相关实验视频

Updated: Jul 20, 2025

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

导致新生儿线粒体疾病的新型FARS2变体的临床和分子表征

Wenqian Chen¹, Preeya Rehsi², Kyle Thompson³

¹Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.

Molecular genetics and metabolism

|July 31, 2023

概括

在FARS2中的致病变体对于线粒体蛋白质合成至关重要,导致严重的早期脑病变. 这项研究详细介绍了一种新的FARS2误解变体R198L,证明了它对线粒体 fenylalanyl-tRNA合成酶的有害结构和功能影响.

科学领域:

生物化学生物化学
遗传学是一个遗传学.
线粒体生物学线粒体生物学

背景情况:

FARS2编码了线粒体氨基-tRNA合成酶 (mtPheRS),这对于线粒体内翻译至关重要.
致病性FARS2变体通常会导致早期发作的性脑病变或晚期发作的性.

研究的目的:

在患有早期线粒体疾病的患者中研究新型化合物异构性FARS2变异的致病性.
描述FARS2误解变异的结构和功能影响 (p.

主要方法:

三重整体外基因组测序以识别FARS2变体.
纤维细胞分析以评估mtPheRS水平和氧化酸化.
高分辨率的晶体结构的确定mtPheRS.
酶性测试以评估p.(Arg198Leu) 突变的影响.

主要成果:

已识别出复合异性FARS2变体,包括一个外2删除和一个误解变体 (c.593G>T, p.
患者的纤维细胞显示mtPheRS水平降低,但氧化酸化完好无损.
这种p.(Arg198Leu) 突变破坏了mtPheRS结构的稳定性,降低了热稳定性和酶活性受损.
活动受损的原因是tRNA^Phe结合亲和力降低和循环速度减慢.

结论:

已识别的FARS2变种,特别是p.(Arg198Leu) missense变种,是致病性的.
这项研究证实了FARS2变种在引起早期线粒体的作用.
结构和功能数据为FARS2相关疾病提供了机械洞察力.

关键词:

在FARS2中,FARS2是FARS2.功能性测试是指功能性测试.线粒体疾病线粒体疾病线粒体inylalanyl-tRNA合成酶的作用变种分类的变种分类

更多相关视频

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing

Published on: February 10, 2023

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

相关概念视频

Animal Mitochondrial Genetics

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...