2025年3月17日,国际顶级学术期刊《自然·遗传学》(Nature Genetics)刊发题为“Genomic analysis of 1325 Camellia accessions sheds light on agronomic and metabolic traits for tea plant improvement”的研究性论文。该研究...2025年3月17日,国际顶级学术期刊《自然·遗传学》(Nature Genetics)刊发题为“Genomic analysis of 1325 Camellia accessions sheds light on agronomic and metabolic traits for tea plant improvement”的研究性论文。该研究由福建省农业科学院茶叶研究所与中国农业科学院农业基因组研究所等多家单位合作完成。本研究通过对茶树及其近缘种的基因组进行深度重测序,构建了全面的茶树基因组遗传变异图谱,进而揭示了茶树的遗传多样性及其驯化状态。其结果为茶树的遗传进化和精准设计育种提供了有益见解以及重要参考资料。展开更多
The short tandem repeat (STR) markers are widely used in human identification and paternity testing in the field of forensic genetics[1].Recent researches on polymorphic STRs have led to their applications to populati...The short tandem repeat (STR) markers are widely used in human identification and paternity testing in the field of forensic genetics[1].Recent researches on polymorphic STRs have led to their applications to population genetics,forensic DNA database,human individual identification,paternity testing,genetic mapping,disease linkage analysis,archaeology and potential inference of the ethnic origin of an individual[2].展开更多
OBJECTIVE To evaluate the association between DNA(cytosine-5)-methyltransferase 3 alpha(DNMT3A)genetic polymorphisms and the disease prognosis of R882 mutation negative acute myeloid leukemia(AML)patients.METHODS DNMT...OBJECTIVE To evaluate the association between DNA(cytosine-5)-methyltransferase 3 alpha(DNMT3A)genetic polymorphisms and the disease prognosis of R882 mutation negative acute myeloid leukemia(AML)patients.METHODS DNMT3A 11 SNPs(rs11695471,rs2289195,rs734693,rs2276598,rs1465825,rs7590760,rs13401241,rs7581217,rs749131,rs41284843 and rs7560488)were genotyped using a MassA RRAY platform or Sanger sequencing method in 317 diagnostic non-FABM3 AML patients without R882 mutation from southern China.AML patients underwent combined chemotherapy with cytarabine and anthracyclines.Overall survival(OS)and Disease-free survival(DFS)as major end points were defined.The prognostic(median OS and DFS)evaluations were performed by Kaplan-Meier curve and Cox′s proportional hazard model.RESULTS We found that the rs2289195 G>A SNP could act as a poor prognostic predictor independently(HR=0.442,P=0.035 for OS;HR=0.431,P=0.031 for DFS),while the rs1465825 T>C SNP and rs7590760 G>C SNP appeared to predict independently poor prognosis for both OS(HR=1.453,P=0.037 for rs1465825;HR=1.584,P=0.063 for rs7590760)and DFS(HR=1.459,P=0.057 for rs1465825;HR=1.965,P=0.017for rs7590760).However,no significant associations between other DNMT3A polymorphisms and prognosis(OS in conjunction with DFS)were observed.CONCLUSION DNMT3A polymorphisms may be potential predictive markers for AML prognosis in R882 mutation negative patients,which might improve prognostic stratification of AML.展开更多
While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from t...While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from the three subjects, we discovered that the three subjects possessed the whole CYP2A6 gene deletion (CYP2A6*4C), a novel genetic polymorphism of the CYP2A6 gene. Genetically engineered Salmonella YG7108 cells expressing human CYP2A6 or CYP2E1 together with the NADPH-CYP reductase were established in our laboratory to compare the mutagen-producing capacity of these enzymes for various N-nitrosamines. We found that CYP2E1 was responsible for the metabolic activation of N-nitrosamines with relatively short alkyl chains, whereas CYP2A6 was involved in the metabolic activation of N-nitrosamines possessing relatively bulky alkyl chains such as a tobacco-specific nitrosamine, NNK, which has been known to cause lung tumor in rodents. Thus, to examine a hypothesis that individuals possessing the CYP2A6*4C have the reduced risk of lung cancer due to the lack of the capacity of the metabolic activation of certain carcinogens in tobacco smoke, a case-control study was performed.展开更多
OBJECTIVE The purpose of the present study was to investigate the impact of fluvas.tatin formulation on the pharmacokinetics-genetic polymorphis relationship.METHODS We compared the difference between the pharmacokine...OBJECTIVE The purpose of the present study was to investigate the impact of fluvas.tatin formulation on the pharmacokinetics-genetic polymorphis relationship.METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release(ER) 80 mg tablet and an immediate-release(IR) 40 mg capsule in terms of drug metabolism enzyme and transporter ge.netic polymorphisms.In this open-label,randomized,two-period,two-treatment,crossover study,ef.fects of BCRP,SLCO1B1,MDR1,CYP2C9,and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using highperformance liquid chromatography-tandem mass spectrometry.RESULTS The SLCO1 B1 T521 C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1 B1 T521 C genotype correlated with the AUC_(0-24) of repeat doses(P=0.01).The CYP2C9*3 genotype correlated with the AUC_(0-24) after the first dose IR40 mg capsule(P<0.05);however,the difference between CYP2C9*1/*1 and CYP2 C9*1/*3 was not statistically significant after repeated doses.CONCLUSION The effect of SLCO1B1T521C on fluvas.tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.展开更多
With the approval of more and more genetically modified(GM)crops in our country,GM safety management has become more important.Transgenic detection is a major approach for transgenic safety management.Nevertheless,a c...With the approval of more and more genetically modified(GM)crops in our country,GM safety management has become more important.Transgenic detection is a major approach for transgenic safety management.Nevertheless,a convenient and visual technique with low equipment requirements and high sensitivity for the field detection of GM plants is still lacking.On the basis of the existing recombinase polymerase amplification(RPA)technique,we developed a multiplex RPA(multi-RPA)method that can simultaneously detect three transgenic elements,including the cauliflower mosaic virus 35S gene(CaMV35S)promoter,neomycin phosphotransferaseⅡgene(NptⅡ)and hygromycin B phosphotransferase gene(Hyg),thus improving the detection rate.Moreover,we coupled this multi-RPA technique with the CRISPR/Cas12a reporter system,which enabled the detection results to be clearly observed by naked eyes under ultraviolet(UV)light(254 nm;which could be achieved by a portable UV flashlight),therefore establishing a multi-RPA visual detection technique.Compared with the traditional test strip detection method,this multi-RPA-CRISPR/Cas12a technique has the higher specificity,higher sensitivity,wider application range and lower cost.Compared with other polymerase chain reaction(PCR)techniques,it also has the advantages of low equipment requirements and visualization,making it a potentially feasible method for the field detection of GM plants.展开更多
The learning algorithms of causal discovery mainly include score-based methods and genetic algorithms(GA).The score-based algorithms are prone to searching space explosion.Classical GA is slow to converge,and prone to...The learning algorithms of causal discovery mainly include score-based methods and genetic algorithms(GA).The score-based algorithms are prone to searching space explosion.Classical GA is slow to converge,and prone to falling into local optima.To address these issues,an improved GA with domain knowledge(IGADK)is proposed.Firstly,domain knowledge is incorporated into the learning process of causality to construct a new fitness function.Secondly,a dynamical mutation operator is introduced in the algorithm to accelerate the convergence rate.Finally,an experiment is conducted on simulation data,which compares the classical GA with IGADK with domain knowledge of varying accuracy.The IGADK can greatly reduce the number of iterations,populations,and samples required for learning,which illustrates the efficiency and effectiveness of the proposed algorithm.展开更多
The follicle stimulating hormone beta-subunit （FSHβ） gene plays an important role in piglets. Marker-assisted selection （MAS） in conjunction with traditional selection methods is most effective for improving the ...The follicle stimulating hormone beta-subunit （FSHβ） gene plays an important role in piglets. Marker-assisted selection （MAS） in conjunction with traditional selection methods is most effective for improving the piglets breeding traits. To find the new SNPs, the polymorphism of it in six pig breeds （Min, Landrace, Yorkshine, Duroc, wild boar, and wild boar × Landrace） was analyzed by using PCR-SSCP and was further compared with each other. Polymorphism was found and the sequencing results showed that there was one silent mutation on exon2 （C48T） and two mutations on exon3 （T422C and A514G）. Genotype distribution of FSHβ in Min and wild boar on exon3 was in accordance with Hardy-Weinberg Law.展开更多
The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan,oxidized by CYP3A4 to produce inactive compounds,is used for treatment o...The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan,oxidized by CYP3A4 to produce inactive compounds,is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite,SN-38,which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin,carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine,paclitaxel,docetaxel,or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1,XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity. EGFR gene mutations and polymorphisms were also associated with EGFR kinase inhibitors response and toxicity.展开更多
Based on chicken＇ consensus map issued in 2000, 17 microsatellites near 4 candidate genes such as IGF2, OBR, GDF8 and APOA 1 in 4 chromosomes （chromosome 5, 7, 8 and 24） were chosen for polymorphism analysis and co...Based on chicken＇ consensus map issued in 2000, 17 microsatellites near 4 candidate genes such as IGF2, OBR, GDF8 and APOA 1 in 4 chromosomes （chromosome 5, 7, 8 and 24） were chosen for polymorphism analysis and construction of linkage map. Combining the technique of PCR and the fluorescent semi-automated detection, genome scanning was performed for 440 chickens, which was derived from China Agricultural University chicken resource families within three generations. The individuals of this resource families were genotyped. The results showed that the number of alleles ranged from 4 to 14; heterozygosity （H） of markers was between 0.3116 and 0.9148. Polymorphic information content （PIC） varied from 0.2672 to 0.8679. Microsatellites along with above-mentioned 4 candidate genes doing as general markers were used to construct linkage map. The spans of 4 linkage maps constructed in the part region of chromosome 5, 7, 8 and 24 were 263.5, 79.9, 206.2 and 104.2 cM, respectively. The order of markers was consistent with that of counterpart of reported consensus map. However, The spans of linkage map were larger than that of consensus map. The constructed linkage maps laid the foundation for mapping quantitative trait loci （QTL） responsible for economically important traits in chicken.展开更多
Reproduction trait plays an important role in pig production. Identification of molecular markers that are linked to litter size may contribute to the genetic development of porcine reproduction traits. In this study,...Reproduction trait plays an important role in pig production. Identification of molecular markers that are linked to litter size may contribute to the genetic development of porcine reproduction traits. In this study, porcine ring finger protein 4 （pRNF4） and Matrix metalloproteinase 9 （pMMP-9） were selected as candidate genes on the basis of their physiological roles in reproduction. Two single-nucleotide polymorphisms （416C〉T in pRNF4 and - 1257G〉A in pMMP-9） that could be detected by PCR restriction fragment length polymorphism （PCR-RFLP） were discovered and tested for statistical associations with litter size traits in three populations. For 416C〉T, TT genotype was associated with a significantly higher （p〈0.05） number of live births than those recorded for CC sows and the additive effect was significant （p〈0.05） in Qingping and Min Pigs populations in later parities. For -1257G〉A, inconsistent results were found in three populations. The results suggested that T allele in pRNF4 gene might confer a high prolificacy in breeding and further studies were needed to confLrm the results.展开更多
Background and objective:Lung cancer is one of the malignant tumors.Gene mutations associated with cellular immune function and regulating the activation and proliferation of immune cells.Several publications have exp...Background and objective:Lung cancer is one of the malignant tumors.Gene mutations associated with cellular immune function and regulating the activation and proliferation of immune cells.Several publications have explored the relationship between cytotoxic T lymphocyte antigen-4(CTLA-4)+49 adenine(A)/guanine(G)polymorphism and susceptibility of lung cancer,but the results remain controversial.Thus,we performed this meta-analysis to derive a more comprehensive estimation of the relationship.Methods:All articles addressed lung cancer and polymorphisms of CTLA-4 were searched from the Pub Med,EMBASE databases published up to June 29,2019.Odds ratios(ORs)with 95%confidence intervals(CIs)were used to assess the strength of association.Publication bias of relevant studies was examined via Begg’s test and funnel plots.Results:The meta-analysis included 8 case-control studies covering 4,430 lung cancer patients and 5,198 healthy controls from September 2008 to April 2020.The overall eligible data indicated that CTLA-4+49 A/G polymorphisms did not correlate with the elevated lung cancer risk in all genetic comparison models(dominant model:OR=1.037,95%CI:0.925-1.161;recessive model:OR=0.968,95%CI:0.888-1.055;allele model:OR=0.992,95%CI:0.933-1.054;homozygous model:OR=0.980,95%CI:0.857-1.121;heterozygous model:OR=1.023,95%CI:0.906-1.154).In further stratified analyses,CTLA-4+49 A/G polymorphism was found to be significantly associated with susceptibility to NSCLC in these models(dominant model:OR=1.404,95%CI:1.074-1.836;allele model:OR=1.273,95%CI:1.034-1.565;homozygous model:OR=1.553,95%CI:1.044-2.310;heterozygous model:OR=1.308,95%CI:1.062-1.611).Conclusion:CTLA-4+49 A/G polymorphism were not associated with the risk of lung cancer but might be a risk factor only in NSCLC.展开更多
Objective Tacrolimus is an immunosuppressive drug with narrow therapeutic range and wide interindividual variation in its pharmacokinetics.Tacrolimus is a substrate of cytochrome P450(CYP)3A5.The aim of this study was...Objective Tacrolimus is an immunosuppressive drug with narrow therapeutic range and wide interindividual variation in its pharmacokinetics.Tacrolimus is a substrate of cytochrome P450(CYP)3A5.The aim of this study was to evaluate whether the A6986G polymorphism is associated with tacrolimus concentration/dose ratio.Methods Fifty-two Chinese renal transplant patients were enrolled in this study.Their body weight,dosage and concentration of tacrolimus were observed.CYP3A5 genotype was determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis.Results A significant association was found between tacrolimus levels per dose/kg/d and CYP3A5 gene A6986G polymorphism(P<0.001).The CYP3A5*3*3 patients have a significantly higher tacrolimus level/dose than CYP3A5*1*1 and CYP3A5*1*3.Conclusions CYP3A5 gene A6986G polymorphism is associated with tacrolimus pharmacokinetics and dose requirements.Pharmacogenetic methods could be employed prospectively to help the dose selection and to individualize immunosuppressive therapy according to the result.展开更多
The BRCA1 Associated RING Domain(BARD1) gene has been identified as a high penetrance gene for breast cancer, whose germline and somatic mutations were reported in both non-BRCA1/2 hereditary site-specific and sporadi...The BRCA1 Associated RING Domain(BARD1) gene has been identified as a high penetrance gene for breast cancer, whose germline and somatic mutations were reported in both non-BRCA1/2 hereditary site-specific and sporadic breast cancer cases. BARD1 plays a crucial role in tumor repression, along with its heterodimeric partner BRCA1. In the current study, we tested the hypothesis that common non-synonymous polymorphisms in BARD1 are associated with breast cancer susceptibility in a case-control study of 507 patients with incident breast cancer and 539 frequency-matched cancer-free controls in Chinese women. We genotyped all three common(minor allele frequency (MAF) > 0.10) non-synonymous polymorphisms(Pro24Ser, Arg378Ser, and Val507Met) in BARD1. We found that the BARD1 Pro24Ser variant genotypes(24Pro/Ser and 24Ser/Ser) and Arg378Ser variant homozygote 378Ser/Ser were associated with a significantly decreased breast cancer risk, compared with their wild-type homozygotes, respectively. Furthermore, a significant locus-locus interaction was evident between Pro24Ser and Arg378Ser (P-int = 0.032). Among the 378Ser variant allele carriers, the 24Pro/Pro wild-type homozygote was associated with a significantly increased breast cancer risk (adjusted OR = 1.81, 95% CI = 1.11-2.95), but the subjects having 24Pro/Ser or Ser/Ser variant genotypes had a significantly decreased risk(adjusted OR = 0.74, 95% CI = 0.56-0.99). In stratified analysis, this locus-locus interaction was more evident among subjects without family cancer history, those with positive estrogen receptor (ER) and individuals with negative progesterone receptor(PR). These findings indicate that the potentially functional polymorphisms Pro24Ser and Arg378Ser in BARD1 may jointly contribute to the susceptibility of breast cancer.展开更多
In order to further study functions of the porcine myostatin gene, we analyzed the polymorphisms of porcine myostatin gene in promoter region among different breeds including Yorkshire, Landrace, Duroc, Junmu, Min pig...In order to further study functions of the porcine myostatin gene, we analyzed the polymorphisms of porcine myostatin gene in promoter region among different breeds including Yorkshire, Landrace, Duroc, Junmu, Min pig and Sanjiang white pig by PCR-RFLPs. The allele T dominated in the imported lean-type pig breeds such as Yorkshire, Landrace and Duroc. No allele A was detected in Junmu and Sanjiang white pig, and the frequencies of three genotypes were about equal in Min pig. The result using X2 analysis showed that the distribution of three genotypes was related to pig breeds.展开更多
Polymorphisms of porcine ob exon 1 and exon 2 among different breeds including Landrace, Duroc, Min pig, Yorkshire pig, double-muscled Yorkshire, Sanjiang pig, wild boar and cross bred pig were analyzed by PCR-SSCP in...Polymorphisms of porcine ob exon 1 and exon 2 among different breeds including Landrace, Duroc, Min pig, Yorkshire pig, double-muscled Yorkshire, Sanjiang pig, wild boar and cross bred pig were analyzed by PCR-SSCP in the current study. Three pairs of primers according to the ob cDNA sequence obtained from GenBank database were designed to amplify the first two exons, which were then genotyped by SSCP. The T to C transversion was found in exon 2, which resulted in 3 genotypes named AA, AB and BB, respectively in these different porcine breeds. There was only genotype of BB in the Min pig, while no allele B was detected in double-muscled Yorkshire, and the 3 genotypes all existed in other breeds. There was significant difference on the genotype frequencies in various breeds. There was a trend that the frequency of allele A was positively associated with muscle ratio distribution on the one hand, and on the other hand, it was linked to the selected direction. So the allele A could be used as a selective marker of high muscle ratio in pig breeding.展开更多
文摘2025年3月17日,国际顶级学术期刊《自然·遗传学》(Nature Genetics)刊发题为“Genomic analysis of 1325 Camellia accessions sheds light on agronomic and metabolic traits for tea plant improvement”的研究性论文。该研究由福建省农业科学院茶叶研究所与中国农业科学院农业基因组研究所等多家单位合作完成。本研究通过对茶树及其近缘种的基因组进行深度重测序,构建了全面的茶树基因组遗传变异图谱,进而揭示了茶树的遗传多样性及其驯化状态。其结果为茶树的遗传进化和精准设计育种提供了有益见解以及重要参考资料。
基金Acknowledgments The current research was supported by the Na- tional Natural Science Foundation of China （81302622）, the Science Technology Foundation of Lanzhou （2012-1-22）, and Youth Science and Tech- nology Foundation of Gansu （1208RYYA073）.
文摘The short tandem repeat (STR) markers are widely used in human identification and paternity testing in the field of forensic genetics[1].Recent researches on polymorphic STRs have led to their applications to population genetics,forensic DNA database,human individual identification,paternity testing,genetic mapping,disease linkage analysis,archaeology and potential inference of the ethnic origin of an individual[2].
基金The project supported by National Naural Science Foundation of China(81422052)Special Topic of the Major Subject of National Science and Technology(2012ZX09509-107)Hunan Provincial Natural Science Foundation of China(13JJ1010)
文摘OBJECTIVE To evaluate the association between DNA(cytosine-5)-methyltransferase 3 alpha(DNMT3A)genetic polymorphisms and the disease prognosis of R882 mutation negative acute myeloid leukemia(AML)patients.METHODS DNMT3A 11 SNPs(rs11695471,rs2289195,rs734693,rs2276598,rs1465825,rs7590760,rs13401241,rs7581217,rs749131,rs41284843 and rs7560488)were genotyped using a MassA RRAY platform or Sanger sequencing method in 317 diagnostic non-FABM3 AML patients without R882 mutation from southern China.AML patients underwent combined chemotherapy with cytarabine and anthracyclines.Overall survival(OS)and Disease-free survival(DFS)as major end points were defined.The prognostic(median OS and DFS)evaluations were performed by Kaplan-Meier curve and Cox′s proportional hazard model.RESULTS We found that the rs2289195 G>A SNP could act as a poor prognostic predictor independently(HR=0.442,P=0.035 for OS;HR=0.431,P=0.031 for DFS),while the rs1465825 T>C SNP and rs7590760 G>C SNP appeared to predict independently poor prognosis for both OS(HR=1.453,P=0.037 for rs1465825;HR=1.584,P=0.063 for rs7590760)and DFS(HR=1.459,P=0.057 for rs1465825;HR=1.965,P=0.017for rs7590760).However,no significant associations between other DNMT3A polymorphisms and prognosis(OS in conjunction with DFS)were observed.CONCLUSION DNMT3A polymorphisms may be potential predictive markers for AML prognosis in R882 mutation negative patients,which might improve prognostic stratification of AML.
文摘While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from the three subjects, we discovered that the three subjects possessed the whole CYP2A6 gene deletion (CYP2A6*4C), a novel genetic polymorphism of the CYP2A6 gene. Genetically engineered Salmonella YG7108 cells expressing human CYP2A6 or CYP2E1 together with the NADPH-CYP reductase were established in our laboratory to compare the mutagen-producing capacity of these enzymes for various N-nitrosamines. We found that CYP2E1 was responsible for the metabolic activation of N-nitrosamines with relatively short alkyl chains, whereas CYP2A6 was involved in the metabolic activation of N-nitrosamines possessing relatively bulky alkyl chains such as a tobacco-specific nitrosamine, NNK, which has been known to cause lung tumor in rodents. Thus, to examine a hypothesis that individuals possessing the CYP2A6*4C have the reduced risk of lung cancer due to the lack of the capacity of the metabolic activation of certain carcinogens in tobacco smoke, a case-control study was performed.
文摘OBJECTIVE The purpose of the present study was to investigate the impact of fluvas.tatin formulation on the pharmacokinetics-genetic polymorphis relationship.METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release(ER) 80 mg tablet and an immediate-release(IR) 40 mg capsule in terms of drug metabolism enzyme and transporter ge.netic polymorphisms.In this open-label,randomized,two-period,two-treatment,crossover study,ef.fects of BCRP,SLCO1B1,MDR1,CYP2C9,and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using highperformance liquid chromatography-tandem mass spectrometry.RESULTS The SLCO1 B1 T521 C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1 B1 T521 C genotype correlated with the AUC_(0-24) of repeat doses(P=0.01).The CYP2C9*3 genotype correlated with the AUC_(0-24) after the first dose IR40 mg capsule(P<0.05);however,the difference between CYP2C9*1/*1 and CYP2 C9*1/*3 was not statistically significant after repeated doses.CONCLUSION The effect of SLCO1B1T521C on fluvas.tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.
基金the Experimental Technology Research Project of Zhejiang University(SYB202138)National Natural Science Foundation of China(32000195)。
文摘With the approval of more and more genetically modified(GM)crops in our country,GM safety management has become more important.Transgenic detection is a major approach for transgenic safety management.Nevertheless,a convenient and visual technique with low equipment requirements and high sensitivity for the field detection of GM plants is still lacking.On the basis of the existing recombinase polymerase amplification(RPA)technique,we developed a multiplex RPA(multi-RPA)method that can simultaneously detect three transgenic elements,including the cauliflower mosaic virus 35S gene(CaMV35S)promoter,neomycin phosphotransferaseⅡgene(NptⅡ)and hygromycin B phosphotransferase gene(Hyg),thus improving the detection rate.Moreover,we coupled this multi-RPA technique with the CRISPR/Cas12a reporter system,which enabled the detection results to be clearly observed by naked eyes under ultraviolet(UV)light(254 nm;which could be achieved by a portable UV flashlight),therefore establishing a multi-RPA visual detection technique.Compared with the traditional test strip detection method,this multi-RPA-CRISPR/Cas12a technique has the higher specificity,higher sensitivity,wider application range and lower cost.Compared with other polymerase chain reaction(PCR)techniques,it also has the advantages of low equipment requirements and visualization,making it a potentially feasible method for the field detection of GM plants.
基金supported by the National Social Science Fund of China(2022-SKJJ-B-084).
文摘The learning algorithms of causal discovery mainly include score-based methods and genetic algorithms(GA).The score-based algorithms are prone to searching space explosion.Classical GA is slow to converge,and prone to falling into local optima.To address these issues,an improved GA with domain knowledge(IGADK)is proposed.Firstly,domain knowledge is incorporated into the learning process of causality to construct a new fitness function.Secondly,a dynamical mutation operator is introduced in the algorithm to accelerate the convergence rate.Finally,an experiment is conducted on simulation data,which compares the classical GA with IGADK with domain knowledge of varying accuracy.The IGADK can greatly reduce the number of iterations,populations,and samples required for learning,which illustrates the efficiency and effectiveness of the proposed algorithm.
基金Supported by National Key Technology R&D Program in the 11th Five Year Plan of China (2008BADB2B01)
文摘The follicle stimulating hormone beta-subunit （FSHβ） gene plays an important role in piglets. Marker-assisted selection （MAS） in conjunction with traditional selection methods is most effective for improving the piglets breeding traits. To find the new SNPs, the polymorphism of it in six pig breeds （Min, Landrace, Yorkshine, Duroc, wild boar, and wild boar × Landrace） was analyzed by using PCR-SSCP and was further compared with each other. Polymorphism was found and the sequencing results showed that there was one silent mutation on exon2 （C48T） and two mutations on exon3 （T422C and A514G）. Genotype distribution of FSHβ in Min and wild boar on exon3 was in accordance with Hardy-Weinberg Law.
文摘The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan,oxidized by CYP3A4 to produce inactive compounds,is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite,SN-38,which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin,carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine,paclitaxel,docetaxel,or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1,XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity. EGFR gene mutations and polymorphisms were also associated with EGFR kinase inhibitors response and toxicity.
基金Supported by Program for New Century Excellent Talents in University(NCET-04-0343)National Natural Science Foundation Key Project(30430510)Excellent Young Teachers Program of MOE.People's Republic of China(1985)
文摘Based on chicken＇ consensus map issued in 2000, 17 microsatellites near 4 candidate genes such as IGF2, OBR, GDF8 and APOA 1 in 4 chromosomes （chromosome 5, 7, 8 and 24） were chosen for polymorphism analysis and construction of linkage map. Combining the technique of PCR and the fluorescent semi-automated detection, genome scanning was performed for 440 chickens, which was derived from China Agricultural University chicken resource families within three generations. The individuals of this resource families were genotyped. The results showed that the number of alleles ranged from 4 to 14; heterozygosity （H） of markers was between 0.3116 and 0.9148. Polymorphic information content （PIC） varied from 0.2672 to 0.8679. Microsatellites along with above-mentioned 4 candidate genes doing as general markers were used to construct linkage map. The spans of 4 linkage maps constructed in the part region of chromosome 5, 7, 8 and 24 were 263.5, 79.9, 206.2 and 104.2 cM, respectively. The order of markers was consistent with that of counterpart of reported consensus map. However, The spans of linkage map were larger than that of consensus map. The constructed linkage maps laid the foundation for mapping quantitative trait loci （QTL） responsible for economically important traits in chicken.
基金Supported by the National Natural Science Foundation of China(31301935)Ph.D.Programs Foundation of Ministry of Education of China(20112325120013)
文摘Reproduction trait plays an important role in pig production. Identification of molecular markers that are linked to litter size may contribute to the genetic development of porcine reproduction traits. In this study, porcine ring finger protein 4 （pRNF4） and Matrix metalloproteinase 9 （pMMP-9） were selected as candidate genes on the basis of their physiological roles in reproduction. Two single-nucleotide polymorphisms （416C〉T in pRNF4 and - 1257G〉A in pMMP-9） that could be detected by PCR restriction fragment length polymorphism （PCR-RFLP） were discovered and tested for statistical associations with litter size traits in three populations. For 416C〉T, TT genotype was associated with a significantly higher （p〈0.05） number of live births than those recorded for CC sows and the additive effect was significant （p〈0.05） in Qingping and Min Pigs populations in later parities. For -1257G〉A, inconsistent results were found in three populations. The results suggested that T allele in pRNF4 gene might confer a high prolificacy in breeding and further studies were needed to confLrm the results.
文摘Background and objective:Lung cancer is one of the malignant tumors.Gene mutations associated with cellular immune function and regulating the activation and proliferation of immune cells.Several publications have explored the relationship between cytotoxic T lymphocyte antigen-4(CTLA-4)+49 adenine(A)/guanine(G)polymorphism and susceptibility of lung cancer,but the results remain controversial.Thus,we performed this meta-analysis to derive a more comprehensive estimation of the relationship.Methods:All articles addressed lung cancer and polymorphisms of CTLA-4 were searched from the Pub Med,EMBASE databases published up to June 29,2019.Odds ratios(ORs)with 95%confidence intervals(CIs)were used to assess the strength of association.Publication bias of relevant studies was examined via Begg’s test and funnel plots.Results:The meta-analysis included 8 case-control studies covering 4,430 lung cancer patients and 5,198 healthy controls from September 2008 to April 2020.The overall eligible data indicated that CTLA-4+49 A/G polymorphisms did not correlate with the elevated lung cancer risk in all genetic comparison models(dominant model:OR=1.037,95%CI:0.925-1.161;recessive model:OR=0.968,95%CI:0.888-1.055;allele model:OR=0.992,95%CI:0.933-1.054;homozygous model:OR=0.980,95%CI:0.857-1.121;heterozygous model:OR=1.023,95%CI:0.906-1.154).In further stratified analyses,CTLA-4+49 A/G polymorphism was found to be significantly associated with susceptibility to NSCLC in these models(dominant model:OR=1.404,95%CI:1.074-1.836;allele model:OR=1.273,95%CI:1.034-1.565;homozygous model:OR=1.553,95%CI:1.044-2.310;heterozygous model:OR=1.308,95%CI:1.062-1.611).Conclusion:CTLA-4+49 A/G polymorphism were not associated with the risk of lung cancer but might be a risk factor only in NSCLC.
基金Project(03GZ3072)supported by the Science end Technology Departmeat of Hunan Provincepproject(2004035206)supported by the China Poatdoctoral Foundationprojecl(30300383)supported by the National Natuml Sciences Foundastion of China
文摘Objective Tacrolimus is an immunosuppressive drug with narrow therapeutic range and wide interindividual variation in its pharmacokinetics.Tacrolimus is a substrate of cytochrome P450(CYP)3A5.The aim of this study was to evaluate whether the A6986G polymorphism is associated with tacrolimus concentration/dose ratio.Methods Fifty-two Chinese renal transplant patients were enrolled in this study.Their body weight,dosage and concentration of tacrolimus were observed.CYP3A5 genotype was determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis.Results A significant association was found between tacrolimus levels per dose/kg/d and CYP3A5 gene A6986G polymorphism(P<0.001).The CYP3A5*3*3 patients have a significantly higher tacrolimus level/dose than CYP3A5*1*1 and CYP3A5*1*3.Conclusions CYP3A5 gene A6986G polymorphism is associated with tacrolimus pharmacokinetics and dose requirements.Pharmacogenetic methods could be employed prospectively to help the dose selection and to individualize immunosuppressive therapy according to the result.
文摘The BRCA1 Associated RING Domain(BARD1) gene has been identified as a high penetrance gene for breast cancer, whose germline and somatic mutations were reported in both non-BRCA1/2 hereditary site-specific and sporadic breast cancer cases. BARD1 plays a crucial role in tumor repression, along with its heterodimeric partner BRCA1. In the current study, we tested the hypothesis that common non-synonymous polymorphisms in BARD1 are associated with breast cancer susceptibility in a case-control study of 507 patients with incident breast cancer and 539 frequency-matched cancer-free controls in Chinese women. We genotyped all three common(minor allele frequency (MAF) > 0.10) non-synonymous polymorphisms(Pro24Ser, Arg378Ser, and Val507Met) in BARD1. We found that the BARD1 Pro24Ser variant genotypes(24Pro/Ser and 24Ser/Ser) and Arg378Ser variant homozygote 378Ser/Ser were associated with a significantly decreased breast cancer risk, compared with their wild-type homozygotes, respectively. Furthermore, a significant locus-locus interaction was evident between Pro24Ser and Arg378Ser (P-int = 0.032). Among the 378Ser variant allele carriers, the 24Pro/Pro wild-type homozygote was associated with a significantly increased breast cancer risk (adjusted OR = 1.81, 95% CI = 1.11-2.95), but the subjects having 24Pro/Ser or Ser/Ser variant genotypes had a significantly decreased risk(adjusted OR = 0.74, 95% CI = 0.56-0.99). In stratified analysis, this locus-locus interaction was more evident among subjects without family cancer history, those with positive estrogen receptor (ER) and individuals with negative progesterone receptor(PR). These findings indicate that the potentially functional polymorphisms Pro24Ser and Arg378Ser in BARD1 may jointly contribute to the susceptibility of breast cancer.
基金Key Items of Plan of Science and Technology of Heilongjiang Province (CGB01B104)
文摘In order to further study functions of the porcine myostatin gene, we analyzed the polymorphisms of porcine myostatin gene in promoter region among different breeds including Yorkshire, Landrace, Duroc, Junmu, Min pig and Sanjiang white pig by PCR-RFLPs. The allele T dominated in the imported lean-type pig breeds such as Yorkshire, Landrace and Duroc. No allele A was detected in Junmu and Sanjiang white pig, and the frequencies of three genotypes were about equal in Min pig. The result using X2 analysis showed that the distribution of three genotypes was related to pig breeds.
文摘Polymorphisms of porcine ob exon 1 and exon 2 among different breeds including Landrace, Duroc, Min pig, Yorkshire pig, double-muscled Yorkshire, Sanjiang pig, wild boar and cross bred pig were analyzed by PCR-SSCP in the current study. Three pairs of primers according to the ob cDNA sequence obtained from GenBank database were designed to amplify the first two exons, which were then genotyped by SSCP. The T to C transversion was found in exon 2, which resulted in 3 genotypes named AA, AB and BB, respectively in these different porcine breeds. There was only genotype of BB in the Min pig, while no allele B was detected in double-muscled Yorkshire, and the 3 genotypes all existed in other breeds. There was significant difference on the genotype frequencies in various breeds. There was a trend that the frequency of allele A was positively associated with muscle ratio distribution on the one hand, and on the other hand, it was linked to the selected direction. So the allele A could be used as a selective marker of high muscle ratio in pig breeding.
