Supplementary Material for: Copy Number Variations in DISC1 and DISC1-Interacting Partners in Major Mental Illness

Robust statistical, genetic and functional evidence supports a role for DISC1 in the aetiology of major mental illness. Furthermore, many of its protein-binding partners show evidence for involvement in the pathophysiology of a range of neurodevelopmental and psychiatric disorders. Copy number variants (CNVs) are suspected to play an important causal role in these disorders. In this study, CNV analysis of DISC1 and its binding partners PAFAH1B1, NDE1, NDEL1, FEZ1, MAP1A, CIT and PDE4B in Scottish and Northern Swedish population-based samples was carried out using multiplex amplicon quantification. Here, we report the finding of rare CNVs in DISC1, NDE1 (together with adjacent genes within the 16p13.11 duplication), NDEL1 (including the overlapping MYH10 gene) and CIT. Our findings provide further evidence for involvement of DISC1 and its interaction partners in neuropsychiatric disorders and also for a role of structural variants in the aetiology of these devastating diseases.

可靠的统计学、遗传学与功能学证据表明，DISC1在重型精神疾病的发病机制中发挥重要作用。此外，其诸多蛋白质结合伴侣均被证实参与了多种神经发育障碍与精神疾病的病理生理过程。拷贝数变异（Copy Number Variants, CNVs）被认为在这类疾病的发病过程中扮演重要的致病角色。本研究针对苏格兰与瑞典北部的人群队列样本，采用多重扩增子定量（multiplex amplicon quantification）技术，对DISC1及其结合伴侣PAFAH1B1、NDE1、NDEL1、FEZ1、MAP1A、CIT与PDE4B开展了拷贝数变异分析。本研究报道了在DISC1、NDE1（伴随16p13.11区域重复内的邻近基因）、NDEL1（包含重叠基因MYH10）以及CIT中检出的稀有拷贝数变异。本研究结果进一步为DISC1及其互作伴侣参与神经精神疾病的发生提供了证据，同时也证实了结构变异在这类危害性极强的疾病发病机制中的作用。