Identification of TSS in the Human Genome Based on a RBF Neural Network

The identification of functional motifs in a DNA sequence is fundamentally a statistical pattern recognition problem. This paper introduces a new algorithm for the recognition of functional transcription start sites （TSSs） in human genome sequences, in which a RBF neural network is adopted, and an improved heuristic method for a 5-tuple feature viable construction, is proposed and implemented in two RBFPromoter and ImpRBFPromoter packages developed in Visual C＋＋ 6.0. The algorithm is evaluated on several different test sequence sets. Compared with several other promoter recognition programs, this algorithm is proved to be more flexible, with stronger learning ability and higher accuracy.

Human genome epidemiology,progress and future

Human genome epidemiology （HUGE） uses sys- tematic applications of epidemiologic methods to as- sess the impact of human genetic variation on health and disease. In the past ten years, human genome epi- demiology has made great progresses along with ad- vances in genomics technologies, which make it pos- sible for the examination of genetic variants in a large sample size at a sufficiently low cost. Genetic associa- tion study in population provides a powerful approach to identify variants or genes associated with disease of interest by comparing distributions of genetic variants between affected and unaffected individuals.

From human genome epidemiology to systems epidemiology:current progress and future perspective

The recent progress in human genome epidemiology(HuGE) is already having a profound impact on the practice of medicine and public health.First,the success of genome-wide association studies has greatly expanded the direction and content of epidemiological researches,including revealing new genetic mechanisms of complex diseases,identifying new targets for therapeutic interventions,and improving application in early screening of high-risk populations.At the same time,large-scale genomic studies make it possible to efficiently explore the gene-environment interactions,which will help better understand the biological pathways of complex diseases and identify individuals who may be more susceptible to diseases.Additionally,the emergence of systems epidemiology aims to integrate multi-omics together with epidemiological data to create a systems network that can comprehensively characterize the diverse range of factors contributing to disease development.These progress will help to apply HuGE findings into practice to improve the health of individuals and populations.

HUMAN GENOME RESEARCH & LEUKEMIA THERAPY IN CHINA

Ⅰ. HGP AND HUMAN GENOME SCIENCE IN CHINA The HGP, standing for "human genome project," is one of the basic research programs of vital importance in life science, now underway in a worldwide scope. Its significance is never to be overestimated when we place any stress on it. As a matter of fact, it will provide an invaluable tool to reveal the essence of human life by

CHINESE HUMAN GENOME PROJECT (HGP) MADE SIGNIFICANT PROGRESS

The first stage of HGP in China (Jan. 1994～Jun. 1997) was sponsored by the National Natural Science Foundation of China in the form of a principle project (total funding: 3,750,000 RMB) entitled "Study on gene structure of some loci in the genome of Chinese nationalities". After 3 and half years’ collaborative work by 19 groups and about 200 scientists distributed in 16 participating labs, coordinated by Prof. Bo-Qing QIANG of the Institute of Basic Medical Sciences, Chinese

The Human Genome Map

ON April 14, 2003, scientists from China, the United States. Japan, Germany, France and Britain announced they had completed sequence mapping of the human genome, marking the end of the Human Genome Project （HGP） started in 1990. Yang Huanming, an academician from the Chinese Academy of Sciences （CAS） and Chairman of the Shenzhen branch of the Beijing Genomics Institute （BGI）. led the group of Chinese experts that contributed to the project. The Chinese team played an integral part in the research unti August 26, 2001.

Human genome editing after the "CRISPR babies":The double-pacing problem and collaborative governance

How to ensure the safe,effective,and ethical use of emerging biotechnologies,such as clustered regularly interspaced short palindromic repeats(CRISPR)-based genome editing,is a global challenge.The occurrence of the"CRISPR babies"in 2018 publicly brought this issue into sharp focus,and led to comprehensive regulatory reforms in China and various countries around the world.The current article analyzes this event-driven regulatory reform in China by elaborating the most salient provisions designed to prevent risk and protect individual rights,public health,and social morality relating to human genome editing in four important sectors of law:biosecurity law,civil code,criminal law and patent law.It highlights that,although regulation is being undertaken,the gaps between the law and advancing technology remain discernible,at both a national and transnational level(i.e.,the "double-pacing problem").Further attention and collaboration will be required to address the ongoing challenges associated with the use of human genome editing.

A legacy of the “1% program”-The “Chinese Chapter” of the human genome reference sequence

The year of 2018 marks the 65th anniversary of the discovery of DNA double helix and the 15th anniversary of the successful completion of the international Human Genome Project (HGP),the two revolutions in life sciences (Sharp, 2014). The year also sees the effective implementation of the "1%Program", the Chinese contribution to the reference sequence of the human genome,which coincides with the 40th anniversary of the founding of the Genetics Society of China, one of the most influential national academic organizations in China.

Working Map of Human Genome Complete

提示:2000年6月26日无疑是世界生物史上最具重大意义的一天。研究机构经过长达十年的研究,公布了人类基因图计划。世界舆论甚至将人类基因组图的研究计划称为“生物学上的阿波罗登月计划”。将此与当年人类成功登月相提并论。 本文中提及的马里兰州罗克维尔市的塞利拉基因组公司在加入了这项研究计划之后,研究计划有了飞快的发展,甚至可以用“更上一层楼”来形容。 人类此举的主要意义有两个方面: 一是,人类将把自己独一无二的遗传密码存入智慧卡,一旦主人生病,医生将根据病人的基因类型配制药物,再也不是同一种病开出同一种药。 二是,了解了人类的基因组的秘密最终将会促进最新药物,或曰“灵丹妙药”的研制。 对人类基因的改变并非轻而易举之事。如同学会了简单的字母只是开始接受教育一样,也许需要100年的时间,大功才能告成。 美国总统克林顿“抢先”发表高论:解破人类基因密码,将永远改变“人类保健的全貌”。对此,立即有专家作出反应说:这一说法还为时尚早。

Phylogenetic analysis of the genomes of two strains of human adenovirus type 3

Human adenovirus type 3 （HAdV-3） is widely prevalent all over the world, especially in Asia. The objective of this study is to carry out complete genomic DNA sequencing and the phylogenetic analysis for two strains （Guangzhou01 and Guangzhou02） of HAdV-3 wild virus isolated from South China. Nasopharyngeal secretion aspirate specimens of sick children were inoculated into HEp-2 and HeLa culture tubes, and the cultures were identified by neutralization assay with type-specific reference rabbit antiserum. Type-specific primers were also utilized to confirm the serotype. The restriction fragments of HAdV genome DNA were cloned into pBlueScript SK （ ＋ ） vectors and sequenced, and the 5＇ and 3＇ ends of the linear HAdV-3 genome were directly sequenced with double purified genomic DNA as templates. General features of the HAdV-3 genome sequences were explored by using several bio-software. Phylogenetic analysis was done with MEGA 3.0 software. The genomic sequences of Guangzhou01 and Guangzhou02 possess the same 4 early regions and 5 late regions and have 39 coding sequences and two RNA coding sequences. Other non-coding regions are conservative. Inverted repeats and palindromes were identified in the genome sequences. The genomes of group B human adenovirus as well as HAdV-3 have close phylogenetic relationship with that of chimpanzee adenovirus type 21. The genomic lengths of these two isolated strains are 35 273 bp and 35 269 bp, respectively. The phylogenetic analysis showed that HAdV-B species has some relationship with certain types of chimpanzee adenovirus.

A NOVEL HUMAN DNA SEQUENCE WITH TUMOR METASTASIS SUPPRESSIVE ACTIVITY

Objective: To isolate human tumor metastasis suppressive DNA sequence and to study the molecular mechanisms regulating tumor metastasis. Methods: A mouse lung adenocarcinoma cell clone 12 derived from its parent cell line LM2, which had been transduced with normal human genomic DNA, was previously reported. Compared with LM2, the metastatic potential of clone 12 was very much decreased. Clone 12 was used in this study to amplify the human DNA fragments by Inter Alu PCR technique. The human DNA fragments obtained were then transfected into LM2 cells and their malignant phenotype was tested in vitro and in vivo, and compared with that of the untransfected LM2 cells.Results Three human DNA fragments of 700, 500 and 300 bp were isolated. DNA sequencing revealed that the 700bp fragment does not show homology with hitherto reported genes and was accepted by the Genbank (pt712 U67835). In vitro proliferation and colony formation in soft agar of the 700 bp fragment-transfected LM2 cells were significantly inhibited as compared to the untransfected LM2 cells. Upon subcutaneous inoculation to syngeneic T739 mice, the 700bp-transfected LM2 cells grew more slowly and smaller tumors developed compared to the untransfected ones. Moreover, lung metastasis was not found in 6 of 10 mice inoculated with the 700bp-transfected LM2 cells, while it was found in 9 of 10 mice inoculated with the untransfected LM2 cells. The difference was statistically significant (P<0.001). The frequency of lymph node metastasis was also statistically different between the 2 groups of mice.Conclusion The newly isolated 700bp human DNA fragment may be a metastasis suppressor gene of malignant tumor.

The complete genomic sequence analysis of human norovirus NVgz01 strain in Guangzhou

The aim of this study is to explore the genomic molecular organization and genogroup of human nomvirus from infected infants in Guangzhou of China. Primers were designed according to the genomic sequence of norovims in the GenBank, and the nomvirus genome was amplified by RT-PCR. The PCR- products were cloned into T vector and sequenced, and the genomic nucleotide sequences were analyzed with the programs CLUSTAL W/X, DNASTAR and RAT （Recombination Analysis Tool）. The NVgz01 strain genome is 7558 bp in length and encodes three open reading frames （GenBank accession No. is DQ369797）. The genomic sequences of NVgz01 were compared with those of nomvirus in GenBank, which revealed that the homology with genogroup Ⅱ ranges between 76%-90%, and genogroup Ⅰ between 43%-44%. The ORF1 region shared 94% and 88% identity with Mc37 and Famiington strains, respectively; the capsid region （ORF2） shared 65% and 94% identity with Mc37 and Farmington strains, respectively. Phylogenetic trees were reconstructed by the neighbor-joining method. Comparative complete sequence analysis of the NVgz01 with reported human norovirus genomic sequences revealed that this isolate belongs to genogroup Ⅱ . The ORF1 and ORF2 regions shared different identity with Mc37 and Fannington strains, suggesting NVgz01 could be a recombinant virus.

The complete genomic sequence analysis of genotype 4 human astrovirus HASTVgz01 strain in Guangzhou

To analyze the genomic molecular structure and genotype of human astrovirus isolated from infant in Guangzhou of China, the primers were designed based on the genomic sequence of astrovirus from the C, enBank and the target sequence were amplified by RT-PCR. Then the PCR-products were cloned to T vector and sequenced. The genomic nucleotide sequences were analyzed by the programs CLUSTAL W and DNASTAR. It was found that the full genomic length of HASTVgz01 strain was 6721 bp and the ORFs were 6558 bp. The 5＇ and 3＇UTR were 82 and 81 nucleotides. The genome included 3 open reading frames （ORFs） ： ORFla, ORFlb and ORF2. The 5＇-terminal ORFla started at nueleotide 83 and extended to nucleotide 2845. ORFlb （nt 2785 to nt 4332） overlaped ORFla by 61 nueleotides. The 3＇-terminal ORF2 began at nucleotide 4325 and terminated at nucleotide 6640. ORF2 had 2316 nucleotides. Compared with other astrovirus sequences in GenBank, the homology of the amino acid sequence of ORF2 of HASTVgz01 strain with that of serotype 4 was 93%. Homology with other serotypes ranged from 61% to 70%. The complete nucleotide sequence of astrovirus HASTVgz01 strain isolated from Guangzhou in China was 6721 bp in length, GenBank accession NO. DQ344027. Comparing the ORF2 of astrovirus HASTVgz01 with the known sequences of types 1-8 the highest homology was serotype 4 （93%）. Comparative sequence analysis of the HASTVgz01 ORF2 with the reported human astrovirus sequences revealed that the isolated astrovirus belongs to genotype （serotype） 4.

Searching for candidate genes for male infertility

<abstract>Aim: We describe an approach to search for candidate genes for male infertility using the two human genome databases: the public University of California at Santa Cruz (UCSC) and private Celera databases which list known and predicted gene sequences and provide related information such as gene function, tissue expression, known mutations and single nucleotide polymorphisms (SNPs). Methods and Results: To demonstrate this in silico research, the following male infertility candidate genes were selected: (1) human BOULE, mutations of which may lead to germ cell arrest at the primary spermatocyte stage, (2) mutations of casein kinase 2 alpha genes which may cause globozoospermia, (3) DMR-N9 which is possibly involved in the spermatogenic defect of myotonic dystrophy and (4) several testes expressed genes at or near the breakpoints of a balanced translocation associated with hypospermatogenesis. We indicate how information derived from the human genome databases can be used to confirm these candidate genes may be pathogenic by studying RNA expression in tissue arrays using in situ hybridization and gene sequencing. Conclusion: The paper explains the new approach to discovering genetic causes of male infertility using information about the human genome.

Haplotype-resolved Chinese male genome assembly based on high-fidelity sequencing

The advantages of both the length and accuracy of high-fidelity(HiFi)reads enable chromosome-scale haplotype-resolved genome assembly.In this study,we sequenced a cell line named HJ,established from a Chinese Han male individual by using HiFi and Hi-C.We assembled two high-quality haplotypes of the HJ genome(haplotype 1(H1):3.1 Gb,haplotype 2(H2):2.9 Gb).The continuity(H1:contig N50=28.2 Mb,H2:contig N50=25.9 Mb)and completeness(BUSCO:H1=94.9%,H2=93.5%)are substantially better than those of other Chinese genomes,for example,HX1,NH1.0,and YH2.0.By comparing HJ genome with GRCh38,we reported the mutation landscape of HJ and found that 176 and 213 N-gaps were filled in H1 and H2,respectively.In addition,we detected 12.9 Mb and 13.4 Mb novel sequences containing 246 and 135 protein-coding genes in H1 and H2,respectively.Our results demonstrate the advantages of HiFi reads in haplotype-resolved genome assembly and provide two high-quality haplotypes of a potential Chinese genome as a reference for the Chinese Han population.

Human Genomics in China——Ten Years Endeavor:From Planning to Implementation

Ten years ago, the Chinese National Human Genome Center at Shanghai (South Center,hereafter) was established in the Zhangjiang

A brief overview of game-changing genetic engineering projects

In recent era,advancement of research involves computational management of large-scale genomic and post-genomic datasets in an obvious way.Rapidly emerging field of bioinformatics,fueled by high-throughput technologies and genomic scale database,is believed to reshape our approach of research to a new level.Genomics has shifted the paradigm of biological perspectives exploring many scopes.Old initiatives paved the path for the newer and more advantageous one.The present review focuses on present initiatives that are implemented till now like the famous Human Genome Project and its influence on digital biology,as well as the projects that followed in its footsteps.Additionally,the authors delve into the future potential of personalized medicine and the use of genetic engineering methods like CRISPR/Cas9 in gene editing,which are thought to have the potential to revolutionize the current treatment strategy.

DNA sequences homologous to hepatitis C virus(HCV) in the extrachromosomal circular DNA in peripheral blood mononuclear cells of HCV-negative subjects

Objective: This study aimed to investigate DNA sequences that are substantially homologous to the corresponding RNA sequence sections of the hepatitis C virus (HCV). These DNA sequences are present in the whole DNA extracted from peripheral blood mononuclear cells (PBMCs) of HCV-negative subjects. We presumed that these experimentally proven 5'-noncoding region (5'-NCR) homologous DNA sequences could be contained in the extrachromosomal circular DNA (eccDNA) fraction as part of the whole cellular DNA. Methods: Home-made polymerase chain reaction (PCR) with whole cellular and isolated eccDNA, nucleotide basic local alignment search tool (BLASTn) alignments, and tests for patterns of methylation in selected sequence sections were performed. Results: The PCR tests revealed DNA sequences of up to 320 bp that broadly matched the corresponding sequence sections of known HCV genotypes. In contrast, BLASTn alignment searches of published HCV 5'-NCR sequences with human genome databases revealed only sequence segments of up to 36 bp of the 5'-NCR. The composition of these sequences shows missing base pairs, base pair mismatches as well as complete homology with HCV reference sequences. These short sequence sections are present in numerous copies on both the same and different chromosomes. The selected sequence region within the DNA sequences of the 5'-NCR revealed a broad diversity of individual patterns of methylation. Conclusions: The experimental results confirm our assumption that parts of the HCV 5'-NCR genomic RNA sequences are present at the DNA level in the eccDNA fraction of PBMCs. The tests for methylation patterns therein revealed individual methylomes which could represent an epigenetic feature. The respective sequence section might be subject to genetic regulation.