NASP gene contributes to autism by epigenetic dysregulation of neural and immune pathways
文献类型：期刊论文
| 作者 | Zhang, Sipeng12; Yang, Jie12; Ji, Dandan12; Meng, Xinyi12; Zhu, Chonggui11; Zheng, Gang10 ; Glessner, Joseph7,8,9; Qu, Hui-Qi9; Cui, Yuechen12; Liu, Yichuan9
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| 刊名 | JOURNAL OF MEDICAL GENETICS
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| 出版日期 | 2024-03-05 |
| 页码 | 12 |
| ISSN号 | 0022-2593 |
| 关键词 | Genetic Variation Psychiatry Epigenomics Mutation Pediatrics |
| DOI | 10.1136/jmg-2023-109385 |
| 通讯作者 | Li, Jin(jli01@tmu.edu.cn) ; Xia, Qianghua(qhxia@tmu.edu.cn) |
| 英文摘要 | Background Epigenetics makes substantial contribution to the aetiology of autism spectrum disorder (ASD) and may harbour a unique opportunity to prevent the development of ASD. We aimed to identify novel epigenetic genes involved in ASD aetiology. Methods Trio-based whole exome sequencing was conducted on ASD families. Genome editing technique was used to knock out the candidate causal gene in a relevant cell line. ATAC-seq, ChIP-seq and RNA-seq were performed to investigate the functional impact of knockout (KO) or mutation in the candidate gene. Results We identified a novel candidate gene NASP (nuclear autoantigenic sperm protein) for epigenetic dysregulation in ASD in a Chinese nuclear family including one proband with autism and comorbid atopic disease. The de novo likely gene disruptive variant tNASP(Q289X) subjects the expression of tNASP to nonsense-mediated decay. tNASP KO increases chromatin accessibility, promotes the active promoter state of genes enriched in synaptic signalling and leads to upregulated expression of genes in the neural signalling and immune signalling pathways. Compared with wild-type tNASP, tNASP(Q289X) enhances chromatin accessibility of the genes with enriched expression in the brain. RNA-seq revealed that genes involved in neural and immune signalling are affected by the tNASP mutation, consistent with the phenotypic impact and molecular effects of nasp-1 mutations in Caenorhabditis elegans. Two additional patients with ASD were found carrying deletion or deleterious mutation in the NASP gene. Conclusion We identified novel epigenetic mechanisms mediated by tNASP which may contribute to the pathogenesis of ASD and its immune comorbidity. |
| 收录类别 | SCI |
| WOS关键词 | SPECTRUM DISORDERS ; CHILDREN ; PROTEIN ; ASTHMA |
| 资助项目 | National Natural Science Foundation of China[82202009] ; Science and Technology Development Fund of Tianjin Education Commission for Higher Education[2020KJ196] ; Tianjin Key Medical Discipline (Specialty) Construction Project[TJYXZDXK-040A] ; Tianjin Outstanding Health Professional Selection and Training Program[TJSJMYXYC- D2-031] |
| WOS研究方向 | Genetics & Heredity |
| 语种 | 英语 |
| 出版者 | BMJ PUBLISHING GROUP |
| WOS记录号 | WOS:001186027600001 |
| 资助机构 | National Natural Science Foundation of China ; Science and Technology Development Fund of Tianjin Education Commission for Higher Education ; Tianjin Key Medical Discipline (Specialty) Construction Project ; Tianjin Outstanding Health Professional Selection and Training Program |
| 源URL | [http://ir.psych.ac.cn/handle/311026/47363]  |
| 专题 | 心理研究所_认知与发展心理学研究室 |
| 通讯作者 | Li, Jin; Xia, Qianghua |
| 作者单位 | 1.Tianjin Med Univ, Dept Bioinformat, Tianjin, Peoples R China 2.Tianjin Med Univ, Dept Cell Biol, Tianjin, Peoples R China 3.Tianjin Med Univ, Dept Rheumatol & Immunol, Gen Hosp, Tianjin, Peoples R China 4.Tianjin Med Univ, Tianjin Anding Hosp, Inst Mental Hlth, Lab Biol Psychiat, Tianjin, Peoples R China 5.Tianjin Med Univ, Sch Basic Med Sci, Dept Bioinformat, Tianjin, Peoples R China 6.Chinese Acad Sci, Inst Psychol, Beijing, Peoples R China 7.Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA USA 8.Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA USA 9.Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA USA 10.Natl Supercomp Ctr Tianjin NSCC TJ, Tianjin, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Sipeng,Yang, Jie,Ji, Dandan,et al. NASP gene contributes to autism by epigenetic dysregulation of neural and immune pathways[J]. JOURNAL OF MEDICAL GENETICS,2024:12. |
| APA | Zhang, Sipeng.,Yang, Jie.,Ji, Dandan.,Meng, Xinyi.,Zhu, Chonggui.,...&Xia, Qianghua.(2024).NASP gene contributes to autism by epigenetic dysregulation of neural and immune pathways.JOURNAL OF MEDICAL GENETICS,12. |
| MLA | Zhang, Sipeng,et al."NASP gene contributes to autism by epigenetic dysregulation of neural and immune pathways".JOURNAL OF MEDICAL GENETICS (2024):12. |
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来源：心理研究所
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