Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
DNA Diagnostic Laboratory (LDD), State University of Rio de Janeiro (UERJ), Rio de Janeiro 20550-013, Brazil.
Genes (Basel). 2023 Sep 22;14(10):1837. doi: 10.3390/genes14101837.
Genetic variants on non-recombining DNA and the hierarchical order in which they accumulate are commonly of interest. This variant hierarchy can be established and combined with information on the population and geographic origin of the individuals carrying the variants to find population structures and infer migration patterns. Further, individuals can be assigned to the characterized populations, which is relevant in forensic genetics, genetic genealogy, and epidemiologic studies. However, there is currently no straightforward method to obtain such a variant hierarchy. Here, we introduce the software SNPtotree v1.0, which uniquely determines the hierarchical order of variants on non-recombining DNA without error-prone manual sorting. The algorithm uses pairwise variant comparisons to infer their relationships and integrates the combined information into a phylogenetic tree. Variants that have contradictory pairwise relationships or ambiguous positions in the tree are removed by the software. When benchmarked using two human Y-chromosomal massively parallel sequencing datasets, SNPtotree outperforms traditional methods in the accuracy of phylogenetic trees for sequencing data with high amounts of missing information. The phylogenetic trees of variants created using SNPtotree can be used to establish and maintain publicly available phylogeny databases to further explore genetic epidemiology and genealogy, as well as population and forensic genetics.
非重组 DNA 上的遗传变异及其累积的层次结构通常是人们关注的焦点。可以建立这种变体层次结构，并将其与携带变体的个体的人口和地理起源信息相结合，以发现人口结构并推断迁移模式。此外，还可以将个体分配到特征化的人群中，这在法医学遗传学、遗传谱系学和流行病学研究中很重要。然而，目前没有直接的方法来获得这种变体层次结构。在这里，我们介绍 SNPtotree v1.0 软件，它可以在没有易错手动排序的情况下，唯一地确定非重组 DNA 上变体的层次顺序。该算法使用成对的变体比较来推断它们的关系，并将组合信息整合到一个系统发育树中。软件会删除具有矛盾的成对关系或在树中位置不明确的变体。当使用两个人类 Y 染色体大规模平行测序数据集进行基准测试时，SNPtotree 在准确性方面优于传统方法，可用于具有大量缺失信息的测序数据的系统发育树。使用 SNPtotree 创建的变体的系统发育树可用于建立和维护公共可用的系统发育数据库，以进一步探索遗传流行病学和谱系学以及人口和法医遗传学。
