自闭症疾病风险基因在神经发育过程中的动态融合
Meilin Fernandez Garcia1, Kayla Retallick-Townsley1,2, April Pruitt3
1Departments of Psychiatry and Genetics, Division of Molecular Psychiatry, Department of Genetics, Wu Tsai Institute, Yale University School of Medicine, New Haven, CT 06511.
bioRxiv : the preprint server for biology
|September 4, 2024
概括
自闭症谱系障碍 (ASD) 风险基因汇聚在共同的目标上,特别是在成熟的谷氨酸神经元中. 这种趋同为开发针对ASD的向治疗提供了新的途径.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 干细胞生物学 干细胞生物学
背景情况:
- 超过100个基因与自闭症谱系障碍 (ASD) 风险有关.
- 这些风险基因在共享的下游途径上的融合仍然不太清楚.
- 细胞背景可能会影响这些风险基因的相互作用.
研究的目的:
- 调查细胞环境是否影响自闭症谱系障碍 (ASD) 风险基因的融合.
- 在不同的神经细胞类型中识别受ASD风险基因影响的共享下游目标和途径.
主要方法:
- 采用了聚合的CRISPR查方法,针对29个ASD功能丧失基因.
- 将这种方法应用于人类诱导的多能干细胞 (hiPSC) 衍生的神经原生细胞,谷氨酸神经元和GABAergic神经元.
- 进行了基因层面和网络层面的分析,以评估基因融合.
主要成果:
- 基因融合在成熟的谷氨酸性神经元中最为明显.
- 融合效应在不同细胞类型的强度,组成和生物作用上有动态变化.
- 融合与ASD基因的功能相似性增加,并由细胞类型特定的基因共同表达模式驱动.
- 自闭症基因的分层导致了药物预测,从而扭转了细胞和行为表型.
结论:
- 自闭症风险基因下游的融合网络代表了治疗干预的关键目标.
- 细胞背景显著影响ASD风险基因的融合.
- 可以根据ASD基因的分层及其融合效应开发个性化治疗策略.
相关概念视频
01:19Autism Spectrum Disorder
77
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.
77
01:28Human Genetics
549
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...
549
01:23Behavioral Genetics and Its Designs
345
Behavior genetics explores how genetic inheritance influences human behavior. It focuses on how genes, passed from parents to offspring, contribute to the development of behavioral traits and tendencies. This branch of genetics seeks to understand the complex interplay between inherited genetic factors and environmental influences in shaping our behaviors.
The primary methodologies used in behavior genetics include family studies, twin studies, and adoption studies, each providing unique...
The primary methodologies used in behavior genetics include family studies, twin studies, and adoption studies, each providing unique...
345
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
01:30Attention-Deficit/Hyperactivity Disorder
50
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by persistent inattention, hyperactivity, and impulsivity. It affects approximately 5-8% of children globally, with around 60-70% of cases persisting into adulthood. ADHD has significant implications for educational attainment, social interactions, and occupational success.
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....
50
01:11Genetic Lingo
102.2K
Overview
102.2K