在刺激的巨细胞中拼接QTL映射将低使用的拼接连接与免疫介导疾病风险联系起来
Omar El Garwany1, Nikolaos I Panousis1, Andrew Knights1
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1RQ, UK.
Nature communications
|August 27, 2025
概括
影响免疫细胞替代拼接 (sQTL) 的基因变异与免疫介导疾病 (IMD) 有关. 较少使用的拼接连接有助于复杂疾病的风险,为疾病机制提供了新的见解.
科学领域:
- 遗传学
- 免疫学
- 分子生物学
背景情况:
- 免疫媒介疾病 (IMD) 经常与非编码基因组区域的遗传风险位置有关.
- 这些非编码变体的功能影响,特别是关于替代拼接,在免疫环境中仍然很不清楚.
研究的目的:
- 研究替代拼接在免疫媒介疾病 (IMD) 风险中的作用.
- 在各种环境刺激下在免疫细胞中绘制拼接定量特征位点 (sQTL).
主要方法:
- 在暴露于各种环境刺激的巨细胞中绘制sQTL.
- 具有已知的IMD相关风险位置的局部化sQTL信号.
- 分析了特定IBD风险基因对PTPN2异形使用的影响.
主要成果:
- 鉴定了超过5734个基因的显著sQTL效应,与先天免疫反应基因的广泛差异拼接.
- 在700多个基因中实现了sQTL信号与IMD风险位的高可靠性同位分 (PP4 ≥0. 75).
- 发现大约一半的这些同位点涉及使用较少的拼接接口 (平均使用比率<0.1).
- 证明IBD风险等位基因改变了PTPN2异型的使用,影响了一个关键的炎症调节器.
结论:
- 替代拼接在免疫介导疾病的遗传结构中起着重要作用.
- 低使用的拼接事件是复杂疾病风险的关键因素.
- 在相关细胞类型的sQTL分析提供了功能性解释IMD风险位的强大方法.
相关概念视频
RNA Splicing
56.9K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.9K
Alternative RNA Splicing
21.7K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.7K
Pre-mRNA Processing: RNA Splicing
5.4K
5.4K
Chromatin Structure and RNA Splicing
2.8K
2.8K
Exon Recombination
3.7K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
3.7K
Mismatch Repair
5.2K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.2K


