揭开先天性脊椎形的遗传架构,与脊柱发育有关
Sen Zhao1,2,3, Hengqiang Zhao1,4,5, Lina Zhao1,4,6
1Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
Nature communications
|February 6, 2024
概括
这项研究确定了先天性脊椎形的遗传原因,揭示了与肌肉相关的机制. 使用先进的测序和RNAseq分析发现了关键的风险基因及其在脊柱发育中的作用.
科学领域:
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
- 整形外科 整形外科 整形外科
背景情况:
- 先天性脊椎形 (CVM) 影响每1000个活产儿中有0.13-0.50个.
- CVM 呈现出显著的位点异质性和复杂的遗传结构.
- 了解CVM的遗传基础对于诊断和治疗至关重要.
研究的目的:
- 为了确定潜在的先天性脊椎形的遗传病因.
- 研究参与脊柱发育和形的生物机制.
- 发现与CVM相关的新型风险基因.
主要方法:
- 来自873个CVM试验组和3794个对照组的外体/基因组测序数据的分析.
- 对超罕见变异的基因负担测试,以确定风险基因.
- 在人类胚胎脊柱上进行单核RNA测序 (snRNAseq),以评估生物相关性.
主要成果:
- 在12.0%的受试者中发现了门德尔病因,这表明了与肌肉相关的疾病机制.
- 基因负担测试发现了重要的风险基因:ITPR2,TBX6,TPO,H6PD和SEC24B.
- snRNAseq揭示了基因信号在心弦 (早期发育) 和肌细胞/肌细胞 (晚期发育) 中的丰富,这些细胞类型涉及到脊柱发育.
结论:
- 这项研究阐明了CVM的遗传结构,确定了关键的风险基因和与肌肉相关的发病因子.
- 这些发现凸显了记节和肌肉前体细胞在人类脊柱发育中的关键作用.
- 这项研究提供了对脊椎发育生物学和脊椎形病变的产生有价值的见解.
相关概念视频
Vertebral Column: Regions and Curvature
3.7K
The vertebral column or spine is a flexible column that supports the head, neck, and body and allows for their movements. It also protects the spinal cord.
Regions of the Vertebral Column
In an adult, the spine is subdivided into five regions: the cervical, the thoracic, the lumbar, the sacral, and the coccygeal region. The spine initially develops as a series of 33 vertebrae; after 20 years of age, the nine bones in the sacral region, five sacral, and four coccygeal bones fuse to form...
Regions of the Vertebral Column
In an adult, the spine is subdivided into five regions: the cervical, the thoracic, the lumbar, the sacral, and the coccygeal region. The spine initially develops as a series of 33 vertebrae; after 20 years of age, the nine bones in the sacral region, five sacral, and four coccygeal bones fuse to form...
3.7K
General Structure of a Vertebra
2.8K
A typical vertebra, with the exception of the sacrum and coccyx, consists of a body, a vertebral arch, and seven different projections termed processes. The anterior portion of the vertebrae, the body, supports about half the body’s weight. The vertebral bodies progressively increase in size and thickness from the cervical region to the lumbar region of the vertebral column. The intervertebral discs present between the bodies of adjacent vertebrae firmly unites them, forming a continuous...
2.8K
Sutures of the Skull
6.7K
The human skull is composed of several bones that come together to protect the brain and support the structures of the face. The junctions where these bones meet are called sutures.
Sutures are immobile joints between adjacent bones of the skull. The narrow gap between the bones is filled with dense, fibrous connective tissue that unites the bones. The long sutures located between the skull bones are not straight but instead follow irregular, tightly twisting paths. These twisting lines tightly...
Sutures are immobile joints between adjacent bones of the skull. The narrow gap between the bones is filled with dense, fibrous connective tissue that unites the bones. The long sutures located between the skull bones are not straight but instead follow irregular, tightly twisting paths. These twisting lines tightly...
6.7K
Neurulation
41.9K
Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...
41.9K
Changes in the Appendicular Skeleton with Age
2.0K
The upper and lower limb initially develops as a small bulge called a limb bud, which appears on the lateral side of the early embryo. The upper limb bud appears near the end of the fourth week of development, with the lower limb bud appearing shortly after.
Initially, the limb buds consist of a core of mesenchyme covered by a layer of ectoderm. The ectoderm at the end of the limb bud thickens to form a narrow crest called the apical ectodermal ridge. This ridge stimulates the underlying...
Initially, the limb buds consist of a core of mesenchyme covered by a layer of ectoderm. The ectoderm at the end of the limb bud thickens to form a narrow crest called the apical ectodermal ridge. This ridge stimulates the underlying...
2.0K
Bone Formation by Intramembranous Ossification
6.2K
Intramembranous ossification is one of the two processes involved in the development of bones within an embryo. The flat bones of the face, most of the cranial bones, and the clavicles are formed via this process. During intramembranous ossification, the bones develop directly from sheets of undifferentiated mesenchymal connective tissue.
The process begins when mesenchymal cells in the embryonic skeleton gather together and differentiate into osteogenic cells, which then develop into ...
The process begins when mesenchymal cells in the embryonic skeleton gather together and differentiate into osteogenic cells, which then develop into ...
6.2K


