SOX7:自闭症关联基因通过分析多个omics数据来识别
Samantha Gonzales1, Jane Zizhen Zhao2, Na Young Choi3
1Department of Biostatistics, Florida International University, Miami, FL 33199.
bioRxiv : the preprint server for biology
|June 9, 2023
概括
这项研究整合了DNA和RNA数据,以确定自闭症谱系障碍 (ASD) 的遗传联系. 发现SOX7基因与ASD有显著的关联,并且在患者中显示出差异性表达,这表明它在ASD发展和作为生物标志物的潜在作用.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 神经科学是一个神经科学.
- 生物标志物发现发现
背景情况:
- 自闭症谱系障碍 (ASD) 具有很高的遗传性,但很少有常见的遗传变异可靠地与诊断有关.
- 大多数已识别的ASD相关突变是非编码的,因此很难确定功能和因果变异.
- 缺乏可靠的生物标志物用于ASD诊断和重度评估的分子机制,需要综合遗传和转录基因方法.
研究的目的:
- 整合全基因组关联研究 (GWAS) 和RNA测序 (RNA-seq) 数据,以确定ASD的潜在因果基因.
- 调查ASD病例和对照之间的基因表达差异.
- 确定潜在的遗传生物标志物用于ASD诊断和治疗策略.
主要方法:
- 进行基因相关性研究,使用来自两个大型ASD队列的GWAS总结统计数据 (发现和复制数据).
- 使用两个独立的RNA-seq数据集,研究了ASD病例和对照之间的差异性基因表达.
- 使用适应性测试和Benjaminini-Hochberg对统计学意义进行校正.
主要成果:
- 在发现GWAS数据中确定了五种与ASD显著相关的基因:KIZ-AS1,KIZ,XRN2,SOX7和LOC101929229 (PINX1-DT).
- 在复制GWAS数据中复制SOX7和LOC101929229的复制关联;KIZ-AS1和KIZ显示了近似复制.
- 在RNA-seq数据集中,SOX7在ASD病例和对照病例之间显示出显著的差异表达,在病例中被上调.
结论:
- 编码参与细胞命运决定的转录因子的SOX7基因与ASD有显著的关联.
- 在ASD患者中SOX7的差异表达表明它在ASD病变发生过程中的潜在作用.
- SOX7代表了一种有希望的候选基因,用于开发新的诊断生物标志物和ASD治疗策略.
相关概念视频
01:33Pleiotropy
40.7K
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,...
40.7K
01:19Autism Spectrum Disorder
166
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.
166
01:11Genome-wide Association Studies-GWAS
13.7K
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...
13.7K
02:24Ribosome Profiling
3.6K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.6K
01:43Sex-linked Disorders
102.4K
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
102.4K