<i>NASP</i> gene contributes to autism by epigenetic dysregulation of neural and immune pathways

doi:10.1136/jmg-2023-109385

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	NASP gene contributes to autism by epigenetic dysregulation of neural and immune pathways
	Zhang, Sipeng 1; Yang, Jie 1; Ji, Dandan 1; Meng, Xinyi 1; Zhu, Chonggui 2; Zheng, Gang3 ; Glessner, Joseph 4,5,6; Qu, Hui-Qi 4; Cui, Yuechen 1; Liu, Yichuan 4; Wang, Wei7 ; Li, Xiumei 1; Zhang, Hao 1; Xiu, Zhanjie 1,8; Sun, Yan1 ; Sun, Ling 9; Li, Jie9 ; Hakonarson, Hakon 4,5,6; Li, Jin 1,10,11; Xia, Qianghua 1,8,12
通讯作者	Li, Jin(jli01@tmu.edu.cn) ; Xia, Qianghua(qhxia@tmu.edu.cn)
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.
关键词	Genetic Variation Psychiatry Epigenomics Mutation Pediatrics
	2024-03-05
语种	英语
DOI	10.1136/jmg-2023-109385
发表期刊	JOURNAL OF MEDICAL GENETICS
ISSN	0022-2593
页码	12
收录类别	SCI
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]
出版者	BMJ PUBLISHING GROUP
WOS关键词	SPECTRUM DISORDERS ; CHILDREN ; PROTEIN ; ASTHMA
WOS研究方向	Genetics & Heredity
WOS类目	Genetics & Heredity
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
引用统计
文献类型	期刊论文
条目标识符	http://ir.psych.ac.cn/handle/311026/47364
专题	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, Prov & Minist Collaborat Innovat Ctr Tianjin Med E, Key Lab Immune Microenvironm & Dis, Tianjin Key Lab Med Epigenet,Sch Basic Med Sci,Min, Tianjin 300070, Peoples R China 2.Tianjin Med Univ, Gen Hosp, Dept Endocrinol, Tianjin, Peoples R China 3.Natl Supercomp Ctr Tianjin NSCC TJ, Tianjin, Peoples R China 4.Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA USA 5.Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA USA 6.Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA USA 7.Chinese Acad Sci, Inst Psychol, Beijing, Peoples R China 8.Tianjin Med Univ, Sch Basic Med Sci, Dept Bioinformat, Tianjin, Peoples R China 9.Tianjin Med Univ, Tianjin Anding Hosp, Inst Mental Hlth, Lab Biol Psychiat, Tianjin, Peoples R China 10.Tianjin Med Univ, Dept Rheumatol & Immunol, Gen Hosp, Tianjin, Peoples R China 11.Tianjin Med Univ, Dept Cell Biol, Tianjin, Peoples R China 12.Tianjin Med Univ, Dept Bioinformat, 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.