Evolutionary Bioinformatics
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A Fast and Specific Alignment Method for Minisatellite Maps
Authors: Sèverine Bérard, François Nicolas, Jérôme Buard, Olivier Gascuel and Eric Rivals
Publication Date: 22 Feb 2007
Evolutionary Bioinformatics 2006:2 303-320
Sèverine Bérard1, François Nicolas2, Jérôme Buard3, Olivier Gascuel2 and Eric Rivals2
1INRA, Département MIA, Toulouse, France. 2LIRMM, UMR 5506 CNRS-Université de Montpellier II, Montpellier, France. 3Institut de Génétique Humaine, UPR-CNRS 1142, Montpellier, France.
Abstract
Background: Variable minisatellites count among the most polymorphic markers of eukaryotic and prokaryotic genomes. This variability can affect gene coding regions, like in the prion protein gene, or gene regulation regions, like for the cystatin B gene, and be associated or implicated in diseases: the Creutzfeld-Jakob disease and the myoclonus epilepsy type 1, for our examples. When it affects neutrally evolving regions, the polymorphism in length (i.e., in number of copies) of minisatellites proved useful in population genetics.
Motivation: In these tandem repeat sequences, different mutational mechanisms let the number of copies, as well as the copies themselves, vary. Especially, the interspersion of events of tandem duplication/contraction and of punctual mutation makes the succession of variant repeats much more informative than the sole allele length. To exploit this information requires the ability to align minisatellite alleles by accounting for both punctual mutations and tandem duplications.
Results: We propose a minisatellite maps alignment program that improves on previous solutions. Our new program is faster, simpler, considers an extended evolutionary model, and is available to the community. We test it on the data set of 609 alleles of the MSY1 (DYF155S1) human minisatellite and confirm its ability to recover known evolutionary signals. Our experiments highlight that the informativeness of minisatellites resides in their length and composition polymorphisms. Exploiting both simultaneously is critical to unravel the implications of variable minisatellites in the control of gene expression and diseases.
Availability: Software is available at http://atgc.lirmm.fr/ms_align/
Keywords: VNTR, tandem repeat, tandem duplication, variable costs, dynamic programming, sequence comparison.
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