National Institute for Physiological Sciences, Tokyo, Japan; Restart Postdoctoral Fellowship of Japan Society for the Promotion of Science, Tokyo, Japan; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Psychiatry Clin Neurosci. 2014 Feb;68(2):85-95. doi: 10.1111/pcn.12128. Epub 2013 Dec 29.
Autism spectrum disorder is a neurodevelopmental disorder present in 1% of the population, characterized by impairments in reciprocal social interaction, communication deficits and restricted patterns of behavior. Approximately 10% of the autism spectrum disorder population is thought to have large chromosomal rearrangements. Copy-number variations (CNV) alter the genome structure either by duplication or deletion of a chromosomal region. The association between CNV and autism susceptibility has become more apparent through the use of methods based on comparative genomic hybridization in screening CNV. The nature of the high CNV rate in the human genome is partly explained by non-allelic homologous recombination between flanking repeated sequences derived from multiple copies of transposons or mobile genetic elements. There are hotspots for CNV in the human genome, such as 16p11.2 and 22q11.2. Genes involved in CNV are supposed to have copy-number dose-dependent effects on the behavior of affected individuals. Animal models give insight into the possible interactions between core genetic loci and additional factors contributing to the phenotypes of each individual. If affected genes code for cellular signaling molecules, reducing the dosage in the intracellular signaling pathway may result in the malfunction of the nervous system. The genetic background of autism spectrum disorder is highly heterogenic and most common or rare CNV do not lead to autism spectrum disorders in the majority of cases, but may occasionally increase the risk of developing an autism spectrum disorder.
自闭症谱系障碍是一种神经发育障碍，在人群中的发病率为 1%，其特征是在互惠的社会互动、沟通障碍和受限的行为模式方面存在缺陷。大约 10%的自闭症谱系障碍患者被认为存在大的染色体重排。拷贝数变异（CNV）通过染色体区域的重复或缺失来改变基因组结构。通过使用基于比较基因组杂交的方法筛查 CNV，CNV 与自闭症易感性之间的关联变得更加明显。人类基因组中高 CNV 率的性质部分可以通过来自转座子或移动遗传元件的多个拷贝的侧翼重复序列之间的非等位基因同源重组来解释。人类基因组中有 CNV 的热点，如 16p11.2 和 22q11.2。涉及 CNV 的基因被认为对受影响个体的行为有拷贝数剂量依赖性影响。动物模型深入了解核心遗传基因座与导致每个个体表型的其他因素之间可能存在的相互作用。如果受影响的基因编码细胞信号分子，那么减少细胞内信号通路中的剂量可能会导致神经系统功能障碍。自闭症谱系障碍的遗传背景高度异质，大多数常见或罕见的 CNV 在大多数情况下不会导致自闭症谱系障碍，但偶尔可能会增加自闭症谱系障碍的发病风险。
