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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Improved linkage analysis of Quantitative Trait Loci using bulk segregants unveils a novel determinant of high ethanol tolerance in yeast
BMC Genomics, Volume 15, No. 1, Article 207, Year 2014
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Description
Background: Bulk segregant analysis (BSA) coupled to high throughput sequencing is a powerful method to map genomic regions related with phenotypes of interest. It relies on crossing two parents, one inferior and one superior for a trait of interest. Segregants displaying the trait of the superior parent are pooled, the DNA extracted and sequenced. Genomic regions linked to the trait of interest are identified by searching the pool for overrepresented alleles that normally originate from the superior parent. BSA data analysis is non-trivial due to sequencing, alignment and screening errors.Results: To increase the power of the BSA technology and obtain a better distinction between spuriously and truly linked regions, we developed EXPLoRA (EXtraction of over-rePresented aLleles in BSA), an algorithm for BSA data analysis that explicitly models the dependency between neighboring marker sites by exploiting the properties of linkage disequilibrium through a Hidden Markov Model (HMM).Reanalyzing a BSA dataset for high ethanol tolerance in yeast allowed reliably identifying QTLs linked to this phenotype that could not be identified with statistical significance in the original study. Experimental validation of one of the least pronounced linked regions, by identifying its causative gene VPS70, confirmed the potential of our method.Conclusions: EXPLoRA has a performance at least as good as the state-of-the-art and it is robust even at low signal to noise ratio's i.e. when the true linkage signal is diluted by sampling, screening errors or when few segregants are available. © 2014 Duitama et al.; licensee BioMed Central Ltd.
Authors & Co-Authors
Duitama, Jorge
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Sánchez-Rodríguez, Aminael
Belgium, Leuven
Ku Leuven
Pulido-Tamayo, Sergio
Belgium, Leuven
Ku Leuven
Belgium, Ghent
Universiteit Gent
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Foulquíe-Moreno, María Remedios
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Thevelein, Johan M.
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Verstrepen, Kevin J.
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Marchal, Kathleen
Belgium, Leuven
Ku Leuven
Belgium, Ghent
Universiteit Gent
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Statistics
Citations: 37
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1186/1471-2164-15-207
ISSN:
14712164
Research Areas
Genetics And Genomics
Study Approach
Quantitative