Defining “mutation” and “polymorphism” in the era of personal genomics

BMC Medical Genomics

Cristiano Ferlini¹  Robert C. Elston²  Deep Pandya¹  Roshan Karki¹ 

[1] Danbury Hospital Research Institute, Western Connecticut Health Network, 131 West Street, Danbury 06810, CT, USA;Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA

关键词: Human genome;    DNA variants;    DNA sequencing;    Precision medicine;    Personal genomics;   

Others  :  1219421
DOI  :  10.1186/s12920-015-0115-z

 received in 2014-10-02, accepted in 2015-07-06,  发布年份 2015

【 摘 要 】

Background

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.

Discussion

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.

Summary

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.

【 授权许可】

   
2015 Karki et al.

【 图 表 】

Fig. 1.

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