用高分辨率微阵列比较基因组杂交分析一个孤独症家系的新生拷贝数变异

Analysis of de novo copy number variations in a family affected with autism spectrum disorders using highresolution array-based comparative genomic hybridization

目的对1个孤独症家系进行新发拷贝数变异（copynumbervariations，CNV）分析。方法应用高分辨率全基因组芯片（AffymetrixCytogeneticsWhole-Genome2．7MArray）检测该家系4名成员的基因组拷贝数，用AffymetrixChromosomeAnalysisSuite软件分析结果。以基因组变异数据库亚洲正常人群及先证者父母、同胞为对照，分析先证者的新发CNV。结果先证者存在89个新发拷贝数变异，其中5号、11号和14号染色体新发CNV总长占染色体全长超过1‰。3p26．1、4q2．2、5p15．2等区域也存在新发CNV，涉及GRM7、GRID2、CTNND2等10个与神经系统发育相关基因。结论先证者多个与神经系统发育相关的基因存在新发拷贝数变异，这为探索孤独症的发病机理提供了新的线索。高分辨率基因组CNV芯片能够快速、准确地检测基因组的微小失衡，在遗传病诊断方面具有广阔的应用前景。

Objective To analyze de novo copy number variations （CNVs） in a Chinese family affected with autism spectrum disorders （ASD）. Methods Affymetrix Cytogenetics Whole-Genome 2. 7M Array assay was performed to identify potential CNVs in four members from the family. Results A total of 89 de novo CNV regions were identified in the autistic siblings. The CNV regions in total have exceeded 1‰ of the lengths of chromosomes 5, 11 and 14. In addition, de novo CNV regions were also identified at 3p26. 1, 4q22.2, and 5p15. 2, which encompassed 10 genes associated with nerve development including GRM7, GRID2 and CTNND2. Conclusion A number of nerve development associated genes were at the de novo CNV sites, which may provide new clues for genetic research of ASD. High-resolution array-comparative genomic hybridization is an effective method for detecting submicroscopic chromosomal imbalances.