自闭症全基因组复制数的变异揭示了无处不在和神经元基因的基因
Joseph T Glessner1, Kai Wang, Guiqing Cai
1Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Nature
|May 1, 2009
概括
这项研究确定了与神经元细胞粘附和无素通路相关的基因拷贝数变异 (CNVs),表明它们在自闭症谱系障碍 (ASD) 遗传易感性中的作用. 这些发现推动了我们对ASD的理解.
科学领域:
- 遗传学 遗传学 是一个
- 神经发育障碍 神经发育障碍
- 基因组学就是基因组学.
背景情况:
- 自闭症谱系障碍 (ASD) 是一种复杂的神经发育状况,具有已知的遗传基础.
- 之前的研究发现了与ASD风险相关的副本数变化 (CNV).
- 需要进行全面的全基因组CNV分析,以确定新的易感位点.
研究的目的:
- 识别与自闭症谱系障碍 (ASDs) 相关的新型拷贝数变异 (CNVs).
- 研究特定基因网络在ASD易感性中的作用.
- 在一个独立的队列中验证发现.
主要方法:
- 使用单核酸多态 (SNP) 阵列进行全基因组CNV分析.
- 859例ASD病例和1,409例对照的基因型定型,在第二个队列中进行验证 (1,336例,110例对照).
- 统计分析以确定与对照组相比,在ASD病例中显著丰富的CNV.
主要成果:
- 在先前已知的ASD相关基因 (例如NRXN1,CNTN4) 中确定了CNV.
- 发现了参与神经元细胞粘附 (NLGN1,ASTN2) 和无素通路 (UBE3A,PARK2,RFWD2,FBXO40) 的新型基因中 CNVs 的丰富.
- 在AK123120上游发现了显著的重复,AK123120是编码互补DNA的基因.
结论:
- 针对神经元细胞粘附和无素降解途径的CNV有助于ASD遗传易感性.
- 这些发现强调了这些基因网络在中枢神经系统发育和ASD中的重要性.
- 鉴定到的CNV,虽然单独罕见,但提供了关于ASD复杂遗传结构的见解.
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%...
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.
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...
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,...
Gene Duplication and Divergence
The seminal work of Ohno in 1970 popularized the idea of gene duplication and divergence. DNA sequence comparison studies reveal that a large portion of the genes in bacteria, archaebacteria, and eukaryotes was generated by gene duplication and divergence, indicating its critical role in evolution.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are characterized.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are characterized.


