与精神分裂症风险相关的SNP影响microRNA 137宿主基因的表达:一项死后研究
Ningping Feng1, Ajeet Mandal1, Ananya Jambhale1
1Human Brain Collection Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, Bldg 10, room 4N218, Bethesda, MD 20892, United States.
Human molecular genetics
|September 6, 2024
概括
在MIR137HG中,精神分裂症风险变异与其不成熟的转录的改变表达有关,这表明在遗传倾向中发挥了作用. 需要进一步验证才能在脑组织中证实这些发现.
科学领域:
- 神经遗传学 神经遗传学
- 分子精神病学分子精神病学
背景情况:
- 常见的MIR137HG和DPYD变异与精神分裂症风险有关,由精神病基因组学联盟 (PGC) 证实.
- 了解这些与风险相关的单核酸多态 (SNP) 的功能影响,对于阐明精神分裂症病因至关重要.
研究的目的:
- 研究MIR137HG基因组区域中与精神分裂症风险相关的SNP与miR-137宿主基因转录的表达之间的关联.
- 检查从精神分裂症和对照患者的死后脑样本中的MIR137HG转录表达.
主要方法:
- 使用定量PCR (qPCR) 和RNA测序 (RNA-Seq) 来分析成熟和不成熟的MIR137HG转录.
- 研究的表达水平在脊侧前额叶皮层 (DLPFC) 和阴前环皮层 (sgACC) 的精神分裂症患者和对照.
主要成果:
- 在精神分裂症病例和对照之间没有观察到成熟的miR-137,MIR137HG或其转录的差异表达.
- 两个PGC识别的精神分裂症风险SNP,rs11165917和rs4274102,与欧洲祖先个体的MIR137HG-203长非编码RNA转录表达有关.
- 对于rs11165917的风险等位基因携带者,MIR137HG-203的表达显著降低,尽管这并未通过短读测序验证.
结论:
- 该研究没有发现精神分裂症中成熟的MIR137HG转录的差异表达.
- 精神分裂症风险SNP可能会影响不成熟的MIR137HG转录的表达,可能会导致遗传风险.
- 需要进一步的研究来验证未成熟的MIR137HG转录在精神分裂症中的作用.
相关概念视频
01:22MicroRNAs
3.0K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
01:29Biological Causes of Schizophrenia
51
Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
51
01:11Genome-wide Association Studies-GWAS
13.2K
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...
13.2K
02:18Alternative RNA Splicing
21.1K
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...
21.1K