一种保护性超级增强剂变体调节SLC7A7调节自闭症谱系障碍风险:一个跨人群研究
Jiao Zhang1, Fang Hou2, Yanlin Chen2
1Department of Maternal and Child Health and MOE (Ministry of Education) Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
概括
一个新的遗传变异,rs1951568-A,在一个超级增强器区域内提供了对自闭症谱系障碍 (ASD) 的保护. 这一发现突显了超强增强剂变体在自闭症发展中的作用,并表明了涉及SLC7A7基因调节的机制.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 基因组法规 基因组法规
背景情况:
- 自闭症谱系障碍 (ASD) 是一种复杂的神经发育状况,具有显著的遗传成分.
- 超级增强剂的作用,关键的基因组调节元素,在ASD病原体的作用还不清楚.
- 在这些调节区域内识别基因变异对于理解ASD病因至关重要.
研究的目的:
- 在与ASD易感基因相关的超级增强剂中识别功能单核酸多态 (SNP).
- 调查这些SNP对ASD风险的贡献.
- 阐明所识别的变种背后的监管机制.
主要方法:
- 集成ASD易感基因,差异表达基因和大脑皮层超强增强剂数据.
- 使用表达式定量特征位置 (eQTL) 分析和功能预测工具来优先考虑SNP.
- 在中国和欧洲人群中进行的病例控制关联研究,随后进行双化酶报告员测定.
主要成果:
- 在调节15个ASD基因的20个超级增强剂中,确定了11个功能性SNP.
- 在SLC7A7超级增强剂中的rs1951568 G>A变异在中国和欧洲队列中显示出与ASD的保护性关联.
- eQTL分析和功能测定表明,rs1951568-A等位基因通过增强转录抑制剂TBX5和ZEB1.1的结合来减少SLC7A7的表达.
结论:
- rs1951568-A变种是ASD的一个新型保护因子.
- 这种保护作用是通过SLC7A7表达在超级增强剂中的调节来实现的.
- 超级增强剂变体是研究ASD遗传结构的一个重要领域.
相关概念视频
Pleiotropy
43.4K
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,...
43.4K
Genome-wide Association Studies-GWAS
15.8K
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...
15.8K
Autism Spectrum Disorder
1.3K
Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by persistent deficits in social communication and interaction alongside restrictive and repetitive behaviors or interests. ASD is sometimes accompanied by intellectual impairment.
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
1.3K
Human Genetics
1.7K
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
1.7K
Comparing Copy Number Variations and SNPs
18.8K
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
18.8K
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
13
The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
13


