In this study, the 454 pyrosequencing technology was used to analyze the DNA of the Microcystis aeruginosa symbiosis system from cyanobacterial algal blooms in Taihu Lake, China. We generated 183 228 reads with an ave...In this study, the 454 pyrosequencing technology was used to analyze the DNA of the Microcystis aeruginosa symbiosis system from cyanobacterial algal blooms in Taihu Lake, China. We generated 183 228 reads with an average length of 248 bp. Running the 454 assembly algorithm over our sequences yielded 22 239 significant contigs. After excluding the M. aeruginosa sequences, we obtained 1 322 assembled contigs longer than 1 000 bp. Taxonomic analysis indicated that four kingdoms were represented in the community: Archaea (n = 9; 0.01%), Bacteria (n = 98 921; 99.6%), Eukaryota (n = 373; 3.7%), and Viruses (n = 18; 0.02%). The bacterial sequences were predominantly Alphaproteobacteria (n = 41 805; 83.3%), Betaproteobacteria (n = 5 254; 10.5%) and Gammaproteobacteria (n = 1 180; 2.4%). Gene annotations and assignment of COG (clusters of orthologous groups) functional categories indicate that a large number of the predicted genes are involved in metabolic, genetic, and environmental information processes. Our results demonstrate the extraordinary diversity of a microbial community in an ectosymbiotic system and further establish the tremendous utility of pyrosequencing.展开更多
Nested in the environment of the nucleus of the cell, the 23 sets of chromosomes that comprise the human genome function as one integrated whole system, orchestrating the expression of thousands of genes underlying th...Nested in the environment of the nucleus of the cell, the 23 sets of chromosomes that comprise the human genome function as one integrated whole system, orchestrating the expression of thousands of genes underlying the biological characteristics of the cell, individual and the species. The extraction of meaningful information from this complex data set depends crucially upon the lens through which the data are examined. We present a biophysical perspective on genomic information encoded in single nucleotide polymorphisms (SNPs), and introduce metrics for modeling information encoded in the genome. Information, like energy, is considered to be a conserved physical property of the universe. The information structured in SNPs describes the adaptation of a human population to a given environment. The maintained order measured by the information content is associated with entropies, energies, and other state variables for a dynamic system in homeostasis. “Genodynamics” characterizes the state variables for genomic populations that are stable under stochastic environmental stresses. The determination of allelic energies allows the parameterization of specific environmental influences upon individual alleles across populations. The environment drives population-based genome variation. From this vantage point, the genome is modeled as a complex, dynamic information system defined by patterns of SNP alleles and SNP haplotypes.展开更多
The human genome is a complex, dynamic information system that encodes principles of life and living systems. These principles are incorporated in the structure of human genome sequence variation and are foundational ...The human genome is a complex, dynamic information system that encodes principles of life and living systems. These principles are incorporated in the structure of human genome sequence variation and are foundational for the continuity of life and human survival. Using first principles of thermodynamics and statistical physics, we have developed analogous “genodynamic tools” for population genomic studies. Characterizing genomic information through the lens of physics has allowed us to develop energy measures for modeling genome-environment interactions. In developing biophysical parameters for genome-environment homeostasis, we found that stable genomic free energy trades off low genomic energy (genomic conservation and increased order) and high genomic entropy (genomic variation) with an environmental potential that drives the variation. In our approach, we assert that common variants are dynamic sites in the genome of a population and that the stability of whole genome adaptation is reflected in the frequencies of maintained diversity in common variants for the population in its environment. In this paper, we address the relativity of whole genome adaptation towards homeostasis. By this we mean that adaptive forces are directly reflected in the frequency distribution of alleles and/or haplotypes of the population relative to its environment, with adaptive forces driving the genome towards homeostasis. The use of genomic energy units as a biophysical metric in DNA sequence variation analyses provides new insights into the foundations of population biology and diversity. Using our biophysical tools, population differences directly reflect the adaptive influences of the environment on populations.展开更多
As a living information and communications system, the genome encodes patterns in single nucleotide polymorphisms (SNPs) reflecting human adaptation that optimizes population survival in differing environments. This p...As a living information and communications system, the genome encodes patterns in single nucleotide polymorphisms (SNPs) reflecting human adaptation that optimizes population survival in differing environments. This paper mathematically models environmentally induced adaptive forces that quantify changes in the distribution of SNP frequencies between populations. We make direct connections between biophysical methods (e.g. minimizing genomic free energy) and concepts in population genetics. Our unbiased computer program scanned a large set of SNPs in the major histocompatibility complex region and flagged an altitude dependency on a SNP associated with response to oxygen deprivation. The statistical power of our double-blind approach is demonstrated in the flagging of mathematical functional correlations of SNP information-based potentials in multiple populations with specific environmental parameters. Furthermore, our approach provides insights for new discoveries on the biology of common variants. This paper demonstrates the power of biophysical modeling of population diversity for better understanding genome-environment interactions in biological phenomenon.展开更多
BACKGROUND The diagnostic and economic value of carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9)and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale.AIM To reassess the d...BACKGROUND The diagnostic and economic value of carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9)and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale.AIM To reassess the diagnostic and economic value of the three tumor biomarkers.METHODS A retrospective analysis of all 32857 subjects who underwent CEA,CA19-9,CA72-4,gastroscopy and colonoscopy from October 2006 to May 2018 was conducted.Then,we assessed the discrimination and clinical usefulness.Total cost,cost per capita and cost-effectiveness ratios were used to evaluate the economic value of two schemes(gastrointestinal endoscopy for all people without blood tests vs both gastroscopy and colonoscopy when blood tests were positive).RESULTS The analysis of 32857 subjects showed that CEA was a qualified biomarker for colorectal cancer(CRC),while the diagnostic efficiencies of CA72-4 were catastrophic for all gastrointestinal cancers(GICs).Regarding early diagnosis,only CEA could be used for early CRC.The combination of biomarkers didn’t greatly increase the area under the curve.The economic indicators of CEA were superior to those of CA19-9,CA72-4 and any combination.At the threshold of 1.8μg/L to 10.4μg/L,all four indicators of CEA were lower than those in the scheme that conducted gastrointestinal endoscopy only.Subgroup analysis implied that the health checkup of CEA for people above 65 years old was economically valuable.CONCLUSION CEA had qualified diagnostic value for CRC and superior economic value for GICs,especially for elderly health checkup subjects.CA72-4 was not suitable as a diagnostic biomarker.展开更多
Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancerrelated death.More than 80%of diagnoses occur at the middle to late stage of the disease,highlighting an urgent need f...Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancerrelated death.More than 80%of diagnoses occur at the middle to late stage of the disease,highlighting an urgent need for novel biomarkers detectable at earlier stages.Recently,aberrantly expressed microRNAs(miRNAs)have received a great deal of attention as potential sensitive and accurate biomarkers for cancer diagnosis and prognosis.This review summarizes the current knowledge about potential miRNA biomarkers for gastric cancer that have been reported in the publicly available literature between 2008 and 2013.Available evidence indicates that aberrantly expressed miRNAs in gastric cancer correlate with tumorigenesis,tumor proliferation,distant metastasis and invasion.Furthermore,tissue and cancer types can be classified using miRNA expression profiles and next-generation sequencing.As miRNAs in plasma/serum are well protected from RNases,they remain stable under harsh conditions.Thus,potential functions of these circulating miRNAs can be deduced and may implicate their diagnostic value in cancer detection.Circulating miRNAs,as well as tissue miRNAs,may allow for the detection of gastric cancer at an early stage,prediction of prognosis,and monitoring of recurrence and/or lymph node metastasis.Taken together,the data suggest that the participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic and prognostic tests for gastric cancer.展开更多
Objective To investigate whether the common variants 45T/G and 276G/T in APM1 gene were associated with hypertension combined with obesity (HO) and related clinical features in Chinese Han population. Methods A case...Objective To investigate whether the common variants 45T/G and 276G/T in APM1 gene were associated with hypertension combined with obesity (HO) and related clinical features in Chinese Han population. Methods A case-control study design was applied. Common polymorphisms of 45T/G and 276G/T were genotyped by PCR product sequencing in 484 cases with HO and 502 controls with normal blood presure and BMI 〈 25. Results The genotype and allele frequencies of 45T/G, 276G/T, and haplotype defined by the two variants in cases did not differ from those in controls. The means of blood pressure, BMI and waist-hip ratio did not differ among genotypes of the two polymorphisms and haplotypes. Among lipid profiles, only serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in T allele carders than that in non-T carriers after adjusting possible confounding factors (1.21 vs 1.32 mmol/L, P=0.0001). Condusion Polymorphisms of 45T/G and 276G/T in APM1 gene are not associated with hypertension or obesity, or their clinical features in Chinese Han population. Common polymorphism of 45T/G might be associated with serum HDL-C levels in Chinese.展开更多
AIM:To investigate the role of hepatitis B virus (HBV) replication in the development of hepatocellular carcinoma (HCC), a nested case-control study was performed to study the relationship between HBV DNA level and ri...AIM:To investigate the role of hepatitis B virus (HBV) replication in the development of hepatocellular carcinoma (HCC), a nested case-control study was performed to study the relationship between HBV DNA level and risk of HCC. METHODS:One hundred and seventy cases of HCC and 276 control subjects free of HCC and cirrhosis were selected for this study. Serum HBV DNA level was measured using fluorescein quantitative polymerase chain reaction at study entry and the last visit. RESULTS:In a binary unconditional logistic regression analysis adjusted for age, cigarette smoking, alcohol consumption and family history of chronic liver diseases, the adjusted odds ratios (95% confidence intervals) of HCC in patients with increasing HBV DNA level were 2.834 (1.237-6.492), 48.403 (14.392-162.789), 42.252 (14.784-120.750), and 14.819 (6.992-31.411) for HBV DNA levels ≥ 104 to < 105; ≥ 105 to < 106; ≥ 106 to < 107; ≥ 107 copies/mL, respectively. Forty-six HCC cases were selected to compare the serums viral loads of HBV DNA at study entry with those at the last visit. The HBV DNA levels measured at the two time points did not differ significantly.CONCLUSION:The findings of this study provide strong longitudinal evidence of an increased risk of HCC associated with persistent elevation of serum HBV DNA level in the 104-107 range.展开更多
Objective To study the association of the apolipoprotein B gene polymorphisms with essential hypertension in Northern Chinese Han population. Methods XbaI and EcoRl polymorphisms of the apolipoprotein B (APOB) gene ...Objective To study the association of the apolipoprotein B gene polymorphisms with essential hypertension in Northern Chinese Han population. Methods XbaI and EcoRl polymorphisms of the apolipoprotein B (APOB) gene were genotyped by polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) method in 503 unrelated hypertensive patients and 490 healthy controls recruited from international collaborative study of cardiovascular disease in Asia (InterAsia). Results The difference in the genotypic distributions could be neglected across the groups. The prevalence of X+ allele in healthy controls (4.8%) was less frequent in Chinese, and there was no significant difference in the frequency of the X+ allele between cases (5.7%) and controls (P=0.38). The observed E- allele frequencies were closely similar among groups (5.9% in cases vs 5.0% in controls, P=0.39). Logitstic regression analyses revealed that the lack of association still persisted after adjustment of other environmental factors. Haplotype analysis showed that X-E+ was most frequent and no haplotype could significantly contribute to essential hypertension. Conclusion The APOB gene XbaI and EcoRI polymorphisms are not associated with essential hypertension in the Northern Chinese Han population. Future studies on single nucleotide polymorphisms in larger samples are needed to further investigate the possible contribution of the APOB gene to essential hypertension.展开更多
The goal of the Human Genome Project (HGP) is to determine a complete and high-quality sequence of the human genome. China, as one of the six member states, takes a region between 3pter and D3S3397 of the human chromo...The goal of the Human Genome Project (HGP) is to determine a complete and high-quality sequence of the human genome. China, as one of the six member states, takes a region between 3pter and D3S3397 of the human chromosome 3 as its share of this historic project, referred as “Beijing Region”. The complete sequence of this region comprises of 17.4 megabasepairs (Mb) with an average GC content of 42% and an average recombination rate of 2.14 cM/Mb. Within Beijing Region, 122 known and 20 novel genes are identified, as well as 42607 single nucleotide polymorphisms (SNPs). Comprehensive analyses also reveal: (i) gene density and GC-content of Beijing Region are in agreement with human cytogenetic maps, i.e. G-minus bands are GC-rich and of a high gene density, whereas G-plus bands are GC-poor and of a relatively low gene density; (ii) the average recombination rate within Beijing Region is rela-tively high compared with other regions of chromosome 3, with the highest recombination rate of 6.06 cM/Mb in the subtelomeric area; (iii) it is most likely that a large gene, associated with the mammary gland, may reside in the 1.1 Mb gene-poor area near the telomere; (iv) many dis-ease-related genes are genetically mapped to Beijing Region, including those associated with cancers and metabolic syndromes. All make Beijing Region an important target for in-depth mo-lecular investigations with a purpose of medical applications.展开更多
Objective To evaluate four candidate variable number tandem repeat (VNTR) loci for genotyping Mycobacterium tuberculosis complex strains. Methods Genomic sequences for two M. tuberculosis strains (CCDC5079 and CCDC...Objective To evaluate four candidate variable number tandem repeat (VNTR) loci for genotyping Mycobacterium tuberculosis complex strains. Methods Genomic sequences for two M. tuberculosis strains (CCDC5079 and CCDC5180) were generated, and using published sequence data, four candidate VNTR loci were identified. The VNTRs were used to genotype 225 Chinese clinical M. tuberculosis complex strains. The discriminatory power of the VNTRs was evaluated using BioNumerics 5.0 software. Results The Hunter-Gaston Index (HGI) for BJ1, BJ2, BJ3, and BJ4 loci was 0.634, 0.917, 0.697, and 0.910, respectively. Combining all four loci gave an HGI value of 0.995, thus confirming that the genotyping had good discriminatory power. The HGI values for BJ1, BJ2, BJ3, and BJ4, obtained from Beijing family strain genotyping, were 0.447, 0.878, 0.315, and 0.850, respectively. Combining all four loci produced an HGI value of 0.988 for genotyping the Beijing family strains. We observed unique patterns for M. boris and M. africanum strains from the four loci. Conclusion We have shown that the four VNTR loci can be successfully used for genotyping M. tuberculosis complex strains. Notably, these new loci may provide additional information about Chinese M. tuberculosis isolates than that currently afforded by established VNTR loci typing.展开更多
Objective: To evaluate the effects of polymorphisms in TLR7 and TLRS(as potential candidate genes) on asthma risk and asthma-related phenotypes. Methods: We consecutively recruited 318 unrelated adult asthmatic pa...Objective: To evaluate the effects of polymorphisms in TLR7 and TLRS(as potential candidate genes) on asthma risk and asthma-related phenotypes. Methods: We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers from the same area of southeast China. Genotyping of each selected SNP was performed using multiplex PCR in conjunction with tagged array single base extension technology. We conducted case-control and case-only association studies between the selected SNPs in TLR7 and TLR8 and asthma or asthma-related phenotypes. Results: The T allele of rs5935436 SNP in TLR7 was protective from developing asthma in males (adjusted ORs = 0.126, 95% CIs = 0.016-0.995). The CT/TT genotype of rs5935436 was less frequent in female asthmatics with allergic rhinitis (adjusted ORs = 0.18, 95% CIs = 0.04-0.90). The homozygote AA of rs3761623 and GG of rs3764880 were positively associated with lower FEV1% and asthma severity in female asthmatics. These results were confirmed by haplotype analysis. Conclusion:TLR7 and TLR8 polymorphisms may play an important role in the pathogenesis of asthma that is gender-dependent. This could be clinically useful, both for identifying patients at risk of asthma and for preventing its occurrence.展开更多
The amino acid biosynthesis and proteolytic system of Lactobacillus bulgaricus (L.Bulgaricus ) is important for its growth in niche-specific environments, as well as for flavour formation in the food industry. Compara...The amino acid biosynthesis and proteolytic system of Lactobacillus bulgaricus (L.Bulgaricus ) is important for its growth in niche-specific environments, as well as for flavour formation in the food industry. Comparative analyses of 4 completed sequences of the L.Bulgaricus strain genome on a genomic scale revealed that genes involved in amino acids synthesis were undergoing reductive evolution. However, the selected industrial strains, namely, L.Bulgaricus 2038 and L.Bulgaricus ND02, retained more complete genes in the amino acid synthesis and proteolytic system category than the laboratory strains, and have some unique genes and pathways for obtaining amino acids that enable these bacteria to adapt to their various environmental niches.展开更多
BACKGROUND: Studies have shown that adenosine triphosphate-binding cassette transporter 1 (ABCA1) gene influences atherosclerosis. Studies have also demonstrated that cerebral infarction does not occur often in pre...BACKGROUND: Studies have shown that adenosine triphosphate-binding cassette transporter 1 (ABCA1) gene influences atherosclerosis. Studies have also demonstrated that cerebral infarction does not occur often in pre-menopausal women. It has been, therefore, assumed that sex plays a role in R219K polymorphism of ABCA1 gene and cerebral infarction. OBJECTIVE: To explore the relationship between lipid metabolism-correlated R219K polymorphism of ABCA1 gene, risk factors of cerebral infarction and lipid level, and to determine whether there were significant differences in gender between R219K polymorphism of ABCA1 gene and cerebral infarction. DESIGN, TIME AND SETTING: A multicentral and non-randomized, controlled study based on gene polymorphism was performed at the Chinese National Human Genome Center, and lipid concentrations were measured at Beijing Xuanwu Hospital. Patients with cerebral infarction and healthy subjects were enrolled from eight hospitals of six provinces of China between October 2002 and December 2004. PARTICIPANTS: There were 177 patients in the cerebral infarction group, including 119 males and 58 females, with a mean age of (60 -+ 13) years, and 234 healthy subjects in the normal control group, including 79 males and 155 females, with a mean age of (58 ± 12) years. METHODS: R219K polymorphism of the ABCA1 gene was detected using polymerase chain reaction-restriction fragment length polymorphism, and blood lipid concentrations were simultaneously measured. MAIN OUTCOME MEASURES: Genotype and allele frequency of R219K polymorphic site, and blood lipid concentrations. RESULTS: RR genotype and R allele frequency of males in the cerebral infarction were significantly greater than males in the normal control group [RR genotype: x2 = 5.305, OR (95% CO, 2.326 (1.120 4.828), P〈 0.05; R allele: x2= 4.219, OR (95% CO, 1.528 (1.019 2.292), P〈 0.05]. In addition, RR genotype and R allele frequency of males were significantly greater than females in the cerebral infarction group [RR genotype: x2= 5.172, OR (95% C/), 2.604 (1.120-6.057), P〈 0.05; R allele: x2= 4.818, OR (95% CO, 1.652 (1.053 2.589), P〈 0.05]. There were no significant differences between genotype and lipid concentrations between the two groups (P〉 0.05). CONCLUSION: The RR genotype of ABCA1 R219K might be associated with onset of cerebral infarction in males, but blood lipid concentrations do not relate to R219K polymorphism.展开更多
Objective Testicular germ cell tumors(TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of...Objective Testicular germ cell tumors(TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed.Methods The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT.Results Black males were diagnosed at a later stage, more commonly with local or distant metastases.The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival(OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality.Conclusion Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.展开更多
基金This paper is dedicated to the late Professor JS Chiao, who initiated the research in China for rifamycin production employing A. mediterranei more than 30 years ago and who continued the endeavor to resolve the mechanism of the 'nitrate stimulating effect' up to the last breath of his life. This work was supported by the National Natural Science Foundation of China (30830002), the National High Technology Research and Development Program of
China (2007AA021301, 2007AA021503), and the Research Unit Fund of Li Ka Shing Institute of Health Sciences (7103506).
基金Supported by the Knowledge Innovation Program of Chinese Academy of Sciences (No. KSCX2-YW-G-073)
文摘In this study, the 454 pyrosequencing technology was used to analyze the DNA of the Microcystis aeruginosa symbiosis system from cyanobacterial algal blooms in Taihu Lake, China. We generated 183 228 reads with an average length of 248 bp. Running the 454 assembly algorithm over our sequences yielded 22 239 significant contigs. After excluding the M. aeruginosa sequences, we obtained 1 322 assembled contigs longer than 1 000 bp. Taxonomic analysis indicated that four kingdoms were represented in the community: Archaea (n = 9; 0.01%), Bacteria (n = 98 921; 99.6%), Eukaryota (n = 373; 3.7%), and Viruses (n = 18; 0.02%). The bacterial sequences were predominantly Alphaproteobacteria (n = 41 805; 83.3%), Betaproteobacteria (n = 5 254; 10.5%) and Gammaproteobacteria (n = 1 180; 2.4%). Gene annotations and assignment of COG (clusters of orthologous groups) functional categories indicate that a large number of the predicted genes are involved in metabolic, genetic, and environmental information processes. Our results demonstrate the extraordinary diversity of a microbial community in an ectosymbiotic system and further establish the tremendous utility of pyrosequencing.
文摘Nested in the environment of the nucleus of the cell, the 23 sets of chromosomes that comprise the human genome function as one integrated whole system, orchestrating the expression of thousands of genes underlying the biological characteristics of the cell, individual and the species. The extraction of meaningful information from this complex data set depends crucially upon the lens through which the data are examined. We present a biophysical perspective on genomic information encoded in single nucleotide polymorphisms (SNPs), and introduce metrics for modeling information encoded in the genome. Information, like energy, is considered to be a conserved physical property of the universe. The information structured in SNPs describes the adaptation of a human population to a given environment. The maintained order measured by the information content is associated with entropies, energies, and other state variables for a dynamic system in homeostasis. “Genodynamics” characterizes the state variables for genomic populations that are stable under stochastic environmental stresses. The determination of allelic energies allows the parameterization of specific environmental influences upon individual alleles across populations. The environment drives population-based genome variation. From this vantage point, the genome is modeled as a complex, dynamic information system defined by patterns of SNP alleles and SNP haplotypes.
文摘The human genome is a complex, dynamic information system that encodes principles of life and living systems. These principles are incorporated in the structure of human genome sequence variation and are foundational for the continuity of life and human survival. Using first principles of thermodynamics and statistical physics, we have developed analogous “genodynamic tools” for population genomic studies. Characterizing genomic information through the lens of physics has allowed us to develop energy measures for modeling genome-environment interactions. In developing biophysical parameters for genome-environment homeostasis, we found that stable genomic free energy trades off low genomic energy (genomic conservation and increased order) and high genomic entropy (genomic variation) with an environmental potential that drives the variation. In our approach, we assert that common variants are dynamic sites in the genome of a population and that the stability of whole genome adaptation is reflected in the frequencies of maintained diversity in common variants for the population in its environment. In this paper, we address the relativity of whole genome adaptation towards homeostasis. By this we mean that adaptive forces are directly reflected in the frequency distribution of alleles and/or haplotypes of the population relative to its environment, with adaptive forces driving the genome towards homeostasis. The use of genomic energy units as a biophysical metric in DNA sequence variation analyses provides new insights into the foundations of population biology and diversity. Using our biophysical tools, population differences directly reflect the adaptive influences of the environment on populations.
文摘As a living information and communications system, the genome encodes patterns in single nucleotide polymorphisms (SNPs) reflecting human adaptation that optimizes population survival in differing environments. This paper mathematically models environmentally induced adaptive forces that quantify changes in the distribution of SNP frequencies between populations. We make direct connections between biophysical methods (e.g. minimizing genomic free energy) and concepts in population genetics. Our unbiased computer program scanned a large set of SNPs in the major histocompatibility complex region and flagged an altitude dependency on a SNP associated with response to oxygen deprivation. The statistical power of our double-blind approach is demonstrated in the flagging of mathematical functional correlations of SNP information-based potentials in multiple populations with specific environmental parameters. Furthermore, our approach provides insights for new discoveries on the biology of common variants. This paper demonstrates the power of biophysical modeling of population diversity for better understanding genome-environment interactions in biological phenomenon.
基金The study was reviewed and approved by the Zhongshan Hospital of Fudan University Institutional Review Board(Approval No.B2018-234).
文摘BACKGROUND The diagnostic and economic value of carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9)and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale.AIM To reassess the diagnostic and economic value of the three tumor biomarkers.METHODS A retrospective analysis of all 32857 subjects who underwent CEA,CA19-9,CA72-4,gastroscopy and colonoscopy from October 2006 to May 2018 was conducted.Then,we assessed the discrimination and clinical usefulness.Total cost,cost per capita and cost-effectiveness ratios were used to evaluate the economic value of two schemes(gastrointestinal endoscopy for all people without blood tests vs both gastroscopy and colonoscopy when blood tests were positive).RESULTS The analysis of 32857 subjects showed that CEA was a qualified biomarker for colorectal cancer(CRC),while the diagnostic efficiencies of CA72-4 were catastrophic for all gastrointestinal cancers(GICs).Regarding early diagnosis,only CEA could be used for early CRC.The combination of biomarkers didn’t greatly increase the area under the curve.The economic indicators of CEA were superior to those of CA19-9,CA72-4 and any combination.At the threshold of 1.8μg/L to 10.4μg/L,all four indicators of CEA were lower than those in the scheme that conducted gastrointestinal endoscopy only.Subgroup analysis implied that the health checkup of CEA for people above 65 years old was economically valuable.CONCLUSION CEA had qualified diagnostic value for CRC and superior economic value for GICs,especially for elderly health checkup subjects.CA72-4 was not suitable as a diagnostic biomarker.
基金Supported by Grants from the National Natural Science Foundation of China,No.30900745the National High-Tech Research and Development Program(863 Program),No.2012AA020103
文摘Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancerrelated death.More than 80%of diagnoses occur at the middle to late stage of the disease,highlighting an urgent need for novel biomarkers detectable at earlier stages.Recently,aberrantly expressed microRNAs(miRNAs)have received a great deal of attention as potential sensitive and accurate biomarkers for cancer diagnosis and prognosis.This review summarizes the current knowledge about potential miRNA biomarkers for gastric cancer that have been reported in the publicly available literature between 2008 and 2013.Available evidence indicates that aberrantly expressed miRNAs in gastric cancer correlate with tumorigenesis,tumor proliferation,distant metastasis and invasion.Furthermore,tissue and cancer types can be classified using miRNA expression profiles and next-generation sequencing.As miRNAs in plasma/serum are well protected from RNases,they remain stable under harsh conditions.Thus,potential functions of these circulating miRNAs can be deduced and may implicate their diagnostic value in cancer detection.Circulating miRNAs,as well as tissue miRNAs,may allow for the detection of gastric cancer at an early stage,prediction of prognosis,and monitoring of recurrence and/or lymph node metastasis.Taken together,the data suggest that the participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic and prognostic tests for gastric cancer.
文摘Objective To investigate whether the common variants 45T/G and 276G/T in APM1 gene were associated with hypertension combined with obesity (HO) and related clinical features in Chinese Han population. Methods A case-control study design was applied. Common polymorphisms of 45T/G and 276G/T were genotyped by PCR product sequencing in 484 cases with HO and 502 controls with normal blood presure and BMI 〈 25. Results The genotype and allele frequencies of 45T/G, 276G/T, and haplotype defined by the two variants in cases did not differ from those in controls. The means of blood pressure, BMI and waist-hip ratio did not differ among genotypes of the two polymorphisms and haplotypes. Among lipid profiles, only serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in T allele carders than that in non-T carriers after adjusting possible confounding factors (1.21 vs 1.32 mmol/L, P=0.0001). Condusion Polymorphisms of 45T/G and 276G/T in APM1 gene are not associated with hypertension or obesity, or their clinical features in Chinese Han population. Common polymorphism of 45T/G might be associated with serum HDL-C levels in Chinese.
基金The National High Technology Research and Development Program of China 863 Project, No. 2006AA02Z4C5
文摘AIM:To investigate the role of hepatitis B virus (HBV) replication in the development of hepatocellular carcinoma (HCC), a nested case-control study was performed to study the relationship between HBV DNA level and risk of HCC. METHODS:One hundred and seventy cases of HCC and 276 control subjects free of HCC and cirrhosis were selected for this study. Serum HBV DNA level was measured using fluorescein quantitative polymerase chain reaction at study entry and the last visit. RESULTS:In a binary unconditional logistic regression analysis adjusted for age, cigarette smoking, alcohol consumption and family history of chronic liver diseases, the adjusted odds ratios (95% confidence intervals) of HCC in patients with increasing HBV DNA level were 2.834 (1.237-6.492), 48.403 (14.392-162.789), 42.252 (14.784-120.750), and 14.819 (6.992-31.411) for HBV DNA levels ≥ 104 to < 105; ≥ 105 to < 106; ≥ 106 to < 107; ≥ 107 copies/mL, respectively. Forty-six HCC cases were selected to compare the serums viral loads of HBV DNA at study entry with those at the last visit. The HBV DNA levels measured at the two time points did not differ significantly.CONCLUSION:The findings of this study provide strong longitudinal evidence of an increased risk of HCC associated with persistent elevation of serum HBV DNA level in the 104-107 range.
基金This work was funded by the National Basic Research Program of China (No. 2006CB503805)the Ministry of Science and Technology of The People’s Republic of China (No.2006AA02Z170,2006AA020706)Beijing Natural Science Foundation (No.7061006).
文摘Objective To study the association of the apolipoprotein B gene polymorphisms with essential hypertension in Northern Chinese Han population. Methods XbaI and EcoRl polymorphisms of the apolipoprotein B (APOB) gene were genotyped by polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) method in 503 unrelated hypertensive patients and 490 healthy controls recruited from international collaborative study of cardiovascular disease in Asia (InterAsia). Results The difference in the genotypic distributions could be neglected across the groups. The prevalence of X+ allele in healthy controls (4.8%) was less frequent in Chinese, and there was no significant difference in the frequency of the X+ allele between cases (5.7%) and controls (P=0.38). The observed E- allele frequencies were closely similar among groups (5.9% in cases vs 5.0% in controls, P=0.39). Logitstic regression analyses revealed that the lack of association still persisted after adjustment of other environmental factors. Haplotype analysis showed that X-E+ was most frequent and no haplotype could significantly contribute to essential hypertension. Conclusion The APOB gene XbaI and EcoRI polymorphisms are not associated with essential hypertension in the Northern Chinese Han population. Future studies on single nucleotide polymorphisms in larger samples are needed to further investigate the possible contribution of the APOB gene to essential hypertension.
文摘The goal of the Human Genome Project (HGP) is to determine a complete and high-quality sequence of the human genome. China, as one of the six member states, takes a region between 3pter and D3S3397 of the human chromosome 3 as its share of this historic project, referred as “Beijing Region”. The complete sequence of this region comprises of 17.4 megabasepairs (Mb) with an average GC content of 42% and an average recombination rate of 2.14 cM/Mb. Within Beijing Region, 122 known and 20 novel genes are identified, as well as 42607 single nucleotide polymorphisms (SNPs). Comprehensive analyses also reveal: (i) gene density and GC-content of Beijing Region are in agreement with human cytogenetic maps, i.e. G-minus bands are GC-rich and of a high gene density, whereas G-plus bands are GC-poor and of a relatively low gene density; (ii) the average recombination rate within Beijing Region is rela-tively high compared with other regions of chromosome 3, with the highest recombination rate of 6.06 cM/Mb in the subtelomeric area; (iii) it is most likely that a large gene, associated with the mammary gland, may reside in the 1.1 Mb gene-poor area near the telomere; (iv) many dis-ease-related genes are genetically mapped to Beijing Region, including those associated with cancers and metabolic syndromes. All make Beijing Region an important target for in-depth mo-lecular investigations with a purpose of medical applications.
基金supported by the project "Transmission Mode of Tuberculosis" (2008ZX100/03-010-02)"Warning Mode of Tuberculosis" (2008ZX10003-008) of the National Key Programme of Mega Infectious Diseasesupported by the project "Mycobacterium tuberculosis genome SNP analysis and research on the origin of the Beijing family strains" (2011SKLID208) of State Key Laboratory for Infectious Disease Prevention and Control
文摘Objective To evaluate four candidate variable number tandem repeat (VNTR) loci for genotyping Mycobacterium tuberculosis complex strains. Methods Genomic sequences for two M. tuberculosis strains (CCDC5079 and CCDC5180) were generated, and using published sequence data, four candidate VNTR loci were identified. The VNTRs were used to genotype 225 Chinese clinical M. tuberculosis complex strains. The discriminatory power of the VNTRs was evaluated using BioNumerics 5.0 software. Results The Hunter-Gaston Index (HGI) for BJ1, BJ2, BJ3, and BJ4 loci was 0.634, 0.917, 0.697, and 0.910, respectively. Combining all four loci gave an HGI value of 0.995, thus confirming that the genotyping had good discriminatory power. The HGI values for BJ1, BJ2, BJ3, and BJ4, obtained from Beijing family strain genotyping, were 0.447, 0.878, 0.315, and 0.850, respectively. Combining all four loci produced an HGI value of 0.988 for genotyping the Beijing family strains. We observed unique patterns for M. boris and M. africanum strains from the four loci. Conclusion We have shown that the four VNTR loci can be successfully used for genotyping M. tuberculosis complex strains. Notably, these new loci may provide additional information about Chinese M. tuberculosis isolates than that currently afforded by established VNTR loci typing.
基金supported by grants from the National Natural Science Foundation of China 30400191 and 30570797
文摘Objective: To evaluate the effects of polymorphisms in TLR7 and TLRS(as potential candidate genes) on asthma risk and asthma-related phenotypes. Methods: We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers from the same area of southeast China. Genotyping of each selected SNP was performed using multiplex PCR in conjunction with tagged array single base extension technology. We conducted case-control and case-only association studies between the selected SNPs in TLR7 and TLR8 and asthma or asthma-related phenotypes. Results: The T allele of rs5935436 SNP in TLR7 was protective from developing asthma in males (adjusted ORs = 0.126, 95% CIs = 0.016-0.995). The CT/TT genotype of rs5935436 was less frequent in female asthmatics with allergic rhinitis (adjusted ORs = 0.18, 95% CIs = 0.04-0.90). The homozygote AA of rs3761623 and GG of rs3764880 were positively associated with lower FEV1% and asthma severity in female asthmatics. These results were confirmed by haplotype analysis. Conclusion:TLR7 and TLR8 polymorphisms may play an important role in the pathogenesis of asthma that is gender-dependent. This could be clinically useful, both for identifying patients at risk of asthma and for preventing its occurrence.
文摘The amino acid biosynthesis and proteolytic system of Lactobacillus bulgaricus (L.Bulgaricus ) is important for its growth in niche-specific environments, as well as for flavour formation in the food industry. Comparative analyses of 4 completed sequences of the L.Bulgaricus strain genome on a genomic scale revealed that genes involved in amino acids synthesis were undergoing reductive evolution. However, the selected industrial strains, namely, L.Bulgaricus 2038 and L.Bulgaricus ND02, retained more complete genes in the amino acid synthesis and proteolytic system category than the laboratory strains, and have some unique genes and pathways for obtaining amino acids that enable these bacteria to adapt to their various environmental niches.
文摘BACKGROUND: Studies have shown that adenosine triphosphate-binding cassette transporter 1 (ABCA1) gene influences atherosclerosis. Studies have also demonstrated that cerebral infarction does not occur often in pre-menopausal women. It has been, therefore, assumed that sex plays a role in R219K polymorphism of ABCA1 gene and cerebral infarction. OBJECTIVE: To explore the relationship between lipid metabolism-correlated R219K polymorphism of ABCA1 gene, risk factors of cerebral infarction and lipid level, and to determine whether there were significant differences in gender between R219K polymorphism of ABCA1 gene and cerebral infarction. DESIGN, TIME AND SETTING: A multicentral and non-randomized, controlled study based on gene polymorphism was performed at the Chinese National Human Genome Center, and lipid concentrations were measured at Beijing Xuanwu Hospital. Patients with cerebral infarction and healthy subjects were enrolled from eight hospitals of six provinces of China between October 2002 and December 2004. PARTICIPANTS: There were 177 patients in the cerebral infarction group, including 119 males and 58 females, with a mean age of (60 -+ 13) years, and 234 healthy subjects in the normal control group, including 79 males and 155 females, with a mean age of (58 ± 12) years. METHODS: R219K polymorphism of the ABCA1 gene was detected using polymerase chain reaction-restriction fragment length polymorphism, and blood lipid concentrations were simultaneously measured. MAIN OUTCOME MEASURES: Genotype and allele frequency of R219K polymorphic site, and blood lipid concentrations. RESULTS: RR genotype and R allele frequency of males in the cerebral infarction were significantly greater than males in the normal control group [RR genotype: x2 = 5.305, OR (95% CO, 2.326 (1.120 4.828), P〈 0.05; R allele: x2= 4.219, OR (95% CO, 1.528 (1.019 2.292), P〈 0.05]. In addition, RR genotype and R allele frequency of males were significantly greater than females in the cerebral infarction group [RR genotype: x2= 5.172, OR (95% C/), 2.604 (1.120-6.057), P〈 0.05; R allele: x2= 4.818, OR (95% CO, 1.652 (1.053 2.589), P〈 0.05]. There were no significant differences between genotype and lipid concentrations between the two groups (P〉 0.05). CONCLUSION: The RR genotype of ABCA1 R219K might be associated with onset of cerebral infarction in males, but blood lipid concentrations do not relate to R219K polymorphism.
基金supported by the National Key Research Program of China 2016YFC1302601。
文摘Objective Testicular germ cell tumors(TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed.Methods The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT.Results Black males were diagnosed at a later stage, more commonly with local or distant metastases.The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival(OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality.Conclusion Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.