与自闭症相关的基因和邻近的 lncRNAs 在关键基因调节网络上融合
Rebecca E Andersen1,2,3,4, Maya Talukdar1,2,3,5, Tyler Sakamoto1,6
1Division of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA.
bioRxiv : the preprint server for biology
|February 3, 2025
概括
自闭症谱系障碍 (ASD) 的遗传变异破坏了基因调节网络 (GRNs). 这项研究揭示了包括IncRNA在内的多种ASD基因如何汇聚到共享的神经发育途径上,为理解ASD提供了一个新的框架.
科学领域:
- 遗传学 遗传学 是一个
- 神经科学是一个神经科学.
- 生物信息学是一种生物信息学.
背景情况:
- 自闭症谱系障碍 (ASD) 与多种不同的遗传变异有关,使核心疾病机制的识别变得复杂.
- 了解受这些独特遗传因素影响的共享生物途径对于开发有效干预措施至关重要.
研究的目的:
- 汇总和分析与ASD相关的不同类型的遗传变异.
- 研究ASD相关基因和长非编码RNAs (lncRNAs) 对基因表达的功能影响.
- 构建一个基因调节网络 (GRN),以识别ASD中的中央调节者.
主要方法:
- 创建共识-ASD数据库来分类遗传变异.
- 对ASD基因和邻近的lncRNAs的CRISPR-Cas13功能质询.
- 基因调控网络 (GRN) 的构建和分析.
主要成果:
- 在七个类别的ASD遗传变异中发现了共同的特征.
- 功能性询问揭示了对其他ASD基因显著丰富的差异性基因表达特征.
- 在GRN中,在ASD基因中断时具有融合性改变活性的中央调节器被确定.
结论:
- 扰乱独特的ASD相关基因导致GRNs的共同,广泛的失调.
- 这为了解包括 lncRNAs 在内的多种基因如何通过神经发育中的融合作用对 ASD 产生贡献提供了一个框架.
- 这些发现强调了网络层面分析对于破译ASD病原学的重要性.
相关概念视频
lncRNA - Long Non-coding RNAs
8.5K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.5K
Genome-wide Association Studies-GWAS
12.4K
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...
12.4K
Cis-regulatory Sequences
9.7K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
9.7K
RNA Polymerase II Accessory Proteins
9.1K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.1K
Combinatorial Gene Control
8.3K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.3K
Non-LTR Retrotransposons
11.4K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.4K


