全球罕见副本数量变化的功能影响在自闭症谱系障碍中的功能影响
Dalila Pinto1, Alistair T Pagnamenta, Lambertus Klei
1The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada.
Nature
|June 10, 2010
概括
自闭症谱系障碍 (ASD) 与罕见的遗传拷贝数变异 (CNV) 的较高负担有关. 这些遗传因素,包括新的基因和途径,为理解ASD提供了新的目标.
科学领域:
- 遗传学 是一个遗传学.
- 神经发育障碍 神经发育障碍
- 生物信息学是一种生物信息学.
背景情况:
- 自闭症谱系障碍 (ASD) 是一种复杂的神经发育状况,其特点是社会互动和沟通缺陷,以及受限制的行为.
- 虽然遗传性很高 (~90%),但ASD的特定遗传原因在很大程度上仍未确定.
- 患有自闭症的个体的认知发展高度可变,从高于平均水平的智力到智力障碍.
研究的目的:
- 研究ASD患者罕见拷贝数变异 (CNV) 的全基因组特征.
- 识别与ASD病因相关的新型遗传因素和途径.
- 为了比较ASD病例中罕见的CNVs负担与匹配的对照.
主要方法:
- 使用密集基因型阵列对全基因组CNV进行分析.
- 996名自闭症个体和1287名欧洲血统的对照人群之间的罕见 (<1%频率) CNV 的比较.
- 鉴定de novo和遗传性CNV,包括家族事件.
主要成果:
- 与对照组相比,ASD病例的罕见基因CNV的全球负担显著增加 (1.19倍,P = 0.012).
- 在之前与ASD和/或智力障碍相关的位置观察到CNVs的更大丰富 (1.69倍,P = 3.4 x 10 ((-4)).
- 发现了与ASD相关的新型基因 (例如SHANK2,SYNGAP1,DLGAP2,DDX53-PTCHD1) 和功能性基因组 (细胞增殖,GTPase/Ras信号传递) 的破坏.
结论:
- 罕见的CNV代表了导致ASD的重要遗传因素.
- 这项研究涉及许多新型基因和途径在ASD病原体.
- 这些发现为了解ASD相关的生物学途径提供了基础.
相关概念视频
Comparing Copy Number Variations and SNPs
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%...
Autism Spectrum Disorder
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.
Genome Copying Errors
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
Pleiotropy
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,...
Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
Genome-wide Association Studies-GWAS
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...


