相关实验视频

Updated: Jul 5, 2025

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

在人类神经管缺陷中识别和功能分析罕见的HECTD1误解变异

Elias Oxman¹, Huili Li², Hong-Yan Wang³

¹Children's National Hospital.

Research square

|January 23, 2024

概括

罕见的HECTD1基因变异与人类神经管缺陷 (NTD) 有关. 这些突变会损害HECTD1的功能.

科学领域:

遗传学遗传学是一个
发展生物学发展生物学
分子生物学分子生物学

背景情况:

神经管缺陷 (NTDs) 是由于神经管闭合失败导致的严重出生缺陷.
在小鼠模型中,HECTD1,一种E3泛素酶,对于神经管闭合至关重要.
之前的研究将细胞外热冲击蛋白90 (eHSP90) 的分泌量增加与Hectd1突变小鼠的异常骨介质形态发生联系起来.

研究的目的:

研究HECTD1序列变异与人类NTD之间的关联.
评估已识别的HECTD1误解变异对HECTD1表达和eHSP90分泌的功能影响.

主要方法:

针对性下一代测序在352个NTD病例和224个对照组的中国队列上进行.
用HEK293T细胞的功能测试来评估蛋白质表达和HECTD1变体对eHSP90分泌的调节功能.
分析了HECTD1的保存和对突变的不耐受性.

主要成果:

在NTD病例中发现了五种罕见的HECTD1误解变异.
这五种变异都显著降低了HECTD1调节eHSP90分泌的能力.
一种变体 (A1084T) 在HEK293T细胞中显著减少了蛋白质表达.
发现HECTD1具有高度保护性,对功能丧失和误解突变不耐受.

结论:

这项研究提供了第一个证据,将HECTD1序列变异与人类NTD联系起来.
在HECTD1的序列变化可能会通过影响eHSP90调节对人类NTDs的病因产生影响.
需要进一步的研究来阐明HECTD1变异对NTDs的贡献的确切机制.

关键词:

HECTD1 是一个对象.神经管缺陷的神经管缺陷头骨中介质组中的一个.细胞外的HSP90 HSP90 的情况.

更多相关视频

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

相关概念视频

Neurulation

Neurulation

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...

Notch Signaling Pathway

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...