揭开心肌病的细胞特征与罕见的变异驱动的基因特征使用多omics分析
Ha-Eun Jeong1, Kyung-Hyun Kim1, Youngjun Kim1
1Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju, 28159, Republic of Korea.
Scientific reports
|December 30, 2025
概括
全基因组测序发现了与心肌病相关的罕见遗传变异. 整合单细胞数据显示,这些变异影响心脏发育和细胞相互作用,为疾病原因提供了新的见解.
科学领域:
- 基因组学和分子生物学
- 心血管研究研究心血管研究
- 单细胞转录组学 单细胞转录组学
背景情况:
- 全基因组测序的进步产生了许多不具特征的变异.
- 心肌病,包括扩张性 (DCM) 和高性 (HCM) 形式,具有复杂的遗传基础.
- 了解罕见变异的功能影响对于疾病诊断和治疗至关重要.
研究的目的:
- 使用全基因组测序,对心肌病患者的罕见遗传变异进行鉴定.
- 通过单细胞转录学来研究受这些变异影响的细胞环境和生物途径.
- 为了识别与心肌病病源相关的新型基因特征.
主要方法:
- 245名韩国心肌病患者的全基因组测序.
- 罕见变异的识别和负担分析.
- 11,664个心脏组织细胞的单细胞RNA测序.
- 与DCM和HCM的人类表现型本体学 (HPO) 术语的相关性分析.
主要成果:
- 发现了3584种罕见变异,包括50种致病性/可能致病性变异.
- 在心脏发育和形态发生路径中丰富的不确定的意义 (VUS) 变异的144个基因签名.
- 在这些基因特征和心肌病表型 (DCM/HCM) 之间发现了显著的相关性.
- 单细胞分析揭示了由变异关联基因影响的细胞异质性和相互作用 (心肌细胞,内皮细胞).
结论:
- 罕见的遗传变异,包括VUS,与心脏发育和心肌病中的瘤完整性有关.
- 心肌细胞和非心肌细胞都在疾病病因学中发挥着关键作用.
- 整合基因组和单细胞数据为心肌病提供了有价值的机制性见解.
相关概念视频
01:25Cardiomyopathy I: Introduction and Classification
471
Cardiomyopathy, or CMP, is a group of diseases affecting the myocardial structure, impairing its ability to pump blood effectively. This condition can lead to arrhythmias, heart failure, or sudden cardiac death.Cardiomyopathies are classified into primary and secondary categories:Primary Cardiomyopathy refers to conditions involving only the heart muscle that are often idiopathic (of unknown cause) or genetic. They primarily affect the myocardium without the involvement of other systemic...
471
01:30Cardiomyopathy II: Dilated Cardiomyopathy
431
Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
431
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
360
Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
360
01:29Cardiomyopathy IV: Restrictive Cardiomyopathy
422
Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
422
02:02Genomics
39.5K
Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
39.5K