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Criteria for selecting microhaplotypes: mixture detection and deconvolution

BACKGROUND: DNA sequencing is likely to become a standard typing method in forensics in the near future. We define a microhaplotype to be a locus with two or more single nucleotide polymorphisms (SNPs) that occur within a short segment of DNA (e.g., 200 bp) that can be covered by a single sequence r...

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Autores principales: Kidd, Kenneth K, Speed, William C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351693/
https://www.ncbi.nlm.nih.gov/pubmed/25750707
http://dx.doi.org/10.1186/s13323-014-0018-3
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author Kidd, Kenneth K
Speed, William C
author_facet Kidd, Kenneth K
Speed, William C
author_sort Kidd, Kenneth K
collection PubMed
description BACKGROUND: DNA sequencing is likely to become a standard typing method in forensics in the near future. We define a microhaplotype to be a locus with two or more single nucleotide polymorphisms (SNPs) that occur within a short segment of DNA (e.g., 200 bp) that can be covered by a single sequence run and collectively define a multiallelic locus. Microhaplotypes can be highly informative for many forensic questions, including detection of mixtures of two or more sources in a DNA sample, a common problem in forensic practice. RESULTS: When all alleles are equally frequent, the probability of detecting three or more alleles in a mixture is at maximum. The classical population genetics concept of effective number of alleles at a locus, termed A(e), converts the unequal allele frequencies at a locus into a value that is equivalent to some number of equally frequent alleles, allowing microhaplotype loci to be ranked. The expectations for the ability to qualitatively detect mixtures are given for different integer values of A(e), and the cumulative probabilities of detecting mixtures based on testing multiple microhaps are shown to exceed 95% with as few as five loci with average A(e) values of even slightly greater than 3.0. CONCLUSIONS: Microhaplotypes with A(e) values of >3 will be exceedingly useful in ordinary forensic practice. Based on our studies, 3-SNP microhaplotypes will sometimes meet this criterion, but 4-SNP microhaplotypes can even exceed this criterion and have values >4. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13323-014-0018-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-43516932015-03-07 Criteria for selecting microhaplotypes: mixture detection and deconvolution Kidd, Kenneth K Speed, William C Investig Genet Research BACKGROUND: DNA sequencing is likely to become a standard typing method in forensics in the near future. We define a microhaplotype to be a locus with two or more single nucleotide polymorphisms (SNPs) that occur within a short segment of DNA (e.g., 200 bp) that can be covered by a single sequence run and collectively define a multiallelic locus. Microhaplotypes can be highly informative for many forensic questions, including detection of mixtures of two or more sources in a DNA sample, a common problem in forensic practice. RESULTS: When all alleles are equally frequent, the probability of detecting three or more alleles in a mixture is at maximum. The classical population genetics concept of effective number of alleles at a locus, termed A(e), converts the unequal allele frequencies at a locus into a value that is equivalent to some number of equally frequent alleles, allowing microhaplotype loci to be ranked. The expectations for the ability to qualitatively detect mixtures are given for different integer values of A(e), and the cumulative probabilities of detecting mixtures based on testing multiple microhaps are shown to exceed 95% with as few as five loci with average A(e) values of even slightly greater than 3.0. CONCLUSIONS: Microhaplotypes with A(e) values of >3 will be exceedingly useful in ordinary forensic practice. Based on our studies, 3-SNP microhaplotypes will sometimes meet this criterion, but 4-SNP microhaplotypes can even exceed this criterion and have values >4. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13323-014-0018-3) contains supplementary material, which is available to authorized users. BioMed Central 2015-01-28 /pmc/articles/PMC4351693/ /pubmed/25750707 http://dx.doi.org/10.1186/s13323-014-0018-3 Text en © Kidd and Speed; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kidd, Kenneth K
Speed, William C
Criteria for selecting microhaplotypes: mixture detection and deconvolution
title Criteria for selecting microhaplotypes: mixture detection and deconvolution
title_full Criteria for selecting microhaplotypes: mixture detection and deconvolution
title_fullStr Criteria for selecting microhaplotypes: mixture detection and deconvolution
title_full_unstemmed Criteria for selecting microhaplotypes: mixture detection and deconvolution
title_short Criteria for selecting microhaplotypes: mixture detection and deconvolution
title_sort criteria for selecting microhaplotypes: mixture detection and deconvolution
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351693/
https://www.ncbi.nlm.nih.gov/pubmed/25750707
http://dx.doi.org/10.1186/s13323-014-0018-3
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