Stanford University, 450 Jane Stanford Way, Stanford, CA 94305, USA.
Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Genes (Basel). 2023 Feb 15;14(2):493. doi: 10.3390/genes14020493.
The powerful utilities of current DNA sequencing technology question the value of developing clinical cytogenetics any further. By briefly reviewing the historical and current challenges of cytogenetics, the new conceptual and technological platform of the 21st century clinical cytogenetics is presented. Particularly, the genome architecture theory (GAT) has been used as a new framework to emphasize the importance of clinical cytogenetics in the genomic era, as karyotype dynamics play a central role in information-based genomics and genome-based macroevolution. Furthermore, many diseases can be linked to elevated levels of genomic variations within a given environment. With karyotype coding in mind, new opportunities for clinical cytogenetics are discussed to integrate genomics back into cytogenetics, as karyotypic context represents a new type of genomic information that organizes gene interactions. The proposed research frontiers include: 1. focusing on karyotypic heterogeneity (e.g., classifying non-clonal chromosome aberrations (NCCAs), studying mosaicism, heteromorphism, and nuclear architecture alteration-mediated diseases), 2. monitoring the process of somatic evolution by characterizing genome instability and illustrating the relationship between stress, karyotype dynamics, and diseases, and 3. developing methods to integrate genomic data and cytogenomics. We hope that these perspectives can trigger further discussion beyond traditional chromosomal analyses. Future clinical cytogenetics should profile chromosome instability-mediated somatic evolution, as well as the degree of non-clonal chromosomal aberrations that monitor the genomic system's stress response. Using this platform, many common and complex disease conditions, including the aging process, can be effectively and tangibly monitored for health benefits.
当前 DNA 测序技术的强大功能使人们质疑进一步开发临床细胞遗传学的价值。通过简要回顾细胞遗传学的历史和当前挑战，提出了 21 世纪临床细胞遗传学的新概念和新技术平台。特别是，基因组结构理论（GAT）已被用作一个新的框架，强调了在基因组时代临床细胞遗传学的重要性，因为核型动力学在基于信息的基因组学和基于基因组的宏观进化中起着核心作用。此外，许多疾病可以与特定环境中基因组变异水平升高相关。考虑到核型编码，讨论了将基因组学整合回细胞遗传学的新机会，因为核型背景代表了一种新的基因组信息类型，它组织了基因相互作用。提出的研究前沿包括：1. 关注核型异质性（例如，对非克隆性染色体异常（NCCA）进行分类、研究嵌合体、异态性和核架构改变介导的疾病）；2. 通过描绘基因组不稳定性和阐明应激、核型动力学与疾病之间的关系来监测体细进化过程；3. 开发整合基因组数据和细胞遗传学的方法。我们希望这些观点能够引发超越传统染色体分析的进一步讨论。未来的临床细胞遗传学应该对染色体不稳定介导的体细胞进化以及监测基因组系统应激反应的非克隆性染色体异常程度进行分析。使用这个平台，可以有效地、有形地监测许多常见和复杂的疾病状况，包括衰老过程，以促进健康。
