Distilling artificial recombinants from large sets of complete mtDNA genomes.
<h4>Background</h4>Large-scale genome sequencing poses enormous problems to the logistics of laboratory work and data handling. When numerous fragments of different genomes are PCR amplified and sequenced in a laboratory, there is a high imminent risk of sample confusion. For genetic mar...
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Autores principales: | , , , , , , , , |
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Formato: | article |
Lenguaje: | EN |
Publicado: |
Public Library of Science (PLoS)
2008
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Materias: | |
Acceso en línea: | https://doaj.org/article/9a48c9a5ac5b4bddbb003d2a3738b99a |
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Sumario: | <h4>Background</h4>Large-scale genome sequencing poses enormous problems to the logistics of laboratory work and data handling. When numerous fragments of different genomes are PCR amplified and sequenced in a laboratory, there is a high imminent risk of sample confusion. For genetic markers, such as mitochondrial DNA (mtDNA), which are free of natural recombination, single instances of sample mix-up involving different branches of the mtDNA phylogeny would give rise to reticulate patterns and should therefore be detectable.<h4>Methodology/principal findings</h4>We have developed a strategy for comparing new complete mtDNA genomes, one by one, to a current skeleton of the worldwide mtDNA phylogeny. The mutations distinguishing the reference sequence from a putative recombinant sequence can then be allocated to two or more different branches of this phylogenetic skeleton. Thus, one would search for two (or three) near-matches in the total mtDNA database that together best explain the variation seen in the recombinants. The evolutionary pathway from the mtDNA tree connecting this pair together with the recombinant then generate a grid-like median network, from which one can read off the exchanged segments.<h4>Conclusions</h4>We have applied this procedure to a large collection of complete human mtDNA sequences, where several recombinants could be distilled by our method. All these recombinant sequences were subsequently corrected by de novo experiments--fully concordant with the predictions from our data-analytical approach. |
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