The homeostasis of the gut microbiome is crucial for human health and for liver function. However, it has not been established whether the gut microbiome influence hepatic progenitor cells (HPCs). HPCs are capable of self-renewal and differentiate into hepatocytes and cholangiocytes; however, HPCs are normally quiescent and are rare in adults. After sustained liver damage, a ductular reaction occurs, and the number of HPCs is substantially increased. Here, we administered five broad-spectrum antibiotics for 14 days to deplete the gut microbiomes of male C57BL/6 mice, and we measured the plasma aminotransferases and other biochemical indices. The expression levels of two HPC markers, SRY-related high mobility group-box gene 9 (Sox9) and cytokeratin (CK), were also measured. The plasma aminotransferase activities were not affected, but the triglyceride, lactate dehydrogenase, low-density lipoprotein, and high-density lipoprotein concentrations were significantly altered; this suggests that liver function is affected by the composition of the gut microbiome. The mRNA expression of Sox9 was significantly higher in the treated mice than it was in the control mice (p < 0.0001), and a substantial expression of Sox9 and CK was observed around the bile ducts. The mRNA expression levels of proinflammatory factors (interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α, and TNF-like weak inducer of apoptosis [Tweak]) were also significantly higher in the antibiotic-treated mice than the levels in the control mice. These data imply that the depletion of the gut microbiome leads to liver damage, negatively impacts the hepatic metabolism and function, and activates HPCs. However, the underlying mechanisms remain to be determined.

Fei Wang;Nan nan Sun;Lan lan Li;Wan wan Zhu;Jianbo Xiu;岩 沈;琪 许

MicrobiologyOpen

2019-10-1

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead.

Zahra Abdellah;Alireza Ahmadi;Shahana Ahmed;Matthew Aimable;Rachael Ainscough;Jeff Almeida;Claire Almond;Andrew Ambler;Karen Ambrose;Kerrie Ambrose;Robert Andrew;Daniel Andrews;Neil Andrews;Dan Andrews;Eva Apweiler;Hazel Arbery;Beth Archer;Gareth Ash;Kevin Ashcroft;Jennifer Ashurst;Robert Ashwell;Deborah Atkin;Andrea Atkinson;Barry Atkinson;John Attwood;Keith Aubin;Katherine Auger;Terry Avis;Anne Babbage;Sarah Babbage;Joanne Bacon;Claire Bagguley;Jonathan Bailey;Andrew Baker;Ruby Banerjee;Simon Bardill;Darren Barker;Gary Barker;Daniel Barker;Karen Barlow;Laurent Baron;Zhu Chen;Songnian Hu;Shengbin Li;Yan Shen;Chaoguang Tian;Qingfa Wu;Huanming Yang;Jun Yu;Zhen Zhu

Nature

2004-10-21

Y-chromosomes from 76 Chinese men covering 33 ethnical minorities throughout China as well as the Han majority were collected as genetic material for the study of Chinese nonrecombinant Y-chromosome (NRY) phylogeny. Of the accepted worldwide NRY haplogroups, three (haplogroups D, C, O) were significant in this sample, extending previous assessments of Chinese genetic diversity. Based on geographic, linguistic, and ethnohistorical information, the 33 Chinese ethnical minorities in our survey were divided into the following four subgroups: North, Tibet, West, and South. Inferred from the distribution of the newfound immediate ancestor lineage haplogroup O*, which has M214 but not M175, we argue that the southern origin scenario of this most common Chinese Y haplogroup is not very likely. We tentatively propose a West/North-origin hypothesis, suggesting that haplogroup O originated in West/North China and mainly evolved in China and thence spread further throughout eastern Eurasia. The nested cladistic analysis revealed in detail a multilayered, multidirectional, and continuous history of ethnic admixture that has shaped the contemporary Chinese population. Our results give some new clues to the evolution and migration of the Chinese population and its subsequence moving about in this land, which are in accordance with the historical records.

Wei Deng;Baochen Shi;Xiaoli He;Zhihua Zhang;Jun Xu;Biao Li;Jian Yang;Lunjiang Ling;Chengping Dai;伯勤 强;岩 沈;润生 陈

Journal of Human Genetics

2004

Capillary electrophoresis (CE) has proved to be a strong tool for DNA analysis and has found abundant applications in the fields of restriction fragment sizing, mutation screening, polymerase chain reaction (PCR) product characterizing and forensic identifying. CE may be the main alternative to slab gel electrophoresis. Capillary nongel electrophoresis is the most favorable mode when aiming for this purpose because of its advantages of long lifetime, easy operation, good reproducibility, and low expense. In this paper, a new kind of sieving matrix, with mannitol as the additive for capillary electrophoresis, as well as related methods and their application for gene analysis were reported. Nine DNA fragments amplified by multiplex PCR from a normal dystrophin gene were well separated by this system. Three different deletions were found in Duchenne muscular dystrophy (DMD) patients. Three to four copies of the sex-determination region of the Y chromosome (SRY) gene, as well as the phenylalanine hydroxylase (PAH) gene, could be detected in mixed samples. The frequencies of short tandem repeats (STR) in PAH genes was analyzed in 61 normal Chinese individuals and 6 phenylketonuria families. One case of prenatal gene diagnosis was performed. By using this matrix, CE coupled with reverse transcription PCR (RT-PCR), the analysis of the alternative splicing expression pattern of the fragile X mental retardation 1 (FMRI) gene in adult lung tissue was achieved.

岩 沈;琪 许;Futian Han;Kan Ding;Fang Song;Yu Fan;Ning Zhu;Guanyun Wu;炳承 林

Electrophoresis

1999

Background A mutation in MEF2A (myocyte enhancer factor-2A) had been reported to be the first gene linked directly to coronary artery disease (CAD). However, an opposing opinion was proposed recently that MEF2A mutations are not a common cause of sporadic CAD. In this study, we screened exon 11 of the MEF2A gene in people of the Han nationality in China and finished some functional analysis of found variations. Materials and methods A gene structural investigation of MEF2A in 257 CAD patients and 154 control individuals were developed in this study. Subsequently, typical MEF2A variations were cloned and expressed in HeLa or 293T cell line to illustrate whether found structure changes could influence the main biological functions of these proteins. At last, another set of gene structural screen was initialized to get more reliable conclusions. Results Totally 16 different variations were detected in exon 11 of this gene in the first set of gene structural screen. By cloning and expressing typical MEF2A proteins in cultured cells, all the acquired MEF2A variations had transcriptional activation capabilities and subcellular localization patterns similar to those of the wild-type protein. Further larger scale genetic screening also revealed that the reported genetic variations of MEF2A did not differ significantly between CAD patients and healthy controls. Conclusions Our results reveal that structural changes of exon 11 in MEF2A are not involved in sporadic CAD in the Han population of China.

Da Peng Dai;Xiao Yang Zhou;Yao Xiao;Feng Xu;Fu Cheng Sun;Fu Sui Ji;Zhi Xin Zhang;Ji Hong Hu;Jian Guo;Jun De Zheng;Jia Mei Dong;卫国 朱;岩 沈;Yi Jian Qian;Qing He;Jian Ping Cai

European Journal of Clinical Investigation

2010-8

We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S.flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E.coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S.flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E.coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis.

奇 金;正宏 袁;建国 徐;Yu Wang;岩 沈;Weichuan Lu;Jinhua Wang;Hong Liu;Jian Yang;Fan Yang;Xiaobing Zhang;Jiyu Zhang;Guowei Yang;Hongtao Wu;涤 瞿;Jie Dong;Lilian Sun;Ying Xue;Ailan Zhao;Yishan Gao;Junping Zhu;Biao Kan;Keyue Ding;Shuxia Chen;Hongsong Cheng;Zhijian Yao;Bingkun He;润生 陈;大龙 马;Boqin Qiang;Yumei Wen;云德 侯;Jun Yu

Nucleic Acids Research

2002-10-15

We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r² of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r² of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.

Kelly A. Frazer;Dennis G. Ballinger;David R. Cox;David A. Hinds;Laura L. Stuve;Richard A. Gibbs;John W. Belmont;Andrew Boudreau;Paul Hardenbol;Suzanne M. Leal;Shiran Pasternak;David A. Wheeler;Thomas D. Willis;Fuli Yu;焕明 杨;长青 曾;Yang Gao;Haoran Hu;Weitao Hu;Chaohua Li;Wei Lin;Siqi Liu;Hao Pan;Xiaoli Tang;Jian Wang;Wei Wang;军 于;Bo Zhang;Qingrun Zhang;Hongbin Zhao;Hui Zhao;Jun Zhou;Stacey B. Gabriel;Rachel Barry;Brendan Blumenstiel;Amy Camargo;Matthew Defelice;Maura Faggart;Mary Goyette;Supriya Gupta;Jamie Moore;Huy Nguyen;Robert C. Onofrio;Melissa Parkin;Jessica Roy;Erich Stahl;Ellen Winchester;Liuda Ziaugra;David Altshuler;岩 沈;Zhijian Yao;Wei Huang;Xun Chu;Yungang He;力 金;Yangfan Liu;Yayun Shen;Weiwei Sun;Haifeng Wang;Yi Wang;Ying Wang;Xiaoyan Xiong;Liang Xu;Mary M.Y. Waye;Stephen K.W. Tsui;Hong Xue;J. Tze Fei Wong;Luana M. Galver;Jian Bing Fan;Kevin Gunderson;Sarah S. Murray;Arnold R. Oliphant;Mark S. Chee;Alexandre Montpetit;Fanny Chagnon;Vincent Ferretti;Martin Leboeuf;Jean François Olivier;Michael S. Phillips;Stéphanie Roumy;Clémentine Sallée;Andrei Verner;Thomas J. Hudson;Pui Yan Kwok;Dongmei Cai;Daniel C. Koboldt;Raymond D. Miller;Ludmila Pawlikowska;Patricia Taillon-Miller;Ming Xiao;立之 徐;William Mak;Qiang Song You;Paul K.H. Tam;Yusuke Nakamura;Takahisa Kawaguchi;Takuya Kitamoto;Takashi Morizono;Atsushi Nagashima;Yozo Ohnishi;Akihiro Sekine;Toshihiro Tanaka;Tatsuhiko Tsunoda;Panos Deloukas;Christine P. Bird;Marcos Delgado;Emmanouil T. Dermitzakis;Rhian Gwilliam;Sarah Hunt;Jonathan Morrison;Don Powell;Barbara E. Stranger;Pamela Whittaker;David R. Bentley;Mark J. Daly;Paul I.W. De Bakker;Jeff Barrett;Yves R. Chretien;Julian Maller;Steve McCarroll;Nick Patterson;Itsik Pe'Er;Alkes Price;Shaun Purcell;Daniel J. Richter;Pardis Sabeti;Richa Saxena;Stephen F. Schaffner;Pak C. Sham;Patrick Varilly;Lincoln D. Stein;Lalitha Krishnan;Albert Vernon Smith;Marcela K. Tello-Ruiz;Gudmundur A. Thorisson;Aravinda Chakravarti;Peter E. Chen;David J. Cutler;Carl S. Kashuk;Shin Lin;Gonçalo R. Abecasis;Weihua Guan;Yun Li;Heather M. Munro;Zhaohui Steve Qin;Daryl J. Thomas;Gilean McVean;Adam Auton;Leonardo Bottolo;Niall Cardin;Susana Eyheramendy;Colin Freeman;Jonathan Marchini;Simon Myers;Chris Spencer;Matthew Stephens;Peter Donnelly;Lon R. Cardon;Geraldine Clarke;David M. Evans;Andrew P. Morris;Bruce S. Weir;Todd A. Johnson;James C. Mullikin;Stephen T. Sherry;Michael Feolo;Andrew Skol;Houcan Zhang;Ichiro Matsuda;Yoshimitsu Fukushima;Darryl R. MacEr;Eiko Suda;Charles N. Rotimi;Clement A. Adebamowo;Ike Ajayi;Toyin Aniagwu;Patricia A. Marshall;Chibuzor Nkwodimmah;Charmaine D.M. Royal;Mark F. Leppert;Missy Dixon;Andy Peiffer;Renzong Qiu;Alastair Kent;Kazuto Kato;Norio Niikawa;Isaac F. Adewole;Bartha M. Knoppers;Morris W. Foster;Ellen Wright Clayton;Jessica Watkin;Donna Muzny;Lynne Nazareth;Erica Sodergren;George M. Weinstock;Imtaz Yakub;Bruce W. Birren;Richard K. Wilson;Lucinda L. Fulton;Jane Rogers;John Burton;Nigel P. Carter;Christopher M. Clee;Mark Griffiths;Matthew C. Jones;Kirsten McLay;Robert W. Plumb;Mark T. Ross;Sarah K. Sims;David L. Willey;竺 陈;Hua Han;乐 康;Martin Godbout;John C. Wallenburg;Paul L'Archevêque;Guy Bellemare;Koji Saeki;Hongguang Wang;Daochang An;Hongbo Fu;Qing Li;Zhen Wang;Renwu Wang;Arthur L. Holden;Lisa D. Brooks;Jean E. McEwen;Mark S. Guyer;Vivian Ota Wang;Jane L. Peterson;Michael Shi;Jack Spiegel;Lawrence M. Sung;Lynn F. Zacharia;Francis S. Collins;Karen Kennedy;Ruth Jamieson;John Stewart

Nature

2007-10-18

铭 黎;Xiong jian Luo;Xu Zhang;Zhao hui Yang;Kun Xiang;Xiao Xiao;兵 宿;Ya li Zhao;岩 沈;琪 许;Xiang ning Chen;Jing chun Chen;Xing yan Liu;Li de Yin;Xiao yuan Ma;Shun ying Yang;Jin Yu;Hong bo Diao;Xiao dong Shi

Schizophrenia Research

2011-7

W. J. Yang;J. F. Huang;C. L. Yao;Z. J. Fan;D. L. Ge;W. Q. Gan;G. Y. Huang;R. T. Hui;岩 沈;伯勤 强;东风 顾

Journal of Medical Genetics

2003-5

Genomics resources that use samples from identified populations raise scientific, social and ethical issues that are, in many ways, inextricably linked. Scientific decisions about which populations to sample to produce the HapMap, an international genetic vadation resource, have raised questions about the relationships between the social identities used to recruit participants and the biological findings of studies that will use the HapMap. The sometimes problematic implications of those complex relationships have led to questions about how to conduct genetic variation research that uses identified populations in an ethical way, including how to involve members of a population in evaluating the risks and benefits posed for everyone who shares that identity. The ways in which these issues are linked is increasingly drawing the scientific and ethical spheres of genomics research closer together.

Morris W. Foster;Ellen Wright Clayton;Bartha M. Knoppers;Renzong Qiu;Alastair Kent;Georgia M. Dunston;Kazuto Kato;Norio Niikawa;Isaac F. Adewole;Jessica Watkin;Houcan Zhang;Changqing Zeng;Ichiro Matsuda;Yoshimitsu Fukushima;Darryl R. Macer;Eiko Suda;Charles N. Rotimi;Clement A. Adebamowo;Toyin Aniagwu;Patricia A. Marshall;Olayemi Matthew;Chibuzor Nkwodimmah;Charmaine D.M. Royal;Mark F. Leppert;Missy Dixon;David L. Valle;Lynn B. Jorde;John W. Belmont;Aravinda Chakravarti;Mildred K. Cho;Troy Duster;Marla Jasperse;Pui Yan Kwok;Julio Licinio;Jeffrey C. Long;Pilar N. Ossorio;Vivian Ota Wang;Patricia Spallone;Sharon F. Terry;Richard A. Gibbs;Paul Hardenbol;Thomas D. Willis;Fuli Yu;David Altshuler;Stacey B. Gabriel;Huanming Yang;Lan Yang Ch'ang;Wei Huang;Bin Liu;Yan Shen;Paul Kwong Hang Tam;Lap Chee Tsui;Mary Miu Yee Waye;Jeffrey Tze Fei Wong;Qingrun Zhang;Mark S. Chee;Luana M. Galver;Semyon Kruglyak;Sarah S. Murray;Arnold R. Oliphant;Alexandre Montpetit;Thomas J. Hudson;Fanny Chagnon;Vincent Ferretti;Martin Leboeuf;Michael S. Phillips;Andrei Verner;Shenghui Duan;Denise L. Lind;Raymond D. Miller;John P. Rice;Nancy L. Saccone;Patricia Taillon-Miller;Ming Xiao;Yusuke Nakamura;Akihiro Sekine;Koki Sorimachi;Toshihiro Tanaka;Yoichi Tanaka;Tatsuhiko Tsunoda;Eiji Yoshino;David R. Bentley;Panos Deloukas;Don Powell;Mark J. Daly;Stephen F. Schaffner;Lincoln D. Stein;Fiona Cunningham;Ardavan Kanani;Gudmundur A. Thorisson;Peter E. Chen;David J. Cutler;Carl S. Kashuk;Shin Lin;Peter Donnelly;Jonathan Marchini;Gilean A.T. McVean;Simon R. Myers;Lon R. Cardon;Gonçalo R. Abecasis;Andrew Morris;Bruce S. Weir;James C. Mullikin;Stephen T. Sherry;Michael Feolo;Erica Sodergren;George M. Weinstock;Bruce W. Birren;Richard K. Wilson;Lucinda L. Fulton;Jane Rogers;Hua Han;Hongguang Wang;Martin Godbout;John C. Wallenburg;Paul L'Archevêque;Guy Bellemare;Kazuo Todani;Takashi Fujita;Satoshi Tanaka;Arthur L. Holden;Eric H. Lai;Francis S. Collins;Jean E. McEwen;Lisa D. Brooks;Mark S. Guyer;Elke Jordan;Jane L. Peterson;Jack Spiegel;Lawrence M. Sung;Lynn F. Zacharia;Karen Kennedy;Michael G. Dunn;Richard Seabrook;Mark Shillito;Barbara Skene;John G. Stewart;Eric S. Lander;Deborah A. Nickerson;Michael Boehnke;Julie A. Douglas;Richard R. Hudson;Leonid Kruglyak;Robert L. Nussbaum

Nature Reviews Genetics

2004-6-1