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Haplotype inference from unphased SNP data in heterozygous polyploids based on SAT

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons97314

Neigenfind,  J.
BioinformaticsCIG, Infrastructure Groups and Service Units, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons97409

Selbig,  J.
BioinformaticsCRG, Cooperative Research Groups, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons97225

Kersten,  B.
BioinformaticsCIG, Infrastructure Groups and Service Units, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

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Neigenfind-2008-Haplotype inference.pdf
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Zitation

Neigenfind, J., Gyetvai, G., Basekow, R., Diehl, S., Achenbach, U., Gebhardt, C., et al. (2008). Haplotype inference from unphased SNP data in heterozygous polyploids based on SAT. BMC Genomics, 9, 356. doi:10.1186/1471-2164-9-356.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0014-26F2-0
Zusammenfassung
ABSTRACT: BACKGROUND: Haplotype inference based on unphased SNP markers is an important task in population genetics. Although there are different approaches to the inference of haplotypes in diploid species, the existing software is not suitable for inferring haplotypes from unphased SNP data in polyploid species, such as the cultivated potato (Solanum tuberosum). Potato species are tetraploid and highly heterozygous. RESULTS: Here we present the software SATlotyper which is able to handle polyploid and polyallelic data. SATlotyper uses the Boolean satisfiability problem to formulate Haplotype Inference by Pure Parsimony. The software excludes existing haplotype inferences, thus allowing for calculation of alternative inferences. As it is not known which of the multiple haplotype inferences are best supported by the given unphased data set, we use a bootstrapping procedure that allows for scoring of alternative inferences. Finally, by means of the bootstrapping scores, it is possible to optimise the phased genotypes belonging to a given haplotype inference. The program is evaluated with simulated and experimental SNP data generated for heterozygous tetraploid populations of potato. We show that, instead of taking the first haplotype inference reported by the program, we can significantly improve the quality of the final result by applying additional methods that include scoring of the alternative haplotype inferences and genotype optimisation. For a sub-population of nineteen individuals, the predicted results computed by SATlotyper were directly compared with results obtained by experimental haplotype inference via sequencing of cloned amplicons. Prediction and experiment gave similar results regarding the inferred haplotypes and phased genotypes. CONCLUSIONS: Our results suggest that Haplotype Inference by Pure Parsimony can be solved efficiently by the SAT approach, even for data sets of unphased SNP from heterozygous polyploids. SATlotyper is freeware and is distributed as a Java JAR file. The software can be downloaded from the webpage of the GABI Primary Database at http://www.gabipd.org/projects/satlotyper/. The application of SATlotyper will provide haplotype information, which can be used in haplotype association mapping studies of polyploid plants.