HLA-DQ, DR allele polymorphism of type 1 diabetes in the Chinese population： a meta-analysis

Background Type 1 diabetes （TID） is a multifactorial disease. This article aims to evaluate the relationship between allele polymorphism of HLA-DQ, DR and TID in the Chinese population. Methods The odds ratios （ORs） of HLA-DQ, DR allele distributions in patients with T1D were analyzed against healthy controls. All the relevant studies in Pubmed and CNKI were identified, and poor qualified studies were excluded. The meta-analysis software REVMAN 4.2 was applied for investigating heterogeneity among individual studies and for summarizing all the studies. The publication bias were also evaluated. Results DQA1＊0301, DQA1＊0501, DQB1＊0201, DQB1＊0302 were the susceptible alleles （all P 〈0.05） in the Chinese population, their merger ORs 2.40, 3.15, 3.66, and 2.67 respectively. DQA1＊0103, DQA1＊0201, DQA1＊0401, DQB1＊0301, DQB1＊0402, DQB1 ＊0501, DQB1＊0503, DQB1＊0601 and DQB1＊0602 were the protective alleles （P 〈0.05）, their merger ORs were 0.11, 0.45, 0.30, 0.38, 0.23, 0.37, 0.25, 0.48, and 0.30 respectively. In serum level, DR3, DR4, DR9 alleles were the susceptible alleles （all P 〈0.05） and their merger ORs were 5.58, 1.53, 1.66, 29.78, and 6.65 respectively. HLA-DR2, DR5, and DR7 alleles were the protective alleles （all P 〈0.05） and their merger ORs were 0.39, 0.51, and 0.50. In genetic type level, DRB1＊04, DRB1＊0301, DRB1＊0901 were the susceptible alleles （all P 〈0.05） and their merger ORs were 2.19, 6.43, 1.31, 3.83, and 8.08. DRBI＊07, DRBI＊08, DRB1＊12, DRB1＊13, DRB1＊14, DRB1＊16, DRBI＊0406 alleles were the protective alleles （all P 〈0.05） and their merger ORswere 0.44, 0.27, 0.45, 0.13, 0.19, 0.40, and 0.27 respectively. Conclusions In the Chinese population, some HLA-DQ, DR alleles are relevant to T1D which are not totally the same as non-Chinese populations.

CYP2C19 Polymorphism and Clinical Outcomes among Patients of Different Races Treated with Clopidogrel:A Systematic Review and Meta-Analysis

Several studies have investigated the association between CYP2C19 polymorphism and clinical outcomes of patients treated with clopidogrel, but few have noticed the difference in association between Westerners and Asians. We searched MEDLINE, EMBASE and Cochrane Library database and conducted a systematic review and meta-analysis. Thirty-six studies involving 44 655 patients with coronary artery disease（CAD） treated with clopidogrel were included, of which more than 68% had undergone percutaneous coronary intervention（PCI）. The primary outcome of our interest was the recurrence of major adverse cardiovascular events（MACE） in those CAD patients. Firstly, we found that the distribution of reduced-function CYP2C19 allele varied between Westerners and Asians. Among Asians, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 42.5% and 10%, respectively. While among Westerners, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 25.5% and 2.4%, respectively. Secondly, the impact of CYP2C19 polymorphism on clinical outcomes of patients treated with clopidogrel varied with races. Among Asians, only 2 reduced-function CYP2C19 mutant allele carriers had the reduced effect of clopidogrel. And the reduced effect was significant only after the 30 th day of treatment. While among Westerners, both 1 and 2 reduced-function CYP2C19 allele carriers had the reduced effect, and it mainly occurred within the first 30 days. Thirdly, the safety of clopidogrel was almost the same among races. Reduced-function allele non-carriers had higher risk for total bleeding but did not have higher risk for major bleeding. It is suggested that CYP2C19 polymorphism affects the efficacy of clopidogrel differently among Westerners and Asians.

polymorphism Analysis of Resistance Genes in Chinese Populations with HIV-1 Infection

Objective: To analyze the genotypes of CCR5 △ 32,CCR2b-64I and SDF 1-3 A and mutation frequencies of allelicgenes in Chinese populations infected with HIV-1. Methods: Genome DNA from peripheral blood mononuclearcells (PBMCs) of 78 HIV-1 infectors was amplified bypolymerase chain reaction (PCR). CCR5, CCR2b and SDF1gene fragments were obtained from restrictive fragmentlength polymorphism (RFLP) and/or CCR△32, CCR5m303,CCR2b-64I and SDF1-3' A allelic genes' mutationalfrequencies were sequenced directly from PCR products. Results: None of CCR5△32, CCR5m303 gene mutationwere found in 78 subjects with HIV-1 infection. The allelicgene mutation frequencies of CCR2b-64I and SDF1-3'Acorresponding to 14.9-34.0% and 17.6-38.2% of 95% CI, were22.79% and 26.92% respectively. Their colony distributionconformed to the Hardy-Weinberg equilibrium. Conclusion: The HIV-1 infections found at present are allsusceptible population of CCR5△32 and CCR5m303. Thepolymorphism and frequencies of CCR5△32, CCR5m303,CCR2b-64I and SDF1-3'A alleles from Chinese HIV-1infected population were disclosed in this study for the firsttime, which is of significance for studying the geneticresistance to susceptibility to HIV-1 infection as well as AIDSdisease progression.

Characterization of CCR5Δ32、CCR2b-641、CX3CR1-2491280M and SDF1-3'A Allelic Polymorphisms in the Chinese Uygur Population

Objective: Allelic polymorphisms of CCR5△32CCR2b-64I,CX3CR1-2491280M and SDF1-3'A associatedwith HIV-1 infection and disease progression wereinvestigated in indigenous Uygur populations from theXinjiang Uygur Autonomous Region of China. Methods: The study population comprised 316 healthyUygur subjects with an age range of 1-80 years old, fromwhom whole peripheral blood samples were collected andnone were HIV-1 seropositive. Genomic DNA samples werepurified using a Qiagen Blood Kit. Genotyping of theaforementioned four alleles was performed using PCR orPCR/RFLP assay, and further confirmed by direct DNAsequencing. Results: The allelic frequencies in Chinese Uygurpopulation were as follows: 3.48% for CCR5△32; 19.45% forCCR2b-64I; 13.8% for CX3CR1-2491280M haplotype, and20.41% for SDF1-3'A. Mutant allele distributions amongUygur populations were in accordance with theHardy-Weinberg equilibrium. No statistical difference wasfound between the frequency of the three HIV coreceptors andtheir respective ligand genes. Conclusion: The frequency of SDF1-3'A andCX3CR1-2491280M haplotypes in these Uygur populationswas similar to that of Caucasian people, while the frequency ofthe CCR2b-64I haplotype more closely matched the HanChinese. The frequency of CCR5△A32 in Uygur populationswas between Caucasian and Hall frequencies, the more closelymatching the frequency in Medi-Asia people. No geneticlinkage between any two of the three HIV coreceptor geneswas found, but obvious genetic linkages existed betweenCX3CR1-249I and CX3CR1-280M,with even higher linkagedegrees than Caucasian people.

Genotypes and polymorphisms of mutant CCR5-△32,CCR2-64I and SDF1-3'A HIV-1 resistance alleles in indigenous Han Chinese

Objective To evaluate the frequencies and polymorphisms of CCR5-△32,CCR2-641 and SDF1-3'A alleles conferring resistance to HIV-1 infection in Chinese population from Han ethnic origin.Methods This cohort was comprised of 1251 subjects(915 men and 336 women)aged 15 -80 years and none was HIV-1 positive.Genotyping of allelic CCR5-△32,CCR2-641 and SDF1-3' A variants was performed using PCR or PCR/RFLP assay,and further confirmed by direct DNA sequencing.Results Our finding shows that the△32 deletion mutation in the CCR5 gene does occur in this population and can be inherited in a Mendelian fashion in indigenous Han Chinese at a very low frequency of 0.00119(n= 1254).The frequencies of mutant CCR2-641 and SDF1-3'A alleles were 0.20023(n = 1251)and 0.2873(n = 893),in this population,which are higher than those found in American Caucasians.Furthermore the polymorphisms of CCR2-641 and SDF1-3' A alleles in the Han Chinese population were different from those in American Caucasians.Statistical analysis showed that the genotype distribution of CCR5-△32,CCR2-641 and SDF1-3' A alleles was in equilibrium according to the Hardy-Weinberg equation.Conclusion The CCR5-△32 mutation may not be a major resistant factor against HIV-1 infection in indigenous Han Chinese.The significance of higher frequencies of CCR2-641 and SDF1-3' A alleles (0.20023 and 0.2791)in the Han population remains to be clarified in HIV-1-positive carriers and AIDS patients.

Genetic diversity in two threatened species in Vietnam:Taxus chinensis and Taxus wallichiana

Taxus chinensis and T. wallichiana in have been threatened in their distribution areas in recent decades because of their over-exploitation and reduction and destruction of native habitats. Determining the genetic diversity in populations of the two species will provide guidelines for their protection and preservation. Two hundred and fifteen trees from six populations of T. chinensis and150 sampled trees of T. wallichiana were sampled. Six microsatellite primer pairs selected from 16 primer pairs were used to investigate genetic variation at the population and species levels. Five yielded polymorphic alleles, and among the 13 putative alleles amplified, 11 were polymorphic（accounting for 76.33 %）.Shannon＇s information index（I） and percentage of polymorphic bands（PPB）（I = 0.202 and PPB = 67.22 % for T. chinensis; I = 0.217 and PPB = 65.03 % for T. wallichiana）. Both species had low levels of genetic diversity（mean Ho= 0.107, He= 0.121 for T. chinensis; Ho= 0.095, He= 0.109 for T. wallichiana）. Genetic differentiation among populations was higher（FST= 0.189） for T. chinensis and lower（0.156） for T.wallichiana, indicating limited gene flow（Nm） among populations for T. chinensis（0.68） and T. wallichiana（0.65）.Variation among individuals of T. chinensis was 63.59 and73.12 % for T. wallichiana. Thus, the threatened status of the two conifers is related to a lack of genetic diversity. All populations are isolated in small forest remnants. An ex situ conservation site should be established with a new population for these species that comprises all the genetic groups for the best chance to improve their fitness under environmental stresses.

Genetic Diversity Analysis of Rice Germplasm in Tripura State of Northeast India Using Drought and Blast Linked Markers

We genotyped 74 rice germplasms including Tripura＇s local landraces, improved varieties, cultivars and breeding lines and other rice varieties using molecular markers for genetic diversity, drought QTLs, and blast resistance genes. The number of alleles per locus ranged from 2 to 5 with an average of 2.9. The polymorphic information content value per locus ranged from 0.059（RM537） to 0.755（RM252） with an average of 0.475. Cluster analysis based on 30 simple sequence repeat markers revealed 5 clusters and also indicated the presence of variability within the rice accessions. The drought QTL q DTY2.1 was found in 56.0% of germplasms and q DTY1.1 was detected in only 6.8% of the germplasms. Out of seven rice blast resistance genes screened, only two rice varieties, RCPL-1-82 and Buh Vubuk（Lubuk）, were positive for four blast resistance genes while only Releng possessed two blast resistance genes. Among 74 rice germplasms, only three accessions, Releng, RCPL1-82 and Buh Vubuk（Lubuk）, possessed both drought-related QTLs and blast resistance genes. Overall, the 74 indigenous rice genotypes showed low level of genetic diversity, which is in contrast to high level of genetic diversity among rice varieties in northeast India, where highlights the good farming practice, conservation of germplasms and the limitation of molecular markers employed in this study. The presence of both drought related QTLs and blast resistance genes in some of the germplasms can be useful in future breeding programmes.

Construction of a Normalized Full-Length cDNA Library of Cephalopod Amphioctopus fangsiao and Development of Microsatellite Markers

Amphioctopus fangsiao is one of the most economically important species and has been considered to be a candidate for aquaculture. In order to facilitate its fine-scale genetic analyses, we constructed a normalized full-length library successfully and developed a set of microsatellite markers in this study. The normalized full-length library had a storage capacity of 6.9×105 independent clones. The recombination efficiency was 95% and the average size of inserted fragments was longer than 1000 bp. A total of 3440 high quality ESTs were obtained, which were assembled into 1803 unigenes. Of these unigenes, 450(25%) were assigned into 33 Gene Ontology terms, 576(31.9%) into 153 Kyoto Encyclopedia of Genes and Genomes pathways, and 275(15.3%) into 22 Clusters of Orthologous Groups. Seventy-six polymorphic microsatellite markers were identified. The number of alleles per locus ranged from 4 to 17, and the observed and expected heterozygosities varied between 0.167 and 0.967 and between 0.326 and 0.944, respectively. Twelve loci were significantly deviated from Hardy-Weinberg equilibrium after Bonferroni correction and no linkage disequilibrium was found between different loci. This study provided not only a useful resource for the isolation of the functional genes, but also a set of informative microsatellites for the assessment of population structure and conservation genetics of A. fangsiao.

Identification of two Major Histocompatibility(MH) Class Ⅱ A Genes and Their Association to Vibrio anguillarum Infection in Half-smooth Tongue Sole(Cynoglossus semilaevis)

Major histocompatibility complex class II antigens are important in vertebrate immune system.In the present study,the full cDNA sequence of class II A gene was synthesized by RACE-PCR from half-smooth tongue sole(Cynoglossus semilaevis),and its open reading frame(ORF) polymorphism was studied.The whole cDNA sequence was 992 bp in length,including the ORF with 717 bp.Twenty-five alleles were identified and clustered into two distinct groups according to the specific nucleotides/amino acids in specific positions.Eleven alleles belonged to Cyse-DAA while fourteen alleles belonged to Cyse-DBA.Four Cyse-DAA alleles were observed in one individual,and three to five Cyse-DBA alleles were observed in each of the three detected individuals,which indicated that at least two loci existed in each gene.Moreover,in order to study the function of the alleles in resistance to infection,200 individuals were intraperitoneally injected with Vibrio anguillarum and the first 20 dead individuals and 20 surviving ones were selected for genotype analysis.Fifty-six alleles were identified among the 40 individuals.Twenty-nine alleles belonged to Cyse-DAA and the other 27 alleles belonged to Cyse-DBA.Eighteen alleles were selected for studying their function in resistance to infection.Alleles Cyse-DAA*0201,Cyse-DAA*1101,Cyse-DBA*0401,Cyse-DBA*1102,Cyse-DBA*1801 and Cyse-DBA*2201 were identi-fied only in surviving individuals,while alleles Cyse-DAA*0901,Cyse-DBA*1101 and Cyse-DBA*1401 occurred more frequently in dead individuals.This study confirmed the existence and polymorphism of two class II A genes as well as the relationship between alleles of class II A genes and disease susceptibility/resistance in half-smooth tongue sole.

Analysis of Allele Specific Expression——A Survey

Allele specific expression is essential for cellular programming and development and the diversity of cellular phenotypes. Traditional analysis methods utilize RNA and depend on single nucleotide polymorphisms,thus to suffer from limited amount of materials for analysis. The rapid development of next-generation sequencing technologies provides more comprehensive and powerful approaches to analyze the genomic, epigenetic, and transcriptomic data, and further to detect and measure allele specific expressions. It will potentially enhance the understanding of the allele specific expressions, their complexities, and the effect on biological processes. In this paper, we extensively review the state-of-art enabling technologies and tools to analyze, detect, and measure allele specific expressions, compare their features, and point out the future trend of the methods.