c.6480-35A>G,一种与Stargardt病相关的新型分支变体
María Rodríguez-Hidalgo1,2, Suzanne E de Bruijn3, Zelia Corradi3
1Department of Neuroscience, Biodonostia Health Research Institute, Donostia-San Sebastián, Spain.
Frontiers in genetics
|October 2, 2023
概括
在Stargardt病患者中发现了ABCA4基因的新型变异c.6480-35A>G. 功能测试证实了它的拼接缺陷,将其归类为可能引起遗传视网膜变的病原体.
科学领域:
- 遗传学 是一个遗传学.
- 眼科医生 眼科 眼科
- 分子生物学分子生物学
背景情况:
- 遗传性视网膜发育不良 (IRDs) 涉及超过280个基因,其中ABCA4变异导致Stargardt病和相关疾病.
- 大约25%的ABCA4变异影响RNA剪接,通常需要功能测试来评估病原性.
研究的目的:
- 为了研究一种新的ABCA4分支变异的致病性,c.6480-35A>G,在西班牙斯塔格特病患者中确定.
- 用in silico和in vitro方法评估这种变体的拼接效应.
主要方法:
- 全基因组测序 (WGS) 在IRD试验中确定了候选变体.
- 在 silico 分析中使用了 SpliceAI 深度学习工具来预测拼接变化.
- 在体外功能验证中,在HEK293T细胞中使用了中基因拼接试验.
主要成果:
- WGS揭示了一种新的分支点变体 (c.6480-35A>G) 和已知的ABCA4基因缺失.
- 由于变种,SpliceAI预测了c.6480-47的高得分接受器增长.
- 中基因试验表明异常拼接,包括内基序列和过早停止子,将变体分类为中度严重.
结论:
- c.6480-35A>G变体的拼接改变效果,通过功能测定和其在第二名患者中的存在得到证实,支持其被归类为可能引起Stargardt病的病原体.
- 这项研究强调了分析非编码区域和使用功能测试来准确分子诊断IRD的重要性.
更多相关视频
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
33.8K
09:37A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
8.3K
相关概念视频
01:20The Retinoblastoma Gene
4.1K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.1K
01:11Genetic Lingo
103.0K
Overview
103.0K
01:11Genome-wide Association Studies-GWAS
13.6K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
13.6K
01:31ABC Transporters: Exporter
4.4K
ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
4.4K