Lomberk Gwen, Urrutia Raul
Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Division of Research, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
Epigenomics. 2025 Feb;17(2):115-124. doi: 10.1080/17501911.2024.2436837. Epub 2024 Dec 4.
Rare and undiagnosed diseases pose significant challenges for understanding their mechanisms, diagnosis, and treatment. The Triple Code Model, an integrative paradigm described here, considers the combined influence of the genetic code, epigenetic code, and nuclear structure (an emerging code), as fundamental biochemical mechanisms underlying many rare diseases. Studies demonstrate dysfunctional membrane and cytoplasmic signals instruct the epigenome to ultimately impact the 3D structure and dynamics of the nucleus, highlighting their close interrelationships. Consequently, this model offers a holistic perspective on rare and undiagnosed diseases by moving beyond a solely genetic view. We propose that this integrated framework will efficiently guide rare disease research by taking it 'Beyond the Base Pairs,' leading to improved diagnostics and personalized treatments.
罕见病和未确诊疾病在理解其发病机制、诊断和治疗方面构成了重大挑战。本文所描述的三联密码模型是一种综合范式，它将遗传密码、表观遗传密码和核结构（一种新兴密码）的综合影响视为许多罕见病背后的基本生化机制。研究表明，功能失调的膜和细胞质信号会指导表观基因组，最终影响细胞核的三维结构和动态变化，凸显了它们之间的密切相互关系。因此，该模型通过超越单纯的遗传学观点，为罕见病和未确诊疾病提供了一个整体视角。我们提出，这个综合框架将通过“超越碱基对”有效地指导罕见病研究，从而改善诊断和个性化治疗。
