Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Oslo, Norway.
PLoS One. 2011;6(10):e26723. doi: 10.1371/journal.pone.0026723. Epub 2011 Oct 28.
Mitochondrial DNA (mtDNA) variation is commonly analyzed in a wide range of different biomedical applications. Cases where more than one individual contribute to a stain genotyped from some biological material give rise to a mixture. Most forensic mixture cases are analyzed using autosomal markers. In rape cases, Y-chromosome markers typically add useful information. However, there are important cases where autosomal and Y-chromosome markers fail to provide useful profiles. In some instances, usually involving small amounts or degraded DNA, mtDNA may be the only useful genetic evidence available. Mitochondrial DNA mixtures also arise in studies dealing with the role of mtDNA variation in tumorigenesis. Such mixtures may be generated by the tumor, but they could also originate in vitro due to inadvertent contamination or a sample mix-up.
METHODS/PRINCIPAL FINDINGS: We present the statistical methods needed for mixture interpretation and emphasize the modifications required for the more well-known methods based on conventional markers to generalize to mtDNA mixtures. Two scenarios are considered. Firstly, only categorical mtDNA data is assumed available, that is, the variants contributing to the mixture. Secondly, quantitative data (peak heights or areas) on the allelic variants are also accessible. In cases where quantitative information is available in addition to allele designation, it is possible to extract more precise information by using regression models. More precisely, using quantitative information may lead to a unique solution in cases where the qualitative approach points to several possibilities. Importantly, these methods also apply to clinical cases where contamination is a potential alternative explanation for the data.
CONCLUSIONS/SIGNIFICANCE: We argue that clinical and forensic scientists should give greater consideration to mtDNA for mixture interpretation. The results and examples show that the analysis of mtDNA mixtures contributes substantially to forensic casework and may also clarify erroneous claims made in clinical genetics regarding tumorigenesis.
线粒体 DNA（mtDNA）变异在广泛的不同医学应用中经常被分析。在从某些生物材料中对一个污渍进行基因分型时，如果有不止一个个体参与，就会产生混合物。大多数法医混合物案件都使用常染色体标记物进行分析。在强奸案件中，Y 染色体标记物通常会提供有用的信息。然而，在重要的情况下，常染色体和 Y 染色体标记物无法提供有用的图谱。在某些情况下，通常涉及少量或降解的 DNA，mtDNA 可能是唯一可用的有用遗传证据。线粒体 DNA 混合物也会出现在研究线粒体 DNA 变异在肿瘤发生中的作用的研究中。这种混合物可能是由肿瘤产生的，但也可能由于无意中的污染或样本混淆而在体外产生。
方法/主要发现：我们介绍了用于混合物解释的统计方法，并强调了需要对基于传统标记物的更知名方法进行修改，以推广到 mtDNA 混合物。考虑了两种情况。首先，假设只有分类的 mtDNA 数据可用，即构成混合物的变体。其次，还可以访问等位变体的定量数据（峰高或面积）。在除了等位基因指定外还可以获得定量信息的情况下，可以通过使用回归模型来提取更精确的信息。更准确地说，在定性方法指向几种可能性的情况下，使用定量信息可能会导致唯一的解决方案。重要的是，这些方法也适用于存在污染是数据潜在替代解释的临床病例。
结论/意义：我们认为，临床和法医科学家应该更加重视 mtDNA 用于混合物解释。结果和示例表明，mtDNA 混合物的分析对法医工作有很大的贡献，并且还可以澄清临床遗传学中关于肿瘤发生的错误说法。
