GOOGA: A platform to synthesize mapping experiments and identify genomic structural diversity

Lex E. Flagel, Benjamin K. Blackman, Lila Fishman, Patrick J. Monnahan, Andrea Sweigart, John K. Kelly

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Understanding genomic structural variation such as inversions and translocations is a key challenge in evolutionary genetics. We develop a novel statistical approach to comparative genetic mapping to detect large-scale structural mutations from low-level sequencing data. The procedure, called Genome Order Optimization by Genetic Algorithm (GOOGA), couples a Hidden Markov Model with a Genetic Algorithm to analyze data from genetic mapping populations. We demonstrate the method using both simulated data (calibrated from experiments on Drosophila melanogaster) and real data from five distinct crosses within the flowering plant genus Mimulus. Application of GOOGA to the Mimulus data corrects numerous errors (misplaced sequences) in the M. guttatus reference genome and confirms or detects eight large inversions polymorphic within the species complex. Finally, we show how this method can be applied in genomic scans to improve the accuracy and resolution of Quantitative Trait Locus (QTL) mapping.

Original languageEnglish (US)
Article numbere1006949
JournalPLoS computational biology
Volume15
Issue number4
DOIs
StatePublished - 2019

Bibliographical note

Funding Information:
Funding support was received from the National Institutes of Health (nih.gov; R01 GM073990-02 to J.K.K.), the University of Virginia, the University of California, Berkeley, an NSF (nsf.gov) Postdoctoral Fellowship in Biology (DBI- 0905958 to BKB), and NSF grants to J. Willis (IOS-1024966) and BKB (IOS-1558035)

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