Centre for Genetic Origins of Health and Disease, School of Biomedical Sciences, The University of Western Australia and School of Biomedical Sciences, Curtin University, MRF Building, 50 Murray St., Perth, WA 6000, Australia.
Centre for Genetic Origins of Health and Disease, School of Biomedical Sciences, The University of Western Australia and School of Biomedical Sciences, Curtin University, MRF Building, 50 Murray St., Perth, WA 6000, Australia; Centre for Clinical Research in Neuropsychiatry, School of Psychiatry and Clinical Neurosciences, University of Western Australia, MRF Building, 50 Murray Street, Perth 6000, Australia; Cooperative Research Centre for Mental Health, Carlton, South Victoria, Australia.
Schizophr Res. 2018 Jul;197:337-345. doi: 10.1016/j.schres.2018.02.034. Epub 2018 Feb 24.
The importance of genomic copy number variants (CNVs) has long been recognized in the etiology of neurodevelopmental diseases. We report here the results from the CNV analysis of whole-genome sequences from 91 multiplex schizophrenia families. Employing four algorithms (CNVnator, Cn.mops, DELLY and LUMPY) to identify CNVs, we find 1231 rare deletions and 287 rare duplications in 300 individuals (77 with schizophrenia (SZ), 32 with schizoaffective disorder (SAD), 82 with another neuropsychiatric diagnosis and 109 unaffected). The size of the CNVs ranges from a few hundred base-pairs to about 1.3Mb. The total burden of CNVs does not differ significantly between affected (SZ and SAD) and unaffected individuals. Parent-to-child transmission rate for rare CNVs affecting exonic regions is significantly higher for affected (SZ and SAD) probands as compared to their siblings, but rates for all CNVs is not. We observe heterogeneity between families in terms of genes involved in CNVs, and find several CNVs involving genes previously implicated in either schizophrenia or other neuropsychiatric disorders.
基因组拷贝数变异（CNVs）在神经发育疾病的病因学中一直具有重要意义。我们在此报告对 91 个多发性精神分裂症家系的全基因组序列进行 CNV 分析的结果。采用 4 种算法（CNVnator、Cn.mops、DELLY 和 LUMPY）来识别 CNVs，我们在 300 个人中发现了 1231 个罕见缺失和 287 个罕见重复，其中 77 人患有精神分裂症（SZ），32 人患有分裂情感障碍（SAD），82 人患有其他神经精神障碍诊断，109 人未受影响。CNVs 的大小从几百个碱基对到大约 1.3Mb 不等。受影响（SZ 和 SAD）和未受影响个体之间的 CNV 总负担没有显著差异。与兄弟姐妹相比，受影响（SZ 和 SAD）先证者的外显子区域罕见 CNVs 的亲代向子代传递率明显更高，但所有 CNVs 的传递率都不高。我们观察到家族之间在涉及 CNVs 的基因方面存在异质性，并发现了几个涉及先前与精神分裂症或其他神经精神障碍相关的基因的 CNVs。
