在皮质层特定基因中的短串重复扩张涉及自闭症谱系障碍的表型严重性和适应性
Jae Hyun Kim1,2, In Gyeong Koh1,2, Hyeji Lee1,2
1Department of Integrated Biomedical and Life Science, Korea University, Seoul, Republic of Korea.
Psychiatry and clinical neurosciences
|May 16, 2024
概括
对于早期大脑发育至关重要的基因的短串重复 (STR) 扩张与自闭症谱系障碍 (ASD) 有关. 这些遗传变异可能会增加自闭症风险和严重程度,影响神经发育.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
背景情况:
- 短串联重复 (STR) 是可变的DNA序列,涉及到各种遗传疾病.
- 在自闭症谱系障碍 (ASD) 中STRs的作用已被显著研究不足.
- 了解导致自闭症的遗传因素对于早期诊断和干预至关重要.
研究的目的:
- 调查STR扩张和ASD之间的遗传关联.
- 识别特定的STR位点,使ASD表型具有风险.
- 探索STR扩展对神经发育基因的功能影响.
主要方法:
- 用634个ASD家族的全基因组测序 (WGS) 数据对12929个STR位点进行全基因组评估.
- 整合单细胞RNA和ATAC测序数据,以优先考虑皮层发育特异性基因中的STRs.
- 应用深度学习模型来预测ASD相关的STR位点的功能.
主要成果:
- 在ASD病例中发现了罕见的STR扩展,特别是在早期皮质层特定基因中,这些基因参与了神经发育.
- 发现STR扩张会破坏增强剂和促进剂的调节活性,这表明一种致病机制.
- 患有ASD携带STR扩张的个体表现出更严重的ASD表型和降低的适应能力.
结论:
- 在皮质层特定基因中的STR扩张代表了ASD的潜在遗传风险因素.
- 这项研究提供了STR扩张与ASD相关的第一个证据,这些证据是在以前研究不足的人群中发现的.
- 在关键的神经发育时期,STR扩张可能会通过破坏基因调节来促进ASD的发病.
相关概念视频
Autism Spectrum Disorder
83
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.
83
Pleiotropy
40.4K
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,...
40.4K
Human Genetics
561
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...
561
Genome-wide Association Studies-GWAS
13.3K
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...
13.3K
Comparing Copy Number Variations and SNPs
17.7K
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%...
17.7K


