Jinyu Wu

Wenzhou Medical University

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Zhong Sheng Sun

Guangdong Provincial People's Hospital

Zhongshan Li

Hubei University of Chinese Medicine

Zhenwei Liu

Wenzhou Medical University

Fangqing Zhao

Chinese Academy of Sciences

Qiyu Bao

Wenzhou Medical University

Zi‐Bing Jin

Beijing Tongren Hospital

Jinchen Li

National Clinical Research

Xiaobing Wang

Wenzhou Medical University

Yi Jiang

Huazhong Agricultural University

Jie Bai

Second Hospital of Tianjin Medical University

Cooperative Institutions

Wenzhou Medical University

168

Chinese Academy of Sciences

University of Chinese Academy of Sciences

Affiliated Eye Hospital of Wenzhou Medical College

University of Queensland

Peking University

Fudan University

Chinese Academy of Medical Sciences & Peking Union Medical College

Sun Yat-sen University

Central South University

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A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies

The American Journal of Human Genetics (2018)

Yuwen Liu Yanyu Liang A. Ercüment Çiçek Zhongshan Li Jinchen Li

10.1016/j.ajhg.2018.03.023

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Citations (36)

Evidence of Extensive Homologous Recombination in the Core Genome ofRickettsia

Comparative and Functional Genomics (2009)

Jinyu Wu Tonghai Yu Qiyu Bao Fangqing Zhao

The important role of homologous recombination has been extensively demonstrated to be fundamental for genetic variation in bacterial genomes. In contrast to extracellular or facultative intracellular bacteria, obligate intracellular bacteria are considered to be less prone to recombination, especially for their core genomes. In Rickettsia, only antigen-related genes were identified to have experienced homologous recombination. In this study, we employed evolutionary genomic approaches to investigate the impact of recombination on the core genome of Rickettsia. Phylogenetic network and phylogenetic compatibility matrix analyses are clearly consistent with the hypothesis that recombination has occurred frequently during Rickettsia evolution. 28% of Rickettsia core genes (194 out of 690) are found to present the evidence of recombination under four independent statistical methods. Further functional classification shows that these recombination events occur across all functional categories, with a significant overrepresentation in the cell wall/membrane/envelope biogenesis, which may provide a molecular basis for the parasite adaptation to host immunity. This evolutionary genomic analysis provides insight into the substantial role of recombination in the evolution of the intracellular pathogenic bacteria Rickettsia.

10.1155/2009/510270

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RRBS-Analyser: A Comprehensive Web Server for Reduced Representation Bisulfite Sequencing Data Analysis

Human Mutation (2013)

Tao Wang Qi Liu Xianfeng Li Xiaobing Wang Jinchen Li

In reduced representation bisulfite sequencing (RRBS), genomic DNA is digested with the restriction enzyme and then subjected to next-generation sequencing, which enables detection and quantification of DNA methylation at whole-genome scale with low cost. However, the data processing, interpretation, and analysis of the huge amounts of data generated pose a bioinformatics challenge. We developed RRBS-Analyser, a comprehensive genome-scale DNA methylation analysis server based on RRBS data. RRBS-Analyser can assess sequencing quality, generate detailed statistical information, align the bisulfite-treated short reads to reference genome, identify and annotate the methylcytosines (5mCs) and associate them with different genomic features in CG, CHG, and CHH content. RRBS-Analyser supports detection, annotation, and visualization of differentially methylated regions (DMRs) for multiple samples from nine reference organisms. Moreover, RRBS-Analyser provides researchers with detailed annotation of DMR-containing genes, which will greatly aid subsequent studies. The input of RRBS-Analyser can be raw FASTQ reads, generic SAM format, or self-defined format containing individual 5mC sites. RRBS-Analyser can be widely used by researchers wanting to unravel the complexities of DNA methylome in the epigenetic community. RRBS-Analyser is freely available at http://122.228.158.106/RRBSAnalyser/.

Analyser

Bisulfite sequencing

Bisulfite

10.1002/humu.22444

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Citations (35)

De novo variants in Chinese ASD trios reveal distinct genetic basis underlying autism with and without developmental delay

Research Square (Research Square) (2021)

Jincheng Wang Juehua Yu Mengdi Wang Lingli Zhang Kan Yang

Abstract Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder causing impairments in social communication and stereotypical behaviors, often with developmental delay or intellectual disabilities (DD/ID). Accruing evidence indicates that ASD is highly heritable and genome-wide studies on ASD cohorts have defined numerous genetic contributors. Notably, since most of these studies have been performed with individuals of European and Hispanic ancestries, thus there is a paucity of genetic analyses of ASD in the East Asian population. Here, we performed whole-exome sequencing on 772 Chinese ASD trios, combining with a previous 369 ASD trios, to identify de novo variants in 1141 ASD trios. We found that ASD without DD/ID carried less disruptive de novo variants than ASD with DD/ID. Surprisingly, we found that expression of genes with de novo variants in ASD without DD/ID were enriched in a subtype of human neural progenitor cells. Importantly, some ASD risk genes identified in this study are not present in the current ASD gene database, suggesting that there may be unique genetic contributors to ASD with the East Asian ancestry. We validated one such novel ASD candidate gene – SLC35G1 by showing that mice harboring heterozygous deletion of Slc35g1 exhibited defects in social interaction behaviors. Together, this work nominates novel ASD candidate genes and suggests that genome-wide genetic studies in ASD cohorts of different ancestries are essential to reveal the comprehensive genetic architecture of ASD.

Candidate gene

Neurodevelopmental disorder

Exome

Genetic architecture

Heritability of autism

10.21203/rs.3.rs-1133175/v1

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Distinct genetic patterns of shared and unique genes across four neurodevelopmental disorders

American Journal of Medical Genetics Part B Neuropsychiatric Genetics (2020)

Yijia Zhang Ruochen Wang Zhenwei Liu Shan Jiang Li-Feng Du

Abstract Neurodevelopmental disorders, including autism spectrum disorder (ASD), intellectual disability (ID), developmental disorders (DD) and epileptic encephalopathy (EE), have a strong clinical comorbidity, which indicates a common genetic etiology across various disorders. However, the underlying genetic mechanisms of comorbidity and specificity remain unknown across neurodevelopmental disorders. Based on de novo mutations, we compared systematically the functional characteristics between shared and unique genes under these disorders, as well as the spatiotemporal trajectory of development in brain and common molecular pathways of all shared genes. We observed that shared genes present more constrained against functional rare genetic variation, and harbor more pathogenic rare variants than do unique genes in each disorder. Furthermore, 71 shared genes formed two clusters related to synaptic transmission, transcription regulation and chromatin regulator. Particularly, we also found that two core genes STXBP1 and SCN2A , that were shared by the four neurodevelopmental disorders showed prominent pleiotropy. Our findings shed light on the shared and specific patterns across neurodevelopmental disorders and will enable us to further comprehend the etiology and provide valuable information for the diagnosis of neurodevelopmental disorders.

Neurodevelopmental disorder

Pleiotropy

Rett Syndrome

10.1002/ajmg.b.32821

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Citations (6)

Immunometabolic shifts in autoimmune disease: Mechanisms and pathophysiological implications

Autoimmunity Reviews (2024)

Yue Chen Qingqing Lin Hui Cheng Qiyu Xiang Wenxian Zhou

Pathophysiology

10.1016/j.autrev.2024.103738

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Identification of De Novo DNMT3A Mutations That Cause West Syndrome by Using Whole-Exome Sequencing

Molecular Neurobiology (2017)

Zhenwei Liu Zhongshan Li Xiao Zhi Yaoqiang Du Zhongdong Lin

Exome

Candidate gene

Neurodevelopmental disorder

10.1007/s12035-017-0483-9

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Citations (10)

A statistical framework for mapping risk genes fromde novomutations in whole-genome sequencing studies

bioRxiv (Cold Spring Harbor Laboratory) (2016)

Yuwen Liu Yanyu Liang A. Ercüment Çiçek Zhongshan Li Jinchen Li

Abstract Analysis of de novo mutations (DNMs) from sequencing data of nuclear families has identified risk genes for many complex diseases, including multiple neurodevelopmental and psychiatric disorders. Most of these efforts have focused on mutations in protein-coding sequences. Evidence from genome-wide association studies (GWAS) strongly suggests that variants important to human diseases often lie in non-coding regions. Extending DNM-based approaches to non-coding sequences is, however, challenging because the functional significance of non-coding mutations is difficult to predict. We propose a new statistical framework for analyzing DNMs from whole-genome sequencing (WGS) data. This method, TADA-Annotations (TADA-A), is a major advance of the TADA method we developed earlier for DNM analysis in coding regions. TADA-A is able to incorporate many functional annotations such as conservation and enhancer marks, learn from data which annotations are informative of pathogenic mutations and combine both coding and non-coding mutations at the gene level to detect risk genes. It also supports meta-analysis of multiple DNM studies, while adjusting for study-specific technical effects. We applied TADA-A to WGS data of ∼300 autism family trios across five studies, and discovered several new autism risk genes. The software is freely available for all research uses.

ENCODE

10.1101/077578

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Trio-based exome sequencing arrests de novo mutations in early-onset high myopia

Proceedings of the National Academy of Sciences (2017)

Zi‐Bing Jin Jinyu Wu Xiu‐Feng Huang Chun-Yun Feng Xue‐Bi Cai

Significance Because preschool children encounter fewer risks from environmental pressures, we propose that the condition of early-onset high myopia (EOHM) is driven by a genetic predisposition more than by environmental factors. In this study, we recruited 18 familial trios to decipher the genetic predisposition using whole-exome sequencing. We identified a cluster of unique genes linked to EOHM, as well as mutations in the reported genes. Notably, we showed that both rare inherited mutations and de novo mutations significantly contributed to EOHM. Expression profiling in ocular tissues and mutant mouse phenotyping demonstrated the pathogenicity of mutations in a unique gene, BSG . Our results provide insights into the genetic basis and molecular mechanisms of childhood high myopia.

Exome

Genetic predisposition

10.1073/pnas.1615970114

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Citations (96)

'RetinoGenetics': a comprehensive mutation database for genes related to inherited retinal degeneration

Database (2014)

Xia Ran W.-J. Cai Xiu‐Feng Huang Q. Liu F. Lu

10.1093/database/bau071

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Citations (19)