Abstract
In forensic science, as well as in molecular anthropology and medical genetics, human mitochondrial DNA (mtDNA) variation is being recorded by aligning mtDNA sequences to the revised Cambridge reference sequence (rCRS). This task is straightforward for the vast majority of nucleotide positions but appears to be difficult for some short sequence stretches, namely, in regions displaying length variation. Earlier guidelines for imposing a unique alignment relied on binary alignment to a standard sequence (the rCRS) and used additional priority rules for resolving ambiguities. It turns out, however, that these rules have not been applied rigorously and led to inconsistent nomenclature. There is no way to adapt the priority rules in a reasonable way because binary alignment to a standard sequence is bound to produce artificial alignments that may place sequences separated by a single mutation at mismatch distance larger than 1. To remedy the situation, we propose a phylogenetic approach for multiple alignment and resulting notation.
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Acknowledgment
We are indebted to Anita Brandstätter, Nina Duftner, Cordula Eichmann, Anna König, Daniela Niederwieser, and Bettina Zimmermann (Institute of Legal Medicine, Innsbruck Medical University) for their excellent technical work and sequence analysis. Thomas J. Parsons (International Commission on Missing Persons, Sarajevo, Bosnia-Herzegovina) and Jodi A. Irwin (Armed Forces DNA Identification Laboratory) are greatly acknowledged for their helpful discussions. We thank Claudio Bravi for drawing our attention to the alignment problems in the Navajo mtDNA dataset. Finally, we appreciated the constructive criticism of one reviewer that helped improve the text.
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Bandelt, HJ., Parson, W. Consistent treatment of length variants in the human mtDNA control region: a reappraisal. Int J Legal Med 122, 11–21 (2008). https://doi.org/10.1007/s00414-006-0151-5
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DOI: https://doi.org/10.1007/s00414-006-0151-5