LARP1的哈普洛缺陷与一种自体主导的神经发育障碍有关
James Chettle1, Raymond J Louie2, Olivia Larner3
1Department of Oncology, University of Oxford, Oxford, UK.
HGG advances
|August 25, 2024
概括
LARP1基因中的遗传变异与自闭症谱系障碍 (ASD) 和其他神经发育障碍 (NDD) 有关. 减少LARP1蛋白质会损害细胞代谢,可能会影响ASD患者的大脑发育.
科学领域:
- 遗传学 是一个遗传学.
- 神经发育障碍 神经发育障碍
- 分子生物学分子生物学
背景情况:
- 自闭症谱系障碍 (ASD) 和其他神经发育障碍 (NDD) 影响着相当一部分人群.
- 虽然多因素,但罕见的遗传变异约占自闭症病例的20%.
- LARP1 (La ribonucleoprotein 1) 是一种RNA结合蛋白,对于mRNA调节至关重要.
研究的目的:
- 调查LARP1基因中新异体变异在ASD和NDD表型中的作用.
- 探索LARP1变异对细胞代谢的功能影响.
- 提出一种机制,将LARP1哈普洛缺陷与神经发育障碍联系起来.
主要方法:
- 对7名具有ASD/NDD表型的无关试验者的案例系列分析.
- 基因分析以识别LARP1.1.中的新型异质合体功能丧失或误解变体.
- 使用永生淋巴细胞进行功能研究,以评估与LARP1蛋白水平相关的细胞代谢 (有氧呼吸和糖解).
主要成果:
- 七个无关联的个体 (6名男性,1名女性) 呈现出与LARP1.1中新异构体变异相关的ASD或NDD表型.
- 较低的LARP1蛋白的细胞水平与有氧呼吸和糖解的降低率有关.
- 在神经发育过程中,LARP1的表达增加,在神经元和星体细胞中观察到更高的水平.
结论:
- 在LARP1中,De novo异构的变异与ASD和其他NDD有关.
- LARP1的哈普洛缺陷导致细胞代谢活动受损.
- 由于LARP1杂交缺陷,胎儿大脑发育中的代谢活动减弱可能会导致ASD和相关的NDD.
关键词:
在ASD中,使用的是ASD.在LARP1中使用LARP.NDD NDD NDD NDD NDD NDD NDD NDD NDD NDD NDD NDD NDD NDD NDD NDD NDD NDD在RBP中使用RBP.这是一种RNA结合蛋白.自闭症自闭症是什么代谢过程中的代谢.神经发育的神经发育.塑性的可塑性 塑性探针和探针可以检测到.更多相关视频
08:22A 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
8.6K
00:06In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
13.6K
相关概念视频
Lysosomal Hydrolases
3.8K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.8K
Pedigree Analysis
84.1K
Overview
84.1K
Long-term Potentiation
55.0K
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre- and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
55.0K
Pleiotropy
40.3K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.3K
Lethal Alleles
15.4K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.4K
Incomplete Dominance
22.2K
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
22.2K
