自閉症スペクトル障害におけるグローバル・レア・コピーの数の変動の機能的影響
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
まとめ
自閉症スペクトル障害 (ASD) は,希少な遺伝複製数変異 (CNVs) の高い負担と関連しています. 新しい遺伝子や経路を含むこれらの遺伝的要因は,ASDを理解するための新しいターゲットを提供します.
科学分野:
- 遺伝学 遺伝学とは
- 神経発達障害 神経発達障害とは
- バイオインフォマティックス
背景:
- 自閉症スペクトル障害 (ASD) は,社会的相互作用とコミュニケーションの欠陥,および制限された行動によって特徴づけられる複雑な神経発達状態です.
- 遺伝性は高い (~90%),ASDの特定の遺伝的原因はほとんど特定されていません.
- ASDを持つ個人の認知発達は,平均以上の知能から知的障害まで,非常に変動します.
研究 の 目的:
- ASD患者における稀な複製数変異 (CNV) の全ゲノム特性を調査する.
- ASDの病因と関連した新しい遺伝的要因と経路を特定する.
- ASD症例における希少なCNVの負担を,マッチングされた対照群と比較するために.
主な方法:
- 密集型遺伝子型配列を用いた全ゲノムにわたるCNVの分析.
- 996人のASD患者と1,287人のヨーロッパの祖先の対照群の間の珍しい (<1%の頻度) CNVの比較.
- 家族的なイベントを含む,de novoおよび遺伝的なCNVの識別.
主要な成果:
- ASD症例は,対照群と比較して,希少で遺伝的なCNVの世界的な負担が著しく高かった (1.19倍,P = 0.012).
- CNVのより大きな濃縮は,以前にASDおよび/または知的障害と関連付けられていた局所で観察されました (1.69倍,P = 3.4 x 10 ((-4)).
- ASDに関連した新しい遺伝子 (例えば,SHANK2,SYNGAP1,DLGAP2,DDX53-PTCHD1) と機能的な遺伝子セット (細胞増殖,GTPase/Rasシグナル伝達) の障害が特定されました.
結論:
- 希少なCNVは,ASDに寄与する重要な遺伝因子です.
- この研究は,ASDの病原性における数多くの新しい遺伝子と経路を示唆している.
- 発見は,ASDの関連生物学的な経路を理解するための基盤を提供します.
関連する概念動画
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%...
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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.
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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.
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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...


