Zhang Yunjia, Chien Wai-Tong, Chan Judy Yuet-Wa, Cheung Tsz-Yan, He Zhiqian, Yip Kai-Hang, Chan Dorothy Fung-Ying, Chong Josephine Shuk-Ching, Waye Mary Miu-Yee, Chair Sek-Ying, Chan Ting-Fung
School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
The State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Comput Struct Biotechnol J. 2025 May 27;27:2233-2242. doi: 10.1016/j.csbj.2025.05.043. eCollection 2025.
Structural variants (SVs) contribute to the genetic architecture of autism spectrum disorder (ASD), but their comprehensive characterization is limited by technological challenges in their detection. Optical genome mapping (OGM) offers a promising alternative, enabling the identification of large-scale SVs that might be overlooked by traditional sequencing methods. This study aimed to use OGM to identify SVs associated with ASD. We generated in-house OGM data from 26 participants diagnosed with ASD, leading to the discovery of 1593 novel SVs. Among them, 114 novel SVs were identified in at least two non-sibling participants, with 57 of them putatively overlapping known gene regions. To validate our findings, two novel SVs were confirmed by Sanger sequencing. The dataset generated in this study can serve as a novel and valuable resource for future research and facilitate the exploration of SVs related to ASD. Our work also underscores the importance of large-scale genomic rearrangements in neurodevelopmental disorders and provides insights into SVs as potential molecular diagnostic and therapeutic targets for ASD.
结构变异（SVs）对自闭症谱系障碍（ASD）的遗传结构有影响，但其全面表征受到检测技术挑战的限制。光学基因组图谱（OGM）提供了一种有前景的替代方法，能够识别传统测序方法可能忽略的大规模SVs。本研究旨在使用OGM识别与ASD相关的SVs。我们从26名被诊断为ASD的参与者中生成了内部OGM数据，发现了1593个新的SVs。其中，114个新的SVs在至少两名非同胞参与者中被识别，其中57个可能与已知基因区域重叠。为了验证我们的发现，通过桑格测序确认了两个新的SVs。本研究生成的数据集可作为未来研究的新颖且有价值的资源，并有助于探索与ASD相关的SVs。我们的工作还强调了大规模基因组重排在神经发育障碍中的重要性，并为SVs作为ASD潜在的分子诊断和治疗靶点提供了见解。
