Conlin Laura K, Landrum Melissa J, Freimuth Robert R, Funke Birgit
Department of Pathology and Laboratory Medicine, Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Clin Chem. 2025 Jan 3;71(1):45-53. doi: 10.1093/clinchem/hvae195.
Genetic testing has traditionally been divided into molecular genetics and cytogenetics, originally driven by the use of different assays and their associated limitations. Cytogenetic technologies such as karyotyping, fluorescent in situ hybridization or chromosomal microarrays are used to detect large "megabase level" copy number variants and other structural variants such as inversions or translocations. In contrast, molecular methodologies are heavily biased toward subgenic "small variants" such as single nucleotide variants, insertions/deletions, and targeted detection of intragenic, exon level deletions or duplications. The boundaries between these approaches are now increasingly blurred as next-generation sequencing technologies and their use for genome-wide analysis are used by both disciplines, therefore eliminating the historic and somewhat artificial separation driven by variant type.
This review discusses the history of genomic nomenclature across both fields, summarizes implementation challenges for the clinical genetics community, and identifies key considerations for enabling a seamless connection of the stakeholders that consume variant descriptions.
Standardization is naturally a lengthy and complex process that requires consensus building between different stakeholders. Developing a standard that not only fits the multitude of needs across the entities that consume genetic variant information but also works equally well for all genetic variant types is an ambitious goal that calls for revisiting this vision.
传统上，基因检测分为分子遗传学和细胞遗传学，最初是由不同检测方法及其相关局限性所驱动。细胞遗传学技术，如核型分析、荧光原位杂交或染色体微阵列，用于检测大的“兆碱基水平”拷贝数变异以及其他结构变异，如倒位或易位。相比之下，分子方法严重偏向于亚基因“小变异”，如单核苷酸变异、插入/缺失，以及基因内、外显子水平缺失或重复的靶向检测。随着下一代测序技术及其在全基因组分析中的应用被这两个领域所采用，这些方法之间的界限现在越来越模糊，因此消除了由变异类型驱动的历史上有些人为的分离。
本综述讨论了这两个领域基因组命名法的历史，总结了临床遗传学领域在实施过程中面临的挑战，并确定了实现无缝连接使用变异描述的利益相关者的关键考虑因素。
标准化自然是一个漫长而复杂的过程，需要不同利益相关者之间达成共识。制定一个不仅能满足使用基因变异信息的众多实体的各种需求，而且对所有基因变异类型都同样适用的标准，是一个雄心勃勃的目标，需要重新审视这一愿景。
