Defining "mutation" and "polymorphism" in the era of personal genomics.
Defining "mutation" and "polymorphism" in the era of personal genomics.
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DOI：
10.1186/s12920-015-0115-z
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发表时间：
2015-07-15
影响因子：
2.7
通讯作者：
Ferlini C
中科院分区：
文献类型：
--
作者：
Karki R;Pandya D;Elston RC;Ferlini C
DNA测序工具的不断进步使得分析人类基因组更便宜、更快捷。虽然这些分析旨在识别与疾病易感性和药物反应有效性相关的复杂变异，但它们模糊了突变和多态性的定义。在个人基因组学时代，建立关于参考基因组使用的明确指导方针至关重要。现在，DNA变异被称为与参考物相比的差异。在测序项目中，单核苷酸多态性（snp）和DNA突变分别被定义为在人群中可检测到的DNA变异，分别为0.1%或< 1%。对同一事件（与引用相比的差异）使用两个术语突变或多态性可能会导致分类问题。这些问题会影响疾病状态和基因组序列之间解释和功能关系的准确性。我们建议通过将突变定义为在配对测序项目中获得的DNA变体来解决这一命名困境，该项目包括同一个体的种系DNA作为参考。此外，术语突变应该伴随着一个限定前缀，表明突变是只发生在体细胞（体细胞突变）还是也发生在种系（种系突变）。我们相信，这种定义上的区别将有助于避免研究人员之间的混淆，并支持同时对种系和体细胞组织进行测序的实践，从而对定义为突变的DNA变异进行分类。
The growing advances in DNA sequencing tools have made analyzing the human genome cheaper and faster. While such analyses are intended to identify complex variants, related to disease susceptibility and efficacy of drug responses, they have blurred the definitions of mutation and polymorphism. In the era of personal genomics, it is critical to establish clear guidelines regarding the use of a reference genome. Nowadays DNA variants are called as differences in comparison to a reference. In a sequencing project Single Nucleotide Polymorphisms (SNPs) and DNA mutations are defined as DNA variants detectable in >1 % or <1 % of the population, respectively. The alternative use of the two terms mutation or polymorphism for the same event (a difference as compared with a reference) can lead to problems of classification. These problems can impact the accuracy of the interpretation and the functional relationship between a disease state and a genomic sequence. We propose to solve this nomenclature dilemma by defining mutations as DNA variants obtained in a paired sequencing project including the germline DNA of the same individual as a reference. Moreover, the term mutation should be accompanied by a qualifying prefix indicating whether the mutation occurs only in somatic cells (somatic mutation) or also in the germline (germline mutation). We believe this distinction in definition will help avoid confusion among researchers and support the practice of sequencing the germline and somatic tissues in parallel to classify the DNA variants thus defined as mutations.