier, and
Wolfram Goessling, and
Shamil R Sunyaev
January 2022,
Methods in molecular biology (Clifton, N.J.),
Ignaty Leshchiner, and
Kristen Alexa, and
Peter Kelsey, and
Ivan Adzhubei, and
Christina A Austin-Tse, and
Jeffrey D Cooney, and
Heidi Anderson, and
Matthew J King, and
Rolf W Stottmann, and
Maija K Garnaas, and
Seungshin Ha, and
Iain A Drummond, and
Barry H Paw, and
Trista E North, and
David R Beier, and
Wolfram Goessling, and
Shamil R Sunyaev
January 2012,
PloS one,
Ignaty Leshchiner, and
Kristen Alexa, and
Peter Kelsey, and
Ivan Adzhubei, and
Christina A Austin-Tse, and
Jeffrey D Cooney, and
Heidi Anderson, and
Matthew J King, and
Rolf W Stottmann, and
Maija K Garnaas, and
Seungshin Ha, and
Iain A Drummond, and
Barry H Paw, and
Trista E North, and
David R Beier, and
Wolfram Goessling, and
Shamil R Sunyaev
January 2015,
Methods in molecular biology (Clifton, N.J.),
Ignaty Leshchiner, and
Kristen Alexa, and
Peter Kelsey, and
Ivan Adzhubei, and
Christina A Austin-Tse, and
Jeffrey D Cooney, and
Heidi Anderson, and
Matthew J King, and
Rolf W Stottmann, and
Maija K Garnaas, and
Seungshin Ha, and
Iain A Drummond, and
Barry H Paw, and
Trista E North, and
David R Beier, and
Wolfram Goessling, and
Shamil R Sunyaev
May 2016,
G3 (Bethesda, Md.),
Ignaty Leshchiner, and
Kristen Alexa, and
Peter Kelsey, and
Ivan Adzhubei, and
Christina A Austin-Tse, and
Jeffrey D Cooney, and
Heidi Anderson, and
Matthew J King, and
Rolf W Stottmann, and
Maija K Garnaas, and
Seungshin Ha, and
Iain A Drummond, and
Barry H Paw, and
Trista E North, and
David R Beier, and
Wolfram Goessling, and
Shamil R Sunyaev
September 2010,
Genetics,
Ignaty Leshchiner, and
Kristen Alexa, and
Peter Kelsey, and
Ivan Adzhubei, and
Christina A Austin-Tse, and
Jeffrey D Cooney, and
Heidi Anderson, and
Matthew J King, and
Rolf W Stottmann, and
Maija K Garnaas, and
Seungshin Ha, and
Iain A Drummond, and
Barry H Paw, and
Trista E North, and
David R Beier, and
Wolfram Goessling, and
Shamil R Sunyaev
October 2018,
Current protocols in molecular biology,
Ignaty Leshchiner, and
Kristen Alexa, and
Peter Kelsey, and
Ivan Adzhubei, and
Christina A Austin-Tse, and
Jeffrey D Cooney, and
Heidi Anderson, and
Matthew J King, and
Rolf W Stottmann, and
Maija K Garnaas, and
Seungshin Ha, and
Iain A Drummond, and
Barry H Paw, and
Trista E North, and
David R Beier, and
Wolfram Goessling, and
Shamil R Sunyaev
August 2009,
Nature methods,
Ignaty Leshchiner, and
Kristen Alexa, and
Peter Kelsey, and
Ivan Adzhubei, and
Christina A Austin-Tse, and
Jeffrey D Cooney, and
Heidi Anderson, and
Matthew J King, and
Rolf W Stottmann, and
Maija K Garnaas, and
Seungshin Ha, and
Iain A Drummond, and
Barry H Paw, and
Trista E North, and
David R Beier, and
Wolfram Goessling, and
Shamil R Sunyaev
December 2019,
Molecular genetics & genomic medicine,
Ignaty Leshchiner, and
Kristen Alexa, and
Peter Kelsey, and
Ivan Adzhubei, and
Christina A Austin-Tse, and
Jeffrey D Cooney, and
Heidi Anderson, and
Matthew J King, and
Rolf W Stottmann, and
Maija K Garnaas, and
Seungshin Ha, and
Iain A Drummond, and
Barry H Paw, and
Trista E North, and
David R Beier, and
Wolfram Goessling, and
Shamil R Sunyaev
January 2014,
Methods in molecular biology (Clifton, N.J.),
Ignaty Leshchiner, and
Kristen Alexa, and
Peter Kelsey, and
Ivan Adzhubei, and
Christina A Austin-Tse, and
Jeffrey D Cooney, and
Heidi Anderson, and
Matthew J King, and
Rolf W Stottmann, and
Maija K Garnaas, and
Seungshin Ha, and
Iain A Drummond, and
Barry H Paw, and
Trista E North, and
David R Beier, and
Wolfram Goessling, and
Shamil R Sunyaev
April 2022,
Scientific reports,
