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Development of the expressed immunoglobulinμchain repertoire during maturation of mice B cells

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Frontiers of Agricultural Science and Engineering 2014年第3期1卷 201-213页

作者： Jingwen LIANG Yingfeng LUO Yi SUN Meng LEI Bing ZHANG songnian hu Yaofeng ZHAO State Key Laboratory of Agrobiotechnology College of Biological SciencesChina Agricultural UniversityBeijing 100094China CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Laboratory of Animal Molecular Genetics College of Animal Science and Veterinary MedicineShandong Agricultural UniversityTaian 271018China

In the bone marrow and spleen,the developing B cell populations undergo both negative and positive selections to shape their B cell receptor repertoire.To gain insight into the shift of the immunoglobulin heavy(IgH)chain repertoire during B cell development,we undertook large scale Igμchain repertoire analysis of pre-B,immature B and spleen B cell populations.We found that the majority of VH gene segments,VH families,JH and D gene segments,were observed to have significantly different usage frequencies when three B cell populations were compared,but the usage profile of the VH,D,and JH genes between different B cell populations showed high correlations.In both productive and nonproductive rearrangements,the length of CDRH3 shortened significantly on average when B cells entered the periphery.However,the CDRH3 length distribution of nonproductive rearrangements did not follow a Gaussian distribution,but decreased successively in the order 3n–2,3n–1 and 3n,suggesting a direct correlation between mRNA stability and CDRH3 length patterns of nonproductive rearrangements.Further analysis of the individual components comprising CDRH3 of productive rearrangements indicated that the decrease in CDRH3 length was largely due to the reduction of N addition at the 5′and 3′junctions.Moreover,with development,the amino acid content of CDRH3 progressed toward fewer positively charged and nonpolar residues but more polar residues.All these data indicated that the expressed Igμchain repertoire,especially the repertoire of CDRH3,was fine-tuned when B cells passed through several checkpoints of selection during the process of maturation.

关键词： immunoglobulin heavy chain variable region repertoire complementarity determining region 3 of the IgH chain(CDRH3)

Cloning and identification of a novel human glioma differentiation related gene GDR1

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Chinese Science Bulletin 2000年第11期45卷 995-999页

作者： Guangtao Li hulin Jin songnian hu Jian Jin Chun Tu Jiangang Yuan Boqin Qiang Peking Union Med Coll Sch Basic MedNatl Ctr Human Genome Res Chinese Acad Med Sci Inst Basic Med SciNatl Lab Med Mol Biol Beijing 100005 Peoples R China

In order to identify the genes associated with glioblastoma differentiation, some ESTs, expressed differentially in the control cell and the differentiated human glioblastoma cell line BT-325 induced by the all-trans retinoid acid, have been isolated by the method of DDRT-PCR. Of the 46 ESTs sequenced, 19 are from new genes. A full-length 1 535-bp cDNA, termed gene GDR1, has been isolated from the human cDNA library using the probe designed according to one of the novel ESTs, HGBB098. The open reading frame of GDR1 gene encodes a putative protein containing 334 amino acid residues. Blast against the current GenBank DMA and protein sequence database did not reveal significant homology with any known proteins. RT-PCR shows that GDR1 mRNA level increased in the differentiated BT-325 cells after being treated with RA. The different expression patterns of GDR1 mRNA in human tissues have been detected through the multiple tissue Northern blot hybridization.

关键词： human glioma GDR1 RT-PCR.

CYP2A6 Polymorphisms Associate with Outcome of S-1 Plus Oxaliplatin Chemotherapy in Chinese Gastric Cancer Patients

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Genomics, Proteomics & Bioinformatics 2017年第4期15卷 255-262页

作者： Lin Yang Shanshan Zou Chang Shu Yan Song Yong-Kun Sun Wen Zhang Aiping Zhou Xinghua Yuan Yi Yang songnian hu Department of Medical Oncology National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Department of Pancreatic and Gastric Surgery National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Gastric carcinoma is a heterogeneous malignant disease involving genetic factors. To identify predictive markers for gastric cancer treatment in Chinese patients, we evaluated the association between polymorphisms of the gene encoding cytochrome P450 2A6 （CYP2A6） and outcomes of S-1 plus oxaliplatin （SOX） chemotherapy treatment. Clinical data on 60 consecutive gastric cancer patients receiving SOX regimen were collected prospectively. We sequenced all exons of CYP2A6 and a total of 22 different polymorphisms were detected in the present study. Comprehensive analyses of these genetic polymorphisms were performed to determine their association with both safety and efficacy of SOX regimen. Our results showcd that polymorphisms of （＇ YP2A6 wcrc associated with the safety and efficacy of SOX treatment. Among them, missense mutations CYP2A6 rs60823196 and rs138978736 could be possible risk 6actors （P 〈 0.05） for severe diarrhea induced by SOX, whereas CYP2A6 rs138978736 could be a conceiwtble predictor for overall survival of patients treated with SOX adjuvant chemotherapy. Further large-scale randomized prospective studies are warranted to confirm these findings.

关键词： CYP2A6 Gastric cancer Pharmacogenomics Polymorphism SOX

Adolescent Mouse Takes on An Active Transcriptomic Expression During Postnatal Cerebral Development

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Genomics, Proteomics & Bioinformatics 2014年第3期12卷 111-119页

作者： Wei Xu Chengqi Xin Qiang Lin Feng Ding Wei Gong Yuanyuan Zhou Jun Yu Peng Cui songnian hu CAS Key Laboratory of Genome Sciences and Information Beijing Institute of Genomics Chinese Academy of Sciences

Postnatal cerebral development is a complicated biological process precisely controlled by multiple genes. To understand the molecular mechanism of cerebral development, we compared dynamics of mouse cerebrum transcriptome through three developmental stages using high-throughput RNA-seq technique. Three libraries were generated from the mouse cerebrum at infancy, adolescence and adulthood, respectively. Consequently, 44,557,729 （infancy）, 59,257,530 （adolescence） and 72,729,636 （adulthood） reads were produced, which were assembled into 15,344, 16,048 and 15,775 genes, respectively. We found that the overall gene expression level increased from infancy to adolescence and decreased later on upon reaching adulthood. The adolescence cerebrum has the most active gene expression, with expression of a large number of reg- ulatory genes up-regulated and some crucial pathways activated. Transcription factor （TF） analysis suggested the similar dynamics as expression profiling, especially those TFs functioning in neurogenesis differentiation, oligodendrocyte lineage determination and circadian rhythm regulation. Moreover, our data revealed a drastic increase in myelin basic protein （MBP）-coding gene expression in adolescence and adulthood, suggesting that the brain myelin may be generated since

关键词： Cerebrum Postnatal development Gene expression Transcriptome High-throughput sequencing

Screening and Assessing 11 Mycobacterium tuberculosis Proteins as Potential Serodiagnostical Markers for Discriminating TB Patients from BCG Vaccinees

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Genomics, Proteomics & Bioinformatics 2009年第3期7卷 107-115页

作者： Guoqiang Zhang Lingxia Zhang Mingcheng Zhang Linlin Pan Fengyu Wang Jun huang Guoli Li Jun Yu songnian hu CAS Key Laboratory of Genome Sciences and Information Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100029 China Graduate University of Chinese Academy of Sciences Beijing 100049 China The Second Hospital Affiliated to the General Hospital of the People＇s Liberation Army Beijing 100091 China

Purified protein derivative （PPD） skin tests often yield poor specificity, so that to develop new serological antigens for distinguishing between Mycobacterium tuberculosis infection and Bacille Calmette-Guerin （BCG） vaccination is a priority, especially for developing countries like China. We predicted the antigenicity for selected open reading frames （ORFs） based on the genome sequences of M. tuberculosis H37Rv and M. boris BCG, as well as their functions and differences of expression under different stimulus. The candidate ORFs were cloned from H37Rv sequences and expressed as recombinant proteins in Escherichia coli. We studied the serodiagnostic potential of 11 purified recombinants by using enzyme-linked immunosorbent assay （ELISA） and involving a cohort composed of 58 TB patients （34 males and 24 females）, 8 healthy volunteers and 50 PPD-negative individuals before and after BCG vaccination. For all the 11 antigens, the median OD values for the sera from TB patients were statistically significantly higher than those for PPD-negative individuals before or after BCG vaccination （P〈0.01）. They had at least 92% specificity in healthy controls and six seroantigens （Rv0251c, Rv1973, Rv2376c, Rv2537c, Rv2785c and Rv3873A） were never reported with seroantigenicities previously. Thus the approach combining comparative genomics, bioinformatics and ELISA techniques can be employed to identify new seroantigens distinguishing M. tuberculosis infection from BCG vaccination.

关键词： comparative genomics M. tuberculosis BCG seroantigen ELISA

Fine-Tuning of MiR528 Accumulation Modulates Flowering Time in Rice

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Molecular Plant 2019年第8期12卷 1103-1113页

作者： Rongxin Yang Pingchuan Li Hailiang Mei Dong Wang Jing Sun Chao Yang Lili Hao Shouyun Cao Chengcai Chu songnian hu Xianwei Song Xiaofeng Cao State Key Laboratory of Plant Genomics and National Center for Plant Gene Research (Beijing) Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Key Laboratory of Molecular Biology and Gene Engineering in Jiangxi Province College of Life ScienceNanchang UniversityNanchangJiangxi 330031China University of Chinese Academy of Sciences Beijing 100049China Center for Excellence in Molecular Plant Sciences Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

In plants,microRNA (miRNA) functions in the post-transcriptional repression of target mRNAs have been well explored.However,the mechanisms regulating the accumulation of miRNAs remain poorly under.stood.Here,we report that distinct mechanisms regulate accumulation of a monocot-specific miRNA,rice (Oryza sativa) miR528.At the transcriptional level,miR528 accumulated to higher levels in older plants than in young seedlings and exhibited aging-modulated gradual accumulation and diurnal rhythms in leaves;at the post-transcriptional level,aging also modulated miR528 levels by enhancing pri-miR528 alter.native splicing.We found that miR528 promotes rice flowering under long-day conditions by targeting RED AND FAR-RED INSENSITIVE2 (OsRFI2).Moreover,natural variations in the MIR528 promoter region caused differences in miR528 expression among rice varieties,which are correlated with their different binding affinities with the transcription factor OsSPL9 that activates the expression of miR528.Taken together,our findings reveal rice plants have evolved sophisticated modes fine-tuning miR528 levels and provide insight into the mechanisms that regulate MIRNA expression in plants.

关键词： miRNA OsSPL9 Alternative splicing Post-transcriptional regulation Natural variation Flowering

Phylogenetic Analysis of Brine Shrimp (Artemia) in China Using DNA Barcoding

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Genomics, Proteomics & Bioinformatics 2008年第3期6卷 155-162页

作者： Weiwei Wang Qibin Luo Haiyan Guo Peter Bossier Gilbert Van Stappen Patrick Sorgeloos Naihong Xin Qishi Sun songnian hu Jun Yu Key Laboratory of Genome Sciences and Information Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100029 China Graduate University of Chinese Academy of Sciences Beijing 100049 China James D. Watson Institute of Genome Sciences Zhejiang University Hangzhou 310008 China School of Traditional Chinese Materia Medica Shenyang Pharmaceutical University Shenyang 110016 China Laboratory of Aquaculture ＆ Artemia Reference Center Ghent University B-9000 Ghent Belgium Salt Research Institute Tianjin 300450 China.

DNA barcoding is a powerful approach for characterizing species of organisms, especially those with almost identical morphological features, thereby helping to to establish phylogenetic relationships and reveal evolutionary histories. In this study, we chose a 648-bp segment of the mitochondrial gene, cytochrome c oxidase subunit 1 （COI）, as a standard barcode region to establish phylogenetic relationships among brine shrimp （Artemia） species from major habitats around the world and further focused on the biodiversity of Artemia species in China, especially in the Tibetan Plateau. Samples from five major salt lakes of the Tibetan Plateau located at altitudes over 4,000 m showed clear differences from other Artemia populations in China. We also observed two consistent amino acid changes, 153A/V and 183L/F, in the COI gene between the high and low altitude species in China. Moreover, indels in the COI sequence were identified in cyst and adult samples unique to the Co Qen population from the Tibetan Plateau, demonstrating the need for additional investigations of the mitochondrial genome among Tibetan Artemia populations.

关键词： Artemia DNA barcoding molecular phylogeny Tibetan Plateau

A systematic identification of Kolobok superfamily transposons in Trichomonas vaginalis and sequence analysis on related transposases

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Journal of Genetics and Genomics 2011年第2期38卷 63-70页

作者： Qingshu Meng Kaifu Chen Lina Ma songnian hu Jun Yu CAS Key Laboratory of Genome Sciences and Information Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100029 China Graduate University of Chinese Academy of Sciences Beijing 100049 China Division of Biostatistics Dan L. Duncan Cancer Center Baylor College of Medicine Houston TX 77030 USA Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX 77030 USA

Transposons are sequence elements widely distributed among genomes of all three kingdoms of life, providing genomic changes and playing significant roles in genome evolution. Trichomonas vaginalis is an excellent model system for transposon study since its genome （- 160 Mb） has been sequenced and is composed of - 65% transposons and other repetitive elements. In this study, we primarily report the identification of Kolobok-type transposons （termed tvBac） in T. vaginalis and the results of transposase sequence analysis. We categorized 24 novel subfamilies of the Kolobok element, including one autonomous subfamily and 23 non-autonomous subfamilies. We also identified a novel H2CH motif in tvBac transposases based on multiple sequence alignment. In addition, we supposed that tvBac and Mutator transposons may have evolved independently from a common ancestor according to our phylogenetic analysis. Our results provide basic information for the understanding of the function and evolution of tvBac transposons in particular and other related transposon families in general.

关键词： Trichomonas vaginalis Transposase Kolobok tvBac

A pangenomic study of Bacillus thuringiensis

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Journal of Genetics and Genomics 2011年第12期38卷 567-576页

作者： Yongjun Fang Zhaolong Li Jiucheng Liu Changlong Shu Xumin Wang Xiaowei Zhang Xiaoguang Yu Duojun Zhao Guiming Liu songnian hu Jie Zhang Ibrahim Al-Mssallem Jun Yu James D. Watson Institute of Genome Sciences College of Life Science Zhejiang University Hangzhou 310058 China CAS Key Laboratory of Genome Science and Information Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100029 China Graduate University of Chinese Academy of Sciences Beijing 100049 China State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant Protection Chinese Academy of Agricultural Sciences Beijing 100193 China The Date Palm Genome Project （DPGP） King Abdulaziz City for Science and Technology （KACST） P.O. Box： 6086 Riyadh 11442 Kingdom of Saudi Arabia

Bacillus thuringiensis（B.thuringiensis） is a soil-dwelling Gram-positive bacterium and its plasmid-encoded toxins（Cry） are commonly used as biological alternatives to pesticides.In a pangenomic study,we sequenced seven B.thuringiensis isolates in both high coverage and base-quality using the next-generation sequencing platform.The B.thuringiensis pangenome was extrapolated to have 4196 core genes and an asymptotic value of 558 unique genes when a new genome is added.Compared to the pangenomes of its closely related species of the same genus,B.thuringiensis pangenome shows an open characteristic,similar to B.cereus but not to B.anthracis;the latter has a closed pangenome. We also found extensive divergence among the seven B.thuringiensis genome assemblies,which harbor ample repeats and single nucleotide polymorphisms（SNPs）.The identities among orthologous genes are greater than 84.5%and the hotspots for the genome variations were discovered in genomic regions of 2.3-2.8 Mb and 5.0-5.6 Mb.We concluded that high-coverage sequence assemblies from multiple strains, before all the gaps are closed,are very useful for pangenomic studies.

关键词： Bacillus thuringiensis（B.thuringiensis） Pseudo-chromosome Pangenome