| 1 | Genomic landscapes of Chinese sporadic autism spectrum disordersrevealed by whole-genome sequencing显示文摘Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD,including de novo mutations,inherited variants,copy number variants (CNVs) and genomic structural variants.A higher mutation rate (Poisson test,P<2.2×10^(-16)) in exonic (1.37×10^(-8)) and 3'-UTR regions (1.42×10^(-8)) was revealed in comparison with that of whole genome (1.05×10^(-8)).Using an integrated model,we identified 87 potentially risk genes (P<0.01) from 4832 genes harboring various rare deleterious variants,including CHD8 and NRXN2,implying that the disorders may be in favor to multiple-hit.In particular,frequent rare inherited mutations of several microcephaly-associated genes (ASPM,WDR62,and ZNF335)were found in ASD.In chromosomal structure analyses,we found four de novo CNVs and one de novo chromosomal rearrangement event,including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1,which causes Angelman syndrome and microcephaly,and a disrupted TNR due to de novo chromosomal translocation t (1;5) (q25.1;q33.2).Taken together,our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD.Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders,such as ASD,could provide novel insights into pathogenesis,diagnosis and treatment. | Jinyu Wu Ping Yu Xin Jin Xiu Xu Jinchen Li Zhongshan Li Mingbang Wang Tao Wang Xueli Wu Yi Jiang Wanshi Cai Junpu Mei Qingjie Min Qiong Xu Bingrui Zhou Hui Guo Ping Wang Wenhao Zhou Zhengmao Hu Yingrui Li Tao Cai Yi Wang Kun Xia Yong-Hui Jiang Zhong Sheng Sun | 2018 | Journal of Genetics and Genomics2018，45，10： | 3 |
| 2 | Microbiota-mediated shaping of mouse spleen structure and immune function characterized by scRNA-seq and Stereo-seq显示文摘Gut microbes exhibit complex interactions with their hosts and shape an organism's immune system throughout its lifespan.As the largest secondary lymphoid organ,the spleen has a wide range of immunological functions.To explore the role of microbiota in regulating and shaping the spleen,we employ scRNA-seq and Stereo-seq technologies based on germ-free(GF)mice to detect differences in tissue size,anatomical structure,cell types,functions,and spatial molecular characteristics.We identify 18 cell types,9 subtypes of T cells,and 7 subtypes of B cells.Gene differential expression analysis reveals that the absence of microorganisms results in alterations in erythropoiesis within the red pulp region and congenital immune deficiency in the white pulp region.Stereo-seq results demonstrate a clear hierarchy of immune cells in the spleen,including marginal zone(MZ)macrophages,MZ B cells,follicular B cells and T cells,distributed in a well-defined pattern from outside to inside.However,this hierarchical structure is disturbed in GF mice.Ccr7 and Cxcl13 chemokines are specifically expressed in the spatial locations of T cells and B cells,respectively.We speculate that the microbiota may mediate the structural composition or partitioning of spleen immune cells by modulating the expression levels of chemokines. | Yin Zhang Juan Shen Wei Cheng Bhaskar Roy Ruizhen Zhao Tailiang Chai Yifei Sheng Zhao Zhang Xueting Chen Weiming Liang Weining Hu Qijun Liao Shanshan Pan Wen Zhuang Yangrui Zhang Rouxi Chen Junpu Mei Hong Wei Xiaodong Fang | 2023 | Journal of Genetics and Genomics2023，50，9： | 0 |
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