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Sample records for harbors genetic polymorphisms

  1. Osteopontin: an early innate immune marker of Escherichia coli mastitis harbors genetic polymorphisms with possible links with resistance to mastitis

    PubMed Central

    Alain, Karin; Karrow, Niel A; Thibault, Catherine; St-Pierre, Jessika; Lessard, Martin; Bissonnette, Nathalie

    2009-01-01

    Background Mastitis is the most important disease in dairy cows and it causes significant lost of profit to producers. Identification of the genes, and their variants, involved in innate immune responses is essential for the understanding of this inflammatory disease and to identify potential genetic markers for resistance to mastitis. The progeny of dairy cows would benefit from receiving favourable alleles that support greater resistance to infection, thus reducing antibiotic use. This study aims to identify a key gene in the innate immune response to mastitis, led us to evaluate its genetic association with somatic cell score (SCS), which is an indicator of clinical mastitis, and to evaluate its impact on other traits related to milk production. Results The osteopontin transcript (SPP1) was identified in the somatic cells from cows experimentally infected with Escherichia coli. By selecting bulls with extreme estimated breeding values (EBVs) for SCS, which is an indicator of mammary gland health, four DNA polymorphisms in the SPP1 genomic sequence were found. Statistical analysis revealed that the SNP SPP1c.-1301G>A has an impact on EBV for SCS (P < 0.001) Using an allele substitution model, SPP1c.-1251C>T, SPP1c.-430G>A, and SPP1c.*40A>C have an impact on SCS whereas SPP1c.-1301G>A has an effect on the EBVs for milk yield (second and third lactations), fat and protein percentages (all three lactations). Analysis revealed statistically significant differences between haplotype groups at a comparison-wise level with sire EBVS for SCS for the first (P = 0.012), second (P < 0.001), and third (P < 0.001) lactations. Conclusion This study reports the link between DNA polymorphisms of SPP1, the number of milk immune cells and, potentially, the susceptibility to mastitis. These SNPs were identified by in silico search to be located in transcription factor recognition sites which factors are presumably involved in the Th1 immune response and in the Th2 regulation pathway. Indeed, one SNP abolished the SP1 recognition site, whereas another SNP affected the transcription binding factor IKAROS. All together, these findings support the genetic potential of these variants in terms of selection for the improvement of mastitis resistance in dairy cows. PMID:19765294

  2. Polymorphic Y chromosomes harbor cryptic variation with manifold functional consequences.

    PubMed

    Lemos, Bernardo; Araripe, Luciana O; Hartl, Daniel L

    2008-01-01

    The paucity of polymorphisms in single-copy genes on the Y chromosome of Drosophila contrasts with data indicating that this chromosome has polymorphic phenotypic effects on sex ratio, temperature sensitivity, behavior, and fitness. We show that the Y chromosome of D. melanogaster harbors substantial genetic diversity in the form of polymorphisms for genetic elements that differentially affect the expression of hundreds of X-linked and autosomal genes. The affected genes are more highly expressed in males, more meagerly expressed in females, and more highly divergent between species. Functionally, they affect microtubule stability, lipid and mitochondrial metabolism, and the thermal sensitivity of spermatogenesis. Our findings provide a mechanism for adaptive phenotypic variation associated with the Y chromosome. PMID:18174442

  3. [Genetic polymorphism and aging].

    PubMed

    Glotov, O S; Baranov, V S

    2007-01-01

    The review of the modern conceptions concerning a role of genetic factors in processes of ageing and longevity is presented. Despite of the various hypotheses explaining mechanisms of ageing, many aspects of this natural stage of life have not been studied yet. Ageing is a process which development is under the control of many endogenous (hereditary) and exogenous (environment) factors. Many questions of interaction of genes and their products-proteins among themselves and with environmental factors remain opened. Ethnic and geographical features of association of those or others polymorphic alleles with longevity and ageing are still not completely clear. Prolongation of the period of active longevity is possible via two methods: by means of modulation of activity of the genes that influence directly on "speed of ageing" with the aid of introduction of geroprotectors protecting an organism from action of endotoxins, and by means of predictive diagnostics and preventive maintenance of frequent multifactorial diseases with the aid of testing polymorphisms in genes of "predisposition". Nowadays testing of the genetic markers which are responsible for hereditary predisposition to the most frequent multifactorial diseases and are the main reasons of ageing and "enemies" of active longevity is quite possible. The basic genes of "predisposition", genes of "ageing" and their polymorphisms are briefly reviewed and some results of testing of these genes are considered. PMID:18306688

  4. Genetics Home Reference: Floating-Harbor syndrome

    MedlinePLUS

    ... unusually high-pitched voice; and, in males, undescended testes (cryptorchidism). How common is Floating-Harbor syndrome? Floating- ... motor ; mutation ; philtrum ; protein ; short stature ; stature ; syndrome ; testes You may find definitions for these and many ...

  5. Cytogenetic biomarkers and genetic polymorphisms.

    PubMed

    Norppa, Hannu

    2004-04-01

    Cytogenetic biomarkers have long been applied in surveillance of human genotoxic exposure and early effects of genotoxic carcinogens. Due to their wide use, it has been possible to evaluate, in international collaborative studies, if a high level of these biomarkers in peripheral lymphocytes is predictive of cancer risk. Thus far, such an association has been observed for chromosomal aberrations (CAs), but not for sister chromatid exchanges (SCEs) or micronuclei (MN). The cancer risk predictivity of CAs was not dependent on the time between CA analysis and cancer detection and did not appear to be explained by tobacco smoking or occupational exposure to carcinogens but was seen in unexposed non-smokers as well. This suggests a role for individual susceptibility factors. Genetic polymorphisms of various xenobiotic-metabolising enzymes, influencing the metabolic activation and detoxification of carcinogens, have been associated with cancer risk, and some of them also appear to affect cytogenetic biomarkers. The lack of glutathione S-transferase M1 (GSTM1 null genotype) is associated with increased sensitivity to genotoxicity of tobacco smoke, and GSTM1 null smokers also show an increased frequency of CAs and SCEs. N-Acetyltransferase (NAT2) slow acetylation genotype and glutathione S-transferase T1 (GSTT1) null genotype seem to elevate the baseline level of CAs and SCEs and CAs, respectively--possibly because of reduced capacity to detoxify some wide-spread or endogenous genotoxins. For some chemicals, in vitro cytogenetic studies with lymphocyte donors representing different genotypes have been able to predict a differential in vivo response. For instance, in vitro SCE induction by styrene and by epoxide metabolites of 1,3-butadiene is modified by GSTM1 and GSTT1 genotypes--which also influence the excretion of specific mercapturic acids in humans exposed to butadiene and styrene. Polymorphisms of DNA repair and folate metabolism are expected to be of special importance in modulating genotoxic effects. Some evidence exists for the effects of X-ray cross complementation group 1 (XRCC1) codon 280 and (in smokers) Xeroderma pigmentosum group D (XPD) codon 23 polymorphisms on baseline CAs, for XRCC1 codon 399 polymorphism on SCEs in smokers, and for methylene tetrahydrofolate reductase (MTHFR) codon 677 and methionine synthase reductase (MTRR) polymorphisms on spontaneous MN. PMID:15093278

  6. Migraine and Genetic Polymorphisms: An Overview

    PubMed Central

    Pizza, Vincenzo; Agresta, Anella; Agresta, Antonio; Lamaida, Eros; Lamaida, Norman; Infante, Francesco; Capasso, Anna

    2012-01-01

    The relationship between genetic polymorphisms and migraine as a cause of an increased risk of thrombotic disorders development is still debated In this respect, factor V Leiden, factor V (H1299R), prothrombin G20210A, factor XIII (V34L), ?-fibrinogen, MTHFR (C677T), MTHFR (A1298C), APO E, PAI-1, HPA-1 and ACE I/D seem to play a determinant role in vascular diseases related to migraine. The present review analyzes both the incidence of the above genetic vascular mutations in migraineurs and the most re-cent developments related to genetic polymorphisms and migraine. PMID:22962564

  7. Genetic polymorphisms and idiopathic generalized epilepsies.

    PubMed

    Lucarini, Nazzareno; Verrotti, Alberto; Napolioni, Valerio; Bosco, Guido; Curatolo, Paolo

    2007-09-01

    In recent years, progress in understanding the genetic basis of idiopathic generalized epilepsies has proven challenging because of their complex inheritance patterns and genetic heterogeneity. Genetic polymorphisms offer a convenient avenue for a better understanding of the genetic basis of idiopathic generalized epilepsy by providing evidence for the involvement of a given gene in these disorders, and by clarifying its pathogenetic mechanisms. Many of these genes encode for some important central nervous system ion channels (KCNJ10, KCNJ3, KCNQ2/KCNQ3, CLCN2, GABRG2, GABRA1, SCN1B, and SCN1A), while many others encode for ubiquitary enzymes that play crucial roles in various metabolic pathways (HP, ACP1, ME2, LGI4, OPRM1, GRIK1, BRD2, EFHC1, and EFHC2). We review the main genetic polymorphisms reported in idiopathic generalized epilepsy, and discusses their possible functional significance in the pathogenesis of seizures. PMID:17765802

  8. Molecular genetics of Psoriasis (Principles, technology, gene location, genetic polymorphism and gene expression)

    PubMed Central

    Al Robaee, Ahmad A.

    2010-01-01

    Summary: Psoriasis is a common inflammatory skin disease with an etiology bases on both environmental and genetic factors. As is the case of many autoimmune diseases its real cause remains poorly defined. However, it is known that genetic factors contribute to disease susceptibility. The linkage analysis has been used to identify multiple loci and alleles that confer risk of the disease. Some other studies have focused upon single nucleotide polymorphisms (SNPs) for mapping of probable causal variants. Other studies, using genome-wide analytical techniques, tried to link the disease to copy number variants (CNVs) that are segments of DNA ranging in size from kilobases to megabases that vary in copy number. CNVs represent an important element of genomic polymorphism in humans and harboring dosage-sensitive genes may cause or predispose to a variety of human genetic diseases. The mechanisms giving rise to SNPs and CNVs can be considered as fundamental processes underlying gene duplications, deletions, insertions, inversions and complex combinations of rearrangements. The duplicated genes being the results of successful copies are fixed and maintained in the population. Conversely, many unsuccessful duplicates remain in the genome as pseudogenes. There is another form of genetic variations termed copy-neutral loss of heterozygosity (LOH) with less information about their potential impact on complex diseases. Additional studies would include associated gene expression variations with either SNPs or CNVs. Now many genetic techniques such as PCR, real time PCR, microarray and restriction fragment length analysis are available for detecting genetic polymorphisms, gene mapping and estimation of gene expression. Recently, the scientists have used these tools to define genetic signatures of disease, to understand genetic causes of disease and to characterize the effects of certain drugs on gene expression. This review highlights the principles, technology and applications on psoriasis. PMID:21475550

  9. Genetic polymorphisms linked to susceptibility to malaria

    PubMed Central

    2011-01-01

    The influence of host genetics on susceptibility to Plasmodium falciparum malaria has been extensively studied over the past twenty years. It is now clear that malaria parasites have imposed strong selective forces on the human genome in endemic regions. Different genes have been identified that are associated with different malaria related phenotypes. Factors that promote severity of malaria include parasitaemia, parasite induced inflammation, anaemia and sequestration of parasitized erythrocytes in brain microvasculature. Recent advances in human genome research technologies such as genome-wide association studies (GWAS) and fine genotyping tools have enabled the discovery of several genetic polymorphisms and biomarkers that warrant further study in host-parasite interactions. This review describes and discusses human gene polymorphisms identified thus far that have been shown to be associated with susceptibility or resistance to P. falciparum malaria. Although some polymorphisms play significant roles in susceptibility to malaria, several findings are inconclusive and contradictory and must be considered with caution. The discovery of genetic markers associated with different malaria phenotypes will help elucidate the pathophysiology of malaria and enable development of interventions or cures. Diversity in human populations as well as environmental effects can influence the clinical heterogeneity of malaria, thus warranting further investigations with a goal of developing new interventions, therapies and better management against malaria. PMID:21929748

  10. Genetic polymorphisms associated with antiepileptic metabolism.

    PubMed

    Lopez-Garcia, Miguel A; Feria-Romero, Iris A; Fernando-Serrano, Hector; Escalante-Santiago, David; Grijalva, Israel; Orozco-Suarez, Sandra

    2014-01-01

    Several factors, including pharmacogenetics, contribute to inter-individual variability in drug response. Many antiepileptic drugs (AEDs) are metabolized by a variety of enzymatic reactions, and the cytochrome P450 (CYP) family has attracted considerable attention. Some of the CYPs exist as genetic (allelic) variants, which may also affect the plasma concentrations or drug exposure. Regarding the metabolism of AEDs, the polymorphic CYP2C9 and CYP2C19 are of particular interest. There have been recent advances in discovering factors such as these, especially those underlying the risk of medication toxicity. This review summarizes the evidence about whether such polymorphisms affect the clinical action of AEDs to facilitate future studies on the pharmacogenetics of epilepsy. We performed Key Words searches in the public databases PubMed, Medscape, and Rxlisty, Pharm GKB for genetic polymorphisms and the NCBI website for the nomenclature of alleles of CYP450, finding that CYP2D6, CYP2C9, CYP3A4, and CYP2D19 were involved in the metabolism of most antiepileptic drugs, given the allele frequency in the population and the associated variability in the clinical response. PMID:24896213

  11. Genetic polymorphisms and susceptibility to lung disease

    PubMed Central

    Lee, Pauline L; West, Carol; Crain, Karen; Wang, Lei

    2006-01-01

    Susceptibility to infection by bacterium such as Bacillus anthracis has a genetic basis in mice and may also have a genetic basis in humans. In the limited human cases of inhalation anthrax, studies suggest that not all individuals exposed to anthrax spores were infected, but rather, individuals with underlying lung disease, particularly asthma, sarcoidosis and tuberculosis, might be more susceptible. In this study, we determined if polymorphisms in genes important in innate immunity are associated with increased susceptibility to infectious and non-infectious lung diseases, particularly tuberculosis and sarcoidosis, respectively, and therefore might be a risk factor for inhalation anthrax. Examination of 45 non-synonymous polymorphisms in ten genes: p47phox (NCF1), p67phox (NCF2), p40phox (NCF4), p22phox (CYBA), gp91phox (CYBB), DUOX1, DUOX2, TLR2, TLR9 and alpha 1-antitrypsin (AAT) in a cohort of 95 lung disease individuals and 95 control individuals did not show an association of these polymorphisms with increased susceptibility to lung disease. PMID:16608528

  12. Genetics: Polymorphisms, Epigenetics, and Something In Between

    PubMed Central

    Maggert, Keith A.

    2012-01-01

    At its broadest sense, to say that a phenotype is epigenetic suggests that it occurs without changes in DNA sequence, yet is heritable through cell division and occasionally from one organismal generation to the next. Since gene regulatory changes are oftentimes in response to environmental stimuli and may be retained in descendent cells, there is a growing expectation that one's experiences may have consequence for subsequent generations and thus impact evolution by decoupling a selectable phenotype from its underlying heritable genotype. But the risk of this overbroad use of “epigenetic” is a conflation of genuine cases of heritable non-sequence genetic information with trivial modes of gene regulation. A look at the term “epigenetic” and some problems with its increasing prevalence argues for a more reserved and precise set of defining characteristics. Additionally, questions arising about how we define the “sequence independence” aspect of epigenetic inheritance suggest a form of genome evolution resulting from induced polymorphisms at repeated loci (e.g., the rDNA or heterochromatin). PMID:22567405

  13. Genetic polymorphisms associated with acute lung injury

    PubMed Central

    Reddy, Anita J; Kleeberger, Steven R

    2009-01-01

    Acute lung injury and acute respiratory distress syndrome are the result of intense inflammation in the lungs leading to respiratory failure. The causes of acute lung injury/acute respiratory distress syndrome are numerous (e.g., pneumonia, sepsis and trauma) but the reasons why certain individuals develop lung injury in response to these stimuli and others do not are not well understood. There is ample evidence in the literature that genehost and geneenvironment interactions may play a large role in the morbidity and mortality associated with this syndrome. In this review, we initially discuss methods for identification of candidate acute lung injury/acute respiratory distress syndrome susceptibility genes using a number of model systems including in vitro cell systems and inbred mice. We then describe examples of polymorphisms in genes that have been associated with the pathogenesis of acute lung injury/acute respiratory distress syndrome in human casecontrol studies. Systematic bench to bedside approaches to understand the genetic contribution to acute lung injury/acute respiratory distress syndrome have provided important insight to this complex disease and continuation of these investigations could lead to the development of novel prevention or intervention strategies. PMID:19761373

  14. Impact of Candidate Genetic Polymorphisms in Prostate Cancer: An Overview.

    PubMed

    Salvi, S; Conteduca, V; Gurioli, G; Calistri, D; Casadio, V; De Giorgi, U

    2016-02-01

    In the last few years, the presence of single nucleotide polymorphisms (SNPs) has been investigated in many tumors as predictor of disease aggressiveness and clinical outcome. We searched for relevant articles from 1998 to 2015 about the impact of SNPs in prostate cancer. Particularly, in this article, we review the pathogenetic, prognostic and predictive significance of gene polymorphisms in prostate tumor, providing a brief overview of studies in which the possible role of genetic variants was investigated in clinical settings. Because conflicting results often emerge about the impact of gene polymorphisms in prostate cancer, further larger studies are warranted in order to introduce gene polymorphism into clinical practice as biomarkers. PMID:26518421

  15. Turner syndrome and genetic polymorphism: a systematic review

    PubMed Central

    de Marqui, Alessandra Bernadete Trovó

    2015-01-01

    Objective: To present the main results of the literature on genetic polymorphisms in Turner syndrome and their association with the clinical signs and the etiology of this chromosomal disorder. Data sources: The review was conducted in the PubMed database without any time limit, using the terms Turner syndrome and genetic polymorphism. A total of 116 articles were found, and based on the established inclusion and exclusion criteria 17 were selected for the review. Data synthesis: The polymorphisms investigated in patients with Turner syndrome were associated with growth deficit, causing short stature, low bone mineral density, autoimmunity and cardiac abnormalities, which are frequently found in patients with Turner syndrome. The role of single nucleotide polymorphisms in the etiology of Turner syndrome, i.e., in chromosomal nondisjunction, was also confirmed. Conclusions: Genetic polymorphisms appear to be associated with Turner syndrome. However, in view of the small number of published studies and their contradictory findings, further studies in different populations are needed in order to clarify the role of genetic variants in the clinical signs and etiology of the Turner syndrome. PMID:25765448

  16. Genetics of Color Polymorphism in the Pea Aphid, Acyrthosiphon pisum

    PubMed Central

    Caillaud, Marina C.; Losey, John E.

    2010-01-01

    The genetic basis of color polymorphism is explored in the pea aphid, Acyrthosiphon pisum (Harris) (Homoptera: Sternorrhyncha), in which two color morphs have been described (pink or green). Laboratory crosses and a Mendelian genetic analysis reveal that color polymorphism in pea aphids is determined by a single biallelic locus, which we name colorama, with alleles P and p, pink being dominant to green. The putative genotypes are Pp or PP for pink morphs, and pp for green morphs. This locus is shown to be autosomal. Last, there was no evidence of influence of the direction of the cross on color inheritance, thus showing that cytoplasmic effects and/or maternally-inherited symbionts play no role in the inheritance of color polymorphism in pea aphids. The existence of a simple genetic determinism for color polymorphism in a system in which genetic investigation is possible may facilitate investigations on the physiological and molecular mechanisms of genetically-based color morph variation, and the establishment of a link between this locus and fitness in a range of ecological conditions. PMID:20673119

  17. The genetic polymorphism of drug transporters: functional analysis approaches.

    PubMed

    Ishikawa, Toshihisa; Tsuji, Akira; Inui, Kenichi; Sai, Yoshimichi; Anzai, Naohiko; Wada, Morimasa; Endou, Hitoshi; Sumino, Yasuhiro

    2004-01-01

    Evidence is accumulating to strongly suggest that drug transporters are one of the determining factors governing the pharmacokinetic profile of drugs. To date, a variety of drug transporters have been cloned and classified as solute carriers and ATP-binding cassette transporters. Such drug transporters are expressed in various tissues such as the intestine, brain, liver, and kidney, and play critical roles in the absorption, distribution and excretion of drugs. However, at the present time, information is limited regarding the genetic polymorphism of drug transporters and its impact on their function. In this context, we have undertaken the functional analyses of the polymorphisms identified in drug transporter genes. This article aims to provide an overview on the functional aspects of the non-synonymous polymorphisms of drug transporters and to present standard methods for the evaluation of the effect of polymorphisms on their function. PMID:14683421

  18. Genetic polymorphisms in Pakistani women with polycystic ovary syndrome.

    PubMed

    Liaqat, Irfana; Jahan, Nusrat; Krikun, Graciela; Taylor, Hugh S

    2015-03-01

    Polycystic ovary syndrome (PCOS) is the major cause of anovulatory infertility. Although the genetic basis of PCOS is not well understood, it is a common metabolic and endocrine disorder. This study investigates the possible genomic variants associated with PCOS in Pakistani women from the Punjab region. DNA samples from 96 patients with genetically unrelated PCOS and 96 controls were analyzed by direct sequencing to determine the polymorphisms of different loci on follicle-stimulating hormone receptor (fshr), follicle-stimulating hormone ? (fshr?), luteinizing hormone chorionic gonadotropin (lhcgr), luteinizing hormone ? (lh?), estrogen receptor ? (esr1), and estrogen receptor ? (esr2) genes. Significant associations were observed within the genotype frequencies, allele frequencies, and multi-single-nucleotide polymorphism (SNP) haplotype analysis of most polymorphisms studied. This study identified new SNPs at positions 605+52 Del/T in lhcgr genes occurring in this particular subpopulation. The strong r (2) value suggests that polymorphisms in the fshr and esr1 genes were in linkage disequilibrium. Our study provides evidence of statistically significant associations between susceptibility to PCOS in Pakistani women and the gene polymorphisms mentioned earlier. This suggests that the susceptible loci for PCOS lie within or very close to the chromosomal regions spanning these genes. PMID:25100445

  19. Harbor porpoise Phocoena phocoena strandings on the Dutch coast: No genetic structure, but evidence of inbreeding

    NASA Astrophysics Data System (ADS)

    van der Plas-Duivesteijn, Suzanne J.; Smit, Femmie J. L.; van Alphen, Jacques J. M.; Kraaijeveld, Ken

    2015-03-01

    Conservation management in the North Sea is often motivated by the population size of marine mammals, like harbor porpoises Phocoena phocoena. In the Dutch part of the North Sea, sighting and stranding data are used to estimate population sizes, but these data give little insight into genetic structuring of the population. In this study we investigated genetic structure among animals stranded at different locations and times of year. We also tested whether there is a link between stranding and necropsy data, and genetic diversity. We made use of both mitochondrial (mtDNA) and microsatellite DNA analysis of samples from dead stranded porpoises along the Dutch coast during 2007. mtDNA analysis showed 6 variable positions in the control region, defining 3 different haplotypes. mtDNA haplotypes were not randomly distributed along the Dutch coastline. However, microsatellite analysis showed that these mtDNA haplotypes did not represent separate groups on a nuclear level. Furthermore, microsatellite analysis revealed no genotypic differences between seasons, locations or genders. The results of this study indicate that the Dutch population is panmictic. In contrast, heterozygosity levels were low, indicating some level of inbreeding in this population. However, this was not corroborated by other indices of inbreeding. This research provided insight into genetic structuring of stranded porpoises in 2007, but data from multiple years should be included to be able to help estimate population sizes.

  20. Population Genetics of Polymorphism and Divergence

    PubMed Central

    Sawyer, S. A.; Hartl, D. L.

    1992-01-01

    Frequencies of mutant sites are modeled as a Poisson random field in two species that share a sufficiently recent common ancestor. The selective effect of the new alleles can be favorable, neutral, or detrimental. The model is applied to the sample configurations of nucleotides in the alcohol dehydrogenase gene (Adh) in Drosophila simulans and Drosophila yakuba. Assuming a synonymous mutation rate of 1.5 X 10(-8) per site per year and 10 generations per year, we obtain estimates for the effective population size (N(e) = 6.5 X 10(6)), the species divergence time (t(div) = 3.74 million years), and an average selection coefficient (? = 1.53 X 10(-6) per generation for advantageous or mildly detrimental replacements), although it is conceivable that only two of the amino acid replacements were selected and the rest neutral. The analysis, which includes a sampling theory for the independent infinite sites model with selection, also suggests the estimate that the number of amino acids in the enzyme that are susceptible to favorable mutation is in the range 2-23 at any one time. The approach provides a theoretical basis for the use of a 2 X 2 contingency table to compare fixed differences and polymorphic sites with silent sites and amino acid replacements. PMID:1459433

  1. Role of genetic polymorphisms in hepatitis C virus chronic infection

    PubMed Central

    Coppola, Nicola; Pisaturo, Mariantonietta; Sagnelli, Caterina; Onorato, Lorenzo; Sagnelli, Evangelista

    2015-01-01

    AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C (CHC). METHODS: We conducted an electronic search on the PubMed and MEDLINE (2000-2014) databases and Cochrane library (2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article. RESULTS: Several studies associated polymorphisms in the interleukin 28B gene on chromosome 19 (19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon (Peg-IFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation. CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies. PMID:26380828

  2. Cytochrome P450 genetic polymorphisms of Mexican indigenous populations.

    PubMed

    Sosa-Macías, Martha; Llerena, Adrián

    2013-01-01

    This review focuses on the genetic polymorphisms of the cytochrome P450 (CYP) genes in Mexican indigenous populations, who are a part of the wide ethnic diversity of this country. These native groups have a particular historical trajectory that is different from the Mexican Mestizos. This variability may be reflected in the frequency distribution of polymorphisms in the CYP genes that encode enzymes involved in the metabolism of drugs and other xenobiotics. Therefore, these polymorphisms may affect drug efficacy and safety in indigenous populations in Mexico. The present study aimed to analyze the prevalence of CYP polymorphisms in indigenous Mexicans and to compare the results with studies in Mexican Mestizos. Because the extrapolation of pharmacogenetic data from Mestizos is not applicable to the majority of indigenous groups, pharmacogenetic studies directed at indigenous populations need to be developed. The Amerindians analyzed in this study showed a low phenotypic (CYP2D6) and genotypic (CYP2D6, CYP2C9) diversity, unlike Mexican Mestizos. The frequency of polymorphisms in the CYP1A1, CYP2C19, CYP2E1, and CYP3A4 genes was more similar among the Amerindians and Mexican Mestizos, with the exception of the CYP1A2 gene, whose *1F variant frequency in Mexican Amerindians was the highest described to date. PMID:24145057

  3. Rabbit MSTN gene polymorphisms and genetic effect analysis.

    PubMed

    Qiao, X B; Xu, K Y; Li, B; Luan, X; Xia, T; Fan, X Z

    2014-01-01

    We analyzed meat samples of nine pure lines of rabbit and its 37 hybrid combinations by sequencing and single-strand conformation polymorphism techniques to explore genetic polymorphisms of all the three exon regions and part of the 5'-regulatory region of the myostatin (MSTN) gene. Thus, we detected a single nucleotide mutation (T?C) on the 476 locus of the 5'-regulatory region, but no mutation sites were detected in the exon areas. The correlation analysis showed that the mutation had some favorable genetic effects, and it resulted in increased liver weight, carcass weight, forelegs weight, back and waist weight, ham weight, and tare weight, whereas it decreased muscle drip loss and cooking loss (P < 0.05). These results suggest that the mutations in the upstream regulatory region of the MSTN gene are beneficial to the rabbit soma development, and the mutations can be used as molecular markers for the selection of the meat quality of rabbits. PMID:24782047

  4. Cytokine genetic polymorphisms and prostate cancer aggressiveness

    PubMed Central

    Zabaleta, Jovanny; Su, L. Joseph; Lin, Hui-Yi; Sierra, Rosa A.; Hall, M. Craig; Sartor, A. Oliver; Clark, Peter E.; Hu, Jennifer J.; Ochoa, Augusto C.

    2009-01-01

    Prostate cancer (PCa) is one of the most common cancers in the world. Inflammation has been described as a risk factor for PCa and depends on the production of cytokines in response to tissue damage or the presence of stimuli that induces cellular stress. Interindividual variation in cytokine production is partially controlled by single-nucleotide polymorphisms (SNPs) that have been associated with differential production of cytokines. We have recently showed that SNP–SNP interactions of cytokine genes are associated with PCa risk. However, little is known about the association of cytokine SNPs and PCa aggressiveness. In this study, we evaluated the association of 15 SNPs in five cytokine genes and aggressiveness of PCa in African- and Caucasian-American individuals. Caucasian Americans with the genotypes IL10−1082GG or IL1B+3954TT had 2.31-fold [95% confidence interval (CI) = 1.13–4.72] and 3.11 (95% CI = 1.20–8.06)-fold risk, respectively, of developing aggressive PCa, as compared with individuals without those genotypes. We did not find any associations in the African-American group. Using Multivariate Adaptive Regression Splines modeling for exploratory SNP–SNP interactions, our results showed that more aggressive PCa in Caucasians Americans is associated with the CT genotype at IL8−47 [odds ratios (OR) = 3.50; 95% CI = 1.13–10.88] or combined genotypes of IL1B−511CC and IL10−1082GG (OR = 3.38; 95% CI = 1.70–6.71). Unfortunately, the same analysis could not be performed in the African-Americans due to limited number of individuals. With limited sample size, the results from this study suggest that SNPs in cytokine genes may be associated with PCa aggressiveness. More extensive studies are warranted to validate our findings. PMID:19474090

  5. High volume molecular genetic identification of single nucleotide polymorphisms using Genetic Bit Analysis Application to human genetic diagnosis

    SciTech Connect

    Boyce-Jacino, M.T.; Reynolds, J.; Nikiforov, T.

    1994-09-01

    The most common type of genetic disease-associated mutation is the single nucleotide polymorphism (SNP). Because most genetic diseases can be caused by multiple SNPs in the same gene, effective routine diagnosis of complex genetic diseases is dependent on a simple and reliable method of interrogating SNP sites. Molecular Tool`s solid phase assay capable of direct genotyping (single base sequencing) of SNP sites, Genetic Bit Analysis (GBA), involves hybridization-capture of a single-stranded PCR product to a sequence-specific, microtiter plate-bound oligonucleotide primer. The captured PCR product then acts as template for single-base extension of the capture primer across the polymorphic site, enabling direct determination of the base composition of the polymorphism through a simple colormetric assay. Genotyping in a high volume, semi-automated, processing system with a current capacity of 100 SNP interrogations per technician per day enables the screening of candidate mutations rapidly and cost-effectively, critically important to comprehensive genetic diagnosis. Using this gel-free technology, we have developed prototype diagnostic tests for CFTR and ApoE polymorphisms which enable direct sequencing of the polymorphic base at each site of interest. Routine clinical diagnosis of genetically complex diseases such as cystic fibrosis is dependent on this combination of robust biochemistry and simple format. Additionally, the ability to transfer the format and biochemistry to any disease gene of interest enables the broad application of this technology to clinical diagnostics, especially for genetically complex diseases.

  6. Interethnic genetic differentiation: GM polymorphism in eastern Senegal.

    PubMed Central

    Blanc, M; Sanchez-Mazas, A; Van Blyenburgh, N H; Sevin, A; Pison, G; Langaney, A

    1990-01-01

    Analysis of GM polymorphism has been performed on 1,806 individuals representing three sympatric ethnic groups--Bedik, Fulani, and Mandenkalu--of eastern Senegal. Haplotype frequencies estimated by maximum likelihood have been used to compute common genetic pools between the three samples and a number of other sub-Saharan African populations. Despite extreme linguistic and sociocultural differentiations and very high levels of endogamy, especially in the Bedik and Niokholo Mandenkalu, the three populations share about 90%-95% of their haplotype frequencies in a system which commonly provides strong genetic differentiations. This supports the view that, despite its importance at a large continental scale level, as it is discussed for a set of populations from many regions of sub-Saharan Africa, sociocultural differentiation usually has little effect on local genetic diversity. PMID:2105642

  7. From twins to genetic polymorphisms: behavioral genetic research in Poland.

    PubMed

    Oniszczenko, W?odzimierz; Dragan, Wojciech ?ukasz

    2014-10-01

    Behavioral genetic research has been conducted at the University of Warsaw for the past 20 years. The work done at the University focuses primarily on the origins of individual differences in temperament and other personality traits. In particular, research is directed toward the traits postulated in the Regulative Theory of Temperament. We also focused on the heritability of socio-political attitudes, risk factors for human health, and post-traumatic stress disorder. The majority of the research that has been carried out is grounded in twin and family studies, although recent work based on molecular techniques has also been developed. This article reviews the most important directions and findings of behavioral genetics research at the University of Warsaw. PMID:25091033

  8. Evaluation of Genetic Polymorphisms in Patients with Multiple Chemical Sensitivity

    PubMed Central

    Cui, Xiaoyi; Lu, Xi; Hiura, Mizue; Oda, Masako; Miyazaki, Wataru; Katoh, Takahiko

    2013-01-01

    Objective Multiple chemical sensitivity (MCS) is a chronic medical condition characterized by symptoms that the affect an individual’s response to low-level chemical exposure. In this study, we identified a chemical sensitive population (CSP) and investigated the effect of genetic polymorphisms on their risk of chemical sensitivity. Methods A quick environment exposure sensitivity (QEESI) questionnaire was used to survey 324 Japanese male workers whose DNA samples had been collected and stored. The following genes, which encode enzymes affecting the metabolic activation of a large number of xenobiotic compounds, were selected and analyzed in order to determine their influence on genetic predisposition to CSP: cytochrome P450 (CYP) 2E1, N-acetyl transferase (NAT) 2, glutathione S-transferase (GST) M1, GSTT1, GSTP1, low Km aldehyde dehydrogenase (ALDH2), and superoxide dismutase (SOD) 2. Results Significant case-control distributed differences were observed in SOD2 polymorphisms and allele frequency distribution in high chemical sensitive subjects. Both the significant adjusted OR of 4.30 (95% CI, 1.23–15.03) and 4.53 (95% CI, 1.52-13.51) were observed in SOD2 Ala/Ala and Val/Ala compared to Val/Val and in SOD2 Ala/Ala compared to Val/Ala compared to Val/Val genetic analysis in the high chemical sensitivity case-control study. Conclusions We observed that high chemical sensitive individuals diagnosed by using Japanese criteria as MCS patients were more significantly associated with SOD2 polymorphisms. PMID:23967348

  9. Potential for Incorporation of Genetic Polymorphism Data in Human Health Risk Assessment

    EPA Science Inventory

    This overview summarizes several EPA assessment publications evaluating the potential impact of genetic polymorphisms in ten metabolizing enzymes on the variability in enzyme function across ethnically diverse populations.

  10. Genetic maps of polymorphic DNA loci on rat chromosome 1

    SciTech Connect

    Ding, Yan-Ping; Remmers, E.F.; Longman, R.E.

    1996-09-01

    Genetic linkage maps of loci defined by polymorphic DNA markers on rat chromosome 1 were constructed by genotyping F2 progeny of F344/N x LEW/N, BN/SsN x LEW/N, and DA/Bkl x F344/Hsd inbred rat strains. In total, 43 markers were mapped, of which 3 were restriction fragment length polymorphisms and the others were simple sequence length polymorphisms. Nineteen of these markers were associated with genes. Six markers for five genes, {gamma}-aminobutyric acid receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}1 (Adrb1), carcinoembryonic antigen gene family member 1 (Cgm1), and lipogenic protein S14 (Lpgp), and 20 anonymous loci were not previously reported. Thirteen gene loci (Myl2, Aldoa, Tnt, Igf2, Prkcg, Cgm4, Calm3, Cgm3, Psbp1, Sa, Hbb, Ins1, and Tcp1) were previously mapped. Comparative mapping analysis indicated that the large portion of rat chromosome 1 is homologous to mouse chromosome 7, although the homologous to mouse chromosome 7, although the homologs of two rat genes are located on mouse chromosomes 17 and 19. Homologs of the rat chromosome 1 genes that we mapped are located on human chromosomes 6, 10, 11, 12, 15, 16, and 19. 38 refs., 1 fig., 3 tabs.

  11. Genetic polymorphisms related to testosterone metabolism in intellectually gifted boys.

    PubMed

    Celec, Peter; Tretinrov, Denisa; Minrik, Gabriel; Ficek, Andrej; Szemes, Tom; Lakatoov, Silvia; Schmidtov, Eva; Tur?a, Jn; Kdai, ?udevt; Ostatnkov, Daniela

    2013-01-01

    Prepubertal testosterone levels are lower in intellectually gifted boys. The aim of this pilot study was to analyze potential genetic factors related to testosterone metabolism in control and gifted boys. Intellectually gifted (IQ>130; n = 95) and control (n = 67) boys were genotyped. Polymorphisms of interests were chosen in genes including androgen and estrogen receptors, 5-alpha reductase, aromatase and sex hormone binding globulin. Significant differences between control and gifted boys in genotype distributions were found for ESR2 (rs928554) and SHBG (rs1799941). A significantly lower number of CAG repeats in the AR gene were found in gifted boys. Our results support the role of genetic factors related to testosterone metabolism in intellectual giftedness. Increased androgen signaling might explain previous results of lower testosterone levels in intellectually gifted boys and add to the understanding of variability in cognitive abilities. PMID:23382957

  12. Genetic polymorphism in pathogenesis of irritable bowel syndrome

    PubMed Central

    Cheung, Cynthia KY; Wu, Justin CY

    2014-01-01

    Irritable bowel syndrome (IBS) is a complex symptom-based disorder without established biomarkers or putative pathophysiology. IBS is a common functional gastrointestinal disorder which is defined as recurrent abdominal pain or discomfort that has at least two of the following symptoms for 3 d per month in the past 3 mo according to ROME III: relief by defecation, onset associated with a change in stool frequency or onset with change in appearance or form of stool. Recent discoveries revealed genetic polymorphisms in specific cytokines and neuropeptides may possibly influence the frequencies and severity of symptoms, as well as the therapeutic responses in treating IBS patients. This review gives new insights on how genetic determinations influence in clinical manifestations, treatment responses and potential biomarkers of IBS. PMID:25548468

  13. Genetic Polymorphisms Related to Testosterone Metabolism in Intellectually Gifted Boys

    PubMed Central

    Celec, Peter; Tretinrov, Denisa; Minrik, Gabriel; Ficek, Andrej; Szemes, Tom; Lakatoov, Silvia; Schmidtov, Eva; Tur?a, Jn; Kdai, ?udevt; Ostatnkov, Daniela

    2013-01-01

    Prepubertal testosterone levels are lower in intellectually gifted boys. The aim of this pilot study was to analyze potential genetic factors related to testosterone metabolism in control and gifted boys. Intellectually gifted (IQ>130; n?=?95) and control (n?=?67) boys were genotyped. Polymorphisms of interests were chosen in genes including androgen and estrogen receptors, 5-alpha reductase, aromatase and sex hormone binding globulin. Significant differences between control and gifted boys in genotype distributions were found for ESR2 (rs928554) and SHBG (rs1799941). A significantly lower number of CAG repeats in the AR gene were found in gifted boys. Our results support the role of genetic factors related to testosterone metabolism in intellectual giftedness. Increased androgen signaling might explain previous results of lower testosterone levels in intellectually gifted boys and add to the understanding of variability in cognitive abilities. PMID:23382957

  14. [MOLECULAR-GENETIC POLYMORPHISM OF chs_H1 GENE IN UKRAINIAN HOP VARIETIES].

    PubMed

    Venzer, A M; Volkova, N E; Sivolap, Yu M

    2015-01-01

    Polymorphism of chs_H1 gene encoding the "true" chalcone synthase was determined by alignment of sequences. The polymorphism associates with single nucleotide changes, insertions or deletions (indels) in the promoter, exons, intron, 3'-untranslated region. The molecular-genetic polymorphism in gene chs_H1 different regions of hop varieties of Polessye Agriculture Institute' breeding NAAS was analyzed. PMID:26638493

  15. Genetic polymorphism of xenobiotic metabolising enzymes, diet and cancer susceptibility.

    PubMed

    Reszka, Edyta; Wasowicz, Wojciech; Gromadzinska, Jolanta

    2006-10-01

    There is increasing evidence identifying the crucial role of numerous dietary components in modifying the process of carcinogenesis. The varied effects exerted by nutrient and non-nutrient dietary compounds on human health and cancer risk are one of the new challenges for nutritional sciences. In the present paper, an attempt is made to review the most recent epidemiological data on interactions between dietary factors and metabolic gene variants in terms of cancer risk. The majority of case-control studies indicate the significant relationship between cancer risk and polymorphic xenobiotic metabolising enzymes in relation to dietary components. The risk of colorectal cancer is associated not only with CYP2E1 high-activity alleles, but also GSTA1 low-activity alleles, among consumers of red or processed meat. Genetic polymorphisms of NAT1 and NAT2 may be also a breast-cancer susceptibility factor among postmenopausal women with a high intake of well-done meat. On the other hand, phytochemicals, especially isothiocyanates, have a protective effect against colorectal and lung cancers in individuals lacking GST genes. Moreover, polymorphism of GSTM1 seems to be involved in the dietary regulation of DNA damage. The European Prospective Investigation into Cancer and Nutrition study shows a significant inverse association between the polycyclic aromatic hydrocarbon-DNA adduct level and dietary antioxidants only among GSTM1-null individuals. However, the absence of a modulatory effect of polymorphic xenobiotic metabolising enzymes and diet on the development of cancer has been indicated by some epidemiological investigations. Studies of interactions between nutrients and genes may have great potential for exploring mechanisms, identifying susceptible populations/individuals and making practical use of study results to develop preventive strategies beneficial to human health. PMID:17010218

  16. The role of genetic polymorphisms in environmental health.

    PubMed Central

    Kelada, Samir N; Eaton, David L; Wang, Sophia S; Rothman, Nathaniel R; Khoury, Muin J

    2003-01-01

    Interest is increasing in the role of variations in the human genome (polymorphisms) in modifying the effect of exposures to environmental health hazards (often referred to as gene-environment interaction), which render some individuals or groups in the population more or less likely to develop disease after exposure. This review is intended for an audience of environmental health practitioners and students and is designed to raise awareness about this rapidly growing field of research by presenting established and novel examples of gene-environment interaction that illustrate the major theme of effect modification. Current data gaps are identified and discussed to illustrate limitations of past research and the need for the application of more robust methods in future research projects. Two primary benefits of incorporating genetics into the existing environmental health research framework are illustrated: a) the ability to detect different levels of risk within the population, and b) greater understanding of etiologic mechanisms. Both offer opportunities for developing new methods of disease prevention. Finally, we describe a basic framework for researchers interested in pursuing health effects research that incorporates genetic polymorphisms. PMID:12826477

  17. Genetic Polymorphism and Expression of CXCR4 in Breast Cancer

    PubMed Central

    Okuyama Kishima, Marina; Brajo de Oliveira, Karen; Ariza, Carolina Batista; de Oliveira, Carlos Eduardo Coral; Losi Guembarovski, Roberta; Banin Hirata, Bruna Karina; de Almeida, Felipe Campos; Vitiello, Glauco Akelinghton Freire; Trugilo, Kleber Paiva; Guembarovski, Alda Fiorina Maria Losi; Jorge Sobrinho, Walter; Campos, Clodoaldo Zago; Watanabe, Maria Angelica Ehara

    2015-01-01

    CXCR4 genetic polymorphisms, as well as their expression level, have been associated with cancer development and prognosis. The present study aimed to investigate the influence of CXCR4 rs2228014 polymorphism on its mRNA and protein expression in breast cancer samples. It was observed that patients presented higher CXCR4 mRNA relative expression (5.7-fold) than normal mammary gland, but this expression was not correlated with patients clinicopathological features (nuclear grade, nodal status, ER status, PR status, p53 staining, Ki67 index, and HER-2 status). Moreover, CXCR4 mRNA relative expression also did not differ regarding the presence or absence of T allele (p = 0.301). In the immunohistochemical assay, no difference was observed for CXCR4 cytoplasmic protein staining in relation to different genotypes (p = 0.757); however, high cytoplasmic CXCR4 staining was verified in invasive breast carcinoma (p < 0.01). All in all, the results from present study indicated that rs2228014 genetic variant does not alter CXCR4 mRNA or protein expression. However, this receptor was more expressed in tumor compared to normal tissue, in both RNA and protein levels, suggesting its promising applicability in the general context of mammary carcinogenesis. PMID:26576337

  18. Genetic polymorphisms of matrix metalloproteinase 3 in primary sclerosing cholangitis

    PubMed Central

    Juran, Brian D.; Atkinson, Elizabeth J.; Schlicht, Erik M.; Larson, Joseph J.; Ellinghaus, David; Franke, Andre; Lazaridis, Konstantinos N.

    2011-01-01

    Background The damaging cholestasis inherent to primary sclerosing cholangitis (PSC) results from bile duct stricturing because of progressive fibrosis. The matrix metalloproteinase 3 (MMP3) degrades a wide range of matrix components and is expressed by activated liver stellate cells, and so is a candidate for involvement with the fibrotic processes underlying PSC. Moreover, the MMP3 gene harbours polymorphisms associated with variation in its activity directly impacting clinical phenotypes. Aims We aimed to examine the influence of MMP3 polymorphisms on PSC risk and progression. Methods Nine single nucleotide polymorphisms (SNPs) tagging the common genetic variation of MMP3 were genotyped in 266 PSC patients and 407 controls. SNPs and inferred haplotypes were assessed for PSC association by logistic regression and score tests. The effect of SNPs on survival to liver transplant or death was analysed using Cox regression, and KaplanMeier curves were constructed. Results No association of PSC with individual SNPs or haplotypes of MMP3 was detected. However, progression to death or liver transplant was significantly associated with homozygosity for minor alleles of rs522616, rs650108 and rs683878, particularly among PSC patients with concurrent ulcerative colitis (UC) (strongest in redundant SNPs rs650108/rs683878, hazard ratio = 3.23, 95% confidence interval 1.457.25, P = 0.004). Conclusions Genetic variation in MMP3 influences PSC progression, possibly in the context of coexisting UC. While the functional variants and specific mechanisms remain unknown, this finding implicates the turnover of the extracellular matrix as an important and variable component of PSC pathogenesis. Efforts to understand this process could form the basis for developing effective treatments, which are currently lacking for PSC. PMID:21134112

  19. Chromosome 12q harbors multiple genetic loci related to asthma and asthma-related phenotypes.

    PubMed

    Raby, Benjamin A; Silverman, Edwin K; Lazarus, Ross; Lange, Christoph; Kwiatkowski, David J; Weiss, Scott T

    2003-08-15

    Chromosome 12q13-24 is among the regions most frequently identified in genome-wide surveys for asthma susceptibility loci, with reports of two distinct clusters of positive linkage signals: one near the interferon gamma locus, the other near the nitric oxide synthase 1 locus. These results suggest that 12q harbors several asthma susceptibility loci. We evaluated this possibility in a subset of families ascertained through the Childhood Asthma Management Program (CAMP) Genetics Ancillary Study. Fifty-five nuclear families with at least two asthmatic siblings (212 individuals) were genotyped using 32 microsatellite markers. Non-parametric linkage analysis was performed for the asthma phenotype (qualitative). Multipoint variance component-based linkage analysis was performed for five quantitative asthma-related traits: (i) percent predicted forced expiratory volume in one second (FEV(1)); (ii) dose of methacholine resulting in 20% fall in FEV(1) from baseline (PC(20)); (iii) post-bronchodilator percent change in FEV(1) (BDPR); (iv) serum eosinophil levels (EOS); and (v) total serum IgE levels (IgE). Three separate and distinct loci demonstrated evidence suggestive of linkage: asthma at 68 cM (exact P-value=0.05), airways responsiveness (PC(20)) at 147 cM (P=0.01), and indices of pulmonary function (FEV1, BDPR) at 134 cM (P=0.05 and P<0.01, respectively). No linkage was observed for the atopy-related phenotypes. We provide further evidence supporting the presence of an asthma susceptibility locus at the proximal end of chromosome 12q, as well as new evidence for additional loci more distally that account for unique features of the asthma phenotype. Fine mapping efforts for these loci are warranted. PMID:12913068

  20. Single nucleotide polymorphism markers for genetic mapping in Drosophila melanogaster

    SciTech Connect

    Hoskins, Roger A.; Phan, Alexander C.; Naeemuddin, Mohammed; Mapa, Felipa A.; Ruddy, David A.; Ryan, Jessica J.; Young, Lynn M.; Wells, Trent; Kopczynski, Casey; Ellis, Michael C.

    2001-04-16

    For nearly a century, genetic analysis in Drosophila melanogaster has been a powerful tool for analyzing gene function, yet Drosophila lacks the molecular genetic mapping tools that have recently revolutionized human, mouse and plant genetics. Here, we describe the systematic characterization of a dense set of molecular markers in Drosophila using an STS-based physical map of the genome. We identify 474 biallelic markers in standard laboratory strains of Drosophila that the genome. The majority of these markers are single nucleotide polymorphisms (SNPs) and sequences for these variants are provided in an accessible format. The average density of the new markers is 1 marker per 225 kb on the autosomes and 1 marker per 1 Mb on the X chromosome. We include in this survey a set of P-element strains that provide additional utility for high-resolution mapping. We demonstrate one application of the new markers in a simple set of crosses to map a mutation in the hedgehog gene to an interval of <1 Mb. This new map resource significantly increases the efficiency and resolution of recombination mapping and will be of immediate value to the Drosophila research community.

  1. Candida milleri species reveals intraspecific genetic and metabolic polymorphisms.

    PubMed

    Vigentini, Ileana; Antoniani, Davide; Roscini, Luca; Comasio, Andrea; Galafassi, Silvia; Picozzi, Claudia; Corte, Laura; Compagno, Concetta; Dal Bello, Fabio; Cardinali, Gianluigi; Foschino, Roberto

    2014-09-01

    Candida milleri, together with Candida humilis, is the most representative yeast species found in type I sourdough ecosystems. In this work, comparison of the ITS region and the D1/D2 domain of 26S rDNA gene partial sequences, karyotyping, mtDNA-RFLP analysis, Intron Splice Site dispersion (ISS-PCR) and (GTG)5 microsatellite analyses, assimilation test of different carbohydrates, and metabolome assessment by FT-IR analysis, were investigated in seventeen strains isolated from four different companies as well as in type strains CBS6897(T) and CBS5658(T). Most isolates were ascribed to C. milleri, even if a strong relatedness was confirmed with C. humilis as well, particularly for three strains. Genetic characterization showed a high degree of intraspecific polymorphism since 12 different genotypes were discriminated. The number of chromosomes varied from 9 to 13 and their size ranged from less than 0.3 to over 2 Mbp. Phenotypic traits let to recognize 9 different profiles of carbon sources assimilation. FT-IR spectra from yeast cells cultivated in different media and collected at different growth phases revealed a diversity of behaviour among strains in accordance with the results of PCR-based fingerprinting. A clear evidence of the polymorphic status of C. milleri species is provided thus representing an important feature for the development of technological applications in bakery industries. PMID:24929720

  2. Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression.

    PubMed

    Zhang, Zhang; Zhang, Yan; Shi, Minglei; Ye, Bingyu; Shen, Wenlong; Li, Ping; Xing, Lingyue; Zhang, Xiaopeng; Hou, Lihua; Xu, Junjie; Zhao, Zhihu; Chen, Wei

    2015-01-01

    Anthrax toxin causes anthrax pathogenesis and expression levels of ANTXR2 (anthrax toxin receptor 2) are strongly correlated with anthrax toxin susceptibility. Previous studies found that ANTXR2 transcript abundance varies considerably in individuals of different ethnic/geographical groups, but no eQTLs (expression quantitative trait loci) have been identified. By using 3C (chromatin conformation capture), CRISPR-mediated genomic deletion and dual-luciferase reporter assay, gene loci containing cis-regulatory elements of ANTXR2 were localized. Two SNPs (single nucleotide polymorphism) at the conserved CREB-binding motif, rs13140055 and rs80314910 in the promoter region of the gene, modulating ANTXR2 promoter activity were identified. Combining these two regulatory SNPs with a previously reported SNP, rs12647691, for the first time, a statistically significant correlation between human genetic variations and anthrax toxin sensitivity was observed. These findings further our understanding of human variability in ANTXR2 expression and anthrax toxin susceptibility. PMID:26703731

  3. Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression

    PubMed Central

    Zhang, Zhang; Zhang, Yan; Shi, Minglei; Ye, Bingyu; Shen, Wenlong; Li, Ping; Xing, Lingyue; Zhang, Xiaopeng; Hou, Lihua; Xu, Junjie; Zhao, Zhihu; Chen, Wei

    2015-01-01

    Anthrax toxin causes anthrax pathogenesis and expression levels of ANTXR2 (anthrax toxin receptor 2) are strongly correlated with anthrax toxin susceptibility. Previous studies found that ANTXR2 transcript abundance varies considerably in individuals of different ethnic/geographical groups, but no eQTLs (expression quantitative trait loci) have been identified. By using 3C (chromatin conformation capture), CRISPR-mediated genomic deletion and dual-luciferase reporter assay, gene loci containing cis-regulatory elements of ANTXR2 were localized. Two SNPs (single nucleotide polymorphism) at the conserved CREB-binding motif, rs13140055 and rs80314910 in the promoter region of the gene, modulating ANTXR2 promoter activity were identified. Combining these two regulatory SNPs with a previously reported SNP, rs12647691, for the first time, a statistically significant correlation between human genetic variations and anthrax toxin sensitivity was observed. These findings further our understanding of human variability in ANTXR2 expression and anthrax toxin susceptibility. PMID:26703731

  4. [Genetic diversity of Besermyan based on mitochondrial DNA polymorphism].

    PubMed

    Grosheva, A N; Shneider, Yu V; Morozova, I Yu; Zhukova, O V; Rychkov, S Yu

    2013-11-01

    The first data on mtDNA diversity in Besermyan, the Finno-Ugric ethnic group, related to Udmurts, are presented. An analysis of mtDNA polymorphism showed that Besermyan stood out from the other populations of Volga-Ural region due to the presence of a large proportion of the mongoloid component. The sample of Besermyan contained East Eurasian haplotypes not detected in ethnic populations of the Volga region and Cisurals, while they were detected in South Siberia, mostly among Turkic-speaking populations. An analysis of the genetic distances between Besermyan and the neighboring ethnic groups showed that Besermyan were distant from other populations of Volga-Ural region and close to Turkic-speaking populations of South Siberia. Thus, the data obtained favor the suggestion on the mixed Udmurto-Turkic origin of Besermyan. PMID:25470935

  5. Lemierre's syndrome and genetic polymorphisms: a case report

    PubMed Central

    Constantin, Jean-Michel; Mira, Jean-Paul; Guerin, Renaud; Cayot-Constantin, Sophie; Lesens, Olivier; Gourdon, Florence; Romaszko, Jean-Pierre; Linval, Philippe; Laurichesse, Henri; Bazin, Jean-Etienne

    2006-01-01

    Background Lemierre's syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction. Case presentation A 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and Lemierre's syndrome. Her DNA was assayed for single nucleotide polymorphisms previously incriminated in the detection of the pathogen, the inflammatory response and the coagulation cascade. We observed functional variations in her Toll like 5 receptor (TLR 5) gene and two coagulation variations (Tissue Factor (TF) 603 and Plasminogen-Activator-Inhibitor-1 (PAI-1) 4G-4G homozygosity) associated with thrombotic events. Conclusion The innate immune response and the prothrombogenic mutations could explain, at least in part, the symptoms of Lemierre's syndrome. Genomic study of several patients with Lemierre's syndrome may reveal its pathophysiology. PMID:16846490

  6. Acute myeloid leukemia of donor origin after allogeneic stem cell transplantation from a sibling who harbors germline XPD and XRCC3 homozygous polymorphisms

    PubMed Central

    2011-01-01

    A 54-year-old woman was diagnosed with infiltrative ductal breast carcinoma. Two years after treatment, the patient developed an acute myeloid leukemia (AML) which harbored del(11q23) in 8% of the blast cells. The patient was submitted for allogeneic stem cell transplantation (aSCT) from her HLA-compatible sister. Ten months after transplantation, she relapsed with an AML with basophilic maturation characterized by CD45low CD33high, CD117+, CD13-/+, HLA Drhigh, CD123high, and CD203c+ blast cells lacking expression of CD7, CD10, CD34, CD15, CD14, CD56, CD36, CD64, and cytoplasmic tryptase. Karyotype analysis showed the emergence of a new clone with t(2;14) and FISH analysis indicated the presence of MLL gene rearrangement consistent with del(11q23). Interestingly, AML blast cell DNA tested with microsatellite markers showed the same pattern as the donor's, suggesting that this AML emerged from donor cells. Additionally, polymorphisms of the XPA, XPD, XRCC1, XRCC3 and RAD51 DNA repair genes revealed three unfavorable alleles with low DNA repair capacity. In summary, we report the first case of AML involving XPD and XRCC3 polymorphisms from donor origin following allogeneic stem cell transplantation and highlight the potential need for careful analysis of DNA repair gene polymorphisms in selecting candidate donors prior to allogeneic stem cell transplantation. PMID:21951951

  7. Patterns of genetic diversity in the polymorphic ground snake (Sonora semiannulata).

    PubMed

    Cox, Christian L; Chippindale, Paul T

    2014-08-01

    We evaluated the genetic diversity of a snake species with color polymorphism to understand the evolutionary processes that drive genetic structure across a large geographic region. Specifically, we analyzed genetic structure of the highly polymorphic ground snake, Sonora semiannulata, (1) among populations, (2) among color morphs (3) at regional and local spatial scales, using an amplified fragment length polymorphism dataset and multiple population genetic analyses, including FST-based and clustering analytical techniques. Based upon these methods, we found that there was moderate to low genetic structure among populations. However, this diversity was not associated with geographic locality at either spatial scale. Similarly, we found no evidence for genetic divergence among color morphs at either spatial scale. These results suggest that despite dramatic color polymorphism, this phenotypic diversity is not a major driver of genetic diversity within or among populations of ground snakes. We suggest that there are two mechanisms that could explain existing genetic diversity in ground snakes: recent range expansion from a genetically diverse founder population and current or recent gene flow among populations. Our findings have further implications for the types of color polymorphism that may generate genetic diversity in snakes. PMID:25060951

  8. SINGLE NUCLEOTIDE POLYMORPHISMS AND INDELS FOR THE DEVELOPMENT OF INTEGRATED PHYSICAL AND GENETIC MAPS OF MAIZE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (InDels) are becoming important genetic markers for major crop species. We amplified genomic regions corresponding to 678 unigenes across 12 maize inbred lines. The amplification products from 592 unigenes were sequenced (17...

  9. Associations between heat shock protein 70 genetic polymorphisms and calving traits in crossbred Brahman cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stressors such as heat, cold, toxins, and oxygen deprivation are known to induce heat shock proteins. Genetic polymorphisms associated with heat shock protein genes have been associated with decreased male and female fertility. Our objectives were to 1) confirm single nucleotide polymorphisms (SNP) ...

  10. KCNJ11: Genetic Polymorphisms and Risk of Diabetes Mellitus

    PubMed Central

    Haghvirdizadeh, Polin; Mohamed, Zahurin; Abdullah, Nor Azizan; Haghvirdizadeh, Pantea; Haerian, Monir Sadat; Haerian, Batoul Sadat

    2015-01-01

    Diabetes mellitus (DM) is a major worldwide health problem and its prevalence has been rapidly increasing in the last century. It is caused by defects in insulin secretion or insulin action or both, leading to hyperglycemia. Of the various types of DM, type 2 occurs most frequently. Multiple genes and their interactions are involved in the insulin secretion pathway. Insulin secretion is mediated through the ATP-sensitive potassium (KATP) channel in pancreatic beta cells. This channel is a heteromeric protein, composed of four inward-rectifier potassium ion channel (Kir6.2) tetramers, which form the pore of the KATP channel, as well as sulfonylurea receptor 1 subunits surrounding the pore. Kir6.2 is encoded by the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene, a member of the potassium channel genes. Numerous studies have reported the involvement of single nucleotide polymorphisms of the KCNJ11 gene and their interactions in the susceptibility to DM. This review discusses the current evidence for the contribution of common KCNJ11 genetic variants to the development of DM. Future studies should concentrate on understanding the exact role played by these risk variants in the development of DM. PMID:26448950

  11. Genetic association study between alpha 1-antichymotrypsin polymorphism and Alzheimer disease in Chinese Han population.

    PubMed

    Tang, G; Jiang, S; Zhang, M; Lin, S; Qian, Y; Wu, X; Wang, D; Jin, T; Gu, N

    2000-04-01

    We investigated a common signal peptide polymorphism in the alpha 1-antichymotrypsin (ACT) gene in 125 sporadic Alzheimer disease (AD) patients and 141 healthy control subjects in Chinese Han population. We found no significant difference in the distribution of ACT polymorphism between AD cases and controls, and failed to detect any effects of ACT genotypes associated with AD. Thus, our data do not support the involvement of ACT polymorphism in the risk of AD in Chinese Han population. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:133-135, 2000. PMID:10893483

  12. Genetic polymorphisms of human UDP-glucuronosyltransferase (UGT) genes and cancer risk.

    PubMed

    Hu, Dong Gui; Mackenzie, Peter I; McKinnon, Ross A; Meech, Robyn

    2016-02-01

    Identification of genetic polymorphisms that contribute to the risk of developing cancers is important for cancer prevention. The most recent human genome GRCh38/hg38 assembly (2013) reveals thousands of genetic polymorphisms in human uridine diphosphoglucuronosyltransferase (UGT) genes. Among these, a large number of polymorphisms at the UGT1A and UGT2B genes have been shown to modulate UGT gene promoter activity or enzymatic activity. Glucuronidation plays an important role in the metabolism and clearance of endogenous and exogenous carcinogenic compounds, and this reaction is primarily catalyzed by the UGT1A and UGT2B enzymes. Therefore, it has long been hypothesized that UGT polymorphisms that reduce the capacity to glucuronidate carcinogens and other types of cancer-promoting molecules (e.g. sex hormones) are associated with an increased risk of developing cancers. A large number of case-control studies have investigated this hypothesis and these studies identified numerous UGT polymorphisms in UGT1A and UGT2B genes as genetic risk factors for a wide variety of cancers, including bladder, breast, colorectal, endometrial, esophageal, head and neck, liver, lung, prostate, and thyroid. These UGT polymorphisms may be cancer causative polymorphisms, or be linked to as yet undefined causative polymorphisms, either in UGT genes or neighboring genes. This article presents a comprehensive review of these case-control studies, discusses current areas of uncertainty, and highlights future research directions in this field. PMID:26828111

  13. The Role of Genetic Polymorphisms in Antioxidant Enzymes and Potential Antioxidant Therapies in Neonatal Lung Disease

    PubMed Central

    Poggi, Chiara

    2014-01-01

    Abstract Significance: Oxidative stress is involved in the development of newborn lung diseases, such as bronchopulmonary dysplasia and persistent pulmonary hypertension of the newborn. The activity of antioxidant enzymes (AOEs), which is impaired as a result of prematurity and oxidative injury, may be further affected by specific genetic polymorphisms or an unfavorable combination of more of them. Recent Advances: Genetic polymorphisms of superoxide dismutase and catalase were recently demonstrated to be protective or risk factors for the main complications of prematurity. A lot of research focused on the potential of different antioxidant strategies in the prevention and treatment of lung diseases of the newborn, providing promising results in experimental models. Critical Issues: The effect of different genetic polymorphisms on protein synthesis and activity has been poorly detailed in the newborn, hindering to derive conclusive results from the observed associations with adverse outcomes. Therapeutic strategies that aimed at enhancing the activity of AOEs were poorly studied in clinical settings and partially failed to produce clinical benefits. Future Directions: The clarification of the effects of genetic polymorphisms on the proteomics of the newborn is mandatory, as well as the assessment of a larger number of polymorphisms with a possible correlation with adverse outcome. Moreover, antioxidant treatments should be carefully translated to clinical settings, after further details on optimal doses, administration techniques, and adverse effects are provided. Finally, the study of genetic polymorphisms could help select a specific high-risk population, who may particularly benefit from targeted antioxidant strategies. Antioxid. Redox Signal. 21, 1863–1880. PMID:24382101

  14. Influence of Multiple Genetic Polymorphisms on Genitourinary Morbidity After Carbon Ion Radiotherapy for Prostate Cancer

    SciTech Connect

    Suga, Tomo; Iwakawa, Mayumi; Tsuji, Hiroshi; Ishikawa, Hitoshi; Oda, Eisei; Noda, Shuhei; Otsuka, Yoshimi; Ishikawa, Atsuko; Ishikawa, Ken-Ichi; Shimazaki, Jun; Mizoe, Jun-Etsu; Tsujii, Hirohiko; Imai, Takashi

    2008-11-01

    Purpose: To investigate the genetic risk of late urinary morbidity after carbon ion radiotherapy in prostate cancer patients. Methods and Materials: A total of 197 prostate cancer patients who had undergone carbon ion radiotherapy were evaluated for urinary morbidity. The distribution of patients with dysuria was as follows: Grade 0, 165; Grade 1, 28; and Grade 2, 4 patients. The patients were divided (2:1) consecutively into the training and test sets and then categorized into control (Grade 0) and case (Grade 1 or greater) groups. First, 450 single nucleotide polymorphisms (SNPs) in 118 candidate genes were genotyped in the training set. The associations between the SNP genotypes and urinary morbidity were assessed using Fisher's exact test. Then, various combinations of the markers were tested for their ability to maximize the area under the receiver operating characteristics (AUC-ROC) curve analysis results. Finally, the test set was validated for the selected markers. Results: When the SNP markers in the SART1, ID3, EPDR1, PAH, and XRCC6 genes in the training set were subjected to AUC-ROC curve analysis, the AUC-ROC curve reached a maximum of 0.86. The AUC-ROC curve of these markers in the test set was 0.77. The SNPs in these five genes were defined as 'risk genotypes.' Approximately 90% of patients in the case group (Grade 1 or greater) had three or more risk genotypes. Conclusions: Our results have shown that patients with late urinary morbidity after carbon ion radiotherapy can be stratified according to the total number of risk genotypes they harbor.

  15. Neuroglobin Genetic Polymorphisms and Their Relationship to Functional Outcomes after Traumatic Brain Injury

    PubMed Central

    Conley, Yvette P.; Poloyac, Samuel M.; Okonkwo, David O.; Ren, Dianxu; Sherwood, Paula R.; Hravnak, Marilyn; Alexander, Sheila A.

    2010-01-01

    Abstract Neuroglobin has shown rich neuroprotective effects against cerebral hypoxia, and therefore has the potential to impact outcomes after traumatic brain injury (TBI). However, to date an association between genetic variation within the human neuroglobin (NGB) gene and recovery post-TBI has not been reported. The purpose of this study was to explore the relationship between NGB genotypes and outcomes (as assessed by the Glasgow Outcome Scale [GOS], the Disability Rating Scale [DRS], and the Neurobehavioral Rating Scale-Revised [NRS-R]) after severe TBI. Genotyping using TaqMan allele discrimination for two tagging single nucleotide polymorphisms (tSNPs) that represent the two haplotype blocks for NGB (rs3783988 and rs10133981) was completed on DNA obtained from 196 Caucasian patients recovering from severe TBI. Patients were dichotomized based on the presence of the variant allele for each tSNP. Chi-square and Fisher's exact tests were used to compare characteristics between groups. Multivariate linear regression was used to examine NGB tSNPs and recovery from severe TBI. Subjects with the TT genotype (wild-type) for rs3783988 were more likely to have better GOS and DRS scores at 3, 6, 12, and 24 months, while rs10133981 genotype was not significantly related to functional outcome. After controlling for age, gender, and Glasgow Coma Scale (GCS) score, those subjects with the rs3783988 TT genotype had more than a 2.65-times greater likelihood of better functional outcomes than individuals with genotypes harboring a variant allele. Data suggest that the haplotype block represented by rs3783988 in NGB appears to influence recovery after severe TBI. Represented within this haplotype block of NGB is the region that codes for the oxygen-binding portion of NGB. PMID:20345238

  16. Reconfiguring phosphorylation signaling by genetic polymorphisms affects cancer susceptibility.

    PubMed

    Wang, Yongbo; Cheng, Han; Pan, Zhicheng; Ren, Jian; Liu, Zexian; Xue, Yu

    2015-06-01

    Large-scale sequencing has characterized an enormous number of genetic variations (GVs), and the functional analysis of GVs is fundamental to understanding differences in disease susceptibility and therapeutic response among and within populations. Using a combination of a sequence-based predictor with known phosphorylation and protein-protein interaction information, we computationally detected 9606 potential phosSNPs (phosphorylation-related single nucleotide polymorphisms), including 720 known, disease-associated SNPs that dramatically modify the human phosSNP-associated kinase-substrate network. Further analyses demonstrated that the proteins in the network are heavily associated in various signaling and cancer pathways, while cancer genes and drug targets are significantly enriched. We re-constructed four population-specific kinase-substrate networks and found that several inherited disease or cancer genes, such as IRS1, RAF1, and EGFR, were differentially regulated by phosSNPs. Thus, phosSNPs may influence disease susceptibility and be involved in cancer development by reconfiguring phosphorylation networks in different populations. Moreover, by systematically characterizing potential phosphorylation-related cancer mutations (phosCMs) in 12 types of cancers, we observed that both types of GVs preferentially occur in the known cancer genes, while a considerable number of phosphorylated proteins, especially those over-representing cancer genes, contain both phosSNPs and phosCMs. Furthermore, it was observed that phosSNPs were significantly enriched in amplification genes identified from breast cancers and tyrosine kinase circuits of lung cancers. Taken together, these results should prove helpful for further elucidation of the functional impacts of disease-associated SNPs. PMID:25722345

  17. A Web-Based Genetic Polymorphism Learning Approach for High School Students and Science Teachers

    ERIC Educational Resources Information Center

    Amenkhienan, Ehichoya; Smith, Edward J.

    2006-01-01

    Variation and polymorphism are concepts that are central to genetics and genomics, primary biological disciplines in which high school students and undergraduates require a solid foundation. From 1998 through 2002, a web-based genetics education program was developed for high school teachers and students. The program included an exercise on using

  18. A Web-Based Genetic Polymorphism Learning Approach for High School Students and Science Teachers

    ERIC Educational Resources Information Center

    Amenkhienan, Ehichoya; Smith, Edward J.

    2006-01-01

    Variation and polymorphism are concepts that are central to genetics and genomics, primary biological disciplines in which high school students and undergraduates require a solid foundation. From 1998 through 2002, a web-based genetics education program was developed for high school teachers and students. The program included an exercise on using…

  19. RAGE Genetic Polymorphisms Are Associated with Risk, Chemotherapy Response and Prognosis in Patients with Advanced NSCLC

    PubMed Central

    Hua, Feng; Wang, Bin; Mao, Wei; Feng, Xueren

    2012-01-01

    Aim To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE) and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC). Method This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, ?429T/C, ?374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. Results All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. Conclusion The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC. PMID:23071492

  20. Preliminary study on genetic variability of Dicrocoelium dendriticum determined by random amplified polymorphic DNA.

    PubMed

    Sandoval, H; Manga-Gonzlez, Y; Campo, R; Garca, P; Castro, J M; Prez de la Vega, M

    1999-03-01

    Genetic variability of adult specimens of Dicrocoelium dendriticum has been studied using random amplified polymorphic DNA (RAPD). The worms were collected from the infected livers of different sheep from several localities in Len province (NW Spain). DNA fragments were amplified by means of decamer primer oligonucleotides of arbitrary sequence. Some primers produce complex and highly variable patterns of amplified DNA in D. dendriticum. Intra- and inter-population genetic variability of adult parasites were analyzed, scoring polymorphic and monomorphic reproducible bands by means of the Jaccard similarity, and dendrograms showing genetic relationships between individuals were obtained using the FITCH method. Genetic variability seems to be high in this parasite and genetic similarity within a population (worms infecting a single animal) is similar to the average similarity between worms from different sheep. These results suggest that each sheep is infected by numerous genetically different parasites from one or more populations of infected ants. PMID:11269322

  1. MTHFR genetic polymorphism increases the risk of preterm delivery

    PubMed Central

    Nan, Yanrong; Li, Hongmei

    2015-01-01

    Aims: This study aimed to investigate the association between the methylene tetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and premature delivery susceptibility. Methods: With matched age and gender, 108 premature delivery pregnant women as cases and 108 healthy pregnant women as controls were recruited in this case-control study. The cases and controls had same gestational weeks. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was adopted to analyze C677T and A1298C polymorphisms of the participants. Linkage disequilibrium (LD) and haplotype analysis were conducted by Haploview software. The differences for frequencies of gene type, allele and haplotypes in cases and controls were tested by chi-square test. The relevant risk of premature delivery was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: TT gene type frequency of C677T polymorphsim was higher in cases than the controls (P=0.004, OR=3.077, 95% CI=1.469-6.447), so was allele T (P=0.002, OR=1.853, 95% CI=1.265-2.716). Whereas, CC gene type of A1298C polymorphism had a lower distribution in cases than the controls (P=0.008, OR=0.095, 95% CI=0.012-0.775), so was allele C (P=0.047, OR=0.610, 95% CI=0.384-0.970). Haplotype analysis and linkage disequilibrium test conducted on the alleles of two polymorphisms in MTHFR gene, we discovered that haplotype T-A had a higher distribution in cases, which indicated that susceptible haplotype T-A was the candidate factor for premature delivery. Conclusions: Gene type TT of MTHFR C677T polymorphism might make premature delivery risk rise while gene type CC of A1298C polymorphism might have protective influence on premature delivery. PMID:26261642

  2. Genetic polymorphisms and coronary artery disease in the south of France.

    PubMed

    Canavy, I; Henry, M; Morange, P E; Tiret, L; Poirier, O; Ebagosti, A; Bory, M; Juhan-Vague, I

    2000-02-01

    Vascular disease is a multifactorial disease that involves atherosclerotic and thrombotic factors. Genetic polymorphisms have been associated with myocardial infarction and angina pectoris. The aim of the present study was to assess the relationship between some genetic polymorphisms and myocardial infarction (MI) or vasospastic angina pectoris in a population from southern France. Genetic polymorphisms of the renin angiotensin system (the D/I polymorphism of the ACE gene and the A1166C polymorphism of the angiotensin II type 1 receptor [AT1R]) and of haemostatic factors (the -675 4G/5G polymorphism of the plasminogen-activator inhibitor 1[PAI-1] gene, and the G to T common point mutation in exon 2, codon 34 of the Factor XIII A-subunit gene) were examined. We assessed the genotype distribution in consecutive coronary artery disease (CAD) patients with MI (n = 201) and vasospastic angina pectoris (n = 43) and in 244 healthy controls comparable in age, sex, body mass index and total cholesterol level. The genotype distribution of AT1R polymorphism was significantly different between controls and patients, the prevalence of the C allele carriers being higher in patients with MI after the age of 45 than in control individuals (61 vs 45%, p <0.01), leading to an odds ratio (OR) of 2 (CI: 1.2-3.4). When looking at the group of patients with vasospastic angina the difference was even higher (76 vs 45%, p <0.01) yielding an OR of 4.3 (CI: 1.4-17.4). Genotype distributions of ACE, PAI-1 and Factor XIII polymorphisms were similar in patients and in controls. This study is in favor of a role of ATIR gene polymorphism in myocardial infarction and vasospastic angina. PMID:10739375

  3. [Genetic polymorphism of FMO3 and its role in drug metabolism and toxicity].

    PubMed

    Gong, Zheng; Wang, Qi

    2015-07-01

    The flavin-containing monooxygenase 3 (FMO3) is an important hepatic microsomal enzyme. Numerous mutations of FMO3 gene have been reported, and polymorphic varients of the gene have been identified. Several studies indicated that variability in the expression of FMO3 involved in some nitrogen, or sulfur-containing durg metabolism. This review summarizes the genetic polymorphism of FMO3 and its role in drug metabolism and toxicity. PMID:26666012

  4. Genetic polymorphisms in C-reactive protein increase cancer susceptibility

    PubMed Central

    Geng, Peiliang; Sa, Rina; Li, Jianjun; Li, Hongtao; Liu, Chen; Liao, Yunmei; Xiang, Lisha; Wang, Ning; Ou, Juanjuan; Xie, Ganfeng; Liang, Houjie

    2016-01-01

    Elevated levels of C-reactive protein (CRP) partially induced by polymorphisms in the CRP gene have been associated with human cancer. The purpose of this study was to test the hypothesis that CRP gene polymorphisms (+942G>C, 1846C>T) modify inherited susceptibility to cancer. We systematically identified the publications addressing the association of CRP gene polymorphisms with cancer susceptibility. Studies that fulfilled all inclusion criteria were considered eligible in this meta-analysis. We analyzed a total of 8 case-control studies. Individuals with the CC genotype were found to have an almost 4?fold higher risk of cancer than those with the GG or GC and GG genotypes. A significant association was also indicated in subgroup of colorectal cancer. Meta-analysis of 1846C>T polymorphism showed increased cancer risk in relation to the 1846?TT genotype (TT vs. CC: OR?=?1.15, 95% CI?=?1.011.31; TT vs. CT?+?CC; OR?=?1.17, 95% CI?=?1.031.32). Similar results were suggested in Caucasian populations and colorectal cancer. These data suggest that both +942G>C and 1846C>T polymorphisms in the CRP gene may influence cancer susceptibility. PMID:26912098

  5. The evolution, maintenance and adaptive function of genetic colour polymorphism in birds.

    PubMed

    Roulin, Alexandre

    2004-11-01

    The hypothesis that ornaments can honestly signal quality only if their expression is condition-dependent has dominated the study of the evolution and function of colour traits. Much less interest has been devoted to the adaptive function of colour traits for which the expression is not, or is to a low extent, sensitive to body condition and the environment in which individuals live. The aim of the present paper is to review the current theoretical and empirical knowledge of the evolution, maintenance and adaptive function of colour plumage traits for which the expression is mainly under genetic control. The finding that in many bird species the inheritance of colour morphs follows the laws of Mendel indicates that genetic colour polymorphism is frequent. Polymorphism may have evolved or be maintained because each colour morph facilitates the exploitation of alternative ecological niches as suggested by the observation that individuals are not randomly distributed among habitats with respect to coloration. Consistent with the hypothesis that different colour morphs are linked to alternative strategies is the finding that in a majority of species polymorphism is associated with reproductive parameters, and behavioural, life-history and physiological traits. Experimental studies showed that such covariations can have a genetic basis. These observations suggest that colour polymorphism has an adaptive function. Aviary and field experiments demonstrated that colour polymorphism is used as a criterion in mate-choice decisions and dominance interactions confirming the claim that conspecifics assess each other's colour morphs. The factors favouring the evolution and maintenance of genetic variation in coloration are reviewed, but empirical data are virtually lacking to assess their importance. Although current theory predicts that only condition-dependent traits can signal quality, the present review shows that genetically inherited morphs can reveal the same qualities. The study of genetic colour polymorphism will provide important and original insights on the adaptive function of conspicuous traits. PMID:15682872

  6. Association of Polymorphism Harbored by Tumor Necrosis Factor Alpha Gene and Sex of Calf with Lactation Performance in Cattle

    PubMed Central

    Yudin, N. S.; Aitnazarov, R. B.; Voevoda, M. I.; Gerlinskaya, L. A.; Moshkin, M. P.

    2013-01-01

    In a majority of mammals, male infants have heavier body mass and grow faster than female infants. Accordingly, male offspring nursing requires a much greater maternal energy contribution to lactation. It is possible that the maternal-fetal immunoendocrine dialog plays an important role in female preparation for lactation during pregnancy. Immune system genes are an integral part of gene regulatory networks in lactation and tumor necrosis factor alpha (TNF?) is a proinflammatory cytokine that also plays an important role in normal mammary gland development. The aim of this study was to evaluate the influence of the sex of calf and/or the -824A/G polymorphism in the promoter region of TNF? gene on milk performance traits in Black Pied cattle over the course of lactation. We also studied the allele frequency differences of -824A/G variants across several cattle breeds, which were bred in different climatic conditions. The G allele frequency decreased gradually over the course of lactation events in the Black Pied dairy cattle because of a higher culling rate of cows with the G/G genotype (p<0.001). In contrast to the genotypes A/A and A/G, cows with G/G genotype showed significant variability of milk and milk fat yield subject to sex of delivered calf. Milk yield and milk fat yield were significantly higher in the case of birth of a bull calf than with a heifer calf (p<0.03). The G allele frequency varies from 48% to 58% in Grey Ukrainian and Black Pied cattle to 77% in aboriginal Yakut cattle. Our results suggest that the TNF? -824A/G gene polymorphism may have an influence on the reproductive efforts of cows over the course of lactation events depending on the sex of progeny. Allocation of resources according to sex of the calf allows optimizing the energy cost of lactation. This may be a probable reason for high G allele frequency in Yakut cattle breeding in extreme environmental conditions. Similarly, the dramatic fall in milk production after birth of a heifer calf increases the probability of culling for the cows with the G/G genotype in animal husbandry. PMID:25049721

  7. [Genetic epidemiology of schizophrenia in the population of the Tomsk region. Study of clinical polymorphism factors].

    PubMed

    Ritsner, M S; Karas', S I; Chernykh, E I

    1990-12-01

    The contribution of genetic, constitutional and environmental factors to the clinical polymorphism of schizophrenia was analysed. A sample from 353 pedigrees of the patients suffering from the manifest forms of schizophrenia which inhabited five districts of Tomsk region was studied using multifactorial threshold and single locus diallele models. It is established that the severity of the psychosis is mainly determined by autosomal genetic factors, the proportion of the affective disorders being specified by gonosomal factors. The type of the course of schizophrenia is closely connected with the patients' somatotype. Common environmental influences and peculiarities of personality before onset are linked with no characteristics of the clinical polymorphism studied. PMID:2150828

  8. A Simplified Technique for Evaluating Human "CCR5" Genetic Polymorphism

    ERIC Educational Resources Information Center

    Falteisek, Luk; Cern, Jan; Jantov, Vanda

    2013-01-01

    To involve students in thinking about the problem of AIDS (which is important in the view of nondecreasing infection rates), we established a practical lab using a simplified adaptation of Thomas's (2004) method to determine the polymorphism of HIV co-receptor CCR5 from students' own epithelial cells. CCR5 is a receptor involved in

  9. Genetic polymorphisms and retinal vein occlusion in an Italian population.

    PubMed

    De Polo, L; Maltese, P E; Rigoni, E; Bertelli, M; Cecchin, S; Staurenghi, G; Stoppa, G

    2015-01-01

    In this study, we assessed the prevalence of polymorphisms in genes involved in hyperhomocysteinemia or hemostasis to shed light on their role, if any, in retinal vein occlusion (RVO). We recruited 37 Italian patients (17 men and 20 women) with a diagnosis of central or branch RVO based on fundus examination and retinal fluorescein angiography, as well as 45 healthy controls. Risk factors and family history of RVO of all subjects were recorded. The distributions of polymorphisms in patients and controls were evaluated using the ?(2) test and OR. We confirmed an increased risk in subjects with dyslipidemia (high density lipoprotein <59 mg/dL: 17.8% of controls, 43.2% of patients, P = 0.0002; low density lipoprotein >130 mg/dL: 26.7% controls, 54.1% patients, P = 0.0002), arterial hypertension (60% controls, 75.7% patients, P = 0.023), and high body mass index (28.9% controls, 70.3% patients, P < 0.0001, and excluded involvement of the selected polymorphisms in RVO. Overall, the tested polymorphisms did not appear to be useful for assessing predisposition or for the diagnosis and prognosis of RVO. PMID:26535647

  10. Stability of underdominant genetic polymorphisms in population networks.

    PubMed

    Lruson, ki J; Reed, Floyd A

    2016-02-01

    Heterozygote disadvantage is potentially a potent driver of population genetic divergence. Also referred to as underdominance, this phenomena describes a situation where a genetic heterozygote has a lower overall fitness than either homozygote. Attention so far has mostly been given to underdominance within a single population and the maintenance of genetic differences between two populations exchanging migrants. Here we explore the dynamics of an underdominant system in a network of multiple discrete, yet interconnected, populations. Stability of genetic differences in response to increases in migration in various topological networks is assessed. The network topology can have a dominant and occasionally non-intuitive influence on the genetic stability of the system. PMID:26656110

  11. Genetic polymorphisms in TNF genes and tuberculosis in North Indians

    PubMed Central

    2010-01-01

    Background Pulmonary tuberculosis, the most common clinical form of mycobacterial diseases, is a granulomatous disease of the lungs caused by Mycobaterium tuberculosis. A number of genes have been identified in studies of diverse origins to be important in tuberculosis. Of these, both tumor necrosis factor ? (TNF-?) and lymphotoxin ? (LT-?) play important immunoregulatory roles. Methods To investigate the association of TNF polymorphisms with tuberculosis in the Asian Indians, we genotyped five potentially functional promoter polymorphisms in the TNFA gene and a LTA_NcoI polymorphism (+252 position) of the LTA gene in a clinically well-defined cohort of North-Indian patients with tuberculosis (N = 185) and their regional controls (N = 155). Serum TNF-? (sTNF-?) levels were measured and correlated with genotypes and haplotypes. Results The comparison of the allele frequencies for the various loci investigated revealed no significant differences between the tuberculosis patients and controls. Also, when the patients were sub-grouped into minimal, moderately advanced and far advanced disease on the basis of chest radiographs, TST and the presence/absence of cavitary lesions, none of the polymorphisms showed a significant association with any of the patient sub-groups. Although a significant difference was observed in the serum TNF-? levels in the patients and the controls, none of the investigated polymorphisms were found to affect the sTNF-? levels. Interestingly, it was observed that patients with minimal severity were associated with lower log sTNF-? levels when compared to the patients with moderately advanced and far advanced severity. However, none of these differences were found to be statistically significant. Furthermore, when haplotypes were analyzed, no significant difference was observed. Conclusions Thus, our findings exclude the TNF genes as major risk factor for tuberculosis in the North Indians. PMID:20537163

  12. Genetic polymorphisms in the vitamin D pathway in relation to lung cancer risk and survival

    PubMed Central

    Kong, Jinyu; Xu, Fangxiu; Qu, Jinli; Wang, Yu; Gao, Ming; Yu, Herbert; Qian, Biyun

    2015-01-01

    Studies have suggested that vitamin D may have protective effects against cancer development or tumor progression. To search for additional evidence, we investigated the role of genetic polymorphisms involved in the vitamin D pathway in non-small cell lung cancer (NSCLC). We evaluated common genetic polymorphisms associated with the vitamin D pathway in relation to NSCLC in a case-control study of 603 newly diagnosed NSCLC patients and 661 matched healthy controls. Seven single nucleotide polymorphisms (SNPs) were genotyped, the expression of CYP27B1 and CYP24A1 were measured in 153 tumor samples and their associations with genotypes and patient survival were also analyzed. In the case-control comparison, we found SNP rs3782130 (CYP27B1), rs7041 (GC), rs6068816 and rs4809957 (CYP24A1) associated with NSCLC risk. The risk of NSCLC was increased with the number of risk alleles. CYP27B1 and CYP24A1 expression were significantly different between tumor and normal tissues in NSCLC. High CYP27B1 expression was associated with better overall survival, and the expression was different by the rs3782130 genotype. The study suggests that some genetic polymorphisms involved in the vitamin D pathway may associate with NSCLC risk, and one of the polymorphisms (rs3782130) may affect gene expression and patient survival. PMID:25544771

  13. Genetic polymorphisms in the vitamin D pathway in relation to lung cancer risk and survival.

    PubMed

    Kong, Jinyu; Xu, Fangxiu; Qu, Jinli; Wang, Yu; Gao, Ming; Yu, Herbert; Qian, Biyun

    2015-02-10

    Studies have suggested that vitamin D may have protective effects against cancer development or tumor progression. To search for additional evidence, we investigated the role of genetic polymorphisms involved in the vitamin D pathway in non-small cell lung cancer (NSCLC). We evaluated common genetic polymorphisms associated with the vitamin D pathway in relation to NSCLC in a case-control study of 603 newly diagnosed NSCLC patients and 661 matched healthy controls. Seven single nucleotide polymorphisms (SNPs) were genotyped, the expression of CYP27B1 and CYP24A1 were measured in 153 tumor samples and their associations with genotypes and patient survival were also analyzed. In the case-control comparison, we found SNP rs3782130 (CYP27B1), rs7041 (GC), rs6068816 and rs4809957 (CYP24A1) associated with NSCLC risk. The risk of NSCLC was increased with the number of risk alleles. CYP27B1 and CYP24A1 expression were significantly different between tumor and normal tissues in NSCLC. High CYP27B1 expression was associated with better overall survival, and the expression was different by the rs3782130 genotype. The study suggests that some genetic polymorphisms involved in the vitamin D pathway may associate with NSCLC risk, and one of the polymorphisms (rs3782130) may affect gene expression and patient survival. PMID:25544771

  14. Paraoxonase1 Genetic Polymorphisms in a Mixed Ancestry African Population

    PubMed Central

    Macharia, M.; Kengne, A. P.; Blackhurst, D. M.; Erasmus, R. T.; Matsha, T. E.

    2014-01-01

    Paraoxonase 1 (PON1) activity is markedly influenced by coding polymorphisms, Q/R at position 192 and M/L at position 55 of the PON1 gene. We investigated the frequencies of these polymorphisms and their effects on PON1 and antioxidant activities in 844 South African mixed ancestry individuals. Genotyping was done using allele-specific TaqMan technology, PON1 activities were measured using paraoxon and phenylacetate, oxidative status was determined by measuring the antioxidant activities of ferric reducing antioxidant power and trolox equivalent antioxidant capacity, and lipid peroxidation markers included malondialdehyde and oxidized LDL. The frequencies of Q192R and L55M were 47.6% and 28.8%, respectively, and the most common corresponding alleles were 192R (60.4%) and 55M (82.6%). The Q192 was significantly associated with 5.8 units' increase in PON1 concentration and 15.4 units' decrease in PONase activity after adjustment for age, sex, BMI, and diabetes, with suggestion of differential effects by diabetes status. The PON1 L55 variant was associated with none of the measured indices. In conclusion, we have shown that the Q192R polymorphism is a determinant of both PON1 concentration and activity and this association appeared to be enhanced in subjects with diabetes. PMID:25477710

  15. [Genetic polymorphisms: implications in the pathogenesis of medullary thyroid carcinoma].

    PubMed

    Rocha, Andreia Possatti da; Magalhães, Patrícia K Ribeiro; Maia, Ana Luiza; Maciel, Lea Maria Zanini

    2007-07-01

    Medullary thyroid carcinoma (MTC) is a rare malignant neoplasia, which may occur on sporadic form or on a hereditary basis. Germ line mutations in the RET proto-oncogene is responsible for hereditary MTC. However, most MTC occur in individuals without family history where the pathogenesis is still unclear. Single nucleotide polymorphisms (SNPs) of the RET gene have been described in the general population as well as in patients with MTC. Even though these allelic variants do not seem to confer any transforming activity to the tyrosine kinase domain of the RET protein, cumulative studies suggest that they could modify disease susceptibility and clinical phenotype in patients with sporadic or hereditary MTC. Polymorphisms located in exons 11 (G691S), 13 (L769L), 14 (S836S), and 15 (S904S) seem to be over-represented in sporadic MTC patients from American and European countries. Here, we discuss the results obtained in different studies as well as describe the frequency of RET polymorphisms in Brazilian patients with sporadic MTC. PMID:17891235

  16. Genetic mapping of the human tryptophan hydroxylase gene on chromosome 11, using an intronic conformational polymorphism

    SciTech Connect

    Nielsen, D.A.; Goldman, D. ); Dean, M. )

    1992-12-01

    The identification of polymorphic alleles at loci coding for functional genes is crucial for genetic association and linkage studies. Since the tryptophan hydroxylase (TPH) gene codes for the rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin, it would be advantageous to identify a polymorphism in this gene. By examining introns of the human TPH gene by PCR amplification and analysis by the single-strand conformation polymorphism (SSCP) technique, an SSCP was revealed with two alleles that occur with frequencies of .40 and .60 in unrelated Caucasians. DNAs from 24 informative CEPH families were typed for the TPH intron polymorphism and analyzed with respect to 10 linked markers on chromosome 11, between p13 and p15, with the result that TPH was placed between D11S151 and D11S134. This region contains loci for several important genes, including those for Beckwith-Wiedemann syndrome and tyrosine hydroxylase. 37 refs., 2 figs., 1 tab.

  17. Genetic mapping of the human tryptophan hydroxylase gene on chromosome 11, using an intronic conformational polymorphism.

    PubMed Central

    Nielsen, D A; Dean, M; Goldman, D

    1992-01-01

    The identification of polymorphic alleles at loci coding for functional genes is crucial for genetic association and linkage studies. Since the tryptophan hydroxylase (TPH) gene codes for the rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin, it would be advantageous to identify a polymorphism in this gene. By examining introns of the human TPH gene by PCR amplification and analysis by the single-strand conformational polymorphism (SSCP) technique, an SSCP was revealed with two alleles that occur with frequencies of .40 and .60 in unrelated Caucasians. DNAs from 24 informative CEPH families were typed for the TPH intron polymorphism and analyzed with respect to 10 linked markers on chromosome 11, between p13 and p15, with the result that TPH was placed between D11S151 and D11S134. This region contains loci for several important genes, including those for Beckwith-Wiedemann syndrome and tyrosine hydroxylase. Images Figure 1 PMID:1463016

  18. Genetic diversity and relationship of chicory (Cichorium intybus L.) using sequence-related amplified polymorphism markers.

    PubMed

    Liang, X Y; Zhang, X Q; Bai, S Q; Huang, L K; Luo, X M; Ji, Y; Jiang, L F

    2014-01-01

    Chicory is a crop with economically important roles and is cultivated worldwide. The genetic diversity and relationship of 80 accessions of chicories and endives were evaluated by sequence-related amplified polymorphism (SRAP) markers to provide a theoretical basis for future breeding programs in China. The polymorphic rate was 96.83%, and the average polymorphic information content was 0.323, suggesting the rich genetic diversity of chicory. The genetic diversity degree of chicory was higher (GS = 0.677) than that of endive (GS = 0.701). The accessions with the highest genetic diversity (effective number of alleles, NE = 1.609; Nei's genetic diversity, H = 0.372; Shannon information index, I = 0.556) were from Italy. The richest genetic diversity was revealed in a chicory line (NE = 1.478, H = 0.289, I = 0.443) among the 3 types (line, wild, and cultivar). The chicory genetic structure of 8 geographical groups showed that the genetic differentiation coefficient (GST) was 14.20% and the number of immigrants per generation (Nm) was 3.020. A GST of 6.80% and an Nm of 6.853 were obtained from different types. This observation suggests that these chicory lines, especially those from the Mediterranean region, have potential for providing rich genetic resources for further breeding programs, that the chicory genetic structure among different countries obviously differs with a certain amount of gene flow, and that SRAP markers could be applied to analyze genetic relationships and classifications of Cichorium intybus and C. endivia. PMID:25299087

  19. Population genetics of speciation in nonmodel organisms: I. Ancestral polymorphism in mangroves.

    PubMed

    Zhou, Renchao; Zeng, Kai; Wu, Wei; Chen, Xiaoshu; Yang, Ziheng; Shi, Suhua; Wu, Chung-I

    2007-12-01

    The level of DNA polymorphism in the ancestral species at the time of speciation can be estimated using DNA sequences from many loci sampled from 2 or more extant species. The comparison between ancestral and extant polymorphism can be informative about the population genetics of speciation. In this study, we collected and analyzed DNA sequences of approximately 60 genes from 4 species of Sonneratia, a common genus of mangroves on the Indo-Pacific coasts. We found that the 3 ancestral species were comparable to each other in terms of level of polymorphism. However, the ancestral species at the time of speciation were substantially more polymorphic than the extant geographical populations. This ancestral polymorphism is in fact larger than, or at least equal to, the level of polymorphism of the entire species across extant geographical populations. The observations are not fully compatible with speciation by strict allopatry. We suggest that, at the time of speciation, the ancestral species consisted of interconnected but strongly divided geographical populations. This population structure would give rise to high level of polymorphism across species range. This approach of studying the speciation history by genomic means should be applicable to nonmodel organisms. PMID:17906000

  20. Genetic polymorphisms associated with overweight and obesity in uncontrolled Type 2 diabetes mellitus.

    PubMed

    Kasim, Nor Bahirah; Huri, Hasniza Zaman; Vethakkan, Shireene Ratna; Ibrahim, Luqman; Abdullah, Bashar Mudhaffar

    2016-04-01

    Generally, obese and overweight individuals display higher free fatty acid levels, which stimulate insulin resistance. The combination of overweight or obesity with insulin resistance can trigger Type 2 diabetes mellitus (T2DM) and are primary contributing factors to the development of uncontrolled T2DM. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to becoming overweight or obese and developing related chronic complications, such as uncontrolled T2DM. This review specifically examines the genetic polymorphisms associated with overweight and obesity in patients with uncontrolled T2DM. Particularly, gene polymorphisms in ADIPOQ (rs1501299 and rs17300539), LepR (rs1137101 and rs1045895), IRS2 (rs1805092), GRB14 (rs10195252 and rs3923113) and PPARG (rs1801282) have been associated with overweight and obesity in uncontrolled T2DM. PMID:26999420

  1. A RAPD method to detect genetic polymorphisms in fish from environmentally impacted areas

    SciTech Connect

    Gordon, D.A.; Wessendarp, T.; Roth, A.C.; Smith, M.K.; Lattier, D.L.; Leonard, A.; Hertzberg, V.

    1994-12-31

    Random Amplified Polymorphic DNA (RAPD), an application of the polymerase chain reaction (PCR), has been used to detect genetic polymorphisms between and within species. Using the method presented here, the authors are attempting to generate statistically significant indices of population heterozygosity for Brown Bullhead catfish from two ecologically impacted inland waterways, the Black and Cuyahoga Rivers, and one reference river, Old Woman Creek. Genomic DNA, purified from nucleated red blood cells (RBCs), was randomly amplified (PCR) using 10 base oligonucleotide primers in an optimized protocol developed in this laboratory. Simplified products were electrophoretically separated in 1.65% agarose containing ethidium bromide. Following electrophoresis, agarose gels were UV irradiated and photographed with positive-negative film. The negatives were processed per manufacturer`s instructions and scanned with a densitometer. Densitometric results were then analyzed with a quantitative analysis computer program. Banding patterns among those individuals analyzed exemplify substantial polymorphisms, which may be used to assess degrees of genetic diversity in a population.

  2. Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus.

    PubMed

    Zhao, Jian; Wu, Hui; Langefeld, Carl D; Kaufman, Kenneth M; Kelly, Jennifer A; Bae, Sang-Cheol; Alarcn, Graciela S; Anaya, Juan-Manuel; Criswell, Lindsey A; Freedman, Barry I; Kamen, Diane L; Gilkeson, Gary S; Jacob, Chaim O; James, Judith A; Merrill, Joan T; Gaffney, Patrick M; Sivils, Kathy Moser; Niewold, Timothy B; Petri, Michelle A; Song, Seung Taek; Jeong, Hye-Jin; Ramsey-Goldman, Rosalind; Reveille, John D; Scofield, R Hal; Stevens, Anne M; Boackle, Susan A; Vil, Luis M; Chang, Deh-Ming; Song, Yeong Wook; Vyse, Timothy J; Harley, John B; Brown, Elizabeth E; Edberg, Jeffrey C; Kimberly, Robert P; Hahn, Bevra H; Grossman, Jennifer M; Tsao, Betty P; La Cava, Antonio

    2015-12-01

    Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE. PMID:26385092

  3. Flavin-containing monooxygenase genetic polymorphism: impact on chemical metabolism and drug development.

    PubMed

    Koukouritaki, Sevasti B; Hines, Ronald N

    2005-12-01

    The flavin-containing monooxygenases (FMOs) metabolize a broad range of therapeutics. Consisting of five gene products in humans (FMO1-5), the different FMO family members exhibit pronounced tissue- and temporal-specific expression patterns. Substantial interindividual differences are also observed, and the inability to modulate with exogenous agents is consistent with an important role for genetic variation. Several rare FMO3 alleles causative for trimethylaminuria have been well characterized. However, the identification and characterization of functional FMO1-5 polymorphisms has been more recent. Although none of these polymorphisms has been associated with an adverse drug reaction, the continued broadening of our therapeutic armamentarium makes such an event likely in the future. Furthermore, at least one example has been reported for a direct association between FMO3 polymorphism and therapeutic efficacy. Thus, it is anticipated that knowledge regarding functionally-relevant FMO genetic variability will become increasingly important for making drug development and patient therapeutic choices. PMID:16296944

  4. Functional Characterization of Genetic Polymorphisms Identified in the Promoter Region of the Bovine PEPS Gene

    PubMed Central

    Ju, Zhihua; Zheng, Xue; Huang, Jinming; Qi, Chao; Zhang, Yan; Li, Jianbin

    2012-01-01

    Peptidase S (PEPS) is a metallopeptidase that cleaves N-terminal residues from proteins and peptides. PEPS is used as a cell maintenance enzyme with critical roles in peptide turnover. The promoter region located upstream of the initiation site plays an important role in regulating gene expression. Polymorphism in the promoter region can alter gene expression and lead to biological changes. In the current study, polymorphisms in the promoter region of the PEPS gene were investigated. Polymerase chain reaction (PCR)-restriction fragment length polymorphism and DNA sequencing methods were used to screen sequence variations in the promoter region of DNA samples from 743 Chinese Holstein cattle. Two polymorphisms (g. ?534 T>C and g. ?2545 G>A) were identified and eight haplotypes were classified by haplotype analysis. The two genetic polymorphisms and haplotypes were associated with fat percentage and somatic cell score in Chinese Holstein cattle. The results of real-time PCR showed that cow kidneys exhibit the highest PEPS expression level. Moreover, bioinformatics analysis predicted that the single-nucleotide polymorphism g. ?534 T>C is located in the core promoter region and in the transcription factor binding sites. The promoter activities of the polymorphism of ?543 T>C were measured by luciferase assay in the human kidney epithelial cell line 293T. Transcriptional activity is significantly lower in cell lines transfected with the reporter construct containing 2.5?kb upstream fragments with ?543 C than in those with wild-type ?543 T. The results indicated that genetic variation at locus ?543 influences PEPS promoter activity. The genetic variation in the promoter region of PEPS gene may regulate PEPS gene transcription and might have consequences at a regulatory level. PMID:22304649

  5. A genetic linkage study of facioscapulohumeral (Landouzy-Djrine) disease with 24 polymorphic DNA probes.

    PubMed Central

    Upadhyaya, M; Sarfarazi, M; Lunt, P W; Broadhead, W; Harper, P S

    1989-01-01

    From analysis of DNA polymorphisms in a panel of 455 subjects from 25 families with facioscapulohumeral (Landouzy-Djrine) disease, we have found no evidence for close linkage of the disease at 24 different genetic loci, including one from a candidate chromosomal region. Added to previous data, our results provide direction for future collaborative linkage studies. PMID:2570156

  6. The application and performance of single nucleotide polymorphism markers for population genetic analyses of Lepidoptera

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Single nucleotide polymorphisms (SNPs) are nucleotide substitution mutations that tend to be at high densities within eukaryotic genomes. The development of assays that detect allelic variation at SNP loci is attractive for genome mapping, population genetics, and phylogeographic applications. A p...

  7. Genetic polymorphism of LDLR (rs688) is associated with primary intracerebral hemorrhage.

    PubMed

    Lee, Jiann-Der; Hsiao, Kuang-Ming; Lee, Tsong-Hai; Kuo, Ya-Wen; Huang, Yen-Chu; Hsu, Huan-Lin; Lin, Ya-Hui; Wu, Chih-Ying; Huang, Ying-Chih; Lee, Meng; Yang, Hsin-Ta; Hsu, Chia-Yu; Pan, Yi-Ting

    2014-02-01

    Intracranial hemorrhage is the third most common cause of cerebrovascular disease. Some polymorphisms that affect clotting factors increase the risk of thrombosis. However, few reports have analyzed the effect of polymorphisms on the hemostatic state in bleeding disorders. The low-density lipoprotein receptor (LDLR) has been shown to contribute to factor VIII (FVIII) homeostasis, which represents a link between LDLR and hemostasis. FVIII plays a pivotal role in the coagulation cascade. Patients with high levels of FVIII are at an increased risk of arterial and venous thrombosis. On the other hand, patients with insufficient FVIII tend to bleed excessively, such as in hemophilia A. In a previous study, analysis of the genetic LDLR variant rs688 provided evidence suggesting that genetic polymorphisms of rs688 are associated with thrombotic cardiovascular diseases. The current study aimed to investigate the potential role of rs688 in primary intracerebral hemorrhage (PICH). This genetic association study was conducted within an isolated Taiwanese population (447 PICH patients and 430 controls). Genotypes C/C and C/T were used as the reference genotypes, and the genotype T/T was found to be associated with a 73% decreased risk of PICH. The preliminary evidence suggests that genetic polymorphisms of LDLR are associated with PICH. PMID:24295502

  8. Genetic Variation Between Two Cucumber Genotypes Inferred from Genome-wide Microsatellite Polymorphism Analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Variability at microsatellite loci has been used widely to infer the extent of genetic diversity among related plant taxa. However, typically, only the most polymorphic loci in the genome were analyzed that may result in a biased, and generally overestimated picture of genome-wide microsatellite div...

  9. Association between interleukin-22 genetic polymorphisms and bladder cancer risk

    PubMed Central

    Zhao, Tao; Wu, XiaoHou; Liu, JiaJi

    2015-01-01

    OBJECTIVE: The cytokine interleukin-22 (IL-22), which is produced by T cells and natural killer cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in bladder cancer has not been investigated. MATERIALS AND METHODS: A prospective hospital-based case-control study comprising 210 patients with pathologically proven bladder cancer and 210 age- and gender-matched healthy controls was conducted. The genotypes of 3 common polymorphisms (-429 C/T, +1046 T/A and +1995 A/C) of the IL-22 gene were determined with fluorogenic 5' exonuclease assays. RESULTS: Patients with bladder cancer had a significantly higher frequency of the IL-22 -429 TT genotype [odds ratio (OR)=2.04, 95% confidence interval (CI)=1.19, 3.49; p=0.009] and -429 T allele (OR=1.42, 95% CI=1.08, 1.87; p=0.01) than the healthy controls. These findings were still significant after a Bonferroni correction. When stratifying according to the stage of bladder cancer, we found that patients with superficial bladder cancer had a significantly lower frequency of the IL-22 -429 TT genotype (OR=0.48, 95% CI=0.23, 0.98; p=0.04). When stratifying according to the grade and histological type of bladder cancer, we found no statistical association. The IL-22 +1046 T/A and IL-22 +1995 A/C gene polymorphisms were not associated with the risk of bladder cancer. CONCLUSION: To the authors' knowledge, this is the first report documenting that the IL-22 -429 C/T gene polymorphism is associated with bladder cancer risk. Additional studies are required to confirm this finding. PMID:26598081

  10. Development and characterization of highly polymorphic long TC repeat microsatellite markers for genetic analysis of peanut

    PubMed Central

    2012-01-01

    Background Peanut (Arachis hypogaea L.) is a crop of economic and social importance, mainly in tropical areas, and developing countries. Its molecular breeding has been hindered by a shortage of polymorphic genetic markers due to a very narrow genetic base. Microsatellites (SSRs) are markers of choice in peanut because they are co-dominant, highly transferrable between species and easily applicable in the allotetraploid genome. In spite of substantial effort over the last few years by a number of research groups, the number of SSRs that are polymorphic for A. hypogaea is still limiting for routine application, creating the demand for the discovery of more markers polymorphic within cultivated germplasm. Findings A plasmid genomic library enriched for TC/AG repeats was constructed and 1401 clones sequenced. From the sequences obtained 146 primer pairs flanking mostly TC microsatellites were developed. The average number of repeat motifs amplified was 23. These 146 markers were characterized on 22 genotypes of cultivated peanut. In total 78 of the markers were polymorphic within cultivated germplasm. Most of those 78 markers were highly informative with an average of 5.4 alleles per locus being amplified. Average gene diversity index (GD) was 0.6, and 66 markers showed a GD of more than 0.5. Genetic relationship analysis was performed and corroborated the current taxonomical classification of A. hypogaea subspecies and varieties. Conclusions The microsatellite markers described here are a useful resource for genetics and genomics in Arachis. In particular, the 66 markers that are highly polymorphic in cultivated peanut are a significant step towards routine genetic mapping and marker-assisted selection for the crop. PMID:22305491

  11. Genetic association of apolipoprotein E polymorphisms with inflammatory bowel disease

    PubMed Central

    Al-Meghaiseeb, Ebtissam Saleh; Al-Otaibi, Mulfi Mubarak; Al-Robayan, Abdulrahman; Al-Amro, Reem; Al-Malki, Ahmd Saad; Arfin, Misbahul; Al-Asmari, Abdulrahman K

    2015-01-01

    AIM: To study the association of apolipoprotein E (APOE) polymorphisms with the susceptibility of inflammatory bowel disease (IBD) in Saudi patients. METHODS: APOE genotyping was performed to evaluate the allele and genotype frequencies in 378 Saudi subjects including IBD patients with ulcerative colitis (n = 84) or Crohns disease (n = 94) and matched controls (n = 200) using polymerase chain reaction and reverse-hybridization techniques. RESULTS: The frequencies of the APOE ?2 allele and ?2/?3 and ?2/?4 genotypes were significantly higher in IBD patients than in controls (P < 0.05), suggesting that the ?2 allele and its heterozygous genotypes may increase the susceptibility to IBD. On the contrary, the frequencies of the ?3 allele and ?3/?3 genotype were lower in IBD patients as compared to controls, suggesting a protective effect of APOE ?3 for IBD. The prevalence of the ?4 allele was also higher in the patient group compared to controls, suggesting that the ?4 allele may also increase the risk of IBD. Our results also indicated that the APOE ?4 allele was associated with an early age of IBD onset. No effect of gender or type of IBD (familial or sporadic) on the frequency distribution of APOE alleles and genotypes was noticed in this study. CONCLUSION: APOE polymorphism is associated with risk of developing IBD and early age of onset in Saudi patients, though further studies with a large-size population are warranted. PMID:25624723

  12. Genetic polymorphisms of flavin-containing monooxygenase (FMO).

    PubMed

    Krueger, Sharon K; Williams, David E; Yueh, Mei-Fei; Martin, Sarah R; Hines, Ronald N; Raucy, Judy L; Dolphin, Colin T; Shephard, Elizabeth A; Phillips, Ian R

    2002-08-01

    Mammalian flavin-containing monooxygenase (FMO) exists as six gene families and metabolizes a plethora of drugs and xenobiotics. The major FMO in adult human liver, FMO3, is responsible for trimethylamine (TMA) N-oxygenation. A number of FMO3 mutant alleles have been described and associated with a disease termed trimethylaminuria (TMAU). The TMAU patient excretes large amounts of TMA in urine and sweat. A more recent ethnically related polymorphism in expression of the major FMO in lung, FMO2, has been described. All Caucasians and Asians genotyped to date are homozygous for a CAG --> TAG amber mutation resulting in a premature stop codon and a nonfunctional protein truncated at AA 472 (wildtype FMO2 is 535 AA). This allele has been designated hFMO2*2A. Twenty-six percent of individuals of African descent and 5% of Hispanics genotyped to date carry at least one allele coding for full-length FMO2 (hFMO2*1 allele). Preliminary evidence indicates that FMO2.1 is very active toward the S-oxygenation of low MW thioureas, including the lung toxicant ethylene thiourea. Polymorphic expression of functional FMO2 in the individuals of African and Hispanic descent may markedly influence drug metabolism and/or xenobiotic toxicity in the lung. PMID:12214664

  13. Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus

    PubMed Central

    Banerjee, Monisha; Saxena, Madhukar

    2014-01-01

    Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia, dyslipidemia, stroke and several other complications. Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes (T2DM). Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases, including T2DM. Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms (SNPs). The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities. This will lead to the understanding of the role of cytokine genes in T2DM risk and development. Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s) for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications. This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease. Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM. PMID:25126395

  14. Analysis of genetic diversity identified by amplified fragment length polymorphism marker in hybrid wheat.

    PubMed

    Ejaz, M; Qidi, Z; Gaisheng, Z; Na, N; Huiyan, Z; Qunzhu, W

    2015-01-01

    Amplified fragment length polymorphism markers were used to assess genetic diversity in 10 male sterile wheat crop lines (hetero-cytoplasm with the same nucleus) in relation to a restorer wheat line. These male sterile lines were evaluated using 64 amplified fragment length polymorphism primer combinations, and 13 primers produced polymorphic bands, generating a total 682 fragments. Of the 682 fragments, 113 were polymorphic. The polymorphic information content and marker index values demonstrated the utility of the primer combinations used in the present study. Unweighted pair group method with arithmetic mean and principal coordinate analysis of the genotypic data revealed clustering of accessions based on genetic relationships, and accessions were separated into 2 groups with their restorer line. Jaccard's similarity coefficient values suggested good variability among the male sterile lines, indicating their utility in breeding programs. The fallouts of analysis of molecular variance showed large within-group population variation, accounting for 77% of variation, while among-group comparison accounted for 23% of the total molecular variation, which was statistically significant. The molecular diversity observed in this study will be useful for selecting appropriate accessions for plant improvement and hybridization through molecular-breeding approaches and for developing suitable conservation strategies. PMID:26345825

  15. Footprints of ancient-balanced polymorphisms in genetic variation data from closely related species.

    PubMed

    Gao, Ziyue; Przeworski, Molly; Sella, Guy

    2015-02-01

    When long-lasting, balancing selection can lead to "trans-species" polymorphisms that are shared by two or more species identical by descent. In such cases, the gene genealogy at the selected site clusters by allele instead of by species, and nearby neutral sites also have unusual genealogies because of linkage. While this scenario is expected to leave discernible footprints in genetic variation data, the specific patterns remain poorly characterized. Motivated by recent findings in primates, we focus on the case of a biallelic polymorphism under ancient balancing selection and derive approximations for summaries of the polymorphism data from two species. Specifically, we characterize the length of the segment that carries most of the footprints, the expected number of shared neutral single nucleotide polymorphisms (SNPs), and the patterns of allelic associations among them. We confirm the accuracy of our approximations by coalescent simulations. We further show that for humans and chimpanzees-more generally, for pairs of species with low genetic diversity levels-these patterns are highly unlikely to be generated by neutral recurrent mutations. We discuss the implications for the design and interpretation of genome scans for ancient balanced polymorphisms in primates and other taxa. PMID:25403856

  16. Footprints of ancient-balanced polymorphisms in genetic variation data from closely related species

    PubMed Central

    Gao, Ziyue; Przeworski, Molly; Sella, Guy

    2015-01-01

    When long-lasting, balancing selection can lead to trans-species polymorphisms that are shared by two or more species identical by descent. In such cases, the gene genealogy at the selected site clusters by allele instead of by species, and nearby neutral sites also have unusual genealogies because of linkage. While this scenario is expected to leave discernible footprints in genetic variation data, the specific patterns remain poorly characterized. Motivated by recent findings in primates, we focus on the case of a biallelic polymorphism under ancient balancing selection and derive approximations for summaries of the polymorphism data from two species. Specifically, we characterize the length of the segment that carries most of the footprints, the expected number of shared neutral single nucleotide polymorphisms (SNPs), and the patterns of allelic associations among them. We confirm the accuracy of our approximations by coalescent simulations. We further show that for humans and chimpanzeesmore generally, for pairs of species with low genetic diversity levelsthese patterns are highly unlikely to be generated by neutral recurrent mutations. We discuss the implications for the design and interpretation of genome scans for ancient balanced polymorphisms in primates and other taxa. PMID:25403856

  17. Genetic Diversity Analysis of South and East Asian Duck Populations Using Highly Polymorphic Microsatellite Markers

    PubMed Central

    Seo, Dongwon; Bhuiyan, Md. Shamsul Alam; Sultana, Hasina; Heo, Jung Min; Lee, Jun Heon

    2016-01-01

    Native duck populations have lower productivity, and have not been developed as much as commercials duck breeds. However, native ducks have more importance in terms of genetic diversity and potentially valuable economic traits. For this reason, population discriminable genetic markers are needed for conservation and development of native ducks. In this study, 24 highly polymorphic microsatellite (MS) markers were investigated using commercial ducks and native East and South Asian ducks. The average polymorphic information content (PIC) value for all MS markers was 0.584, indicating high discrimination power. All populations were discriminated using 14 highly polymorphic MS markers by genetic distance and phylogenetic analysis. The results indicated that there were close genetic relationships among populations. In the structure analysis, East Asian ducks shared more haplotypes with commercial ducks than South Asian ducks, and they had more independent haplotypes than others did. These results will provide useful information for genetic diversity studies in ducks and for the development of duck traceability systems in the market. PMID:26949947

  18. Genetic Diversity Analysis of South and East Asian Duck Populations Using Highly Polymorphic Microsatellite Markers.

    PubMed

    Seo, Dongwon; Bhuiyan, Md Shamsul Alam; Sultana, Hasina; Heo, Jung Min; Lee, Jun Heon

    2016-04-01

    Native duck populations have lower productivity, and have not been developed as much as commercials duck breeds. However, native ducks have more importance in terms of genetic diversity and potentially valuable economic traits. For this reason, population discriminable genetic markers are needed for conservation and development of native ducks. In this study, 24 highly polymorphic microsatellite (MS) markers were investigated using commercial ducks and native East and South Asian ducks. The average polymorphic information content (PIC) value for all MS markers was 0.584, indicating high discrimination power. All populations were discriminated using 14 highly polymorphic MS markers by genetic distance and phylogenetic analysis. The results indicated that there were close genetic relationships among populations. In the structure analysis, East Asian ducks shared more haplotypes with commercial ducks than South Asian ducks, and they had more independent haplotypes than others did. These results will provide useful information for genetic diversity studies in ducks and for the development of duck traceability systems in the market. PMID:26949947

  19. Effect of CYP1A1 and GSTM1 genetic polymorphisms on bone tumor susceptibility.

    PubMed

    Li, L; Li, J G; Liu, C Y; Ding, Y J

    2015-01-01

    Tumor gene polymorphisms are often associated with individual susceptibility to genetic diseases. Cytochrome P4501A1 (CYP1A1) and glutathione S-transferase mu 1 (GSTM1) gene polymorphisms are closely related to the susceptibility of the body to chemical carcinogens in the environment. Therefore, we explored the relationship between CYP1A1 and GSTM1 gene polymorphisms and susceptibility to bone tumors. Multiplex-polymerase chain reaction (PCR), allelic-specific PCR, and PCR-restriction fragment length polymorphism techniques were used to analyze CYP1A1 and GSTM1 gene polymorphisms in 52 bone tumor patients and 100 healthy subjects. The allelic variation frequency of the CYP1A1 gene at exon 7 (Ile 462 Val) in bone tumor patients was 0.462, which was significantly higher than that in the normal controls (0.223). The frequency of the absence of the GSTM1 homozygous genotype in the patients (0.65) was also markedly higher than that in the control group (0.41). Subjects with CYP1A1 Val/Val homozygous mutations and absence of the GSTM1 homozygous genotype were at markedly increased risk of developing bone tumors [ORs 4.15 (95%CI: 1.268-13.30) and 2.35 (95%CI: 1.15-4.85), respectively]. The OR for the combined effect of the CYP1A1 and GSTM1 gene polymorphisms was 8.55 (95%CI: 1.75-41.50). CYP1A1 and GSTM1 polymorphisms are genetic risk factors in patients with bone tumors, and the allelic variation of these genes increases the risk of bone tumor occurrence. PMID:26681006

  20. Physical-capacity-related genetic polymorphisms in children with cystic fibrosis.

    PubMed

    Yvert, Thomas; Santiago, Catalina; Santana-Sosa, Elena; Verde, Zoraida; Gmez-Gallego, Felix; Lpez-Mojares, Luis M; Prez, Margarita; Garatachea, Nuria; Lucia, Alejandro

    2015-02-01

    In patients with cystic fibrosis (CF), physical capacity (PC) has been correlated with mortality risk. In turn, PC is dependent on genetic factors. This study examines several polymorphisms associated with PC and health-related phenotype traits (VO2peak, FEV1, FVC, PImax and muscular strength) in a group of children with CF (n = 66, primary purpose). The same analyses were also performed in a control group of healthy children (n = 113, secondary purpose). The polymorphisms determined were classified as muscle function polymorphisms (ACE rs1799752; AGT rs699; ACTN3 rs1815739; PTK2 rs7843014 and rs7460; MSTN rs1805086; TRHR rs7832552; NOS3 rs2070744) or energy metabolism polymorphisms (PPARGC1A rs8192678; NRF1 rs6949152; NRF2 rs12594956; TFAM rs1937; PPARD rs2267668; ACSL1 rs6552828). No significant polymorphism/phenotype correlations were detected in children with CF, with marginal associations being observed between NOS3 rs2070744 and VO2peak and FEV1, as well as between PPARGC1A rs8192678 and FEV1. Overall, similar findings were observed in the control group, i.e., no major associations. The PC-related polymorphisms examined seem to have no effects on the PC or health of children with CF. PMID:25051205

  1. Functional genetic polymorphisms and female reproductive disorders: Part IIendometriosis

    PubMed Central

    Tempfer, C.B.; Simoni, M.; Destenaves, B.; Fauser, B.C.J.M.

    2009-01-01

    BACKGROUND Endometriosis has a strong genetic component, and numerous genetic studies have been reported. METHODS We have systematically reviewed these studies and included 114 in our final selection. RESULTS We found no consistent evidence linking endometriosis with specific polymorphisms in genes encoding inflammatory mediators, proteins involved in sex steroid metabolism, vascular function and tissue remodelling. Although a number of polymorphisms have been associated with endometriosis in selected populations, the associations have not been independently confirmed, either because only single studies were carried out on these markers/genes or because other studies reported no association. The most solid evidence linking specific polymorphisms to endometriosis came from studies investigating glutathione-S-transferase, a phase II detoxification enzyme. Carriage of the GSTT1 null deletion variant showed consistent association with endometriosis with a 29% increased risk; however, it cannot be excluded that this result was due to publication bias, and this association should be independently confirmed in large-scale, well-designed casecontrol studies. CONCLUSIONS The evidence of an association between genetic polymorphisms and endometriosis is weak. Carriage of the GSTT1 null deletion may moderately increase the risk of this disease. We suggest that the methodology of association studies should be improved in order to identify and validate associations in endometriosis. PMID:18805939

  2. Mephenytoin and sparteine oxidation: genetic polymorphisms in Denmark.

    PubMed Central

    Drhse, A; Bathum, L; Brsen, K; Gram, L F

    1989-01-01

    The oxidation of mephenytoin was polymorphic in 358 healthy Danish volunteers. The ratio between the chromatographic peak areas of (S)- and (R)-mephenytoin (S/R) in 12 h urine was less than or equal to 0.48 in 349 extensive metabolizers (EM) and greater than or equal to 1 in 9 (2.5%) poor metabolizers (PM). Concomitant intake of mephenytoin and sparteine and subsequent assay by gas chromatography had no influence on the test results (mephenytoin S/R ratio or sparteine metabolic ratio). Among ten parents and seven siblings to six unrelated PM of mephenytoin only one (1/17 = 5.9%) was a PM. The pedigrees were compatible with an autosomal recessive mode of inheritance. PMID:2757884

  3. Genetic Polymorphism in Extracellular Regulators of Wnt Signaling Pathway

    PubMed Central

    Sharma, Ashish Ranjan; Seo, Eun-Min; Nam, Ju-Suk

    2015-01-01

    The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively. PMID:25945348

  4. [A feasibility analysis on individualized acupuncture treatment of irritable bowel syndrome under help of genetic polymorphism technique].

    PubMed

    Wu, Xiao-Liang; Sun, Jian-Hua; Liu, Lan-Ying; Fu, Hai-Yang; Jiao, Dai-Yan; Shu, Yan-Ye; Chen, Dong; Liu, Cheng-Yong; Zhan, Dao-Wei; Zhang, Wei

    2014-06-01

    Along with the application of genetic polymorphism techniques to individualized treatment of clinical disorders, the screening of polymorphisms markers of serotonin (5-HT) transporter (SERT) is a hot-spot of researches on irritable bowel syndrome (IBS). In the present paper, the authors introduce 1) optimized schemes of diagnosis and treatment of IBS on the basis of syndrome-differentiation for acupuncture in combination with Chinese herbal medicines, and application of 5-HT transporter polymorphism, 2) application of genetic polymorphism to researches on IBS, and 3) feasibility of genetic polymorphism techniques for guiding individualized treatment of IBS. Up to now, serotonin transporter length polymorphic region (5-HTTLPR), serotonin transporter intron 2 variable number of tandem repeat (Stin 2 VNTR) and single nucleotide polymorphism rs 25531 in the long allele of the 5-HTTLPR have been identified. On the basis of the treatment of IBS, we need establishing a set of guide lines for the individualized acupuncture treatment. The genotyping methods for genetic polymorphism should be widely used in this research field. 5-HT TLPR/ Stin 2 VNTR/rs 25531 polymorphisms would have a bright future in the field of IBS research and treatment. PMID:25069205

  5. Genetic polymorphism in sex hormone metabolism and prostate cancer risk.

    PubMed

    Ersekerci, E; Sofikerim, M; Taheri, S; Demirtas, A; Halis, F

    2015-01-01

    We compared single-nucleotide polymorphisms for point mutations in cytochrome P450 genes, including cytochrome P450c17? (CYP17), cytochrome P450 aromatase (CYP19), steroid-5-a-reductase (SRD5A2), and prostate-specific antigen (PSA) involved in androgen and estrogen production. Between January 2008 and January 2010, 90 patients were enrolled in the study. Of these patients, 28 were diagnosed with benign prostatic hyperplasia and 32 with prostate cancer, while 30 subjects were included as a control group. CYP19 1531 C>T, SRD5A2 gene V89L, CYP17 gene -34 T/C, PSA-158 (G/A) regions were evaluated for the association between polymorphisms and benign prostatic hyperplasia and prostate cancer in study population. Age, body mass index, peak urinary flow rate (Q max), voided urine volume, post-void residual urine volume, total PSA, free PSA, free/total PSA ratio, prostate weights measured by transrectal ultrasonography, erectile dysfunction score, and international prostate symptom score were compared between groups. No statistically significant difference in CYP19 1531 C>T, SRD5A2 V89L, and CYP17 -34T/C was observed in both groups when compared to the control group. The homozygote variant of PSA- 158 (G/A) was significantly lower for prostate cancer. Age, total PSA, free PSA, free/total PSA ratio, prostate weight, and Q max were evaluated using multi-variant analysis. Only Q max was significant for the homozygote variant. The probability of being homozygous was 5.8- fold higher in subjects with Q max >14 mL/s. In the Turkish population, the homozygote variant of PSA-158 (G/A) was significantly lower for prostate cancer. PMID:26214411

  6. USF-1 genetic polymorphisms confer a high risk of nonalcoholic fatty liver disease in Chinese population

    PubMed Central

    Wang, Ying; Wang, Bai-Fang; Tong, Jing; Chang, Bing; Wang, Bing-Yuan

    2015-01-01

    Genetic polymorphisms in upstream transcription factor 1 (USF1) were investigated for their links to increased risk of nonalcoholic fatty liver disease (NAFLD) in Chinese population. Between January 2013 and April 2014, 174 patients with NAFLD in the First Affiliated Hospital of China Medical University were selected for this study. A group of 100 healthy subjects were identified as the control group. The MALDI-TOF-MS, a mass spectrometry based technique, was used to detect USF-1 genetic polymorphisms using PCR amplified DNA products. Furthermore, Automatic Chemistry Analyzer (ACA) was used to determine the clinical indicators. Genotypes, allele frequencies and clinical indicators were measured to assess NAFLD risk in relation to the SNPs. USF-1 rs6427573 genetic polymorphisms were associated with an increased risk of NAFLD (AA vs. GG: OR = 3.16, 95% CI = 1.56-6.43, P = 0.001; GA + AA vs. GG: OR = 1.87, 95% CI = 1.13-3.09, P = 0.015; GG + AA vs. AA: OR = 2.96, 95% CI = 1.49-5.88, P = 0.001; G vs. A: OR = 2.10, 95% CI = 1.43-3.09, P < 0.001). Similarly, rs2516839 polymorphisms also conferred a risk for NAFLD (AA vs. GG: OR = 2.49, 95% CI = 1.43-4.34, P = 0.001; GA + AA vs. GG: OR = 1.69, 95% CI = 1.02-2.78, P = 0.041). On the other hand, rs3737787 and rs2774279 showed no statistical significances in the NAFLD group and control group (P > 0.05). Two USF-1 genetic polymorphisms, rs6427573 and rs2516839, may present an increased risk of NAFLD. PMID:25932200

  7. Effects of Lead Exposure and Genetic Polymorphisms on ALAD and GPx Activities in Brazilian Battery Workers.

    PubMed

    da Cunha Martins, Airton; Mazzaron Barcelos, Gustavo Rafael; Jacob Ferreira, Anna Laura Bechara; de Souza, Marilesia Ferreira; de Syllos Cólus, Ilce Mara; Antunes, Lusânia Maria Greggi; Bastos Paoliello, Monica Maria; Adeyemi, Joseph A; Barbosa, Fernando

    2015-01-01

    Lead (Pb) is a toxic metal that is widely used by metallurgical industries such as car battery recycling. Exposure to the metal may modify the redox status of the cells and consequently result in changes in activities of important enzymes such as delta-aminolevulinic acid dehydratase (ALAD) and glutathione peroxidase (GPx). Similarly, genetic polymorphisms may modulate the activities of enzymes related to detoxification processes of the metal and may modify Pb body burden. Therefore, the aims of the present study were (i) to evaluate the correlation between blood lead levels (BLL) and activities of the enzymes ALAD and GPx, and (ii) to determine whether activities of these enzymes may be influenced by polymorphisms in ALAD and GPx genes in Brazilian automotive battery workers chronically exposed to Pb, as well as the effects of these polymorphisms on BLL. Our study included 257 participants; BLL were determined by inductively couple plasma-mass spectrometry (ICP-MS), and the activities of the enzymes ALAD and GPx were quantified spectrophotometrically; and genotyping of ALAD (rs1800435) and GPx-1 (rs1800668) polymorphisms was performed by TaqMan assays (real-time polymerase chain reaction, RT-PCR). Significant negative correlations were found between BLL and ALAD activity. Subjects who carried at least one polymorphic allele for ALAD gene displayed markedly lower ALAD activities, while no significant effect was observed regarding GPx-1 polymorphism and activity of the same enzyme. Further, ALAD and GPx-1 polymorphisms exerted no marked influence on BLL. Taken together, our results showed that BLL affected ALAD but not GPx activities, and these were not modulated by polymorphisms in ALAD and GPx gene. Further, the rs1800435 SNP showed a tendency to modulate ALAD activity, while the rs1800668 SNP did not modulate GPx activity in Brazilian automotive battery workers exposed to Pb. PMID:26275098

  8. Harbor lights

    PubMed

    Maden

    2000-12-01

    Illuminating Life: Selected Papers from Cold Spring Harbor (1903-1969) by J. Witkowski Cold Spring Harbor Laboratory Press (2000) pp. 383 + xvi. ISBN 0-87969-566-8 $25.00 If you are anywhere on the spectrum from frequent Cold Spring Harbor visitor to someone who barely knows that Symposia of that name were until recently published in maroon covers, and if you want to learn more of the history of this remarkable research centre, then this book is for you. At first sight, Illuminating Life looks like a coffee table book, but it is much more than that. Jan Witkowski has assembled a history of the Cold Spring Harbor Laboratories from their inception in 1890 through to 1968, illustrated by a selection of research papers from 1903 to 1969. Each one or two papers is preceded by an interpretative essay and a biographical note on the principal author(s), and the whole is introduced by an informative historical preface. At the end are three obituaries from the literature summarizing the lives of three key players, Davenport, Harris and Demerec. For a book of this size and compass, the essentials can be assimilated remarkably quickly, and at $25 the book is exceptional value for money. First read the preface. Then the essays. These are gems, and at two or three pages each there is no need to postpone them until later! Then dip into a few research papers. Then re-read the preface. Then you will know a lot about Cold Spring Harbor. If you read the obituaries you will know even more. Here are just a few impressions. On p. 364 there is a photograph of one of the early buildings, the James Laboratory. The laboratory was constructed for $12,000 in 1928 for biophysics research (p117). It looks tiny, but in the early years of the Symposia, which were then on biophysical topics, it housed a galaxy of summer visitors including Curtis and Cole (electrophysiology), J. Z. Young (nerve conduction), Davison and Danielli (need one say more?) and many others. If biophysics under Reginald Harris (1924-36) was what made Cold Spring Harbor Quantitative, then the quest for the genetic material and its properties is what has made it most widely famed. The book brings out the seminal contributions of Demerec, both as scientist and as director (1941-60) and of McClintock, Hershey, Cairns (director 1963-8) and others. The chosen research papers include many that are landmarks in science, from maize to bacteria and phage, and generally they are easy to read. They are largely devoid of the ponderous throat-clearing and innumerable citations that are so much a part of scientific literature today. Many examples could be given of such ease of style and freedom from excess verbage, but one will suffice here. 'Aggregation of DNA is often suspected but seldom studied. In phage &lgr; we found a DNA that can form characteristic and stable complexes. A first account of them is given here'. That is the entire introduction in Hershey, A. D., Burgi, E. and Ingraham, L. (1963), Cohesion of DNA molecules isolated from phage &lgr;. Proc. Nat. Acad. Sci. USA 49, 748-755. The paper by de Lucia and Cairns (1969) on 'Isolation of an E. coli strain with a mutation affecting DNA polymerase' is a fitting choice with which to conclude the compilation. In the late 1960s something seemed not quite right about the Kornberg enzyme as the putative engine of replication. Several suspicious inconsistencies were accumulating. How to test these suspicions? Random mutagenesis, a precise and rapid screening assay applicable to thousands of isolates. The rest is history. What of the last thirty years? The spine of the cover says, rather enigmatically, 'Volume 1'; the reviewer could find no statement elsewhere in the book that more is to follow. Perhaps we can look forward to Volume 2. Surely that volume will contain, among many other landmark papers, one called 'An amazing sequence arrangement at the 5 ends of Adenovirus 2 messenger RNA'. PMID:11069757

  9. Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling

    PubMed Central

    de Albuquerque, Felipe Neves; Brandão, Andréa Araujo; da Silva, Dayse Aparecida; Mourilhe-Rocha, Ricardo; Duque, Gustavo Salgado; Gondar, Alyne Freitas Pereira; Neves, Luiza Maceira de Almeida; Bittencourt, Marcelo Imbroinise; Pozzan, Roberto; de Albuquerque, Denilson Campos

    2014-01-01

    Background The role of angiotensin-converting enzyme genetic polymorphisms as a predictor of echocardiographic outcomes on heart failure is yet to be established. The local profile should be identified so that the impact of those genotypes on the Brazilian population could be identified. This is the first study on exclusively non-ischemic heart failure over a follow-up longer than 5 years. Objective To determine the distribution of angiotensin-converting enzyme genetic polymorphism variants and their relation with echocardiographic outcome of patients with non-ischemic heart failure. Methods Secondary analysis of the medical records of 111 patients and identification of the angiotensin-converting enzyme genetic polymorphism variants, classified as DD (Deletion/Deletion), DI (Deletion/Insertion) or II (Insertion/Insertion). Results The cohort means were as follows: follow-up, 64.9 months; age, 59.5 years; male sex, 60.4%; white skin color, 51.4%; use of beta-blockers, 98.2%; and use of angiotensin-converting-enzyme inhibitors or angiotensin receptor blocker, 89.2%. The angiotensin-converting enzyme genetic polymorphism distribution was as follows: DD, 51.4%; DI, 44.1%; and II, 4.5%. No difference regarding the clinical characteristics or treatment was observed between the groups. The final left ventricular systolic diameter was the only isolated echocardiographic variable that significantly differed between the angiotensin-converting enzyme genetic polymorphisms: 59.2 ± 1.8 for DD versus 52.3 ± 1.9 for DI versus 59.2 ± 5.2 for II (p = 0.029). Considering the evolutionary behavior, all echocardiographic variables (difference between the left ventricular ejection fraction at the last and first consultation; difference between the left ventricular systolic diameter at the last and first consultation; and difference between the left ventricular diastolic diameter at the last and first consultation) differed between the genotypes (p = 0.024; p = 0.002; and p = 0.021, respectively). Conclusion The distribution of the angiotensin-converting enzyme genetic polymorphisms differed from that of other studies with a very small number of II. The DD genotype was independently associated with worse echocardiographic outcome, while the DI genotype, with the best echocardiographic profile (increased left ventricular ejection fraction and decreased left ventricular diameters). PMID:24270863

  10. Genetic Aberrations in Childhood Acute Lymphoblastic Leukaemia: Application of High-Density Single Nucleotide Polymorphism Array

    PubMed Central

    Sulong, Sarina

    2010-01-01

    Screening of the entire human genome using high-density single nucleotide polymorphism array (SNPA) has become a powerful technique used in cancer genetics and population genetics studies. The GeneChip Mapping Array, introduced by Affymetrix, is one SNPA platform utilised for genotyping studies. This GeneChip system allows researchers to gain a comprehensive view of cancer biology on a single platform for the quantification of chromosomal amplifications, deletions, and loss of heterozygosity or for allelic imbalance studies. Importantly, this array analysis has the potential to reveal novel genetic findings involved in the multistep development of cancer. Given the importance of genetic factors in leukaemogenesis and the usefulness of screening the whole genome, SNPA analysis has been utilised in many studies to characterise genetic aberrations in childhood acute lymphoblastic leukaemia. PMID:22135543

  11. Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage and Repair

    PubMed Central

    Sterpone, Silvia; Cozzi, Renata

    2010-01-01

    It is well known that ionizing radiation (IR) can damage DNA through a direct action, producing single- and double-strand breaks on DNA double helix, as well as an indirect effect by generating oxygen reactive species in the cells. Mammals have evolved several and distinct DNA repair pathways in order to maintain genomic stability and avoid tumour cell transformation. This review reports important data showing a huge interindividual variability on sensitivity to IR and in susceptibility to developing cancer; this variability is principally represented by genetic polymorphisms, that is, DNA repair gene polymorphisms. In particular we have focussed on single nucleotide polymorphisms (SNPs) of XRCC1, a gene that encodes for a scaffold protein involved basically in Base Excision Repair (BER). In this paper we have reported and presented recent studies that show an influence of XRCC1 variants on DNA repair capacity and susceptibility to breast cancer. PMID:20798883

  12. Multiple sclerosis in families: risk factors beyond known genetic polymorphisms.

    PubMed

    Akkad, Denis A; Lee, De-Hyung; Bruch, Kathrin; Haghikia, Aiden; Epplen, Jörg T; Hoffjan, Sabine; Linker, Ralf A

    2016-04-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that predominantly affects young adults. The genetic contributions to this multifactorial disease were underscored by genome wide association studies and independent replication studies. A weighted genetic risk score (wGRS) was recently established using the identified MS risk loci in order to predict MS outcome including clinical and paraclinical features. Here, we present the results on a family with several affected siblings including a monozygotic triplet. The individuals were genotyped for 57 non-MHC risk loci as well as the HLA DRB1*1501 tagging SNP rs3135388 with subsequent calculation of the wGRS. Additionally, SNP array based analyses for aberrant chromosomal regions were performed for all individuals. PMID:26865406

  13. Vitiligo: pathomechanisms and genetic polymorphism of susceptible genes.

    PubMed

    Shajil, E M; Chatterjee, Sreejata; Agrawal, Deepali; Bagchi, T; Begum, Rasheedunnisa

    2006-07-01

    Vitiligo is a depigmenting disorder resulting from the loss of melanocytes in the skin and affects 1-4% of the world population. Incidence of vitiligo is found to be 0.5-2.5% in India with a high prevalence of 8.8% in Gujarat and Rajasthan states. The cellular and molecular mechanisms that lead to melanocyte destruction in this disorder are not yet been fully elucidated. Genetic factors, neural factors, toxic ROS metabolites, autoantibodies and autoreactive T lymphocytes may be the causative agents for the selective destruction of melanocytes. Three major hypotheses of pathogenesis of vitiligo are neural, autoimmune and oxidative stress hypotheses, however none of them explains the pathogenesis of vitiligo in toto. Genetics of vitiligo is characterized by incomplete penetrance, multiple susceptibility loci and genetic heterogeneity. Recent advances in this field are linkage and association of candidate gene studies. The linkage and association studies provide a strong evidence for the presence of multiple vitiligo susceptibility genes on different chromosomes. Several candidate genes for vitiligo are identified from different populations. In this review, we have provide an overview of different hypotheses of vitiligo pathogenesis, and discuss the recent advances in this field with special reference to linkage, association and candidate gene approach. PMID:16872041

  14. Genetic polymorphisms associated with breast cancer in malaysian cohort.

    PubMed

    Chahil, Jagdish Kaur; Munretnam, Khamsigan; Samsudin, Nurulhafizah; Lye, Say Hean; Hashim, Nikman Adli Nor; Ramzi, Nurul Hanis; Velapasamy, Sharmila; Wee, Ler Lian; Alex, Livy

    2015-04-01

    Genome-wide association studies have discovered multiple single nucleotide polymorphisms (SNPs) associated with the risk of common diseases. The objective of this study was to demonstrate the replication of previously published SNPs that showed statistical significance for breast cancer in the Malaysian population. In this case-control study, 80 subjects for each group were recruited from various hospitals in Malaysia. A total of 768 SNPs were genotyped and analyzed to distinguish risk and protective alleles. A total of three SNPs were found to be associated with increased risk of breast cancer while six SNPs showed protective effect. All nine were statistically significant SNPs (p ≤ 0.01), five SNPs from previous studies were successfully replicated in our study. Significant modifiable (diet) and non-modifiable (family history of breast cancer in first degree relative) risk factors were also observed. We identified nine SNPs from this study to be either conferring susceptibility or protection to breast cancer which may serve as potential markers in risk prediction. PMID:25883419

  15. Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population

    PubMed Central

    Yan, Xiaojuan; Yang, Feng; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Ma, Kezhong; Li, Yi; Zhu, Jun; Ding, Jianqiang

    2015-01-01

    Background VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1–1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement. Material/Methods A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1–1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed. Results Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all P<0.05). Warfarin maintenance dose in VKORC1–1639 G/A AG + GG carriers was obviously higher than in AA carriers (P<0.001). As compared with patients with TT genotype in VKORC1 1173 C/T, warfarin maintenance dose was apparently higher in patients with CT genotype (P<0.001). Linear regression analysis revealed that gender, operation method, method for heart valve replacement, as well as VKORC1–1639 G/A and 1173 C/T gene polymorphisms were significantly related to warfarin maintenance dose (all P<0.05). Conclusions VKORC1 gene polymorphisms are key genetic factors to affect individual differences in warfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose. PMID:26583785

  16. Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population.

    PubMed

    Yan, Xiaojuan; Yang, Feng; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Ma, Kezhong; Li, Yi; Zhu, Jun; Ding, Jianqiang

    2015-01-01

    BACKGROUND VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1-1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement. MATERIAL AND METHODS A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1-1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed. RESULTS Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all P<0.05). Warfarin maintenance dose in VKORC1-1639 G/A AG + GG carriers was obviously higher than in AA carriers (P<0.001). As compared with patients with TT genotype in VKORC1 1173 C/T, warfarin maintenance dose was apparently higher in patients with CT genotype (P<0.001). Linear regression analysis revealed that gender, operation method, method for heart valve replacement, as well as VKORC1-1639 G/A and 1173 C/T gene polymorphisms were significantly related to warfarin maintenance dose (all P<0.05). CONCLUSIONS VKORC1 gene polymorphisms are key genetic factors to affect individual differences in warfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose. PMID:26583785

  17. Cigarette smoking, genetic polymorphisms and colorectal cancer risk: the Fukuoka Colorectal Cancer Study

    PubMed Central

    2010-01-01

    Background It is uncertain whether smoking is related to colorectal cancer risk. Cytochrome P-450 CYP1A1, glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are important enzymes in the metabolism of tobacco carcinogens, and functional genetic polymorphisms are known for these enzymes. We investigated the relation of cigarette smoking and related genetic polymorphisms to colorectal cancer risk, with special reference to the interaction between smoking and genetic polymorphism. Methods We used data from the Fukuoka Colorectal Cancer Study, a population-based case-control study, including 685 cases and 778 controls who gave informed consent to genetic analysis. Interview was conducted to assess lifestyle factors, and DNA was extracted from buffy coat. Results In comparison with lifelong nonsmokers, the odds ratios (OR) of colorectal cancer for <400, 400-799 and ≥800 cigarette-years were 0.65 (95% confidence interval [CI], 0.45-0.89), 1.16 (0.83-1.62) and 1.14 (0.73-1.77), respectively. A decreased risk associated with light smoking was observed only for colon cancer, and rectal cancer showed an increased risk among those with ≥400 cigarette-years (OR 1.60, 95% CI 1.04-2.45). None of the polymorphisms under study was singly associated with colorectal cancer risk. Of the gene-gene interactions studied, the composite genotype of CYP1A1*2A or CYP1A1*2C and GSTT1 polymorphisms was associated with a decreased risk of colorectal cancer, showing a nearly statistically significant (Pinteraction = 0.06) or significant interaction (Pinteraction = 0.02). The composite genotypes of these two polymorphisms, however, showed no measurable interaction with cigarette smoking in relation to colorectal cancer risk. Conclusions Cigarette smoking may be associated with increased risk of rectal cancer, but not of colon cancer. The observed interactions between CYP1A1 and GSTT1 polymorphisms warrant further confirmation. PMID:20534171

  18. Genetic Variation Among World Populations: Inferences From 100 Alu Insertion Polymorphisms

    PubMed Central

    Watkins, W. Scott; Rogers, Alan R.; Ostler, Christopher T.; Wooding, Steve; Bamshad, Michael J.; Brassington, Anna-Marie E.; Carroll, Marion L.; Nguyen, Son V.; Walker, Jerilyn A.; Prasad, B.V. Ravi; Reddy, P. Govinda; Das, Pradipta K.; Batzer, Mark A.; Jorde, Lynn B.

    2003-01-01

    We examine the distribution and structure of human genetic diversity for 710 individuals representing 31 populations from Africa, East Asia, Europe, and India using 100 Alu insertion polymorphisms from all 22 autosomes. Alu diversity is highest in Africans (0.349) and lowest in Europeans (0.297). Alu insertion frequency is lowest in Africans (0.463) and higher in Indians (0.544), E. Asians (0.557), and Europeans (0.559). Large genetic distances are observed among African populations and between African and non-African populations. The root of a neighbor-joining network is located closest to the African populations. These findings are consistent with an African origin of modern humans and with a bottleneck effect in the human populations that left Africa to colonize the rest of the world. Genetic distances among all pairs of populations show a significant product-moment correlation with geographic distances (r = 0.69, P < 0.00001). FST, the proportion of genetic diversity attributable to population subdivision is 0.141 for Africans/E. Asians/Europeans, 0.047 for E. Asians/Indians/Europeans, and 0.090 for all 31 populations. Resampling analyses show that ?50 Alu polymorphisms are sufficient to obtain accurate and reliable genetic distance estimates. These analyses also demonstrate that markers with higher FST values have greater resolving power and produce more consistent genetic distance estimates. PMID:12805277

  19. Genetic diversity in Capsicum germplasm based on microsatellite and random amplified microsatellite polymorphism markers.

    PubMed

    Rai, Ved Prakash; Kumar, Rajesh; Kumar, Sanjay; Rai, Ashutosh; Kumar, Sanjeet; Singh, Major; Singh, Sheo Pratap; Rai, Awadesh Bahadur; Paliwal, Rajneesh

    2013-10-01

    A sound knowledge of the genetic diversity among germplasm is vital for strategic germplasm collection, maintenance, conservation and utilisation. Genomic simple sequence repeats (SSRs) and random amplified microsatellite polymorphism (RAMPO) markers were used to analyse diversity and relationships among 48 pepper (Capsicum spp.) genotypes originating from nine countries. These genotypes covered 4 species including 13 germplasm accessions, 30 improved lines of 4 domesticated species and 5 landraces derived from natural interspecific crosses. Out of 106 SSR markers, 25 polymorphic SSR markers (24%) detected a total of 76 alleles (average, 3.04; range, 2-5). The average polymorphic information content (PIC) was 0.69 (range, 0.29-0.92). Seventeen RAMPO markers produced 87 polymorphic fragments with average PIC of 0.63 (range, 0.44-0.81). Dendrograms based on SSRs and RAMPOs generated two clusters. All 38 Capsicum annuum genotypes and an interspecific landrace clustered together, whereas nine non-annuum (three Capsicum frutescens, one Capsicum chinense, one Capsicum baccatum and four interspecific landraces) genotypes clustered separately. Genetic variation within non-annuum genotypes was greater than the C. annuum genotypes. Distinctness of interspecific derivative landraces grown in northeast India was validated; natural crossing between sympatric Capsicum species has been proposed as the mechanism of their origin. PMID:24431527

  20. Genetic polymorphisms in the metabolic pathway and non-Hodgkin lymphoma survival

    PubMed Central

    Han, Xuesong; Zheng, Tongzhang; Foss, Francine M.; Lan, Qing; Holford, Theodore R.; Rothman, Nathaniel; Ma, Shuangge; Zhang, Yawei

    2010-01-01

    Background Metabolic pathway enzymes, such as Cytochrome P450 (CYP), glutathione S-transferase (GST), and N-Acetyltransferases (NAT) are involved in activation and detoxification of environmental carcinogens as well as drug metabolism. We hypothesized that the genetic variations in such metabolic pathways may affect NHL prognosis and survival. Methodology/Principal Findings Follow-up information of 469 female NHL incident cases diagnosed during 1995-2000 in Connecticut were abstracted from Connecticut Tumor Registry in 2008; survival analyses were conducted using the Kaplan-Meier method, and hazard ratios (HR) were estimated by Cox Proportional Hazard models adjusting for demographic and tumor characteristics which were suggested by previous studies to be determinants of NHL survival. Our results identified nine SNPs from five metabolism genes (CYP2E1, GSTP1, GSTT1, NAT1 and NAT2) that were associated with NHL survival. Specifically, polymorphisms in NAT1 and NAT2 genes were associated with diffuse large B-cell lymphoma survival; polymorphisms in GSTT1 was associated with follicular lymphoma survival; and polymorphisms in CYP2E1, GSTP1 and NAT1 were associated with survival of chronic lymphocytic leukemia/small lymphocytic lymphoma. Conclusions/Significance Our study suggests that genetic polymorphisms in metabolic pathways may help improving the prediction of NHL survival and prognosis. PMID:20029944

  1. Prospective study of MTHFR genetic polymorphisms as a possible etiology of male infertility.

    PubMed

    Li, S-S; Li, J; Xiao, Z; Ren, A-G; Jin, L

    2014-01-01

    The aim of this study was to explore the relationship between 2 genetic polymorphisms of the methylenetetrahydrofolate reductase gene (MTHFR), C677T and A1298C, and determine the long-term reproductive outcome in infertile men. This was a prospective study conducted in an andrology clinic. Men with a 1-year history of infertility were assessed for the MTHFR polymorphisms at a 5-year follow-up. We compared the MTHFR C677T and A1298C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism between men who did and did not bear children during follow-up. Of the 215 men who were infertile at 1 year, 82 (38.1%) remained infertile and 133 (61.9%) achieved natural conception during the 5-year follow-up, with the highest rate in the first year (32.6%). The MTHFR 677TT genotype (homozygote) was associated with a substantially increased risk of infertility during follow-up [odds ratio (OR) = 10.242; 95% confidence interval (CI) = 1.257-83.464] relative to the MTHFR 677CC genotype (wild-type). Risk of infertility was not increased by the MTHFR A1298C polymorphism alone, but was increased by the combination of polymorphisms MTHFR C677T and MTHFR A1298C (OR = 11.818; 95%CI = 1.415-98.674). The homozygous MTHFR C677T genotype was a risk factor for male infertility during 5-year follow-up, whereas a correlation between MTHFR A1298C and infertility was not observed. The MTHFR C677T and MTHFR A1298C polymorphisms had additive effects on male infertility. PMID:24737513

  2. Investigation of genetic polymorphisms related to the outcome of radiotherapy for prostate cancer patients.

    PubMed

    Cintra, Hellen Silva; Pinezi, Juliana Castro Dourado; Machado, Graziella Dias Pinheiro; de Carvalho, Gustavo Moura; Carvalho, Ana Terra Silva; dos Santos, Thalles Eduardo Dias; Marciano, Ricardo Duarte; Soares, Renata de Bastos Asceno

    2013-01-01

    The purpose of this study was to evaluate the association between ATM, TP53 and MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy. The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362, rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by direct sequencing of PCR fragments from 48 patients with histologically proven prostate adenocarcinoma and treated with external beam radiation. The side effects were classified according to the Radiation Therapy Oncology Group (RTOG) score. The results showed no association between clinical characteristics and the development of radiation toxicities (P > 0.05). The C>T transition in the position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.0002-0.227, P = 0.003). The intronic TP53 polymorphism at position 16250 (rs17883323) was associated with chronic urinary toxicity (OR: 0.071, 95%CI 0.006-0.784, P = 0.032). No significant associations were found for the remaining polymorphisms (P > 0.05). The results show that clinical characteristics were not determinant on the developing of radiation sensitivity in prostate cancer patients, and intronic TP53 polymorphisms would be associated with increased acute and chronic radiation toxicities. These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in patients undergoing radiotherapy. PMID:24324286

  3. Investigation of Genetic Polymorphisms Related to the Outcome of Radiotherapy for Prostate Cancer Patients

    PubMed Central

    Cintra, Hellen Silva; Pinezi, Juliana Castro Dourado; Machado, Graziella Dias Pinheiro; de Carvalho, Gustavo Moura; Carvalho, Ana Terra Silva; dos Santos, Thalles Eduardo Dias; Marciano, Ricardo Duarte; Soares, Renata de Bastos Asceno

    2013-01-01

    The purpose of this study was to evaluate the association between ATM, TP53 and MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy. The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362, rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by direct sequencing of PCR fragments from 48 patients with histologically proven prostate adenocarcinoma and treated with external beam radiation. The side effects were classified according to the Radiation Therapy Oncology Group (RTOG) score. The results showed no association between clinical characteristics and the development of radiation toxicities (P > 0.05). The C>T transition in the position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.00020.227, P = 0.003). The intronic TP53 polymorphism at position 16250 (rs17883323) was associated with chronic urinary toxicity (OR: 0.071, 95%CI 0.0060.784, P = 0.032). No significant associations were found for the remaining polymorphisms (P > 0.05). The results show that clinical characteristics were not determinant on the developing of radiation sensitivity in prostate cancer patients, and intronic TP53 polymorphisms would be associated with increased acute and chronic radiation toxicities. These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in patients undergoing radiotherapy. PMID:24324286

  4. Genetic discovery in Xylella fastidiosa through sequence analysis of selected randomly amplified polymorphic DNAs.

    PubMed

    Chen, Jianchi; Civerolo, Edwin L; Jarret, Robert L; Van Sluys, Marie-Anne; de Oliveira, Mariana C

    2005-02-01

    Xylella fastidiosa causes many important plant diseases including Pierce's disease (PD) in grape and almond leaf scorch disease (ALSD). DNA-based methodologies, such as randomly amplified polymorphic DNA (RAPD) analysis, have been playing key roles in genetic information collection of the bacterium. This study further analyzed the nucleotide sequences of selected RAPDs from X. fastidiosa strains in conjunction with the available genome sequence databases and unveiled several previously unknown novel genetic traits. These include a sequence highly similar to those in the phage family of Podoviridae. Genome comparisons among X. fastidiosa strains suggested that the "phage" is currently active. Two other RAPDs were also related to horizontal gene transfer: one was part of a broadly distributed cryptic plasmid and the other was associated with conjugal transfer. One RAPD inferred a genomic rearrangement event among X. fastidiosa PD strains and another identified a single nucleotide polymorphism of evolutionary value. PMID:15723179

  5. Association of genetic polymorphisms with fertilization in the chicken.

    PubMed

    Morton, J R; Gilmour, D G

    1972-01-01

    Associations between fertilization rate and genotypes at four polymorphic loci were studied in three relatively non-inbred populations of Light Sussex chickens. In sires the genotypes tested were at theB blood-group locus only; in dams, at theB locus and three egg-white loci. Data were available for purebred matings of related substrains 6D and 6F and the ancestor strain 6 from which they were derived and for crossbred matings of 6D and 6F by two related Rhode Island Red/New Hampshire strains.In analyses of variance by dam genotypes within sires, no locus or combination of loci had a significant effect on fertilization rate. In analyses by sire and damB blood-group genotypes, no significant effects were found in 6F. SireB genotypes showed a very significant effect (P<0.001) on fertilization rate in 6D, and in 6. The latter effect was not fully acceptable since there was a significant (P<0.02) sirex damB genotypes interaction effect in 6. This interaction took the form of a lowered fertility in matings where sire and dam had the sameB genotype. The significant main effect in 6D was due to significant differences between the fertilization rates of the three most frequent sire genotypes. The same differences were not found in the other two strains. Similarly, significant sireB genotype differences in the Rhode Island Red/New Hampshire mates of 6F were not repeated in those of 6D.Combination of this result with those from our previous work with embryonic mortality in these strains is still insufficient fully to explain the continued segregation of four alleles at theB blood group locus. PMID:24430831

  6. Genetic polymorphism characteristics of Brucella canis isolated in China.

    PubMed

    Di, Dongdong; Cui, Buyun; Wang, Heng; Zhao, Hongyan; Piao, Dongri; Tian, Lili; Tian, Guozhong; Kang, Jingli; Mao, Xiang; Zhang, Xiaojun; Du, Pengfei; Zhu, Lin; Zhao, Zhuo; Mao, Lingling; Yao, Wenqing; Guan, Pingyuan; Fan, Weixing; Jiang, Hai

    2014-01-01

    In China, brucellosis is an endemic disease typically caused by Brucella melitensis infection (biovars 1 and 3). Brucella canis infection in dogs has not traditionally recognized as a major problem. In recent years however, brucellosis resulting from Brucella canis infection has also been reported, suggesting that infections from this species may be increasing. Data concerning the epidemiology of brucellosis resulting from Brucella canis infection is limited. Therefore, the purpose of this study was to assess the diversity among Chinese Brucella canis strains for epidemiological purposes. First, we employed a 16-marker VNTR assay (Brucella MLVA-16) to assess the diversity and epidemiological relationship of 29 Brucella canis isolates from diverse locations throughout China with 38 isolates from other countries. MLVA-16 analysis separated the 67 Brucella canis isolates into 57 genotypes that grouped into five clusters with genetic similarity coefficients ranging from 67.73 to 100%. Moreover, this analysis revealed a new genotype (2-3-9-11-3-1-5-1:118), which was present in two isolates recovered from Guangxi in 1986 and 1987. Second, multiplex PCR and sequencing analysis were used to determine whether the 29 Chinese Brucella canis isolates had the characteristic BMEI1435 gene deletion. Only two isolates had this deletion. Third, amplification of the omp25 gene revealed that 26 isolates from China had a T545C mutation. Collectively, this study reveals that considerable diversity exists among Brucella canis isolates in China and provides resources for studying the genetic variation and microevolution of Brucella. PMID:24465442

  7. Genetic Polymorphism Characteristics of Brucella canis Isolated in China

    PubMed Central

    Wang, Heng; Zhao, Hongyan; Piao, Dongri; Tian, Lili; Tian, Guozhong; Kang, Jingli; Mao, Xiang; Zhang, Xiaojun; Du, Pengfei; Zhu, Lin; Zhao, Zhuo; Mao, Lingling; Yao, Wenqing; Guan, Pingyuan; Fan, Weixing; Jiang, Hai

    2014-01-01

    In China, brucellosis is an endemic disease typically caused by Brucella melitensis infection (biovars 1 and 3). Brucella canis infection in dogs has not traditionally recognized as a major problem. In recent years however, brucellosis resulting from Brucella canis infection has also been reported, suggesting that infections from this species may be increasing. Data concerning the epidemiology of brucellosis resulting from Brucella canis infection is limited. Therefore, the purpose of this study was to assess the diversity among Chinese Brucella canis strains for epidemiological purposes. First, we employed a 16-marker VNTR assay (Brucella MLVA-16) to assess the diversity and epidemiological relationship of 29 Brucella canis isolates from diverse locations throughout China with 38 isolates from other countries. MLVA-16 analysis separated the 67 Brucella canis isolates into 57 genotypes that grouped into five clusters with genetic similarity coefficients ranging from 67.73 to 100%. Moreover, this analysis revealed a new genotype (2-3-9-11-3-1-5-1:118), which was present in two isolates recovered from Guangxi in 1986 and 1987. Second, multiplex PCR and sequencing analysis were used to determine whether the 29 Chinese Brucella canis isolates had the characteristic BMEI1435 gene deletion. Only two isolates had this deletion. Third, amplification of the omp25 gene revealed that 26 isolates from China had a T545C mutation. Collectively, this study reveals that considerable diversity exists among Brucella canis isolates in China and provides resources for studying the genetic variation and microevolution of Brucella. PMID:24465442

  8. Genetic Polymorphism and Evolution in Parthenogenetic Animals. I. Polyploid Curculionidae

    PubMed Central

    Suomalainen, Esko; Saura, Anssi

    1973-01-01

    The genetic variability at enzyme loci in different triploid and tetraploid parthenogenetic weevil populations has been elucidated by starch gel electrophoresis. The overall genotype of individual weevils belonging to different populations has been determined for over 25 loci. The results are compared with those obtained for diploid bisexual races of either the same or closely related species. The variation within a parthenogenetic population differs from that in diploid, sexually reproducing populations, i.e. the allele frequencies are not in a Hardy-Weinberg equilibrium. The results indicate that apomictic parthenogenetic populations can differentiate genetically. The genotypes within a population resemble each other more than genotypes belonging to different populations. It is evident that evolution still continueseven if slowed downin parthenogenetic weevils. A comparison between the allele relationships in geographically isolated polyploid parthenogenetic populations and related diploid bisexual forms does not support the hypothetical hybrid origin of parthenogenesis and polyploidy in weevils. Parthenogenesis within a parthenogenetic weevil species is evidently monophyletic. PMID:17248626

  9. Genetic relatedness of artichoke (Cynara scolymus L.) hybrids using random amplified polymorphic DNA (RAPD) fingerprinting.

    PubMed

    Sharaf-Eldin, M A; Al-Tamimi, A; Alam, P; Elkholy, S F; Jordan, J R

    2015-01-01

    The artichoke (Cynara scolymus L.) is an important food and medicinal crop that is cultivated in Mediterranean countries. Morphological characteristics, such as head shape and diameter, leaf shape, and bract shape, are mainly affected by environmental conditions. A molecular marker approach was used to analyze the degree of polymorphism between artichoke hybrid lines. The degree of genetic difference among three artichoke hybrids was evaluated using random amplified polymorphic DNA-PCR (RAPD-PCR). In this study, the DNA fingerprints of three artichoke lines (A13-010, A11-018, and A12-179) were generated, and a total of 10 decamer primers were applied for RAPD-PCR analyses. Polymorphism  (16.66 to 62.50%) was identified using eight arbitrary decamers and total genomic DNA extracted from the hybrids. Of the 59 loci detected, there were 25 polymorphic and 34 monomorphic loci. Jaccard's similarity index (JSI) ranged between 1.0 and 0.84. Based on the unweighted pair group method with arithmetic mean (UPGMA) similarity matrix and dendrogram, the results indicated that two hybrids (A13-010 and A11-018) were closely related to each other, and the A12-179 line showed more divergence. When identifying correct accessions, consideration of the genetic variation and genetic relationships among the genotypes are required. The RAPD-PCR fingerprinting of artichoke lines clearly showed that it is possible to analyze the RAPD patterns for correlation between genetic means and differences or resemblance between close accessions (A13-010 and A11- 018) at the genomic level. PMID:26782491

  10. Lack of genetic polymorphism among peregrine falcons Falco peregrinus of Fiji

    USGS Publications Warehouse

    Talbot, S.L.; Palmer, A.G.; Sage, G.K.; Sonsthagen, S.A.; Swem, T.; Brimm, D.J.; White, C.M.

    2011-01-01

    We compared levels of genetic diversity and isolation among peregrine falcons Falco peregrinus from two South Pacific island complexes (Fiji and Vanuatu: F. p. nesiotes), relative to other island and mainland populations. Fragment data from 12 microsatellite loci and sequence information from the control region of the mitochondrial DNA indicated levels of genetic variation in the South Pacific populations were lower than other island and mainland populations. Indeed, diversity varied from extremely low (Vanuatu) to completely absent (Fiji). We find little support for a hypothesis that populations on Fiji or Vanuatu were colonized via Australia. The complete lack of polymorphism in peregrine falcons of Fiji is remarkable, and to our knowledge has not been observed in a natural avian population. This lack of polymorphism, and the inability to test for decrease in polymorphism using museum samples, precludes testing whether the lack of genetic diversity in the population on Fiji is due to a recent bottleneck, or sustained isolation over evolutionary time. Increased fertility in eggs of Fiji peregrines upon outbreeding with males from other areas is consistent with inbreeding depression within a population typified by heterozygote deficiency. ?? 2011 The Authors.

  11. Lack of genetic polymorphism among peregrine falcons Falco peregrinus of Fiji

    USGS Publications Warehouse

    Talbot, Sandra; Palmer, A.G.; Sage, G.K.; Sonsthagen, Sarah A.; Swem, T.; Brimm, D.J.

    2014-01-01

    We compared levels of genetic diversity and isolation among peregrine falcons Falco peregrinus from two South Pacific island complexes (Fiji and Vanuatu: F. p. nesiotes), relative to other island and mainland populations. Fragment data from 12 microsatellite loci and sequence information from the control region of the mitochondrial DNA indicated levels of genetic variation in the South Pacific populations were lower than other island and mainland populations. Indeed, diversity varied from extremely low (Vanuatu) to completely absent (Fiji). We find little support for a hypothesis that populations on Fiji or Vanuatu were colonized via Australia. The complete lack of polymorphism in peregrine falcons of Fiji is remarkable, and to our knowledge has not been observed in a natural avian population. This lack of polymorphism, and the inability to test for decrease in polymorphism using museum samples, precludes testing whether the lack of genetic diversity in the population on Fiji is due to a recent bottleneck, or sustained isolation over evolutionary time. Increased fertility in eggs of Fiji peregrines upon outbreeding with males from other areas is consistent with inbreeding depression within a population typified by heterozygote deficiency.

  12. The Roles of Genetic Polymorphisms and Human Immunodeficiency Virus Infection in Lipid Metabolism

    PubMed Central

    de Almeida, Elaine Regina Delicato; Reiche, Edna Maria Vissoci; Flauzino, Tamires; Watanabe, Maria Angelica Ehara

    2013-01-01

    Dyslipidemia has been frequently observed among individuals infected with human immunodeficiency virus type 1 (HIV-1), and factors related to HIV-1, the host, and antiretroviral therapy (ART) are involved in this phenomenon. This study reviews the roles of genetic polymorphisms, HIV-1 infection, and highly active antiretroviral therapy (HAART) in lipid metabolism. Lipid abnormalities can vary according to the HAART regimen, such as those with protease inhibitors (PIs). However, genetic factors may also be involved in dyslipidemia because not all patients receiving the same HAART regimen and with comparable demographic, virological, and immunological characteristics develop variations in the lipid profile. Polymorphisms in a large number of genes are involved in the synthesis of structural proteins, and enzymes related to lipid metabolism account for variations in the lipid profile of each individual. As some genetic polymorphisms may cause dyslipidemia, these allele variants should be investigated in HIV-1-infected patients to identify individuals with an increased risk of developing dyslipidemia during treatment with HAART, particularly during therapy with PIs. This knowledge may guide individualized treatment decisions and lead to the development of new therapeutic targets for the treatment of dyslipidemia in these patients. PMID:24319689

  13. 4P: fast computing of population genetics statistics from large DNA polymorphism panels

    PubMed Central

    Benazzo, Andrea; Panziera, Alex; Bertorelle, Giorgio

    2015-01-01

    Massive DNA sequencing has significantly increased the amount of data available for population genetics and molecular ecology studies. However, the parallel computation of simple statistics within and between populations from large panels of polymorphic sites is not yet available, making the exploratory analyses of a set or subset of data a very laborious task. Here, we present 4P (parallel processing of polymorphism panels), a stand-alone software program for the rapid computation of genetic variation statistics (including the joint frequency spectrum) from millions of DNA variants in multiple individuals and multiple populations. It handles a standard input file format commonly used to store DNA variation from empirical or simulation experiments. The computational performance of 4P was evaluated using large SNP (single nucleotide polymorphism) datasets from human genomes or obtained by simulations. 4P was faster or much faster than other comparable programs, and the impact of parallel computing using multicore computers or servers was evident. 4P is a useful tool for biologists who need a simple and rapid computer program to run exploratory population genetics analyses in large panels of genomic data. It is also particularly suitable to analyze multiple data sets produced in simulation studies. Unix, Windows, and MacOs versions are provided, as well as the source code for easier pipeline implementations. PMID:25628874

  14. Interleukin-18 genetic polymorphisms contribute differentially to the susceptibility to Crohns disease

    PubMed Central

    Gao, Su-Jun; Zhang, Li; Lu, Wei; Wang, Lu; Chen, Lei; Zhu, Zhen; Zhu, Hai-Hang

    2015-01-01

    AIM: To investigate the correlation between interleukin-18 (IL-18) gene polymorphisms and the risk of developing Crohns disease (CD). METHODS: The PubMed, CISCOM, CINAHL, Web of Science, EBSCO, Cochrane Library, MEDLINE, EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1st, 2013. Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis. A meta-analysis was conducted using a random-effects model with STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated. RESULTS: Seven case-control studies, with a total of 1930 CD cases and 1930 healthy subjects, met our inclusion criteria. The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238 G>C polymorphisms may correlate with an increased risk of CD under five genetic models (all P < 0.05). Furthermore, we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models (C allele vs A allele: OR = 2.03, 95%CI: 1.20-3.43, P = 0.008; CC vs AA+AC: OR = 2.39, 95%CI: 1.2-4.43, P = 0.006; CC vs AC: OR = 2.31, 95%CI: 1.22-4.38, P = 0.010). However, such associations were not found for the IL-18 rs917997 C>T, codon 35 A>C and rs1946519 G>T polymorphisms (all P > 0.05). A subgroup analysis was conducted to investigate the effect of ethnicity on an individuals susceptibility to CD. Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans (all P < 0.05), but not among Caucasians (all P > 0.05). CONCLUSION: This meta-analysis indicated that the IL-18 rs1946518 A>C, rs187238 G>C and rs360718 A>C polymorphisms may contribute to susceptibility to CD, especially among Asians and Africans. These polymorphisms are known to reduce IL-18 mRNA and protein levels. PMID:26229413

  15. Genetic diversity and population structure in Harpadon nehereus based on sequence-related amplified polymorphism markers.

    PubMed

    Zhu, Z H; Li, H Y; Qin, Y; Wang, R X

    2014-01-01

    In this study, the genetic diversity among ten populations of the Bombay duck was studied on the basis of sequence-related amplified polymorphism (SRAP). The ten populations were collected from the East China Sea and South China Sea areas. A total of 98 loci were obtained from 292 individuals using eight SRAP primers. The average proportion of polymorphic loci, genetic diversity (H), and Shannon's information index were 75.20%, 0.2478, and 0.3735, respectively. Nei's genetic distance and Shannon's information index between the ten populations ranged from 0.0410 to 0.3841 and from 0.2396 to 0.4506, and the averages Nei's gene diversity index (H = 0.2478) and Shannon's information index (I = 0.3735) at the population level were high. AMOVA showed that most of the variation was within populations (71.74%), and only 28.26% of the variation was between populations. The neighbor-joining tree based on genetic distance revealed that significant genealogical structure existed throughout the examined range of the Bombay duck. The results demonstrated that SRAP marker was an effective tool for the assessment of genetic diversity in the Bombay duck. The results could be used for further protection of the germplasm resource of the Bombay duck. PMID:25117356

  16. Human Xq28 inversion polymorphism: From sex linkage to Genomics - A genetic mother lode.

    PubMed

    Kirby, Cait S; Kolber, Natalie; Salih Almohaidi, Asmaa M; Bierwert, Lou Ann; Saunders, Lori; Williams, Steven; Merritt, Robert

    2016-03-01

    An inversion polymorphism of the filamin and emerin genes at the tip of the long arm of the human X-chromosome serves as the basis of an investigative laboratory in which students learn something new about their own genomes. Long, nearly identical inverted repeats flanking the filamin and emerin genes illustrate how repetitive elements can lead to alterations in genome structure (inversions) through nonallelic homologous recombination. The near identity of the inverted repeats is an example of concerted evolution through gene conversion. While the laboratory in its entirety is designed for college level genetics courses, portions of the laboratory are appropriate for courses at other levels. Because the polymorphism is on the X-chromosome, the laboratory can be used in introductory biology courses to enhance understanding of sex-linkage and to test for Hardy-Weinberg equilibrium in females. More advanced topics, such as chromosome interference, the molecular model for recombination, and inversion heterozygosity suppression of recombination can be explored in upper-level genetics and evolution courses. DNA isolation, restriction digests, ligation, long PCR, and iPCR provide experience with techniques in molecular biology. This investigative laboratory weaves together topics stretching from molecular genetics to cytogenetics and sex-linkage, population genetics and evolutionary genetics. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:191-201, 2016. PMID:26956943

  17. Genetic Analysis of 430 Chinese Cynodon dactylon Accessions Using Sequence-Related Amplified Polymorphism Markers

    PubMed Central

    Huang, Chunqiong; Liu, Guodao; Bai, Changjun; Wang, Wenqiang

    2014-01-01

    Although Cynodon dactylon (C. dactylon) is widely distributed in China, information on its genetic diversity within the germplasm pool is limited. The objective of this study was to reveal the genetic variation and relationships of 430 C. dactylon accessions collected from 22 Chinese provinces using sequence-related amplified polymorphism (SRAP) markers. Fifteen primer pairs were used to amplify specific C. dactylon genomic sequences. A total of 481 SRAP fragments were generated, with fragment sizes ranging from 260–1800 base pairs (bp). Genetic similarity coefficients (GSC) among the 430 accessions averaged 0.72 and ranged from 0.53–0.96. Cluster analysis conducted by two methods, namely the unweighted pair-group method with arithmetic averages (UPGMA) and principle coordinate analysis (PCoA), separated the accessions into eight distinct groups. Our findings verify that Chinese C. dactylon germplasms have rich genetic diversity, which is an excellent basis for C. dactylon breeding for new cultivars. PMID:25338051

  18. Genetic analysis of 430 Chinese Cynodon dactylon accessions using sequence-related amplified polymorphism markers.

    PubMed

    Huang, Chunqiong; Liu, Guodao; Bai, Changjun; Wang, Wenqiang

    2014-01-01

    Although Cynodon dactylon (C. dactylon) is widely distributed in China, information on its genetic diversity within the germplasm pool is limited. The objective of this study was to reveal the genetic variation and relationships of 430 C. dactylon accessions collected from 22 Chinese provinces using sequence-related amplified polymorphism (SRAP) markers. Fifteen primer pairs were used to amplify specific C. dactylon genomic sequences. A total of 481 SRAP fragments were generated, with fragment sizes ranging from 260-1800 base pairs (bp). Genetic similarity coefficients (GSC) among the 430 accessions averaged 0.72 and ranged from 0.53-0.96. Cluster analysis conducted by two methods, namely the unweighted pair-group method with arithmetic averages (UPGMA) and principle coordinate analysis (PCoA), separated the accessions into eight distinct groups. Our findings verify that Chinese C. dactylon germplasms have rich genetic diversity, which is an excellent basis for C. dactylon breeding for new cultivars. PMID:25338051

  19. Prevalence of MTHFR C677T single nucleotide polymorphism in genetically isolated populations in Jordan.

    PubMed

    Dajani, Rana; Fathallah, Raja; Arafat, Ala; AbdulQader, Mohammed Emad; Hakooz, Nancy; Al-Motassem, Yousef; El-Khateeb, Mohammad

    2013-10-01

    Methylenetetrahydrofolate reductase (MTHFR) C677T single nucleotide polymorphism is a major inherited risk factor of venous thromboembolism. We sought to determine its prevalence in genetically isolated populations of Chechens and Circassians in Jordan. The MTHFR C677T mutation was analyzed from blood samples taken from 120 random unrelated Chechens and 72 Circassians. The prevalence of the MTHFR mutation in the Chechen population was 27.5% (allele frequency 15%); the prevalence among the Circassians was 50% (allele frequency 29.2%). The prevalence in the Chechen population is similar to that in Jordan and other world populations, but it is higher in the Circassian population. This study will contribute to understanding the interaction between genetic and environmental risk factors underlying thrombosis and will be useful in deciding which genetic variants should be tested in a clinical genetic testing service. PMID:23749065

  20. Association between pepsinogen C gene polymorphism and genetic predisposition to gastric cancer

    PubMed Central

    Liu, Hui-Jie; Guo, Xiao-Lin; Dong, Ming; Wang, Lan; Yuan, Yuan

    2003-01-01

    AIM: To identify a molecular marker for gastric cancer, and to investigate the relationship between the polymorphism of pepsinogen C (PGC) gene and the genetic predisposition to gastric cancer. METHODS: A total of 289 cases were involved in this study. 115 cases came from Shenyang area, a low risk area of gastric cancer, including 42 unrelated controls and 73 patients with gastric cancer. 174 cases came from Zhuanghe area, a high-risk area of gastric cancer, including 113 unrelated controls, and 61 cases from gastric cancer kindred families. The polymorphism of PGC gene was detected by polymerase chain reaction (PCR) and the relation between the genetic polymorphism of PGC and gastric cancer was examined. RESULTS: Four alleles, 310 bp (allele 1), 400 bp (allele 2), 450 bp (allele 3), and 480 bp (allele 4) were detected by PCR. The frequency of allele 1 was higher in patients with gastric cancer than that in controls. Genotypes containing homogenous allele 1 were significantly more frequent in patients with gastric cancer than that in controls (0.33, 0.14, ?2 = 3.86, P < 0.05). There was no significant difference between the control group of Zhuanghe and the group of gastric cancer kindred. But the frequency of allele 1 was higher in control group of Zhuanghe area than that in control group of Shenyang area and genotypes containing homogenous allele 1 were significantly more frequent in the control group of Zhuanghe area than those in control group of Shenyang area (0.33, 0.14, ?2 = 4.32, P < 0.05). In the group of gastric cancer kindred the frequency of allele 1 was significantly higher than that in control group of Shenyang area (0.5164, 0.3571, ?2 = 4.47, P < 0.05). Genotypes containing homogenous allele 1 were significantly more frequent in the group of gastric cancer kindred than those in control group of Shenyang area (0.36, 0.14, ?2 = 4.91, P < 0.05). CONCLUSION: These results suggest that there is some relation between pepsinogen C gene polymorphism and gastric cancer, and the person with homogenous allele 1 predisposes to gastric cancer than those with other genotypes. Pepsinogen C gene polymorphism may be used as a genetic marker for a genetic predisposition to gastric cancer. The distribution of pepsinogen C gene polymorphism in Zhuanghe, a high-risk area of gastric cancer, is different from that in Shenyang, a low risk area of gastric cancer. PMID:12508350

  1. A population genetics study of Anopheles darlingi (Diptera: Culicidae) from Colombia based on random amplified polymorphic DNA-polymerase chain reaction and amplified fragment lenght polymorphism markers.

    PubMed

    González, Ranulfo; Wilkerson, Richard; Suárez, Marco Fidel; García, Felipe; Gallego, Gerardo; Cárdenas, Heiber; Posso, Carmen Elisa; Duque, Myriam Cristina

    2007-06-01

    The genetic variation and population structure of three populations of Anopheles darlingi from Colombia were studied using random amplified polymorphic markers (RAPDs) and amplified fragment length polymorphism markers (AFLPs). Six RAPD primers produced 46 polymorphic fragments, while two AFLP primer combinations produced 197 polymorphic fragments from 71 DNA samples. Both of the evaluated genetic markers showed the presence of gene flow, suggesting that Colombian An. darlingi populations are in panmixia. Average genetic diversity, estimated from observed heterozygosity, was 0.374 (RAPD) and 0.309 (AFLP). RAPD and AFLP markers showed little evidence of geographic separation between eastern and western populations; however, the F ST values showed high gene flow between the two western populations (RAPD: F ST = 0.029; Nm: 8.5; AFLP: F ST = 0.051; Nm: 4.7). According to molecular variance analysis (AMOVA), the genetic distance between populations was significant (RAPD:phiST = 0.084; AFLP:phiST = 0.229, P < 0.001). The F ST distances and AMOVAs using AFLP loci support the differentiation of the Guyana biogeographic province population from those of the Chocó-Magdalena. In this last region, Chocó and Córdoba populations showed the highest genetic flow. PMID:17568929

  2. Polymorphic simple sequence repeat regions in chloroplast genomes: applications to the population genetics of pines.

    PubMed Central

    Powell, W; Morgante, M; McDevitt, R; Vendramin, G G; Rafalski, J A

    1995-01-01

    Simple sequence repeats (SSRs), consisting of tandemly repeated multiple copies of mono-, di-, tri-, or tetranucleotide motifs, are ubiquitous in eukaryotic genomes and are frequently used as genetic markers, taking advantage of their length polymorphism. We have examined the polymorphism of such sequences in the chloroplast genomes of plants, by using a PCR-based assay. GenBank searches identified the presence of several (dA)n.(dT)n mononucleotide stretches in chloroplast genomes. A chloroplast (cp) SSR was identified in three pine species (Pinus contorta, Pinus sylvestris, and Pinus thunbergii) 312 bp upstream of the psbA gene. DNA amplification of this repeated region from 11 pine species identified nine length variants. The polymorphic amplified fragments were isolated and the DNA sequence was determined, confirming that the length polymorphism was caused by variation in the length of the repeated region. In the pines, the chloroplast genome is transmitted through pollen and this PCR assay may be used to monitor gene flow in this genus. Analysis of 305 individuals from seven populations of Pinus leucodermis Ant. revealed the presence of four variants with intrapopulational diversities ranging from 0.000 to 0.629 and an average of 0.320. Restriction fragment length polymorphism analysis of cpDNA on the same populations previously failed to detect any variation. Population subdivision based on cpSSR was higher (Gst = 0.22, where Gst is coefficient of gene differentiation) than that revealed in a previous isozyme study (Gst = 0.05). We anticipate that SSR loci within the chloroplast genome should provide a highly informative assay for the analysis of the genetic structure of plant populations. Images Fig. 2 PMID:7644491

  3. COMT val158met and 5-HTTLPR genetic polymorphisms moderate executive control in cannabis users.

    PubMed

    Verdejo-Garca, Antonio; Fagundo, Ana Beatriz; Cuenca, Aida; Rodriguez, Joan; Cuys, Elisabet; Langohr, Klaus; de Sola Llopis, Susana; Civit, Ester; Farr, Mag; Pea-Casanova, Jordi; de la Torre, Rafael

    2013-07-01

    The adverse effects of cannabis use on executive functions are still controversial, fostering the need for novel biomarkers able to unveil individual differences in the cognitive impact of cannabis consumption. Two common genetic polymorphisms have been linked to the neuroadaptive impact of ?9-tetrahydrocannabinol (THC) exposure and to executive functions in animals: the catechol-O-methyltransferase (COMT) gene val158met polymorphism and the SLC6A4 gene 5-HTTLPR polymorphism. We aimed to test if these polymorphisms moderate the harmful effects of cannabis use on executive function in young cannabis users. We recruited 144 participants: 86 cannabis users and 58 non-drug user controls. Both groups were genotyped and matched for genetic makeup, sex, age, education, and IQ. We used a computerized neuropsychological battery to assess different aspects of executive functions: sustained attention (CANTAB Rapid Visual Information Processing Test, RVIP), working memory (N-back), monitoring/shifting (CANTAB ID/ED set shifting), planning (CANTAB Stockings of Cambridge, SOC), and decision-making (Iowa Gambling Task, IGT). We used general linear model-based analyses to test performance differences between cannabis users and controls as a function of genotypes. We found that: (i) daily cannabis use is not associated with executive function deficits; and (ii) COMT val158met and 5-HTTLPR polymorphisms moderate the link between cannabis use and executive performance. Cannabis users carrying the COMT val/val genotype exhibited lower accuracy of sustained attention, associated with a more strict response bias, than val/val non-users. Cannabis users carrying the COMT val allele also committed more monitoring/shifting errors than cannabis users carrying the met/met genotype. Finally, cannabis users carrying the 5-HTTLPR s/s genotype had worse IGT performance than s/s non-users. COMT and SLC6A4 genes moderate the impact of cannabis use on executive functions. PMID:23449176

  4. Association of Genetic Polymorphisms of EGFR with Glioma in a Chinese Population

    PubMed Central

    Wang, Xinyu; Zhang, Huawei; Wang, Donghai

    2015-01-01

    Objective: Several studies indicated that genetic polymorphisms in the epidermal growth factor receptor (EGFR) gene were associated with glioma risk. However, the relationship between EGFR genetic polymorphisms and glioma remains unclear in the Chinese population. Methods: We designed a casecontrol study by selecting 300 histologically confirmed adult glioma patients and 300 cancer-free controls to analyze the distribution of EGFR genotype. Two single-nucleotide polymorphisms, rs730437 and rs1468727, were genotyped by using the polymerase chain reaction-restriction fragment length polymorphism method. Results: We found that the CC genotype of rs1468727 was more common in the glioma group than in the control group (p=0.021). We also found that the C allele frequency was higher in the glioma group than that in the control group (p=0.005; odds ratio [OR]=1.38, 95% confidence interval [CI]: 1.1011.740). For rs730437, we found both the AA genotype (p=0.011) and A allele frequency (p=0.003; OR=0.703; 95% CI: 0.5580.886) were significantly lower in the glioma patients than in the control subjects, respectively. Haplotype analysis showed that the A T haplotype frequency was higher in the control group than in the glioma group (p=0.005; OR=0.722; 95% CI: 0.5750.908). However, the CC haplotype frequency was higher in the glioma group than in the control group (p=0.003; OR=1.423; 95% CI: 1.1291.793). Conclusion: Our study indicates that polymorphisms in the EGFR gene are associated with glioma susceptibility in the Chinese population. PMID:25514356

  5. Investigating the potential genetic association between RANBP9 polymorphisms and the risk of schizophrenia.

    PubMed

    Bae, Joon Seol; Kim, Jason Yongha; Park, Byung-Lae; Cheong, Hyun Sub; Kim, Jeong-Hyun; Namgoong, Suhg; Kim, Ji-On; Park, Chul Soo; Kim, Bong-Jo; Lee, Cheol-Soon; Lee, Migyung; Choi, Woo Hyuk; Shin, Tae-Min; Hwang, Jaeuk; Shin, Hyoung Doo; Woo, Sung-Il

    2015-04-01

    Schizophrenia is a serious mental disorder that is affected by genetic and environmental factors. As the disease has a high heritability rate, genetic studies identifying candidate genes for schizophrenia have been conducted in various populations. The gene for human Ran?binding protein 9 (RANBP9) is a newly discovered candidate gene for schizophrenia. As RANBP9 is a small guanosine?5'?triphosphate?binding protein that interacts with the disrupted in schizophrenia 1 protein, it is considered to be an important molecule in the pathogenesis of schizophrenia. However, to date, no study has examined the possible association between the genetic variations of RANBP9 and the risk of schizophrenia. In the present study, it was hypothesized that RANBP9 variations may influence the risk of schizophrenia. In order to investigate the association between RANBP9 polymorphisms and the risk of schizophrenia and smooth pursuit eye movement (SPEM) abnormalities, a case?control association analysis was performed. Using a TaqMan assay, five single?nucleotide polymorphisms and an insertion/deletion variation within the start codon region of RANBP9 were genotyped. Five major haplotypes were identified in 449 patients with schizophrenia and 393 unrelated healthy individuals as controls (total, n=842). However, the association analyses revealed no associations between all genetic variants and schizophrenia and SPEM abnormality. To the best of our knowledge, this is the first study to investigate an association between RANBP9 polymorphisms and schizophrenia and SPEM abnormality. The findings of allele frequencies and association results in this study may aid in further genetic etiological studies in schizophrenia in various populations. PMID:25482375

  6. Relationship between CYP17A1 Genetic Polymorphism and Essential Hypertension in a Chinese Population

    PubMed Central

    Dai, Chuan-Fang; Xie, Xiang; Ma, Yi-Tong; Yang, Yi-Ning; Li, Xiao-Mei; Fu, Zhen-Yan; Liu, Fen; Chen, Bang-Dang; Gai, Min-Tao

    2015-01-01

    The relationship between CYP17A1 genetic polymorphisms and essential hypertension (EH) remains unclear. The aim of this study was to investigate the association of CYP17A1 genetic polymorphisms with EH in Han and Uighur populations in China. A Han population including 558 people (270 EH patients and 288 controls) and a Uighur population including 473 people (181 EH patients and 292 controls) were selected. Five single-nucleotide polymorphisms (SNPs) (rs4919686, rs1004467, rs4919687, rs10786712, and rs2486758) were genotyped using real-time PCR (TaqMan). In the Uighur population, for the total and the men, rs4919686, rs4919687 and rs10786712 were found to be associated with EH (rs4919686: P?0.02, rs4919687: P?0.002, rs10786712: P?0.004, respectively). The difference remained statistically significant after the multivariate adjustment (all P<0.05). The overall distributions of the haplotypes established by SNP1-SNP3, SNP1-SNP4, SNP1-SNP3-SNP5 and SNP1-SNP4-SNP5 were significantly different between the EH patients and the control subjects (for the total: P=0.013, P=0.008, P=0.032, P=0.010, for men: P<0.001, P=0.001, P=0.010, P=0.00). In the Han population, for men, rs2486758 was found to be associated with EH in a recessive model (P=0.007); the significant difference was not retained after the adjustment for the covariates (date not shown). The A allele of rs4919686 could be a susceptible genetic marker, and the T allele of rs10786712 could be a protective genetic marker of EH. The AC genotype of rs4919686, the AG genotype of rs4919687 and the TT genotype of rs10786712 could be protective genetic markers of EH. PMID:26618050

  7. Novel Polymorphic Microsatellite Markers Reveal Genetic Differentiation between Two Sympatric Types of Galaxea fascicularis

    PubMed Central

    Nakajima, Yuichi; Shinzato, Chuya; Satoh, Noriyuki; Mitarai, Satoshi

    2015-01-01

    The reef-building, scleractinian coral, Galaxea fascicularis, is classified into soft and hard types, based on nematocyst morphology. This character is correlated with the length of the mitochondrial non-coding region (mt-Long: soft colony type, and nematocysts with wide capsules and long shafts; mt-Short: hard colony type, and nematocysts with thin capsules and short shafts). We isolated and characterized novel polymorphic microsatellite markers for G. fascicularis using next-generation sequencing. Based upon the mitochondrial non-coding region, 53 of the 97 colonies collected were mt-Long (mt-L) and 44 were mt-Short (mt-S). Among the 53 mt-L colonies, 27 loci were identified as amplifiable, polymorphic microsatellite loci, devoid of somatic mutations and free of scoring errors. Eleven of those 27 loci were also amplifiable and polymorphic in the 44 mt-S colonies; these 11 are cross-type microsatellite loci. The other 16 loci were considered useful only for mt-L colonies. These 27 loci identified 10 multilocus lineages (MLLs) among the 53 mt-L colonies (NMLL/N = 0.189), and the 11 cross-type loci identified 7 MLLs in 44 mt-S colonies (NMLL/N = 0.159). Significant genetic differentiation between the two types was detected based on the genetic differentiation index (FST = 0.080, P = 0.001). Bayesian clustering also indicated that these two types are genetically isolated. While nuclear microsatellite genotypes also showed genetic differentiation between mitochondrial types, the mechanism of divergence is not yet clear. These markers will be useful to estimate genetic diversity, differentiation, and connectivity among populations, and to understand evolutionary processes, including divergence of types in G. fascicularis. PMID:26147677

  8. CYP2D6 Genetic Polymorphisms and Phenotypes in Different Ethnicities of Malaysian Breast Cancer Patients.

    PubMed

    Chin, Fee Wai; Chan, Soon Choy; Abdul Rahman, Sabariah; Noor Akmal, Sharifah; Rosli, Rozita

    2016-01-01

    The cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) is an enzyme that is predominantly involved in the metabolism of tamoxifen. Genetic polymorphisms of the CYP2D6 gene may contribute to inter-individual variability in tamoxifen metabolism, which leads to the differences in clinical response to tamoxifen among breast cancer patients. In Malaysia, the knowledge on CYP2D6 genetic polymorphisms as well as metabolizer status in Malaysian breast cancer patients remains unknown. Hence, this study aimed to comprehensively identify CYP2D6 genetic polymorphisms among 80 Malaysian breast cancer patients. The genetic polymorphisms of all the 9 exons of CYP2D6 gene were identified using high-resolution melting analysis and confirmed by DNA sequencing. Seven CYP2D6 alleles consisting of CYP2D6*1, CYP2D6*2, CYP2D6*4, CYP2D6*10, CYP2D6*39, CYP2D6*49, and CYP2D6*75 were identified in this study. Among these alleles, CYP2D6*10 is the most common allele in both Malaysian Malay (54.8%) and Chinese (71.4%) breast cancer patients, whereas CYP2D6*4 in Malaysian Indian (28.6%) breast cancer patients. In relation to CYP2D6 genotype, CYP2D6*10/*10 is more frequently observed in both Malaysian Malay (28.9%) and Chinese (57.1%) breast cancer patients, whereas CYP2D6*4/*10 is more frequently observed in Malaysian Indian (42.8%) breast cancer patients. In terms of CYP2D6 phenotype, 61.5% of Malaysian Malay breast cancer patients are predicted as extensive metabolizers in which they are most likely to respond well to tamoxifen therapy. However, 57.1% of Chinese as well as Indian breast cancer patients are predicted as intermediate metabolizers and they are less likely to gain optimal benefit from the tamoxifen therapy. This is the first report of CYP2D6 genetic polymorphisms and phenotypes in Malaysian breast cancer patients for different ethnicities. These data may aid clinicians in selecting an optimal drug therapy for Malaysian breast cancer patients, hence improve the clinical outcome of the patients. PMID:26510986

  9. Genetic polymorphisms of TNFA and IL-1A and generalized aggressive periodontitis.

    PubMed

    Barnea, Teodora Virginia; Sava, Anca; Gentimir, Carmen; Goriuc, Ancu?a; Boi?teanu, Otilia; Chelaru, Liliana; Iancu, Roxana Irina; Avram, C?t?lina Anda; Acatrinei, Drago? Daniel; Bogza, Elena Geanina; R?ducanu, Oana Cristina; Cioloca, Daniel Petru; Vasincu, Decebal; Costuleanu, Marcel

    2015-01-01

    Virulent bacteria could cause gingival fibroblasts apoptosis through lipopolysaccharide release during generalized aggressive periodontitis (GAgP) development and evolution. We showed that treatment with lipopolysaccharide (LPS, 1 ?g/mL) for 30 days induced the decrease in the number of cultured rat gingival fibroblasts as compared to control group, which received no treatment. GAgP is considered to have also a genetic etiology, so the aim of our study was to evaluate if some polymorphisms of tumor necrosis factor-alpha (TNFA) and interleukin 1A (IL-1A) genes are associated with GAgP in a sample of Romanian population. We selected a group of 32 subjects (22 cases and 10 controls) for studying the TNFA (-857) polymorphism and 97 subjects (66 cases and 31 controls) for IL-1A (-889) polymorphism. The single nucleotide polymorphisms were genotyped by real-time polymerase chain reaction for all subjects. The genotype and allelic distribution tended to be equally between the cases and the controls group. Similar results were obtained for the dominant and recessive model. The difference between the two groups did not reach statistic significance for neither of the two studied polymorphisms [p=0.76 for TNFA (-857) and p=0.84 for IL-1A (-889)]. The data suggest that TNFA (-857) C/T and IL-1A (-889) C/T polymorphisms are not associated with susceptibility to GAgP in this Romanian population, potentially because of the small sample size. This is the first such study for Romanian northeastern population. PMID:26193214

  10. Random Amplified Polymorphic Markers as Indicator for Genetic Conservation Program in Iranian Pheasant (Phasianus colchicus)

    PubMed Central

    Elyasi Zarringhabaie, Ghorban; Javanmard, Arash; Pirahary, Ommolbanin

    2012-01-01

    The objective of present study was identification of genetic similarity between wild Iran and captive Azerbaijan Pheasant using PCR-RAPD markers. For this purpose, in overall, 28 birds were taken for DNA extraction and subsequently 15 arbitrary primers were applied for PCR-RAPD technique. After electrophoresis, five primers exhibited sufficient variability which yielded overall 65 distinct bands, 59 polymorphic bands, for detalis, range of number of bands per primer was 10 to 14, and produced size varied between 200 to 1500 bp. Highest and lowest polymorphic primers were OPC5, OPC16 (100%) and OPC15 (81%), respectively. Result of genetic variation between two groups was accounted as nonsignificant (8.12%) of the overall variation. According to our expectation the wild Iranian birds showed higher genetic diversity value than the Azerbaijan captive birds. As general conclusion, two pheasant populations have almost same genetic origin and probably are subpopulations of one population. The data reported herein could open the opportunity to search for suitable conservation strategy to improve richness of Iran biodiversity and present study here was the first report that might have significant impact on the breeding and conservation program of Iranian pheasant gene pool. Analyses using more regions, more birds, and more DNA markers will be useful to confirm or to reject these findings. PMID:23002388

  11. Relationships of related genetic polymorphisms and individualized medication of tacrolimus in patients with renal transplantation

    PubMed Central

    Zhu, Lin; Zhang, Jing; Song, Hongtao; Wang, Qinghua; Tan, Jianming; Wu, Weizhen; Lin, Meiqin

    2015-01-01

    The aim of this study was to establish clinical and genetic factors-based individual administration model of tacrolimus for Chinese Han patients after renal transplantation (RT). The genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 in 216 RT patients were detected by PCR-RFLP, the genetic and clinical factors and blood concentration/dose body weight (C/D) values of tacrolimus were performed the single factor correlation analysis, and established the dose prediction algorithm of tacrolimus by stepwise multiple regression analysis. CYP3A5*3, hematocrit and albumin were correlated with the C/D values of tacrolimus, the best regression model could explain 28.3% reason of individual dose differences of tacrolimus, among which CYP3A5*3 polymorphism could explain 23.5%. The genetic factors played an important role in the dose differences of tacrolimus, the patients should be checked CYP3A5*3 genotype before administration of tacrolimus to predict the tacrolimus doses, thus helping to improve the safety and effectiveness of tacrolimus application. PMID:26770526

  12. Novel polymorphic microsatellite markers for Bellamya and their application in population genetics of three species.

    PubMed

    Gu, Q H; Cheng, Q Q; Li, X J; Zhou, C J

    2015-01-01

    Bellamya is a widely distributed freshwater snail genus in China; however, its genetic diversity is completely unknown. Sixty-five novel microsatellite loci were isolated and characterized from a microsatellite-enriched library of Bellamya aeruginosa genomic DNA. Most of the 65 loci were successfully amplified. We found high polymorphic information content values for these loci, ranging from 0.235 to 0.892. There were 3 to 12 alleles per locus, and the HE and HO varied from 0.425 to 0.953 and 0.026 to 1.000, respectively. Fifteen loci deviated significantly from Hardy-Weinberg equilibrium after Bonferroni's correction. All 65 SSR markers were tested in an additional five Bellamya species, and 96.9% of the 325 locus/taxon combinations tested resulted in cross-species amplification. Seven polymorphic microsatellite markers were randomly selected for comparison among nine populations of three species. All populations had moderate to high genetic diversity. In genetic distance-based cluster analysis, the populations of B. aeruginosa and B. dispiralis formed species-based clusters, whereas populations of B. angularia did not. The three examined Bellamya species could be differentiated using SSR markers. These microsatellite loci should be useful for genetic diversity analysis, analysis of phylogenetic relationship, and species delimitation of Bellamya. PMID:26634483

  13. Genetic Analysis of Diversity within a Chinese Local Sugarcane Germplasm Based on Start Codon Targeted Polymorphism

    PubMed Central

    Que, Youxiong; Pan, Yongbao; Lu, Yunhai; Yang, Cui; Yang, Yuting; Huang, Ning; Xu, Liping

    2014-01-01

    In-depth information on sugarcane germplasm is the basis for its conservation and utilization. Data on sugarcane molecular markers are limited for the Chinese sugarcane germplasm collections. In the present study, 20 start codon targeted (SCoT) marker primers were designed to assess the genetic diversity among 107 sugarcane accessions within a local sugarcane germplasm collection. These primers amplified 176 DNA fragments, of which 163 were polymorphic (92.85%). Polymorphic information content (PIC) values ranged from 0.783 to 0.907 with a mean of 0.861. Unweighted pair group method of arithmetic averages (UPGMA) cluster analysis of the SCoT marker data divided the 107 sugarcane accessions into six clusters at 0.674 genetic similarity coefficient level. Relatively abundant genetic diversity was observed among ROC22, ROC16, and ROC10, which occupied about 80% of the total sugarcane acreage in China, indicating their potential breeding value on Mainland China. Principal component analysis (PCA) partitioned the 107 sugarcane accessions into two major groups, the Domestic Group and the Foreign Introduction Group. Each group was further divided based on institutions, where the sugarcane accessions were originally developed. The knowledge of genetic diversity among the local sugarcane germplasm provided foundation data for managing sugarcane germplasm, including construction of a core collection and regional variety distribution and subrogation. PMID:24779012

  14. [Genetic diversity analysis of Chinese stylo anthracnose pathogens using random amplified polymorphic DNA].

    PubMed

    Yi, Kexian; Huang, Junsheng; Liu, Guodao; Pauline, Weeds; Sukumar, Charkraborty

    2003-06-01

    Genetic diversity of 43 Colletotrichum gloeosporioides isolates from stylo in China were analyzed using random amplified polymorphic DNA (RAPD) with eight arbitrary 10-base oligonucleotide primers compared with 276 isolates from other countries including two of Colletotrichum cutaturn based on a wide survey and disease sample collection. The results showed a good DNA polymorphism between isolates. The amplified fragments were between 0.3-2.8 kb. Chinese isolates were grouped in clusters II, III and VI with the majority in cluster VI based on six clusters of isolates from South America, the centre of origin of Stylosanthes genus. The genetic variation in the Chinese pathogen population was very limited compared with that in South America, the centre of host-pathogen diversity. The results also showed that a genetic variation in Chinese population of Colletotrichum gloeosporioides existed, though this variation was less significant. Isolates grouped by geographic origin and host species or genotypes indicated isolates from different host species or genotypes had their own parasitic specialization on genetic basis and pathogens from different countries evolved in their own way relatively. PMID:16279206

  15. Genetic Diversity Analysis of Hypsizygus marmoreus with Target Region Amplification Polymorphism

    PubMed Central

    Qiu, Chengshu; Yan, Wenjuan; Deng, Wangqiu; Song, Bin; Li, Taihui

    2014-01-01

    Hypsizygus marmoreus is an industrialized edible mushroom. In the present paper, the genetic diversity among 20 strains collected from different places of China was evaluated by target region amplification polymorphism (TRAP) analysis; the common fragment of TRAPs was sequenced and analyzed. Six fixed primers were designed based on the analysis of H. marmoreus sequences from GenBank database. The genomic DNA extracted from H. marmoreus was amplified with 28 TRAP primer combinations, which generated 287 bands. The average of amplified bands per primer was 10.27 (mean polymorphism is 69.73%). The polymorphism information content (PIC) value for TRAPs ranged from 0.32 to 0.50 (mean PIC value per TRAP primer combination is 0.48), which indicated a medium level of polymorphism among the strains. A total of 36 sequences were obtained from TRAP amplification. Half of these sequences could encode the known or unknown proteins. According to the phylogenetic analysis based on TRAP result, the 20 strains of H. marmoreus were classified into two main groups. PMID:25013861

  16. Genetic Polymorphisms Involved in Folate Metabolism and Maternal Risk for Down Syndrome: A Meta-Analysis

    PubMed Central

    Balduino Victorino, Daniella; de Godoy, Moacir Fernandes; Goloni-Bertollo, Eny Maria; Pavarino, rika Cristina

    2014-01-01

    Inconclusive results of the association between genetic polymorphisms involved in folate metabolism and maternal risk for Down syndrome (DS) have been reported. Therefore, this meta-analysis was conducted. We searched electronic databases through May, 2014, for eligible studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association, which was estimated by fixed or random effects models. Heterogeneity among studies was evaluated using Q-test and I2 statistic. Subgroup and sensitivity analyses were also conducted. Publication bias was estimated using Begg's and Egger's tests. A total of 17 case-controls studies were included. There was evidence for an association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS. In the subgroup analysis, increased maternal risk for DS was found in Caucasians. Additionally, the polymorphic heterozygote MTHFD1 1958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies conformed to Hardy-Weinberg equilibrium. Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.844ins68, no significant associations have been found, neither in the overall analyses nor in the stratified analyses by ethnicity. In conclusion, our meta-analysis suggested that the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS. PMID:25544792

  17. Genetic polymorphisms involved in folate metabolism and maternal risk for down syndrome: a meta-analysis.

    PubMed

    Balduino Victorino, Daniella; de Godoy, Moacir Fernandes; Goloni-Bertollo, Eny Maria; Pavarino, rika Cristina

    2014-01-01

    Inconclusive results of the association between genetic polymorphisms involved in folate metabolism and maternal risk for Down syndrome (DS) have been reported. Therefore, this meta-analysis was conducted. We searched electronic databases through May, 2014, for eligible studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association, which was estimated by fixed or random effects models. Heterogeneity among studies was evaluated using Q-test and I (2) statistic. Subgroup and sensitivity analyses were also conducted. Publication bias was estimated using Begg's and Egger's tests. A total of 17 case-controls studies were included. There was evidence for an association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS. In the subgroup analysis, increased maternal risk for DS was found in Caucasians. Additionally, the polymorphic heterozygote MTHFD1 1958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies conformed to Hardy-Weinberg equilibrium. Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.844ins68, no significant associations have been found, neither in the overall analyses nor in the stratified analyses by ethnicity. In conclusion, our meta-analysis suggested that the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS. PMID:25544792

  18. Genetic polymorphism of APOB is associated with diabetes mellitus in sickle cell disease

    PubMed Central

    Zhang, Xu; Zhang, Wei; Saraf, Santosh L.; Nouraie, Mehdi; Han, Jin; Gowhari, Michel; Hassan, Johara; Miasnikova, Galina; Sergueeva, Adelina; Nekhai, Sergei; Kittles, Rick; Machado, Roberto F.; Garcia, Joe G N; Gladwin, Mark T.; Steinberg, Martin H.; Sebastiani, Paola; McClain, Donald A.; Gordeuk, Victor R.

    2015-01-01

    Environmental variations have strong influences in the etiology of type 2 diabetes mellitus. In this study, we investigated the genetic basis of diabetes in patients with sickle cell disease (SCD), a Mendelian disorder accompanied by distinct physiological conditions of hypoxia and hyperactive erythropoiesis. Compared to the general African-American population, the prevalence of diabetes as assessed in two SCD cohorts of 856 adults was low, but it markedly increased with older age and overweight. Meta-analyses of over 5 million single nucleotide polymorphisms (SNPs) in the two SCD cohorts identified a SNP, rs59014890, the C allele of which associated with diabetes risk at P= 3.210-8 and, surprisingly, associated with decreased APOB expression in peripheral blood mononuclear cells (PBMCs). The risk allele of the APOB polymorphism was associated with overweight in 181 SCD adolescents, with diabetes risk in 592 overweight, non-SCD African Americans ?45 years of age, and with elevated plasma lipid concentrations in general populations. In addition, lower expression level of APOB in PBMCs was associated with higher values for percent hemoglobin A1C and serum total cholesterol and triglyceride concentrations in patients with Chuvash polycythemia, a congenital disease with elevated hypoxic responses and increased erythropoiesis at normoxia. Our study reveals a novel, environment-specific genetic polymorphism that may affect key metabolic pathways contributing to diabetes in SCD. PMID:26025476

  19. Individual Variations in Inorganic Arsenic Metabolism Associated with AS3MT Genetic Polymorphisms

    PubMed Central

    Agusa, Tetsuro; Fujihara, Junko; Takeshita, Haruo; Iwata, Hisato

    2011-01-01

    Individual variations in inorganic arsenic metabolism may influence the toxic effects. Arsenic (+3 oxidation state) methyltransferase (AS3MT) that can catalyze the transfer of a methyl group from S-adenosyl-l-methionine (AdoMet) to trivalent arsenical, may play a role in arsenic metabolism in humans. Since the genetic polymorphisms of AS3MT gene may be associated with the susceptibility to inorganic arsenic toxicity, relationships of several single nucleotide polymorphisms (SNPs) in AS3MT with inorganic arsenic metabolism have been investigated. Here, we summarize our recent findings and other previous studies on the inorganic arsenic metabolism and AS3MT genetic polymorphisms in humans. Results of genotype dependent differences in arsenic metabolism for most of SNPs in AS3MT were Inconsistent throughout the studies. Nevertheless, two SNPs, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the populations examined for the analysis. Thus, these SNPs may be useful indicators to predict the arsenic metabolism via methylation pathways. PMID:21731446

  20. Genetic polymorphisms and cerebrovascular disease in children with sickle cell anemia from Rio de Janeiro, Brazil.

    PubMed

    Filho, Isaac Lima da Silva; Leite, Ana Claudia Celestino Bezerra; Moura, Patrcia Gomes; Ribeiro, Georgina Severo; Cavalcante, Andra Cony; Azevedo, Flvia Carolina Marques de; Andrada-Serpa, Maria Jos de

    2011-06-01

    The aim of the present work was to examine possible genetic risk factors related to the occurrence of cerebrovascular disease (CVD) in Brazilian population, the frequency of ?(S)-globin gene haplotypes and co-inheritance with ?-thalassemia (-?(3.7kb)) and single nucleotide polymorphism of methylenetetrahydrofolate reductase (MTHFR-C677T), Factor V Leiden (FV-G1691A) and prothrombin (PT-G20210A) genes in children from Rio de Janeiro. Ninety four children with sickle cell anemia (SCA) were included, 24 patients with cerebrovascular involvement and 70 patients without CVD as control group. The mean age of children at the time of the cerebrovascular event was similar to the control group. The frequency of -?(3.7kb) thalassemia was similar in both groups (p=0.751). Children with Bantu/Atypical ?(S)-globin gene haplotype presented 15 times more chance (OR=15.4 CI 95% 2.9-81.6) of CVD than the other ?(S)-globin gene haplotypes. The C677T polymorphism of MTHFR gene was similar in both groups (p=0.085). No mutation in the FV Leiden or PT genes was found. A large study seems necessary to establish the role of these genetic polymorphisms in Brazilian miscegenated population. PMID:21755116

  1. [Genetic polymorphisms of SLCO1B1 for drug pharmacokinetics and its clinical implications].

    PubMed

    Takane, Hiroshi

    2011-01-01

    Various drug transporters are selectively expressed in single or multiple tissues, such as the intestine, liver and kidney, where these transporters play various roles in drug absorption, distribution and excretion. Genetic polymorphisms in drug transporters as well as drug-metabolizing enzymes are associated with interindividual differences in drug disposition, efficacy and toxicity. Organic anion transporting polypeptide 1B1 (OATP1B1, gene SLCO1B1) is expressed on the basolateral membrane of hepatocytes and can facilitate hepatic uptake of certain clinically relevant drugs such as statins except for fluvastatin, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, antidiabetic drug (repaglinide) and anticancer drugs (SN-38 and methotrexate). Some single nucleotide polymorphisms or haplotypes of the SLCO1B1 gene have been identified and demonstrated to have functional significance for transporter activity. For examples, the SLCO1B1*15 haplotype (or 521T>C genotype) results in decreased uptake activity of SN-38 from systemic circulation, leading to increased plasma concentration of SN-38 and an enhanced risk of neutropenia. This review focuses on the impact of genetic polymorphisms of the SLCO1B1 gene on transport activity, and implications for the clinical efficacy and toxicity of clinically useful drugs. PMID:22041697

  2. Genetic basis of a color pattern polymorphism in the Coqui Frog Eleutherodactylus coqui.

    PubMed

    O'Neill, Eric M; Beard, Karen H

    2010-01-01

    Many species of frog exhibit striking color and pattern polymorphisms, but the genetic bases of these traits are not known for most species. The coqui frog, Eleutherodactylus coqui, a species endemic to the island of Puerto Rico, exhibits a wide variety of color and pattern polymorphisms including 4 discrete stripe patterns on its dorsal surface and an unstriped morph. We conducted breeding experiments to determine the mode of inheritance for these 5 dorsal color patterns in E. coqui. We analyzed results from 14 different cross types, which included 1519 offspring from 71 clutches. We found that color patterns segregate at ratios consistent with a single autosomal locus, 5-allele model, in which all alleles coding for stripes are codominant and the allele coding for the unstriped morph is recessive. We propose that this locus be named "stripes" with alleles B (interocular bar), L (dorsolateral stripes), N (narrow middorsal stripe), W (wide middorsal stripe), and u (unstriped). The results of this experiment suggest the genetic basis of stripe patterns in this well-studied species and provide a model for studying the evolution and maintenance of this phenotypic polymorphism. PMID:20643755

  3. Lung Cancer Risk and Genetic Polymorphisms in DNA Repair Pathways: A Meta-Analysis

    PubMed Central

    Kiyohara, Chikako; Takayama, Koichi; Nakanishi, Yoichi

    2010-01-01

    Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. We conducted a meta-analysis of epidemiologic studies on the association between genetic polymorphisms in both base excision repair and nucleotide excision repair pathways, and lung cancer. We found xeroderma pigmentosum complementation group A (XPA) G23A (odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.610.94), 8-oxoguanine DNA glycosylase 1 (OGG1) Ser326Cys (OR = 1.22, 95%?CI = 1.021.45), and excision repair cross-complementing group 2 (ERCC2) Lys751Gln (OR = 1.27, 95%?CI = 1.101.46) polymorphisms were associated with lung cancer risk. Considering the data available, it can be conjectured that if there is any risk association between a single SNP and lung cancer, the risk fluctuation will probably be minimal. Advances in the identification of new polymorphisms and in high-throughput genotyping techniques will facilitate the analysis of multiple genes in multiple DNA repair pathways. Therefore, it is likely that the defining feature of future epidemiologic studies will be the simultaneous analysis of large samples of cases and controls. PMID:20981350

  4. Comparison of Randomly Amplified Polymorphic DNA with Amplified Fragment Length Polymorphism To Assess Genetic Diversity and Genetic Relatedness within Genospecies III of Pseudomonas syringae

    PubMed Central

    Clerc, Agathe; Manceau, Charles; Nesme, Xavier

    1998-01-01

    Recently, DNA pairing analyses showed that Pseudomonas syringae pv. tomato and related pathovars, including P. syringae pv. maculicola, form a genomic species (Pseudomonas tomato) (L. Gardan, H. L. Shafik, and P. A. D. Grimont, p. 445448, in K. Rudolph, T. J. Burr, J. W. Mansfield, D. Stead, A. Vivian, and J. von Kietzell, ed., Pseudomonas syringae Pathovars and Related Pathogens, 1997). The genetic diversity of 23 strains belonging to this genomic species and 4 outgroup strains was analyzed with randomly amplified polymorphic DNA (RAPD) and amplified fragment length polymorphic (AFLP) techniques. Simple boiling of P. syringae cells was suitable for subsequent DNA amplification to obtain reliable patterns in RAPD and AFLP analyses. In general, the grouping of P. syringae strains by both analysis techniques corresponded well with the classification obtained from an RFLP analysis of ribosomal DNA operons, DNA pairing studies, and an analysis of pathogenicity data. However, two strains of P. syringae pv. maculicola produced distinct DNA patterns compared to the DNA patterns of other P. syringae pv. maculicola strains; these patterns led us to assume that horizontal transfer of DNA could occur between bacterial populations. Both techniques used in this study have high discriminating power because strains of P. syringae pv. tomato and P. syringae pv. maculicola which were indistinguishable by other techniques, including pathogenicity tests on tomato, were separated into two groups by both RAPD and AFLP analyses. In addition, data analysis showed that the AFLP method was more efficient for assessing intrapathovar diversity than RAPD analysis and allowed clear delineation between intraspecific and interspecific genetic distances, suggesting that it could be an alternative to DNA pairing studies. However, it was not possible to distinguish the two races of P. syringae pv. tomato on the basis of an analysis of the data provided by either the AFLP or RAPD technique. PMID:16349533

  5. Genetic polymorphism of the beta-2 adrenergic receptor in atopic and non-atopic subjects.

    PubMed

    Potter, P C; Van Wyk, L; Martin, M; Lentes, K U; Dowdle, E B

    1993-10-01

    To investigate a possible genetic basis for reported differences in beta-2 receptor expression in atopic subjects, DNA from 42 atopic children (22 asthmatics and 22 with allergic rhinitis) and 30 non-atopic subjects was Southern blotted and Ban-1 restriction fragment polymorphisms (RFLPS) were studied using a 2.6 kb probe of the human beta-2 receptor gene. Two alleles 3.1 kb and 2.9 kb were identified. Homozygotes and heterozygotes for the two alleles were found with equal frequency in the atopic patients who had asthma and in those who had allergic rhinitis only. The gene frequencies for the upper and lower alleles were 0.45 and 0.55 respectively. Our studies do not provide evidence for an association between a particular polymorphic form of the human beta-2 receptor gene and atopy. PMID:10780896

  6. Genetic variation in hemp and marijuana (Cannabis sativa L.) according to amplified fragment length polymorphisms.

    PubMed

    Datwyler, Shannon L; Weiblen, George D

    2006-03-01

    Cannabis sativa L. (Cannabaceae) is one of the earliest known cultivated plants and is important in the global economy today as a licit and an illicit crop. Molecular markers distinguishing licit and illicit cultivars have forensic utility, but no direct comparison of hemp and marijuana amplified fragment length polymorphism (AFLP) has been made to date. Genetic variation was surveyed in three populations of fiber hemp and a potent cultivar of marijuana using AFLP markers. Ten primer pairs yielded 1206 bands, of which 88% were polymorphic. Eighteen bands represented fixed differences between all fiber populations and the drug cultivar. These markers have practical utility for (1) establishing conspiracy in the cultivation and distribution of marijuana, (2) identifying geographic sources of seized drugs, and (3) discriminating illegal, potent marijuana cultivars from hemp where the cultivation of industrial hemp is permitted. PMID:16566773

  7. A worldwide population study of the Ag-system haplotypes, a genetic polymorphism of human low-density lipoprotein.

    PubMed Central

    Breguet, G; Btler, R; Btler-Brunner, E; Sanchez-Mazas, A

    1990-01-01

    The aim of this investigation is to examine the distribution of the Ag immunological polymorphism in human populations on a worldwide scale and to look for possible explanations of this distribution in the field of modern human peopling history and Ag-system evolution. Extensive Ag-antigene typings were carried out on 13 human population samples, including sub-Saharan African, European, west and east Asiatic, Melanesian, Australian aborigine, and Amerindian groups. Complete Ag-haplotype frequencies were estimated by maximum-likelihood-score procedures, and the data were analyzed by genetic distance computations and principal coordinate projections. With the exception of the Amerindian sample, the Ag polymorphism is shown to be highly polymorphic in all the populations tested. Their genetic relationships appear to be closely correlated to their geographical distribution. This suggests that the Ag system has evolved as a neutral or nearly neutral polymorphism and that it is highly informative for modern human peopling history studies. From the worldwide Ag haplotypic distributions, a model for the Ag molecular structure is derived. According to this model and to the most recent results obtained from molecular data, the establishment of the Ag polymorphism could be explained by several mutations and recombination events between the haplotypes most frequently found in human populations today. As a conclusion, genetic and paleontological data suggest that the genetic structure of caucasoid populations (located from North Africa to India) may be the least differentiated from an ancestral genetic stock. Worldwide genetic differentiations are properly explained as the results of westward and eastward human migrations from a Near East-centered but undefined geographical area where modern humans may have originated. The importance of Ag polymorphism analyses for the reconstruction of human settlement history and origins is discussed in the light of the main conclusions of the most recent genetic polymorphism studies. PMID:1689953

  8. Sequence-Related Amplified Polymorphism (SRAP) markers for assessing interrelationships and genetic diversity among members of the Saccharum complex

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Characterization of wild germplasm provides essential information on genetic diversity that breeders utilize for crop improvement. The potential of the sequence-related amplified polymorphism (SRAP) technique, which preferentially amplifies gene-rich regions, was evaluated to assess the genetic rela...

  9. Assessment of genetic diversity and relationships among wild and cultivated Tunisian plums (Prunus spp) using random amplified microsatellite polymorphism markers.

    PubMed

    Ben Tamarzizt, H; Ben Mustapha, S; Baraket, G; Abdallah, D; Salhi-Hannachi, A

    2015-01-01

    The usefulness of random amplified microsatellite polymorphism markers to study the genetic diversity and relationships among cultivars belonging to Prunus salicina and P. domestica and their wild relatives (P. insititia and P. spinosa) was investigated. A total of 226 of 234 bands were polymorphic (96.58%). The 226 random amplified microsatellite polymorphism markers were screened using 15 random amplified polymorphic DNA and inter-simple sequence repeat primers combinations for 54 Tunisian plum accessions. The percentage of polymorphic bands (96.58%), the resolving power of primers values (135.70), and the polymorphic information content demonstrated the efficiency of the primers used in this study. The genetic distances between accessions ranged from 0.18 to 0.79 with a mean of 0.24, suggesting a high level of genetic diversity at the intra- and interspecific levels. The unweighted pair group with arithmetic mean dendrogram and principal component analysis discriminated cultivars efficiently and illustrated relationships and divergence between spontaneous, locally cultivated, and introduced plum types. These procedures showed continuous variation that occurs independently of the status of the species and geographical origin of the plums. In this study, random amplified microsatellite polymorphism was found to be as a reliable molecular marker for fingerprinting and for examining the diversity study of the plum and its relatives. PMID:25867340

  10. Rapid recent human evolution and the accumulation of balanced genetic polymorphisms.

    PubMed

    Wills, Christopher

    2011-01-01

    All evolutionary change can be traced to alterations in allele frequencies in populations over time. DNA sequencing on a massive scale now permits us to follow the genetic consequences as our species has diverged from our close relatives and as we have colonized different parts of the world and adapted to them. But it has been difficult to disentangle natural selection from many other factors that alter frequencies. These factors include mutation and intragenic reciprocal recombination, gene conversion, segregation distortion, random drift, and gene flow between populations (these last two are greatly influenced by splits and coalescences of populations over time). The first part of this review examines recent studies that have had some success in dissecting out the role of natural selection, especially in humans and Drosophila. Among many examples, these studies include those that have followed the rapid evolution of traits that may permit adaptation to high altitude in Tibetan and Andean populations. In some cases, directional selection has been so strong that it may have swept alleles close to fixation in the span of a few thousand years, a rapidity of change that is also sometimes encountered in other organisms. The second part of the review summarizes data showing that remarkably few alleles have been carried completely to fixation during our recent evolution. Some of the alleles that have not reached fixation may be approaching new internal equilibria, which would indicate polymorphisms that are maintained by balancing selection. Finally, the review briefly examines why genetic polymorphisms, particularly those that are maintained by negative frequency dependence, are likely to have played an important role in the evolution of our species. A method is suggested for measuring the contribution of these polymorphisms to our gene pool. Such polymorphisms may add to the ability of our species to adapt to our increasingly complex and challenging environment. PMID:21718163

  11. Genetic polymorphisms of serum amyloid A1 and coronary artery disease risk.

    PubMed

    Xie, X; Ma, Y-T; Yang, Y-N; Li, X-M; Zheng, Y-Y; Liu, F; Ma, X; Fu, Z-Y; Yu, Z-X; Chen, Y; Chen, B-D; Huang, Y

    2015-03-01

    Serum amyloid A (SAA) protein is not only an inflammatory factor but also an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of high-density lipoprotein cholesterol (HDL-C). However, the relationship between genetic polymorphisms of SAA and coronary artery disease (CAD) remains unclear. A total of four single nucleotide polymorphisms (rs12218, rs4638289, rs7131332, and rs11603089) of the SAA gene were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in two independent case-control studies, one of the Han population (1416 CAD patients and 1373 control subjects) and the other of the Uygur population (588 CAD patients and 529 control subjects). We found that the rs12218 CC genotype was more frequent among the CAD patients than among the controls in both the Han (8.3% vs. 4.8%, P?Genetic polymorphisms in SAA1 are associated with CAD in the Han and Uygur populations in western China. PMID:25656165

  12. Adaptation to abiotic stress in the oyster Crassostrea angulata relays on genetic polymorphisms.

    PubMed

    Cross, Ismael; Merlo, Manuel A; Rodríguez, María E; Portela-Bens, Silvia; Rebordinos, Laureana

    2014-12-01

    Here we describe the whole genome re-sequencing of the Portuguese oyster Crassostrea angulata, an edible cupped oyster of major commercial importance with an important role as biosensor of coastal water pollution. We sequenced the genome of the C. angulata to 29.3-fold coverage using ABI SOLID system. Comparisons of the sequences with the reference assembly of the Pacific oyster (Crassostrea gigas), yielded 129 million SNPs, 151,620 from which were located in 20,908 genes from the C. gigas database. The analysis of Gene Ontology (GO) terms associated with gene regions containing SNPs, revealed that significant GO terms showing differences between the two oyster species, were related to activities of response to stress caused both by drying and by metal contamination. In the Biological Process domain, the GO terms ion transport, phosphorylation and proteolysis processes, among others, showed many polymorphic genes in C. angulata. These processes are related to combating genotoxic and hypo-osmotic stress in the oyster. It is noteworthy that more than 200 polymorphic genes were associated with DNA repair processes. These results reveal that most of the gene polymorphisms observed in C. angulata are associated with processes related to genome adaptation to abiotic stress in estuarine regions and support that genetic polymorphisms may be the base to the observed ability of C. angulata to retain the phenomenally high concentrations of toxic heavy metals. Our results also provide the framework for future investigations to establish the molecular basis of phenotypic variation of adaptive traits and should contribute to the management of the species' genetic resources. PMID:25462456

  13. Association of Romo1 gene genetic polymorphisms with risk of gastric cancer in northwestern Chinese population.

    PubMed

    Wu, Hua; Gu, Yuan-Hui; Wei, Li; Guo, Tian-Kang; Zhao, Yong; Su, Gang; Li, Jiong; Xie, Xiao-Dong

    2015-07-01

    Increased expression of reactive oxygen species modulator 1 protein-triggered reactive oxygen species production was reported in the mitochondria of various cancer cell lines. To date there is no report on association between Romo1 gene polymorphisms and gastric cancer risk. To investigate the relationship between Romo1 gene polymorphisms and GC risk, we conducted a case-control study in a population from northwest China (358 GC patients and 412 healthy controls). The genotypes of two SNPs were determined with PCR-denaturing high-performance liquid chromatography and direct DNA sequencing. We found that the genotype and allele distributions of two polymorphisms were significantly different in GC patients compared with controls, When the wild type of two loci were served as the reference group, respectively, significantly increased risk for gastric cancer were associated with rs6060566 TC genotype (Adjusted OR?=?1.525, 95 % CI =1.126-2.138), rs6060567 GC genotype (Adjusted OR?=?1.641, 95 % CI =1.238-2.291) and CC genotype (Adjusted OR?=?1.594, 95 % CI =1.102-2.973). This effect was more pronounced in patients with smoking, alcohol consumption, H.pylori infection,and male patients subgroups. Haplotypes analysis of two genetic variants showed that the most common haplotype TG displayed the strongest evidence of association with GC (corrected P?=?9.30??10(-5)), and was associated with protection against GC (OR?=?0.584). Whereas the CC haplotypes had significant correlation with GC risk (OR?=?1.732). These findings suggested genetic polymorphisms of Romo1 gene were associated with significant risk of GC in Northwestern Chinese population, which is strengthened by alcohol use, smoking, H.pylori infection or male patients. PMID:25374412

  14. Genetic Polymorphisms of Metastasis Suppressor Gene NME1 and Breast Cancer Survival

    PubMed Central

    Qu, Shimian; Long, Jirong; Cai, Qiuyin; Shu, Xiao-Ou; Cai, Hui; Gao, Yu-Tang; Zheng, Wei

    2009-01-01

    Purpose Ample evidence supports an important role of tumor metastasis suppressor genes in cancer metastatic processes. We evaluated the association of genetic polymorphisms of tumor metastasis suppressor gene NME1 with breast cancer prognosis in a follow-up study of patients with primary breast cancer and further investigated the functions of these polymorphisms. Experimental Design NME1 genotypes were analyzed in a cohort of 1134 breast cancer patients recruited as part of the Shanghai Breast Cancer Study who were followed for a median of 7.1 years. In vitro biochemical analyses were carried out to examine the function of NME1 gene polymorphisms. Results Single nucleotide polymorphisms (SNPs) in the promoter region of the NME1 gene were found to be associated with breast cancer prognosis. Patients carrying the C allele in rs16949649 were associated with higher breast cancer-specific mortality (HR =1.4, 95% CI =1.11.9) as compared to those carrying the wild-type allele, and the association was more evident in patients with an early stage cancer (HR=1.7, 95% CI =1.22.5). SNP rs2302254 was also associated with breast cancer prognosis, and the association was statistically significant for the risk of breast cancer relapse, metastasis, and death (HR=1.3, 95% CI, 1.01.6). In vitro biochemical analyses showed that minor alleles in rs2302254 and rs3760468, which is in strong linkage disequilibrium with rs16949646, altered nuclear proteins binding capacity and reduced NME1 promoter activity, supporting the results from an association study of these SNPs with breast cancer survival. Conclusion Promoter polymorphisms in the NME1 gene may alter its expression and influence breast cancer survival. PMID:18676749

  15. Genetic polymorphism and natural selection in the malaria parasite Plasmodium falciparum.

    PubMed Central

    Escalante, A A; Lal, A A; Ayala, F J

    1998-01-01

    We have studied the genetic polymorphism at 10 Plasmodium falciparum loci that are considered potential targets for specific antimalarial vaccines. The polymorphism is unevenly distributed among the loci; loci encoding proteins expressed on the surface of the sporozoite or the merozoite (AMA-1, CSP, LSA-1, MSP-1, MSP-2, and MSP-3) are more polymorphic than those expressed during the sexual stages or inside the parasite (EBA-175, Pfs25, PF48/45, and RAP-1). Comparison of synonymous and nonsynonymous substitutions indicates that natural selection may account for the polymorphism observed at seven of the 10 loci studied. This inference depends on the assumption that synonymous substitutions are neutral, which we test by analyzing codon bias and G+C content in a set of 92 gene loci. We find evidence for an overall trend towards increasing A+T richness, but no evidence for mutation bias. Although the neutrality of synonymous substitutions is not definitely established, this trend towards an A+T rich genome cannot explain the accumulation of substitutions at least in the case of four genes (AMA-1, CSP, LSA-1, and PF48/45) because the Gleft and right arrow C transversions are more frequent than expected. Moreover, the Tajima test manifests positive natural selection for the MSP-1 and, less strongly, MSP-3 polymorphisms; the McDonald-Kreitman test manifests natural selection at LSA-1 and PF48/45. We conclude that there is definite evidence for positive natural selection in the genes encoding AMA-1, CSP, LSA-1, MSP-1, and Pfs48/45. For four other loci, EBA-175, MSP-2, MSP-3, and RAP-1, the evidence is limited. No evidence for natural selection is found for Pfs25. PMID:9584096

  16. CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis.

    PubMed

    Han, S W; Sa, K H; Kim, S I; Lee, S I; Park, Y W; Lee, S S; Yoo, W H; Soe, J S; Nam, E J; Lee, J; Park, J Y; Kang, Y M

    2012-11-01

    The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA. PMID:22924548

  17. Genetic Contribution of Polymorphisms in Glutathione S-Transferases to Brain Tumor Risk.

    PubMed

    Geng, Peiliang; Li, Jianjun; Wang, Ning; Ou, Juanjuan; Xie, Ganfeng; Sa, Rina; Liu, Chen; Xiang, Lisha; Li, Hongtao; Liang, Houjie

    2016-04-01

    Existing data have shown a major effect of glutathione S-transferase (GST) single-nucleotide polymorphisms on activities of detoxification-related enzymes, and it is the functional importance that leads to extensive research on the association of GST polymorphisms with the risk of developing brain tumor. Previously reported associations, nevertheless, remain inconsistent. This study aimed to reevaluate the association with new information from recent research articles. We weekly searched multiple databases, aiming to cover all studies looking at the associations being examined in this work. Eligibility of studies was evaluated based on predesigned inclusion criteria. To assess the association of GST polymorphisms with brain tumor risk, we calculated genotypic ORs by comparing the number of genotypes between cases and controls. We also detected interstudy heterogeneity, publication bias, and single studies' influence. A total of 13 research articles were identified through databases and hand search. We found significantly elevated risk of brain tumor associated with GSTT1 null status in individuals of European ethnicity (OR 1.46, 95 % CI 1.12-1.92). In the analysis of GSTP1 I105V, we observed that Val/Val genotype compared to the Ile/Ile genotype was more prone to a reduced brain tumor risk (OR 0.77, 95 % CI 0.64-0.93). Such major effects were similarly seen for GSTP1 A114V (OR 1.14, 95 % CI 1.01-1.29 for Val/Val + Ala/Val vs. Ala/Ala). When data were limited to glioma, we found a significant elevation associated with the combination of Val/Val and Ala/Val genotypes (OR 1.18, 95 % CI 1.01-1.37). However, no clear association was detected between other polymorphisms investigated and glioma. These statistical data suggest that some of the polymorphisms at GST loci are possibly associated with the genetic risk of brain tumor. PMID:25735248

  18. Genetic Association Between CDKN1B rs2066827 Polymorphism and Susceptibility to Cancer

    PubMed Central

    Lu, Yongchao; Gao, Kejian; Zhang, Miao; Zhou, Aiyan; Zhou, Xiaoming; Guan, Zhongan; Shi, Xuewen; Ge, Shujian

    2015-01-01

    Abstract Much attention has been directed to the association between cancer risk and rs2066827 polymorphism of the CDKN1B gene. However, the results are indefinitive and inconclusive. This study was devised to evaluate the hypothesis that rs2066827 polymorphism is associated with the risk of cancer. Computer-based databases (EMBASE, PubMed, and CNKI) were used to seek all casecontrol studies evaluating rs2066827 polymorphism and susceptibility to cancer. The genetic risk was assessed by calculating pooled odds ratio (OR) with its corresponding 95% confidence interval (CI). Fixed-effects pooled ORs were calculated by the MantelHaenszel method (Ph?>?0.05), and random-effects pooled ORs were estimated by the DerSimonianLaird method (Ph?polymorphism and cancer risk were available for 9038 cancer cases and 11,596 controls participating in 17 studies. Carriage of a TG genotype was associated with a minor but significant decrease in the risk of cancer (pooled OR 0.92, 95% CI: 0.860.99; model, TG vs. TT). We observed a moderately decreased risk of ovarian cancer based on 1829 cases and 2868 controls (pooled OR 0.85, 95% CI: 0.740.97; model, TG vs. TT). A slightly deceased risk of cancer was also indicated in Caucasians consisting of 6707 cases and 8279 controls (pooled OR 0.91, 95% CI: 0.850.98; model, TG vs. TT). These data suggest that carriage of a TG genotype at rs2066827 polymorphism may be associated with decreased susceptibility to cancer, ovarian cancer in particular. PMID:26579796

  19. Genetic polymorphisms in MMP 2, 9 and 3 genes modify lung cancer risk and survival

    PubMed Central

    2012-01-01

    Background Matrix metalloproteases (MMPs) are proteolytic enzymes that contribute to all stages of tumour progression, including the later stages of invasion and metastasis. Genetic variants in the MMP genes may influence the biological function of these enzymes and change their role in carcinogenesis and progression. We have investigated the association between the -735 C/T, the -1171 5A/6A, and the -1562 C/T polymorphisms in the MMP2, MMP3 and MMP9 genes, respectively, and the risk and survival of lung cancer. Methods The case-control study includes 879 lung cancer patients and 803 controls from a Caucasian population in Spain (CAPUA study). Genotypes were determined by PCR-RFLP. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. The Kaplan-Meier method, long-rank test and Cox's were used for the survival analysis. Results The MMP9 -1562 T/T genotype was associated with a statistically significant decreased risk of developing lung cancer (OR = 0.23; 95% CI: 0.06-0.85), whereas no association was found for the MMP2 -735 C/T and MMP3 -1171 5A/6A polymorphisms. The MMP2 -735 T/T genotype was statistically significantly associated with a decreased survival in non-small cell lung cancer (NSCLC) patients, identified as an independent prognosis factor of survival (hazard ratio (HR) = 1.79; 95% CI: 1.00-3.20). In contrast, no association was found between the MMP3 -1171 5A/6A and the MMP9 -1562 C/T polymorphisms and survival. Conclusions These findings support the hypothesis that the MMP9 -1562 C/T polymorphism is associated with a protective effect against the development of lung cancer and suggest that the MMP2 -735 C/T polymorphism modify the length of survival in NSCLC patients. PMID:22455335

  20. Maintenance of a genetic polymorphism with disruptive natural selection in stickleback.

    PubMed

    Marchinko, Kerry B; Matthews, Blake; Arnegard, Matthew E; Rogers, Sean M; Schluter, Dolph

    2014-06-01

    The role of natural selection in the maintenance of genetic variation in wild populations remains a major problem in evolution. The influence of disruptive natural selection on genetic variation is especially interesting because it might lead to the evolution of assortative mating or dominance [1, 2]. In theory, variation can persist at a gene under disruptive natural selection, but the process is little studied and there are few examples [3, 4]. We report a stable polymorphism in the bony armor of threespine stickleback maintained with a deficit of heterozygotes at the major underlying gene, Ectodysplasin (Eda) [5]. The deficit vanishes at the embryo life stage only to re-emerge in adults, indicating that disruptive natural selection, rather than nonrandom mating, is the cause. The mechanism enabling long-term persistence of the polymorphism is unknown, but disruptive selection is predicted to be frequency dependent, favoring homozygous genotypes when they become rare. Further research on the ecological and evolutionary processes affecting individual genes will ultimately lead to a better understanding of the causes of genetic variation in populations. PMID:24856211

  1. Genetic polymorphism of plasminogen and vitamin D binding protein in red deer (Cervus elaphus L.).

    PubMed

    Tate, M L; Dodds, K G; Thomas, K J; McEwan, K M

    1992-01-01

    Genetic polymorphism was detected in the red deer (Cervus elaphus L.), plasma proteins, plasminogen (PLG) and vitamin D binding protein (GC) using antiserum to human proteins. The affinity of the antisera to deer plasma was less than 10% that of a human standard but they bound specifically to proteins of molecular weight expected for GC and PLG. Three codominant alleles of GC and five of PLG were observed. In a set 124 farmed deer calves and their parents, six calves had genotypes which were not consistent with the expectations of inheritance. Further inconsistencies were found when variation in isocitrate dehydrogenase (IDH) and transferrin (TRF) was examined. Using genetic models which included pedigree error parameters the data were shown to be consistent with genetic inheritance of all loci in a data set containing approximately 4.8% (SE 1.4%) parent-progeny pedigree mismatches. In samples from four deer populations representative of the red deer introduced to New Zealand the GC and PLG polymorphisms provided a probability of paternity exclusion (PE) of between 0.34 and 0.54 and when IDH and TRF were also included the PE was between 0.46 and 0.66. The four populations differed significantly in allele frequency, which supports historical evidence that they originate from separate introductions of small numbers of European red deer. PMID:1503269

  2. Amplified fragment length polymorphism (AFLP) analysis of genetic variation in Moringa oleifera Lam

    PubMed

    Muluvi; Sprent; Soranzo; Provan; Odee; Folkard; McNicol; Powell

    1999-03-01

    Moringa oleifera is an important multipurpose tree introduced to Africa from India at the turn of this century. Despite limited knowledge of the levels of genetic diversity and relatedness of introduced populations, their utilization as a source of seed for planting is widespread. In order to facilitate reasoned scientific decisions on its management and conservation and prepare for a selective breeding programme, genetic analysis of seven populations was performed using amplified fragment length polymorphism (AFLP) markers. The four pairs of AFLP primers (PstI/MseI) generated a total of 236 amplification products of which 157 (66.5%) were polymorphic between or within populations. Analysis of molecular variance (AMOVA) revealed significant differences between regions and populations, even though outcrossing perennial plants are expected to maintain most variation within populations. A phenetic tree illustrating relationships between populations suggested at least two sources of germplasm introductions of Kenya. The high levels of population differentiation detected suggest that provenance source is an important factor in the conservation and exploitation of M. oleifera genetic resources. PMID:10199008

  3. Genetic relationships and variation in the Stylosanthes guianensis species complex assessed by random amplified polymorphic DNA.

    PubMed

    Kazan, K; Manners, J M; Cameron, D F

    1993-02-01

    Genetic variation in the five taxonomic groups of the Stylosanthes guianensis (Aubl.) Sw. complex was investigated using random amplified polymorphic DNA markers (RAPDs). DNA samples from four plants of each of 45 accessions within the S. guianensis species complex were analyzed using 20 oligonucleotides of random sequence. Little variation was found within each of the 18 accessions (1-7% of total RAPD bands in pairwise comparisons) and none within each of the other 27 accessions. However, higher levels of polymorphisms were observed both within (index of genetic distance = 1 - F = 0.16-0.248) and between (1 - F = 0.254-0.408) the five taxa. This level of differentiation at the DNA level supported an earlier classification of the taxa as distinct species. A phenogram based on band sharing was constructed to show genetic relationships among the taxa studied. This phenogram corroborated the description of relationships based on morphological-agronomic characteristics, seed protein patterns, rhizobial affinities, crossability, and pollen stainability of the hybrids. In this phenogram, the most similar species were S. grandiflora and S. hippocampoides (1 - F = 0.264), with S. acuminata also showing closest similarity to these two species (1 - F = 0.277 and 0.283, respectively). Stylosanthes gracilis accessions showed the closest similarity (1 - F = 0.296) to S. guianensis ssp. guianensis accessions. Lowest similarity values (1 - F = 0.335-0.411) were found between these two species and S. grandiflora, S. acuminata, and S. hippocampoides. PMID:8458571

  4. Genetic polymorphisms of RAGE and risk of ulcerative colitis in a Chinese population.

    PubMed

    Wang, Jiafeng; Zeng, Juncheng; Wang, Hao; Ye, Shicai; Bi, Yuntian; Zhou, Yulan; Li, Keshen; Zhou, Yu

    2016-02-01

    The receptor for advanced glycation end products (RAGE) and its proinflammatory ligands are critically implicated in the pathological progression of ulcerative colitis (UC). Functional polymorphisms in the regulatory elements and/or ligand-binding regions of the RAGE gene affect the expression and function of RAGE and thus may increase susceptibility to UC. In this study, a total of 266 unrelated UC patients and 247 control subjects were analyzed for 3 RAGE single nucleotide polymorphisms (SNPs) (-429 T/C, -374 T/A, and G82S) using an improved small-amplicon high resolution melting curve (HRM) analysis assay. Serum levels of soluble RAGE (sRAGE) were determined by a double sandwich ELISA system. The genotypes, alleles and haplotypes were analyzed and compared between UC patients and control subjects. Three pairs of genotyping primers for three RAGE polymorphism loci (-429 T/C, -374 T/A, and G82S) were developed based on HRM. Significant differences in the allele distribution of the G82S polymorphism was found among UC cases and controls from a Chinese population. Carriers of the RAGE G82S variant genotype were at higher risk of UC (OR=2.594, 95% CI: 1.778-3.784, P<0.001) than homozygous wild-type individuals. Further analyses revealed that the 82 (GS+SS) variant genotype was associated with patients who have extended UC (OR=1.924, 95% CI: 1.163-3.181, P=0.010), and a family history of inflammatory bowel disease (IBD) (OR=1.923, 95% CI: 1.049-3.521, P=0.032). The polymorphisms -374 T/A and -429 T/C did not demonstrate any association with UC, but an association was found between the -374(TA+AA) variant genotypes and the serum sRAGE level (P=0.002). Moreover, haplotypes T/A/A and T/A/G showed significantly different frequencies between UC patients and controls (OR=3.337, 95% CI: 1.892-6.091, P=0.026; OR=0.530, 95% CI: 0.351-0.801, P=0.002). The present study developed novel primers based on HRM to provide preliminary evidence in a Chinese population that the RAGE polymorphism is involved in genetic susceptibility to UC and that the 82(GS+SS) genotype of G82S is a risk factor for UC. Furthermore, RAGE polymorphisms may be related to the location of UC as well as a family history of IBD in a Chinese population. PMID:26349055

  5. CLPTM1L Genetic Polymorphisms and Interaction With Smoking and Alcohol Drinking in Lung Cancer Risk

    PubMed Central

    Xun, Xiaojie; Wang, Huijuan; Yang, Hua; Wang, Hong; Wang, Bo; Kang, Longli; Jin, Tianbo; Chen, Chao

    2014-01-01

    Abstract Genetic variants of cleft lip and palate trans-membrane 1-like (CLPTM1L) genes in the p15.33 region of chromosome 5 were previously identified to influence susceptibility to lung cancer. We examined the association of single nucleotide polymorphisms (SNPs) in CLPTM1L genes with lung cancer and explored their potential effects on the relationship between environmental risk factors (smoking, drinking) and lung cancer in a Chinese Han population. We genotyped 9 single nucleotide polymorphisms (SNPs) of CLPTM1L in a casecontrol study with 228 lung cancer cases and 301 controls from northwest China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression. We identified that the minor alleles of rs451360, rs402710, and rs31484 in CLPTM1L were associated with a 0.52-fold, 0.76-fold, and 0.70-fold decreased risk of lung cancer in allelic model analysis, respectively. In the genetic model analysis, we found rs402710 and rs401681 were associated with decreased lung cancer risk. Further stratification analysis showed that rs380286 displayed a significantly decreased lung cancer risk (OR?=?0.65, P?=?0.041) in the non-drinkers. In addition, Haplotype GTTATCTGT was found to be associated with decreased lung cancer risk (OR?=?0.50, P?=?0.033). Our results verified that genetic variants of CLPTM1L contribute to lung cancer susceptibility in the northwest Chinese Han population. Additionally, we found that consumption of alcohol may interact with CLPTM1L polymorphisms to contribute to overall lung cancer susceptibility. PMID:25526467

  6. [Pearl Harbor.

    ERIC Educational Resources Information Center

    Johnson, Jennifer, Ed.

    1992-01-01

    This issue of "Loblolly Magazine" was written in observance of the 50th anniversary of the U.S. entrance into World War II. The publication features interviews conducted by East Texas high school students with Clarence Otterman, one of the few survivors of the crew of the USS Arizona, which was bombed during the attack on Pearl Harbor, and with a

  7. Genetic diversity analysis of Capsicum spp germplasm bank accessions based on α/β-esterase polymorphism.

    PubMed

    Monteiro, E R; Bronzato, A R; Orasmo, G R; Lopes, A C A; Gomes, R L F; Mangolin, C A; Machado, M F P S

    2013-01-01

    Genetic diversity and structure were analyzed in 10 accessions belonging to Banco Ativo de Germoplasma de Capsicum located at Federal University of Piauí in northwestern Brazil that receives pepper samples grown in community gardens in various regions and Brazilian states. Selections were made from seeds of C. chinense (4 accessions), C. annuum (5 accessions), and C. baccatum (1 accession). Samples consisting of leaves were collected from 4-10 plants of each accession (a total of 85 plants). Native polyacrylamide gel electrophoresis was used to identify α- and β-esterase polymorphisms. Polymorphism was clearly detected in 5 loci. Sixteen alleles were found at 5 α/β-esterase loci of the three Capsicum species. In the C. chinense samples, the highest HO and HE values were 0.3625 and 0.4395, respectively, whereas in C. annuum samples, HO and HE values were 0.2980 and 0.3310, respectively; the estimated HO and HE values in C. chinense samples were higher than those detected in C. annuum samples. A deficit of homozygous individuals was found in C. chinense (FIS = -0.6978) and C. annuum (FIS = 0.7750). Genetic differentiation between C. chinense and C. annuum at these loci was high (FST = 0.1867) indicating that C. chinense and C. annuum are genetically structured species for α/β- esterase isozymes. The esterase analysis showed high genetic diversity among the C. chinense and C. annuum samples and very high genetic differentiation (FST = 0.6321) among the C. chinense and C. annuum samples and the C. baccatum accession. PMID:23661440

  8. Development of polymorphic microsatellite loci for conservation genetic studies of the coral reef fish Centropyge bicolor.

    PubMed

    Herrera, M; Saenz-Agudelo, P; Nanninga, G B; Berumen, M L

    2015-09-01

    A total of 23 novel polymorphic microsatellite marker loci were developed for the angelfish Centropyge bicolor through 454 sequencing, and further tested on two spatially separated populations (90 individuals each) from Kimbe Bay in Papua New Guinea. The mean s.e. number of alleles per locus was 1465 105, and mean s.e. observed (HO ) and expected (HE ) heterozygosity frequencies were 0676 0021 and 0749 0018, respectively. The markers reported here constitute the first specific set for this genus and will be useful for future conservation genetic studies in the Indo-Pacific region. PMID:26272332

  9. Genetic Association between Neurotrophin-3 Polymorphisms and Alzheimer's Disease in Japanese Patients

    PubMed Central

    Nagata, Tomoyuki; Shibata, Nobuto; Shinagawa, Shunichiro; Nakayama, Ritsuko; Kuerban, Bolati; Ohnuma, Tohru; Arai, Heii; Nakayama, Kazuhiko; Yamada, Hisashi

    2013-01-01

    Background Some polymorphisms of the neurotrophin family have previously been investigated as candidate genes for Alzheimer's disease (AD). In the present study, we examined whether neurotrophin-3 (NTF-3) polymorphisms are genetic risk factors in patients with AD. Methods From a sample of 507 subjects, we recruited 248 age-matched subjects divided into 2 groups: AD patients (n = 143) and normal controls (NCs) (n = 105). We identified 3 representative NTF-3 single nucleotide polymorphisms (SNPs): rs6332, rs6489630, and rs4930767. Next, we statistically compared the allele frequencies of each SNP between the AD and NC groups in the early-onset (<65 years) cases under a more limited age-matched condition. Results We found a significant association between rs6332 and the total group of AD patients (p = 0.013) and significant associations between both rs6332 (p = 0.033) and rs6489630 (p = 0.035) and early-onset AD patients. Conclusion These results suggest that NTF-3 SNPs may not only be associated with AD itself, but also with early-onset AD in Japanese patients, assuming that the NTF-3 gene may have age-related effects on neurodegenerative diseases. PMID:24174922

  10. Genome-Wide Patterns of Genetic Polymorphism and Signatures of Selection in Plasmodium vivax

    PubMed Central

    Cornejo, Omar E.; Fisher, David; Escalante, Ananias A.

    2015-01-01

    Plasmodium vivax is the most prevalent human malaria parasite outside of Africa. Yet, studies aimed to identify genes with signatures consistent with natural selection are rare. Here, we present a comparative analysis of the pattern of genetic variation of five sequenced isolates of P. vivax and its divergence with two closely related species, Plasmodium cynomolgi and Plasmodium knowlesi, using a set of orthologous genes. In contrast to Plasmodium falciparum, the parasite that causes the most lethal form of human malaria, we did not find significant constraints on the evolution of synonymous sites genome wide in P. vivax. The comparative analysis of polymorphism and divergence across loci allowed us to identify 87 genes with patterns consistent with positive selection, including genes involved in the exportome of P. vivax, which are potentially involved in evasion of the host immune system. Nevertheless, we have found a pattern of polymorphism genome wide that is consistent with a significant amount of constraint on the replacement changes and prevalent negative selection. Our analyses also show that silent polymorphism tends to be larger toward the ends of the chromosomes, where many genes involved in antigenicity are located, suggesting that natural selection acts not only by shaping the patterns of variation within the genes but it also affects genome organization. PMID:25523904

  11. Mitochondrial DNA polymorphism, sex ratio distorters and population genetics in the isopod Armadillidium vulgare.

    PubMed

    Rigaud, T; Bouchon, D; Souty-Grosset, C; Raimond, R

    1999-08-01

    Two maternally inherited sex ratio distorters (SRD) impose female-biased sex ratios on the wood louse Armadillidium vulgare by feminizing putative males. These SRD are (i) an intracytoplasmic bacterium of the genus Wolbachia, and (ii) another non-Mendelian element of unknown nature: the f element. Mitochondrial DNA variation was investigated in A. vulgare field populations to trace the evolution of host-SRD relationships and to investigate the effect of SRD on host cytoplasmic polymorphism. The Wolbachia endosymbionts showed no polymorphism in their ITS2 sequence and were associated with two closely related mitochondrial types. This situation probably reflects a single infection event followed by a slight differentiation of mitochondria. There was no association between the f element and a given mitochondrial type, which may confirm the fact that this element can be partially paternally transmitted. The spreading of a maternally inherited SRD in a population should reduce the mitochondrial diversity by a hitchhiking process. In A. vulgare, however, a within-population mtDNA polymorphism was often found, because of the deficient spread of Wolbachia and the partial paternal inheritance of the f element. The analysis of molecular variance indicated that A. vulgare populations are genetically structured, but without isolation by distance. PMID:10430591

  12. Genetic polymorphism in alcohol dehydrogenase 2 (ADH2) gene and alcoholic liver cirrhosis risk

    PubMed Central

    He, Lei; Deng, Tao; Luo, He-Sheng

    2015-01-01

    The alcohol dehydrogenase 2 (ADH2) gene has been implicated in the development of alcoholic liver cirrhosis (ALC). However, the results are inconsistent. In this study, a meta-analysis was performed to assess the associations between the ADH2 polymorphism and the risk of ALC. Relevant studies were retrieved by searching PubMed, Web of Science, CNKI, Wanfang and VIP databases up to January 10, 2015. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using the fixed- or random effects model. A total of 21 case-control studies included 1812 cases and 3468 controls were included. Overall, the ADH2 polymorphism was associated with a decreased risk of ALC in all four genetic models (dominant model: OR=0.56, 95% CI: 0.38-0.83; recessive model: OR=0.59, 95% CI: 0.39-0.91; *1/*2 vs. *1/*1: OR=0.58, 95% CI: 0.40-0.85; *2/*2 vs *1/*1: OR=0.35, 95% CI: 0.16-0.75). Besides, in stratification analysis by ethnicity, similar results were observed in Asian populations, however, we detected no association in Caucasian populations under recessive and homozygote comparison model. The pooled evidence suggests that ADH2 polymorphism may be an important protective factor for alcoholic liver cirrhosis, especially for Asians. PMID:26221330

  13. Genetic polymorphisms in ?-defensin II gene in Amazon sheep from Brazil.

    PubMed

    Souza, B B; Barbosa, E M; Azevedo, J S N; Campelo, J E G; Rodrigues, L F S; Pinheiro, L M L; Silva, S C B; Schierholt, A S; Souza, P H; Gonalves, E C; Silva Filho, E

    2015-01-01

    The northern region of Brazil produces a large number of sheep, with Par being the largest sheep breeding state in the region. In the Amazon region, livestock production is a challenge due to the high diversity of pathogens affecting humans and animals. Defensins are antimicrobial peptides acting as a first barrier against micro-organisms and present high variation in different organisms. The objective of this study was to detect polymorphisms in exon II in ?-defensin II in Amazon sheep. The gene was amplified by PCR from DNA extracted from 47 sheep blood samples from the Santa Ins breed. Products were sequenced, aligned and analyzed. Three single nucleotide polymorphism (SNP) positions were observed with transition substitutions (A?G) at positions 1643, 1659, and 1750. The 1643 and 1750 SNPs showed a low variability and significant deviations from Hardy-Weinberg equilibrium (HWE) (P < 0.05) meanwhile the SNP 1659 showed moderate absence of genetic variability and deviation from HWE (P > 0.05). Polymorphisms at 1643 and 1659 were predicted to modify amino acids in the peptide chain (isoleucine to valine and arginine to lysine, respectively) with no effects on protein function. Results from this study suggest that SNPs are important markers for ?-defensin II efficiency studies on the immune system of sheep in the Brazilian Amazon. PMID:26505431

  14. Genetic effects of polymorphisms in myogenic regulatory factors on chicken muscle fiber traits.

    PubMed

    Yang, Zhi-Qin; Qing, Ying; Zhu, Qing; Zhao, Xiao-Ling; Wang, Yan; Li, Di-Yan; Liu, Yi-Ping; Yin, Hua-Dong

    2015-06-01

    The myogenic regulatory factors is a family of transcription factors that play a key role in the development of skeletal muscle fibers, which are the main factors to affect the meat taste and texture. In the present study, we performed candidate gene analysis to identify single-nucleotide polymorphisms in the MyoD, Myf5, MyoG, and Mrf4 genes using polymerase chain reaction-single strand conformation polymorphism in 360 Erlang Mountain Chickens from three different housing systems (cage, pen, and free-range). The general linear model procedure was used to estimate the statistical significance of association between combined genotypes and muscle fiber traits of chickens. Two polymorphisms (g.39928301T>G and g.11579368C>T) were detected in the Mrf4 and MyoD gene, respectively. The diameters of thigh and pectoralis muscle fibers were higher in birds with the combined genotypes of GG-TT and TT-CT (p<0.05). Moreover, the interaction between housing system and combined genotypes has no significant effect on the traits of muscle fiber (p>0.05). Our findings suggest that the combined genotypes of TT-CT and GG-TT might be advantageous for muscle fiber traits, and could be the potential genetic markers for breeding program in Erlang Mountain Chickens. PMID:25925055

  15. Gene-Based Single Nucleotide Polymorphism Markers for Genetic and Association Mapping in Common Bean

    PubMed Central

    2012-01-01

    Background In common bean, expressed sequence tags (ESTs) are an underestimated source of gene-based markers such as insertion-deletions (Indels) or single-nucleotide polymorphisms (SNPs). However, due to the nature of these conserved sequences, detection of markers is difficult and portrays low levels of polymorphism. Therefore, development of intron-spanning EST-SNP markers can be a valuable resource for genetic experiments such as genetic mapping and association studies. Results In this study, a total of 313 new gene-based markers were developed at target genes. Intronic variation was deeply explored in order to capture more polymorphism. Introns were putatively identified after comparing the common bean ESTs with the soybean genome, and the primers were designed over intron-flanking regions. The intronic regions were evaluated for parental polymorphisms using the single strand conformational polymorphism (SSCP) technique and Sequenom MassARRAY system. A total of 53 new marker loci were placed on an integrated molecular map in the DOR364 × G19833 recombinant inbred line (RIL) population. The new linkage map was used to build a consensus map, merging the linkage maps of the BAT93 × JALO EEP558 and DOR364 × BAT477 populations. A total of 1,060 markers were mapped, with a total map length of 2,041 cM across 11 linkage groups. As a second application of the generated resource, a diversity panel with 93 genotypes was evaluated with 173 SNP markers using the MassARRAY-platform and KASPar technology. These results were coupled with previous SSR evaluations and drought tolerance assays carried out on the same individuals. This agglomerative dataset was examined, in order to discover marker-trait associations, using general linear model (GLM) and mixed linear model (MLM). Some significant associations with yield components were identified, and were consistent with previous findings. Conclusions In short, this study illustrates the power of intron-based markers for linkage and association mapping in common bean. The utility of these markers is discussed in relation with the usefulness of microsatellites, the molecular markers by excellence in this crop. PMID:22734675

  16. Association between 11 genetic polymorphisms in folate-metabolising genes and head and neck cancer risk.

    PubMed

    Galbiatti, Ana Lvia Silva; da Silva, Lidia Maria Rebolho Batista; Ruiz-Cintra, Mariangela Torreglosa; Raposo, Luis Srgio; Manglia, Jos Victor; Pavarino, Erika Cristina; Goloni-Bertollo, Eny Maria

    2012-07-01

    Genetic polymorphisms in folate metabolism may affect the risk of head and neck cancer (HNSCC) due to its involvement in DNA methylation and synthesis. We conducted a case-control study (265 HNSCC cases and 466 non-cancer controls) to investigate associations of MTHFR C677T and A1298C, MTR A2756G, MTRR A66G, RFC1 A80G, MTHFD1 G1958A, CBS 844ins68, TC2 C776G and A67G, SHMT C1420T and BHMT G742A polymorphisms with HNSCC risk. Interactions between polymorphisms and survival time, tobacco and alcohol habits, age, gender and tumour staging (TNM classification) were evaluated by multiple logistic regression analysis. We found that age ? 49 years (P<0.001), male gender (P=0.03), tobacco habit (P<0.001), MTHFR 1298AC/CC (P=0.028), MTR 2756AG/GG (P=0.010) and RFC1 80AG/GG (P=0.015) genotypes were associated with an increased risk of HNSCC. There were interactions between lower survival and CBS 844ins68 (P=0.005); age ? 49 years and MTR 2756 AG/GG (P=0.004) and RFC1 80AG/GG (P=0.006) genotypes; male gender and MTHFR 1298 AC/CC (P=0.030), MTR 2756 AG/GG (P=0.006) and RFC1 80 AG/GG (P=0.009); tobacco non-habit and MTHFD1 1958GA/AA (P=0.040); tobacco and MTHFR 1298 AC/CC (P=0.054) and MTR 2756 AG/GG (P=0.010); alcohol non-consume and RFC1 80 AG/GG (P=0.008) with HNSCC increased risk. MTHFR C677CT/TT genotypes were less frequently in advanced tumours (P=0.04). In conclusion, our data provide evidence that folate metabolism genetic polymorphisms associated with variables as advanced age, male gender, tobacco and alcohol increase HNSCC development; CBS 844ins68 and MTHFR C677T polymorphisms are associated with less survival time and advanced stage tumours, respectively. PMID:22051736

  17. [Genetic Polymorphism of Durum Wheat (Triticum durum Desf.) Accessions of Azerbaijan].

    PubMed

    Hajiyev, E S; Akparov, Z I; Aliyev, R T; Seidova, S V; Izzatullayeva, V I; Babayeva, S M; Abbasov, M A

    2015-09-01

    The genetic diversity of 110 durum wheat genotypes of Azerbaijan was evaluated by ISSR markers. A total of 107 fragments were determined, ranging from 9 to 18 per locus. ISSR primers have revealed a high level of polymorphism (average 82%) among different durum wheat varieties and botanical varieties. The ISSR markers used in the study were quite informative and made it possible to distinguish all durum wheat accessions from each other. Cluster analysis based on ISSR data classified the accessions into 11 major groups. No linkage was observed between the collection site and genetic structure of the samples. On the other hand, a few accessions were detected as unique genotypes and tended to form separate clusters. The estimated gene diversity value was high, both within the whole collection and within the different groups of botanical varieties. PMID:26606797

  18. Mapping quantitative trait loci for milk production and genetic polymorphisms of milk proteins in dairy sheep

    PubMed Central

    2005-01-01

    In this paper, we present recent advances in the molecular dissection of complex traits in dairy sheep and discuss their possible impact on breeding schemes. In the first step, we review the literature data on genetic polymorphisms and the effects of sheep ?s1-casein and ?-lactoglobulin loci. It is concluded that the results are rather inconsistent and cannot be used in dairy sheep selection. In a second step, we describe the strategy implemented in France, Italy and Spain taking advantage of the genetic maps for QTL detection. These studies were part of a European project, called "genesheepsafety", which investigated both milk production and functional traits. Preliminary QTL results are presented for production traits. PMID:15601591

  19. Human population genetic structure detected by pain-related mu opioid receptor gene polymorphisms

    PubMed Central

    López Soto, Eduardo Javier; Catanesi, Cecilia Inés

    2015-01-01

    Several single nucleotide polymorphisms (SNPs) in the Mu Opioid Receptor gene (OPRM1) have been identified and associated with a wide variety of clinical phenotypes related both to pain sensitivity and analgesic requirements. The A118G and other potentially functional OPRM1 SNPs show significant differences in their allele distributions among populations. However, they have not been properly addressed in a population genetic analysis. Population stratification could lead to erroneous conclusions when they are not taken into account in association studies. The aim of our study was to analyze OPRM1 SNP variability by comparing population samples of the International Hap Map database and to analyze a new population sample from the city of Corrientes, Argentina. The results confirm that OPRM1 SNP variability differs among human populations and displays a clear ancestry genetic structure, with three population clusters: Africa, Asia, and Europe-America. PMID:26273217

  20. [Genetic polymorphism of flax Linum usitatissimum based on use of molecular cytogenetic markers].

    PubMed

    Rachinskaia, O A; Lemesh, V A; Muravenko, O V; Iurkevich, O Iu; Guzenko, E V; Bol'sheva, N L; Bogdanova, M V; Samatadze, T E; Popov, K V; Malyshev, S V; Shostak, N G; Heller, K; Khotyleva, L V; Zelenin, A V

    2011-01-01

    Using a set of approaches based on the use of molecular cytogenetic markers (DAPI/C-banding, estimation of the total area of DAPI-positive regions in prophase nuclei, FISH with 26S and 5S rDNA probes) and the microsatellite (SSR-PCR) assay, we studied genomic polymorphism in 15 flax (Linum usitatissimum L.) varieties from different geographic regions belonging to three directions of selection (oil, fiber, and intermediate flaxes) and in the k-37 x Viking hybrid. All individual chromosomes have been identified in the karyotypes of these varieties on the basis of the patterns of differential DAPI/C-banding and the distribution of 26S and 5S rDNA, and idiograms of the chromosomes have been generated. Unlike the oil flax varieties, the chromosomes in the karyotypes of the fiber flax varieties have, as a rule, pericentromeric and telomeric DAPI-positive bands of smaller size, but contain larger intercalary regions. Two chromosomal rearrangements (chromosome 3 inversions) were discovered in the variety Luna and in the k-37 x Viking hybrid. In both these forms, no colocalization of 26S rDNA and 5S rDNA on the satellite chromosome was detected. The SSR assay with the use of 20 polymorphic pairs of primers revealed 22 polymorphic loci. Based on the SSR data, we analyzed genetic similarity of the flax forms studied and constructed a genetic similarity dendrogram. The genotypes studied here form three clusters. The oil varieties comprise an independent cluster. The genetically related fiber flax varieties Vita and Luna, as well as the landrace Lipinska XIII belonging to the intermediate type, proved to be closer to the oil varieties than the remaining fiber flax varieties. The results of the molecular chromosomal analysis in the fiber and oil flaxes confirm their very close genetic similarity. In spite of this, the combined use of the chromosomal and molecular markers has opened up unique possibilities for describing the genotypes of flax varieties and creating their genetic passports. PMID:21446184

  1. Genetic diversity and relationships among Chinese Eucommia ulmoides cultivars revealed by sequence-related amplified polymorphism, amplified fragment length polymorphism, and inter-simple sequence repeat markers.

    PubMed

    Li, Y; Wang, S H; Li, Z Q; Jin, C F; Liu, M H

    2014-01-01

    Sequence-related amplified polymorphism (SRAP), amplified fragment length polymorphism (AFLP), and inter-simple sequence repeat (ISSR) markers were used to estimate the genetic diversity and relationships among Eucommia ulmoides cultivars in China. A total of 240, 192, and 150 DNA fragments were detected by 10 SRAP primer combinations, 10 AFLP primer combinations, and 10 ISSR primers, among which 89.2, 65.1, and 88.0% of the fragments were polymorphic, respectively. Cluster analysis revealed that Qinzhong No. 3, Xiaoyeci, Qinzhong No. 1, and Qinzhong No. 2 formed independent clusters. The other 15 cultivars exhibited two clusters. The results of this study will help in the selection of parents for both genome mapping and crossbreeding purposes. PMID:25366761

  2. Genetic polymorphisms of pharmacogenomic VIP variants in the lhoba population of southwest China

    PubMed Central

    He, Yongjun; Yang, Hua; Geng, Tingting; Feng, Tian; Yuan, Dongya; Kang, Longli; Luo, Manling; Jin, Tianbo

    2015-01-01

    Background: It is well-established that differences among ethnic groups in drug responses are primarily due to the genetic diversity of pharmacogenes. A number of genes or variants that play a crucial role in drug responses have been designated Very Important Pharmacogenes (VIP) by the PharmGKB database. Clarifying the polymorphic distribution of VIPs in different ethnic groups will aid in personalized medicine for specific populations. Methods: We sequenced 85 VIP variants in the Lhoba population based on the PharmGKB database. The polymorphic distribution of the 85 VIP variants in 100 Lhoba subjects was determined and compared with that of 11 major HapMap populations, including ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI. We used ?2 tests to identify significantly different loci between these populations. We downloaded SNP allele frequencies from the ALlele FREquency Database to observe the global genetic variation distribution for these specific loci. And then we used Structure software to perform the genetic structure analysis of 12 populations. Results: Based on comparisons of selected available loci, we found that 23, 28, 16, 10, 20, 16, 24, 19, 22, 21 and 36 of the selected VIP variant genotype frequencies in the Lhoba population differed from those of the ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI populations, respectively. In addition, Pairwise FST values and clustering analyses also showed the VIP variants in Lhoba exhibited a close genetic affinity with CHD, CHB and JPT populations. Conclusion: Our results complement pharmacogenomic data on the Lhoba ethnic group and may be helpful in the diagnosis of certain diseases in minorities. PMID:26722533

  3. [Hyperlipoprotein (a)-emia determined by genetic polymorphisms in apolipoprotein (a) gene].

    PubMed

    Ichinose, Akitada

    2008-11-01

    Prothrombotic and proatherogenic risk factors, including elevated lipoprotein (a), predispose an individual to initial and recurrent ischemic stroke. An increased plasma level of lipoprotein (a), over 25-30 mg/dL, is called hyperlipoprotein (a)-emia, and is largely determined by genetic polymorphisms in apolipoprotein (a). Apolipoprotein (a) is a major protein component of lipoprotein (a), and is connected with apolipoprotein B-100 of low density lipoprotein. The size of apolipoprotein (a) and concentration of lipoprotein (a) vary widely among individuals as well as between ethnic groups. The size of apolipoprotein (a) and plasma concentrations of lipoprotein (a) are inversely related. Accordingly, the number of tandemly repeated structures, named kringle-4 domains, determines the size of apolipoprotein (a), and consequently the plasma lipoprotein (a) level. In addition, the efficiency of apolipoprotein (a) gene expression is a determinant of lipoprotein (a) concentrations, since lipoprotein (a) levels vary more than 200-fold even among the individuals having the same apolipoprotein (a) size. First, we identified haplotypes in the 5'-promoter region of the apolipoprotein (a) gene as a regulating factor of plasma lipoprotein (a) levels. Second, a pentanucleotide repeat polymorphism upstream of the promoter region was also reported to affect plasma lipoprotein (a) levels. Third, two functional single nucleotide polymorphisms were identified in a distal enhancer region situated approximately 20 kb from the apolipoprotein (a) gene. Finally, several polymorphisms were identified in the kringle-4 domains, and found to influence plasma lipoprotein (a) levels as well as the lysine/fibrin-binding function. Since lower molecular weight forms of apolipoprotein (a) are closely associated with the incidence of ischemic stroke, both high plasma concentrations of lipoprotein (a) and small sizes (i. e., number of kringle-4 repeats in the gene) of apolipoprotein (a) are risk factors for the development of atherothrombosis. PMID:19069164

  4. Genetic Polymorphism G894T and the Prognosis of Heart Failure Outpatients

    PubMed Central

    Tardin, Oziel Marcio Araujo; Pereira, Sabrina Bernardez; Velloso, Monica Wanderley Monores; Balieiro, Henrique Miller; Costa, Bruno; Alves, Thiago Oliveira e; Giro, Camila; Pessoa, Leandro Pontes; Ribeiro, Georgina Severo; Mesquita, Evandro Tinoco

    2013-01-01

    Background Previous studies have analyzed the role of the genetic polymorphism of endothelial nitric oxide synthase on heart failure prognosis. However, there are no studies relating the G894T and heart failure in Brazil. Objective To evaluate the association between G894T GP and the prognosis of a sample of Brazilian outpatients with heart failure. Methods Cohort study included 145 patients with systolic heart failure, followed for up to 40 months (mean = 22), at two university hospitals, in the State of Rio de Janeiro. We evaluated the relationship between G894T and the following outcomes: reverse remodeling, improvement in functional class (NYHA), and mortality and hospitalization rates. The diameters of the left atrium and ventricle, as well as the ejection fraction of the left ventricle, were evaluated at baseline and at 6 months to assess reverse remodeling. The improvement in functional class was evaluated after 6 months, and mortality rate and hospitalization were evaluated during follow-up. Race was self-declared. G894T polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Results The genotypic frequencies were GG (40%), GT (48.3%) and TT (11.7%). The allele frequency was guanine (64.1%) and thiamine (35.8%). There were no differences between the genotype or allelic frequencies according to self declared race, either as baseline characteristics. There was no relationship between genotype or allele frequency and the outcome measures. Conclusion No association was observed between the G894T polymorphism (Glu298Asp) and prognosis in this sample of Brazilian outpatients with systolic heart failure. PMID:23949326

  5. Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan

    PubMed Central

    Hsu, Ling-I; Wu, Meei-Maan; Wang, Yuan-Hung; Lee, Cheng-Yeh; Yang, Tse-Yen; Hsiao, Bo-Yu; Chen, Chien-Jen

    2015-01-01

    Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.018.83; OR = 2.04, 95% CI = 0.994.27; OR = 1.74, 95% CI = 1.003.02, resp.). However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated. PMID:26295053

  6. A genetic polymorphism in RBP4 is associated with coronary artery disease.

    PubMed

    Wan, Ke; Zhao, Jianxun; Deng, Ying; Chen, Xi; Zhang, Qing; Zeng, Zhi; Zhang, Li; Chen, Yucheng

    2014-01-01

    Insulin resistance and obesity is influenced by the retinol binding protein 4 (RBP4) adipokine. This study aims to determine if genetic polymorphisms in RBP4 are associated with the risk of coronary artery disease (CAD) in Chinese patients. RBP4 polymorphisms were analyzed by high resolution melting (HRM) analysis in a case-control study of 392 unrelated CAD patients and 368 controls from China. The Gensini score was used to determine the severity of CAD. The genotypic and allelic frequencies of RBP4 single-nucleotide polymorphisms were evaluated for associations with CAD and severity of disease. The A allele frequency was significantly higher in CAD case groups compared to control groups (16.7% vs. 8.8%) at the RBP4 rs7094671 locus. Compared to the G allele, this allele was associated with a higher risk of CAD (OR = 2.07 (1.50-2.84)). Polymorphisms at rs7094671 were found to associate with CAD using either a dominant or recessive model (OR, 95% CI: 1.97, 1.38-2.81; 3.81, 1.53-9.51, respectively). Adjusting for sex, history of smoking, serum TC, TG, LDL-c, and HDL-c, the risk of CAD for carriers remained signi?cantly higher in both dominant and recessive models (OR, 95% CI: 1.68, 1.12-2.51; 2.74, 1.00-7.52, respectively). However, this SNP was not significantly associated with severity of CAD using angiographic scores in multivariable linear regression models (p = 0.373). The RBP4 rs7094671 SNP is associated with CAD; however, our results do not indicate that this locus is associated with clinical severity of CAD or the extent of coronary lesions. PMID:25479076

  7. Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan.

    PubMed

    Hsu, Ling-I; Wu, Meei-Maan; Wang, Yuan-Hung; Lee, Cheng-Yeh; Yang, Tse-Yen; Hsiao, Bo-Yu; Chen, Chien-Jen

    2015-01-01

    Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01-8.83; OR = 2.04, 95% CI = 0.99-4.27; OR = 1.74, 95% CI = 1.00-3.02, resp.). However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated. PMID:26295053

  8. Genetic Polymorphisms of Dihydropyrimidinase in a Japanese Patient with Capecitabine-Induced Toxicity

    PubMed Central

    Akai, Fumika; Hosono, Hiroki; Hishinuma, Eiji; Hirasawa, Noriyasu

    2015-01-01

    Dihydropyrimidinase (DHP) is the second enzyme in the catabolic pathway of uracil, thymine, and chemotherapeutic fluoropyrimidine agents such as 5-fluorouracil (5-FU). Thus, DHP deficiency might be associated with 5-FU toxicity during fluoropyrimidine chemotherapy. We performed genetic analyses of the family of a patient with advanced colon cancer who underwent radical colectomy followed by treatment with 5-FU prodrug capecitabine and developed severe toxicity attributable to a lack of DHP. We measured urinary uracil and dihydrouracil, and genotyped DPYS in the patient and her family. We also measured the allele frequency of DPYS polymorphisms in 391 unrelated Japanese subjects. The patient had compound heterozygous missense and nonsense polymorphisms comprising c.1001A>G (p.Gln334Arg) in exon 6 and c.1393C>T (p.Arg465Ter) in exon 8, which are known to result in a DHP enzyme with little or no activity. The urinary dihydrouracil/uracil ratio in the patient was 17.08, while the mean ± SD urinary dihydrouracil/uracil ratio in family members who were heterozygous or homozygous for wild-type DPYS was 0.25 ± 0.06. In unrelated subjects, 8 of 391 individuals were heterozygous for the c.1001A>G mutation, while the c.1393C>T mutation was not identified. This is the first report of a DHP-deficient patient with DPYS compound heterozygous polymorphisms who was treated with a fluoropyrimidine, and our findings suggest that polymorphisms in the DPYS gene are pharmacogenomic markers associated with severe 5-FU toxicity in Japanese patients. PMID:25915935

  9. A Genetic Polymorphism in RBP4 Is Associated with Coronary Artery Disease

    PubMed Central

    Wan, Ke; Zhao, Jianxun; Deng, Ying; Chen, Xi; Zhang, Qing; Zeng, Zhi; Zhang, Li; Chen, Yucheng

    2014-01-01

    Insulin resistance and obesity is influenced by the retinol binding protein 4 (RBP4) adipokine. This study aims to determine if genetic polymorphisms in RBP4 are associated with the risk of coronary artery disease (CAD) in Chinese patients. RBP4 polymorphisms were analyzed by high resolution melting (HRM) analysis in a case-control study of 392 unrelated CAD patients and 368 controls from China. The Gensini score was used to determine the severity of CAD. The genotypic and allelic frequencies of RBP4 single-nucleotide polymorphisms were evaluated for associations with CAD and severity of disease. The A allele frequency was significantly higher in CAD case groups compared to control groups (16.7% vs. 8.8%) at the RBP4 rs7094671 locus. Compared to the G allele, this allele was associated with a higher risk of CAD (OR = 2.07 (1.502.84)). Polymorphisms at rs7094671 were found to associate with CAD using either a dominant or recessive model (OR, 95% CI: 1.97, 1.382.81; 3.81, 1.539.51, respectively). Adjusting for sex, history of smoking, serum TC, TG, LDL-c, and HDL-c, the risk of CAD for carriers remained significantly higher in both dominant and recessive models (OR, 95% CI: 1.68, 1.122.51; 2.74, 1.007.52, respectively). However, this SNP was not significantly associated with severity of CAD using angiographic scores in multivariable linear regression models (p = 0.373). The RBP4 rs7094671 SNP is associated with CAD; however, our results do not indicate that this locus is associated with clinical severity of CAD or the extent of coronary lesions. PMID:25479076

  10. Genetic polymorphism of six DNA loci in six population groups of India.

    PubMed

    Ahmad, Shazia; Seshadri, M

    2007-08-01

    The genetic profile based on autosomal markers, four microsatellite DNA markers (D8S315, FES, D8S592, and D2S1328) and two minisatellite DNA markers (TPMT and PDGFA), were analyzed in six endogamous populations to examine the effect of geographic and linguistic affiliation on the genetic affinities among the groups. The six populations are from three different states of India and are linguistically different. Marathas from western India speak Marathi, an Indo-European language. Arayas, Muslims, Ezhavas, and Nairs from Kerala state of South India speak Malayalam, and Iyers from Tamil Nadu state speak Tamil. Genomic DNA was extracted from peripheral blood samples of random, normal, healthy individuals. Locus-specific PCR amplification was carried out, followed by electrophoresis of the amplicons and genotyping. All the loci were highly polymorphic and followed Hardy-Weinberg equilibrium, except for loci D8S315 and PDGFA in Iyers and Marathas, respectively. All six loci had high heterozygosity (average heterozygosity ranged from 0.73 to 0.76) and high polymorphism information content (0.57-0.90). The extent of gene differentiation among the six populations (G(ST) = 0.030) was greater than that for four Kerala populations (G(ST) = 0.011), suggesting proximity between the four Kerala populations. This result conforms with the cultural and linguistic background of the populations. The extent of diversity found among the populations probably resulted from the strict endogamous practices that they follow. PMID:18075006

  11. Genetic and Molecular Basis of QTL of Diabetes in Mouse: Genes and Polymorphisms

    PubMed Central

    Gao, Peng; Jiao, Yan; Xiong, Qing; Wang, Cong-Yi; Gerling, Ivan; Gu, Weikuan

    2008-01-01

    A systematic study has been conducted of all available reports in PubMed and OMIM (Online Mendelian Inheritance in Man) to examine the genetic and molecular basis of quantitative genetic loci (QTL) of diabetes with the main focus on genes and polymorphisms. The major question is, What can the QTL tell us? Specifically, we want to know whether those genome regions differ from other regions in terms of genes relevant to diabetes. Which genes are within those QTL regions, and, among them, which genes have already been linked to diabetes? whether more polymorphisms have been associated with diabetes in the QTL regions than in the non-QTL regions. Our search revealed a total of 9038 genes from 26 type 1 diabetes QTL, which cover 667,096,006 bp of the mouse genomic sequence. On one hand, a large number of candidate genes are in each of these QTL; on the other hand, we found that some obvious candidate genes of QTL have not yet been investigated. Thus, the comprehensive search of candidate genes for known QTL may provide unexpected benefit for identifying QTL genes for diabetes. PMID:19471607

  12. Characterization of polymorphic microsatellite markers and genetic diversity in wild bronze featherback, Notopterus notopterus (Pallas, 1769).

    PubMed

    Gupta, Arti; Lal, Kuldeep K; Punia, Peyush; Singh, Rajeev K; Mohindra, Vindhya; Sah, Rama S; Kumar, Rajesh; Luhariya, Rupesh K; Dwivedi, Arvind K; Masih, Prachi; Mishra, R M; Jena, J K

    2013-12-01

    Six polymorphic microsatellite DNA loci were identified in the primitive fish, bronze featherback, Notopterus notopterus for the first time and demonstrated significant population genetic structure. Out of the six primers, one primer (NN90) was specific to N. notopterus (microsatellite sequence within the RAG1 gene) and five primers were product of successful cross-species amplification. Sixty-four primers available from 3 fish species of order Osteoglossiformes and families Notopteridae and Osteoglossidae were tested to amplify homologous microsatellite loci in N. notopterus. Fifteen primer pairs exhibited successful cross-priming PCR product. However, polymorphism was detected only at five loci. To assess the significance of these six loci (including NN90) in population genetic study, 215 samples of N. notopterus from five rivers, viz Satluj, Gomti, Yamuna, Brahmaputra and Mahanadi were analyzed. The five sample sets displayed different diversity levels and observed heterozygosity ranged from 0.6036 to 0.7373. Significant genotype heterogeneity (P < 0.0001) and high FST (0.2205) over all loci indicated that the samples are not drawn from the same genepool. The identified microsatellite loci are promising for use in fine-scale population structure analysis of N. notopterus. PMID:24072656

  13. Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism

    PubMed Central

    Krueger, Sharon K.; Williams, David E.

    2005-01-01

    Flavin-containing monooxygenase (FMO) oxygenates drugs and xenobiotics containing a “soft-nucleophile”, usually nitrogen or sulfur. FMO, like cytochrome P450 (CYP), is a monooxygenase, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate. FMO and CYP also exhibit similar tissue and cellular location, molecular weight, substrate specificity, and exist as multiple enzymes under developmental control. The human FMO functional gene family is much smaller (5 families each with a single member) than CYP. FMO does not require a reductase to transfer electrons from NADPH and the catalytic cycle of the 2 monooxygenases is strikingly different. Another distinction is the lack of induction of FMOs by xenobiotics. In general, CYP is the major contributor to oxidative xenobiotic metabolism. However, FMO activity may be of significance in a number of cases and should not be overlooked. FMO and CYP have overlapping substrate specificities, but often yield distinct metabolites with potentially significant toxicological/pharmacological consequences. The physiological function(s) of FMO are poorly understood. Three of the 5 expressed human FMO genes, FMO1, FMO2 and FMO3, exhibit genetic polymorphisms. The most studied of these is FMO3 (adult human liver) in which mutant alleles contribute to the disease known as trimethylaminuria. The consequences of these FMO genetic polymorphisms in drug metabolism and human health are areas of research requiring further exploration. PMID:15922018

  14. Impact of genetic polymorphisms on chemotherapy toxicity in childhood acute lymphoblastic leukemia

    PubMed Central

    Gervasini, Guillermo; Vagace, Jose M.

    2012-01-01

    The efficacy of chemotherapy in pediatric acute lymphoblastic leukemia (ALL) patients has significantly increased in the last 20 years; as a result, the focus of research is slowly shifting from trying to increase survival rates to reduce chemotherapy-related toxicity. At the present time, the cornerstone of therapy for ALL is still formed by a reduced number of drugs with a highly toxic profile. In recent years, a number of genetic polymorphisms have been identified that can play a significant role in modifying the pharmacokinetics and pharmacodynamics of these drugs. The best example is that of the TPMT gene, whose genotyping is being incorporated to clinical practice in order to individualize doses of mercaptopurine. However, there are additional genes that are relevant for the metabolism, activity, and/or transport of other chemotherapy drugs that are widely use in ALL, such as methotrexate, cyclophosphamide, vincristine, L-asparaginase, etoposide, cytarabine, or cytotoxic antibiotics. These genes can also be affected by genetic alterations that could therefore have clinical consequences. In this review we will discuss recent data on this field, with special focus on those polymorphisms that could be used in clinical practice to tailor chemotherapy for ALL in order to reduce the occurrence of serious adverse effects. PMID:23189085

  15. [Genetic diversity and relationships of northern eurasia populations for polymorphic Alu-insertions].

    PubMed

    Khitrinskaia, I Iu; Khar'kov, V N; Voevoda, M I; Stepanova, V A

    2014-01-01

    We for the first time have examined the autosomal gene pool of the Siberia, Central Asian and the Far East populations (27 populations of 12 ethnic groups) using a set of polymorphic Alu insertions in the human genome. The results of the analysis testify (i) to a significant level of genetic diversity in the Northern Eurasian populations and (ii) to a considerable differentiation of gene pool in the population of this region. It has been shown that at the CD4 locus, the frequency of Alu (-) is inversely related to the Mongoloid component of the population, the lowest and highest frequencies of the Alu deletion at locus CD4 were recorded respectively in Eskimo (0.012) and Russian and Ukrainian (0.35). The analysis of gene flow proved Caucasoid populations (Russian, Tajik and Uzbek), as well as those of Turkic ethnic groups from the Southern Siberia (Altaians and Tuvinians) and Khanty and Mansy populations to be the recipients of a considerable gene flow from the outside of the concerned population system, as compared with the East Siberian and the Far East ethnic groups. The results of the correlation analysis received with use polymorphic Alu insertion testify to the greatest correlation of genetic distances with anthropological characteristics of populations. PMID:25842827

  16. Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer

    PubMed Central

    Thomas, F; Motsinger-Reif, A A; Hoskins, J M; Dvorak, A; Roy, S; Alyasiri, A; Myerson, R J; Fleshman, J W; Tan, B R; McLeod, H L

    2011-01-01

    Background: There is a large degree of variation in tumour response and host toxicities associated with neoadjuvant chemoradiation for rectal cancer patients. We performed a complimentary pharmacogenetic study to investigate germline polymorphisms of genes involved in 5-fluorouracil (5-FU) and irinotecan pathways and their potential association with clinical outcomes and toxicities from neoadjuvant chemoradiation in patients with rectal cancer treated in a prospective genotype-directed study. Methods: The germline DNA of 131 patients was genotyped for 10 variants in TYMS, MTHFR, DPYD, UGT1A1, ABCC1 and SLCO1B1 genes. Ninety-six patients were treated with 5-FU/radiotherapy (RT) and 35 received 5-FU/RT/irinotecan. Relationships between genetic variants and adverse events, tumour response, overall and disease-free survivals were assessed. Results: MTHFR 1298A>C and MTHFR diplotypes (for 677C>T and 1298A>C) were associated with chemoradiation-related toxicity when 5-FU was used alone. MTHFR haplotypes (677C1298C) and diplotypes (CATA and TATA) showed, respectively, a protective and a negative effect on the incidence of severe diarrhoea or mucositis. No association was observed between genetic markers and drug response. Conclusion: MTHFR polymorphisms can potentially predict toxicity in patients treated with 5-FU as a single chemotherapeutic drug. PMID:22045187

  17. Fatal Methadone Toxicity: Potential Role of CYP3A4 Genetic Polymorphism

    PubMed Central

    Richards-Waugh, Lauren L.; Primerano, Donald A.; Dementieva, Yulia; Kraner, James C.; Rankin, Gary O.

    2014-01-01

    Methadone is difficult to administer as a therapeutic agent because of a wide range of interindividual pharmacokinetics, likely due to genetic variability of the CYP450 enzymes responsible for metabolism to its principal metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). CYP3A4 is one of the primary CYP450 isoforms responsible for the metabolism of methadone to EDDP in humans. The purpose of this study was to evaluate the role of CYP3A4 genetic polymorphisms in accidental methadone fatalities. A study cohort consisting of 136 methadone-only and 92 combined methadone/benzodiazepine fatalities was selected from cases investigated at the West Virginia and Kentucky Offices of the Chief Medical Examiner. Seven single nucleotide polymorphisms (SNPs) were genotyped within the CYP3A4 gene. Observed allelic and genotypic frequencies were compared with expected frequencies obtained from The National Center for Biotechnology Information dbSNP database. SNPs rs2242480 and rs2740574 demonstrated an apparent enrichment within the methadone-only overdose fatalities compared with the control group and the general population. This enrichment was not apparent in the methadone/benzodiazepine cases for these two SNPs. Our findings indicate that there may be two or more SNPs on the CYP3A4 gene that cause or contribute to the methadone poor metabolizer phenotype. PMID:25217544

  18. Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism.

    PubMed

    Krueger, Sharon K; Williams, David E

    2005-06-01

    Flavin-containing monooxygenase (FMO) oxygenates drugs and xenobiotics containing a "soft-nucleophile", usually nitrogen or sulfur. FMO, like cytochrome P450 (CYP), is a monooxygenase, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate. FMO and CYP also exhibit similar tissue and cellular location, molecular weight, substrate specificity, and exist as multiple enzymes under developmental control. The human FMO functional gene family is much smaller (5 families each with a single member) than CYP. FMO does not require a reductase to transfer electrons from NADPH and the catalytic cycle of the 2 monooxygenases is strikingly different. Another distinction is the lack of induction of FMOs by xenobiotics. In general, CYP is the major contributor to oxidative xenobiotic metabolism. However, FMO activity may be of significance in a number of cases and should not be overlooked. FMO and CYP have overlapping substrate specificities, but often yield distinct metabolites with potentially significant toxicological/pharmacological consequences. The physiological function(s) of FMO are poorly understood. Three of the 5 expressed human FMO genes, FMO1, FMO2 and FMO3, exhibit genetic polymorphisms. The most studied of these is FMO3 (adult human liver) in which mutant alleles contribute to the disease known as trimethylaminuria. The consequences of these FMO genetic polymorphisms in drug metabolism and human health are areas of research requiring further exploration. PMID:15922018

  19. CD24 and APC Genetic Polymorphisms in Pancreatic Cancers as Potential Biomarkers for Clinical Outcome

    PubMed Central

    Shamai, Sivan; Nabiochtchikov, Ilana; Kraus, Sarah; Zigdon, Sally; Kazanov, Dina; Itzhak-Klutch, Michal; Eizner, Carmit

    2015-01-01

    Background There are no validated biomarkers that correlate with the prognosis of pancreatic ductal adenocarcinoma (PDA). The CD24 and adenomatous polyposis coli (APC) genes are important in the malignant transformation of gastrointestinal cells. This study examined APC and CD24 genetic polymorphisms and their possible impact on survival of patients with PDA. Methods Clinical and pathological data as well as blood samples for extracting DNA were obtained for 73 patients with PDA. Real-time PCR assessed genetic variants of APC (I1307K and E1317Q), and four different single nucleotide polymorphisms (SNPs) in the CD24 gene: C170T (rs52812045), TG1527del (rs3838646), A1626G (rs1058881) and A1056G (rs1058818). Results The median age at diagnosis was 64 (4190) years. Thirty-one patients (42.5%) were operable, 16 (22%) had locally advanced disease and 26 (35.5%) had disseminated metastatic cancer. The malignancy-related mortality rate was 84%. Median survival was 14 months (11.2516.74). Survival was similar for wild-type (WT), heterozygous and homozygous variants of the APC or CD24 genes. The three most frequent CD24 SNP combinations were: heterozygote for A1626G and WT for the rest of the alleles (14% of patients), heterozygote for C170T, A1626G, A1056G and WT for the rest (14% of patients), and heterozygote for C170T, A1056G and WT for the rest (10% of patients). All patients were APC WT. The first two groups were significantly younger at diagnosis than the third group. Conclusions Specific polymorphisms in the APC and CD24 genes may play a role in pancreatic cancer development. Correlation with survival requires a larger cohort. PMID:26394139

  20. Genetic polymorphisms in the thioredoxin 2 (TXN2) gene and risk for spina bifida.

    PubMed

    Wen, Shu; Lu, Wei; Zhu, Huiping; Yang, Wei; Shaw, Gary M; Lammer, Edward J; Islam, Ana; Finnell, Richard H

    2009-02-01

    TXN2 encodes human thioredoxin 2, a small redox protein important in cellular antioxidant defenses, as well as in the regulation of apoptosis. Txn2 knockout mice fail to complete neural tube closure by E10.5 and die in utero. We hypothesized that genetic variation in human TXN2 gene may alter the function of the encoded protein in a manner associated with an increased risk for neural tube defects (NTDs). A DNA re-sequencing effort of the human TXN2 gene was taken. After a variation in the promoter was identified, the transcriptional activity of different alleles was investigated. The possible association between these variations and the risk of spina bifida was further evaluated in a subset of samples obtained from a large population-based case-control study in California in two different ethnicity groups, non-Hispanic white and Hispanic white. We identified a novel promoter insertion polymorphism located 9 base pairs upstream of the transcription start site of exon 1(-9 insertion). The GA, G and GGGA insertions were associated with a marked decrease of transcriptional activity when overexpressed in both U2-OS (an osteosarcoma cell line) and 293 cells (derived from human embryonic kidney). Further analysis revealed that the GA insertion was associated with increased spina bifida risk for Hispanic whites. Our study revealed a novel Ins/Del polymorphism in the human TXN2 gene proximal promoter region that altered the transcriptional activity and is associated with spina bifida risk. This polymorphism may be a genetic modifier of spina bifida risk in this California population. PMID:19165900

  1. Construction of a Genetic Linkage Map Based on Amplified Fragment Length Polymorphism Markers and Development of Sequence-Tagged Site Markers for Marker-Assisted Selection of the Sporeless Trait in the Oyster Mushroom (Pleurotus eryngii)

    PubMed Central

    Ueda, Jun; Obatake, Yasushi; Murakami, Shigeyuki; Fukumasa, Yukitaka; Matsumoto, Teruyuki

    2012-01-01

    A large number of spores from fruiting bodies can lead to allergic reactions and other problems during the cultivation of edible mushrooms, including Pleurotus eryngii (DC.) Qul. A cultivar harboring a sporulation-deficient (sporeless) mutation would be useful for preventing these problems, but traditional breeding requires extensive time and labor. In this study, using a sporeless P. eryngii strain, we constructed a genetic linkage map to introduce a molecular breeding program like marker-assisted selection. Based on the segregation of 294 amplified fragment length polymorphism markers, two mating type factors, and the sporeless trait, the linkage map consisted of 11 linkage groups with a total length of 837.2 centimorgans (cM). The gene region responsible for the sporeless trait was located in linkage group IX with 32 amplified fragment length polymorphism markers and the B mating type factor. We also identified eight markers closely linked (within 1.2 cM) to the sporeless locus using bulked-segregant analysis-based amplified fragment length polymorphism. One such amplified fragment length polymorphism marker was converted into two sequence-tagged site markers, SD488-I and SD488-II. Using 14 wild isolates, sequence-tagged site analysis indicated the potential usefulness of the combination of two sequence-tagged site markers in cross-breeding of the sporeless strain. It also suggested that a map constructed for P. eryngii has adequate accuracy for marker-assisted selection. PMID:22210222

  2. Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinsons disease susceptibility in Chinese Han population

    PubMed Central

    Dai, Yi; Wu, Yuquan; Li, Yansheng

    2015-01-01

    Objective: The aim of this study was to explore the genetic association of cyclooxygenase-2 (COX2) gene promoter region polymorphisms with Parkinsons disease (PD) susceptibility in Chinese Han population. Methods: The genotyping of COX2 gene polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 patients with PD and 120 healthy persons. The association strength of gene polymorphism with disease was measured by odds ratio (OR) and 95% confidence interval (95% CI) calculated using ?2 test which also evaluated the Hardy-Weinberg equilibrium (HWE) of gene polymorphism in controls. The linkage disequilibrium and haplotype were also analyzed as evidence in the analysis of association. Results: On condition that the genotypes distributions of COX2 -1290A>G, -1195G>A, -765G>C in the control group all conformed to HWE, however, only the homozygous genotype AA of -1195G>A polymorphism showed an association with PD (OR=0.432, 95% CI=0.196-0.950). In addition, in haplotype analysis, G-A-C haplotype frequency in cases was significantly lower than the controls, compared with the common haplotype A-G-G (P=0.031, OR=0.375, 95% CI=0.149-0.940). Conclusions: COX2 -1195G>A polymorphism might play a protective role in the onset of PD and G-A-C haplotype in this three promoter region polymorphisms also showed a negative association. PMID:26722563

  3. Evaluation of genetic diversity in Chinese kale (Brassica oleracea L. var. alboglabra Bailey) by using rapid amplified polymorphic DNA and sequence-related amplified polymorphism markers.

    PubMed

    Zhang, J; Zhang, L G

    2014-01-01

    Chinese kale is an original Chinese vegetable of the Cruciferae family. To select suitable parents for hybrid breeding, we thoroughly analyzed the genetic diversity of Chinese kale. Random amplified polymorphic DNA (RAPD) and sequence-related amplified polymorphism (SRAP) molecular markers were used to evaluate the genetic diversity across 21 Chinese kale accessions from AVRDC and Guangzhou in China. A total of 104 bands were detected by 11 RAPD primers, of which 66 (63.5%) were polymorphic, and 229 polymorphic bands (68.4%) were observed in 335 bands amplified by 17 SRAP primer combinations. The dendrogram showed the grouping of the 21 accessions into 4 main clusters based on RAPD data, and into 6 clusters based on SRAP and combined data (RAPD + SRAP). The clustering of accessions based on SRAP data was consistent with petal colors. The Mantel test indicated a poor fit for the RAPD and SRAP data (r = 0.16). These results have an important implication for Chinese kale germplasm characterization and improvement. PMID:24615113

  4. Exploiting the Extraordinary Genetic Polymorphism of Ciona for Developmental Genetics with Whole Genome Sequencing

    PubMed Central

    Abdul-Wajid, Sarah; Veeman, Michael T.; Chiba, Shota; Turner, Thomas L.; Smith, William C.

    2014-01-01

    Studies in tunicates such as Ciona have revealed new insights into the evolutionary origins of chordate development. Ciona populations are characterized by high levels of natural genetic variation, between 1 and 5%. This variation has provided abundant material for forward genetic studies. In the current study, we make use of deep sequencing and homozygosity mapping to map spontaneous mutations in outbred populations. With this method we have mapped two spontaneous developmental mutants. In Ciona intestinalis we mapped a short-tail mutation with strong phenotypic similarity to a previously identified mutant in the related species Ciona savignyi. Our bioinformatic approach mapped the mutation to a narrow interval containing a single mutated gene, α-laminin3,4,5, which is the gene previously implicated in C. savignyi. In addition, we mapped a novel genetic mutation disrupting neural tube closure in C. savignyi to a T-type Ca2+ channel gene. The high efficiency and unprecedented mapping resolution of our study is a powerful advantage for developmental genetics in Ciona, and may find application in other outbred species. PMID:24532781

  5. Candidate Human Genetic Polymorphisms and Severe Malaria in a Tanzanian Population

    PubMed Central

    Nadjm, Behzad; Mtove, George; Wangai, Hannah; Sepulveda, Nuno; Campino, Susana G.; Maxwell, Caroline; Olomi, Raimos; Rockett, Kirk R.; Jeffreys, Anna; Riley, Eleanor M.; Reyburn, Hugh; Drakeley, Christopher

    2012-01-01

    Human genetic background strongly influences susceptibility to malaria infection and progression to severe disease and death. Classical genetic studies identified haemoglobinopathies and erythrocyte-associated polymorphisms, as protective against severe disease. High throughput genotyping by mass spectrometry allows multiple single nucleotide polymorphisms (SNPs) to be examined simultaneously. We compared the prevalence of 65 human SNP's, previously associated with altered risk of malaria, between Tanzanian children with and without severe malaria. Five hundred children, aged 110 years, with severe malaria were recruited from those admitted to hospital in Muheza, Tanzania and compared with matched controls. Genotyping was performed by Sequenom MassArray, and conventional PCR was used to detect deletions in the alpha-thalassaemia gene. SNPs in two X-linked genes were associated with altered risk of severe malaria in females but not in males: heterozygosity for one or other of two SNPs in the G6PD gene was associated with protection from all forms of severe disease whilst two SNPs in the gene encoding CD40L were associated with respiratory distress. A SNP in the adenyl cyclase 9 (ADCY9) gene was associated with protection from acidosis whilst a polymorphism in the IL-1? gene (IL1A) was associated with an increased risk of acidosis. SNPs in the genes encoding IL-13 and reticulon-3 (RTN3) were associated with increased risk of cerebral malaria. This study confirms previously known genetic associations with protection from severe malaria (HbS, G6PD). It identifies two X-linked genes associated with altered risk of severe malaria in females, identifies mutations in ADCY9, IL1A and CD40L as being associated with altered risk of severe respiratory distress and acidosis, both of which are characterised by high serum lactate levels, and also identifies novel genetic associations with severe malaria (TRIM5) and cerebral malaria(IL-13 and RTN3). Further studies are required to test the generality of these associations and to understand their functional consequences. PMID:23144702

  6. Characterization of genetic diversity in chickpea using SSR markers, Start Codon Targeted Polymorphism (SCoT) and Conserved DNA-Derived Polymorphism (CDDP).

    PubMed

    Hajibarat, Zahra; Saidi, Abbas; Hajibarat, Zohreh; Talebi, Reza

    2015-07-01

    To evaluate the genetic diversity among 48 genotypes of chickpea comprising cultivars, landraces and internationally developed improved lines genetic distances were evaluated using three different molecular marker techniques: Simple Sequence Repeat (SSR); Start Codon Targeted (SCoT) and Conserved DNA-derived Polymorphism (CDDP). Average polymorphism information content (PIC) for SSR, SCoT and CDDP markers was 0.47, 0.45 and 0.45, respectively, and this revealed that three different marker types were equal for the assessment of diversity amongst genotypes. Cluster analysis for SSR and SCoT divided the genotypes in to three distinct clusters and using CDDP markers data, genotypes grouped in to five clusters. There were positive significant correlation (r?=?0.43, P?polymorphism for varieties were higher than that of genotypes, and CDDP had superiority over SCoT and SSR markers. These results suggest that efficiency of SSR, SCOT and CDDP markers was relatively the same in fingerprinting of chickpea genotypes. To our knowledge, this is the first detailed report of using targeted DNA region molecular marker (CDDP) for genetic diversity analysis in chickpea in comparison with SCoT and SSR markers. Overall, our results are able to prove the suitability of SCoT and CDDP markers for genetic diversity analysis in chickpea for their high rates of polymorphism and their potential for genome diversity and germplasm conservation. PMID:26261401

  7. Association between Genetic Polymorphisms in DEFB1 and Susceptibility to Digestive Diseases

    PubMed Central

    Huang, Yin-Peng; Wang, Tian-Yi; Wang, Wei; Sun, Hong-Zhi

    2015-01-01

    Background Aberrant expression of defensins is implicated in the pathogenesis of digestive diseases. However, the contribution of specific defensins and the influence of their genetic polymorphisms on the progression of digestive diseases remain controversial. In the present meta-analysis, we investigated the association between DEFB1 SNPs and the susceptibility to digestive diseases. Material/Methods Case-control studies that reported the correlation between DEFB1 SNPs and the susceptibility to digestive diseases were identified through electronic databases searches, and high-quality studies that satisfied our inclusion criteria were selected for this meta-analysis. Statistical analyses were performed utilizing STATA software version 12.0. Results The present meta-analysis revealed that patients with digestive diseases exhibited higher frequencies of the DEFB1 genetic variants rs11362G>A, rs1800972C>G, and rs1799946G>A compared to healthy controls under the allele model. Subgroup analysis based on country showed that the rs1800972C>G variant under allele model and rs1799946G>A are associated with the susceptibility to digestive diseases in Hungarian and Italian populations, respectively. Subgroup analysis based on disease type showed that: (1) rs11362G>A variant was strongly associated with severe acute pancreatitis (SAP) and chronic gastritis, (2) frequency of rs1800972C>G variant was higher in SAP subgroup, and (3) frequency of rs1799946G>A variant was positively associated with the susceptibility to Crohns disease (CD) under the allele model and with SAP. Conclusions Our meta-analysis provides evidence that DEFB1 genetic polymorphisms rs11362G>A, rs1800972C>G and rs1799946G>A are important contributing factors to the development of digestive diseases. PMID:26232989

  8. Methylenetetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility.

    PubMed

    Kumar, Pradeep; Yadav, Upendra; Rai, Vandana

    2015-12-01

    There are several evidences supporting the role of 5-10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in breast cancer (BC). Case control association studies on breast cancer have been repeatedly performed over the last two decades, but results are inconsistent. We performed a meta-analysis to confirm the association between MTHFR C677T polymorphism and BC risk. The articles were retrieved by searching the PubMed, Google Scholar, and Springer Link databases. Crude odds ratios (OR) with 95% confidence intervals (CIs) was used to assess the strength of association between C677T polymorphism and BC. Publication bias was assessed by Egger's and Begg-Mazumdar tests. Meta-analysis was performed with Open Meta Analyst. Total 75 studies with 31,315 cases and 35, 608 controls were found suitable for the inclusion in the present meta-analysis. The results of meta-analysis suggested that there were moderate significant association between C677T polymorphism and BC risk using overall comparisons in five genetic models (T vs. C: OR = 1.08, 95% CI = 1.03-1.13, p = < 0.001; TT + CT vs. CC: OR = 1.06, 95% CI = 1.02-1.09, p = < 0.001; TT vs. CC: OR = 1.17, 95% CI = 1.06-1.28, p = 0.001; CT vs. CC OR = 1.05, 95% CI = 1.01-1.08, p = 0.005; TT vs. CT + CC: OR = 1.12, 95% CI = 1.03-1.22, p = 0.005). In conclusion, results of present meta-analysis showed modest association between MTHFR C677T polymorphism with breast cancer in total studies. However, sub-group analysis results based on ethnicity showed strong significant association between TT genotype and breast cancer (TT vs. CC; OR°=°1.26; 95% CI: 1.06-1.51; p = 0.009) in Asian population but in Caucasian population such association was not observed (TT vs. CC; OR°=°1.08; 95% CI: 0.99-1.14; p = 0.05). PMID:26629412

  9. Methylenetetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility

    PubMed Central

    Kumar, Pradeep; Yadav, Upendra; Rai, Vandana

    2015-01-01

    There are several evidences supporting the role of 510 methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in breast cancer (BC). Case control association studies on breast cancer have been repeatedly performed over the last two decades, but results are inconsistent. We performed a meta-analysis to confirm the association between MTHFR C677T polymorphism and BC risk. The articles were retrieved by searching the PubMed, Google Scholar, and Springer Link databases. Crude odds ratios (OR) with 95% confidence intervals (CIs) was used to assess the strength of association between C677T polymorphism and BC. Publication bias was assessed by Egger's and Begg-Mazumdar tests. Meta-analysis was performed with Open Meta Analyst. Total 75 studies with 31,315 cases and 35, 608 controls were found suitable for the inclusion in the present meta-analysis. The results of meta-analysis suggested that there were moderate significant association between C677T polymorphism and BC risk using overall comparisons in five genetic models (T vs. C: OR=1.08, 95% CI=1.031.13, p=<0.001; TT+CT vs. CC: OR=1.06, 95% CI=1.021.09, p=<0.001; TT vs. CC: OR=1.17, 95% CI=1.061.28, p=0.001; CT vs. CC OR=1.05, 95% CI=1.011.08, p=0.005; TT vs. CT+CC: OR=1.12, 95% CI=1.031.22, p=0.005). In conclusion, results of present meta-analysis showed modest association between MTHFR C677T polymorphism with breast cancer in total studies. However, sub-group analysis results based on ethnicity showed strong significant association between TT genotype and breast cancer (TT vs. CC; OR=1.26; 95% CI: 1.061.51; p=0.009) in Asian population but in Caucasian population such association was not observed (TT vs. CC; OR=1.08; 95% CI: 0.991.14; p=0.05). PMID:26629412

  10. Impact of malaria on genetic polymorphism and genetic diseases in Africans and African Americans.

    PubMed Central

    Miller, L H

    1994-01-01

    The high mortality from malaria in sub-Sahara Africa selected multiple genes that give the population a selective advantage. Identification of the genetic basis for resistance may suggest unusual approaches to development of malarial vaccines and antimalarial drugs. Some of these genes may be deleterious, although of selective advantage within the African setting, and need to be identified for counseling for disease prevention. PMID:8146132

  11. Genetic Contributions to Age-Related Decline in Executive Function: A 10-Year Longitudinal Study of COMT and BDNF Polymorphisms

    PubMed Central

    Erickson, Kirk I.; Kim, Jennifer S.; Suever, Barbara L.; Voss, Michelle W.; Francis, B. Magnus; Kramer, Arthur F.

    2008-01-01

    Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single nucleotide polymorphism in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age. PMID:18958211

  12. Genetic map of randomly amplified DNA polymorphisms closely linked to the mating type locus of tetrahymenta thermophila

    SciTech Connect

    Lynch, T.J.; Brickner, J.; Orias, E.; Nakano, K.J.

    1995-12-01

    We have used the PCR-based randomly amplified polymorphic DNA (RAPD) method to efficiently identify and map DNA polymorphisms in the ciliated protozoan Tetrahymena thermophila. The polymorphisms segregate as Mendelian genetic markers. A targeted screen, using DNA from pooled meiotic segregants, yielded the polymorphisms most closely linked to the mat locus. A total of 10 polymorphisms linked to the mat-Pmr segment of the left arm of micronuclear chromosome 2 have been identified. This constitutes the largest linkage group described in T. thermophila. We also provide here the first crude estimate of the frequency of meiotic recombination in the mat region, 20 kb/cM. This frequency is much higher than that observed in most other eukaryotes. Special features of Tetrahymena genetics enhanced the power of the RAPD method: the ability to obtain in a single step meiotic segregants that are whole-genome homozygotes and the availability of nullisomic strains permitting quick deletion mapping of polymorphisms to micronuclear chromosomes or chromosomes segments. The RAPD method appears to provide a practical and relatively inexpensive approach to the construction of a high-resolution map of the Tetrahymena genome. 39 refs., 5 figs., 4 tabs.

  13. A genetic polymorphism evolving in parallel in two cell compartments and in two clades

    PubMed Central

    2013-01-01

    Background The enzyme phosphoenolpyruvate carboxykinase, PEPCK, occurs in its guanosine-nucleotide-using form in animals and a few prokaryotes. We study its natural genetic variation in Colias (Lepidoptera, Pieridae). PEPCK offers a route, alternative to pyruvate kinase, for carbon skeletons to move between cytosolic glycolysis and mitochondrial Krebs cycle reactions. Results PEPCK is expressed in both cytosol and mitochondrion, but differently in diverse animal clades. In vertebrates and independently in Drosophila, compartment-specific paralogous genes occur. In a contrasting expression strategy, compartment-specific PEPCKs of Colias and of the silkmoth, Bombyx, differ only in their first, 5?, exons; these are alternatively spliced onto a common series of following exons. In two Colias species from distinct clades, PEPCK sequence is highly variable at nonsynonymous and synonymous sites, mainly in its common exons. Three major amino acid polymorphisms, Gly 335 ? Ser, Asp 503 ? Glu, and Ile 629 ? Val occur in both species, and in the first two cases are similar in frequency between species. Homology-based structural modelling shows that the variants can alter hydrogen bonding, salt bridging, or van der Waals interactions of amino acid side chains, locally or at one another?s sites which are distant in PEPCK?s structure, and thus may affect its enzyme function. We ask, using coalescent simulations, if these polymorphisms? cross-species similarities are compatible with neutral evolution by genetic drift, but find the probability of this null hypothesis is 0.001???P???0.006 under differing scenarios. Conclusion Our results make the null hypothesis of neutrality of these PEPCK polymorphisms quite unlikely, but support an alternative hypothesis that they are maintained by natural selection in parallel in the two species. This alternative can now be justifiably tested further via studies of PEPCK genotypes? effects on function, organismal performance, and fitness. This case emphasizes the importance, for evolutionary insight, of studying gene-specific mechanisms affected by natural genetic variation as an essential complement to surveys of such variation. PMID:23311980

  14. Analysis of multiple genetic polymorphisms in aggressive- and slow-growing abdominal aortic aneurysms

    PubMed Central

    Duellman, Tyler; Warren, Christopher L.; Matsumura, Jon; Yang, Jay

    2014-01-01

    Introduction The natural history of abdominal aortic aneurysm (AAA) suggests that some remain slow in growth rate while many develop a more accelerated growth rate reaching a threshold for intervention. We hypothesized that different mechanisms are responsible for AAA that remain slow-growth and never become actionable versus the aggressive-AAA that require intervention may be reflected by distinct associations with genetic polymorphisms. Methods 168 control and 141 AAA subjects all with ultrasound or CT imaging studies covering about 5 years were identified and the AAA growth rate determined from the serial imaging data. Genetic polymorphisms all previously reported as showing significant correlation with AAA: angiotensin 1 receptor (AT1R) (rs5186), interleukin-10 (IL-10) (rs1800896), methyl-tetrahydrofolate reductase (MTHFR) (rs1801133), low density lipoprotein receptor-related protein 1 (LRP1) (rs1466535), angiotensin converting enzyme (ACE) (rs1799752) and several MMP9 SNPs with functional effects on the expression or function were determined by analysis of the genomic DNA. Results AAA subjects were classified as slow-growth rate- (<3.25 mm /yr; n=81) vs. aggressive-AAA (growth rate >3.25 mm /yr, those presenting with a rupture, or those with maximal aortic diameter >5.5 cm (male) or >5.0 cm (female); n=60) and discriminating confounds between the groups identified by logistic regression. Analyses identified MMP9 p-2502 SNP (P=0.029, OR=0.54 (0.31-0.94)) as a significant confound discriminating between control- vs. slow-growth AAA, MMP-9 D165N (P=0.035) and LRP1 (P=0.034) between control vs. aggressive-AAA, and MTHFR (P=0.048, OR=2.99 (1.01-8.86)), MMP9 p-2502 (P=0.037, OR=2.19 (1.05-4.58), and LRP1 (P=0.046, OR= 4.96 (1.03-23.9)) as the statistically significant confounds distinguishing slow- vs. aggressive-AAA. Conclusion Logistic regression identified different genetic confounds for the slow-growth rate-and aggressive-AAA indicating a potential for different genetic influences on AAA of distinct aggressiveness. Future logistic regression studies investigating for potential genetic or clinical confounds for this disease should take into account the growth rate and size of AAA to better identify confounds likely to be associated with aggressive AAA likely to require intervention. PMID:24801553

  15. GENETIC DIVERSITY AND STRUCTURE OF AN ESTUARINE FISH (FUNDULUS HETEROCLITUS) INDIGENOUS TO A HIGHLY CONTAMINATED URBAN HARBOR

    EPA Science Inventory

    Intense directional selection on isolated populations can result in loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that toxic pollutants, specifically, polychlor...

  16. GENETIC DIVERSITY AND STRUCTURE OF AN ESTUARINE FISH (FUNDULUS HETEROCLITIS) INDIGENOUS TO SITES ASSOCIATED WITH A HIGHLY CONTAMINATED URBAN HARBOR

    EPA Science Inventory

    Intense directional selection on isolated populations can result in loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that toxic pollutants, specifically, polychlor...

  17. Association of endometriosis risk and genetic polymorphisms involving biosynthesis of sex steroids and their receptors: an updating meta-analysis.

    PubMed

    Hu, Xueying; Zhou, Yang; Feng, Qiming; Wang, Rensheng; Su, Li; Long, Jianxiong; Wei, Bo

    2012-09-01

    The objective of our study is to assess the association of endometriosis risk and genetic polymorphisms involving biosynthesis of sex steroids and their receptors. A systematic search of three databases was conducted. Twenty-seven studies on the association of the cytochrome P450 subfamily 17 (CYP17), estrogen receptor gene (ER), progesterone receptor gene (PR), 17-beta-hydroxysteroid dehydrogenase type 1 gene (HSD17B1), and cytochrome P450 subfamily 19 (CYP19) polymorphisms with endometriosis risk were identified. When all groups were pooled, we found an association between HSD17B1 (A variant allele vs. G wild allele: odds ratio (OR)=1.42, 95% confidence interval (CI)=1.10-1.84, P=0.007) and PR (P2 variant allele vs. P1 wild allele, OR=1.43, 95% CI=0.99-2.08, P=0.058) polymorphisms and endometriosis risk, while failing to detect links with CYP17, ER, and CYP19 polymorphisms examined. In the subgroup analysis, a significant association of CYP17 and ER?-PvuII polymorphisms with endometriosis was found neither in a Caucasian population nor in an Asian population. The findings of our study suggest that HSD17B1 and PR polymorphisms are associated with an increased risk of endometriosis. Further investigation into the association between CYP17, ER, PR, HSD17B1, and CYP19 polymorphisms and endometriosis risk is warranted and should include larger sample sizes. PMID:22613790

  18. Genetic diversity in populations of Slovak Spotted cattle based on single nucleotide polymorphisms analyses.

    PubMed

    Morav?kov, Nina; Trakovick, Anna; Navrtilov, Alica

    2013-01-01

    The aim of this study was to identify SNPs in leptin (LEP), leptin receptor (LEPR) and growth hormone (GH) genes in order to analyze genetic diversity of Slovak Spotted cattle. The total numbers of blood samples were taken from 353 Slovak Spotted cows originating from four farms. Genomic DNA was isolated by phenol-chloroform extraction method and analyzed by PCR-RFLP method. After digestion with restriction, enzymes were detected in whole population of cow's alleles with frequency: LEP/Sau3AI A 0.84 and B 0.16 (0.0152); LEPR/BseGI C 0.95 and T 0.05 (0.0089) and GH/AluI L 0.70 and V 0.30 (0.0188). Based on the observed vs. expected genotypes frequencies populations across loci were in Hardy-Weinberg equilibrium (P\\>0.05). Predominant for SNP LEP/Sau3AI was AA genotype (0.70), for SNP LEPR/T945M CC genotype (0.91), and LL genotype (0.48) was most frequent for SNP GH/AluI. The observed heterozygosity of SNPs across populations was also transferred to the low or median polymorphic information content 0.24 (He 0.28), 0.08 (He 0.09) and 0.33 (He 0.47) for LEP, LEPR and GH genes, respectively. Within genetic variability estimating negative values of fixation indexes FIS (-0.09-0.05) and FIT (-0.07-0.03) indicating heterozygote excess were observed. The value of FST indexes (0.018-0.023) shows very low levels of genetic differentiation in allele frequencies of loci among evaluated subpopulations. The low values of genetic distances (0.0018-0.0159) indicated high genetic relatedness among animals in subpopulations caused probably by common ancestry used in breeding program at farms. PMID:24432337

  19. Additive genetic risk from five serotonin system polymorphisms interacts with interpersonal stress to predict depression.

    PubMed

    Vrshek-Schallhorn, Suzanne; Stroud, Catherine B; Mineka, Susan; Zinbarg, Richard E; Adam, Emma K; Redei, Eva E; Hammen, Constance; Craske, Michelle G

    2015-11-01

    Behavioral genetic research supports polygenic models of depression in which many genetic variations each contribute a small amount of risk, and prevailing diathesis-stress models suggest gene-environment interactions (G×E). Multilocus profile scores of additive risk offer an approach that is consistent with polygenic models of depression risk. In a first demonstration of this approach in a G×E predicting depression, we created an additive multilocus profile score from 5 serotonin system polymorphisms (1 each in the genes HTR1A, HTR2A, HTR2C, and 2 in TPH2). Analyses focused on 2 forms of interpersonal stress as environmental risk factors. Using 5 years of longitudinal diagnostic and life stress interviews from 387 emerging young adults in the Youth Emotion Project, survival analyses show that this multilocus profile score interacts with major interpersonal stressful life events to predict major depressive episode onsets (hazard ratio [HR] = 1.815, p = .007). Simultaneously, there was a significant protective effect of the profile score without a recent event (HR = 0.83, p = .030). The G×E effect with interpersonal chronic stress was not significant (HR = 1.15, p = .165). Finally, effect sizes for genetic factors examined ignoring stress suggested such an approach could lead to overlooking or misinterpreting genetic effects. Both the G×E effect and the protective simple main effect were replicated in a sample of early adolescent girls (N = 105). We discuss potential benefits of the multilocus genetic profile score approach and caveats for future research. PMID:26595467

  20. Novel Genetic Polymorphisms That Further Delineate the Phylogeny of the Mycobacterium tuberculosis Complex

    PubMed Central

    Huard, Richard C.; Fabre, Michel; de Haas, Petra; Claudio Oliveira Lazzarini, Luiz; van Soolingen, Dick; Cousins, Debby; Ho, John L.

    2006-01-01

    In a previous report, we described a PCR protocol for the differentiation of the various species of the Mycobacterium tuberculosis complex (MTC) on the basis of genomic deletions (R. C. Huard, L. C. de Oliveira Lazzarini, W. R. Butler, D. van Soolingen, and J. L. Ho, J. Clin. Microbiol. 41:1637-1650, 2003). That report also provided a broad cross-comparison of several previously identified, phylogenetically relevant, long-sequence and single-nucleotide polymorphisms (LSPs and SNPs, respectively). In the present companion report, we expand upon the previous work (i) by continuing the evaluation of known MTC phylogenetic markers in a larger collection of tubercle bacilli (n = 125), (ii) by evaluating additional recently reported MTC species-specific and interspecific polymorphisms, and (iii) by describing the identification and distribution of a number of novel LSPs and SNPs. Notably, new genomic deletions were found in various Mycobacterium tuberculosis strains, new species-specific SNPs were identified for Mycobacterium canettii, Mycobacterium microti, and Mycobacterium pinnipedii, and, for the first time, intraspecific single-nucleotide DNA differences were discovered for the dassie bacillus, the oryx bacillus, and the two Mycobacterium africanum subtype I variants. Surprisingly, coincident polymorphisms linked one M. africanum subtype I genotype with the dassie bacillus and M. microti with M. pinnipedii, thereby suggesting closer evolutionary ties within each pair of species than had been previously thought. Overall, the presented data add to the genetic definitions of several MTC organisms as well as fine-tune current models for the evolutionary history of the MTC. PMID:16740934

  1. Novel genetic polymorphisms that further delineate the phylogeny of the Mycobacterium tuberculosis complex.

    PubMed

    Huard, Richard C; Fabre, Michel; de Haas, Petra; Lazzarini, Luiz Claudio Oliveira; van Soolingen, Dick; Cousins, Debby; Ho, John L

    2006-06-01

    In a previous report, we described a PCR protocol for the differentiation of the various species of the Mycobacterium tuberculosis complex (MTC) on the basis of genomic deletions (R. C. Huard, L. C. de Oliveira Lazzarini, W. R. Butler, D. van Soolingen, and J. L. Ho, J. Clin. Microbiol. 41:1637-1650, 2003). That report also provided a broad cross-comparison of several previously identified, phylogenetically relevant, long-sequence and single-nucleotide polymorphisms (LSPs and SNPs, respectively). In the present companion report, we expand upon the previous work (i) by continuing the evaluation of known MTC phylogenetic markers in a larger collection of tubercle bacilli (n = 125), (ii) by evaluating additional recently reported MTC species-specific and interspecific polymorphisms, and (iii) by describing the identification and distribution of a number of novel LSPs and SNPs. Notably, new genomic deletions were found in various Mycobacterium tuberculosis strains, new species-specific SNPs were identified for "Mycobacterium canettii," Mycobacterium microti, and Mycobacterium pinnipedii, and, for the first time, intraspecific single-nucleotide DNA differences were discovered for the dassie bacillus, the oryx bacillus, and the two Mycobacterium africanum subtype I variants. Surprisingly, coincident polymorphisms linked one M. africanum subtype I genotype with the dassie bacillus and M. microti with M. pinnipedii, thereby suggesting closer evolutionary ties within each pair of species than had been previously thought. Overall, the presented data add to the genetic definitions of several MTC organisms as well as fine-tune current models for the evolutionary history of the MTC. PMID:16740934

  2. Frequency of genetic polymorphisms of ADAM33 and their association with allergic rhinitis among Jordanians.

    PubMed

    Zihlif, Malek; Mahafza, Tareq; Obeidat, Nathir M; Froukh, Tawfiq; Shaban, Mazen; Al-Akhras, Fatima M; Zihlif, Nadwa; Naffa, Randa

    2013-12-01

    Allergic rhinitis is a chronic inflammatory disease that is assumed to be due to an interaction between different genetic and/or environmental factors. A disintegrin and metalloprotease domain 33 (ADAM33) has been extensively studied as a susceptibility gene in asthma and has been linked to bronchial hyper-responsiveness. In this study, we investigated the association between ADAM33 single nucleotide polymorphisms and the incidence of allergic rhinitis among the Jordanian population. We conducted a case-control association study on 120 adult individuals diagnosed with allergic rhinitis and 128 normal healthy controls. 8 single-nucleotide polymorphisms in ADAM33 were genotyped using PCR-RFLP method. No significant differences in the allelic frequencies of all SNPs tested between AR patients and the control volunteers were found, although S2 C/G SNP showed a tendency toward significance with P=0.06. On the genotype level significant association were found in the following genotypes: T1 AA, T1 AG, T2 GG, T2 AG, T+1 GG, T+1 AG, V4 CG, S2 CC, S2 CG, Q-1AA. Seven haplotypes were present only within AR patients and eight haplotypes were completely absent from the AR patients. Three haplotypes exhibited significant association with AR P ? 0.05, two of them were present only in AR patients. In conclusion, the polymorphisms in the ADAM33 gene are associated with susceptibility to AR in the Jordanian population. Furthermore, the haplotype of the tested SNPs were also associated with the risk of AR. PMID:24035932

  3. Study of the generated genetic polymorphisms during the photocatalytic elimination of Klebsiella pneumoniae in water.

    PubMed

    Venieri, Danae; Fraggedaki, Antonia; Binas, Vassilios; Zachopoulos, Apostolos; Kiriakidis, George; Mantzavinos, Dionissios

    2015-03-01

    Klebsiella pneumoniae is considered to be an emerging pathogen persisting under extreme environmentally stressed conditions. The aim of the present study is the investigation of inactivation rates of this pathogen in water by means of heterogeneous photocatalytic treatment under solar irradiation and the induced genetic variance applying RAPD-PCR as a molecular typing tool. Novel Mn- and Co-doped TiO2 catalysts were assessed in terms of their disinfection efficiency. The reference strain of K. pneumoniae proved to be readily inactivated, since disinfection occurred rapidly (i.e. after only 10 min of treatment) and low levels of bacterial regrowth were recorded in the dark and under natural sunlight. Binary doped titania exhibited the best photocatalytic activity, verifying the synergistic effect induced by composite dopants. Applying RAPD analysis to viable cells after treatment we concluded that increasing the treatment time led to considerable alteration of RAPD profiles and the homology coefficient ranged almost between 35 and 60%. RAPD-PCR proved to be a useful typing molecular tool that under standardized conditions exhibits highly reproducible results. Genetic variation among isolates increased in relation to the period of treatment and prolonged irradiation in each case affected the overall alteration in band patterns. RAPD patterns were highly diverse between treated and untreated isolates when disinfection was performed with the Co-doped titania. The broad spectrum of genetic variance and generated polymorphisms has the potential to increase the already significant virulence of the species. PMID:25248131

  4. Genetic map of the chicken Z chromosome using random amplified polymorphic DNA (RAPD) markers.

    PubMed

    Levin, I; Crittenden, L B; Dodgson, J B

    1993-04-01

    Commercially important traits of domestic animals have often been genetically linked to sex chromosomes, such as the Z chromosome of chickens. Using a backcross mapping population between two divergent, inbred lines and random-amplified polymorphic DNA (RAPD)-PCR markers, a genetic map of the chicken Z chromosome has been generated. Thirteen Z-linked RAPD markers were identified, mapped, and linked to two RFLPs and one phenotypic marker. The protocol used also generated RAPD markers for the W chromosome. The linkage distances obtained suggest that the RAPD markers are widely distributed throughout the Z chromosome and are likely to be linked to most or all traits of interest on this chromosome. The map provides a preliminary estimate of genetic to physical distance of about 0.5 Mb per centimorgan for the Z chromosome in chickens (male-specific recombination). A similar approach should be applicable to facilitate the mapping and analysis of sex-linked traits in other domestic animals. PMID:8486362

  5. Geographical patterns of genetic variation in two species of Stylosanthes Sw. using amplified fragment length polymorphism.

    PubMed

    Sawkins, M C; Maass, B L; Pengelly, B C; Newbury, H J; Ford-Lloyd, B V; Maxted, N; Smith, R

    2001-08-01

    Understanding the extent and distribution of genetic diversity within a species is essential for the development of effective conservation strategies. The objective of this study was to assess genetic variation using amplified fragment length polymorphisms (AFLP) in two species of the tropical legume genus Stylosanthes Sw. Annual, S. humilis (2n = 20) and perennial, S. viscosa (2n = 20) are found throughout tropical America, and are sympatric for much of their range of distribution. One hundred and eleven accessions, covering a wide geographical range, were selected for AFLP analysis. Binary data matrices derived from DNA banding patterns were analysed using the software programs NTSYS-PC and ARLEQUIN. Several accessions were found to be misidentified. Of the S. humilis accessions, the overall average similarity value was (0.72) slightly higher than the value obtained for S. viscosa (0.67). Cluster analysis and principal coordinate analysis grouped accessions from both species by geographical origin, with a few exceptions. Analysis of molecular variance (AMOVA) in S. humilis revealed 59.4% of the variation among groups formed from the cluster analysis. This was highly significant (P < 0.001). For S. viscosa AMOVA also revealed more variation among than within groups (66.5%). This was also highly significant (P < 0.001). The majority of accessions of both species conserved ex situ are of Brazilian and Venezuelan origin. This study has identified areas in Central America and Mexico for which novel genetic variation may be found and where conservation activities should be focused. PMID:11555239

  6. Genetic diversity and relationships in cultivars of Lolium multiflorum Lam. using sequence-related amplified polymorphism markers.

    PubMed

    Huang, L K; Jiang, X Y; Huang, Q T; Xiao, Y F; Chen, Z H; Zhang, X Q; Miao, J M; Yan, H D

    2014-01-01

    Sequence-related amplified polymorphism (SRAP) markers were used to analyze and estimate the genetic variability, level of diversity, and relationships among 20 cultivars and strains of annual ryegrass (Lolium multiflorum Lam.). Eighteen SRAP primer combinations generated 334 amplification bands, of which 298 were polymorphic. The polymorphism information content ranged from 0.4715 (me10 + em1) to 0.5000 (me5 + em7), with an average of 0.4921. The genetic similarity coefficient ranged from 0.4304 to 0.8529, and coefficients between 0.65 and 0.90 accounted for 90.00%. The cluster analysis separated the accessions into five groups partly according to their germplasm resource origins. PMID:25501225

  7. Molecular genetics of avian proteins. XIII. Protein polymorphism in three species of Australian passerines.

    PubMed

    Manwell, C; Baker, C M

    1975-12-01

    An introduced species, the house sparrow (Passer domesticus), and two Australian native species, the welcome swallow (Hirundo tahitica neoxena) and the fairy martin (Petrochelidon ariel), have moderately low levels of protein polymorphism compared with domesticated or semi-wild 'managed' species of birds. Genetically varient proteins in these birds include transferrin, esterase, phosphoglucomutase, NADP-dependent isocitrate dehydrogenases, phosphogluconate dehydrogenase (decarboxylating) and glucose-6-phosphate dehydrogenase. Egg-white protein polymorphism confirms heterogeneity of egg colour, markings and shape, and suggests that approximately 10% of the 'clutches' in house sparrow nests represent infidelity (intraspecific nest parasitism). For the four enzymes capable of supplying reduced NADP for reductive biosyntheses in growth and detoxification, the house sparrow has more heterozygosity (29%) than either the welcome swallow (9-4%) or the fairy martin (2-3%) and the difference is highly significant statistically. The results are discussed in relation to possible biochemical correlates of MacArthur and Wilson's (1967) evolutionary strategies or r or K selection. PMID:1225289

  8. DNA methyltransferase 3a rs1550117 genetic polymorphism predicts poor survival in gastric cancer patients

    PubMed Central

    Wang, Chuan; Jia, Zhifang; Ma, Hongxi; Cao, Donghui; Wu, Xing; Wen, Simin; You, Lili; Cao, Xueyuan; Jiang, Jing

    2015-01-01

    DNA methyltransferase 3a (DNMT3a) have been suggested to play a crucial role in human cancer prognosis. Single nucleotide polymorphisms (SNPs) in DNMT3a genes may have an impact on the prognosis of cancers. This study aimed to investigate the association between SNPs of DNMT3a gene and prognosis of gastric cancer (GC). Two sites of DNMT3a SNPs, rs1550117 and rs13420827 were selected and genotyped using TaqMan assay in 447 GC patients who received gastrectomy. Effects of genotypes on clinical outcomes of GC were calculated by Kaplan-Meier survival analysis and Cox regression model. We found that the AG or AA genotype of rs1550117 was associated with significantly poorer survival and increased death risk of GC compared with GG genotype (dominant model: HR=1.35, 95% CI=1.01-1.80, P=0.043). Further multivariate Cox regression analysis revealed that in addition to the known factors including male, larger tumor sizes and high clinical stage, rs1550117 variant was an independently predictive factor for survival in GC patients. No significant association was found between rs13420827 genetic variants and GC prognosis. Our findings first demonstrated that DNMT3a rs1550117 polymorphism may be a potential biomarker in predicting overall survival of GC patients. PMID:26823816

  9. Fas promoter polymorphisms: genetic predisposition to sarcoidosis in African-Americans

    PubMed Central

    Wasfi, Y. S.; Silveira, L. J.; Jonth, A.; Hokanson, J. E.; Fingerlin, T.; Sato, H.; Parsons, C. E.; Lympany, P.; Welsh, K.; du Bois, R. M.; Newman, L. S.; Maier, L. A.

    2011-01-01

    Apoptosis may perpetuate some forms of inflammation. Of the apoptotic pathway proteins, Fas is particularly overexpressed in sarcoidosis. We hypothesized that Fas promoter single nucleotide polymorphisms (SNPs) contribute to the development and severity of sarcoidosis. Associations of known Fas promoter SNPs (?670, ?690 and ?1377) and deduced haplotypes with sarcoidosis and sarcoidosis severity were evaluated using matched casecontrol (n = 656 pairs) and casecomparison (n = 656) studies, respectively, using conditional logistic regression. HardyWeinberg equilibrium was confirmed for all three polymorphisms in African-Americans (AA), and for the ?670 and ?1377 in whites. Genotype and allele frequencies were significantly different between whites and AA. Race-stratified analysis revealed that a common haplotype, ?1377G/?690T/?670G, was associated with sarcoidosis [odds ratio (OR) = 1.78, P = 0.05] only in AA. The haplotype ?1377G/?690C/?670A was negatively associated with sarcoidosis (OR = 0.39, P = 0.03) only in AA. In conclusion, the consistency of these findings suggests that Fas promoter genetic variants may be related to sarcoidosis disease risk in AA. PMID:18588573

  10. Selection of single nucleotide polymorphisms and genotype quality for genomic prediction of genetic merit in dairy cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A process to prepare high-density genotypic data for use in genomic prediction of genetic merit was developed. Marker genotypes from over 51,000 single nucleotide polymorphisms (SNP) were generated for 3,139 Holstein bulls on the Illumina Bovine SNP50™ chip. The SNP were categorized by minor allele ...

  11. A high-density simple sequence repeat and single nucleotide polymorphism genetic map of the tetraploid cotton genome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cotton genome complexity was investigated with a saturated molecular genetic map that combined several sets of microsatellites or simple sequence repeats (SSR) and the first major public set of single nucleotide polymorphism (SNP) markers in cotton genomes (Gossypium spp.), and that was constructed ...

  12. Analysis of Single Nucleotide Polymorphisms in Three Genes Shows Evidence for Genetic Isolation of Certain Aspergillus flavus Vegetative Compatibility Groups

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic exchange among populations of asexual filamentous fungi is presumed to be limited to isolates in the same vegetative compatibility group (VCG). To test this hypothesis, we compared the distribution of single nucleotide polymorphisms (SNP's) in Aspergills flavus isolates from six different V...

  13. ASSOCIATIONS OF THE PORCINE IMMUNE RESPONSE AND GENETIC POLYMORPHISMS WITH THE SHEDDING OF SALMONELLA ENTERICA SEROVAR TYPHIMURIUM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major focus of our collaborative research is to investigate the porcine response to infection with Salmonella to 1) identify porcine genes differentially regulated during infection and 2) identify and associate genetic polymorphisms within these genes with infection status across swine populations...

  14. A preliminary report on the genetic variation in pointed gourd (Trichosanthes dioica Roxb.) as assessed by random amplified polymorphic DNA.

    PubMed

    Adhikari, S; Biswas, A; Bandyopadhyay, T K; Ghosh, P D

    2014-06-01

    Pointed gourd (Trichosanthes dioica Roxb.) is an economically important cucurbit and is extensively propagated through vegetative means, viz vine and root cuttings. As the accessions are poorly characterized it is important at the beginning of a breeding programme to discriminate among available genotypes to establish the level of genetic diversity. The genetic diversity of 10 pointed gourd races, referred to as accessions was evaluated. DNA profiling was generated using 10 sequence independent RAPD markers. A total of 58 scorable loci were observed out of which 18 (31.03%) loci were considered polymorphic. Genetic diversity parameters [average and effective number of alleles, Shannon's index, percent polymorphism, Nei's gene diversity, polymorphic information content (PIC)] for RAPD along with UPGMA clustering based on Jaccard's coefficient were estimated. The UPGMA dendogram constructed based on RAPD analysis in 10 pointed gourd accessions were found to be grouped in a single cluster and may represent members of one heterotic group. RAPD analysis showed promise as an effective tool in estimating genetic polymorphism in different accessions of pointed gourd. PMID:24873909

  15. Estimating Genetic Relationships Among Semi-Dormant and Nondormant Alfalfa Cultivars with Sequence Related Amplified Polymorphisms (SRAPs)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of the present study was to assess the utility of molecular marker data generated by Sequence Related Amplified Polymorphisms (SRAPs) to assess genetic relationships among semi-dormant and non-dormant modern alfalfa cultivars using bulked DNAs. Marker data was also used to examine rel...

  16. Target region amplification polymorphism (TRAP) for assessing genetic diversity and marker-trait associations in chickpea (Cicer arietinum l.) germplasm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Utilization of crop diversity held in genebanks is dependent on knowledge of useful traits including those identified genotypically. Target region amplification polymorphism (TRAP) markers were used to evaluate the genetic diversity and relationship among a sample of 263 chickpea landrace germplasm ...

  17. A genetic variation map for chicken with 2.8 million single nucleotide polymorphisms

    PubMed Central

    2008-01-01

    Summary We describe a genetic variation map for the chicken genome containing 2.8 million single nucleotide polymorphisms (SNPs), based on a comparison of the sequences of 3 domestic chickens (broiler, layer, Silkie) to their wild ancestor Red Jungle Fowl (RJF). Subsequent experiments indicate that at least 90% are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about 5 SNP/kb for almost every possible comparison between RJF and domestic lines, between two different domestic lines, and within domestic lines - contrary to the idea that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated prior to domestication, and there is little to no evidence of selective sweeps for adaptive alleles on length scales of greater than 100 kb. PMID:15592405

  18. A genetic variation map for chicken with 2.8 million single nucleotide polymorphisms

    SciTech Connect

    Wong, G K; Hillier, L; Brandstrom, M; Croojmans, R; Ovcharenko, I; Gordon, L; Stubbs, L; Lucas, S; Glavina, T; Kaiser, P; Gunnarsson, U; Webber, C; Overton, I

    2005-02-20

    We describe a genetic variation map for the chicken genome containing 2.8 million single nucleotide polymorphisms (SNPs), based on a comparison of the sequences of 3 domestic chickens (broiler, layer, Silkie) to their wild ancestor Red Jungle Fowl (RJF). Subsequent experiments indicate that at least 90% are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about 5 SNP/kb for almost every possible comparison between RJF and domestic lines, between two different domestic lines, and within domestic lines--contrary to the idea that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated prior to domestication, and there is little to no evidence of selective sweeps for adaptive alleles on length scales of greater than 100 kb.

  19. Comparison of model-based tests and selection strategies to detect genetic polymorphisms influencing pharmacokinetic parameters.

    PubMed

    Bertrand, Julie; Comets, Emmanuelle; Mentre, France

    2008-01-01

    We evaluate by simulation three model-based methods to test the influence of a single nucleotide polymorphism on a pharmacokinetic parameter of a drug: analysis of variance (ANOVA) on the empirical Bayes estimates of the individual parameters, likelihood ratio test between models with and without genetic covariate, and Wald tests on the parameters of the model with covariate. Analyses are performed using the FO and FOCE method implemented in the NONMEM software. We compare several approaches for model selection based on tests and global criteria. We illustrate the results with pharmacokinetic data on indinavir from HIV-positive patients included in COPHAR 2-ANRS 111 to study the gene effect prospectively. Only the tests based on the EBE obtain an empirical type I error close to the expected 5%. The approximation made with the FO algorithm results in a significant inflation of the type I error of the LRT and Wald tests. PMID:18991109

  20. Genetic characterization and polymorphisms for parentage testing of the Jeju horse using 20 microsatellite loci.

    PubMed

    Choi, Sung-Kyoon; Cho, Chang-Yeon; Yeon, Sung-Heum; Cho, Byung-Wook; Cho, Gil-Jae

    2008-10-01

    Genetic characterization of the Jeju horse (JH) was performed to construct a correct pedigree of the JH family. A total of 111 horses including 79 JH were genotyped using 20 microsatellite loci. The number of alleles varied from 5 to 11 (mean 7.45) in the JH. The observed heterozygosity and expected heterozygosity ranged from 0.293 to 0.891 and from 0.357 to 0.841, respectively. The polymorphic information contents (PIC) ranged from 0.335 to 0.816. AHT4, ASB2, ASB17, ASB23, CA425, HMS2, HMS3, HTG10, LEX3 and VHL20 loci had relatively high PIC values (> 0.7). The total exclusion probability (PE) of the 20 microsatellite loci was 0.9999 in the JH. These results provide basic information for developing an accurate pedigree and will be useful in making decisions regarding conservation of the JH. PMID:18981670

  1. Genetic polymorphisms and the development of invasive bacterial infections in children.

    PubMed

    Esposito, Susanna; Bosis, Samantha; Orenti, Annalisa; Spena, Silvia; Montinaro, Valentina; Bianchini, Sonia; Zampiero, Alberto; Principi, Nicola

    2016-03-01

    To evaluate the associations between single nucleotide polymorphisms (SNPs) of factors involved in the development of invasive bacterial disease (IBD) in children, 47 SNPs of 18 candidate genes were analysed in 49 children with IBD and 100 controls. The G/T genotype of TLR2 rs2149356 and the C genotype of LTA rs2229094 were associated with significantly reduced risk of developing IBD (P = 0.04 and P = 0.05, respectively), whereas the C/T genotype of RFP175 rs1585110 was associated with a significantly higher risk of developing IBD (P = 0.02). These results support the evidence that some genetic variants of factors involved in innate immunity may influence IBD risk in children. PMID:26684632

  2. Genetic polymorphism of 17 Y-STR loci in Han Chinese living in Lanzhou.

    PubMed

    Sun, Hong-bing; Yang, Xin; Ha, Fei; Zhang, Zi-long

    2013-12-01

    The genetic polymorphism across 17 Y-STR loci in a population of Han Chinese in Lanzhou was investigated. Haplotypes and allele frequencies for the 17 Y-chromosomal STRs loci DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635, DYS392, Y GATA H4, DYS437, DYS438 and DYS448 were determined in 500 healthy unrelated autochthonous males from Lanzhou. The results showed that no shared haplotypes were observed. Gene diversity values ranged from 0.3987 (DYS391) to 0.9740 (DYS385a,b). It was concluded that these loci will be very useful for human identification in forensic cases and paternity tests within the Han Chinese population inhabiting Lanzhou. PMID:24337856

  3. Genetic polymorphisms in the immune response: A focus on kidney transplantation.

    PubMed

    Stojanova, Jana; Pouch, Lucie; Picard, Nicolas

    2016-03-01

    The modulation of the immune system following solid organ transplantation has made considerable progress with new immunosuppressive regimens and has considerably improved rejections rates. The improvement in long-term allograft survival is, however, modest. A complex network of cytokines, chemokines, adhesion, activation and co-stimulatory molecules are the frontline contributors to allograft rejection, which in turn determines the evolution of graft function and its long-term survival. Polymorphisms in these genes influence protein levels and presumably their signaling effects. In this review, we present a relevant panel of candidate genes related to the immune system in the context of solid organ transplantation; we discuss the most convincing reports of genetic associations with outcomes in renal transplantation and highlight the most promising loci among the vast body of literature. PMID:26171975

  4. Total homocysteine, B-vitamins and genetic polymorphisms in patients with classical phenylketonuria.

    PubMed

    Huemer, Martina; Fdinger, Manuela; Bodamer, Olaf A; Mhl, Adolf; Herle, Marion; Weigmann, Claudia; Ulmer, Hanno; Stckler-Ipsiroglu, Sylvia; Mslinger, Dorothea

    2008-05-01

    Hyperhomocysteinemia has occasionally been reported in patients with phenylketonuria (PKU) and B-vitamin deficiency. In our study total homocysteine (tHcy) and B-vitamins were measured in treated PKU patients and healthy controls. In the patients, dietary parameters and genetic polymorphisms affecting the Hcy pathway were investigated to identify parameters modulating tHcy. A case control study including 37 PKU patients and 63 healthy controls was conducted. t-Tests for independent samples were used to test between groups. Multiple regressions with tHcy as dependent variable were calculated. Hardy-Weinberg expectations were tested against the observed distribution of genotypes applying the Chi-square goodness-of-fit method. THcy concentrations were not significantly different (p=0.059) while folate and cobalamin (Cbl) concentrations were significantly higher in PKU patients compared to controls. However, 29.7% of patients had tHcy concentrations >97th centile. THcy did not vary with age nor correlate with folate and Cbl concentrations probably due to high saturatory levels. The presence of genetic polymorphisms had no impact on tHcy. In conclusion, in PKU patients treated with amino acid mixtures enriched with B-vitamins, tHcy is not significantly higher than in healthy controls, but tHcy concentrations exceed the 97th centile in about one third of patients. Even higher B-vitamin saturation may be required to further decrease tHcy concentrations and factors generally influencing tHcy such as betaine are to be investigated in PKU patients in the future. PMID:18249021

  5. Ancient Genetic Signatures of Orang Asli Revealed by Killer Immunoglobulin-Like Receptor Gene Polymorphisms

    PubMed Central

    NurWaliyuddin, Hanis Z. A.; Norazmi, Mohd N.; Edinur, Hisham A.; Chambers, Geoffrey K.; Panneerchelvam, Sundararajulu; Zafarina, Zainuddin

    2015-01-01

    The aboriginal populations of Peninsular Malaysia, also known as Orang Asli (OA), comprise three major groups; Semang, Senoi and Proto-Malays. Here, we analyzed for the first time KIR gene polymorphisms for 167 OA individuals, including those from four smallest OA subgroups (Che Wong, Orang Kanaq, Lanoh and Kensiu) using polymerase chain reaction-sequence specific primer (PCR-SSP) analyses. The observed distribution of KIR profiles of OA is heterogenous; Haplotype B is the most frequent in the Semang subgroups (especially Batek) while Haplotype A is the most common type in the Senoi. The Semang subgroups were clustered together with the Africans, Indians, Papuans and Australian Aborigines in a principal component analysis (PCA) plot and shared many common genotypes (AB6, BB71, BB73 and BB159) observed in these other populations. Given that these populations also display high frequencies of Haplotype B, it is interesting to speculate that Haplotype B may be generally more frequent in ancient populations. In contrast, the two Senoi subgroups, Che Wong and Semai are displaced toward Southeast Asian and African populations in the PCA scatter plot, respectively. Orang Kanaq, the smallest and the most endangered of all OA subgroups, has lost some degree of genetic variation, as shown by their relatively high frequency of the AB2 genotype (0.73) and a total absence of KIR2DL2 and KIR2DS2 genes. Orang Kanaq tradition that strictly prohibits intermarriage with outsiders seems to have posed a serious threat to their survival. This present survey is a demonstration of the value of KIR polymorphisms in elucidating genetic relationships among human populations. PMID:26565719

  6. Genetic polymorphism of metallothionein 2A and risk of laryngeal cancer in a Polish population.

    PubMed

    Starska, Katarzyna; Krze?lak, Anna; Forma, Ewa; Olszewski, Jurek; Lewy-Trenda, Iwona; Osuch-Wjcikiewicz, Ewa; Bry?, Magdalena

    2014-07-01

    Metallothioneins are intracellular regulators of many biological mechanisms including differentiation, proliferation, angiogenesis and invasion, which are crucial processes in carcinogenesis. This study examines the association between three single-nucleotide polymorphisms at loci -5 A/G (rs28366003) and -209 A/G (rs1610216) in the core promoter region and at locus +838 C/G (rs10636) in 3'UTR region of the metallothionein 2A (MT2A) gene with squamous cell laryngeal cancer (SCLC) risk, as well as with tumor invasiveness according to tumor front grading (TFG). Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism technique in 323 genetically unrelated individuals with SCLC and 418 randomly selected healthy volunteers. Only one SNP (rs28366003) was significantly related to laryngeal cancer in the study population. Compared with homozygous common allele carriers, heterozygous and homozygous for the G variant had significantly increased risk of SCLC [adjusted odds ratio (OR) = 2.90, 95 % confidence interval (CI) 1.53-5.21, p dominant < 0.001]. The A/G allele carriers at rs28366003 MT2A were at higher risk of SCLC development (OR = 2.63, 95 % CI 1.41-2.85, p < 0.001]. There was a significant association between the rs28366003 and stage and TFG classification. Most carriers of minor allele had a higher stage (OR = 2.76, 95 % CI 1.11-7.52, p = 0.03), increased cancer aggressiveness, as defined by a higher total TFG score (>18 points) (OR = 3.76, 95 % CI 1.15-12.56, p = 0.03) and diffuse tumor growth (OR = 5.86, 95 % Cl 0.72-44.79, p = 0.08). The results of this study raise a possibility that a genetic variation of MT2A may be implicated in the etiology of laryngeal cancer in a Polish population. PMID:24952512

  7. Association of genetic polymorphisms in the telomerase reverse transcriptase gene with prostate cancer aggressiveness.

    PubMed

    Wu, Dapeng; Yu, Hongjie; Sun, Jielin; Qi, Jun; Liu, Qiang; Li, Ruipeng; Zheng, Siqun Lily; Xu, Jianfeng; Kang, Jian

    2015-07-01

    Telomerase reverse transcriptase (TERT), encoded by the TERT gene, is an essential component of telomerase, essential for the maintenance of telomere DNA length, chromosomal stability and cellular immortality. The aim of the present study was to evaluate the association between common genetic variations across the TERT gene region and prostate cancer (PCa) aggressiveness in a Chinese population. A total of 12 TERT tagging single-nucleotide polymorphisms (SNPs) were genotyped on the Sequenom Mass-ARRAY iPLEX platform in a case-case study with 1,210 Chinese patients with PCa. Unconditional logistic regression was used to investigate the association of genotypes with PCa aggressiveness, Gleason grade and risk of developing early-onset PCa. It was observed that the C allele of the TERT intron 2 SNP (rs2736100) was significantly associated with reduced risk of PCa aggressiveness [odds ratio (OR)=0.81; 95% confidence interval (CI): 0.66-0.99; P=0.037]. This allele was also significantly correlated with a reduced risk of developing a tumor with a high Gleason score (>7; OR=0.83; 95% CI: 0.70-0.99; P=0.039). The T allele of the intron 4 SNP (rs10069690) was found to be significantly associated with a decreased risk for an aggressive form of PCa (OR=0.76; 95% CI: 0.59-0.97; P=0.030). In addition, the A allele of rs10078761 located at the 3' end of the TERT gene exhibited a statistically significant association with the reduced risk of developing a higher grade disease (OR=0.48; 95% CI: 0.28-0.81; P=0.006). However, no association between TERT polymorphisms and age at diagnosis was observed in the present study. The present findings demonstrated for the first time, to the best of our knowledge, that genetic variations across the TERT gene are associated with PCa aggressiveness in a Chinese Han population. PMID:25738283

  8. Genetic Variation in Natural Populations of Five Drosophila Species and the Hypothesis of the Selective Neutrality of Protein Polymorphisms

    PubMed Central

    Ayala, Francisco J.; Tracey, Martin L.; Barr, Lorraine G.; McDonald, John F.; Prez-Salas, Santiago

    1974-01-01

    We have studied genetic variation at 3032 loci coding for enzymes in natural populations of five species of Drosophila. The average proportion of heterozygous loci per individual is 17.7 0.4%. The average proportion of polymorphic loci per population is 69.2 2.6% or 49.8 2.2%, depending on what criterion of polymorphism is used. The following generalizations are advanced: (1) The amount of genetic polymorphism varies considerably from locus to locus. (2) At a given locus, populations of the same species are very similar in the amount and pattern of genetic variation. (3) However, at some loci large differences sometimes occur between local populations of the same species. (4) The amount of variation at a given locus is approximately the same in all five species. (5) When different species are compared, the pattern of the variation is either essentially identical or totally different at a majority of loci. We have tested the hypothesis that protein polymorphisms are selectively neutral by examining four predictions derived from the hypothesis. Our results are at variance with every one of the predictions. We have measured the amount of genetic differentiation, D, between taxa of various degrees of evolutionary divergence. The average value of D is 0.033 for local populations, 0.228 for subspecies, 0.226 for semispecies, 0.538 for sibling species, and 1.214 for morphologically distinguishable species. Our results indicate that a substantial degree of genetic differentiation (22.8 allelic substitutions for every 100 loci) occurs between allopatric populations that have diverged to the point where they might become different species if they were to become sympatric. However, very little additional genetic change is required for the development of complete reproductive isolation. After the speciation process is completed, species continue to diverge genetically from each other. PMID:4847156

  9. Identifying Litchi (Litchi chinensis Sonn.) Cultivars and Their Genetic Relationships Using Single Nucleotide Polymorphism (SNP) Markers.

    PubMed

    Liu, Wei; Xiao, Zhidan; Bao, Xiuli; Yang, Xiaoyan; Fang, Jing; Xiang, Xu

    2015-01-01

    Litchi is an important fruit tree in tropical and subtropical areas of the world. However, there is widespread confusion regarding litchi cultivar nomenclature and detailed information of genetic relationships among litchi germplasm is unclear. In the present study, the potential of single nucleotide polymorphism (SNP) for the identification of 96 representative litchi accessions and their genetic relationships in China was evaluated using 155 SNPs that were evenly spaced across litchi genome. Ninety SNPs with minor allele frequencies above 0.05 and a good genotyping success rate were used for further analysis. A relatively high level of genetic variation was observed among litchi accessions, as quantified by the expected heterozygosity (He = 0.305). The SNP based multilocus matching identified two synonymous groups, 'Heiye' and 'Wuye', and 'Chengtuo' and 'Baitangli 1'. A subset of 14 SNPs was sufficient to distinguish all the non-redundant litchi genotypes, and these SNPs were proven to be highly stable by repeated analyses of a selected group of cultivars. Unweighted pair-group method of arithmetic averages (UPGMA) cluster analysis divided the litchi accessions analyzed into four main groups, which corresponded to the traits of extremely early-maturing, early-maturing, middle-maturing, and late-maturing, indicating that the fruit maturation period should be considered as the primary criterion for litchi taxonomy. Two subpopulations were detected among litchi accessions by STRUCTURE analysis, and accessions with extremely early- and late-maturing traits showed membership coefficients above 0.99 for Cluster 1 and Cluster 2, respectively. Accessions with early- and middle-maturing traits were identified as admixture forms with varying levels of membership shared between the two clusters, indicating their hybrid origin during litchi domestication. The results of this study will benefit litchi germplasm conservation programs and facilitate maximum genetic gains in litchi breeding programs. PMID:26261993

  10. Identifying Litchi (Litchi chinensis Sonn.) Cultivars and Their Genetic Relationships Using Single Nucleotide Polymorphism (SNP) Markers

    PubMed Central

    Liu, Wei; Xiao, Zhidan; Bao, Xiuli; Yang, Xiaoyan; Fang, Jing; Xiang, Xu

    2015-01-01

    Litchi is an important fruit tree in tropical and subtropical areas of the world. However, there is widespread confusion regarding litchi cultivar nomenclature and detailed information of genetic relationships among litchi germplasm is unclear. In the present study, the potential of single nucleotide polymorphism (SNP) for the identification of 96 representative litchi accessions and their genetic relationships in China was evaluated using 155 SNPs that were evenly spaced across litchi genome. Ninety SNPs with minor allele frequencies above 0.05 and a good genotyping success rate were used for further analysis. A relatively high level of genetic variation was observed among litchi accessions, as quantified by the expected heterozygosity (He = 0.305). The SNP based multilocus matching identified two synonymous groups, ‘Heiye’ and ‘Wuye’, and ‘Chengtuo’ and ‘Baitangli 1’. A subset of 14 SNPs was sufficient to distinguish all the non-redundant litchi genotypes, and these SNPs were proven to be highly stable by repeated analyses of a selected group of cultivars. Unweighted pair-group method of arithmetic averages (UPGMA) cluster analysis divided the litchi accessions analyzed into four main groups, which corresponded to the traits of extremely early-maturing, early-maturing, middle-maturing, and late-maturing, indicating that the fruit maturation period should be considered as the primary criterion for litchi taxonomy. Two subpopulations were detected among litchi accessions by STRUCTURE analysis, and accessions with extremely early- and late-maturing traits showed membership coefficients above 0.99 for Cluster 1 and Cluster 2, respectively. Accessions with early- and middle-maturing traits were identified as admixture forms with varying levels of membership shared between the two clusters, indicating their hybrid origin during litchi domestication. The results of this study will benefit litchi germplasm conservation programs and facilitate maximum genetic gains in litchi breeding programs. PMID:26261993

  11. Haplotype structure strongly affects recombination in a maize genetic interval polymorphic for Helitron and retrotransposon insertions

    PubMed Central

    He, Limei; Dooner, Hugo K.

    2009-01-01

    We have asked here how the remarkable variation in maize haplotype structure affects recombination. We compared recombination across a genetic interval of 9S in 2 highly dissimilar heterozygotes that shared 1 parent. The genetic interval in the common haplotype is ≈100 kb long and contains 6 genes interspersed with gene-fragment-bearing Helitrons and retrotransposons that, together, comprise 70% of its length. In one heterozygote, most intergenic insertions are homozygous, although polymorphic, enabling us to determine whether any recombination junctions fall within them. In the other, most intergenic insertions are hemizygous and, thus, incapable of homologous recombination. Our analysis of the frequency and distribution of recombination in the interval revealed that: (i) Most junctions were circumscribed to the gene space, where they showed a highly nonuniform distribution. In both heterozygotes, more than half of the junctions fell in the stc1 gene, making it a clear recombination hotspot in the region. However, the genetic size of stc1 was 2-fold lower when flanked by a hemizygous 25-kb retrotransposon cluster. (ii) No junctions fell in the hypro1 gene in either heterozygote, making it a genic recombination coldspot. (iii) No recombination occurred within the gene fragments borne on Helitrons nor within retrotransposons, so neither insertion class contributes to the interval's genetic length. (iv) Unexpectedly, several junctions fell in an intergenic region not shared by all 3 haplotypes. (v) In general, the ability of a sequence to recombine correlated inversely with its methylation status. Our results show that haplotypic structural variability strongly affects the frequency and distribution of recombination events in maize. PMID:19416860

  12. The Genetic Polymorphisms and Colonization Process of Olive Fly Populations in Turkey

    PubMed Central

    Dogaç, Ersin; Kandemir, İrfan; Taskin, Vatan

    2013-01-01

    The olive fruit fly, Bactrocera oleae, is the most important pest of olives in olive growing regions worldwide, especially in the Mediterranean basin and North America. Despite the economic importance of the olive fly, the colonization route of this species is unclear. We used nuclear microsatellite markers and mitochondrial DNA to provide information about the population structure and invasion route of olive fly populations in Turkey, as representative of the Eastern Mediterranean region. Adult fly samples were collected from 38 sublocations covering all olive growing regions in Turkey. The simple sequence variability data revealed a significant genetic variability in olive fly populations and a certain degree of differentiation between Mediterranean and Aegean populations. Mediterranean populations harbor higher levels of microsatellite variation than Aegean populations, which points to the eastern part of the Mediterranean as the putative source of invasion. mtDNA results suggest olive flies from the western part of Turkey are closely related to Italo-Aegean flies of the Mediterranean basin and the olive fly populations have invaded the northern part of the Mediterranean basin through western Turkey. In addition, finding specific American haplotypes in high frequencies might indicate that Turkey is the possible source of American olive fly populations. In order to more precisely characterize the population structure and invasion routes of this organism, more DNA-based sequence analysis should be carried out worldwide. PMID:23457499

  13. The genetic polymorphisms and colonization process of olive fly populations in Turkey.

    PubMed

    Doga, Ersin; Kandemir, ?rfan; Taskin, Vatan

    2013-01-01

    The olive fruit fly, Bactrocera oleae, is the most important pest of olives in olive growing regions worldwide, especially in the Mediterranean basin and North America. Despite the economic importance of the olive fly, the colonization route of this species is unclear. We used nuclear microsatellite markers and mitochondrial DNA to provide information about the population structure and invasion route of olive fly populations in Turkey, as representative of the Eastern Mediterranean region. Adult fly samples were collected from 38 sublocations covering all olive growing regions in Turkey. The simple sequence variability data revealed a significant genetic variability in olive fly populations and a certain degree of differentiation between Mediterranean and Aegean populations. Mediterranean populations harbor higher levels of microsatellite variation than Aegean populations, which points to the eastern part of the Mediterranean as the putative source of invasion. mtDNA results suggest olive flies from the western part of Turkey are closely related to Italo-Aegean flies of the Mediterranean basin and the olive fly populations have invaded the northern part of the Mediterranean basin through western Turkey. In addition, finding specific American haplotypes in high frequencies might indicate that Turkey is the possible source of American olive fly populations. In order to more precisely characterize the population structure and invasion routes of this organism, more DNA-based sequence analysis should be carried out worldwide. PMID:23457499

  14. Effective utilization of genetic information for athletes and coaches: focus on ACTN3 R577X polymorphism

    PubMed Central

    Kikuchi, Naoki; Nakazato, Koichi

    2015-01-01

    Training variants (type, intensity, and duration of exercise) can be selected according to individual aims and fitness assessment. Recently, various methods of resistance and endurance training have been used for muscle hypertrophy and VO2max improvement. Although several genetic variants are associated with elite athletic performance and muscle phenotypes, genetic background has not been used as variant for physical training. ACTN3 R577X is a well-studied genetic polymorphism. It is the only genotype associated with elite athletic performance in multiple cohorts. This association is strongly supported by mechanistic data from an Actn3-knockout mouse model. In this review, possible guidelines are discussed for effective utilization of ACTN3 R577X polymorphism for physical training. PMID:26526670

  15. The influence of genetic drift on the formation and stability of polymorphisms arising from negative frequency-dependent selection.

    PubMed

    Zhao, Lei; Waxman, David

    2016-02-21

    We consider the simplest form of negative frequency-dependent selection in a biallelic haploid population, where the selection coefficient of a mutant allele is a linear function of the allele?s frequency, and changes from positive to negative as the frequency is increased. In an effectively infinite population this behaviour leads to a stable polymorphism. We present a theoretical investigation of what occurs in a finite population, where a long-lived polymorphism may be formed, but which fluctuates and ultimately disappears due to random genetic drift. We model the dynamics as a branching process and explicitly take into account differences between the census population size and the effective population size, which play different roles in the dynamics. We characterise the behaviour of the population in terms of three distinct timescales associated with: (i) early loss of mutant alleles, (ii) achievement of the long-lived polymorphism, (iii) disappearance of the polymorphism. Timescales (i) and (iii) depend on the effective population size and are, as a consequence, affected by random genetic drift, while timescale (ii) depends primarily on the census size and is relatively insensitive to genetic drift. Analysis and simulations of the branching process clarify the different influences of the census and effective population sizes. One substantial quantitative difference, between populations where the effective and census population sizes coincide and where they differ, lies in the number of mutant alleles in the long-lived polymorphism. This number is approximately proportional to the census size. Thus assuming the census size equals a much smaller effective population size predicts a much smaller number of mutants in the long-lived polymorphism. PMID:26656188

  16. Genetic polymorphism between and within Meloidogyne species detected with RAPD markers.

    PubMed

    Castagnone-Sereno, P; Vanlerberghe-Masutti, F; Leroy, F

    1994-12-01

    Genetic analyses were conducted on root-knot nematode populations belonging to the four major species of the genus Meloidogyne and originating from many countries throughout the world. Discrete genetic markers used in this study were random genomic DNA sequences amplified by the polymerase chain reaction (RAPD). Primers of 17-30 nucleotides with 30-55% G + C content were tested. Five of them generated a total of 74 scorable markers that provided reliable polymorphisms both between and within species. Using RAPD patterns alone or in combination, all the Meloidogyne species and populations studied could be unambiguously discriminated. Based on the presence or absence of bands, maximum-parsimony analysis of the data resulted in clustering of species and populations congruent with previous isoenzymatic and molecular data. The resulting tree confirmed the early divergence of M. hapla from the other species and also that M. arenaria is closer to M. javanica than it is to M. incognita. The boot-strap analysis significantly supported most of the specific branching observed in the topology but did not identify the three M. arenaria populations as a monophyletic group. PMID:7828838

  17. Genetic polymorphism of Hucul horse population based on 17 microsatellite loci.

    PubMed

    Fornal, Agnieszka; Radko, Anna; Piestrzy?ska-Kajtoch, Agata

    2013-01-01

    Short tandem repeat (STR) loci, i.e. microsatellites are a class of genetic markers commonly used for population studies and parentage control. This study determined the usefulness of microsatellite markers recommended by International Society for Animal Genetics (ISAG) for identification and pedigree analysis in horses based on the example of Polish Hucul horse population (Equus caballus). The set of seventeen microsatellites loci was tested (AHT4, AHT5, ASB2, HMS2, HMS3, HMS6, HMS7, HTG10, HTG4, HTG6, HTG7, VHL20, ASB17, ASB23, CA425, HMS1, LEX3) for 216 individuals. All samples were genotyped and mean number of alleles per locus was estimated (7.00). Means of observed (Ho) and expected (He) heterozygosity were calculated 0.7288 and 0.7027, respectively. The observed heterozygosity was similar to the results of research on Hucul horse population in another area of Carpathians Mountains. The average polymorphism information content (PIC) for analyses of seventeen microsatellite markers indicates the usefulness of this set of markers for Hucul horse parentage testing. PMID:24432328

  18. Impact of the BDNF Val66Met Polymorphism on Cognition: Implications for Behavioral Genetics

    PubMed Central

    Dincheva, Iva; Glatt, Charles E.; Lee, Francis S.

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factor family and is implicated as a modulator of neuronal survival and differentiation, synaptic plasticity, and higher order cognitive functions such as learning and memory. A common single-nucleotide polymorphism (SNP) has been identified in the human BDNF gene (BDNF Val66Met) that leads to decreased BDNF secretion and impairments in specific forms of learning in humans. To better understand the impact of this SNP on biological function, the authors generated a mouse model containing the BDNF Met allele, which they found to replicate the key phenotypes observed in humans and provided further insight into the functional impact of this SNP in vivo. They used a bottom-up approach to study the BDNF SNP, which provided external validation in biologically less complex, genetically uniform systems, which minimized the variability inherent in human studies. In this review, the authors discuss the impact of the BDNF SNP on learning and memory while providing arguments for the relevance of a vertically integrated approach to studying human genetic variants. PMID:22367929

  19. Genetic imaging of the association of oxytocin receptor gene (OXTR) polymorphisms with positive maternal parenting

    PubMed Central

    Michalska, Kalina J.; Decety, Jean; Liu, Chunyu; Chen, Qi; Martz, Meghan E.; Jacob, Suma; Hipwell, Alison E.; Lee, Steve S.; Chronis-Tuscano, Andrea; Waldman, Irwin D.; Lahey, Benjamin B.

    2013-01-01

    Background: Well-validated models of maternal behavior in small-brain mammals posit a central role of oxytocin in parenting, by reducing stress and enhancing the reward value of social interactions with offspring. In contrast, human studies are only beginning to gain insights into how oxytocin modulates maternal behavior and affiliation. Methods: To explore associations between oxytocin receptor genes and maternal parenting behavior in humans, we conducted a genetic imaging study of women selected to exhibit a wide range of observed parenting when their children were 4–6 years old. Results: In response to child stimuli during functional magnetic resonance imaging (fMRI), hemodynamic responses in brain regions that mediate affect, reward, and social behavior were significantly correlated with observed positive parenting. Furthermore, single nucleotide polymorphisms (SNPs) (rs53576 and rs1042778) in the gene encoding the oxytocin receptor were significantly associated with both positive parenting and hemodynamic responses to child stimuli in orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus. Conclusions: These findings contribute to the emerging literature on the role of oxytocin in human social behavior and support the feasibility of tracing biological pathways from genes to neural regions to positive maternal parenting behaviors in humans using genetic imaging methods. PMID:24550797

  20. Ecogenetics of mercury: from genetic polymorphisms and epigenetics to risk assessment and decision-making.

    PubMed

    Basu, Niladri; Goodrich, Jaclyn M; Head, Jessica

    2014-06-01

    The risk assessment of mercury (Hg), in both humans and wildlife, is made challenging by great variability in exposure and health effects. Although disease risk arises following complex interactions between genetic ("nature") and environmental ("nurture") factors, most Hg studies thus far have focused solely on environmental factors. In recent years, ecogenetic-based studies have emerged and have started to document genetic and epigenetic factors that may indeed influence the toxicokinetics or toxicodynamics of Hg. The present study reviews these studies and discusses their utility in terms of Hg risk assessment, management, and policy and offers perspectives on fruitful areas for future research. In brief, epidemiological studies on populations exposed to inorganic Hg (e.g., dentists and miners) or methylmercury (e.g., fish consumers) are showing that polymorphisms in a number of environmentally responsive genes can explain variations in Hg biomarker values and health outcomes. Studies on mammals (wildlife, humans, rodents) are showing Hg exposures to be related to epigenetic marks such as DNA methylation. Such findings are beginning to increase understanding of the mechanisms of action of Hg, and in doing so they may help identify candidate biomarkers and pinpoint susceptible groups or life stages. Furthermore, they may help refine uncertainty factors and thus lead to more accurate risk assessments and improved decision-making. PMID:24038486

  1. Genetic Polymorphisms Analysis of Pharmacogenomic VIP Variants in Miao Ethnic Group of Southwest China.

    PubMed

    Jin, Tianbo; Aikemu, Ainiwaer; Zhang, Mingxi; Geng, Tingting; Feng, Tian; Kang, Longli; Luo, Man Lin

    2015-01-01

    BACKGROUND Genetic polymorphisms have a potential clinical role in determining both inter-individual and inter-ethnic differences in drug efficacy, but we have not found any pharmacogenomics information regarding minorities, such as the Miao ethnic group. Our study aimed to screen numbers of the Miao ethnic group for genotype frequencies of VIP variants and to determine differences between the Miao and other human populations worldwide. MATERIAL AND METHODS In this study, we genotyped 66 Very Important Pharmacogene (VIP) variants selected from PharmGKB in 98 unrelated, healthy Miao individuals from the Guizhou province and compared our data with 12 other populations, including 11 populations from the HapMap data set and Xi'an Han Chinese. RESULTS Using the ?2 test, we found that the allele frequencies of the VDR rs1544410 and VKORC1 (rs9934438) variants in the Miao population are quite different from that in other ethnic groups. Furthermore, we found that genotype frequencies of rs1801133 (MTHFR) in the 13 selected populations are significantly different. Population structure and F-statistics (Fst) analysis show that the genetic background of the Miao is relatively close to that of Chinese in metropolitan Denver, CO, USA (CHD). CONCLUSIONS Our results help complete the information provided by the pharmacogenomics database of the Miao ethnic group and provide a theoretical basis for safer drug administration, which may be useful for diagnosing and treating diseases in this population. PMID:26632549

  2. Genetic Polymorphisms Analysis of Pharmacogenomic VIP Variants in Miao Ethnic Group of Southwest China

    PubMed Central

    Jin, Tianbo; Aikemu, Ainiwaer; Zhang, Mingxia; Geng, Tingting; Feng, Tian; Kang, Longli; Luo, Manlin

    2015-01-01

    Background Genetic polymorphisms have a potential clinical role in determining both inter-individual and inter-ethnic differences in drug efficacy, but we have not found any pharmacogenomics information regarding minorities, such as the Miao ethnic group. Our study aimed to screen numbers of the Miao ethnic group for genotype frequencies of VIP variants and to determine differences between the Miao and other human populations worldwide. Material/Methods In this study, we genotyped 66 Very Important Pharmacogene (VIP) variants selected from PharmGKB in 98 unrelated, healthy Miao individuals from the Guizhou province and compared our data with 12 other populations, including 11 populations from the HapMap data set and Xian Han Chinese. Results Using the ?2 test, we found that the allele frequencies of the VDR rs1544410 and VKORC1 (rs9934438) variants in the Miao population are quite different from that in other ethnic groups. Furthermore, we found that genotype frequencies of rs1801133 (MTHFR) in the 13 selected populations are significantly different. Population structure and F-statistics (Fst) analysis show that the genetic background of the Miao is relatively close to that of Chinese in metropolitan Denver, CO, USA (CHD). Conclusions Our results help complete the information provided by the pharmacogenomics database of the Miao ethnic group and provide a theoretical basis for safer drug administration, which may be useful for diagnosing and treating diseases in this population. PMID:26632549

  3. Genetic Load of Loss-of-Function Polymorphic Variants in Great Apes.

    PubMed

    de Valles-Ibáñez, Guillem; Hernandez-Rodriguez, Jessica; Prado-Martinez, Javier; Luisi, Pierre; Marquès-Bonet, Tomàs; Casals, Ferran

    2016-01-01

    Loss of function (LoF) genetic variants are predicted to disrupt gene function, and are therefore expected to substantially reduce individual's viability. Knowing the genetic burden of LoF variants in endangered species is of interest for a better understanding of the effects of declining population sizes on species viability. In this study, we have estimated the number of LoF polymorphic variants in six great ape populations, based on whole-genome sequencing data in 79 individuals. Our results show that although the number of functional variants per individual is conditioned by the effective population size, the number of variants with a drastic phenotypic effect is very similar across species. We hypothesize that for those variants with high selection coefficients, differences in effective population size are not important enough to affect the efficiency of natural selection to remove them. We also describe that mostly CpG LoF mutations are shared across species, and an accumulation of LoF variants at olfactory receptor genes in agreement with its pseudogenization in humans and other primate species. PMID:26912403

  4. Lack of genetic association of cholesteryl ester transfer protein polymorphisms with late onset Alzheimers disease.

    PubMed

    Zhu, Haiyan; Gopalraj, Rangaraj K; Kelly, Jeremiah F; Bennett, David A; Estus, Steven

    Dysregulation of cholesterol homeostasis may be associated with the pathogenesis of coronary artery disease (CAD) and Alzheimers disease (AD). Recently, several single nucleotide polymorphisms (SNPs) in cholesteryl ester transfer protein (CETP) were associated with altered plasma CETP concentrations, cholesterol concentrations and CAD. Hence, these CETP SNPs represent excellent candidates for evaluating association with AD. To date, one study has evaluated the association between a single CETP SNP and AD. In this study, we examined three CETP SNPs to evaluate the genetic association of CETP with late onset AD on two study cohorts: the Religious Orders Study (ROS) series, including 85 AD and 70 non-AD individuals, and the University of Kentucky (UKY) series, including 78 AD and 84 non-AD individuals. Significant association between CETP genotypes or haplotypes and late onset AD was not detected in these two study cohorts. Moreover, the CETP genotypes and haplotypes were not significantly associated with AD when the populations were stratified for the presence or absence of apolipoprotein E4 (apoE4). In summary, CETP genetic variants were not associated with AD in two series. PMID:15882786

  5. [Molecular genetic differentiation of ethnic populations in Southern and Eastern Siberia based on mitochondrial DNA polymorphism].

    PubMed

    Derenko, M V; Maliarchuk, B A; Denisova, G A; Dambueva, I K; Kakpakov, V T; Dorzhu, Ch M; Luzina, F A; Lotosh, E A; Ondar, U N; Kaplina, M I; Zakharov, I A

    2002-10-01

    Using the data on mitochondrial DNA (mtDNA) polymorphism, genetic structures of the ethnic groups inhabiting South and East Siberia, including Altaians, Buryats, Tuvinians, Todjins, Tofalars, Yakuts, and Evenks were described. Mitochondrial gene pools of the populations examined were characterized by different ratios between Mongoloid (M*, C, D, E/G, G, A, B, and F) and Caucasoid (H, HV, I, J, K, T, U, and X) mtDNA lineages. All the populations studied carried a marked Mongoloid component, maximum frequency of which was observed in Evenks (92.4%) and Buryats (90.1%). Maximum frequencies of Caucasoid mtDNA lineages were detected in Tofalars (20.7%) and Yakuts (14.5%). Statistically significant interpopulation differences regarding the frequencies of mtDNA haplogroups were observed between all populations examined, excluding the pairs of Evenks-Yakuts, Evenks-Tuvinians, and Tuvinians-Todjins. Differentiation of the ethnic groups inhabiting South and East Siberia, as well as Central and Middle Asia, is discussed based on genetic, linguistic, and anthropological data. PMID:12449652

  6. Genetic Diversity of Thottapalayam Virus, a Hantavirus Harbored by the Asian House Shrew (Suncus murinus) in Nepal

    PubMed Central

    Kang, Hae Ji; Kosoy, Michael Y.; Shrestha, Sanjaya K.; Shrestha, Mrigendra P.; Pavlin, Julie A.; Gibbons, Robert V.; Yanagihara, Richard

    2011-01-01

    Despite the recent discovery of genetically divergent hantaviruses in shrews of multiple species in widely separated geographic regions, data are unavailable about the genetic diversity and phylogeography of Thottapalayam virus (TPMV), a hantavirus originally isolated from an Asian house shrew (Suncus murinus) captured in southern India more than four decades ago. To bridge this knowledge gap, the S, M, and L segments of hantavirus RNA were amplified by reverse transcription polymerase chain reaction from archival lung tissues of Asian house shrews captured in Nepal from January to September 1996. Pair-wise alignment and comparison revealed approximately 80% nucleotide and > 94% amino acid sequence similarity to prototype TPMV. Phylogenetic analyses, generated by maximum likelihood and Bayesian methods, showed geographic-specific clustering of TPMV, similar to that observed for rodent- and soricid-borne hantaviruses. These findings confirm that the Asian house shrew is the natural reservoir of TPMV and suggest a long-standing virushost relationship. PMID:21896819

  7. Study of population genetic polymorphism and gene flow rate in Indian snow trout, Schizothorax richardsonii fish of Himalaya, India.

    PubMed

    Sivaraman, G K; Barat, A; Ali, S; Mahanta, P C

    2014-11-01

    The genetic polymorphism and gene flow rate among the Indian snow trout fish population S. richadsonii from three different locations viz., Chirapani stream of Champawat district, Kosi and Gola river of Nainital district, Uttarakhand State, India were assessed by employing twenty numbers of Randomly Amplified Polymorphic DNA (RAPD) markers. The overall percent polymorphisms among these three populations were 14.76 with 6.56, 4.92 and 3.28 in Chirapani, Kosi and Gola river population, respectively. Chirapani population had higher proportion of polymorphic loci as compared to the Kosi and Gola. The higher value of genetic distance (0.1565) was obtained between Chirapani and Gola population and the lower value of genetic distance was observed between Chirapani and Kosi (0.1058) river population. The cluster analysis revealed that in the formation of two clusters, one consisted of Chirapani and Kosi and the other was Gola fish population. Gst estimates among these populations showed some extent of homogeneity with lower genetic differentiation rate between populations and further suggested that higher tolerance to mutation, as expected that RAPD bands, arose from both coding and non-coding DNA regions. The findings revealed that the rate of gene flow in three populations seemed very low i.e. highly conserved its genetic diversity in their natural waterbodies and indicative of little migration among populations (geographically isolated and not the possibilities man made interventions/introduction of similar kind of fish species). It is further concluded that the Chirapani, Kosi and Gola river populations of S. richardsonii were being conserved naturally in their habitat and the species actual genetic potential were being maintained (adaptation to local climatic conditions, reproduction, production traits and disease resistance trait etc) in their natural habitat. PMID:25522514

  8. Polymorphic microsatellite loci from two enriched genomic libraries for the genetic analysis of the miiuy croaker, Miichthys miiuy (Sciaenidae).

    PubMed

    Wang, R X; Xu, T J; Sun, Y N; He, G Y

    2010-01-01

    Twelve polymorphic microsatellites from the (AG)(13) and (CA)(13) enriched genomic libraries of Miichthys miiuy were isolated and characterized in a test population; the number of alleles ranged from two to nine. The observed and expected heterozygosities ranged from 0.1923 to 1.0000 and from 0.2633 to 0.8337, respectively. Three loci deviated from Hardy-Weinberg equilibrium, and linkage disequilibrium between five pairs of loci was significant. These polymorphic microsatellite loci can be used for genetic diversity analysis and molecular-assisted breeding of M. miiuy. PMID:20486088

  9. Genetic Analysis of IL-17 Gene Polymorphisms in Gout in a Male Chinese Han Population

    PubMed Central

    Li, Hua; Guo, Mingzhen; Liu, Shiguo; Li, Changgui

    2016-01-01

    Interleukin (IL)-17 is a proinflammatory cytokine mainly secreted by activated T helper 17 cells and involved in inflammatory immune responses. This study aimed to investigate the association between IL-17 variants as well as serum IL-17 levels with gout in male Chinese Han individuals. A total of 1,101 male gout patients and 1,239 ethic-matched controls were enrolled. Genetic distributions of three variants (rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA) were detected by real-time polymerase chain reaction using the Taqman probe method. The plasma concentrations of IL-17A and IL-17F were measured in 228 gout patients and 198 controls that came from above samples by an enzyme-linked immunosorbent assay. No significant differences were observed in the genetic distribution of these polymorphisms between cases and controls (rs2275913: χ2 = 0.15, p = 0.928 by genotype, χ2 = 0.14, p = 0.711 by allele; rs763780: χ2 = 2.24, p = 0.326 by genotype, χ2 = 0.26, p = 0.609 by allele; rs4819554: χ2 = 1.79, p = 0.409 by genotype, χ2 = 1.46, p = 0.227 by allele). Levels of serum IL-17A and IL-17F were significantly decreased in gout patients (both p<0.001). However, no difference was observed in acute gout patients between different genotypic carriers of rs2275913 and rs763780 regarding serum IL-17A and IL-17F levels (p>0.05). Although the genetic variants in IL-17 we studied in this research do not appear to be involved in the development of gout in male Chinese Han individuals, the IL-17 cytokine family may participate in gouty inflammation in an undefined way, which requires further validation. PMID:26890073

  10. Genetic polymorphisms of Echinococcus granulosus sensu stricto in the Middle East.

    PubMed

    Yanagida, Tetsuya; Mohammadzadeh, Tahereh; Kamhawi, Shaden; Nakao, Minoru; Sadjjadi, Seyed Mahmoud; Hijjawi, Nawal; Abdel-Hafez, Sami K; Sako, Yasuhito; Okamoto, Munehiro; Ito, Akira

    2012-12-01

    Echinococcus granulosus sensu stricto is a cosmopolitan parasite causing cystic echinococcosis in humans and livestock. Recent molecular phylogeographic studies suggested the rapid dispersal of the parasite by the anthropogenic movement of domestic animal hosts. In the present study, genetic polymorphism of E. granulosus s. s. in the Middle East, where the domestication started, was investigated to validate the dispersal history of the parasite. Thirty-five and 26 hydatid cysts were collected from Iran and Jordan, respectively, and mitochondrial cytochrome c oxidase subunit I (cox1) gene was sequenced. Chinese and Peruvian specimens were also analyzed for comparison. Haplotype network analysis demonstrated the existence of a common haplotype EG01 in all populations. Although EG01 and its one-step neighbors were the majority in all regions, most of the neighboring haplotypes were unique in each locality. Haplotype diversity was high but nucleotide diversity was low in Iran, Jordan and China. Both diversities were lowest and only a few haplotypes were found in Peru. Neutrality indices were significantly negative in Iran, Jordan and China, and positive but not significant in Peru. Pairwise fixation index was significant for all pairwise comparisons, indicating genetic differentiation among populations. These results suggest a evolutionary history of E. granulosus s. s. in which a genetic subgroup including EG01 was selected at the dawn of domestication, and then it was rapidly dispersed worldwide through the diffusion of stock raising. To approach the origin of the ancestral strain, extensive sampling is needed in many endemic regions. To evaluate the hypothetical evolutionary scenario, further study is needed to analyze specimens from diverse host species in wider regions. PMID:22668837

  11. French invasive Asian tiger mosquito populations harbor reduced bacterial microbiota and genetic diversity compared to Vietnamese autochthonous relatives

    PubMed Central

    Minard, G.; Tran, F. H.; Van, Van Tran; Goubert, C.; Bellet, C.; Lambert, G.; Kim, Khanh Ly Huynh; Thuy, Trang Huynh Thi; Mavingui, P.; Valiente Moro, C.

    2015-01-01

    The Asian tiger mosquito Aedes albopictus is one of the most significant pathogen vectors of the twenty-first century. Originating from Asia, it has invaded a wide range of eco-climatic regions worldwide. The insect-associated microbiota is now recognized to play a significant role in host biology. While genetic diversity bottlenecks are known to result from biological invasions, the resulting shifts in host-associated microbiota diversity has not been thoroughly investigated. To address this subject, we compared four autochthonous Ae. albopictus populations in Vietnam, the native area of Ae. albopictus, and three populations recently introduced to Metropolitan France, with the aim of documenting whether these populations display differences in host genotype and bacterial microbiota. Population-level genetic diversity (microsatellite markers and COI haplotype) and bacterial diversity (16S rDNA metabarcoding) were compared between field-caught mosquitoes. Bacterial microbiota from the whole insect bodies were largely dominated by Wolbachia pipientis. Targeted analysis of the gut microbiota revealed a greater bacterial diversity in which a fraction was common between French and Vietnamese populations. The genus Dysgonomonas was the most prevalent and abundant across all studied populations. Overall genetic diversities of both hosts and bacterial microbiota were significantly reduced in recently established populations of France compared to the autochthonous populations of Vietnam. These results open up many important avenues of investigation in order to link the process of geographical invasion to shifts in commensal and symbiotic microbiome communities, as such shifts may have dramatic impacts on the biology and/or vector competence of invading hematophagous insects. PMID:26441903

  12. Clopidogrel response variability: impact of genetic polymorphism and platelet biomarkers for predicting adverse outcomes poststenting.

    PubMed

    Golukhova, Elena Z; Ryabinina, Mariya N; Bulaeva, Naida I; Grigorian, Marina V; Kubova, Maida Ch; Serebruany, Victor L

    2015-01-01

    The aim of this study was to triage platelet reactivity and adverse vascular outcomes after dual antiplatelet therapy due to percutaneous coronary intervention (PCI) dependent on CYP2C19*2 and CYP2C19*3 genotypes in patients with coronary artery disease. Fifty-five patients with coronary artery disease were studied serially pre-PCI and post-PCI. Platelet reactivity was assessed by conventional light transmission aggregometry, VerifyNow Analyzer, and thromboelastography with platelet mapping. Genetic testing was performed with allele-specific real-time polymerase chain reaction. Adverse events included vascular death, acute myocardial infarction, repeated PCI, definite stent thrombosis, and angina recurrence. The common genotype (GG) was found in 39 patients, heterozygous polymorphism CYP2C19 (GA) G681A allele was detected in 14 patients, and the rare homozygous polymorphism CYP2C19 (AA) G681A allele was exhibited in 2 patients. There were no CYP2C19*3 (Trp212Ter) carriers among index patients. The platelet reactivity was higher in patients with heterozygous and homozygous carriers compared with GG genotype. The largest differences were observed among GG, GA, and AA genotypes, which correlated with the average values of platelet aggregation (P = 0.02). There was a significant link between adverse events and high platelet reactivity assessed by light transmission aggregometry (P = 0.002). We found a trend between different genotype and VerifyNow readings (P = 0.057); moreover, their cumulative impact on adverse events was significant (P = 0.041). Platelet reactivity is higher in patients with heterozygous and homozygous carriers of CYP2C19*2 versus common genotype and may predict an increased risk of clopidogrel response variability and/or experiencing adverse cardiac events. PMID:25946232

  13. Prediction Formulas for Individual Opioid Analgesic Requirements Based on Genetic Polymorphism Analyses

    PubMed Central

    Yoshida, Kaori; Nishizawa, Daisuke; Ichinomiya, Takashi; Ichinohe, Tatsuya; Hayashida, Masakazu; Fukuda, Ken-ichi; Ikeda, Kazutaka

    2015-01-01

    Background The analgesic efficacy of opioids is well known to vary widely among individuals, and various factors related to individual differences in opioid sensitivity have been identified. However, a prediction model to calculate appropriate opioid analgesic requirements has not yet been established. The present study sought to construct prediction formulas for individual opioid analgesic requirements based on genetic polymorphisms and clinical data from patients who underwent cosmetic orthognathic surgery and validate the utility of the prediction formulas in patients who underwent major open abdominal surgery. Methods To construct the prediction formulas, we performed multiple linear regression analyses using data from subjects who underwent cosmetic orthognathic surgery. The dependent variable was 24-h postoperative or perioperative fentanyl use, and the independent variables were age, gender, height, weight, pain perception latencies (PPL), and genotype data of five single-nucleotide polymorphisms (SNPs). To examine the utility of the prediction formulas, we performed simple linear regression analyses using subjects who underwent major open abdominal surgery. Actual 24-h postoperative or perioperative analgesic use and the predicted values that were calculated using the multiple regression equations were incorporated as dependent and independent variables, respectively. Results Multiple linear regression analyses showed that the four SNPs, PPL, and weight were retained as independent predictors of 24-h postoperative fentanyl use (R2 = 0.145, P = 5.66 10-10) and the two SNPs and weight were retained as independent predictors of perioperative fentanyl use (R2 = 0.185, P = 1.99 10-15). Simple linear regression analyses showed that the predicted values were retained as an independent predictor of actual 24-h postoperative analgesic use (R2 = 0.033, P = 0.030) and perioperative analgesic use (R2 = 0.100, P = 1.09 10-4), respectively. Conclusions We constructed prediction formulas, and the possible utility of these prediction formulas was found in another type of surgery. PMID:25615449

  14. Regional Brain Shrinkage over Two Years: Individual Differences and Effects of Pro-Inflammatory Genetic Polymorphisms

    PubMed Central

    Persson, N.; Ghisletta, P.; Dahle, C.L.; Bender, A.R.; Yang, Y.; Yuan, P.; Daugherty, A.M.; Raz, N.

    2014-01-01

    We examined regional changes in brain volume in healthy adults (N = 167, age 19-79 years at baseline; N = 90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (HC), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the HC, CbH, In, OF, and the PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants mediated shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1βC-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFRC677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ε4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan. PMID:25264227

  15. Impact of Intercellular Adhesion Molecule-1 Genetic Polymorphisms on Coronary Artery Disease Susceptibility in Taiwanese Subjects.

    PubMed

    Chou, Chi-Hung; Ueng, Kwo-Chang; Liu, Yu-Fan; Wu, Chih-Hsien; Yang, Shun-Fa; Wang, Po-Hui

    2015-01-01

    The principal pathogenesis of coronary artery disease (CAD) is coronary artery atherosclerosis, a chronic inflammatory disease of the vessel walls of the coronary artery. Intercellular adhesion molecule-1 (ICAM-1) displays an important role in the development of the inflammation reaction and atherosclerosis. Few studies report the association of ICAM-1 genetic polymorphisms with CAD in Taiwanese subjects. Therefore, we conducted a study to associate the single nucleotide polymorphisms (SNPs) of ICAM-1, rs5491, rs5498, rs281432 and rs3093030 with CAD. Five hundred and twenty-five male and female subjects, who received elective coronary angiography in Taiwan Chung Shan Medical University Hospital, were recruited to determine four ICAM-1 SNPs by real time-polymerase chain reaction and genotyping. The relationships among ICAM-1 SNPs, haplotypes, demographic and characteristics and CAD were analyzed. This study showed that rs281432 (C8823G) was the only ICAM-1 SNP which affect the development of CAD. Multivariate analysis revealed that ICAM-1 SNP rs281432 CC/CG [p=0.016; odds ratio (OR): 2.56, 95% confidence interval (CI): 1.19-5.56], male gender (p=0.018; OR: 1.66, 95% CI: 1.09-2.51), aspirin use in the past 7 days (p=0.001; OR: 2.05, 95% CI: 1.33-3.14), hypertension (p<0.001; OR: 2.15, 95% CI: 1.42-3.25), serum cardiac troponin I elevation (p<0.001; OR: 2.14, 95% CI: 1.47-3.24) and severe angina in recent 24 hours (p=0.001; OR: 1.97, 95% CI: 1.31- 2.95) increase the risk of CAD. In conclusion, ICAM-1 SNP rs281432 is an independent factor to predict the development of CAD. ICAM-1 SNP rs281432 homozygotic mutant GG can reduce the susceptibility to the CAD in Taiwanese subjects. PMID:26078712

  16. Genetic polymorphisms in metabolic enzymes and susceptibility to anti-tuberculosis drug-induced hepatic injury.

    PubMed

    Feng, F M; Guo, M; Chen, Y; Li, S M; Zhang, P; Sun, S F; Zhang, G S

    2014-01-01

    We examined the relationships between N-transacetylase 2 (NAT2), cytochrome P450 (CYP) 2E1 enzyme, glutathione S-transferase M1, T1 (GSTM1/GSTT1) gene polymorphisms, and anti-tuberculosis drug-induced hepatic injury (ADIH). A one-to-one matched case-control study was carried out using clinical data. NAT2, CYP2E1, GSTM1, and GSTT1 polymorphisms were identified in 173 pairs of research subjects. Statistical analysis was performed to determine risk factors of ADIH. The results showed that low body mass index and alcohol consumption were risk factors of ADIH, with odds ratios of 6.852 and 3.203, respectively. The frequencies of NAT2 slow acetylator, CYP2E1 -1259G>C, -1019C>T wild-type, and the GSTM1 null genotype were higher in the case group than in the control group, with odds ratios of 2.260, 2.696, 4.714, and 2.440, respectively. GSTT1 was not found to be related to ADIH. Interactive analysis showed that NAT2 slow acetylator and the GSTM1 null genotype were mutually synergistic, while an antagonistic relationship was observed between the CYP2E1 wild-type genotype and the other 3 genetic types. The risks of hepatic injury were higher after anti-tuberculosis therapy in patients carrying the NAT2 slow acetylator, CYP2E1 -1259G>C, -1019C>T wild-type, and GSTM1 null genotype. PMID:25501156

  17. Genetic Polymorphisms in Inflammasome-Dependent Innate Immunity among Pediatric Patients with Severe Renal Parenchymal Infections

    PubMed Central

    Cheng, Chi-Hui; Lee, Yun-Shien; Chang, Chee-Jen; Lin, Jui-Che; Lin, Tzou-Yien

    2015-01-01

    Background Inflammasome innate immune response activation has been demonstrated in various inflammatory diseases and microbial infections. However, to our knowledge, no study has examined the inflammasome-dependent pathways in patients with urinary tract infection. Defective or variant genes associated with innate immunity are believed to alter the host’s susceptibility to microbial infection. This study investigated genetic polymorphisms in genes encoding inflammasomes and the subsequent released cytokines in pediatric patients with severe renal parenchymal infections. Methodology This study included patients diagnosed with acute pyelonephritis (APN) and acute lobar nephronia (ALN) who had no underlying disease or structural anomalies other than vesicoureteral reflux (VUR). Single nucleotide polymorphism (SNP) genotyping was performed in the genes associated with inflammasome formation and activation (NLRP3, CARD8) and subsequent IL–1β cytokine generation (IL–1β). Principal Findings A total of 40 SNPs were selected for initial genotyping. Analysis of samples from 48 patients each and 96 controls revealed that only nine SNPs (five SNPs in NLRP3; three SNPs in CARD8; one SNP in IL–1β) had heterozygosity rates >0.01. Hardy–Weinberg equilibrium was satisfied for the observed genotype frequencies of these SNPs. Analysis excluding patients with VUR, a well-known risk factor for severe UTIs, revealed a lower frequency of the CC genotype in NLRP3 (rs4612666) in patients with APN and ALN than in controls. Correction for multiple-SNP testing showed that the non-VUR subgroup of the APN+ALN combined patient groups remained significantly different from the control group (P < 0.0055). Conclusions This study is the first to suggest that the inflammasome-dependent innate immunity pathway is associated with the pathogenesis of pediatric severe renal parenchymal infections. Further investigation is warranted to clarify its pathogenic mechanism. PMID:26444566

  18. Plasmodium falciparum and Plasmodium vivax specific lactate dehydrogenase: genetic polymorphism study from Indian isolates.

    PubMed

    Keluskar, Priyadarshan; Singh, Vineeta; Gupta, Purva; Ingle, Sanjay

    2014-08-01

    Control and eradication of malaria is hindered by the acquisition of drug resistance by Plasmodium species. This has necessitated a persistent search for novel drugs and more efficient targets. Plasmodium species specific lactate dehydrogenase is one of the potential therapeutic and diagnostic targets, because of its indispensable role in endoerythrocytic stage of the parasite. A target molecule that is highly conserved in the parasite population can be more effectively used in diagnostics and therapeutics, hence, in the present study polymorphism in PfLDH (Plasmodiumfalciparum specific LDH) and PvLDH (Plasmodiumvivax specific LDH) genes was analyzed using PCR-single strand confirmation polymorphism (PCR-SSCP) and sequencing. Forty-six P. falciparum and thirty-five P. vivax samples were screened from different states of India. Our findings have revealed presence of a single PfLDH genotype and six PvLDH genotypes among the studied samples. Interestingly, along with synonymous substitutions, nonsynonymous substitutions were reported to be present for the first time in the PvLDH genotypes. Further, through amino acid sequence alignment and homology modeling studies we observed that the catalytic residues were conserved in all PvLDH genotypes and the nonsynonymous substitutions have not altered the enzyme structure significantly. Evolutionary genetics studies have confirmed that PfLDH and PvLDH loci are under strong purifying selection. Phylogenetic analysis of the pLDH gene sequences revealed that P. falciparum compared to P. vivax, has recent origin. The study therefore supports PfLDH and PvLDH as suitable therapeutic and diagnostic targets as well as phylogenetic markers to understand the genealogy of malaria species. PMID:24953504

  19. The cytochrome P450 2D6*10 genetic polymorphism alters postoperative analgesia

    PubMed Central

    Wei, Xiao-Bin; Xiao, Xi; Han, Zhou-Xin; Lin, Dan-Qin; Yu, Ping

    2015-01-01

    The present study was aimed to investigate the effects of the cytochrome P450 (CYP) 2D6*10 genetic polymorphism on postoperative patient-controlled morphine usage. A total of 114 patients were selected, and 102 patients completed the study. Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was used to determine the CYP2D6*10 genotype, and patients were categorized into three groups according to CYP2D6 genotype: heterozygous (m/w), wild-type homozygous (w/w), and mutant homozygous (m/m). Total morphine usage and visual analogue score (VAS) were determined 72 hours after the operation and compared across the three genotype groups. Statistical methods used to analyze results were the ?2 test, analysis of variance, and multiple linear regression analysis; P<0.05 was considered to be statistically significant. The cumulative use of morphine in the m/w group was significantly higher than that in the m/m group between T0.5 and T4h (P<0.05). There were no significant differences in the loading dose of morphine or VAS among the different genotypes within 72 hours of operation. Patients carrying the CYP2D6*10 m/w genotype required higher doses of morphine at T0.5~T4h compared to the m/m group, and therefore received a higher cumulative dose of morphine post-operation. This phenomenon may be due to a decreased ability to synthesize endogenous opioid peptide. PMID:25932231

  20. Regional brain shrinkage over two years: individual differences and effects of pro-inflammatory genetic polymorphisms.

    PubMed

    Persson, N; Ghisletta, P; Dahle, C L; Bender, A R; Yang, Y; Yuan, P; Daugherty, A M; Raz, N

    2014-12-01

    We examined regional changes in brain volume in healthy adults (N=167, age 19-79years at baseline; N=90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the Hc, CbH, In, OF, and PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants modified shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1? (IL-1? C-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFR C677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ?4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC, thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan. PMID:25264227

  1. VKORC1 and CD-14 genetic polymorphisms associate with susceptibility to cardiovascular and cerebrovascular diseases

    PubMed Central

    Du, Jian; Zhang, Zhiguo; Ge, Yuanyuan; Zhen, Juan; Leng, Jiyan; Wang, Jianmeng

    2015-01-01

    Objective: To investigate the associations of VKORC1 rs2359612 and rs9923231 and CD-14 rs2569190 with susceptibility to cardiovascular and cerebrovascular diseases (CCVD). Methods: A case-control study was conducted with 614 cases of CCVD patients selected at our hospital between January 2011 and June 2012 as case group and 590 healthy individuals participating physical examination during the same period as control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to detect genotypes of VKORC1 and CD-14 genetic polymorphisms. SHEsis software was used to conduct haplotype analysis and logistic regression analysis was used to identify risk factors for CCVD. Results: The genotype and allele frequencies of VKORC1 rs2359612 and rs9923231 and CD-14 rs2569190 between the case and control groups were statistically different (all P<0.05). Haplotype analysis showed that the frequencies of CAT and TAT haplotypes were significantly higher while the frequencies of TAC and TGC haplotypes were significantly lower in the case group than those in the control group (P = 0.013, 0.029, 0.019 and 0.042, respectively). Logistic regression analysis showed that age, systolic pressure, smoking history and VKORC1 rs2359612 maybe risk factors for CCVD; and body mass index (BMI), diastolic pressure and VKORC1 rs9923231 may be protective factors for CCVD (all P<0.05). Conclusion: VKORC1 rs2359612 and rs9923231, and CD-14 rs2569190 might associate with susceptibility to CCVD. CAT and TAT haplotypes may be risk factors while TAC and TGC haplotype may be protective factors for CCVD. PMID:26884960

  2. Genetic Associations with Diabetes: Meta-Analyses of 10 Candidate Polymorphisms

    PubMed Central

    Wang, Qinwen; Xu, Leiting; Bu, Shizhong; Huang, Yi; Zhang, Cheng; Ye, Huadan; Xu, Xuting; Liu, Qiong; Ye, Meng; Mai, Yifeng; Duan, Shiwei

    2013-01-01

    Aims The goal of our study is to investigate the combined contribution of 10 genetic variants to diabetes susceptibility. Methods Bibliographic databases were searched from 1970 to Dec 2012 for studies that reported on genetic association study of diabetes. After a comprehensive filtering procedure, 10 candidate gene variants with informative genotype information were collected for the current meta-anlayses. Using the REVMAN software, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the combined contribution of the selected genetic variants to diabetes. Results A total of 37 articles among 37,033 cases and 54,716 controls were involved in the present meta-analyses of 10 genetic variants. Three variants were found to be significantly associated with type 1 diabetes (T1D): NLRP1 rs12150220 (OR = 0.71, 95% CI = 0.55–0.92, P = 0.01), IL2RA rs11594656 (OR = 0.86, 95% CI = 0.82–0.91, P<0.00001), and CLEC16A rs725613 (OR = 0.71, 95% CI = 0.55–0.92, P = 0.01). APOA5 −1131T/C polymorphism was shown to be significantly associated with of type 2 diabetes (T2D, OR = 1.27, 95% CI = 1.03–1.57, P = 0.03). No association with diabetes was showed in the meta-analyses of other six genetic variants, including SLC2A10 rs2335491, ATF6 rs2070150, KLF11 rs35927125, CASQ1 rs2275703, GNB3 C825T, and IL12B 1188A/C. Conclusion Our results demonstrated that IL2RA rs11594656 and CLEC16A rs725613 are protective factors of T1D, while NLRP1 rs12150220 and APOA5 −1131T/C are risky factors of T1D and T2D, respectively. PMID:23922971

  3. Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle, Fujian Province

    PubMed Central

    Cai, Lin; Yu, Shun-Zhang; Zhang, Zuo-Feng

    2001-01-01

    AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristcs, diet intake, and alcohol and tobacco consumption of indivduals in our study were completed by a standardized questionnaire. PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 indivduals in gastric cancer group (6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significan difference between the two groups (two-tailed Fisher’s exact test, P = 0.066). Indivduals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR = 1.50) and C2/C2 (OR = 7.34) than indivduals in control group (χ² = 4.597, for trend P = 0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among indivduals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that indivduals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effct in the development of gastric cancer in Changle county, Fujian Province. PMID:11854903

  4. Dectin-1 Polymorphism: A Genetic Disease Specifier in Autism Spectrum Disorders?

    PubMed Central

    Bennabi, Meriem; Delorme, Richard; Oliveira, José; Fortier, Catherine; Lajnef, Mohamed; Boukouaci, Wahid; Feugeas, Jean-Paul; Marzais, François; Gaman, Alexandru; Charron, Dominique; Ghaleh, Bijan; Krishnamoorthy, Rajagopal; Leboyer, Marion; Tamouza, Ryad

    2015-01-01

    Introduction In autism spectrum disorders (ASD), complex gene-environment interactions contribute to disease onset and progress. Given that gastro-intestinal dysfunctions are common in ASD, we postulated involvement of microbial dysbiosis in ASD and investigated, under a case-control design, the influence of DNA polymorphisms in the CLEC7A gene that encodes a pivotal fungal sensor, Dectin-1. Material and methods DNAs from 478 ASD patients and 351 healthy controls (HC) were analyzed for the CLEC7A rs16910631G/A and rs2078178 A/G single nucleotide polymorphisms (SNPs). Differences in the distribution of allele, genotype and haplotype by Chi-square testing and nonparametric analysis by Kruskal-Wallis/Mann–Whitney tests, where appropriate, were performed. The free statistical package R.2.13 software was used for the statistical analysis. Results We found that the CLEC7A rs2078178 G allele and GG genotype were more prevalent in HC as compared to ASD but failed to reach statistical significance for the latter (pc = 0.01, 0.06 respectively). However, after phenotype-based stratification, the CLEC7A rs2078178 G allele and GG genotype were found to be significantly more frequent in the Asperger group as compared to other ASD subsets (pc = 0.02, 0.01), a finding reinforced by haplotype analysis (rs2078178/rs16910631 G-G/G-G) (pc = 0.002). Further, intellectual quotient (IQ)-based stratification of ASD patients revealed that IQ values increase linearly along the CLEC7A rs2078178 AA, AG and GG genotypes (p = 0.05) and in a recessive manner (GG vs. AA+AG p = 0.02), further confirmed by haplotype distribution (CLEC7A rs2078178-16910631; A-G/A-G, A-G/G-G and G-G/G-G, p = 0.02, G-G/G-G vs. others, p = 0.01). Conclusion Our data suggest that the genetic diversity of CLEC7A gene influences the ASD phenotype by behaving as a disease specifier and imply that the genetic control of innate immune response could determine the ASD phenotype. PMID:26352598

  5. Genetic polymorphisms in adipokine genes and the risk of obesity: a systematic review and meta-analysis.

    PubMed

    Yu, Zhangbin; Han, Shuping; Cao, Xingguo; Zhu, Chun; Wang, Xuejie; Guo, Xirong

    2012-02-01

    Polymorphisms in adipokine genes, such as leptin (LEP), leptin receptor (LEPR), resistin (RETN), adiponectin (ADIPOQ), interleukin-1? (IL-1?), IL-6 (IL-6), and tumor necrosis factor-? (TNF-?) may be involved in the development of obesity. We conducted a systematic review of published evidence on the association between different adipokine genes and the risk of obesity. Librarian-designed searches of PubMed and HuGeNet, review of reference lists from published reviews and content expert advice identified potentially eligible studies. The genotyping information and polymorphisms of different adipokine genes, numbers of genotyped cases and controls and frequencies of genotypes were extracted from 48 eligible studies included in this review. Twenty-one polymorphisms each associated with obesity in at least one study were identified. Polymorphisms in the adipokine genes, LEP, LEPR, and RETN were not associated with obesity susceptibility, whereas ADIPOQ G276T (T vs. G: odds ratio (OR), 1.59; 95% confidence interval (CI), 1.39-1.81), IL-1? C3953T (CC vs. CT+TT: OR, 1.61; 95% CI, 1.18-2.20), and TNF-? G308A (GG vs. GA+AA: OR, 1.19; 95% CI, 1.02-1.39) polymorphisms were associated with an increased risk of obesity. The IL-6 G174C polymorphism was also associated obesity when using allelic comparisons, the recessive genetic model and the dominant genetic model with OR (95% CI) of 1.95 (1.37-2.77), 1.44 (1.15-1.80), and 1.36 (1.16-1.59), respectively. No significant evidence of publication bias was present. However, these "null" results were underpowered due to a small pooled sample size, and analysis of additional case-control studies with larger sample sizes should provide further clarifications. PMID:21660081

  6. Interleukin-18 gene 105A/C genetic polymorphism is associated with the susceptibility of Kawasaki disease.

    PubMed

    Chen, Shih-Yin; Wan, Lei; Huang, Yu-Chuen; Sheu, Jim Jinn-Chyuan; Lan, Yu-Ching; Lai, Chih-Ho; Lin, Cheng-Wen; Chang, Jeng Sheng; Tsai, Yuhsin; Liu, Shih-Ping; Lin, Ying-Ju; Tsai, Fuu-Jen

    2009-01-01

    Interleukin-18 (IL-18)-656T/G, -607A/C, and -137C/G promoter polymorphisms had been reported associated with Kawasaki disease (KD). An IL-18 genetic A/C polymorphism at coding position 105 (rs549908) has been linked with asthma, rheumatoid, and systemic lupus erythematosus. We tested a hypothesis that the IL-18 105A/C genetic polymorphism confers KD susceptibility. Study participants were Taiwanese KD patients and a healthy control group. Our data indicated that the frequency of C allele was significantly higher in the patient group (13.9%) than in the control group (2.7%; P<0.0001, odds ratio [OR]=5.93; 95% confidence interval [CI]=2.57-13.73). Therefore, persons with the C allele may have higher risk of developing KD. In addition, compared with the haplotype frequencies between case and control groups, the KD patients with TACC haplotype appeared to be a significant "at-risk" haplotype compared with other haplotypes (OR: 4.62, 95% CI: 1.71-12.43; P=0.001). KD patient with the TAGA haplotype appeared to be a significant "protective" haplotype compared with other haplotypes (OR: 0.51, 95% CI:0.29-0.89; P=0.017). Our results suggest that 105A/C polymorphism and the haplotypes in IL-18 gene are associated with the risk of KD in Taiwanese population. PMID:19288449

  7. What the Genetic Background of Individuals with Asthma and Obesity Can Reveal: Is ?2-Adrenergic Receptor Gene Polymorphism Important?

    PubMed

    Danielewicz, Hanna

    2014-09-01

    The goal of this review was to evaluate the association of ?2-adrenergic receptor (ADRB2) gene polymorphisms with asthma and obesity. Asthma is the most common pediatric inflammatory disorder. The prevalence, severity, and hospitalization index for asthma have increased markedly in the last several decades. Interestingly, asthma is often diagnosed along with obesity. Genetic factors are essential for both conditions, and some of the candidate pleiotropic genes thought to be involved in the development of these diseases are ADRB2, vitamin D receptor (VDR), leptin (LEP), protein kinase C alpha (PRKCA), and tumor necrosis factor alpha (TNF?). The ADRB2 has been studied in multiple populations and more than 80 polymorphisms, mainly single-nucleotide polymorphisms, have been identified. For nonsynonymous Arg16Gly, Gln27Glu, and Thr164Ile, functional effects have been shown. In vivo, these polymorphisms have been evaluated to determine their association with both obesity and asthma, but the results are inconsistent and depend on the population studied or how the disease was defined. Currently, there are only few reports describing the genetic background for the comorbidity of asthma and obesity. PMID:25276484

  8. IL-17 and IL-22 genetic polymorphisms in HBV vaccine non- and low-responders among healthcare workers

    PubMed Central

    Borzooy, Zohreh; Streinu-Cercel, Adrian; Mirshafiey, Abbass; Khamseh, Azam; Mahmoudie, Masoud Karkhaneh; Navabi, Shadi Sadat; Nosrati, Marjan; Najafi, Zahra; Hosseini, Mostafa; Jazayeri, Seyed Mohammad

    2016-01-01

    Background Healthcare workers constitute a population at high risk for HBV infection. Efficient vaccination options are available; however, the individual response to HBV vaccination may vary widely between subjects, potentially due to cytokine profiles and genetic variations. In the present study, we investigated the relationship between IL-17 and IL-22 gene polymorphisms versus non- and low-responsiveness to HBV vaccination in healthcare workers. Methods We selected the following IL-17 and IL-22 polymorphisms: rs4711998 (A/G) from IL-17 and rs2227501 (A/T), rs2227503 (A/G), rs1026786 (A/G) from IL-22 sequences genes. These were determined by polymerase chain reaction restriction fragment length polymorphisms. Results The IL-17 rs4711998 GG genotype had a significantly lower frequency in non-responders compared to low-responders (p=0.025). However, we did not identify a relationship between IL-22 rs1026780, rs2227501 and rs2227503 genotypes and the anti-HBs response following HBV vaccination. Conclusion These data suggest that genetic variation in rs4711998 polymorphisms in the IL-17 cytokine may influence vaccine-induced immune responses to HBV vaccine in healthcare workers.

  9. A regimen combining the Wee1 inhibitor AZD1775 with HDAC inhibitors targets human acute myeloid leukemia cells harboring various genetic mutations.

    PubMed

    Zhou, L; Zhang, Y; Chen, S; Kmieciak, M; Leng, Y; Lin, H; Rizzo, K A; Dumur, C I; Ferreira-Gonzalez, A; Dai, Y; Grant, S

    2015-04-01

    AZD1775 targets the cell cycle checkpoint kinase Wee1 and potentiates genotoxic agent cytotoxicity through p53-dependent or -independent mechanisms. Here, we report that AZD1775 interacted synergistically with histone deacetylase inhibitors (HDACIs, for example, Vorinostat), which interrupt the DNA damage response, to kill p53-wild type (wt) or -deficient as well as FLT3-ITD leukemia cells in association with pronounced Wee1 inhibition and diminished cdc2/Cdk1 Y15 phosphorylation. Similarly, Wee1 shRNA knockdown significantly sensitized cells to HDACIs. Although AZD1775 induced Chk1 activation, reflected by markedly increased Chk1 S296/S317/S345 phosphorylation leading to inhibitory T14 phosphorylation of cdc2/Cdk1, these compensatory responses were sharply abrogated by HDACIs. This was accompanied by premature mitotic entry, multiple mitotic abnormalities and accumulation of early S-phase cells displaying increased newly replicated DNA, culminating in robust DNA damage and apoptosis. The regimen was active against patient-derived acute myelogenous leukemia (AML) cells harboring either wt or mutant p53 and various next-generation sequencing-defined mutations. Primitive CD34(+)/CD123(+)/CD38(-) populations enriched for leukemia-initiating progenitors, but not normal CD34(+) hematopoietic cells, were highly susceptible to this regimen. Finally, combining AZD1775 with Vorinostat in AML murine xenografts significantly reduced tumor burden and prolonged animal survival. A strategy combining Wee1 with HDACI inhibition warrants further investigation in AML with poor prognostic genetic aberrations. PMID:25283841

  10. A regimen combining the Wee1 inhibitor AZD1775 with HDAC inhibitors targets human acute myeloid leukemia cells harboring various genetic mutations

    PubMed Central

    Zhou, Liang; Zhang, Yu; Chen, Shuang; Kmieciak, Maciej; Leng, Yun; Lin, Hui; Rizzo, Kathryn A.; Dumur, Catherine I.; Ferreira-Gonzalez, Andrea; Dai, Yun; Grant, Steven

    2015-01-01

    AZD1775 targets the cell cycle checkpoint kinase Wee1 and potentiates genotoxic agent cytotoxicity through p53-dependent or -independent mechanisms. Here, we report that AZD1775 interacted synergistically with histone deacetylase inhibitors (HDACIs e.g., Vorinostat), which interrupt the DNA damage response (DDR), to kill p53-wild type or -deficient as well as FLT3-ITD leukemia cells in association with pronounced Wee1 inhibition and diminished cdc2/Cdk1 Y15 phosphorylation. Similarly, Wee1 shRNA knock-down significantly sensitized cells to HDACIs. While AZD1775 induced Chk1 activation, reflected by markedly increased Chk1 S296/S317/S345 phosphorylation leading to inhibitory T14 phosphorylation of cdc2/Cdk1, these compensatory responses were sharply abrogated by HDACIs. This was accompanied by premature mitotic entry, multiple mitotic abnormalities, and accumulation of early S-phase cells displaying increased newly replicated DNA, culminating in robust DNA damage and apoptosis. The regimen was active against patient-derived AML cells harboring either wild type or mutant p53, and various NGS-defined mutations. Primitive CD34+/CD123+/CD38? populations enriched for leukemia-initiating progenitors, but not normal CD34+ hematopoietic cells, were highly susceptible to this regimen. Finally, combining AZD1775 with Vorinostat in AML murine xenografts significantly reduced tumor burden and prolonged animal survival. A strategy combining Wee1 with HDACI inhibition warrants further investigation in AML with poor prognostic genetic aberrations. PMID:25283841

  11. Start codon targeted (SCoT) polymorphism reveals genetic diversity in wild and domesticated populations of ramie (Boehmeria nivea L. Gaudich.), a premium textile fiber producing species

    PubMed Central

    Satya, Pratik; Karan, Maya; Jana, Sourav; Mitra, Sabyasachi; Sharma, Amit; Karmakar, P.G.; Ray, D.P.

    2015-01-01

    Twenty-four start codon targeted (SCoT) markers were used to assess genetic diversity and population structure of indigenous, introduced and domesticated ramie (Boehmeria nivea L. Gaudich.). A total of 155 genotypes from five populations were investigated for SCoT polymorphism, which produced 136 amplicons with 87.5% polymorphism. Polymorphism information content and resolving power of the SCoT markers were 0.69 and 3.22, respectively. The Indian ramie populations exhibited high SCoT polymorphism (> 50%), high genetic differentiation (GST = 0.27) and moderate gene flow (Nm = 1.34). Analysis of molecular variance identified significant differences for genetic polymorphism among the populations explaining 13.1% of the total variation. The domesticated population exhibited higher genetic polymorphism and heterozygosity compared to natural populations. Cluster analysis supported population genetic analysis and suggested close association between introduced and domesticated genotypes. The present study shows effectiveness of employing SCoT markers in a cross pollinated heterozygous species like Boehmeria, and would be useful for further studies in population genetics, conservation genetics and cultivar improvement. PMID:25750860

  12. Start codon targeted (SCoT) polymorphism reveals genetic diversity in wild and domesticated populations of ramie (Boehmeria nivea L. Gaudich.), a premium textile fiber producing species.

    PubMed

    Satya, Pratik; Karan, Maya; Jana, Sourav; Mitra, Sabyasachi; Sharma, Amit; Karmakar, P G; Ray, D P

    2015-02-01

    Twenty-four start codon targeted (SCoT) markers were used to assess genetic diversity and population structure of indigenous, introduced and domesticated ramie (Boehmeria nivea L. Gaudich.). A total of 155 genotypes from five populations were investigated for SCoT polymorphism, which produced 136 amplicons with 87.5% polymorphism. Polymorphism information content and resolving power of the SCoT markers were 0.69 and 3.22, respectively. The Indian ramie populations exhibited high SCoT polymorphism (>50%), high genetic differentiation (GST=0.27) and moderate gene flow (Nm=1.34). Analysis of molecular variance identified significant differences for genetic polymorphism among the populations explaining 13.1% of the total variation. The domesticated population exhibited higher genetic polymorphism and heterozygosity compared to natural populations. Cluster analysis supported population genetic analysis and suggested close association between introduced and domesticated genotypes. The present study shows effectiveness of employing SCoT markers in a cross pollinated heterozygous species like Boehmeria, and would be useful for further studies in population genetics, conservation genetics and cultivar improvement. PMID:25750860

  13. Relationship of Genetic Polymorphisms of the Chemokine, CCL5, and Its Receptor, CCR5, with Coronary Artery Disease in Taiwan.

    PubMed

    Ting, Ke-Hsin; Ueng, Kwo-Chang; Chiang, Whei-Ling; Chou, Ying-Erh; Yang, Shun-Fa; Wang, Po-Hui

    2015-01-01

    The chemokine receptor CCR5 polymorphism, which confers resistance to HIV infection, has been associated with reduced risk of cardiovascular disease. However, the association of the chemokine, CCL5, and its receptor, CCR5, polymorphism and coronary artery disease (CAD) in the Taiwanese has not been studied. In this study, 483 subjects who received elective coronary angiography were recruited from Chung Shan Medical University Hospital. CCL5-403 and CCR5-59029 were determined by polymerase chain reaction-restriction fragment length polymorphism. We found that CCL5-403 with TT genotype frequencies was significantly associated with the risk of CAD group (odds ratio = 3.063 and p = 0.012). Moreover, the frequencies of CCR5-59029 with GG or GA genotype were higher than AA genotype in acute coronary syndrome individuals (odds ratio = 1.853, CI = 1.176-2.921, p = 0.008). In conclusion, we found that CCL5-403 polymorphism may increase genetic susceptibility of CAD. CCL5-403 or CCR5-59029 single nucleotide polymorphism may include genotype score and it may predict cardiovascular event. PMID:26688689

  14. Genetic Polymorphisms of Interleukin-1 Alpha and the Vitamin D Receptor in Mexican Mestizo Patients with Intervertebral Disc Degeneration

    PubMed Central

    Cervin Serrano, Salvador; González Villareal, Dalia; Aguilar-Medina, Maribel; Romero-Navarro, Jose Guillermo; Romero Quintana, Jose Geovanni; Arámbula Meraz, Eliakym; Osuna Ramírez, Ignacio; Picos-Cárdenas, Veronica; Granados, Julio; Estrada-García, Iris; Sánchez-Schmitz, Guzman; Ramos-Payán, Rosalío

    2014-01-01

    Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population. PMID:25506053

  15. Genetic polymorphisms of CASR and cancer risk: evidence from meta-analysis and HuGE review

    PubMed Central

    Jeong, Sohyun; Kim, Jae Hyun; Kim, Myeong Gyu; Han, Nayoung; Kim, In-Wha; Kim, Therasa; Oh, Jung Mi

    2016-01-01

    Background CASR gene appears to be involved in cancer biology and physiology. However, a number of studies investigating CASR polymorphisms and cancer risks have presented inconclusive results. Thus, a systematic review and a meta-analysis of the effect of CASR polymorphisms on several cancer risks were performed to suggest a statistical evidence for the association of CASR polymorphisms with cancer risks. Methods MEDLINE, EMBASE, Web of Science, Scopus, and the HuGE databases were searched. Nineteen articles of case–control and cohort studies were included for the final analysis. Results The colorectal cancer risk was reduced in proximal (odds ratio [OR] =0.679, P=0.001) and distal (OR =0.753, P=0.026) colon sites with GG genotype of CASR rs1042636 and increased in distal colon site (OR =1.418, P=0.039) with GG genotype of rs1801726 by additive genetic model. The rs17251221 demonstrated noticeable associations that carrying a homozygote variant increases breast and prostate cancer risk considerably. Conclusion The significant association of CASR polymorphisms with several cancer risks was observed in this review. In particular, the act of CASR polymorphisms as a tumor suppressor or an oncogene differs by cancer site and can be the research target for tumorigenesis. PMID:26929638

  16. Relationship of Genetic Polymorphisms of the Chemokine, CCL5, and Its Receptor, CCR5, with Coronary Artery Disease in Taiwan

    PubMed Central

    Ting, Ke-Hsin; Ueng, Kwo-Chang; Chiang, Whei-Ling; Chou, Ying-Erh; Yang, Shun-Fa; Wang, Po-Hui

    2015-01-01

    The chemokine receptor CCR5 polymorphism, which confers resistance to HIV infection, has been associated with reduced risk of cardiovascular disease. However, the association of the chemokine, CCL5, and its receptor, CCR5, polymorphism and coronary artery disease (CAD) in the Taiwanese has not been studied. In this study, 483 subjects who received elective coronary angiography were recruited from Chung Shan Medical University Hospital. CCL5-403 and CCR5-59029 were determined by polymerase chain reaction-restriction fragment length polymorphism. We found that CCL5-403 with TT genotype frequencies was significantly associated with the risk of CAD group (odds ratio = 3.063 and p = 0.012). Moreover, the frequencies of CCR5-59029 with GG or GA genotype were higher than AA genotype in acute coronary syndrome individuals (odds ratio = 1.853, CI = 1.1762.921, p = 0.008). In conclusion, we found that CCL5-403 polymorphism may increase genetic susceptibility of CAD. CCL5-403 or CCR5-59029 single nucleotide polymorphism may include genotype score and it may predict cardiovascular event. PMID:26688689

  17. SOCS3 Genetic Polymorphism Is Associated With Clinical Features and Prognosis of Hepatocellular Carcinoma Patients Receiving Hepatectomy

    PubMed Central

    Jiang, Bei-ge; Yang, Yuan; Liu, Hui; Gu, Fang-ming; Yang, Yun; Zhao, Lin-Hao; Yuan, Sheng-xian; Wang, Ruo-yu; Zhang, Jin; Zhou, Wei-ping

    2015-01-01

    Abstract Previous studies showed that suppressor of cytokine signaling 3 (SOCS3) protein is associated with incidence and progression of hepatocellular carcinoma (HCC); however, the association between the genetic polymorphism of SOCS3 gene and HCC remains unknown. A total of 254 HCC patients and 354 healthy controls were enrolled. All HCC patients underwent partial hepatectomy as initial treatment and were followed. Three SOCS3 gene polymorphisms, namely, rs4969170 A>G, rs8064821 C>T, and rs12953258 C>A were determined. Our data show that the rs4969170 A>G polymorphism dramatically affects the susceptibility to HCC in our cohorts. Logistic regression analyses revealed that the rs4969170 GG is a risk factor for HCC after the adjustment with confounding factors. The rs4969170A>G polymorphism is also associated with the clinical features of HCC patients and predicts the postoperative relapse-free survival and overall survival. The rs4969170GG genotype carrier had a worse prognosis than the rs4969170AG and rs4969170AA carrier. Our findings suggest that the rs4969170A>G polymorphism of SOCS3 gene may be used as a prognostic predictor for HCC patients who underwent surgical treatment. PMID:26447993

  18. Development of a single nucleotide polymorphism genotyping microarray platform for the identification of bovine milk protein genetic polymorphisms.

    PubMed

    Chessa, S; Chiatti, F; Ceriotti, G; Caroli, A; Consolandi, C; Pagnacco, G; Castiglioni, B

    2007-01-01

    The objective of this study was to develop and validate a fast method for typing the main mutations of bovine milk protein genes by using microarray technology. An approach based on the ligation detection reaction (LDR) and a universal array (UA) was used. Polymorphisms in both the coding and noncoding sequences of alpha(S1)-casein, beta-casein, kappa-casein, and beta-lactoglobulin genes were considered because of their well-known effects on milk composition and cheese production. A total of 22 polymorphic sites, corresponding to 21 different variants, were included in the diagnostic microarray. First, a multiplex PCR was developed to amplify all the DNA target sequences simultaneously. Second, the LDR-UA assay was implemented. The method was validated by analyzing 100 Italian Friesian DNA samples, which were also genotyped by conventional methods both at the protein level by means of milk isoelectrofocusing and at the molecular level using PCR-RFLP and PCR-single strand conformation polymorphism techniques. The genotypes obtained using the LDR-UA approach were in full agreement with those obtained by the conventional analyses. An important result of the LDR-UA assay was a more accurate genotyping of the different milk protein alleles than was found with conventional typing methods. At the kappa-casein gene, in fact, 4 samples were heterozygous (3 reference samples and 1 validation sample) for an allele coding for Thr(136) and Ala(148). This variant, which can be considered as the wild type of the genus Bos, is not usually identifiable by the conventional typing methods used. The multiplex PCR-LDR-UA approach developed provides for an accurate, inexpensive, and high-throughput assay that does not exhibit false positive or false negative signals, thus making it highly suitable for animal genotyping. PMID:17183114

  19. Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations

    PubMed Central

    Will, Britta; Zhou, Li; Vogler, Thomas O.; Ben-Neriah, Susanna; Schinke, Carolina; Tamari, Roni; Yu, Yiting; Bhagat, Tushar D.; Bhattacharyya, Sanchari; Barreyro, Laura; Heuck, Christoph; Mo, Yonkai; Parekh, Samir; McMahon, Christine; Pellagatti, Andrea; Boultwood, Jacqueline; Montagna, Cristina; Silverman, Lewis; Maciejewski, Jaroslaw; Greally, John M.; Ye, B. Hilda; List, Alan F.; Steidl, Christian

    2012-01-01

    Even though hematopoietic stem cell (HSC) dysfunction is presumed in myelodysplastic syndrome (MDS), the exact nature of quantitative and qualitative alterations is unknown. We conducted a study of phenotypic and molecular alterations in highly fractionated stem and progenitor populations in a variety of MDS subtypes. We observed an expansion of the phenotypically primitive long-term HSCs (lineage?/CD34+/CD38?/CD90+) in MDS, which was most pronounced in higher-risk cases. These MDS HSCs demonstrated dysplastic clonogenic activity. Examination of progenitors revealed that lower-risk MDS is characterized by expansion of phenotypic common myeloid progenitors, whereas higher-risk cases revealed expansion of granulocyte-monocyte progenitors. Genome-wide analysis of sorted MDS HSCs revealed widespread methylomic and transcriptomic alterations. STAT3 was an aberrantly hypomethylated and overexpressed target that was validated in an independent cohort and found to be functionally relevant in MDS HSCs. FISH analysis demonstrated that a very high percentage of MDS HSC (92% 4%) carry cytogenetic abnormalities. Longitudinal analysis in a patient treated with 5-azacytidine revealed that karyotypically abnormal HSCs persist even during complete morphologic remission and that expansion of clonotypic HSCs precedes clinical relapse. This study demonstrates that stem and progenitor cells in MDS are characterized by stage-specific expansions and contain epigenetic and genetic alterations. PMID:22753872

  20. Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations.

    PubMed

    Will, Britta; Zhou, Li; Vogler, Thomas O; Ben-Neriah, Susanna; Schinke, Carolina; Tamari, Roni; Yu, Yiting; Bhagat, Tushar D; Bhattacharyya, Sanchari; Barreyro, Laura; Heuck, Christoph; Mo, Yonkai; Parekh, Samir; McMahon, Christine; Pellagatti, Andrea; Boultwood, Jacqueline; Montagna, Cristina; Silverman, Lewis; Maciejewski, Jaroslaw; Greally, John M; Ye, B Hilda; List, Alan F; Steidl, Christian; Steidl, Ulrich; Verma, Amit

    2012-09-01

    Even though hematopoietic stem cell (HSC) dysfunction is presumed in myelodysplastic syndrome (MDS), the exact nature of quantitative and qualitative alterations is unknown. We conducted a study of phenotypic and molecular alterations in highly fractionated stem and progenitor populations in a variety of MDS subtypes. We observed an expansion of the phenotypically primitive long-term HSCs (lineage(-)/CD34(+)/CD38(-)/CD90(+)) in MDS, which was most pronounced in higher-risk cases. These MDS HSCs demonstrated dysplastic clonogenic activity. Examination of progenitors revealed that lower-risk MDS is characterized by expansion of phenotypic common myeloid progenitors, whereas higher-risk cases revealed expansion of granulocyte-monocyte progenitors. Genome-wide analysis of sorted MDS HSCs revealed widespread methylomic and transcriptomic alterations. STAT3 was an aberrantly hypomethylated and overexpressed target that was validated in an independent cohort and found to be functionally relevant in MDS HSCs. FISH analysis demonstrated that a very high percentage of MDS HSC (92% 4%) carry cytogenetic abnormalities. Longitudinal analysis in a patient treated with 5-azacytidine revealed that karyotypically abnormal HSCs persist even during complete morphologic remission and that expansion of clonotypic HSCs precedes clinical relapse. This study demonstrates that stem and progenitor cells in MDS are characterized by stage-specific expansions and contain epigenetic and genetic alterations. PMID:22753872

  1. The impact of genetic polymorphisms of drug metabolizing enzymes on the pharmacodynamics of clopidogrel under steady state conditions.

    PubMed

    Nakkam, Nontaya; Tiamkao, Somsak; Kanjanawart, Sirimas; Tiamkao, Siriporn; Vannaprasaht, Suda; Tassaneeyakul, Wongwiwat; Tassaneeyakul, Wichittra

    2015-08-01

    Clopidogrel is an antiplatelet drug that requires biotransformation steps to its active metabolite via cytochromes P450 (CYP), particularly CYP2C19 and CYP3A5 as well as paraoxonase-1 (PON1). The impact of CYP3A5 and PON1 genetic polymorphisms on the response of this drug is unclear. This study aimed to elucidate the degree of genetic polymorphisms of key drug metabolizing enzymes on the antiplatelet effect of clopidogrel. Thirty-five healthy subjects were treated with 75 mg/day clopidogrel for 7 days and serial blood samples were collected for measurement of antiplatelet effect using whole blood impedance aggregometry and VerifyNow(®) P2Y12 methods. The areas under the antiplatelet effect-time curves, maximal and minimal antiplatelet effects of clopidogrel obtained from both methods were significantly different among subjects with different CYP2C19 genotypes. In contrast, these pharmacodymamic parameters measured by both methods of subjects with different PON1 or CYP3A5 genotypes were not significantly different. Among the heterozygous CYP2C19*2 subjects, all pharmacodynamic parameters measured by whole blood impedance aggregometry were significantly different between subjects with different CYP3A5*3 genotypes. Our data suggests that CYP2C19 genetic polymorphism play a major role in the clopidogrel response, however, the impact of CYP3A5 genetic polymorphism, may be pronounced in the subjects who carried the loss-functional allele of CYP2C19. PMID:26099919

  2. Relationships between genetic polymorphisms of E670G in PCSK9 gene and coronary artery disease: a meta-analysis

    PubMed Central

    Adi, Dilare; Xie, Xiang; Liu, Fen; Ma, Yi-Tong; Abudoukelimu, Mayila; Wu, Yun; An, Yong; Yang, Yi-Ning; Li, Xiao-Mei; Fu, Zhen-Yan; Wang, Yong-Tao; Chen, Bang-Dang

    2015-01-01

    Objective: Proprotein convertase subtilisin-like kexin type 9 (PCSK9) gene E670G Polymorphism has been reported to be associated with coronary artery disease (CAD) and risk factors. However, the results remain controversial. We sought to perform a meta-analysis to investigate the relationships between genetic polymorphisms of E670G in PCSK9 gene and the risk of CAD. Methods: Literature searches were performed to identify all published relevant case-control studies without any language restrictions. Meta-analysis was conducted using the Review Manager software (version 5.2). Heterogeneity was investigated and measured using Cochrans Q-statistic and the inconsistency index (I2) test; Crude odds ratios (OR) with their corresponding 95% confidence interval (CI) were calculated. Results: A total of 5 case-control studies among 871 patients with CAD and 1144 control subjects were included in the meta-analysis. we found a correlation between PCSK9 genetic polymorphisms and increased risk for CAD under all of the genetic model (allele model: OR: 1.56, 95% CI: 1.21-2.01, P < 0.001; dominant model: OR: 1.46, 95% CI: 1.14-1.88, P = 0.003; recessive model: OR: 3.46, 95% CI: 1.19-10.10, P = 0.02; homozygous model: OR: 3.89, 95% CI: 1.35-11.20, P = 0.01; Heterozygous model: OR: 1.43, 95% CI: 1.08-1.92, P = 0.01; respectively). Conclusion: The results of the meta-analysis indicated that genetic polymorphism of E670G in PCSK9 gene might be involved in pathogenesis of CAD; the 670G carriers may be closely related to the risk of CAD. PMID:26550250

  3. Glutathione S-Transferase Gene Polymorphisms: Modulator of Genetic Damage in Gasoline Pump Workers.

    PubMed

    Priya, Kanu; Yadav, Anita; Kumar, Neeraj; Gulati, Sachin; Aggarwal, Neeraj; Gupta, Ranjan

    2015-11-01

    This study investigated genetic damage in gasoline pump workers using the cytokinesis blocked micronucleus (CBMN) assay. Blood and urine samples were collected from 50 gasoline pump workers and 50 control participants matched with respect to age and other confounding factors except for exposure to benzene through gasoline vapors. To determine the benzene exposure, phenol was analyzed in urinary samples of exposed and control participants. Urinary mean phenol level was found to be significantly high (P < 0.05) in exposed workers. The CBMN frequency was found to be significantly higher in gasoline pump workers (6.70 1.78) when compared to control individuals (2.20 0.63; P < 0.05). We also investigated influence of polymorphisms of GSTM1, GSTT1, and GSTP1 genes on CBMN frequency. The individuals having GSTM1 and GSTT1 null genotypes had significantly higher frequency of CBMN (P < 0.05). Our study indicates that chronic and long-term exposure of gasoline vapors can increase genotoxic risk in gasoline pump workers. PMID:26467191

  4. Genetic polymorphisms of Echinococcus tapeworms in China as determined by mitochondrial and nuclear DNA sequences.

    PubMed

    Nakao, Minoru; Li, Tiaoying; Han, Xiumin; Ma, Xiumin; Xiao, Ning; Qiu, Jiamin; Wang, Hu; Yanagida, Tetsuya; Mamuti, Wulamu; Wen, Hao; Moro, Pedro L; Giraudoux, Patrick; Craig, Philip S; Ito, Akira

    2010-03-01

    The genetic polymorphisms of Echinococcus spp. in the eastern Tibetan Plateau and the Xinjiang Uyghur Autonomous Region were evaluated by DNA sequencing analyses of genes for mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear elongation factor-1 alpha (ef1a). We collected 68 isolates of Echinococcus granulosus sensu stricto (s.s.) from Xinjiang and 113 isolates of E. granulosus s. s., 49 isolates of Echinococcus multilocularis and 34 isolates of Echinococcus shiquicus from the Tibetan Plateau. The results of molecular identification by mitochondrial and nuclear markers were identical, suggesting the infrequency of introgressive hybridization. A considerable intraspecific variation was detected in mitochondrial cox1 sequences. The parsimonious network of cox1 haplotypes showed star-like features in E. granulosus s. s. and E. multilocularis, but a divergent feature in E. shiquicus. The cox1 neutrality indexes computed by Tajima's D and Fu's Fs tests showed high negative values in E. granulosus s. s. and E. multilocularis, indicating significant deviations from neutrality. In contrast, the low positive values of both tests were obtained in E. shiquicus. These results suggest the following hypotheses: (i) recent founder effects arose in E. granulosus and E. multilocularis after introducing particular individuals into the endemic areas by anthropogenic movement or natural migration of host mammals, and (ii) the ancestor of E. shiquicus was segregated into the Tibetan Plateau by colonising alpine mammals and its mitochondrial locus has evolved without bottleneck effects. PMID:19800346

  5. Genetic polymorphism of the kappa-casein gene in Brazilian cattle.

    PubMed

    Azevedo, A L S; Nascimento, C S; Steinberg, R S; Carvalho, M R S; Peixoto, M G C D; Teodoro, R L; Verneque, R S; Guimares, S E F; Machado, M A

    2008-01-01

    Frequencies of kappa-casein gene alleles were determined in 1316 animals from the Brazilian Bos indicus genetic groups (Sindhi cows, Gyr sires, Gyr cows, Guzerat sires, Guzerat cows, Nellore sires, and Gyr x Holstein crossbreds) by means of polymerase chain reaction-restriction fragment length polymorphism analysis using two independent restriction nucleases (Hinf I and HaeIII). The genotyping of kappa-casein alleles (A and B) is of practical importance, since the B allele is found to correlate with commercially valuable parameters of cheese yielding efficiency. The frequencies of the B allele of kappa-casein among breeds ranged from 0.01 to 0.30. The Sindhi breed had the highest frequency for the B allele (0.30), while the frequencies of this allele in other breeds ranged from 0.01 to 0.18. A wide variation in the B allele frequency among B. indicus breeds was found suggesting that molecular selection for animals carrying the B allele could impact breeding programs for dairy production. PMID:18752189

  6. [Study on mitochondrial DNA genetic polymorphism of some yak breeds in China].

    PubMed

    Lai, Song-Jia; Wang, Ling; Liu, Yi-Ping; Li, Xue-Wei

    2005-05-01

    This study determined yak's complete sequence of mitochondrial DNA control region (D-loop) of 35 individuals in 5 yak breeds at the first time. The result showed that the length of D-loop in yak was 891 -895 bp. Content of nucleotide T, C, A, G were 28.5%, 25.3%, 32.5% and 13.7% respectively. There were 55 polymorphic sites (6.16% in total analyzed sites). The transition,transversion and insertion/deletion were found in this region.24 haplotypes was defined in this study, in which haplotype H4 and H6 were major haplotypes of Chinese yak. The distribution of all the haplotypes among the breeds was disequilibrium. The average diversity of haplotypes were 0.9697 +/-0.0180, indicating the abundance of haplotypes of yak's D-loop. The average nucleotide difference and the nucleotide diversity in Chinese yak breeds were 10.936% and 1.231% respectively. Nucleotide divergence and Kimura 2-parameter distance between yak breeds were 0.760% -2.155%, and 0.000-0.029 respectively. The results indicated that the genetic diversity of Chinese yak was very abundant. Analysis of molecular variance and network construction results indicated that there was significant divergence among Chinese yak breeds. The network construction indicated that Chinese yak had been divided into 2 types and had probably 2 maternal origins or 2 domesticated places. PMID:16018255

  7. Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms.

    PubMed

    Figueroa, Jonine D; Koutros, Stella; Colt, Joanne S; Kogevinas, Manolis; Garcia-Closas, Montserrat; Real, Francisco X; Friesen, Melissa C; Baris, Dalsu; Stewart, Patricia; Schwenn, Molly; Johnson, Alison; Karagas, Margaret R; Armenti, Karla R; Moore, Lee E; Schned, Alan; Lenz, Petra; Prokunina-Olsson, Ludmila; Banday, A Rouf; Paquin, Ashley; Ylaya, Kris; Chung, Joon-Yong; Hewitt, Stephen M; Nickerson, Michael L; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Malats, Núria; Fraumeni, Joseph F; Chanock, Stephen J; Chatterjee, Nilanjan; Rothman, Nathaniel; Silverman, Debra T

    2015-11-01

    Few studies have demonstrated gene/environment interactions in cancer research. Using data on high-risk occupations for 2258 case patients and 2410 control patients from two bladder cancer studies, we observed that three of 16 known or candidate bladder cancer susceptibility variants displayed statistically significant and consistent evidence of additive interactions; specifically, the GSTM1 deletion polymorphism (P interaction ≤ .001), rs11892031 (UGT1A, P interaction = .01), and rs798766 (TMEM129-TACC3-FGFR3, P interaction = .03). There was limited evidence for multiplicative interactions. When we examined detailed data on a prevalent occupational exposure associated with increased bladder cancer risk, straight metalworking fluids, we also observed statistically significant additive interaction for rs798766 (TMEM129-TACC3-FGFR3, P interaction = .02), with the interaction more apparent in patients with tumors positive for FGFR3 expression. All statistical tests were two-sided. The interaction we observed for rs798766 (TMEM129-TACC3-FGFR3) with specific exposure to straight metalworking fluids illustrates the value of integrating germline genetic variation, environmental exposures, and tumor marker data to provide insight into the mechanisms of bladder carcinogenesis. PMID:26374428

  8. Genetic influences on insight problem solving: the role of catechol-O-methyltransferase (COMT) gene polymorphisms

    PubMed Central

    Jiang, Weili; Shang, Siyuan; Su, Yanjie

    2015-01-01

    People may experience an “aha” moment, when suddenly realizing a solution of a puzzling problem. This experience is called insight problem solving. Several findings suggest that catecholamine-related genes may contribute to insight problem solving, among which the catechol-O-methyltransferase (COMT) gene is the most promising candidate. The current study examined 753 healthy individuals to determine the associations between 7 candidate single nucleotide polymorphisms on the COMT gene and insight problem-solving performance, while considering gender differences. The results showed that individuals carrying A allele of rs4680 or T allele of rs4633 scored significantly higher on insight problem-solving tasks, and the COMT gene rs5993883 combined with gender interacted with correct solutions of insight problems, specifically showing that this gene only influenced insight problem-solving performance in males. This study presents the first investigation of the genetic impact on insight problem solving and provides evidence that highlights the role that the COMT gene plays in insight problem solving. PMID:26528222

  9. Examination of Genetic Relatedness of Marine Synechococcus spp. by Using Restriction Fragment Length Polymorphisms

    PubMed Central

    Douglas, Susan E.; Carr, Noel

    1988-01-01

    The relatedness of several marine Synechococcus spp. was estimated by DNA hybridization. Strains isolated from various geographical locations and representing a diversity of DNA base compositions and phycobiliprotein profiles were compared by restriction fragment length polymorphisms for a number of genes. DNAs from two marine red algae and a cryptomonad alga (which exhibit a phycobiliprotein composition similar to that of the marine Synechococcus spp.) and Synechococcus strain PCC6301 (Anacystis nidulans) were also included in the comparison. Strains WH8008, WH8018, and WH7805 were shown to be very similar to one another, as were strains WH7802 and WH7803. Strains WH8110 and WH5701 were clearly unrelated to any of the other strains, and no marine Synechococcus isolate showed any similarity to the freshwater Synechococcus strain PCC6301 or the eucaryotic algae. The method is relatively straightforward and sensitive and uses a variety of basic molecular biology techniques. Its utility in ascertaining the genetic relatedness and diversity of marine Synechococcus spp. and possible extension to field studies are discussed. Images PMID:16347797

  10. Genetic Polymorphisms Associated with Rubella Virus-Specific Cellular Immunity Following MMR Vaccination

    PubMed Central

    Kennedy, Richard B.; Ovsyannikova, Inna G.; Haralambieva, Iana H.; Lambert, Nathaniel D.; Pankratz, V. Shane; Poland, Gregory A.

    2014-01-01

    Rubella virus causes a relatively benign disease in most cases, although infection during pregnancy can result in serious birth defects. An effective vaccine has been available since the early 1970s and outbreaks typically do not occur among highly vaccinated (?2 doses) populations. Nevertheless, considerable inter-individual variation in immune response to rubella immunization does exist, with single dose seroconversion rates ~95%. Understanding the mechanisms behind this variability may provide important insights into rubella immunity. In the current study, we examined associations between single nucleotide polymorphisms (SNPs) in selected cytokine, cytokine receptor, and innate/antiviral genes and immune responses following rubella vaccination in order to understand genetic influences on vaccine response. Our approach consisted of a discovery cohort of 887 subjects ages 1122 at the time of enrollment and a replication cohort of 542 older adolescents and young adults (ages 1840). Our data indicate that SNPs near the butyrophilin genes (BTN3A3/BTN2A1) and cytokine receptors (IL10RB/IFNAR1) are associated with variations in IFN? secretion and that multiple SNPs in the PVR gene, as well as SNPs located in the ADAR gene, exhibit significant associations with rubella virus-specific IL-6 secretion. This information may be useful, not only in furthering our understanding immune responses to rubella vaccine, but also in identifying key pathways for targeted adjuvant use to boost immunity in those with weak or absent immunity following vaccination. PMID:25098560

  11. Genetic polymorphisms in very important pharmacogenomic (VIP) variants in the Tibetan population.

    PubMed

    Jin, T B; Xun, X J; Shi, X G; Yuan, D Y; Feng, T; Geng, T T; Kang, L L

    2015-01-01

    Genetic polymorphisms of very important pharmacogenomic (VIP) variants are important for personalized medicine. However, these have not been extensively studied in the Tibetan population. In this study, 82 VIP variants were detected in the Tibetan and Han (HAN) populations from northwestern China. Subsequently, we compared the differences between the Tibetan population and ten populations, including the HAN, Japanese in Tokyo (JPT), Mexican ancestry in Los Angeles (MEX), Toscans in Italy (TSI), African ancestry in Southwest USA (ASW), Luhya in California Webuye, Kenya (LWK), Gujarati Indians in Houston, Texas (GIH), Maasai in Kinyawa, Kenya (MKK), Yoruba in Ibadan, Nigeria (YRI), and Utah residents with Northern and Western European ancestry from the CEPH collection (CEU). Using the ?(2) test, we identified differences in the frequency distribution of 4, 4, 7, 10, 11, 11, 13, 15, 19, and 20 loci in the Tibetan population, compared to the HAN, JPT, MEX, TSI, ASW, LWK, GIH, MKK, YRI, and CEU populations, respectively [P < 0.05/(82*10)]. rs2115819, rs9934438, and rs689466, located in the ALOX5 (arachidonate 5-lipoxygenase), VKORC1 (vitamin K epoxide reductase complex, subunit 1) and PTGS2 (prostaglandin-endoperoxide synthase 2) genes, respectively, in the Tibetan population were different from those in most of the populations. Our results complement the information provided by the database of pharmacogenomics on Tibetan people, and provide an avenue for personalized treatment in the Tibetan population. PMID:26505400

  12. Genetic polymorphisms associated with rubella virus-specific cellular immunity following MMR vaccination.

    PubMed

    Kennedy, Richard B; Ovsyannikova, Inna G; Haralambieva, Iana H; Lambert, Nathaniel D; Pankratz, V Shane; Poland, Gregory A

    2014-11-01

    Rubella virus causes a relatively benign disease in most cases, although infection during pregnancy can result in serious birth defects. An effective vaccine has been available since the early 1970s and outbreaks typically do not occur among highly vaccinated (≥2 doses) populations. Nevertheless, considerable inter-individual variation in immune response to rubella immunization does exist, with single-dose seroconversion rates ~95 %. Understanding the mechanisms behind this variability may provide important insights into rubella immunity. In the current study, we examined associations between single nucleotide polymorphisms (SNPs) in selected cytokine, cytokine receptor, and innate/antiviral genes and immune responses following rubella vaccination in order to understand genetic influences on vaccine response. Our approach consisted of a discovery cohort of 887 subjects aged 11-22 at the time of enrollment and a replication cohort of 542 older adolescents and young adults (age 18-40). Our data indicate that SNPs near the butyrophilin genes (BTN3A3/BTN2A1) and cytokine receptors (IL10RB/IFNAR1) are associated with variations in IFNγ secretion and that multiple SNPs in the PVR gene, as well as SNPs located in the ADAR gene, exhibit significant associations with rubella virus-specific IL-6 secretion. This information may be useful, not only in furthering our understanding immune responses to rubella vaccine, but also in identifying key pathways for targeted adjuvant use to boost immunity in those with weak or absent immunity following vaccination. PMID:25098560

  13. Autoimmune Hepatitis in Brazilian Children: IgE and Genetic Polymorphisms in Associated Genes

    PubMed Central

    de Oliveira, La Campos; Goldberg, Anna Carla; Marin, Maria Lucia Carnevale; Schneidwind, Karina Rosa; Frade, Amanda Farage; Kalil, Jorge; Miura, Irene Kasue; Pugliese, Renata Pereira Sustovich; Danesi, Vera Lucia Baggio; Porta, Gilda

    2015-01-01

    Pediatric autoimmune hepatitis (AIH) patients present hypergammaglobulinemia, periportal CD8+ cytotoxic T cell infiltration, and cirrhosis. Autoantibody profile defines AIH types 1 and 2 in addition to strong association with HLA-DRB1. We previously detected increased IgE serum levels and sought to compare clinical and histological features according to IgE levels in AIH (n = 74, ages 114 years) patients. Additionally, we typed 117 patients and 227 controls for functional polymorphisms of IL4, IL13, IL5, and IL4RA genes involved in IgE switching and eosinophil maturation that might contribute to overall genetic susceptibility to AIH. Serum IgE levels were high in 55% of AIH-1, but only in 12% of AIH-2 (P = 0.003) patients. Liver IgE was present in 91.3% of AIH-1 patients. The A alleles at both IL13 rs20541 and IL4RA rs1805011 were associated with AIH-1 (P = 0.024, OR = 1.55 and P < 0.0001, OR = 2.15, resp.). Furthermore, individuals presenting homozygosis for the A allele at IL4RA rs1805011 and HLA-DRB1?03 and/or ?13 allele had sixfold greater risk to develop the disease (OR = 14.00, P < 0.001). The novel association suggests an additional role for IgE-linked immune response genes in the pathogenesis of AIH. PMID:26693492

  14. Genetic diversity and phylogenetic relationship among Tunisian cactus species (Opuntia) as revealed by random amplified microsatellite polymorphism markers.

    PubMed

    Bendhifi Zarroug, M; Baraket, G; Zourgui, L; Souid, S; Salhi Hannachi, A

    2015-01-01

    Opuntia ficus indica is one of the most economically important species in the Cactaceae family. Increased interest in this crop stems from its potential contribution to agricultural diversification, application in the exploitation of marginal lands, and utility as additional income sources for farmers. In Tunisia, O. ficus indica has been affected by drastic genetic erosion resulting from biotic and abiotic stresses. Thus, it is imperative to identify and preserve this germplasm. In this study, we focused on the use of random amplified microsatellite polymorphisms to assess genetic diversity among 25 representatives of Tunisian Opuntia species maintained in the collection of the National Institute of Agronomic Research of Tunisia. Seventy-two DNA markers were screened to discriminate accessions using 16 successful primer combinations. The high percentage of polymorphic band (100%), the resolving power value (5.68), the polymorphic information content (0.94), and the marker index (7.2) demonstrated the efficiency of the primers tested. Therefore, appropriate cluster analysis used in this study illustrated a divergence among the cultivars studied and exhibited continuous variation that occurred independently of geographic origin. O. ficus indica accessions did not cluster separately from the other cactus pear species, indicating that their current taxonomical classifications are not well aligned with their genetic variability or locality of origin. PMID:25730081

  15. Genetic differentiation of Octopus minor (Mollusca, Cephalopoda) off the northern coast of China as revealed by amplified fragment length polymorphisms.

    PubMed

    Yang, J M; Sun, G H; Zheng, X D; Ren, L H; Wang, W J; Li, G R; Sun, B C

    2015-01-01

    Octopus minor (Sasaki, 1920) is an economically important cephalopod that is found in the northern coastal waters of China. In this study, we investigated genetic differentiation in fishery populations using amplified fragment length polymorphisms (AFLPs). A total of 150 individuals were collected from five locations: Dalian (DL), Yan-tai (YT), Qingdao (QD), Lianyungang (LY), and Zhoushan (ZS), and 243 reproducible bands were amplified using five AFLP primer combinations. The percentage of polymorphic bands ranged from 53.33 to 76.08%. Nei's genetic identity ranged from 0.9139 to 0.9713, and the genetic distance ranged from 0.0291 to 0.0900. A phylogenetic tree was constructed using the unweighted pair group method with arithmetic mean, based on the genetic distance. The DL and YT populations originated from one clade, while the QD, LY, and ZS populations originated from another. The results indicate that the O. minor stock consisted of two genetic populations with an overall significantly analogous FST value (0.1088, P < 0.05). Most of the variance was within populations. These findings will be important for more sustainable octopus fisheries, so that this marine resource can be conserved for its long-term utilization. PMID:26634529

  16. [Genetic diversity of wild reindeer (Rangifer tarandus) of Taimyr: analysis of polymorphism of the control region of mitochondrial DNA].

    PubMed

    Kholodova, M V; Kolpashchikov, L A; Kuznetsova, M V; Baranova, A I

    2011-01-01

    Based on an analysis of the polymorphism of nucleotide sequences (n = 111) of the control region (left domain) of mtDNA, the genetic diversity of the largest population of wild reindeer Rangifer tarandus in Eurasia, which inhabits Taimyr peninsula, was studied. High levels of gaplotypic (H) and nucleotide (pi) diversity (0.987 and 0.018, respectively) were revealed, which indicate the long existence of this population and the sufficiently stable growth of the population. The absence of long periods of abrupt decrease in the number of the Taimyr population of wild reindeer and/or facts of formation of its genetic diversity as a result of mixing of genetically distant conspecific populations is supported by the data on the distribution pattern of frequencies of pair differences between nucleotide sequences and the topology of the phylogenetic tree. The low level of genetic differences between reindeer from the western, central, and eastern groups reflects their common origin and close kinship. PMID:21442907

  17. Associations between Salivary Testosterone Levels, Androgen-Related Genetic Polymorphisms, and Self-Estimated Ejaculation Latency Time

    PubMed Central

    Jern, Patrick; Westberg, Lars; Ankarberg-Lindgren, Carina; Johansson, Ada; Gunst, Annika; Sandnabba, N Kenneth; Santtila, Pekka

    2014-01-01

    Introduction Recently, testosterone (T) has been shown to be associated with premature ejaculation (PE) symptoms in the literature. Furthermore, studies suggest that the etiology of PE is partly under genetic control. Aim The aim of this study was to reassess findings suggesting an association between testosterone (T) and a key symptom of PE, ejaculation latency time (ELT), as well as exploratively investigating associations between six androgen-related genetic polymorphisms and ELT. Materials and Methods Statistical analyses were performed on a population-based sample of 1,429 Finnish men aged 1845 years (M = 26.9, SD = 4.7). Genotype information was available for 1,3451,429 of these (depending on the polymorphism), and salivary T samples were available from 384 men. Two androgen receptor gene-linked, two 5-alpha-reductase type 2-gene-linked, and two sex hormone-binding globuline gene-linked polymorphisms were genotyped. Main Outcome Measures Ejaculatory function was assessed using self-reported ELT. Results We found no association between salivary T levels and ELT. We found a nominally significant association between a 5-alpha-reductase type 2-gene-linked polymorphism (rs2208532) and ELT, but this association did not remain significant after correction for multiple testing. One single nucleotide polymorphism in the sex hormone-binding globulin gene (rs1799941) moderated (significantly after correction for multiple testing) the association between salivary T and ELT, so that A:A genotype carriers had significantly lower salivary T levels as a function of increasing ELT compared with other genotype groups. Conclusions We were unable to find support for the hypothesis suggesting an association between T levels and ELT, possibly because of the low number of phenotypically extreme cases (the sample used in the present study was population based). Our results concerning genetic associations should be interpreted with caution until replication studies have been conducted. Jern P, Westberg L, Ankarberg-Lindgren C, Johansson A, Gunst A, Sandnabba NK, and Santtila P. Associations between salivary testosterone levels, androgen-related genetic polymorphisms, and self-estimated ejaculation latency time. Sex Med 2014;2:107114. PMID:25356307

  18. Genetic variations and polymorphisms in the ezrin gene are associated with age-related cataract

    PubMed Central

    Lin, Qinghong; Zhou, Nan; Zhang, Na; Zhu, Bidan; Hu, Shanshan; Zhou, Zhou

    2013-01-01

    Purpose Age-related cataract (ARC) is a complex multifactorial disorder, including genetic and environmental factors. Ezrin (EZR), a member of the ezrin/radixin/moesin (ERM) protein family, plays a crucial role in the development of the lens as a plasma membranecytoskeleton linker. We conducted this study to investigate the role of genetic variations of ezrin and the relationship between single nucleotide polymorphisms (SNPs) in EZR and susceptibility to ARC in a Chinese population. Methods A total of 205 sporadic age-related cataract patients and 218 unrelated random healthy controls participated in our study. Genomic DNA was extracted from peripheral blood leukocytes. All exons of EZR were sequenced after being amplified with polymerase chain reaction. The functional consequences of the mutations were analyzed using PolyPhen2. SNP statistical analysis was performed using SNPstats. Results We found three novel variations in 205 patients. None presented in the 218 controls, including c.441C>G, c.924G>C, and c.1503G>A. PolyPhen2 predicted that the c.924G>C mutation probably had pathogenicity. Compared with the healthy controls, the rs5881286 -/GT genotype and - allele frequencies (p=0.0012; odds ratio [OR]=3.37; 95% confidence interval [CI]=1.706.70; p=3.96e-5; ?2=18.98, respectively), rs2242318 T/C genotype and C allele frequencies (p=0.0045; OR=3.40; 95% CI=1.706.79; p=8.82e-6; ?2=21.86, respectively), and rs144581330 A/G genotype and G allele frequencies (p=0.0472; OR=14.46; 95% CI=1.29162.43; p=0.0244, ?2=6.99, respectively) were higher in the patients with age-related cataract. SNP rs144581330 in exon 2 was also predicted to be probably damaging by PolyPhen2. Haplotype association including the - allele of rs5881286, C allele of rs2242318, and A allele of rs144581330 exhibited significantly higher distribution in the patients with ARC (p=8.0e-4; OR=3.38; 95% CI=1.666.87). Conclusions This study suggests that the genetic variations and SNPs in the gene EZR possibly contribute to the development of age-related cataracts in the Chinese population. PMID:23882136

  19. Endothelial nitric oxide synthase gene polymorphisms and genetic susceptibility to prostate cancer.

    PubMed

    Medeiros, R; Morais, A; Vasconcelos, A; Costa, S; Pinto, D; Oliveira, J; Lopes, C

    2002-08-01

    The endothelial cell-specific form of nitric oxide synthases (ecNOS) is localized at 7q35-q36 and is involved in vascular development and tumour growth in human prostate cancer. We have conducted a case-control study to investigate the prevalence of two polymorphisms at intron 4 (ecNOS4a/b) and exon 7 (Glu-Asp298) of ecNOS gene in 125 prostate cancer (PCa) patients and in 153 controls. We observed that the a-allele (aa or ab genotypes from ecNOS4a/b) was over-presented in the group of PCa with Gleason histological grade >or=7 (P=0.041). With regard to the Glu-Asp298 polymorphism, patients with the T-allele were younger than patients with no T-allele (P=0.037), and a statistically significant difference was noted in the Glu-Asp298 genotype distribution between cases with advanced disease and cases with localized disease (P=0.0013). When comparing cases and controls with logistic regression analysis we observed that the presence of the a-allele is associated with prostate cancer risk (odds ratio (OR) 1.83; 95% confidence interval (CI) 1.06-3.17; P=0.029), to high histological grade (Gleason >or=7) of PCa (OR 2.18; 95% CI 0.95-4.98; P=0.062) and with the risk of progression of the cancer disease (OR 2.85; 95% CI 1.19-6.82; P=0.018). Furthermore, we found that carriers with the combination of the a-allele (aa and ab ecNOS4a/b genotypes) and T-allele (GT and TT from Glu-Asp298) have a threefold increase in prostate cancer risk (OR 3.13; 95% CI 1.41-6.91, P=0.004). In summary, we have identified an NO-related genetic risk factor for prostate cancer that may help in understanding the molecular mechanism involved in the individual susceptibility to prostate cancer. PMID:12195160

  20. Genetic Polymorphisms of Platelet Receptors in Patients with Acute Myocardial Infarction and Resistance to Antiplatelet Therapy

    PubMed Central

    Ulehlova, Jana; Kucerova, Jana; Krcova, Vera; Vaclavik, Jan; Indrak, Karel

    2014-01-01

    Methods: The studied group comprises 124 patients with acute myocardial infarction on dual antiplatelet therapy with acetylsalicylic acid (ASA) and thienopyridines. Antiplatelet therapy was monitored by platelet-rich plasma light transmittance aggregometry (LTA) using the APACT 4004 analyzer (Helena Laboratories) and by whole blood impedance aggregometry (multiple electrode aggregometry [MEA]) using the Multiplate analyzer (Dynabyte). Platelet aggregation was detected after stimulation with arachidonic acid for detection of aspirin resistance and with adenosine diphosphate (ADP) and prostaglandin E1 for detection of thienopyridine resistance. To determine the frequencies of P2Y12 (i-744T>C; rs2046934), P2Y12 (34C>T; rs6785930), COX-1 (-842A>G; rs10306114), GPVI (13254T>C; rs1613662), and GPIbA (5T>C; rs2243093) polymorphisms, DNA of patients with AIM was tested by real-time-polymerase chain reaction and melting curve analysis using the LightCycler 480 analyzer (Roche Diagnostics). Results: The cut-off points used for patients with effective ASA therapy are 25% of aggregated platelets and 220 area under the curve (AUC)/min if LTA or MEA, respectively. The cut-off points used for effective thienopyridine therapy are 45% of aggregated platelets or 298 AUC/min, respectively. Both LTA and MEA found that aspirin and thienopyridine therapies failed in 14.51% and 25.8%, respectively. The data were statistically processed using the SPSS version 15 software (SPSS, Inc.). Associations between receptor mutation status and response to therapy were assessed with Fisher's exact test. The significance level was set at 0.05. Conclusion: The aim of our work was to use the two functional laboratory methods described earlier to assess both aspirin and thienopyridine resistance and to determine the contribution of genetic polymorphisms of platelet receptors to resistance to antiplatelet therapy in AIM. Fisher's exact test showed a significant statistical correlation between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of COX1_A1 (-A842G). Fisher's exact test showed no statistically significant correlations between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of GP1bA (-5T>C) and GP6 (T13254C). Fisher's exact test showed no statistically significant correlation between mutational statuses of the receptors P2RY12 (i-T744C), P2RY12 (C34T), GP1bA (-5T>C), or GP6 (T13254C) and response to antiplatelet therapy with 75 mg of clopidogrel. PMID:25093390

  1. The Association between PTPN22 Genetic Polymorphism and Juvenile Idiopathic Arthritis (JIA) Susceptibility: An Updated Meta-Analysis

    PubMed Central

    DI, Yazhen; ZHONG, Shilling; WU, Ling; LI, Yunyan; SUN, Nan

    2015-01-01

    Background: Limited studies have focused on the association between the protein tyrosine phosphates non-receptor type 22 (PTPN22) genetic polymorphisms and Juvenile idiopathic arthritis (JIA) susceptibility in different populations, but the results were inconclusive. Therefore, this meta-analysis of PTPN22 polymorphism (1858 C>T) was performed to get a precise systematic estimation. The rs number of the PTPN22 polymorphism (1858 C>T) is 4. Methods: A systematic literature search strategy was carried out using English databases (PubMed, Embase.) for the eligible studies. We ultimately identified 11 records from 10 articles involving the relationship between PTPN22 genetic polymorphisms and JIA risk from PubMed and Embase databases. Overall, 4552 cases and 10161 controls were investigated in this study to evaluate the association between PTPN22 (C allele vs. T allele) genotype and JIA susceptibility. Results: Analysis using random effects model showed an increased risk of JIA with T allele of rs2476601 vs. A allele (P<0.001). Subgroup analysis suggested that the PTPN22 polymorphism (1858C>T) was significantly associated with JIA risk in America population (OR=1.52, 95% CI:1.301.78). Additionally, the subgroup analysis also showed that the associations were still significant in case number more than 500 (OR=1.38, 95% CI: 1.041.83), while in the case number less than 500 was OR=1.55, 95% CI: 1.391.72. Conclusions: SNPs of PTPN22 (1858C>T) showed an increased risk of developing JIA. PMID:26587490

  2. Genetic polymorphisms of C-reactive protein increase susceptibility to HBV-related hepatocellular carcinoma in a Guangxi male population

    PubMed Central

    Lao, Xianjun; Ren, Shan; Lu, Yu; Yang, Dongmei; Qin, Xue; Li, Shan

    2015-01-01

    C-reactive protein (CRP) is a biomarker of inflammation and the production has been shown to be influenced by genetic variation in CRP gene. HBV-related hepatocellular carcinoma (HCC) is a typical inflammation-related disease occurs mainly in men. The present study was designed to investigate the association between CRP polymorphisms and HBV-related HCC risk in a Chinese male population. The CRP rs2794521 and rs3093059 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) in 158 HBV patients with HCC, 207 HBV patients without HCC, and 150 unrelated healthy controls. A significant increased HCC risk in HBV patients were observed for the rs3093059 SNP comparing with those without HCC (C allele vs. T allele: adjusted OR=1.56, 95% CI, 1.07-2.29, P=0.021; TC vs. TT: adjusted OR=1.77, 95% CI, 1.13-2.76, P=0.012; TC/CC vs. TT: adjusted OR=1.76, 95% CI, 1.14-2.71, P=0.011). However, we did not observe any significant association of rs3093059 polymorphism with HCC when compared with healthy controls. With respect to rs2794521 polymorphism, no significant associations of this polymorphism with HCC risk were found in this population. In haplotype analysis between HBV patients with HCC and HBV patients without HCC, the TC haplotype was found correlated with a significant increased HCC risk (OR=1.803, 95% CI, 1.237-2.335, P<0.001). We concluded that the CRP rs3093059 polymorphism may play a significant role in the development of HBV-related HCC in the Guangxi male population. PMID:26884882

  3. Correlation between XRCC1 Arg399Gln genetic polymorphisms and susceptibility to bladder cancer: a meta-analysis

    PubMed Central

    Liu, Nannan; Fei, Xiawei; Shen, Yi; Shi, Weifeng; Ma, Jinhong

    2016-01-01

    The relationship between XRCC1 polymorphisms and bladder cancer has been widely studied. Here, our meta-analysis was conducted to evaluate the correlations between common genetic polymorphisms in XRCC1 and susceptibility to bladder cancer. In order to derive a more precise estimation of the association, 27 clinical case-control studies (which met all the inclusion criteria) were included in this meta-analysis. A total of 8,539 cancer cases and 10,750 controls were involved in this meta-analysis. Overall, no significant association was detected in allelic model (A allele vs T allele odds ratio [OR] =0.87, 95% confidence interval [CI], 0.711.06), homozygote comparison (AA vs GG OR =1.12, 95% CI, 0.681.85), heterozygote comparison (AT vs TT OR =1.01, 95% CI, 0.811.26), dominant model (AA + AG vs GG OR =0.93, 95% CI, 0.851.02), and recessive model (AA vs AG + GG OR =1.01, 95% CI, 0.881.15), but a moderately significant association was found for AG vs GG (OR =0.241, 95% CI =0.170.35). Subgroup analysis based on ethnicity. Ethnicity analysis suggested that genetic polymorphisms in XRCC1 were not correlated with increased bladder cancer risk among Asians (all P>0.05). Therefore, we concluded that XRCC1 genetic polymorphism may not contribute to bladder cancer susceptibility in the present meta-analysis, and further well-designed studies with a large sample size are warranted to validate our conclusion. PMID:26869802

  4. IL-10 Genetic Polymorphisms Were Associated with Valvular Calcification in Han, Uygur and Kazak Populations in Xinjiang, China

    PubMed Central

    Ma, Yi-Tong; Wulasihan, Muhuyati; Huang, Ying; Adi, Dilare; Yang, Yi-Ning; Ma, Xiang; Li, Xiao-Mei; Xie, Xiang; Huang, Ding; Liu, Fen; Chen, Bang-Dang

    2015-01-01

    Objective Valvular calcification occurs via ongoing endothelial injury associated with inflammation. IL-10 is an anti-inflammatory cytokine and 75% of the variation in IL-10 production is genetically determined. However, the relationship between genetic polymorphisms of IL-10 and valvular calcification has not been studied. The objective of this study was to investigate the association between valvular calcification and IL-10 genetic polymorphisms in the Han, Uygur and Kazak populations in China. Patients and Methods All of the participants were selected from subjects participating in the Cardiovascular Risk Survey (CRS) study. The single nucleotide polymorphisms (SNPs) rs1800871 and rs1800872 of the IL-10 gene were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Three independent case-control studies involving the Han population, the Uygur population and the Kazak population were used in the analysis. Results For the Han and Kazak populations, rs1800871 was found to be associated with valvular calcification in the recessive model, and the difference remained statistically significant following multivariate adjustment (p<0.001, p=0.031, respectively). For the Han, Uygur and Kazak populations, rs1800872 was found to be associated with valvular calcification in the dominant model, and the difference remained statistically significant following multivariate adjustment (p<0.001, p=0.009, and p=0.023,respectively) Conclusion Both rs1800871 and rs1800872 of the IL-10 gene are associated with valvular calcification in the Han and Kazak populations in China. Rs1800872 is also associated with valvular calcification in the Uygur population. PMID:26039365

  5. Association of MTHFR genetic polymorphisms with venous thromboembolism in Uyghur population in Xinjiang, China

    PubMed Central

    Li, Zhao; Yadav, Umesh; Mahemuti, Ailiman; Tang, Bao-Peng; Upur, Halmurat

    2015-01-01

    Background: The aim of this study was to reveal the association between Methylene tetrahydrofolate reductase (MTHFR) gene mutations (C677T, A1298C and C1317T) and risk of venous thromboembolism (VTE) in Han and Uyghur population in Xinjiang. Material and method: We conducted a case control study composed of 246 cases, including 86 Uyghur and 160 Han ethnic diagnosed VTE were admitted in the First Affiliated Hospital of Xinjiang Medical University between January 2008 to December 2012, and 292 population including 122 Uyghur ethnic and 170 Han ethnic were studied as controls. To detect the polymorphism of MTHFR gene C677T, A1298T, and C1317T, Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied. Fluorescence polarization immunoassay was adopted to determine the plasma levels Homocysteine (Hcy), folic acid and vitaminB12 (VitB12). The association of the polymorphism of MTHFR and levels Hcy, folic acid and VitB12 with VTE was analyzed. Results: The MTHFR gene C677T genotypes distribution in Uyghur VTE patients and control groups were: TT (27.91% vs. 12.29%), CT (41.86% vs. 52.46%) and CC (30.23% vs. 35.25%), respectively; and in Han VTE patients and control groups were: TT (27.49% vs. 14.71%), CT (44.38% vs. 53.53%) and CC (28.13% vs. 31.76%), respectively, and there were significant differences in TT genotype of MTHFRC677T between VTE patients and controls in both Uyghur and Han ethnic (Uyghur: x2=8.070, P=0.005; Han: x2=8.159, P=0.004). However, there were no significant differences in the MTHFR gene A1298T and C1317T genotyping distribution frequency in Uygur and Han ethnic between VTE patients and controls (P>0.05). Plasma levels of Hcy in MTHFR gene TT genotype were statistically higher than CT and CC genotype (P<0.05). After adjusting for age, gender, smoking, hypertension, hyperlipidemia, diabetes and MTHFR genotype for plasma Hcy levels, multifactor logistic regression analysis showed (OR=1.025, 95% CI 1.003-1.046, P=0.024) and obesity (OR=4.660, 95% CI 1.417-15.324, P=0.011) were independent risk factors for Uygur ethnic with VTE while plasma Hcy levels (OR=1.020, 95% CI 1.006-1.034, P=0.004) and smoking (OR=2.867, 95% CI 1.062-6.586, P=0.024) were independent risk factors for Han ethnic with VTE. Conclusions: Our finding supports significant role of MTHFR gene in VTE and evidence of genetically determined HHcy contribute a risk for VTE, and a smoker with tHcy has positive association with a risk of VTE. PMID:26770360

  6. Several genetic polymorphisms interact with overweight/obesity to influence serum lipid levels

    PubMed Central

    2012-01-01

    Background Information about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on serum lipid profiles is still scarce. The present study was undertaken to detect ten SNPs and their interactions with overweight/obesity on serum lipid levels. Methods A total of 978 normal weight and 751 overweight/obese subjects of Bai Ku Yao were randomly selected from our previous stratified randomized cluster samples. Normal weight, overweight and obesity were defined as a body mass index (BMI) < 24, 24–28, and > 28 kg/m2; respectively. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) A1 and ApoB levels were measured. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII, hepatic lipase gene (LIPC) -250G>A, endothelial lipase gene (LIPG) 584C>T, methylenetetrahydrofolate reductase (MTHFR) 677C>T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T>C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions were detected by factorial design covariance analysis. Results The genotypic and allelic frequencies of LIPC and PCSK9 were different between normal weight and overweight/obese subjects, the genotypic frequency of LIPG and allelic frequency of MYLIP were also different between normal weight and overweight/obese subjects (P < 0.05-0.001). The levels of TC, ApoA1 (ABCA-1); TC, LDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TG, HDL-C, and ApoA1 (LIPG); TC, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); HDL-C and ApoA1 (MYLIP) in normal weight subjects were different among the genotypes (P < 0.01-0.001). The levels of LDL-C, ApoB and ApoA1/ApoB (ABCA-1); HDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TC, HDL-C, ApoA1 and ApoB (LIPG); TC, TG, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); TC, TG and ApoB (MYLIP); TG (PCSK9); TG, ApoA1 and ApoB (PPARD); and TC, HDL-C, LDL-C, ApoA1 and ApoB (SCARB1) in overweight/obese subjects were different among the genotypes (P < 0.01-0.001). The SNPs of ABCA-1 (LDL-C and ApoA1/ApoB); LIPC (TC, LDL-C, ApoA1 and ApoB); LIPG (ApoB); MTHFR (TC, TG and LDL-C); MYLIP (TC and TG); PCSK9 (TG, HDL-C, ApoB and ApoA1/ApoB); PPARD (TG and ApoA1/ApoB); and SCARB1 (TG, ApoA1 and ApoB) interacted with overweight/obesity to influence serum lipid levels (P < 0.05-0.001). Conclusions The differences in serum lipid levels between normal weight and overweight/obese subjects might partly result from different genetic polymorphisms and the interactions between several SNPs and overweight/obesity. PMID:23039238

  7. Loss of heterozygosity analyzed by single nucleotide polymorphism array in cancer

    PubMed Central

    Zheng, Hai-Tao; Peng, Zhi-Hai; Li, Sheng; He, Lin

    2005-01-01

    Neoplastic progression is generally characterized by the accumulation of multiple genetic alterations including loss of tumor suppression gene function. Loss of heterozygosity (LOH) has been used to identify genomic regions that harbor tumor suppressor genes and to characterize different tumor types, pathological stages and progression. LOH pattern has been detected by allelotyping using restriction fragment length polymorphism, and later by simple sequence length polymorphisms (SSLPs or microsatellite) for 10 years. This paper reviews the detection of LOH by recently developed single nucleotide polymorphism (SNP) arrays (all analyzed by Affymetrix array); furthermore, its advantage and disadvantage were analyzed in several kinds of cancer. PMID:16425377

  8. XRCC1 and XPD genetic polymorphisms and susceptibility to age-related cataract: A meta-analysis

    PubMed Central

    Chi, Xin-Xin; Liu, You-Yu; Shi, Su-Ning; Cong, Zhuang; Liang, Yu-Qing

    2015-01-01

    Objective This meta-analysis aimed to determine the relationships between XRCC1 Arg399Gln (rs25487 G>A) and XPD Lys751Gln (rs1052559 A>C) polymorphisms and susceptibility to age-related cataract. Methods Medline (19662013), the Cochrane Library Database (Issue 12, 2013), EMBASE (19802013), CINAHL (19822013), Web of Science (19452013) and the Chinese Biomedical Database (CBM; 19822013) were searched without language restrictions. Various combinations of the keywords and MeSH terms were used to screen for potentially relevant studies, specifically genetic polymorphisms or SNPs or variation or single nucleotide polymorphism or polymorphism or mutation or variant; X-ray repair cross complementing protein 1 or Xeroderma Pigmentosum Group D Protein or X-ray repair cross complementing protein 1 or Xeroderma Pigmentosum Group D Protein or XPD or Xeroderma Pigmentosum Complementation Group D Protein or ERCC2 or XRCC1 or XRCC1 DNA repair protein; and Cataract or Membranous Cataract or Pseudoaphakia. Meta-analyses were conducted using Stata 12.0 software. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (95% CI) were calculated. Results Six independent case-control studies were included in the meta-analysis. Our results indicated that the association between the genetic polymorphisms of XRCC1 Arg399Gln G>A and XPD Lys751Gln A>C and increased susceptibility to age-related cataracts was statistically significant (XRCC1 Arg399Gln: OR=1.30, 95% CI=1.171.44, p<0.001; XPD Lys751Gln: OR=1.25, 95% CI=1.121.40, p<0.001, respectively). Ethnicity-stratified analysis indicated that the XRCC1 Arg399Gln G>A polymorphism was correlated with the development and progression of age-related cataract in China, India, and Turkey in the allele model and the dominant model. For the XPD Lys751Gln A>C variant, the association with the pathogenesis of age-related cataract in China and Turkey in the allele model and the dominant model was investigated. Conclusions The association of XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms with age-related cataract susceptibility observed in our meta-analyses supports the view that XRCC1 and XPD may play important roles in susceptibility to age-related cataract. PMID:25873778

  9. Interaction between MLL3 genetic polymorphisms, smoking, and alcohol drinking in laryngeal cancer: a case-control study.

    PubMed

    Chen, Dong; Gong, Liang; Jiang, Qichuan; Wang, Xuefeng; Zhang, Bin

    2016-03-01

    A previous study indicated that MLL3 genetic polymorphisms were associated with human cancer. However, whether MLL3 genetic variants are associated with the risk of laryngeal cancer is not clear. This study investigated the association between MLL3 gene polymorphisms and laryngeal cancer in a Chinese population. Four polymorphisms of the MLL3 gene (rs6943984, rs4725443, rs3800836, rs6464211) were genotyped using the TaqMan method in 592 patients with larynx cancer and 602 age- and sex-matched noncancer controls. We found that rs6943984 and rs4725443 of the MLL3 gene were significantly associated with the risk of larynx cancer after Bonferroni correction. The minor allele A for rs6943984 was associated with increased larynx cancer risk (P < 0.001, OR = 1.960, 95% CI = 1.587-2.420). C allele frequency (0.151) for rs4725443 was significantly higher in the case group than the control group (0.072, P < 0.001). Haplotype analyses showed that haplotypes A-T-A-C and G-T-G-C increased the risk of laryngeal cancer (OR = 2.406, 95% CI: 1.820-3.180, P < 0.001; OR = 1.399, 95% CI: 1.180-1.659, respectively), and haplotypes G-T-A-C and G-T-G-T significantly reduced the risk of laryngeal cancer (OR = 0.332, 95% CI: 0.271-0.408, P < 0.001; OR = 0.742, 95% CI: 0.607-0.908, respectively). We also found that MLL3 rs6943984 and rs4725443 polymorphisms had synergistic effects with smoking or alcohol drinking for the risk of laryngeal cancer. This study indicated that MLL3 genetic polymorphisms and haplotypes were associated with larynx cancer in a Chinese population. There was a mutually synergistic effect between smoking, alcohol drinking, and MLL3 gene polymorphisms for laryngeal cancer. PMID:26818916

  10. Genetic polymorphisms as determinants for disease preventive effects of vitamin E

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polymorphisms in genes involved in vitamin E uptake, distribution, metabolism and molecular action may be important determinants for the protective effects of vitamin E supplementation. The haptoglobin 2-2 polymorphism is associated with increased production of oxygen free radicals and the consequen...

  11. Reliable In Silico Identification of Sequence Polymorphisms and Their Application for Extending the Genetic Map of Sugar Beet (Beta vulgaris)

    PubMed Central

    Holtgrwe, Daniela; Srensen, Thomas Rosleff; Viehver, Prisca; Schneider, Jessica; Schulz, Britta; Borchardt, Dietrich; Kraft, Thomas; Himmelbauer, Heinz; Weisshaar, Bernd

    2014-01-01

    Molecular markers are a highly valuable tool for creating genetic maps. Like in many other crops, sugar beet (Beta vulgaris L.) breeding is increasingly supported by the application of such genetic markers. Single nucleotide polymorphism (SNP) based markers have a high potential for automated analysis and high-throughput genotyping. We developed a bioinformatics workflow that uses Sanger and 2nd-generation sequence data for detection, evaluation and verification of new transcript-associated SNPs from sugar beet. RNAseq data from one parent of an established mapping population were produced by 454-FLX sequencing and compared to Sanger ESTs derived from the other parent. The workflow established for SNP detection considers the quality values of both types of reads, provides polymorphic alignments as well as selection criteria for reliable SNP detection and allows painless generation of new genetic markers within genes. We obtained a total of 14,323 genic SNPs and InDels. According to empirically optimised settings for the quality parameters, we classified these SNPs into four usability categories. Validation of a subset of the in silico detected SNPs by genotyping the mapping population indicated a high success rate of the SNP detection. Finally, a total of 307 new markers were integrated with existing data into a new genetic map of sugar beet which offers improved resolution and the integration of terminal markers. PMID:25302600

  12. Genetic diversity and relatedness of sweet cherry (prunus avium L.) cultivars based on single nucleotide polymorphic markers.

    PubMed

    Fernandez I Marti, Angel; Athanson, Blessing; Koepke, Tyson; Font I Forcada, Carolina; Dhingra, Amit; Oraguzie, Nnadozie

    2012-01-01

    Most previous studies on genetic fingerprinting and cultivar relatedness in sweet cherry were based on isoenzyme, RAPD, and simple sequence repeat (SSR) markers. This study was carried out to assess the utility of single nucleotide polymorphism (SNP) markers generated from 3' untranslated regions (UTR) for genetic fingerprinting in sweet cherry. A total of 114 sweet cherry germplasm representing advanced selections, commercial cultivars, and old cultivars imported from different parts of the world were screened with seven SSR markers developed from other Prunus species and with 40 SNPs obtained from 3' UTR sequences of Rainier and Bing sweet cherry cultivars. Both types of marker study had 99 accessions in common. The SSR data was used to validate the SNP results. Results showed that the average number of alleles per locus, mean observed heterozygosity, expected heterozygosity, and polymorphic information content values were higher in SSRs than in SNPs although both set of markers were similar in their grouping of the sweet cherry accessions as shown in the dendrogram. SNPs were able to distinguish sport mutants from their wild type germplasm. For example, "Stella" was separated from "Compact Stella." This demonstrates the greater power of SNPs for discriminating mutants from their original parents than SSRs. In addition, SNP markers confirmed parentage and also determined relationships of the accessions in a manner consistent with their pedigree relationships. We would recommend the use of 3' UTR SNPs for genetic fingerprinting, parentage verification, gene mapping, and study of genetic diversity in sweet cherry. PMID:22737155

  13. Choice of methodology for assessing genetic impacts of environmental stressors: polymorphism and reproducibility of RAPD and AFLP fingerprints.

    PubMed

    Bagley, M J; Anderson, S L; May, B

    2001-08-01

    PCR-based multi-locus DNA fingerprints represent one of the most informative and cost-effective measures of genetic diversity and are useful population-level biomarkers of toxicologic and other anthropogenic impacts. However, concerns about reproducibility of DNA fingerprints have limited their wider use in environmental biology. We assessed polymorphism and reproducibility of two common fingerprinting techniques, RAPD (randomly amplified polymorphic DNA) and AFLP (amplified fragment length polymorphism), in pedigreed populations of rainbow trout (Oncorhynchus mykiss) to derive general rules for selective removal of problematic fingerprint bands. We found that by excluding bands that comprised less than 1% of total intensity, and by excluding the largest and smallest 10% of the bands, we could achieve nearly 100% reproducibility of AFLP fingerprints. Similar application of band exclusion criteria to RAPD fingerprints did not significantly enhance their reproducibility, and at least 15% of RAPD bands were not fully repeatable, heritable, or transmittable. The RAPD technique produced more polymorphic fingerprints than AFLP; however, considering that a substantial proportion of RAPD markers did not demonstrate Mendelian inheritance patterns, the AFLP methodology is to be preferred for future research. PMID:11501435

  14. Analysis of the genetic composition of anther-derived potato by randomly amplified polymorphic DNA and simple sequence repeats.

    PubMed

    Veilleux, R E; Shen, L Y; Paz, M M

    1995-12-01

    Randomly amplified polymorphic DNA (RAPD) and simple sequence repeat (SSR) analyses were used to characterize the genetic composition of anther-derived plants of a diploid potato clone, CP2 (Solanum chacoense 80-1 x S. phureja 1-3). The ploidy of anther-derived plants was first determined by flow cytometry. A total of 44 decamer primers was screened for RAPD polymorphism. The loci that segregated were selected and scored. The monoploids had less than half as many loci carrying RAPD markers compared with the anther donor. Among 14 anther-derived diploids, 5 were identified as homozygous by marker frequency similar to monoploids and 9 as heterozygous. Five of seven SSRs obtained from published potato sequences were polymorphic in CP2. CP2 was found to be heterozygous with two alleles at four SSR loci (TC/TA, AAG, AGA, CTT) and three alleles at a ACTC locus. Primer pairs flanking each of the five polymorphic SSRs revealed that monoploids had only the allele contributed by S. chacoense 80-1. Homozygous diploids had only one band per SSR locus, whereas heterozygous diploids displayed more than one allele for at least one SSR locus. Results of the SSR analysis supported the findings based on RAPD markers; the same five diploid clones were characterized as homozygous by both SSR and RAPD markers. PMID:8654912

  15. Association of VEGF Genetic Polymorphisms with Recurrent Spontaneous Abortion Risk: A Systematic Review and Meta-Analysis

    PubMed Central

    Xu, Xinghua; Du, Chigang; Li, Huihui; Du, Jing; Yan, Xue; Peng, Lina; Li, Guangyao; Chen, Zi-Jiang

    2015-01-01

    Background Studies of the associations between the genetic polymorphisms of the vascular endothelial growth factor (VEGF) gene and recurrent spontaneous abortion (RSA) have revealed conflicting results. The present meta-analysis was performed to provide a more precise estimation of these relationships and to explore potential sources of heterogeneity that may have influenced the reported disparities. Methods An extensive literature search for relevant studies was conducted on PubMed, Embase, and The Cochrane Library through June 6, 2014. Crude odds ratio (OR) with 95% confidence intervals were calculated. Results 10 case-control studies including 1,832 RSA patients and 2,271 healthy controls were identified. Meta-analysis indicated that rs1570360, rs3025039, rs2010963, and rs3025020 polymorphisms in the VEGF gene correlated with elevated RSA risk. The rs1570360 variant was statistically significantly relevant to RSA risk among non-Asian populations. Interestingly, the rs3025039 variant was statistically significantly relevant to RSA risk among Asian populations. Conclusions The current meta-analysis indicates that rs1570360, rs3025039, rs2010963, and rs3025020 polymorphisms increase RSA susceptibility. Moreover, rs1570360 and rs3025039 polymorphisms may play various roles in RSA susceptibility in various geographic groups. PMID:25894555

  16. Genetic distribution and association analysis of DRD2 gene polymorphisms with major depressive disorder in the Chinese Han population

    PubMed Central

    He, Mei; Yan, Hong; Duan, Zhao-Xia; Qu, Wei; Gong, Hai-Yan; Fan, Zheng-Li; Kang, Jian-Yi; Li, Bing-Cang; Wang, Jian-Min

    2013-01-01

    Dopamine D2 receptor is involved in reward-mediating mesocorticolimbic pathways. It plays an important role in major depressive disorder (MDD). Three gene polymorphisms Taq1A, C957T and -141C ins/del, were identified in the DRD2 gene among the Western population. These variants in the DRD2 gene might be associated with the susceptibility of MDD patients through affecting the bioeffects of endogenous dopamine neurotransmission. However, little is known about their occurrence in Chinese population and their association with the susceptibility of patients with major depressive disorder. In this study, a total of 338 unrelated adult Chinese Han population, including 224 healthy volunteers and 114 patients with major depressive disorder, were recruited. DRD2 polymorphisms (Taq1A and -141C ins/del) were detected using restriction fragment length polymorphism (RFLP) analysis and the C957T were detected by sequencing directly. As a result, three polymorphisms were identified in Chinese Han population and all were common SNP. However, we could detect no evidence of genetic association between 3 markers in DRD2 and major depressive disorder in the Chinese Han population. To conclude, this result suggests that Taq1A, C957T and -141C ins/del of DRD2 gene may not be associated with major depressive disorder, also may be the sample sizes too small to allow a meaningful test. PMID:23696934

  17. The effect of genetic polymorphisms of TLR2 and TLR4 in Turkish patients with coronary artery disease.

    PubMed

    Guven, Mehmet; Ismailoglu, Ziya; Batar, Bahadir; Unal, Selin; Onaran, Ilhan; Karadag, Bilgehan; Ongen, Zeki

    2015-03-01

    Coronary artery disease (CAD), being a multifactorial disease process, has been suggested to be associated by the interaction of both environmental and genetic risk factors. Toll-like receptors (TLRs) are related to the receptors of the innate immune system which serves as the recognition of the conserved pathogen motifs and the activation of the signals that stimulate inflammatory genes. In this study, we investigated the relationship between the polymorphisms in the TLR2-Arg753Gly, TLR4-Asp299Gly and Thr399Ile gene and CAD. The study population consisted of 300 patients (149 men, 151 women) with angiographically documented CAD. The polymorphisms were genotyped by real time PCR. No association between TLR2-Arg677Trp or TLR4-Asp299Gly and -Thr399Ile gene polymorphisms and the presence or the severity of CAD was observed. On the other hand, the TLR2-Arg753Arg genotype seemed to have a protective effect against development of CAD (OR=0.17; 95% CI=0.04-0.83). Our findings suggest that TLR2-Arg753Gly polymorphism is associated with CAD susceptibility in Turkish patients. PMID:25542811

  18. Effects of omeprazole and genetic polymorphism of CYP2C19 on the clopidogrel active metabolite.

    PubMed

    Boulenc, Xavier; Djebli, Nassim; Shi, Juan; Perrin, Laurent; Brian, William; Van Horn, Robert; Hurbin, Fabrice

    2012-01-01

    Clopidogrel is an antiplatelet agent widely used in cardiovascular diseases and an inactive prodrug that needs to be converted to an active metabolite in two sequential metabolic steps. Several CYP450 isoforms involved in these two steps have been described, although the relative contribution in vivo of each enzyme is still under debate. CYP2C19 is considered to be the major contributor to active metabolite formation. In the current study, net CYP2C19 contribution to the active metabolite formation was determined from exposure of the active metabolite in two clinical studies (one phase I study with well balanced genetic polymorphic populations and a meta-analysis with a total of 396 healthy volunteers) at different clopidogrel doses. CYP2C19 involvements were estimated to be from 58 to 67% in intermediate metabolizers (IMs), from 58 to 72% in extensive metabolizers (EMs), and from 56 to 74% in ultrarapid metabolizers (UMs), depending on the study and the dose. For this purpose, a static model was proposed to estimate the net contribution of a given enzyme to the secondary metabolite formation. This static model was compared with a dynamic approach (Simcyp model) and showed good consistency. In parallel, in vitro investigations showed that omeprazole is a mechanism-based inhibitor of CYP2C19 with K(I) of 8.56 ?M and K(inact) of 0.156 min(-1). These values were combined with the net CYP2C19 contribution to the active metabolite formation, through a static approach, to predict the inhibitory effect at 80-mg omeprazole doses in EM, IM, and UM CYP2C19 populations, with good consistency, compared with observed clinical values. PMID:22004687

  19. Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia.

    PubMed

    Bruzzoni-Giovanelli, Heriberto; Gonzlez, Juan R; Sigaux, Franois; Villoutreix, Bruno O; Cayuela, Jean Michel; Guilhot, Jolle; Preudhomme, Claude; Guilhot, Franois; Poyet, Jean-Luc; Rousselot, Philippe

    2015-11-01

    Little is known about inherited factors associated with the risk of developing chronic myelogenous leukemia (CML). We used a dedicated DNA chip containing 16 561 single nucleotide polymorphisms (SNPs) covering 1 916 candidate genes to analyze 437 CML patients and 1 144 healthy control individuals. Single SNP association analysis identified 139 SNPs that passed multiple comparisons (1% false discovery rate). The HDAC9, AVEN, SEMA3C, IKBKB, GSTA3, RIPK1 and FGF2 genes were each represented by three SNPs, the PSM family by four SNPs and the SLC15A1 gene by six. Haplotype analysis showed that certain combinations of rare alleles of these genes increased the risk of developing CML by more than two or three-fold. A classification tree model identified five SNPs belonging to the genes PSMB10, TNFRSF10D, PSMB2, PPARD and CYP26B1, which were associated with CML predisposition. A CML-risk-allele score was created using these five SNPs. This score was accurate for discriminating CML status (AUC: 0.61, 95%CI: 0.58-0.64). Interestingly, the score was associated with age at diagnosis and the average number of risk alleles was significantly higher in younger patients. The risk-allele score showed the same distribution in the general population (HapMap CEU samples) as in our control individuals and was associated with differential gene expression patterns of two genes (VAPA and TDRKH). In conclusion, we describe haplotypes and a genetic score that are significantly associated with a predisposition to develop CML. The SNPs identified will also serve to drive fundamental research on the putative role of these genes in CML development. PMID:26474455

  20. Genetic polymorphisms in 85 DNA repair genes and bladder cancer risk.

    PubMed

    Michiels, Stefan; Laplanche, Agns; Boulet, Thomas; Dessen, Philippe; Guillonneau, Bertrand; Mjean, Arnaud; Desgrandchamps, Franois; Lathrop, Mark; Sarasin, Alain; Benhamou, Simone

    2009-05-01

    Several defense mechanisms have been developed and maintained during the evolution to protect human cells against damage produced from exogenous or endogenous sources. We examined the associations between bladder cancer and a panel of 652 polymorphisms from 85 genes involved in maintenance of genetic stability [base excision repair, nucleotide excision repair, double-strand break repair (DSBR) and mismatch repair, as well as DNA synthesis and cell cycle regulation pathways] in 201 incident bladder cancer cases and 326 hospital controls. Score statistics were used to test differences in haplotype frequencies between cases and controls in an unconditional logistic regression model. To account for multiple testing, we associated to each P-value the expected proportion of false discoveries (q-value). Haplotype analysis revealed significant associations (P < 0.01) between bladder cancer and two genes (POLB and FANCA) with an associated q-value of 24%. A permutation test was also used to determine whether, in each pathway analyzed, there are more variants whose allelic frequencies are different between cases and controls as compared with what would be expected by chance. Differences were found for cell cycle regulation (P = 0.02) and to a lesser extent for DSBR (P = 0.05) pathways. These results hint to a few potential candidate genes; however, our study was limited by the small sample size and therefore low statistical power to detect associations. It is anticipated that genome-wide association studies will open new perspectives for interpretation of the results of extensive candidate gene studies such as ours. PMID:19237606

  1. Visfatin expression and genetic polymorphism in patients with traumatic brain injury

    PubMed Central

    Xiao, Hong; Cheng, Ming; Zhang, Li-Jun; Liu, Ke

    2015-01-01

    Objective: To discover the expression of visfatin and its genetic mutation and clinical significance in patients with traumatic brain injury. Methods: 99 cases of traumatic brain injury patients admitted to Chongqing Emergency Medical Center from June 2013 to December 2014. There were 56 male and 43 female with an average age of 45.2 years. Through diagnosis, the 99 patients conditions were all relatively in accordance with traumatic brain injury standard; meanwhile, the patients were divided into mild, moderate and severe traumatic brain injury according to GCS criteria when they admitted to clinics. 33 people were enrolled in each group. To highlight the results, 40 healthy people were enrolled in the control group with 25 males and 15 females. ELISA was used to detect serum visfatin level in 99 patients. Single base extension was used to detect visfatin gene promoter -1535C/T polymorphism. Results: By examination we found that visfatin gene -1535C > T locus had three genotypes: TT, TC and CC, respectively. By examination we obtained that genotype distribution and allele frequency showed no significance between the experimental group and the control group (P > 0.05). Through analysis we can get that serum visfatin level in patients with traumatic brain injury was significantly higher than that in the control group. CC genotype are mostly patients with severe traumatic brain injury, and its serum visfatin level was higher than that with CT and TT genotype (all P < 0.05). CT and TT genotype carriers were most mild and moderate traumatic brain injury patients. Conclusion: Expression of visfatin and its gene mutation in patients with traumatic brain injury were closely related to the severity of the disease. PMID:26309659

  2. Genetic Dissection of New Genotypes of Drumstick Tree (Moringa oleifera Lam.) Using Random Amplified Polymorphic DNA Marker

    PubMed Central

    Rufai, Shamsuddeen; Hanafi, M. M.; Rafii, M. Y.; Ahmad, S.; Arolu, I. W.; Ferdous, Jannatul

    2013-01-01

    The knowledge of genetic diversity of tree crop is very important for breeding and improvement program for the purpose of improving the yield and quality of its produce. Genetic diversity study and analysis of genetic relationship among 20 Moringa oleifera were carried out with the aid of twelve primers from, random amplified polymorphic DNA marker. The seeds of twenty M. oleifera genotypes from various origins were collected and germinated and raised in nursery before transplanting to the field at University Agricultural Park (TPU). Genetic diversity parameter, such as Shannon's information index and expected heterozygosity, revealed the presence of high genetic divergence with value of 1.80 and 0.13 for Malaysian population and 0.30 and 0.19 for the international population, respectively. Mean of Nei's gene diversity index for the two populations was estimated to be 0.20. In addition, a dendrogram constructed, using UPGMA cluster analysis based on Nei's genetic distance, grouped the twenty M. oleifera into five distinct clusters. The study revealed a great extent of variation which is essential for successful breeding and improvement program. From this study, M. oleifera genotypes of wide genetic origin, such as T-01, T-06, M-01, and M-02, are recommended to be used as parent in future breeding program. PMID:23862149

  3. Identification of Pyrus Single Nucleotide Polymorphisms (SNPs) and Evaluation for Genetic Mapping in European Pear and Interspecific Pyrus Hybrids

    PubMed Central

    Troggio, Michela; Malnoy, Mickael; Velasco, Riccardo; Fontana, Paolo; Won, KyungHo; Durel, Charles-Eric; Perchepied, Laure; Schaffer, Robert; Wiedow, Claudia; Bus, Vincent; Brewer, Lester; Gardiner, Susan E.; Crowhurst, Ross N.; Chagn, David

    2013-01-01

    We have used new generation sequencing (NGS) technologies to identify single nucleotide polymorphism (SNP) markers from three European pear (Pyrus communis L.) cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium II 8K array. We then evaluated this apple and pear Infinium II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear (Old HomeבLouise Bon Jersey) and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd.) and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array) were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality. PMID:24155917

  4. avpr1a length polymorphism is not associated with either social or genetic monogamy in free-living prairie voles

    PubMed Central

    Mabry, Karen E.; Streatfeild, Craig A.; Keane, Brian; Solomon, Nancy G.

    2010-01-01

    Recent discoveries of single-gene influences on social behaviour have generated a great deal of interest in the proximate mechanisms underlying the expression of complex behaviours. Length polymorphism in a microsatellite in the regulatory region of the gene encoding the vasopressin 1a receptor (avpr1a) has been associated with both inter- and intra-specific variation in socially monogamous behaviour in voles (genus Microtus) under laboratory conditions. Here, we evaluate the relationship between avpr1a length polymorphism and social associations, genetic monogamy, and reproductive success in free-living prairie vole (M. ochrogaster) populations. We found no evidence of a relationship between avpr1a microsatellite length and any of our correlates of either social or genetic monogamy in the field. Our results, especially when taken in conjunction with those of recent experimental studies in semi-natural enclosures, suggest that avpr1a polymorphism is unlikely to have been a major influence in the evolution or maintenance of social monogamy in prairie voles under natural conditions. PMID:21442019

  5. Tubulin-based polymorphism (TBP): a new tool, based on functionally relevant sequences, to assess genetic diversity in plant species.

    PubMed

    Bardini, Mauro; Lee, David; Donini, Paolo; Mariani, Anna; Gian, Silvia; Toschi, Marcello; Lowe, Chris; Breviario, Diego

    2004-04-01

    TBP (tubulin-based polymorphism) is a new molecular marker based tool that relies on the presence of intron-specific DNA polymorphisms of the plant beta-tubulin gene family. The multifunctional and essential role of the tubulin proteins is reflected in the conservation of regions within their primary amino acid sequence. The ubiquitous nature of this gene family can be exploited using primers that amplify the first intron of different beta-tubulin isotypes, revealing specific fingerprints. The method is rapid, simple, and reliable and does not require preliminary sequence information of the plant genome of interest. The ability of TBP to discriminate between accessions and species in oilseed rape, coffee, and lotus is shown. In all cases, TBP was able to detect specific genetic polymorphisms in the context of a simplified and readily appreciable pattern of DNA amplification. The application of TBP for assessing genetic diversity and genome origins in disseminated plant landraces rather than in highly inbred cultivated species is also discussed. PMID:15060580

  6. Effect of GSTM1 and GSTT1 Polymorphisms on Genetic Damage in Humans Populations Exposed to Radiation From Mobile Towers.

    PubMed

    Gulati, Sachin; Yadav, Anita; Kumar, Neeraj; Kanupriya; Aggarwal, Neeraj K; Kumar, Rajesh; Gupta, Ranjan

    2016-04-01

    All over the world, people have been debating about associated health risks due to radiation from mobile phones and mobile towers. The carcinogenicity of this nonionizing radiation has been the greatest health concern associated with mobile towers exposure until recently. The objective of our study was to evaluate the genetic damage caused by radiation from mobile towers and to find an association between genetic polymorphism of GSTM1 and GSTT1 genes and DNA damage. In our study, 116 persons exposed to radiation from mobile towers and 106 control subjects were genotyped for polymorphisms in the GSTM1 and GSTT1 genes by multiplex polymerase chain reaction method. DNA damage in peripheral blood lymphocytes was determined using alkaline comet assay in terms of tail moment (TM) value and micronucleus assay in buccal cells (BMN). There was a significant increase in BMN frequency and TM value in exposed subjects (3.65 ± 2.44 and 6.63 ± 2.32) compared with control subjects (1.23 ± 0.97 and 0.26 ± 0.27). However, there was no association of GSTM1 and GSTT1 polymorphisms with the level of DNA damage in both exposed and control groups. PMID:26238667

  7. Patterns of differentiation in a colour polymorphism and in neutral markers reveal rapid genetic changes in natural damselfly populations.

    PubMed

    Abbott, J K; Bensch, S; Gosden, T P; Svensson, E I

    2008-03-01

    The existence and mode of selection operating on heritable adaptive traits can be inferred by comparing population differentiation in neutral genetic variation between populations (often using F(ST) values) with the corresponding estimates for adaptive traits. Such comparisons indicate if selection acts in a diversifying way between populations, in which case differentiation in selected traits is expected to exceed differentiation in neutral markers [F(ST )(selected) > F(ST )(neutral)], or if negative frequency-dependent selection maintains genetic polymorphisms and pulls populations towards a common stable equilibrium [F(ST) (selected) < F(ST) (neutral)]. Here, we compared F(ST) values for putatively neutral data (obtained using amplified fragment length polymorphism) with estimates of differentiation in morph frequencies in the colour-polymorphic damselfly Ischnura elegans. We found that in the first year (2000), population differentiation in morph frequencies was significantly greater than differentiation in neutral loci, while in 2002 (only 2 years and 2 generations later), population differentiation in morph frequencies had decreased to a level significantly lower than differentiation in neutral loci. Genetic drift as an explanation for population differentiation in morph frequencies could thus be rejected in both years. These results indicate that the type and/or strength of selection on morph frequencies in this system can change substantially between years. We suggest that an approach to a common equilibrium morph frequency across all populations, driven by negative frequency-dependent selection, is the cause of these temporal changes. We conclude that inferences about selection obtained by comparing F(ST) values from neutral and adaptive genetic variation are most useful when spatial and temporal data are available from several populations and time points and when such information is combined with other ecological sources of data. PMID:18284565

  8. Morph-specific genetic and environmental variation in innate and acquired immune response in a color polymorphic raptor.

    PubMed

    Gangoso, Laura; Roulin, Alexandre; Ducrest, Anne-Lyse; Grande, Juan Manuel; Figuerola, Jordi

    2015-08-01

    Genetic color polymorphism is widespread in nature. There is an increasing interest in understanding the adaptive value of heritable color variation and trade-off resolution by differently colored individuals. Melanin-based pigmentation is often associated with variation in many different life history traits. These associations have recently been suggested to be the outcome of pleiotropic effects of the melanocortin system. Although pharmacological research supports that MC1R, a gene with a major role in vertebrate pigmentation, has important immunomodulatory effects, evidence regarding pleiotropy at MC1R in natural populations is still under debate. We experimentally assessed whether MC1R-based pigmentation covaries with both inflammatory and humoral immune responses in the color polymorphic Eleonora's falcon. By means of a cross-fostering experiment, we disentangled potential genetic effects from environmental effects on the covariation between coloration and immunity. Variation in both immune responses was primarily due to genetic factors via the nestlings' MC1R-related color genotype/phenotype, although environmental effects via the color morph of the foster father also had an influence. Overall, dark nestlings had lower immune responses than pale ones. The effect of the color morph of the foster father was also high, but in the opposite direction, and nestlings raised by dark eumelanic foster fathers had higher immune responses than those raised by pale foster fathers. Although we cannot completely discard alternative explanations, our results suggest that MC1R might influence immunity in this species. Morph-specific variation in immunity as well as pathogen pressure may therefore contribute to the long-term maintenance of genetic color polymorphism in natural populations. PMID:25834999

  9. Genetic polymorphism of estrogen receptor alpha gene in Egyptian women with type II diabetes mellitus

    PubMed Central

    Motawi, Tarek M.K.; El-Rehany, Mahmoud A.; Rizk, Sherine M.; Ramzy, Maggie M.; el-Roby, Doaa M.

    2015-01-01

    Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha gene including the XbaI and PvuII restriction enzyme polymorphisms. The aim of this study was to determine if ESRα gene polymorphisms are associated with type 2 diabetes mellitus and correlated with lipid profile. Ninety diabetic Egyptian patients were compared with forty healthy controls. ESRα genotyping of PvuII and XbaI was performed using restriction fragment length polymorphism analysis. Our study showed that there is more significant difference in the frequency of C and G polymorphic allele between patients and control groups in PvuII and XbaI respectively. Also carriers of minor C and G alleles of PvuII and XbaI gene polymorphisms were associated with increased fasting blood glucose and disturbance in lipid profile as there is an increase in total cholesterol, triglycerides and Low density lipoprotein. So findings of present study suggest the possibility that PvuII and XbaI polymorphisms in ERα are related to T2DM and with increased serum lipids among Egyptian population. PMID:26401488

  10. Single-Nucleotide Polymorphism Markers from De-Novo Assembly of the Pomegranate Transcriptome Reveal Germplasm Genetic Diversity

    PubMed Central

    Ophir, Ron; Sherman, Amir; Rubinstein, Mor; Eshed, Ravit; Sharabi Schwager, Michal; Harel-Beja, Rotem; Bar-Ya'akov, Irit; Holland, Doron

    2014-01-01

    Pomegranate is a valuable crop that is grown commercially in many parts of the world. Wild species have been reported from India, Turkmenistan and Socotra. Pomegranate fruit has a variety of health-beneficial qualities. However, despite this crop's importance, only moderate effort has been invested in studying its biochemical or physiological properties or in establishing genomic and genetic infrastructures. In this study, we reconstructed a transcriptome from two phenotypically different accessions using 454-GS-FLX Titanium technology. These data were used to explore the functional annotation of 45,187 fully annotated contigs. We further compiled a genetic-variation resource of 7,155 simple-sequence repeats (SSRs) and 6,500 single-nucleotide polymorphisms (SNPs). A subset of 480 SNPs was sampled to investigate the genetic structure of the broad pomegranate germplasm collection at the Agricultural Research Organization (ARO), which includes accessions from different geographical areas worldwide. This subset of SNPs was found to be polymorphic, with 10.7% loci with minor allele frequencies of (MAF<0.05). These SNPs were successfully used to classify the ARO pomegranate collection into two major groups of accessions: one from India, China and Iran, composed of mainly unknown country origin and which was more of an admixture than the other major group, composed of accessions mainly from the Mediterranean basin, Central Asia and California. This study establishes a high-throughput transcriptome and genetic-marker infrastructure. Moreover, it sheds new light on the genetic interrelations between pomegranate species worldwide and more accurately defines their genetic nature. PMID:24558460

  11. Plasmodium falciparum Na+/H+ Exchanger (pfnhe-1) Genetic Polymorphism in Indian Ocean Malaria-Endemic Areas

    PubMed Central

    Andriantsoanirina, Valrie; Khim, Nimol; Ratsimbasoa, Arsene; Witkowski, Benoit; Benedet, Christophe; Canier, Lydie; Bouchier, Christiane; Tichit, Magali; Durand, Rmy; Mnard, Didier

    2013-01-01

    To date, 11 studies conducted in different countries to test the association between Plasmodium falciparum Na+/H+ exchanger gene (pfnhe-1; PF13_0019) polymorphisms and in vitro susceptibility to quinine have generated conflicting data. In this context and to extend our knowledge of the genetic polymorphism of Pfnhe gene, we have sequenced the ms4760 locus from 595 isolates collected in the Comoros (N = 250; an area with a high prevalence of chloroquine and sulfadoxine-pyrimethamine resistance) and Madagascar (N = 345; a low drug-resistance area). Among them, 29 different alleles were observed, including 8 (27%) alleles not previously described. Isolates from the Comoros showed more repeats in block II (DNNND), which some studies have found to be positively associated with in vitro resistance to quinine, compared with isolates from Madagascar. Additional studies are required to better define the mechanisms underlying quinine resistance, which involve multiple gene interactions. PMID:23208889

  12. Association of TCF7L2 Genetic Polymorphisms with Type 2 Diabetes Mellitus in the Uygur Population of China

    PubMed Central

    Yao, Hua; Wang, Zhiqiang; Wang, Tingting; Ma, Yan; Su, Yinxia; Ma, Qi; Wang, Li; Zhu, Jun

    2015-01-01

    Background: Genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene have been reported to be strongly associated with type 2 diabetes mellitus (T2DM) in Icelandic, Danish and American populations and further replicated in other European populations, African Americans, Mexican Americans, and Asian populations. The aim of the present study was to investigate the association of TCF7L2 gene polymorphisms with T2DM in a Uygur population of China. Methods: 877 T2DM patients and 871 controls were selected for the present study. Two single nucleotide polymorphisms (SNPs) (rs12255372 and rs7901695) were genotyped by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The associations of SNPs and haplotypes with T2DM and linkage disequilibrium (LD) structure of the TCF7L2 gene were analyzed. Results: For total participants and male, the distribution of rs12255372 alleles and the dominant model (Guanine Guanine (GG) genotype vs. Guanine Thymine (GT) genotype + Thymine Thymine (TT) genotype) showed significant difference between T2DM and control subjects (for allele: p = 0.013 and p = 0.002, respectively; for dominant model: p = 0.028 and p = 0.008, respectively). The distribution of rs7901695 alleles and the dominant model (TT genotype vs. Thymine Cytosine (TC) genotype + Cytosine Cytosine (CC) genotype) for total participants and male showed significant difference between T2DM and control subjects (for allele: both p = 0.001; for dominant model: p = 0.006 and p = 0.008, respectively). Conclusions: Our data suggested that the genetic polymorphisms of the TCF7L2 gene were associated with T2DM in the Uygur population of China. PMID:26393635

  13. Genetic polymorphisms of inflammatory response gene TNF-? and its influence on sporadic pancreatic neuroendocrine tumors predisposition risk.

    PubMed

    Karakaxas, Dimitrios; Gazouli, Maria; Coker, Ahmet; Agalianos, Christos; Papanikolaou, Ioannis S; Patapis, Pavlos; Liakakos, Theodoros; Dervenis, Christos

    2014-10-01

    The diagnosed incidence of pancreatic neuroendocrine tumors (pNETs) is increasing; however, their etiology remains poorly understood. PNETs are a rare, heterogeneous group of tumors arising from the endocrine cells of the pancreas, and genetic risk factors for sporadic pNETs are inadequately understood. It is known that pNETs secrete biogenic amines, hormones and growth factors, tumor necrosis factor-a (TNF-?) being one of them. Furthermore, cytokines and other proinflammatory mediators have been implicated in inflammatory pancreatic diseases including pancreatitis and cancer. The aim of our study was to analyze TNF-? promoter gene polymorphisms as risk factors for pNETs using germline DNA collected in a population-based case-control study of pancreatic cancer [42 pNET cases, 78 pancreatic ductal adenocarcinoma (PDAC) cases, 17 intraductal papillary mucinous neoplasm (IPMN) and 98 healthy controls] conducted in the Athens, Greece and Izmir, Turkey areas. For subsequent analysis, we excluded cases and controls with known genetic syndromes. The CC genotype at the -1031 position was more frequent in pNET and IPMN patients (p=0.0002 and p=0.009, respectively), suggesting its possible role in pNET development. Furthermore, the AA genotype at the -308 position was overrepresented in IPMN cases (p=0.03), and AA genotype at the -238 position was more frequent in PDAC cases (p=0.03) compared to healthy individuals. With regard to tumor characteristics, no statistically significant association was detected. Our findings suggest the putative role of TNF-? -1031 polymorphism in the development of pNET and IPMN, whereas the -308 polymorphism seems to be overrepresented among IPMN cases and -238 polymorphism among PDAC cases. PMID:25213764

  14. p53 Codon 72 Genetic Polymorphism in Asthmatic Children: Evidence of Interaction With Acid Phosphatase Locus 1

    PubMed Central

    Verrotti, Alberto; Giannini, Cosimo; Verini, Marcello; Chiarelli, Francesco; Neri, Anna; Magrini, Andrea

    2014-01-01

    Several lines of evidence are implicating an increased persistence of apoptotic cells in patients with asthma. This is largely due to a combination of inhibition, or defects in the apoptotic process and/or impaired apoptotic cell removal mechanisms. Among apoptosis-inducing genes, an important role is played by p53. In the present study, we have investigated the possible relationship between p53 codon 72 polymorphism and asthma and the interaction with ACP1, a genetic polymorphism involved in the susceptibility to allergic asthma. We studied 125 asthmatic children and 123 healthy subjects from the Caucasian population of Central Italy. p53 codon 72 and ACP1 polymorphisms were evaluated using a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method. There is a statistically significant association between p53 codon 72 polymorphism and allergic asthma: Arg/Arg genotype is more represented in asthmatic patients than in controls (P=0.018). This association, however, is present in subjects with low ACP1 activity A/A and A/B only (P=0.023). The proportion of children with A/A and A/B genotype carrying Arg/Arg genotype is significantly high in asthmatic children than in controls (OR=1.941; 95% C.I. 1.042-3.628). Our finding could have important clinical implications since the subjects with A/A and A/B genotypes of ACP1 carrying Arg/Arg genotype are more susceptible to allergic asthma than Pro/Pro genotype. PMID:24843801

  15. Association of Symptoms and Severity of Rift Valley Fever with Genetic Polymorphisms in Human Innate Immune Pathways

    PubMed Central

    Hise, Amy G.; Traylor, Zachary; Hall, Noémi B.; Sutherland, Laura J.; Dahir, Saidi; Ermler, Megan E.; Muiruri, Samuel; Muchiri, Eric M.; Kazura, James W.; LaBeaud, A. Desirée; King, Charles H.; Stein, Catherine M.

    2015-01-01

    Background Multiple recent outbreaks of Rift Valley Fever (RVF) in Africa, Madagascar, and the Arabian Peninsula have resulted in significant morbidity, mortality, and financial loss due to related livestock epizootics. Presentation of human RVF varies from mild febrile illness to meningoencephalitis, hemorrhagic diathesis, and/or ophthalmitis with residual retinal scarring, but the determinants for severe disease are not understood. The aim of the present study was to identify human genes associated with RVF clinical disease in a high-risk population in Northeastern Province, Kenya. Methodology/Principal Findings We conducted a cross-sectional survey among residents (N = 1,080; 1–85 yrs) in 6 villages in the Sangailu Division of Ijara District. Participants completed questionnaires on past symptoms and exposures, physical exam, vision testing, and blood collection. Single nucleotide polymorphism (SNP) genotyping was performed on a subset of individuals who reported past clinical symptoms consistent with RVF and unrelated subjects. Four symptom clusters were defined: meningoencephalitis, hemorrhagic fever, eye disease, and RVF-not otherwise specified. SNPs in 46 viral sensing and response genes were investigated. Association was analyzed between SNP genotype, serology and RVF symptom clusters. The meningoencephalitis symptom phenotype cluster among seropositive patients was associated with polymorphisms in DDX58/RIG-I and TLR8. Having three or more RVF-related symptoms was significantly associated with polymorphisms in TICAM1/TRIF, MAVS, IFNAR1 and DDX58/RIG-I. SNPs significantly associated with eye disease included three different polymorphisms TLR8 and hemorrhagic fever symptoms associated with TLR3, TLR7, TLR8 and MyD88. Conclusions/Significance Of the 46 SNPs tested, TLR3, TLR7, TLR8, MyD88, TRIF, MAVS, and RIG-I were repeatedly associated with severe symptomatology, suggesting that these genes may have a robust association with RVFV-associated clinical outcomes. Studies of these and related genetic polymorphisms are warranted to advance understanding of RVF pathogenesis. PMID:25756647

  16. Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population

    PubMed Central

    Ban, Yoshiyuki; Taniyama, Matsuo; Yanagawa, Tatsuo; Yamada, Satoru; Maruyama, Taro; Kasuga, Akira; Ban, Yoshio

    2001-01-01

    Background Vitamin D has been shown to exert manifold immunomodulatory effects. Type 1 diabetes mellitus (T1DM) is regarded to be immune-mediated and vitamin D prevents the development of diabetes in the NOD mouse. We studied the association between T1DM and the initiation codon polymorphism in exon 2 of the vitamin D receptor gene in a Japanese population. We also investigated associations between the vitamin D receptor polymorphism and GAD65-antibody (Ab) positivity. We carried out polymerase chain reaction-restriction fragment length polymorphism analysis in 110 Japanese T1DM patients and 250 control subjects. GAD65 antibodies were assessed in 78 patients with T1DM. Results We found a significantly higher prevalence of the F allele / the FF genotype in the patients compared to the controls (P = 0.0069 and P = 0.014, respectively). Genotype and allele frequencies differed significantly between GAD65-Ab-positive patients and controls (P = 0.017 and P = 0.012, respectively), but neither between GAD65-Ab-negative patients and controls (P = 0.68 and P = 0.66, respectively) nor between GAD65-Ab-positive and -negative patients (P = 0.19 and P = 0.16, respectively). Conclusions Our findings suggest that the vitamin D receptor initiation codon polymorphism influences genetic susceptibility to T1DM among the Japanese. This polymorphism is also associated with GAD65-Ab-positive T1DM, although the absence of a significant difference between GAD65-Ab-negative patients and controls might be simply due to the small sample size of patients tested for GAD65 antibodies. PMID:11445000

  17. CHARLOTTE HARBOR IR, 2002

    EPA Science Inventory

    The 2002 Charlotte Harbor Implementation Review (IR) summarizes the progress and challenges ahead for the Charlotte Harbor National Estuary Program (CHNEP). The implementation review report requires seven components: Status of CCMP implementation (programmatic progress); Environm...

  18. HLA-DR polymorphism in a Senegalese Mandenka population: DNA oligotyping and population genetics of DRB1 specificities.

    PubMed Central

    Tiercy, J M; Sanchez-Mazas, A; Excoffier, L; Shi-Isaac, X; Jeannet, M; Mach, B; Langaney, A

    1992-01-01

    HLA class II loci are useful markers in human population genetics, because they are extremely variable and because new molecular techniques allow large-scale analysis of DNA allele frequencies. Direct DNA typing by hybridization with sequence-specific oligonucleotide probes (HLA oligotyping) after enzymatic in vitro PCR amplification detects HLA allelic polymorphisms for all class II loci. A detailed HLA-DR oligotyping analysis of 191 individuals from a geographically, culturally, and genetically well-defined western African population, the Mandenkalu, reveals a high degree of polymorphism, with at least 24 alleles and a heterozygosity level of .884 for the DRB1 locus. The allele DRB1*1304, defined by DNA sequencing of the DRB1 first-domain exon, is the most frequent allele (27.1%). It accounts for an unusually high DR13 frequency, which is nevertheless within the neutral frequency range. The next most frequent specificities are DR11, DR3, and DR8. Among DRB3-encoded alleles, DR52b (DRB3*02) represents as much as 80.7% of all DR52 haplotypes. A survey of HLA-DR specificities in populations from different continents shows a significant positive correlation between genetic and geographic differentiation patterns. A homozygosity test for selective neutrality of DR specificities is not significant for the Mandenka population but is rejected for 20 of 24 populations. Observed high heterozygosity levels in tested populations are compatible with an overdominant model with a small selective advantage for heterozygotes. PMID:1496990

  19. Genetic Polymorphism and Molecular Epidemiology of Leishmania (Viannia) braziliensis from Different Hosts and Geographic Areas in Brazil

    PubMed Central

    Cupolillo, Elisa; Brahim, Lcia Regina; Toaldo, Cristiane B.; de Oliveira-Neto, Manoel Paes; de Brito, Maria Edileuza Felinto; Falqueto, Aloisio; de Farias Naiff, Maricleide; GrimaldiJr., Gabriel

    2003-01-01

    Numerical zymotaxonomy and variability of the internal transcribed spacers (ITS) between the small and large subunits of the rRNA genes were used to examine strain variation and relationships in natural populations of Leishmania (Viannia) braziliensis. A total of 101 strains from distinct hosts and Brazilian geographic regions were assigned to 15 zymodemes clustered in two major genetic groups. The great number of isolates (48.5%) placed in zymodeme IOC/Z-27 were collected on the Atlantic coast. The high molecular diversity found in populations in the Amazon Basin was related to the great number of sandfly vector(s) in that region. The results of the restriction fragment length polymorphism analysis of the ITS depicted considerable intraspecific variation. Genotypic groups A, B, and C contained 39, 40, and 22 isolates, which were divided into 16, 10, and 15 genotypes, respectively. The genetic polymorphism observed demonstrates the degree of diversity of L. (V.) braziliensis strains from different regions where they are endemic. The results reinforce the clonal theory for Leishmania parasites showing the genetic diversity of this pathogen and an association of L. (V.) braziliensis genotypes with specific transmission cycles, probably reflecting an adaptation of different clones to the vector species involved. PMID:12843052

  20. First Insights into the Genetic Diversity of the Pinewood Nematode in Its Native Area Using New Polymorphic Microsatellite Loci

    PubMed Central

    Mallez, Sophie; Castagnone, Chantal; Espada, Margarida; Vieira, Paulo; Eisenback, Jonathan D.; Mota, Manuel; Guillemaud, Thomas; Castagnone-Sereno, Philippe

    2013-01-01

    The pinewood nematode, Bursaphelenchus xylophilus, native to North America, is the causative agent of pine wilt disease and among the most important invasive forest pests in the East-Asian countries, such as Japan and China. Since 1999, it has been found in Europe in the Iberian Peninsula, where it also causes significant damage. In a previous study, 94 pairs of microsatellite primers have been identified in silico in the pinewood nematode genome. In the present study, specific PCR amplifications and polymorphism tests to validate these loci were performed and 17 microsatellite loci that were suitable for routine analysis of B. xylophilus genetic diversity were selected. The polymorphism of these markers was evaluated on nematodes from four field origins and one laboratory collection strain, all originate from the native area. The number of alleles and the expected heterozygosity varied between 2 and 11 and between 0.039 and 0.777, respectively. First insights into the population genetic structure of B. xylophilus were obtained using clustering and multivariate methods on the genotypes obtained from the field samples. The results showed that the pinewood nematode genetic diversity is spatially structured at the scale of the pine tree and probably at larger scales. The role of dispersal by the insect vector versus human activities in shaping this structure is discussed. PMID:23554990

  1. First insights into the genetic diversity of the pinewood nematode in its native area using new polymorphic microsatellite loci.

    PubMed

    Mallez, Sophie; Castagnone, Chantal; Espada, Margarida; Vieira, Paulo; Eisenback, Jonathan D; Mota, Manuel; Guillemaud, Thomas; Castagnone-Sereno, Philippe

    2013-01-01

    The pinewood nematode, Bursaphelenchus xylophilus, native to North America, is the causative agent of pine wilt disease and among the most important invasive forest pests in the East-Asian countries, such as Japan and China. Since 1999, it has been found in Europe in the Iberian Peninsula, where it also causes significant damage. In a previous study, 94 pairs of microsatellite primers have been identified in silico in the pinewood nematode genome. In the present study, specific PCR amplifications and polymorphism tests to validate these loci were performed and 17 microsatellite loci that were suitable for routine analysis of B. xylophilus genetic diversity were selected. The polymorphism of these markers was evaluated on nematodes from four field origins and one laboratory collection strain, all originate from the native area. The number of alleles and the expected heterozygosity varied between 2 and 11 and between 0.039 and 0.777, respectively. First insights into the population genetic structure of B. xylophilus were obtained using clustering and multivariate methods on the genotypes obtained from the field samples. The results showed that the pinewood nematode genetic diversity is spatially structured at the scale of the pine tree and probably at larger scales. The role of dispersal by the insect vector versus human activities in shaping this structure is discussed. PMID:23554990

  2. Genetic polymorphism and molecular epidemiology of Leishmania (Viannia) braziliensis from different hosts and geographic areas in Brazil.

    PubMed

    Cupolillo, Elisa; Brahim, Lcia Regina; Toaldo, Cristiane B; de Oliveira-Neto, Manoel Paes; de Brito, Maria Edileuza Felinto; Falqueto, Aloisio; de Farias Naiff, Maricleide; Grimaldi, Gabriel

    2003-07-01

    Numerical zymotaxonomy and variability of the internal transcribed spacers (ITS) between the small and large subunits of the rRNA genes were used to examine strain variation and relationships in natural populations of Leishmania (Viannia) braziliensis. A total of 101 strains from distinct hosts and Brazilian geographic regions were assigned to 15 zymodemes clustered in two major genetic groups. The great number of isolates (48.5%) placed in zymodeme IOC/Z-27 were collected on the Atlantic coast. The high molecular diversity found in populations in the Amazon Basin was related to the great number of sandfly vector(s) in that region. The results of the restriction fragment length polymorphism analysis of the ITS depicted considerable intraspecific variation. Genotypic groups A, B, and C contained 39, 40, and 22 isolates, which were divided into 16, 10, and 15 genotypes, respectively. The genetic polymorphism observed demonstrates the degree of diversity of L. (V.) braziliensis strains from different regions where they are endemic. The results reinforce the clonal theory for Leishmania parasites showing the genetic diversity of this pathogen and an association of L. (V.) braziliensis genotypes with specific transmission cycles, probably reflecting an adaptation of different clones to the vector species involved. PMID:12843052

  3. Genetic polymorphisms in inflammatory response genes and their associations with breast cancer risk

    PubMed Central

    Wang, Zhi; Liu, Qiu-Lian; Sun, Wu; Yang, Chun-Jing; Tang, Lei; Zhang, Xian; Zhong, Xiao-Ming

    2014-01-01

    Aim To explore the association of NFKB1 c.-798_-795delATTG (rs28362491), NFKBIA c.-949C>T (rs2233406), IL-8 c.-352A>T (rs4073), IL-10 c.-854T>C (rs1800871), TNF c.-418G>A (rs361525), and TNF c.-488G>A (rs1800629) polymorphisms with breast cancer risk in an East Chinese population. Methods We conducted a case-control study including 975 study participants (474 breast cancer patients and 501 female controls without cancer) and genotyped the polymorphisms employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was used to assess the association of the polymorphisms with breast cancer risk. Results We found that the ins/del and del/del genotypes of NFKB1 polymorphism and TT genotype of IL-10 polymorphism significantly increased breast cancer risk (NFKB1 ins/del odds ratio [OR] 1.69, 95% [CI] 1.23-2.33, P?=?0.001; NFKB1 del/del OR 2.42, 95% CI 1.72-3.42, P?polymorphism, GA and AA genotypes of TNF c.-418G>A polymorphism, and GA genotype of TNF c.-488G>A polymorphism significantly reduced breast cancer risk (IL-8 TT OR 0.48, 95% CI 0.33-0.72, P?polymorphism significantly reduced the risk among pre-menopausal women (OR 0.63, 95% CI 0.40-0.99, P?=?,043), but not among post-menopausal women. Conclusions NFKB1, NFKBIA, IL-8, IL-10, and TNF polymorphisms could serve as useful predictive biomarkers for breast cancer risk among women in East China. PMID:25559835

  4. Genetic polymorphism at an odorant receptor gene (Or39) among mosquitoes of the Anopheles gambiae complex in Senegal (West Africa)

    PubMed Central

    2014-01-01

    Background Olfaction plays a significant role in insect behavior during critical steps of their life-cycle, such as host-seeking during foraging or the search for a mate. Here, we explored genetic polymorphism within and divergence between sibling species of the African malaria mosquito, Anopheles gambiae sensu lato in the gene sequence and encoded peptides of an odorant receptor, Or39. This study included sympatric specimens of An. gambiae sensu stricto, An. coluzzii and An. arabiensis sampled together in the village of Dielmo, Senegal. Results A 1,601bp genomic sequence composed of 6 exons and 5 introns was obtained for Or39 from 68 mosquitoes in each of the 3 species. DNA sequence analysis revealed a high level of molecular polymorphism (??=?0.0154; Haplotype diversity?=?0.867) and high overall genetic differentiation between taxa (Fst?>?0.92, P?polymorphisms in An. gambiae and An. arabiensis as well as species-specific mutations also occurred in the first extracellular domain. Conclusions Although obtained from a limited number of specimens, our results point towards genetic differences between cryptic species within the An. gambiae complex in a gene of biological relevance that might be of evolutionary significance when exposed to disruptive selective forces. PMID:24886539

  5. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients.

    PubMed

    do Nascimento, Wenna Gleyce Arajo; Cilio, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurcio Galvo; Donadi, Eduardo Antnio; de Oliveira Crispim, Janaina Cristiana

    2014-06-01

    Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45-4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients. PMID:25071398

  6. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients

    PubMed Central

    do Nascimento, Wenna Gleyce Arajo; Cilio, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurcio Galvo; Donadi, Eduardo Antnio; de Oliveira Crispim, Janaina Cristiana

    2014-01-01

    Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.454.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients. PMID:25071398

  7. Systems Level Analysis of Systemic Sclerosis Shows a Network of Immune and Profibrotic Pathways Connected with Genetic Polymorphisms

    PubMed Central

    Mahoney, J. Matthew; Taroni, Jaclyn; Martyanov, Viktor; Wood, Tammara A.; Greene, Casey S.; Pioli, Patricia A.; Hinchcliff, Monique E.; Whitfield, Michael L.

    2015-01-01

    Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited) are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6–12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes using a gene-gene interaction network, and place the genetic risk loci in the context of the intrinsic subsets. To identify gene expression modules common to three independent datasets from three different clinical centers, we developed a consensus clustering procedure based on mutual information of partitions, an information theory concept, and performed a meta-analysis of these genome-wide gene expression datasets. We created a gene-gene interaction network of the conserved molecular features across the intrinsic subsets and analyzed their connections with SSc-associated genetic polymorphisms. The network is composed of distinct, but interconnected, components related to interferon activation, M2 macrophages, adaptive immunity, extracellular matrix remodeling, and cell proliferation. The network shows extensive connections between the inflammatory- and fibroproliferative-specific genes. The network also shows connections between these subset-specific genes and 30 SSc-associated polymorphic genes including STAT4, BLK, IRF7, NOTCH4, PLAUR, CSK, IRAK1, and several human leukocyte antigen (HLA) genes. Our analyses suggest that the gene expression changes underlying the SSc subsets may be long-lived, but mechanistically interconnected and related to a patients underlying genetic risk. PMID:25569146

  8. Genetic polymorphisms in the 9p21 region associated with risk of multiple cancers

    PubMed Central

    Li, Wen-Qing; Pfeiffer, Ruth M.; Hyland, Paula L.; Shi, Jianxin; Gu, Fangyi; Wang, Zhaoming; Bhattacharjee, Samsiddhi; Luo, Jun; Yeager, Meredith; Deng, Xiang; Hu, Nan; Taylor, Philip R.; Albanes, Demetrius; Caporaso, Neil E.; Gapstur, Susan M.; Amundadottir, Laufey; Chanock, Stephen J.; Chatterjee, Nilanjan; Landi, Maria Teresa; Tucker, Margaret A.; Goldstein, Alisa M.; Yang, Xiaohong R.

    2014-01-01

    The chromosome 9p21 region has been implicated in the pathogenesis of multiple cancers. We analyzed 9p21 single nucleotide polymorphisms (SNPs) from eight genome-wide association studies (GWAS) with data deposited in dbGaP, including studies of esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), pancreatic cancer, renal cell carcinoma (RCC), lung cancer (LC), breast cancer (BrC), bladder cancer (BC) and prostate cancer (PrC). The number of subjects ranged from 2252 (PrC) to 7619 (LC). SNP-level analyses for each cancer were conducted by logistic regression or random-effects meta-analysis. A subset-based statistical approach (ASSET) was performed to combine SNP-level P values across multiple cancers. We calculated gene-level P values using the adaptive rank truncated product method. We identified that rs1063192 and rs2157719 in the CDKN2A/2B region were significantly associated with ESCC and rs2764736 (3? of TUSC1) was associated with BC (P ? 2.59 10?6). ASSET analyses identified four SNPs significantly associated with multiple cancers: rs3731239 (CDKN2A intronic) with ESCC, GC and BC (P = 3.96 10? 4); rs10811474 (3? of IFNW1) with RCC and BrC (P = 0.001); rs12683422 (LINGO2 intronic) with RCC and BC (P = 5.93 10? 4) and rs10511729 (3? of ELAVL2) with LC and BrC (P = 8.63 10? 4). At gene level, CDKN2B, CDKN2A and CDKN2B-AS1 were significantly associated with ESCC (P ? 4.70 10? 5). Rs10511729 and rs10811474 were associated with cis-expression of 9p21 genes in corresponding cancer tissues in the expression quantitative trait loci analysis. In conclusion, we identified several genetic variants in the 9p21 region associated with the risk of multiple cancers, suggesting that this region may contribute to a shared susceptibility across different cancer types. PMID:25239644

  9. Genetic polymorphisms in the 9p21 region associated with risk of multiple cancers.

    PubMed

    Li, Wen-Qing; Pfeiffer, Ruth M; Hyland, Paula L; Shi, Jianxin; Gu, Fangyi; Wang, Zhaoming; Bhattacharjee, Samsiddhi; Luo, Jun; Xiong, Xiaoqin; Yeager, Meredith; Deng, Xiang; Hu, Nan; Taylor, Philip R; Albanes, Demetrius; Caporaso, Neil E; Gapstur, Susan M; Amundadottir, Laufey; Chanock, Stephen J; Chatterjee, Nilanjan; Landi, Maria Teresa; Tucker, Margaret A; Goldstein, Alisa M; Yang, Xiaohong R

    2014-12-01

    The chromosome 9p21 region has been implicated in the pathogenesis of multiple cancers. We analyzed 9p21 single nucleotide polymorphisms (SNPs) from eight genome-wide association studies (GWAS) with data deposited in dbGaP, including studies of esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), pancreatic cancer, renal cell carcinoma (RCC), lung cancer (LC), breast cancer (BrC), bladder cancer (BC) and prostate cancer (PrC). The number of subjects ranged from 2252 (PrC) to 7619 (LC). SNP-level analyses for each cancer were conducted by logistic regression or random-effects meta-analysis. A subset-based statistical approach (ASSET) was performed to combine SNP-level P values across multiple cancers. We calculated gene-level P values using the adaptive rank truncated product method. We identified that rs1063192 and rs2157719 in the CDKN2A/2B region were significantly associated with ESCC and rs2764736 (3' of TUSC1) was associated with BC (P ? 2.59 10(-6)). ASSET analyses identified four SNPs significantly associated with multiple cancers: rs3731239 (CDKN2A intronic) with ESCC, GC and BC (P = 3.96 10(-) (4)); rs10811474 (3' of IFNW1) with RCC and BrC (P = 0.001); rs12683422 (LINGO2 intronic) with RCC and BC (P = 5.93 10(-) (4)) and rs10511729 (3' of ELAVL2) with LC and BrC (P = 8.63 10(-) (4)). At gene level, CDKN2B, CDKN2A and CDKN2B-AS1 were significantly associated with ESCC (P ? 4.70 10(-) (5)). Rs10511729 and rs10811474 were associated with cis-expression of 9p21 genes in corresponding cancer tissues in the expression quantitative trait loci analysis. In conclusion, we identified several genetic variants in the 9p21 region associated with the risk of multiple cancers, suggesting that this region may contribute to a shared susceptibility across different cancer types. PMID:25239644

  10. Isolation and characterization by direct amplification of length polymorphisms (DALP) of codominant genetic markers with Mendelian inheritance in Neoseiulus californicus (Acari: Phytoseiidae).

    PubMed

    Perrot-Minno, M J; Lagnel, J; Desmarais, E; Navajas, M

    2000-01-01

    We report the first application of a new method designed to isolate polymorphic loci in any organism, the direct amplification of length polymorphism. Five polymorphic loci were readily isolated in the predatory mite Neoseiulus californicus (Acari: Phytoseiidae). Two to five alleles were identified among 46 isofemale lines based on fragment size variation due to micro-deletions/insertions. Genotyping F1 and F2 progenies from controlled heterogametic crosses and backcrosses allowed to establish the Mendelian inheritance of these alleles, their codominance, and pairwise recombination rates. Nucleotidic sequence divergence due to single base substitution was also found in the flanking regions of the polymorphism. We discuss the usefulness of these markers in studies of reproductive systems as well as population genetics, in particular, in mite species where the amount of DNA or richness in microsatellites could be limiting factors in the isolation of polymorphic loci. PMID:11345316

  11. The Genetic Basis of a Rare Flower Color Polymorphism in Mimulus lewisii Provides Insight into the Repeatability of Evolution

    PubMed Central

    Nutter, Laura I.; Cross, Kaitlyn A.

    2013-01-01

    A long-standing question in evolutionary biology asks whether the genetic changes contributing to phenotypic evolution are predictable. Here, we identify a genetic change associated with segregating variation in flower color within a population of Mimulus lewisii. To determine whether these types of changes are predictable, we combined this information with data from other species to investigate whether the spectrum of mutations affecting flower color transitions differs based on the evolutionary time-scale since divergence. We used classic genetic techniques, along with gene expression and population genetic approaches, to identify the putative, loss-of-function mutation that generates rare, white flowers instead of the common, pink color in M. lewisii. We found that a frameshift mutation in an anthocyanin pathway gene is responsible for the white-flowered polymorphism found in this population of M. lewisii. Comparison of our results with data from other species reveals a broader spectrum of flower color mutations segregating within populations relative to those that fix between populations. These results suggest that the genetic basis of fixed differences in flower color may be predictable, but that for segregating variation is not. PMID:24312531

  12. Genetic structure is correlated with phenotypic divergence rather than geographic isolation in the highly polymorphic strawberry poison-dart frog.

    PubMed

    Wang, Ian J; Summers, Kyle

    2010-02-01

    Phenotypic and genetic divergence can be influenced by a variety of factors, including sexual and natural selection, genetic drift and geographic isolation. Investigating the roles of these factors in natural systems can provide insight into the relative influences of allopatric and ecological modes of biological diversification in nature. The strawberry poison frog, Dendrobates pumilio, presents an excellent opportunity for this kind of research, displaying a diverse array of colour morphs and inhabiting a heterogeneous landscape that includes oceanic islands, fragmented rainforest patches and wide expanses of suitable habitat. In this study, we use 15 highly polymorphic microsatellite loci to estimate population structure and gene flow among populations from across the range of D. pumilio and a causal modelling framework to statistically test 12 hypotheses regarding the geographic and phenotypic variables that explain genetic differentiation within this system. Our results demonstrate that the genetic distance between populations is most strongly associated with differences in dorsal coloration. Previous experimental studies have shown that phenotypic differences can result in sexual and natural selection against non-native phenotypes, and our results now show that these forces lead to genetic isolation between different colour morphs in the wild, presenting a potential case of incipient speciation through selection. PMID:20025652

  13. Methylenetetrahydrofolate reductase genetic polymorphisms and esophageal squamous cell carcinoma susceptibility: A meta-analysis of case-control studies

    PubMed Central

    Shujuan, Yang; Jianxing, Zhang; Xin-yue, Chen

    2013-01-01

    Objectives: Genetic factors and environmental factors play a role in pathogenesis of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the association of folate intake and Methylenetetrahydrofolate reductase C677T polymorphism with ESCC was conflicting. We conducted a meta-analysis to investigate the association of MTHFR C677T and folate intake with esophageal cancer risk. Methodology: MEDLINE, EMBASE and the Chinese Biomedical Database were searched in our study. The quality of studies were evaluated by predefined scale, and The association of polymorphisms of MTHFR C677T and folate intake and ESCC risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs). Results: Nineteen studies (4239 cases and 5575 controls) were included for meta-analysis. A significant association was seen between individuals with MTHFR 677 CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC risk (p<0.05). Low intake of folate had significantly higher risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high intake of folate did not find significant high risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]. Conclusions: Our meta-analysis indicated the folate intake and MTHFR 677CT/TT are associated with the risk of ESCC, and folate showed a significant interaction with polymorphism of MTHFR C677T. PMID:24353609

  14. Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1

    PubMed Central

    2011-01-01

    Background Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been associated with asthma and atopy. We aimed to examine how genetic polymorphisms in innate immunity pathways interact with endotoxin to influence asthma risk in children. Methods In a previous analysis of 372 children from the Boston Home Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG) involved in innate immune pathways were associated with asthma, and 5 SNPs in 3 genes (CD80, STAT4, IRAK2) were associated with eczema. We tested these SNPs for interaction with early life endotoxin exposure (n = 291), in models for asthma and eczema by age 6. Results We found a significant interaction between endotoxin and a SNP (rs156265) in ACAA1 (p = 0.0013 for interaction). Increased endotoxin exposure (by quartile) showed protective effects for asthma in individuals with at least one copy of the minor allele (OR = 0.39 per quartile increase in endotoxin, 95% CI 0.15 to 1.01). Endotoxin exposure did not reduce the risk of asthma in children homozygous for the major allele. Conclusion Our findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1. PMID:22151743

  15. Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1.

    TOXLINE Toxicology Bibliographic Information

    Sordillo JE; Sharma S; Poon A; Lasky-Su J; Belanger K; Milton DK; Bracken MB; Triche EW; Leaderer BP; Gold DR; Litonjua AA

    2011-01-01

    BACKGROUND: Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been associated with asthma and atopy. We aimed to examine how genetic polymorphisms in innate immunity pathways interact with endotoxin to influence asthma risk in children.METHODS: In a previous analysis of 372 children from the Boston Home Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG) involved in innate immune pathways were associated with asthma, and 5 SNPs in 3 genes (CD80, STAT4, IRAK2) were associated with eczema. We tested these SNPs for interaction with early life endotoxin exposure (n = 291), in models for asthma and eczema by age 6.RESULTS: We found a significant interaction between endotoxin and a SNP (rs156265) in ACAA1 (p = 0.0013 for interaction). Increased endotoxin exposure (by quartile) showed protective effects for asthma in individuals with at least one copy of the minor allele (OR = 0.39 per quartile increase in endotoxin, 95% CI 0.15 to 1.01). Endotoxin exposure did not reduce the risk of asthma in children homozygous for the major allele.CONCLUSION: Our findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1.

  16. Genetic polymorphisms of interleukin genes and the risk of Alzheimer's disease: An update meta-analysis

    PubMed Central

    Mun, Myung-Jin; Kim, Jin-Ho; Choi, Ji-Young; Jang, Won-Cheoul

    2016-01-01

    Objectives Recently, several meta-analyses have reported an association between interleukin (IL) gene polymorphisms and the risk of Alzheimer's disease (AD). Several further papers discussing the relationship with the risk of AD have recently been published. The aim of this meta-analysis was to re-evaluate and update the associations between IL gene polymorphisms and the risk of AD. Methods The search sources were PubMed, Science Direct, Scopus, and Google Scholar up to July 2015, and the following search terms were used: “interleukin 1 or interleukin 6 or interleukin 10” and “variant or polymorphism or SNP” in combination with “Alzheimer's disease”. A meta-analysis using the pooled odds ratios and 95% confidence intervals was carried out to assess the associations between four polymorphisms of IL genes (− 889C > T in IL-1α, − 511C > T in IL-1β, − 174G > C in IL-6 and − 1082G > A in IL-10) and the risk of AD under the heterozygous, homozygous, dominant, and recessive models with fixed- or random-effects models. Results A total of 21,864 cases and 40,321 controls from 93 individual studies were included in this meta-analysis. Our results indicated that the − 889C > T polymorphism was strongly associated with the increased risk of AD. However, three polymorphisms were not associated with the risk of AD. Conclusions Similar to previous meta-analyses, our updated meta-analysis suggested that the − 889C > T polymorphism may be a factor in AD. However, the results of our meta-analysis of the − 174G > C polymorphism differed from those of previous meta-analyses. Consequently, we suggest that the − 174G > C polymorphism may not be a risk factor for AD. PMID:27014584

  17. Meta-analysis of association between the genetic polymorphisms on chromosome 11q and Alzheimer's disease susceptibility.

    PubMed

    Ji, Weidong; Xu, Lanling; Zhou, Haiyun; Wang, Suishan; Fang, Yan

    2015-01-01

    Alzheimer's disease (AD) is a neurodegenerative disease mostly occurred in the elderly. Genetic mutation is one of well-established risk factors for AD. Several polymorphisms on chromosome 11q were reported to be associated with AD susceptibility. Hence we performed a meta-analysis to systematically assess the association between the most-reported polymorphisms on chromosome 11q (rs10793294, rs7115850, rs7101429, rs4945261, rs2373115, rs670142, rs610932, rs541458 and rs3851179) and AD risk. A comprehensive literature search in the electronic databases was performed to identify all eligible studies. The pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the association between 11q variants and AD risk by using the allelic model. Sensitivity analysis was carried out to analyze the influence of single study on the overall results. Begg's funnel plots and Egger's test were used to assess the publication biases among studies. All the statistical analyses were conducted by using STATA 12.0 Software (Stata Corp, College Station, TX, USA). A total of 35 eligible articles were included in our meta-analysis. Our data showed that the polymorphism of rs610932 were significantly associated with lower AD risk with a pooled OR of 0.88 (95% CI: 0.84-0.92, P=0.005). The other SNPs of rs494526 (OR=0.83, 95% CI: 0.65-1.00, P<0.001), rs2373115 (OR=0.85, 95% CI: 0.75-0.95, P<0.001) and rs670139 (OR=1.09, 95% CI: 1.05-1.12, P=0.554) were shown to be correlated with lower AD risk. Subgroup analysis revealed a similar result in Caucasians. But only the rs610932 polymorphism was found to be associated with lower AD risk in Asians. The polymorphism of rs610932 was shown to be a risk factor for AD while the other three genetic variants (rs494526, rs2373115 and rs610932) may act as protective factors against AD. PMID:26770425

  18. Meta-analysis of association between the genetic polymorphisms on chromosome 11q and Alzheimers disease susceptibility

    PubMed Central

    Ji, Weidong; Xu, Lanling; Zhou, Haiyun; Wang, Suishan; Fang, Yan

    2015-01-01

    Alzheimers disease (AD) is a neurodegenerative disease mostly occurred in the elderly. Genetic mutation is one of well-established risk factors for AD. Several polymorphisms on chromosome 11q were reported to be associated with AD susceptibility. Hence we performed a meta-analysis to systematically assess the association between the most-reported polymorphisms on chromosome 11q (rs10793294, rs7115850, rs7101429, rs4945261, rs2373115, rs670142, rs610932, rs541458 and rs3851179) and AD risk. A comprehensive literature search in the electronic databases was performed to identify all eligible studies. The pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the association between 11q variants and AD risk by using the allelic model. Sensitivity analysis was carried out to analyze the influence of single study on the overall results. Beggs funnel plots and Eggers test were used to assess the publication biases among studies. All the statistical analyses were conducted by using STATA 12.0 Software (Stata Corp, College Station, TX, USA). A total of 35 eligible articles were included in our meta-analysis. Our data showed that the polymorphism of rs610932 were significantly associated with lower AD risk with a pooled OR of 0.88 (95% CI: 0.84-0.92, P=0.005). The other SNPs of rs494526 (OR=0.83, 95% CI: 0.65-1.00, P<0.001), rs2373115 (OR=0.85, 95% CI: 0.75-0.95, P<0.001) and rs670139 (OR=1.09, 95% CI: 1.05-1.12, P=0.554) were shown to be correlated with lower AD risk. Subgroup analysis revealed a similar result in Caucasians. But only the rs610932 polymorphism was found to be associated with lower AD risk in Asians. The polymorphism of rs610932 was shown to be a risk factor for AD while the other three genetic variants (rs494526, rs2373115 and rs610932) may act as protective factors against AD.

  19. Genetic effects of common polymorphisms in estrogen receptor alpha gene on osteoarthritis: a meta-analysis

    PubMed Central

    Ma, Hecheng; Wu, Weiqian; Yang, Xiaodi; Liu, Jianguo; Gong, Yubao

    2015-01-01

    Objective: The estrogen receptor alpha (ESR1) gene has been implicated in the etiology of osteoarthritis (OA). However, the results are conflicting. We assessed the association of three common ESR1 polymorphisms, rs2234693, rs9340799 and rs2228480, with OA in this meta-analysis. Methods: A comprehensive search was performed to identify related studies. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed or random effects model. Results: 15 studies (7036 cases and 9669 controls) for rs2234693 polymorphism, 14 studies (3904 cases and 6991 controls) for rs9340799 and 3 studies (331 cases and 619 controls) for rs2228480 polymorphism were identified. The final results indicated that the G allele in ESR1 rs9340799 was associated with decreased OA risk (GG+GA vs. AA: OR=0.878, 95% CI=0.792-0.972, P=0.012; G vs. A: OR=0.902, 95% CI=0.836-0.975, P=0.009). The A allele in rs2228480 might be associated with increased OA risk. But no significant association of rs2234693 polymorphism with OA susceptibility was observed. Conclusions: This meta-analysis indicates rs9340799 and rs2228480 rather than rs2234693 polymorphisms are associated with the incidence of OA. Some stable associations should be further confirmed in future. PMID:26550281

  20. ACE insertion/deletion polymorphism and diabetic nephropathy: clinical implications of genetic information.

    PubMed

    Ha, Sung-Kyu

    2014-01-01

    Approximately 20-40% of diabetic patients develop nephropathy which is the leading cause of ESRD in developed countries. The ACE I/D polymorphism is thought to be a marker for functional polymorphism which regulates circulating and tissue ACE activity. While the initial study found a protective effect of the II genotype on the development of nephropathy in IDDM patients, subsequent studies have addressed the role of ACE I/D polymorphism in the development and progression of diabetic nephropathy. RAAS blockers are the first line drugs for the treatment hypertension associated with diabetes and have been widely used in everyday clinical practice for the purpose of reducing proteinuria in patients with various renal diseases. However, the antiproteinuric effect of RAAS blockers is variable and the percentage of reducing proteinuria is in the range of 20-80%. The antiproteinuric effect of RAAS blockers may be related to a number of factors: the type or the dose of RAAS blockers, the duration of therapy, the level of sodium intake, and the type of patient's ACE I/D genotype. Besides the nongenetic factors, drug responses, can be influenced by ACE gene polymorphism. In this review, we discuss the relationship between ACE I/D polymorphism and diabetic nephropathy and therapeutic response of RAAS blockers. PMID:25587546

  1. ACE Insertion/Deletion Polymorphism and Diabetic Nephropathy: Clinical Implications of Genetic Information

    PubMed Central

    Ha, Sung-Kyu

    2014-01-01

    Approximately 20–40% of diabetic patients develop nephropathy which is the leading cause of ESRD in developed countries. The ACE I/D polymorphism is thought to be a marker for functional polymorphism which regulates circulating and tissue ACE activity. While the initial study found a protective effect of the II genotype on the development of nephropathy in IDDM patients, subsequent studies have addressed the role of ACE I/D polymorphism in the development and progression of diabetic nephropathy. RAAS blockers are the first line drugs for the treatment hypertension associated with diabetes and have been widely used in everyday clinical practice for the purpose of reducing proteinuria in patients with various renal diseases. However, the antiproteinuric effect of RAAS blockers is variable and the percentage of reducing proteinuria is in the range of 20–80%. The antiproteinuric effect of RAAS blockers may be related to a number of factors: the type or the dose of RAAS blockers, the duration of therapy, the level of sodium intake, and the type of patient's ACE I/D genotype. Besides the nongenetic factors, drug responses, can be influenced by ACE gene polymorphism. In this review, we discuss the relationship between ACE I/D polymorphism and diabetic nephropathy and therapeutic response of RAAS blockers. PMID:25587546

  2. Genetic polymorphisms of CC chemokine receptor 3 in Japanese and British asthmatics.

    PubMed

    Fukunaga, K; Asano, K; Mao, X Q; Gao, P S; Roberts, M H; Oguma, T; Shiomi, T; Kanazawa, M; Adra, C N; Shirakawa, T; Hopkin, J M; Yamaguchi, K

    2001-01-01

    Whole genome scan analyses have revealed that chromosomal region 3p21-24, which contains a gene cluster of CC chemokine receptors such as CCR3, is possibly linked to asthma. Because CCR3 ligands play a pivotal role in the selective recruitment and activation of inflammatory cells in the asthmatic airway, the authors examined whether there is any association between asthma and the CCR3 gene polymorphisms. Three polymorphisms were identified using the single stranded conformational polymorphism method in Japanese (Asian) and British (Caucasian) subjects; one silent mutation T51C and two missense mutations G824A and T971C. These polymorphisms were examined in 391 Japanese subjects (210 asthmatics and 181 nonasthmatic controls) and 234 British subjects (142 asthmatics and 92 nonasthmatic controls). Asthma diagnosis was based on episodic symptoms, documented wheeze, and the presence of reversible airflow limitation. CCR3 T51C demonstrated a significant association with the diagnosis of asthma in the British population (odds ratio 2.35, p<0.01), but not in the Japanese population. Multiple logistic regression analysis also showed that CCR3 T51C was associated with asthma (odds ratio 2.83, p < 0.02), independent of atopic phenotypes such as high levels of total or house dust mite-specific immunoglobulin-E in serum. In conclusion, a significant association between asthma and CCR3 T51C polymorphism localized on chromosome 3p21 was found. PMID:11307756

  3. Population genetic analysis of insertion-deletion polymorphisms in a Brazilian population using the Investigator DIPplex kit.

    PubMed

    Ferreira Palha, Teresinha de Jesus Brabo; Ribeiro Rodrigues, Elzemar Martins; Cavalcante, Giovanna Chaves; Marrero, Andrea; de Souza, Ilada Rainha; Seki Uehara, Clineu Julien; Silveira da Motta, Carlos Henrique Ares; Koshikene, Daniela; da Silva, Dayse Aparecida; de Carvalho, Elizeu Fagundes; Chemale, Gustavo; Freitas, Jorge M; Alexandre, Ldia; Paranaiba, Renato T F; Soler, Mirella Perruccio; Santos, Sidney

    2015-11-01

    The aim of this study was to estimate the diversity of 30 insertion/deletion (INDEL) markers (Investigator() DIPplex kit) in a sample of 519 individuals from six Brazilian states and to evaluate their applicability in forensic genetics. All INDEL markers were found to be highly polymorphic in the Brazilian population and were in Hardy-Weinberg equilibrium. To determine their forensic suitability in the Brazilian population, the markers were evaluated for discrimination power, match probability and exclusion power. The combined discrimination power (CDP), combined match power (CMP) and combined power of exclusion (CPE) were higher than 0.999999, 3.4 10(-13) and 0.9973, respectively. Further comparison of 29 worldwide populations revealed significant genetic differences between continental populations and a closer relationship between the Brazilian and European populations. PMID:26036184

  4. [Molecular-genetic polymorphism of wheat cell lines resistant to metabolites of G. graminis var. tritici and osmotic stress].

    PubMed

    Bavol, A V; Zinchenko, M O; Dubrovna, O V

    2014-01-01

    It was analyzed polymorphism of DNA loci, flanked by inverted repeats of LTR retrotransposon Cassandra, in cell lines of bread wheat, resistant to the metabolites of ophiobolus root rot (G. graminis var. tritici), under osmotic stress and induced from them plant-regenerants. The differences in the polynucleotide sequences of DNA at the direct and step cell selection it was identified. Assessment of the level of genetic divergence showed that calluses obtained at the direct selection and calluses in the later stages of step selection were the most genetically distant from the original forms (D(NL) = 0.4855), this means that at the sublethal doses of selective factors occur the most significant changes at the genome of the investigated objects. In contrast to the original form at the spectra of products DNA amplification of calluses and regenerated plants showed the emergence of bands approximately 638 bp length, which may indicate the activation of retrotransposon Cassandra. PMID:24791474

  5. Bovine dopamine receptors DRD1, DRD4, and DRD5: genetic polymorphisms and diversities among ten cattle breeds.

    PubMed

    Sifuentes-Rincón, A M; Trejo-Tapia, A G; Randel, R D; Ambriz-Morales, P; Parra-Bracamonte, G M

    2016-01-01

    The aim of this study was to analyze the allelic frequency distribution and segregation among breeds and/or between different cattle genetic groups of four novel single nucleotide polymorphisms of the bovine DRD1 and DRD5 genes and one reported SNP from the DRD4 gene. One hundred and nine-animals from ten different cattle breeds were genotyped and allelic frequencies for each locus were estimated. There were significant differences in the allelic frequencies (P < 0.05) among breeds for the DRD1 and DRD5 markers. The allelic frequencies for markers DRD1-825A>G and DRD5-378C>T were also significantly different between groups differing in genetic background. Because differences in temperament have been reported between Bos taurus taurus and B. taurus indicus breeds and their crosses, further studies are needed to investigate if any association exists between described markers and cattle behavior traits. PMID:26909995

  6. Armadillos exhibit less genetic polymorphism in North America than in South America: nuclear and mitochondrial data confirm a founder effect in Dasypus novemcinctus (Xenarthra).

    PubMed

    Huchon, D; Delsuc, F; Catzeflis, F M; Douzery, E J

    1999-10-01

    Heterozygosity at eight nuclear enzymatic loci and mitochondrial DNA control region (D-loop) sequence polymorphism was compared between North and South American nine-banded armadillos (Dasypus novemcinctus: Xenarthra, Dasypodidae). All markers revealed a striking genetic homogeneity amongst Texas, Louisiana, and Mississippi individuals, vs. the usual level of polymorphism for the French Guiana population. This may reflect a founder effect during colonization of North America. Occurrence of polymorphism in the D-loop microsatellite motif of North American armadillos suggests a recent recovery of mitochondrial variability. Phylogeographic analyses using Dasypus kappleri as outgroup provides evidence for a clear separation between North and South American control region haplotypes. PMID:10583836

  7. Application of Wavelet Packet Transform to detect genetic polymorphisms by the analysis of inter-Alu PCR patterns

    PubMed Central

    2010-01-01

    Background The analysis of Inter-Alu PCR patterns obtained from human genomic DNA samples is a promising technique for a simultaneous analysis of many genomic loci flanked by Alu repetitive sequences in order to detect the presence of genetic polymorphisms. Inter-Alu PCR products may be separated and analyzed by capillary electrophoresis using an automatic sequencer that generates a complex pattern of peaks. We propose an algorithmic method based on the Haar-Walsh Wavelet Packet Transformation (WPT) for an efficient detection of fingerprint-type patterns generated by PCR-based methodologies. We have tested our algorithmic approach on inter-Alu patterns obtained from the genomic DNA of three couples of monozygotic twins, expecting that the inter-Alu patterns of each twins couple will show differences due to unavoidable experimental variability. On the contrary the differences among samples of different twins are supposed to originate from genetic variability. Our goal is to automatically detect regions in the inter-Alu pattern likely associated to the presence of genetic polymorphisms. Results We show that the WPT algorithm provides a reliable tool to identify sample to sample differences in complex peak patterns, reducing the possible errors and limits associated to a subjective evaluation. The redundant decomposition of the WPT algorithm allows for a procedure of best basis selection which maximizes the pattern differences at the lowest possible scale. Our analysis points out few classifying signal regions that could indicate the presence of possible genetic polymorphisms. Conclusions The WPT algorithm based on the Haar-Walsh wavelet is an efficient tool for a non-supervised pattern classification of inter-ALU signals provided by a genetic analyzer, even if it was not possible to estimate the power and false positive rate due to the lacking of a suitable data base. The identification of non-reproducible peaks is usually accomplished comparing different experimental replicates of each sample. Moreover, we remark that, albeit we developed and optimized an algorithm able to analyze patterns obtained through inter-Alu PCR, the method is theoretically applicable to whatever fingerprint-type pattern obtained analyzing anonymous DNA fragments through capillary electrophoresis, and it could be usefully applied on a wide range of fingerprint-type methodologies. PMID:21143911

  8. Genetic Polymorphisms in CYP2E1: Association with Schizophrenia Susceptibility and Risperidone Response in the Chinese Han Population

    PubMed Central

    Wei, Zhiyun; Shen, Lu; Xiong, Yuyu; Wu, Xi; Niu, Jiamin; Han, Xia; Tian, Zhengan; Yang, Lun; Feng, Guoyin; He, Lin; Qin, Shengying

    2012-01-01

    Background CYP2E1 is a member of the cytochrome P450 superfamily, which is involved in the metabolism and activation of both endobiotics and xenobiotics. The genetic polymorphisms of CYP2E1 gene (Chromosome 10q26.3, Accession Number NC_000010.10) are reported to be related to the development of several mental diseases and to be involved in the clinical efficacy of some psychiatric medications. We investigated the possible association of CYP2E1 polymorphisms with susceptibility to schizophrenia in the Chinese Han Population as well as the relationship with response to risperidone in schizophrenia patients. Methods In a case-control study, we identified 11 polymorphisms in the 5' flanking region of CYP2E1 in 228 schizophrenia patients and 384 healthy controls of Chinese Han origin. From among the cases, we chose 130 patients who had undergone 8 weeks of risperidone monotherapy to examine the relationship between their response to risperidone and CYP2E1 polymorphisms. Clinical efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS). Results Statistically significant differences in allele or genotype frequencies were found between cases and controls at rs8192766 (genotype p?=?0.0048, permutation p?=?0.0483) and rs2070673 (allele: p?=?0.0018, permutation p?=?0.0199, OR?=?1.4528 95%CI?=?1.14871.8374; genotype: p?=?0.0020, permutation p?=?0.0225). In addition, a GTCAC haplotype containing 5 SNPs (rs3813867, rs2031920, rs2031921, rs3813870 and rs2031922) was observed to be significantly associated with schizophrenia (p?=?7.47E-12, permutation p<0.0001). However, no association was found between CYP2E1 polymorphisms/haplotypes and risperidone response. Conclusions Our results suggest that CYP2E1 may be a potential risk gene for schizophrenia in the Chinese Han population. However, polymorphisms of the CYP2E1 gene may not contribute significantly to individual differences in the therapeutic efficacy of risperidone. Further studies in larger groups are warranted to confirm our results. PMID:22606226

  9. Recent divergence, intercontinental dispersal and shared polymorphism are shaping the genetic structure of amphi-Atlantic peatmoss populations.

    PubMed

    Szövényi, P; Terracciano, S; Ricca, M; Giordano, S; Shaw, A J

    2008-12-01

    Several lines of evidence suggest that recent long-distance dispersal may have been important in the evolution of intercontinental distribution ranges of bryophytes. However, the absolute rate of intercontinental migration and its relative role in the development of certain distribution ranges is still poorly understood. To this end, the genetic structure of intercontinental populations of six peatmoss species showing an amphi-Atlantic distribution was investigated using microsatellite markers. Methods relying on the coalescent were applied (IM and MIGRATE) to understand the evolution of this distribution pattern in peatmosses. Intercontinental populations of the six peatmoss species were weakly albeit significantly differentiated (average F(ST) = 0.104). This suggests that the North Atlantic Ocean is acting as a barrier to gene flow even in bryophytes adapted to long-range dispersal. The im analysis suggested a relatively recent split of intercontinental populations dating back to the last two glacial periods (9000-289,000 years ago). In contrast to previous hypotheses, analyses indicated that both ongoing migration and ancestral polymorphism are important in explaining the intercontinental genetic similarity of peatmoss populations, but their relative contribution varies with species. Migration rates were significantly asymmetric towards America suggesting differential extinction of genotypes on the two continents or invasion of the American continent by European lineages. These results indicate that low genetic divergence of amphi-Atlantic populations is a general pattern across numerous flowering plants and bryophytes. However, in bryophytes, ongoing intercontinental gene flow and retained shared ancestral polymorphism must both be considered to explain the genetic similarity of intercontinental populations. PMID:19121003

  10. Genetic Diversity and Relatedness of Sweet Cherry (Prunus Avium L.) Cultivars Based on Single Nucleotide Polymorphic Markers

    PubMed Central

    Fernandez i Marti, Angel; Athanson, Blessing; Koepke, Tyson; Font i Forcada, Carolina; Dhingra, Amit; Oraguzie, Nnadozie

    2012-01-01

    Most previous studies on genetic fingerprinting and cultivar relatedness in sweet cherry were based on isoenzyme, RAPD, and simple sequence repeat (SSR) markers. This study was carried out to assess the utility of single nucleotide polymorphism (SNP) markers generated from 3′ untranslated regions (UTR) for genetic fingerprinting in sweet cherry. A total of 114 sweet cherry germplasm representing advanced selections, commercial cultivars, and old cultivars imported from different parts of the world were screened with seven SSR markers developed from other Prunus species and with 40 SNPs obtained from 3′ UTR sequences of Rainier and Bing sweet cherry cultivars. Both types of marker study had 99 accessions in common. The SSR data was used to validate the SNP results. Results showed that the average number of alleles per locus, mean observed heterozygosity, expected heterozygosity, and polymorphic information content values were higher in SSRs than in SNPs although both set of markers were similar in their grouping of the sweet cherry accessions as shown in the dendrogram. SNPs were able to distinguish sport mutants from their wild type germplasm. For example, “Stella” was separated from “Compact Stella.” This demonstrates the greater power of SNPs for discriminating mutants from their original parents than SSRs. In addition, SNP markers confirmed parentage and also determined relationships of the accessions in a manner consistent with their pedigree relationships. We would recommend the use of 3′ UTR SNPs for genetic fingerprinting, parentage verification, gene mapping, and study of genetic diversity in sweet cherry. PMID:22737155

  11. The use of genetic markers for detecting DNA polymorphism, genotype identification and phylogenetic relationships among banana cultivars.

    PubMed

    Venkatachalam, L; Sreedhar, R V; Bhagyalakshmi, N

    2008-06-01

    Genetic variations and relationships among 21 commercially important banana cultivars of South India were evaluated using 50 decamer RAPD primers and 12 ISSR primers. The primers were selected after a preliminary screening of several such primers for their ability to produce clear and reproducible patterns of multiple bands. The analyses resulted in the amplification of totally 641 bands of 200-3100bp, of which 382 bands were polymorphic, corresponding to nearly 60% genetic diversity. The RAPD and ISSR surveys between pairs of 21 cultivars revealed 60.15% and 56.73% of polymorphic bands, respectively. A strong linear relationship was observed between the Resolving power (Rp) of the primer and its ability to distinguish genotypes. Based on these data, a genetic similarity matrix was established and a dendrogram for each set of primers was developed by UPGMA. The genetic similarity coefficients in RAPD analysis ranged from 0.3177 to 0.7818 and in ISSR analysis from 0.1800 to 0.8462. A fingerprinting key was generated where the presence/absence of specific RAPD/ISSR bands were recorded for each cultivar. The presence of a specific RAPD (OPC-5(800)) band was observed for an endemic cultivar--Nanjanagudu Rasabale (NR). The study resulted in the identification and molecular classification of South Indian banana cultivars of which Robusta and Williams are global and others have either limited geographical distribution or purely endemic to South India. A group of eight cultivars was identified that are highly distinct from one another. The members of this group may be useful for generating 2X and 4X breeding populations for further use in breeding secondary triploid hybrids. PMID:18434209

  12. Genetic Polymorphisms of the Glycine N-Methyltransferase and Prostate Cancer Risk in the Health Professionals Follow-Up Study

    PubMed Central

    Chen, Marcelo; Huang, Yi-Ling; Huang, Yu-Chuen; Shui, Irene M.; Giovannucci, Edward; Chen, Yen-Ching; Chen, Yi-Ming Arthur

    2014-01-01

    Purpose Glycine N-methyltransferase (GNMT) affects genetic stability by regulating the ratio of S-adenosylmethionine to S-adenosylhomocysteine, by binding to folate, and by interacting with environmental carcinogens. In Taiwanese men, GNMT was found to be a tumor susceptibility gene for prostate cancer. However, the association of GNMT with prostate cancer risk in other ethnicities has not been studied. It was recently reported that sarcosine, which is regulated by GNMT, increased markedly in metastatic prostate cancer. We hereby explored the association of GNMT polymorphisms with prostate cancer risk in individuals of European descent from the Health Professionals Follow-up Study (HPFS). Methods A total of 661 incident prostate cancer cases and 656 controls were identified from HPFS. The GNMT short tandem repeat polymorphism 1 (STRP1), 4-bp insertion/deletion polymorphisms (INS/DEL) and the single nucleotide polymorphism rs10948059 were genotyped to test for their association with prostate cancer risk. Results The rs10948059 T/T genotype was associated with a 1.62-fold increase in prostate cancer risk (95% confidence interval (CI): 1.18, 2.22) when compared with the C/C genotype. The STRP1 ≥16GAs/≥16GAs genotype was associated with decreased risk of prostate cancer when compared with the <16GAs/<16GAs genotype (odds ratio (OR) = 0.68; 95% CI: 0.46, 1.01). INS/DEL was not associated with prostate cancer risk. Haplotypes containing the rs10948059 T allele were significantly associated with increased prostate cancer risk. Conclusion In men of European descent, the GNMT rs10948059 and STRP1 were associated with prostate cancer risk. Compared to the study conducted in Taiwanese men, the susceptibility GNMT alleles for prostate cancer had a reverse relationship. This study highlights the differences in allelic frequencies and prostate cancer susceptibility in different ethnicities. PMID:24800880

  13. Association between genetic polymorphism in NFKB1 and NFKBIA and coronary artery disease in a Chinese Han population

    PubMed Central

    Lai, Hongmei; Chen, Qingjie; Li, Xiaomei; Ma, Yitong; Xu, Rui; Zhai, Hui; Liu, Fen; Chen, Bangdang; Yang, Yining

    2015-01-01

    Objectives: Prior studies have demonstrated NF-?B plays an important role in the development and progression of inflammatory diseases. The aim of this study was to investigate whether promoter polymorphisms in NFKB1 and NFKBIA gene are associated with coronary artery disease (CAD) in a Chinese Han population. Methods: A total of 1140 Han CAD patients and 1156 Han control subjects were genotyped for 4 single-nucleotide polymorphisms (SNPs) in the promoter region of NFKBIA gene (rs3138053, rs2233406, rs2233409) and NFKB1 gene (-94 ins/del ATTG, rs28362491) by using the TaqMan SNP genotyping assays, and then NFKBIA haplotype blocks were reconstructed according to our genotyping data. Results: For total, men, and women, the distribution of genotypes, alleles of rs3138053, rs2233406, rs2233409 and haplotype polymorphisms showed no significant difference between CAD cases and controls. None of the studied NFKBIA SNPs were associated with CAD. For total, men, and women, there was significant difference in the distribution of the genotypes (P=0.001, P=0.024, P= 0.022) and alleles (P=0.001, P=0.012, P=0.031) of rs28362491 in CAD cases and controls. For total, men, and women, the rs28362491 was associated with increased risk of CAD in a recessive model after adjustment for covariates (OR=1.505, 95% CI 1.190 to 1.903, P=0.001; OR=1.469, 95% CI 1.082-1.993, P=0.014; OR=1.622, 95% CI 1.118 to 2.352, P=0.011, respectively). Conclusions: In our study, the -94 ins/del ATTG polymorphism in NFKB1 promoter is associated with CAD susceptibility in Chinese Han population, providing a new insight into the genetics of CAD in Chinese Han population. PMID:26885097

  14. Genetic polymorphism in three glutathione s-transferase genes and breast cancer risk

    SciTech Connect

    Woldegiorgis, S.; Ahmed, R.C.; Zhen, Y.; Erdmann, C.A.; Russell, M.L.; Goth-Goldstein, R.

    2002-04-01

    The role of the glutathione S-transferase (GST) enzyme family is to detoxify environmental toxins and carcinogens and to protect organisms from their adverse effects, including cancer. The genes GSTM1, GSTP1, and GSTT1 code for three GSTs involved in the detoxification of carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and benzene. In humans, GSTM1 is deleted in about 50% of the population, GSTT1 is absent in about 20%, whereas the GSTP1 gene has a single base polymorphism resulting in an enzyme with reduced activity. Epidemiological studies indicate that GST polymorphisms increase the level of carcinogen-induced DNA damage and several studies have found a correlation of polymorphisms in one of the GST genes and an increased risk for certain cancers. We examined the role of polymorphisms in genes coding for these three GST enzymes in breast cancer. A breast tissue collection consisting of specimens of breast cancer patients and non-cancer controls was analyzed by polymerase chain reaction (PCR) for the presence or absence of the GSTM1 and GSTT1 genes and for GSTP1 single base polymorphism by PCR/RFLP. We found that GSTM1 and GSTT1 deletions occurred more frequently in cases than in controls, and GSTP1 polymorphism was more frequent in controls. The effective detoxifier (putative low-risk) genotype (defined as presence of both GSTM1 and GSTT1 genes and GSTP1 wild type) was less frequent in cases than controls (16% vs. 23%, respectively). The poor detoxifier (putative high-risk) genotype was more frequent in cases than controls. However, the sample size of this study was too small to provide conclusive results.

  15. Genetic polymorphisms and activity of PON1 in a Mexican population

    SciTech Connect

    Rojas-Garcia, A.E.; Solis-Heredia, M.J.; Pina-Guzman, B.; Vega, L.; Lopez-Carrillo, L.; Quintanilla-Vega, B. . E-mail: mquintan@cinvestav.mx

    2005-06-15

    Human paraoxonase (PON1) plays a role in detoxification of organophosphorus (OP) compounds by hydrolyzing the bioactive oxons, and in reducing oxidative low-density lipoproteins, which may protect against atherosclerosis. Some PON1 polymorphisms have been found to be responsible for variations in catalytic activity and expression and have been associated with susceptibility to OP poisoning and vascular diseases. Both situations are of public health relevance in Mexico. Therefore, the aim of this study was to evaluate PON1 phenotype and the frequencies of polymorphisms PON1 -162, -108, 55, and 192 in a Mexican population. The studied population consisted of unrelated individuals (n = 214) of either gender, 18-52 years old. Serum PON1 activity was assayed using phenylacetate and paraoxon as substrates. PON1 variants, -162, 55, and 192, were determined by real-time PCR using the TaqMan System, and PON1 -108 genotype by PCR-RFLP. We found a wide interindividual variability of PON1 activity with a unimodal distribution; the range of enzymatic activity toward phenylacetate was 84.72 to 422.0 U/mL, and 88.37 to 1645.6 U/L toward paraoxon. All four PON1 polymorphisms showed strong linkage disequilibrium (D% >90). PON1 polymorphisms -108, 55, and 192 were independently associated with arylesterase activity; whereas the activity toward paraoxon was related only with PON1 192 polymorphism, suggesting that this polymorphism is determinant to infer PON1 activity. A better understanding of the phenotype and genotypes of PON1 in Mexican populations will facilitate further epidemiological studies involving PON1 variability in OP poisoning and in the development of atherosclerosis.

  16. Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes.

    PubMed Central

    Costerousse, O; Allegrini, J; Lopez, M; Alhenc-Gelas, F

    1993-01-01

    The expression of angiotensin-I converting enzyme (ACE; EC 3.4.15.1) in human circulating mononuclear cells was studied. T-lymphocytes contained the highest level of enzyme, approx. 28 times more per cell than monocytes. No activity was detected in B-lymphocytes. ACE was present mainly in the microsomal fraction, where it was found to be the major membrane-bound bradykinin-inactivating enzyme. An mRNA for ACE was detected and characterized after reverse transcription and amplification by PCR in T-lymphocytes and several T-cell leukaemia cell lines. We have previously observed that the interindividual variability in the levels of ACE in plasma is, in part, genetically determined and influenced by an insertion/deletion polymorphism of the ACE gene. To investigate the mechanisms involved in the regulation of ACE biosynthesis, the ACE levels of T-lymphocytes from 35 healthy subjects having different ACE genotypes were studied. These levels varied widely between individuals but were highly reproducible and influenced by the polymorphism of the ACE gene. T-lymphocyte levels of ACE were significantly higher in subjects who were homozygote for the deletion than in the other subjects. These results show that ACE is expressed in T-lymphocytes and indicate that the level of ACE expression in cells synthesizing the enzyme is genetically determined. Images Figure 3 PMID:8382480

  17. BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related SCT.

    PubMed

    Piras, I S; Angius, A; Andreani, M; Testi, M; Lucarelli, G; Floris, M; Marktel, S; Ciceri, F; La Nasa, G; Nasa, G La; Fleischhauer, K; Roncarolo, M G; Bulfone, A; Gregori, S; Bacchetta, R

    2014-11-01

    The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic SCT (allo-HSCT). We applied whole-genome analysis to investigate genetic variants-other than HLA class I and II-associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 ?-Thalassemic patients. We identified two single-nucleotide polymorphisms (SNPs) in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong linkage disequilibrium between each other (R(2)=0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P<0.00001 for BAT2 SNP rs11538264, and P<0.0001 for BAT3 SNP rs10484558), whereas the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs 2.6%, nominal P=1.15 10(-8); and adjusted P=0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent a novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT. PMID:25111513

  18. BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related stem cell transplantation

    PubMed Central

    Piras, Ignazio Stefano; Angius, Andrea; Andreani, Marco; Testi, Manuela; Lucarelli, Guido; Floris, Matteo; Marktel, Sarah; Ciceri, Fabio; La Nasa, Giorgio; Fleischhauer, Katharina; Roncarolo, Maria Grazia; Bulfone, Alessandro

    2014-01-01

    The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We applied a whole genome analysis to investigate genetic variants - other than HLA class I and II - associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 ?-Thalassemic patients. We identified two single nucleotide polymorphisms in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong Linkage Disequilibrium between each other (R2=0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P < 0.00001 for BAT2 SNP rs11538264, and P < 0.0001 for BAT3 SNP rs10484558). Whereas, the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs. 2.6%, nominal P = 1.1510?8; and adjusted P = 0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT. PMID:25111513

  19. Hyperhomocysteinemia and related genetic polymorphisms correlate with ulcerative colitis in Chinese Han population in Central China [corrected].

    PubMed

    Jiang, Yi; Xia, Xuanping; Wang, Wenxing; Lin, Limiao; Xu, Changlong; Cai, Zhenzai; Zheng, Bo; Pei, Jihua; Shen, Sujian; Xia, Bing

    2012-01-01

    Increased levels of homocysteine are found systemically and in intestinal mucosa of patients with inflammatory bowel disease, and, specifically, in ulcerative colitis (UC). However, there are controversial reports regarding the factors contributing to increased levels of homocysteine in UC. Furthermore, little information is available regarding the relationship between hyperhomocysteinemia (HHcy), vitamin status, and genetic polymorphisms of homocysteine-related enzymes in these patients. This study examined four functional polymorphisms linked to homocysteine metabolism (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G), and evaluated plasma levels of homocysteine, folate, and vitamin B(12) in 310 consecutive patients with UC and 936 age- and sex-matched healthy controls from southeast China. The variant allele and genotypic frequencies in MTHFR A1298C, MTR A2756G and MTRR A66G genes were significantly higher in patients with UC compared to healthy controls. Further, HHcy and low levels of folate and vitamin B(12) were more frequent in patients with UC. The MTR 2756G allele, extent of the disease, and gender were the independent determinants of HHcy in these patients. These findings suggest that genetic and nutritional factors have a synergetic effect on HHcy in patients with UC. In conclusion, our data highlight a prevention strategy for moderation of HHcy and supplementation with folate and vitamine B(12) in patients with UC from Southeast China. PMID:21947961

  20. Genetic polymorphisms of PCSK2 are associated with glucose homeostasis and progression to type 2 diabetes in a Chinese population

    PubMed Central

    Chang, Tien-Jyun; Chiu, Yen-Feng; Sheu, Wayne H-H.; Shih, Kuang-Chung; Hwu, Chii-Min; Quertermous, Thomas; Jou, Yuh-Shan; Kuo, Shan-Shan; Chang, Yi-Cheng; Chuang, Lee-Ming

    2015-01-01

    Proprotein convertase subtilisin/kexin type 2 (PCSK2) is a prohormone processing enzyme involved in insulin and glucagon biosynthesis. We previously found the genetic polymorphism of PCSK2 on chromosome 20 was responsible for the linkage peak of several glucose homeostasis parameters. The aim of this study is to investigate the association between genetic variants of PCSK2 and glucose homeostasis parameters and incident diabetes. Total 1142 Chinese participants were recruited from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study, and 759 participants were followed up for 5 years. Ten SNPs of the PCSK2 gene were genotyped. Variants of rs6044695 and rs2284912 were associated with fasting plasma glucose, and variants of rs2269023 were associated with fasting plasma glucose and 1-hour plasma glucose during OGTT. Haplotypes of rs4814605/rs1078199 were associated with fasting plasma insulin levels and HOMA-IR. Haplotypes of rs890609/rs2269023 were also associated with fasting plasma glucose, fasting insulin and HOMA-IR. In the longitudinal study, we found individuals carrying TA/AA genotypes of rs6044695 or TC/CC genotypes of rs2284912 had lower incidence of diabetes during the 5-year follow-up. Our results indicated that PCSK2 gene polymorphisms are associated with pleiotropic effects on various traits of glucose homeostasis and incident diabetes. PMID:26607656

  1. Genetic polymorphisms of PCSK2 are associated with glucose homeostasis and progression to type 2 diabetes in a Chinese population.

    PubMed

    Chang, Tien-Jyun; Chiu, Yen-Feng; Sheu, Wayne H-H; Shih, Kuang-Chung; Hwu, Chii-Min; Quertermous, Thomas; Jou, Yuh-Shan; Kuo, Shan-Shan; Chang, Yi-Cheng; Chuang, Lee-Ming

    2015-01-01

    Proprotein convertase subtilisin/kexin type 2 (PCSK2) is a prohormone processing enzyme involved in insulin and glucagon biosynthesis. We previously found the genetic polymorphism of PCSK2 on chromosome 20 was responsible for the linkage peak of several glucose homeostasis parameters. The aim of this study is to investigate the association between genetic variants of PCSK2 and glucose homeostasis parameters and incident diabetes. Total 1142 Chinese participants were recruited from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study, and 759 participants were followed up for 5 years. Ten SNPs of the PCSK2 gene were genotyped. Variants of rs6044695 and rs2284912 were associated with fasting plasma glucose, and variants of rs2269023 were associated with fasting plasma glucose and 1-hour plasma glucose during OGTT. Haplotypes of rs4814605/rs1078199 were associated with fasting plasma insulin levels and HOMA-IR. Haplotypes of rs890609/rs2269023 were also associated with fasting plasma glucose, fasting insulin and HOMA-IR. In the longitudinal study, we found individuals carrying TA/AA genotypes of rs6044695 or TC/CC genotypes of rs2284912 had lower incidence of diabetes during the 5-year follow-up. Our results indicated that PCSK2 gene polymorphisms are associated with pleiotropic effects on various traits of glucose homeostasis and incident diabetes. PMID:26607656

  2. Association of genetic polymorphisms in HTR3A and HTR3E with diarrhea predominant irritable bowel syndrome

    PubMed Central

    Gu, Qiao-Yan; Zhang, Jun; Feng, Yi-Chao; Dai, Guang-Rong; Du, Wei-Ping

    2015-01-01

    Objective: The present study aims to investigate the relationship between genetic polymorphisms in HTR3A and HTR3E and diarrhea predominant irritable bowel syndrome (D-IBS) in a Chinese population. Methods: We enrolled 500 D-IBS patients and 500 age- and sex-matched healthy control subjects to detect the genotypes in HTR3A and HTR3B gene by using of PCR-RFLP method. Results: There were significant difference between the D-IBS patients and the health control subjects in the distribution of genotype and allele of rs1062613 in HTR3A gene. As regarding rs62625044 in HTR3E gene, we found there was a significant different between the case and the control group in the distribution of GA genotype and A allele in female but not in male. Conclusion: The present study suggested that there are associations of D-IBS risk with genetic polymorphisms in HTR3A and HTR3E. PMID:26064388

  3. Genetic polymorphisms, Biochemical Factors, and Conventional Risk Factors in Young and Elderly North Indian Patients With Acute Myocardial Infarction.

    PubMed

    Kaur, Rupinder; Das, Reena; Ahluwalia, Jasmina; Kumar, Rohit Manoj; Talwar, K K

    2016-03-01

    This study compared genetic polymorphisms (factor V Leiden [FVL] 1691G/A, factor VII [FVII] 10976G/A, FVII HVR4, platelet membrane glycoproteins GP1BA 1018C/T, GP1BA VNTR, integrin ITGB3 1565T/C, ITGA2 807C/T and methylenetetrahydrofolate reductase [MTHFR] 677C/T), biochemical (fibrinogen and homocysteine), and conventional risk factors in 184 young and 166 elderly north Indian patients with acute myocardial infarction (AMI). Univariate analysis revealed higher prevalence of hypertension and obesity in elderly patients while smoking, alcohol intake, and low socioeconomic status in young patients (P < .001). Although mean fibrinogen predominated (P = .01) in elderly patients, mean homocysteine was higher (P < .001) among young patients. Prevalence of hyperhomocysteinemia was greater in young than in elderly patients (odds ratio: 2.8, 95% confidence interval: 1.8-4.4, P < .001); however, genetic polymorphisms were equally prevalent in young and elderly patients. Multiple logistic regression analysis showed smoking (P < .001), alcohol intake (P = .046), and hyperhomocysteinemia (P = .001) to be associated with AMI in the young patients while hypertension (P = .006) in elderly patients. To conclude, smoking, alcohol intake, and elevated homocysteine are the risk factors for AMI among young while hypertension among elderly patients. PMID:25155498

  4. Shortened leukocyte telomere length in type 2 diabetes mellitus: genetic polymorphisms in mitochondrial uncoupling proteins and telomeric pathways.

    PubMed

    Zhou, Yuling; Ning, Zhixin; Lee, Yvonne; Hambly, Brett D; McLachlan, Craig S

    2016-12-01

    Current debate in type 2 diabetes (T2DM) has focused on shortened leukocyte telomere length (LTL) as the result of a number of possible causes, including polymorphisms in mitochondrial uncoupling proteins (UCPs) leading to oxidative stress, telomere regulatory pathway gene polymorphisms, or as a direct result of associated cardiovascular complications inducing tissue organ inflammation and oxidative stress. There is evidence that a heritable shorter telomere trait is a risk factor for development of T2DM. This review discusses the contribution and balance of genetic regulation of UCPs and telomere pathways in the context of T2DM. We discuss genotypes that are well known to influence the shortening of LTL, in particular OBFC1 and telomerase genotypes such as TERC. Interestingly, the interaction between short telomeres and T2DM risk appears to involve mitochondrial dysfunction as an intermediate process. A hypothesis is presented that genetic heterogeneity within UCPs may directly affect oxidative stress that feeds back to influence the fine balance of telomere regulation, cell cycle regulation and diabetes risk and/or metabolic disease progression. PMID:26951191

  5. Genetic Association of CHRNB3 and CHRNA6 Gene Polymorphisms with Nicotine Dependence Syndrome Scale in Korean Population

    PubMed Central

    Won, Wang-Youn; Park, ByungLae; Choi, Sam-Wook; Kim, LyoungHyo; Kwon, Min; Kim, Jae-Hwa; Lee, Chang-Uk; Shin, Hyoung Doo

    2014-01-01

    Objective Cholinergic nicotinic receptor (CHRN) gene family has been known to mediate the highly additive effects of nicotine in the body, and implicated nicotine dependence (ND) and related phenotypes. Previous studies have found that CHRNA6-CHRNB3 cluster polymorphisms were significantly associated with the risk of ND and various tobacco behaviors. The aim of study was to evaluate the genetic association of CHRNB3 and CHRNA6 polymorphisms with the risk of ND based on the Fagerstrom Test for Nicotine Dependence (FTND) score and five subscales of nicotine dependence syndrome scale (NDSS) in Korean population. Methods Six SNPs in CHRNA6-CHRNB3 cluster were analyzed in 576 Korean subjects. Association analysis using logistic models and regression analysis with NDSS were performed. Results There was no association in the case-control analysis, whereas all six SNPs were significantly associated with drive factor among NDSS in subgroup based on the FTND score. CHRNB3 rs4954 and CHRNA6 rs16891604 showed significant associations with NDSSF1 (drive) in dominant models among moderate to severe ND among smokers after correction (pcorr=0.02 and 0.001, respectively), whereas other four SNPs showed significant associations among mild ND after correction (pcorr=0.03-0.02 in dominant model). Conclusion This study showed that the genetic influence of CHRNB3-CHRNA6 cluster polymorphisms are found in a ND endophenotype (drive) using NDSS subscales, rather than the risk of ND in Korean population. Our findings might be the first report for the association of CHRNB3-CHRNA6 cluster with ND-related phenotypes in Korean and might offer an approach to elucidating the molecular mechanisms of ND and ND-related phenotypes. PMID:25110504

  6. Genetic analysis of ABCG2 and SLC2A9 gene polymorphisms in gouty arthritis in a Korean population

    PubMed Central

    Kim, Yun Sung; Kim, Yunsuek; Park, Geon; Kim, Seong-Kyu; Choe, Jung-Yoon; Park, Byung Lae; Kim, Hyun Sook

    2015-01-01

    Background/Aims: Gout is a common inf lammatory arthritis triggered by the crystallization of uric acid in the joints. Serum uric acid levels are highly heritable, suggesting a strong genetic component. Independent studies to confirm the genetic associations with gout in various ethnic populations are warranted. We investigated the association of polymorphisms in the ABCG2 and SLC2A9 genes with gout in Korean patients and healthy individuals. Methods: We consecutively enrolled 109 patients with gout and 102 healthy controls. The diagnosis of gout was based on the preliminary criteria of the America College of Rheumatology. Genomic DNA was extracted from whole blood samples. We identified single nucleotide polymorphism (SNP) changes in the ABCG2 and SLC2A9 genes using a direct sequencing technique. rs2231142 in ABCG2 and rs6449213 and rs16890979 in SLC2A9 and nearby regions were amplified by polymerase chain reaction. Results: Patients with gout had significantly higher A/A genotype (29.3% vs. 4.9%, respectively) and A allele (52.8% vs. 26.5%, respectively) frequencies of rs2231142 in ABCG2 than did controls (?2 = 29.42, p < 0.001; odds ratio, 3.32; 95% confidence interval, 2.11 to 5.20). We found novel polymorphisms (c.881A>G and c.1002+78G>A) in the SLC2A9 gene. The univariate logistic regression analysis revealed that the c.881A>G and c.1002+78G>A SNPs were significantly higher in patients than in controls. Conclusions: We demonstrated a significant association between rs2231142 in the ABCG2 gene and gout and identified novel SNPs, c.881A>G and c.1002+78G>A, in the SLC2A9 gene that may be associated with gout in a Korean population. PMID:26552468

  7. Genetic relationship and diversity in a sesame (Sesamum indicum L.) germplasm collection using amplified fragment length polymorphism (AFLP)

    PubMed Central

    Laurentin, Hernán E; Karlovsky, Petr

    2006-01-01

    Background Sesame is an important oil crop in tropical and subtropical areas. Despite its nutritional value and historic and cultural importance, the research on sesame has been scarce, particularly as far as its genetic diversity is concerned. The aims of the present study were to clarify genetic relationships among 32 sesame accessions from the Venezuelan Germplasm Collection, which represents genotypes from five diversity centres (India, Africa, China-Korea-Japan, Central Asia and Western Asia), and to determine the association between geographical origin and genetic diversity using amplified fragment length polymorphism (AFLP). Results Large genetic variability was found within the germplasm collection. A total of 457 AFLP markers were recorded, 93 % of them being polymorphic. The Jaccard similarity coefficient ranged from 0.38 to 0.85 between pairs of accessions. The UPGMA dendrogram grouped 25 of 32 accessions in two robust clusters, but it has not revealed any association between genotype and geographical origin. Indian, African and Chinese-Korean-Japanese accessions were distributed throughout the dendrogram. A similar pattern was obtained using principal coordinates analysis. Genetic diversity studies considering five groups of accessions according to the geographic origin detected that only 20 % of the total diversity was due to diversity among groups using Nei's coefficient of population differentiation. Similarly, only 5% of the total diversity was attributed to differences among groups by the analysis of molecular variance (AMOVA). This small but significant difference was explained by the fact that the Central Asia group had a lower genetic variation than the other diversity centres studied. Conclusion We found that our sesame collection was genetically very variable and did not show an association between geographical origin and AFLP patterns. This result suggests that there was considerable gene flow among diversity centres. Future germplasm collection strategies should focus on sampling a large number of plants. Covering many diversity centres is less important because each centre represents a major part of the total diversity in sesame, Central Asia centre being the only exception. The same recommendation holds for the choice of parents for segregant populations used in breeding projects. The traditional assumption that selecting genotypes of different geographical origin will maximize the diversity available to a breeding project does not hold in sesame. PMID:16483380

  8. [Acute gastroenteritis caused by a Vibrio cholerae non-O1, non-O139 strain harboring a genetic region homologous to the VpaI-7 pathogenicity island].

    PubMed

    Ulloa F, Mara T; Porte, Lorena; Braun J, Stephanie; Dabanch P, Jeannette; Fica C, Alberto; Henrquez A, Tania; Osorio A, Carlos G

    2011-10-01

    Pathogenic Vibrio cholerae isolates, the etiologic agents of cholera, generally express one of two O antigens (O1 or O139). Most environmental isolates are nonpathogenic and are referred to as "non-O1, non-O139". However some V. cholerae non-O1, non-O139 strains are clearly pathogenic and have caused outbreaks or sporadic cases of gastroenteritis and extraintestinal infections in humans. We report a case of acute gastroenteritis by a V. cholerae non-O1, non-O139 harboring a genetic region homologous to a segment of the VpaI-7 V. parahaemolyticus pathogenicity island. PMID:22051624

  9. A LCP 85-384 genetic linkage map enriched with polymorphic SSR markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sugarcane (Saccharum spp. hybrids) cultivars, such as Q165, R570 and LCP 85-384, have been used to construct genetic segregation populations for the development of genetic linkage maps. Based on the genetic linkage map for a selfed-progeny population of R570, the French research group at CIRAD tagge...

  10. Intraspecific chromosomal and genetic polymorphism in Brassica napus L. detected by cytogenetic and molecular markers.

    PubMed

    Amosova, Alexandra V; Zemtsova, Lyudmila V; Grushetskaya, Zoya E; Samatadze, Tatiana E; Mozgova, Galina V; Pilyuk, Yadviga E; Volovik, Valentina T; Melnikova, Natalia V; Zelenin, Alexandr V; Lemesh, Valentina A; Muravenko, Olga V

    2014-04-01

    The application of DNA intercalator 9-aminoacridine allowed us to increase the resolution of chromosome C-banding and DAPI-banding patterns and to investigate chromosomal polymorphism in karyotypes of seven spring and six winter rape varieties. It was shown that the pericentromeric and intercalary C-bands of most of the chromosomes in spring rape were smaller in size and less polymorphic than those of winter rape. More 26S and 5S rDNA sites were found in the winter rape karyotypes than the spring varieties. Separate or colocalized 26S and 5S rDNA sites were revealed on chromosomes 4, 5, 6, 8, 10, 14, 15, 16 and 18. Intervarietal and intravarietal polymorphism of the number and chromosomal localization of rDNA sites were detected. The generalized idiogram of chromosomes of 13 Brassica napus varieties with account of all possibilities of C-banding patterns as well as localization of 26S and 5S rDNA sites were constructed. Polymorphism of the examined molecular and cytogenetic markers as well as the heterozygosis level of FAE1.1 gene controlling erucic acid synthesis in rapeseed was higher in the winter varieties than in the spring ones. The obtained data were in a atisfactory agreement with increased tolerance to environmental stress conditions of winter rape. PMID:24840830

  11. Genetic Association Between NFKBIA -881A>G Polymorphism and Cancer Susceptibility.

    PubMed

    Geng, Peiliang; Ou, Juanjuan; Li, Jianjun; Liao, Yunmei; Wang, Ning; Sa, Rina; Xiang, Lisha; Liang, Houjie

    2015-08-01

    Several epidemiological studies have focused on the role of nuclear factor-kappa-B inhibitor-alpha (NFKBIA) -881 A>G polymorphism in cancer susceptibility. However, the published data have led to contentious results. This study was designed to examine the association between -881 A>G polymorphism and cancer risk.Comprehensive search of PubMed, Web of science and Embase, identified a total of 5 case-control studies. To assess the association, comparison among all subjects plus subgroup analysis by ethnicity was performed and odds ratio (OR) along with 95% confidence interval (CI) was calculated with the fixed-effect model or the random-effects model dependent on the heterogeneity.The pooling data consisting of 1965 cancer cases and 2717 cancer-free controls demonstrated no significant association with overall cancer risk. However, the subgroup of Asian populations showed statistical evidence for an increase in risk of cancer (GG vs. AA, OR, 2.14; 95% CI, 1.03-4.46; GG?+?GA vs. AA, OR, 1.22; 95% CI, 1.01-1.47; GG vs. GA?+?AA, OR, 2.09; 95% CI, 1.01-4.34).This investigation on the association of -881 A>G polymorphism and cancer susceptibility reveals that -881 A>G polymorphism may act as a candidate for cancer development in Asian populations. PMID:26252270

  12. Calving traits of crossbred Brahman Cows are Associated with Heat Shock Protein 70 Genetic Polymorphisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives were to: 1) identify single nucleotide polymorphisms (SNP) located in the promoter region of the bovine heat shock protein 70 gene, and 2) evaluate associations between Hsp70 SNP and calving rates of Brahman-influenced cows. Specific primers were designed for PCR amplification of a 539 b...

  13. Dopaminergic Modulation of Cognitive Preparation for Overt Reading: Evidence from the Study of Genetic Polymorphisms.

    PubMed

    Arnold, Christiane; Gispert, Suzana; Bonig, Halvard; von Wegner, Frederic; Somasundaram, Sriramya; Kell, Christian A

    2016-04-01

    Choosing and implementing the rules for contextually adequate behavior depends on frontostriatal interactions. Observations in Parkinson's disease and pharmacological manipulations of dopamine transmission suggest that these corticobasal loops are modulated by dopamine. To determine, therefore, the physiological contributions of dopamine to task-rule-related processing, we performed a cue-target fMRI reading paradigm in 71 healthy participants and investigated the effects of COMT Val158Met, DAT1 VNTR 9/10, and DRD2/ANKK1 polymorphisms. The DRD2/ANKK1 polymorphism did not affect results. Intermediate prefrontal dopamine concentrations in COMT Val158Met heterozygotes facilitated preparatory interactions between the mesial prefrontal cortex and the left striatum during preparation for overt reading. To our knowledge, this is the first report of an inverted U-shaped curve modulation of cognition-related brain activity by prefrontal dopamine levels. In contrast, a linear effect of COMT Val158Met and DAT1 VNTR 9/10 polymorphisms on preparatory activity in the left inferior frontal gyrus pointed to a negative interaction between tonic lateral prefrontal and phasic subcortical dopamine. The COMT Val158Met polymorphism affected also feedforward and feedback processing in the sensorimotor speech system. Our results suggest that dopamine modulates corticobasal interactions on both the cortical and subcortical level but differently depending on the specific cognitive subprocesses involved. PMID:25596589

  14. Genetic differentiation among 6 populations of red deer (Cervus elaphus L.) in Poland based on microsatellite DNA polymorphism.

    PubMed

    Radko, Anna; Zalewski, D; Rubi?, Dominika; Szumiec, Agnieszka

    2014-12-01

    Recently, there has been considerable interest in genetic differentiation in the Cervidae family. A common tool used to determine genetic variation in different species, breeds and populations is DNA analysis, which allows for direct determination of the differences and changes within a group of animals. Because the analysis of microsatellite polymorphism in different Cervidae populations revealed considerable genetic variability in individual populations, it was important to test a set of markers in animals from these populations.The study was performed with muscle tissue and blood samples collected from a total of 793 red deer. Six groups (subpopulations) of red deer were defined according to region: Masurian (330 animals), Bieszczady (194 animals), Ma?opolska (80 animals), Sudety (76 animals), Lower Silesian (62 animals) and Lubusz (51 animals). The analysis involved 12 STR markers (BM1818, OarAE129, OarFCB5, OarFCB304, RM188, RT 1, RT 13, T26, T156, T193, T501, TGLA53), for which conditions for simultaneous amplification were established.Based on this study, it is concluded that the chosen set of 12 microsatellite markers could be used to evaluate the genetic structure and to monitor changes in Poland's red deer population. PMID:25475981

  15. Genetic association studies of endothelial nitric oxide synthase gene polymorphisms in women with unexplained recurrent pregnancy loss: a systematic and meta-analysis.

    PubMed

    Cao, Yunlei; Zhang, Zhaofeng; Xu, Jianhua; Wang, Jian; Yuan, Wei; Shen, Yueping; Du, Jing

    2014-06-01

    Recurrent pregnancy loss (RPL) is a multifactorial disorder, both genetic and environmental factors contribute to the development of RPL. Recently, the association between endothelial nitric oxide synthase (eNOS) gene polymorphisms and unexplained recurrent pregnancy loss (URPL) has been reported, and the results were inconsistent. Hence, we performed the meta-analysis to drive a more precise estimation of association between eNOS polymorphisms and URPL. Odds ratio (OR) and its 95% confidence interval were calculated under co-dominant (AA vs. BB, TT vs. GG) and additive (A vs. B, T vs. G) genetic models. Studies of eNOS intron 4 VNTR and Glu298Asp were separated by ethnicities. 13 studies included 1,769 URPL cases and 1,376 healthy controls on eNOS intron 4 VNTR polymorphism, and 11 studies were involved in Glu298Asp polymorphism with 1,498 URPL cases and 1,123 healthy controls. The integrated results showed that eNOS Glu298Asp polymorphism was associated with URPL [ORs were 1.91 (1.42-2.56), P < 0.001; 1.67 (1.36-2.04), P < 0.001, respectively]. When analyses were separated by ethnic subgroups, the association between eNOS Glu298Asp polymorphism and URPL was only observed in East Asians [OR = 1.88 (1.52-2.33), P < 0.001 under additive model], and there was no association between eNOS intron 4 VNTR polymorphism and URPL in Caucasians and East Asians. The results indicated a significant association between eNOS Glu298Asp polymorphism and URPL in East Asians. No association was observed between eNOS intron 4 VNTR polymorphism and URPL in Caucasians and East Asians. PMID:24562681

  16. Genetic association between hOGG1 C8069G polymorphism and colorectal cancer risk

    PubMed Central

    Sun, Xiaoge; Yang, Hao; Lin, Yu; Zhao, Jianguo; Bao, Yinna; Liu, Xiulan; Qi, Zhen; Wang, Shaojun; Huang, Congxiu; Yu, Zhilong

    2015-01-01

    Background: hOGG1 C8069G polymorphism has been extensively investigated in single studies as well as meta-analyses in terms of the association with colorectal cancer (CRC). But the results remain contradictory. This study was undertaken to comprehensively evaluate the association of the commonly studied hOGG1 C8069G polymorphism and the susceptibility to CRC. Methods: By searching the electronic databases of PubMed, Embase, and Web of science, 16 available publications consisting of 4,866 cases and 7,363 controls were finally included in our meta-analysis. Stratified analyses by ethnicity and source of control were also carried out to further assess the association between hOGG1 C8069G polymorphism and CRC risk. Results: hOGG1 C8069G polymorphism was not observed to have statistical significance with the susceptibility to CRC (ORCC vs. GG = 0.97, 95% CI = 0.91-1.05; P = 0.995; ORCC + CG vs. GG = 0.98, 95% CI = 0.93-1.04; P = 0.993; ORCC vs. CG + GG = 0.96, 95% CI = 0.90-1.02; P = 0.339; ORallele C vs. allele G = 0.98, 95% CI = 0.94-1.02; P = 0.912; ORCG vs. GG = 0.95, 95% CI = 0.88-1.03; P = 0.526). Similarly, no association was found in the subgroup analysis by ethnicity or the source of control. Conclusions: The results of our meta-analysis did not demonstrate any evidence for significant association between hOGG1 C8069G polymorphism and CRC risk. Future large-scale studies are expected to be conducted to further confirm our findings.

  17. Population Genetic Structure of Clinical and Environmental Isolates of Blastomyces dermatitidis, Based on 27 Polymorphic Microsatellite Markers ▿ †

    PubMed Central

    Meece, Jennifer K.; Anderson, Jennifer L.; Fisher, Matthew C.; Henk, Daniel A.; Sloss, Brian L.; Reed, Kurt D.

    2011-01-01

    Blastomyces dermatitidis, a thermally dimorphic fungus, is the etiologic agent of North American blastomycosis. Clinical presentation is varied, ranging from silent infections to fulminant respiratory disease and dissemination to skin and other sites. Exploration of the population genetic structure of B. dermatitidis would improve our knowledge regarding variation in virulence phenotypes, geographic distribution, and difference in host specificity. The objective of this study was to develop and test a panel of microsatellite markers to delineate the population genetic structure within a group of clinical and environmental isolates of B. dermatitidis. We developed 27 microsatellite markers and genotyped B. dermatitidis isolates from various hosts and environmental sources (n=112). Assembly of a neighbor-joining tree of allele-sharing distance revealed two genetically distinct groups, separated by a deep node. Bayesian admixture analysis showed that two populations were statistically supported. Principal coordinate analysis also reinforced support for two genetic groups, with the primary axis explaining 61.41% of the genetic variability. Group 1 isolates average 1.8 alleles/locus, whereas group 2 isolates are highly polymorphic, averaging 8.2 alleles/locus. In this data set, alleles at three loci are unshared between the two groups and appear diagnostic. The mating type of individual isolates was determined by PCR. Both mating type-specific genes, the HMG and α-box domains, were represented in each of the genetic groups, with slightly more isolates having the HMG allele. One interpretation of this study is that the species currently designated B. dermatitidis includes a cryptic subspecies or perhaps a separate species. PMID:21705544

  18. Adaptive Color Polymorphism and Unusually High Local Genetic Diversity in the Side-Blotched Lizard, Uta stansburiana

    PubMed Central

    Micheletti, Steven; Parra, Eliseo; Routman, Eric J.

    2012-01-01

    Recently, studies of adaptive color variation have become popular as models for examining the genetics of natural selection. We examined color pattern polymorphism and genetic variation in a population of side-blotched lizards (Uta stansburiana) that is found in habitats with both dark (lava) and light colored (granite) substrates. We conducted a limited experiment for adult phenotypic plasticity in laboratory conditions. We recorded both substrate and lizard color patterns in the field to determine whether lizards tended to match their substrate. Finally we examined genetic variation in a gene (melanocortin 1 receptor) that has been shown to affect lizard color in other species and in a presumably neutral gene (mitochondrial cytochrome b). Populations were sampled in the immediate area of the lava flows as well as from a more distant site to examine the role of population structure. Our captive Uta did not change color to match their background. We show that side-blotched lizards tend to match the substrate on which it was caught in the field and that variation in the melanocortin 1 receptor gene does not correlate well with color pattern in this population. Perhaps the most remarkable result is that this population of side-blotched lizards shows extremely high levels of variation at both genetic markers, in the sense of allele numbers, with relatively low levels of between-allele sequence variation. Genetic variation across this small region was as great or greater than that seen in samples of pelagic fish species collected worldwide. Statistical analysis of genetic variation suggests rapid population expansion may be responsible for the high levels of variation. PMID:23133520

  19. Population genetic structure of clinical and environmental isolates of Blastomyces dermatitidis, based on 27 polymorphic microsatellite markers.

    PubMed

    Meece, Jennifer K; Anderson, Jennifer L; Fisher, Matthew C; Henk, Daniel A; Sloss, Brian L; Reed, Kurt D

    2011-08-01

    Blastomyces dermatitidis, a thermally dimorphic fungus, is the etiologic agent of North American blastomycosis. Clinical presentation is varied, ranging from silent infections to fulminant respiratory disease and dissemination to skin and other sites. Exploration of the population genetic structure of B. dermatitidis would improve our knowledge regarding variation in virulence phenotypes, geographic distribution, and difference in host specificity. The objective of this study was to develop and test a panel of microsatellite markers to delineate the population genetic structure within a group of clinical and environmental isolates of B. dermatitidis. We developed 27 microsatellite markers and genotyped B. dermatitidis isolates from various hosts and environmental sources (n=112). Assembly of a neighbor-joining tree of allele-sharing distance revealed two genetically distinct groups, separated by a deep node. Bayesian admixture analysis showed that two populations were statistically supported. Principal coordinate analysis also reinforced support for two genetic groups, with the primary axis explaining 61.41% of the genetic variability. Group 1 isolates average 1.8 alleles/locus, whereas group 2 isolates are highly polymorphic, averaging 8.2 alleles/locus. In this data set, alleles at three loci are unshared between the two groups and appear diagnostic. The mating type of individual isolates was determined by PCR. Both mating type-specific genes, the HMG and ?-box domains, were represented in each of the genetic groups, with slightly more isolates having the HMG allele. One interpretation of this study is that the species currently designated B. dermatitidis includes a cryptic subspecies or perhaps a separate species. PMID:21705544

  20. Population genetic structure of clinical and environmental isolates of Blastomyces dermatitidis, Based on 27 Polymorphic Microsatellite Markers

    USGS Publications Warehouse

    Meece, J.K.; Anderson, J.L.; Fisher, M.C.; Henk, D.A.; Sloss, Brian L.; Reed, K.D.

    2011-01-01

    Blastomyces dermatitidis, a thermally dimorphic fungus, is the etiologic agent of North American blastomycosis. Clinical presentation is varied, ranging from silent infections to fulminant respiratory disease and dissemination to skin and other sites. Exploration of the population genetic structure of B. dermatitidis would improve our knowledge regarding variation in virulence phenotypes, geographic distribution, and difference in host specificity. The objective of this study was to develop and test a panel of microsatellite markers to delineate the population genetic structure within a group of clinical and environmental isolates of B. dermatitidis. We developed 27 microsatellite markers and genotyped B. dermatitidis isolates from various hosts and environmental sources (n = 112). Assembly of a neighbor-joining tree of allele-sharing distance revealed two genetically distinct groups, separated by a deep node. Bayesian admixture analysis showed that two populations were statistically supported. Principal coordinate analysis also reinforced support for two genetic groups, with the primary axis explaining 61.41% of the genetic variability. Group 1 isolates average 1.8 alleles/locus, whereas group 2 isolates are highly polymorphic, averaging 8.2 alleles/locus. In this data set, alleles at three loci are unshared between the two groups and appear diagnostic. The mating type of individual isolates was determined by PCR. Both mating type-specific genes, the HMG and ??-box domains, were represented in each of the genetic groups, with slightly more isolates having the HMG allele. One interpretation of this study is that the species currently designated B. dermatitidis includes a cryptic subspecies or perhaps a separate species. ?? 2011, American Society for Microbiology.

  1. Analysis of genetic polymorphisms affecting the four phospholipase C (plc) genes in Mycobacterium tuberculosis complex clinical isolates.

    PubMed

    Viana-Niero, C; de Haas, P E; van Soolingen, D; Leo, S C

    2004-04-01

    The Mycobacterium tuberculosis genome contains four highly related genes which present significant similarity to Pseudomonas aeruginosa genes encoding phospholipase C enzymes. Three of these genes, plcA, plcB and plcC, are organized in tandem (locus plcABC). The fourth gene, plcD, is located in a different region. This study investigates variations in plcABC and plcD genes in clinical isolates of M. tuberculosis, Mycobacterium africanum and 'Mycobacterium canettii'. Genetic polymorphisms were examined by PCR, Southern blot hybridization, sequence analysis and RT-PCR. Seven M. tuberculosis isolates contain insertions of IS6110 elements within plcA, plcC or plcD. In 19 of 25 M. tuberculosis isolates examined, genomic deletions were identified, resulting in loss of parts of genes or complete genes from the plcABC and/or plcD loci. Partial plcD deletion was observed in one M. africanum isolate. In each case, deletions were associated with the presence of a copy of the IS6110 element and in all occurrences IS6110 was transposed in the same orientation. A mechanism of deletion resulting from homologous recombination of two copies of IS6110 was recognized in a group of genetically related M. tuberculosis isolates. Five M. tuberculosis isolates presented major polymorphisms in the plcABC and plcD regions, along with loss of expression competence that affected all four plc genes. Phospholipase C is a well-known bacterial virulence factor. The precise role of phospholipase C in the pathogenicity of M. tuberculosis is unknown, but considering the potential importance that the plc genes may have in the virulence of the tubercle bacillus, the study of isolates cultured from patients with active tuberculosis bearing genetic variations affecting these genes may provide insights into the significance of phospholipase C enzymes for tuberculosis pathogenicity. PMID:15073306

  2. ARID5B Genetic Polymorphisms Contribute to Racial Disparities in the Incidence and Treatment Outcome of Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Xu, Heng; Cheng, Cheng; Devidas, Meenakshi; Pei, Deqing; Fan, Yiping; Yang, Wenjian; Neale, Geoff; Scheet, Paul; Burchard, Esteban G.; Torgerson, Dara G.; Eng, Celeste; Dean, Michael; Antillon, Frederico; Winick, Naomi J.; Martin, Paul L.; Willman, Cheryl L.; Camitta, Bruce M.; Reaman, Gregory H.; Carroll, William L.; Loh, Mignon; Evans, William E.; Pui, Ching-Hon; Hunger, Stephen P.; Relling, Mary V.; Yang, Jun J.

    2012-01-01

    Purpose Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome. Patients and Methods We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95% European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10% Native American ancestry; 330 cases and 541 controls). We determined the relationships between ARID5B SNP genotype and ALL relapse risk in 1,605 children treated on the Children's Oncology Group (COG) P9904/9905 clinical trials. Results Among 49 ARID5B SNPs interrogated, 10 were significantly associated with ALL susceptibility in both whites and Hispanics (P < .05), with risk alleles consistently more frequent in Hispanics than in whites. rs10821936 exhibited the most significant association in both races (P = 8.4 10?20 in whites; P = 1 10?6 in Hispanics), and genotype at this SNP was highly correlated with local Native American genetic ancestry (P = 1.8 10?8). Multivariate analyses in Hispanics identified an additional SNP associated with ALL susceptibility independent of rs10821936. Eight ARID5B SNPs were associated with both ALL susceptibility and relapse hazard; the alleles related to higher ALL incidence were always linked to poorer treatment outcome and were more frequent in Hispanics. Conclusion ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease. PMID:22291082

  3. Predisposition to Childhood Otitis Media and Genetic Polymorphisms within the Toll-Like Receptor 4 (TLR4) Locus

    PubMed Central

    Kentala, Erna; Hammarn-Malmi, Sari; Bhutta, Mahmood F.; MacArthur, Carol J.; Wilmot, Beth; Casselbrant, Margaretha; Conley, Yvette P.; Weeks, Daniel E.; Mandel, Ellen M.; Vaarala, Outi; Kallio, Anna; Melin, Merit; Nieminen, Janne K.; Leinonen, Eira; Kere, Juha; Mattila, Petri S.

    2015-01-01

    Background Predisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts. Methods We investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls. A positive association signal was followed up in a tagging approach and tested in an independent Finnish cohort of 205 cases, in a British cohort of 1269 trios, as well as in two cohorts from the United States (US); one with 403 families and the other with 100 cases and 104 controls. Results In the initial Finnish cohort, the SNP rs5030717 in the TLR4 gene region showed significant association (OR 1.33, P = .003) to OM. Tagging SNP analysis of the gene found rs1329060 (OR 1.33, P = .002) and rs1329057 (OR 1.29, P = .003) also to be associated. In the more severe phenotype the association was stronger. This finding was supported by an independent Finnish case cohort, but the associations failed to replicate in the British and US cohorts. In studies on TLR4 signaling in 20 study subjects, the three-marker risk haplotype correlated with a decreased TNF? secretion in myeloid dendritic cells. Conclusions The TLR4 gene locus, regulating the innate immune response, influences the genetic predisposition to childhood OM in a subpopulation of patients. Environmental factors likely modulate the genetic components contributing to the risk of OM. PMID:26177520

  4. Potential relationship between single nucleotide polymorphisms used in forensic genetics and diseases or other traits in European population.

    PubMed

    Pombar-Gomez, Maria; Lopez-Lopez, Elixabet; Martin-Guerrero, Idoia; Garcia-Orad Carles, Africa; de Pancorbo, Marian M

    2015-05-01

    Single nucleotide polymorphisms (SNPs) are an interesting option to facilitate the analysis of highly degraded DNA by allowing the reduction of the size of the DNA amplicons. The SNPforID 52-plex panel is a clear example of the use of non-coding SNPs in forensic genetics. However, nonstop advances in studies of genetic polymorphisms are leading to the discovery of new associations between SNPs and diseases. The aim of this study was to perform a comprehensive review of the state of association between the 52 SNPs in the 52-plex panel and diseases or other traits related to their treatment, such as drug response characters. In order to achieve this goal, we have conducted a bioinformatic search for each SNP included in the panel and the SNPs in linkage disequilibrium (LD) with them in the European population (r (2)  > 0.8). A total of 424 SNPs (52 in the panel and 372 in LD) were investigated in PubMed, Scopus, and dbSNP databases. Our results show that three SNPs in the SNPforID 52-plex panel (rs2107612, rs1979255, rs1463729) have been associated with diseases such as hypertension or macular degeneration, as well as drug response. Similarly, three out of the 372 SNPs in LD (rs2107614, r (2)  = 0.859; rs765250, r (2)  = 0.858; rs11064560, r (2)  = 0,887) are also associated with various pathologies. In view of these results, we propose the need for a periodic review of the SNPs used in forensic genetics in order to keep their associations with diseases or related phenotypes updated and to evaluate their continuity in forensic panels for avoiding legal and ethical conflicts. PMID:25763762

  5. Predictive impact of genetic polymorphisms in DNA repair genes on susceptibility and therapeutic outcomes to colorectal cancer patients.

    PubMed

    Sun, Kang; Gong, Aixia; Liang, Pin

    2015-03-01

    Several hereditary syndromes characterized by defective DNA repair are associated with high risk of colorectal cancer (CRC). To explore whether common polymorphisms in DNA repair genes affect risk and prognosis of CRC, we evaluated the association between single nucleotide polymorphisms (SNPs) in XPG, XPC, and WRN gene and susceptibility of CRC, and clinical outcomes in a population-based case-control study. A total of 890 CRC cases and 910 controls recruited into the study provided a biologic sample. Individuals with variant genotypes of XPC Ala499Val appeared to be associated with the increased risk of CRC. WRN Cys1367Arg variants carriers showed an increased susceptibility for CRC. More importantly, the risk of CRC increased further in a combined analysis of multiple polymorphisms. Furthermore, stratified analyses revealed that XPG Arg1104His polymorphism was associated with tumor differentiation of CRC patients (P?=?0.043). Log-rank test and adjusted multivariate Cox regression analysis verified that XPG Arg1104His variants were associated with a longer disease-free survival (DFS) [CG genotype: adjusted HR (95% confidence interval (CI))?=?0.163 (0.107-0.248), P?polymorphism and prognosis in CRC patients. Our findings will add to the literature on the impact of genetic variation in DNA repair genes involved in susceptibility for CRC and therapeutic outcomes in response to oxaliplatin-based chemotherapy. PMID:25355595

  6. Role of Genetic Polymorphisms in NFKB-Mediated Inflammatory Pathways in Response to Primary Chemoradiation Therapy for Rectal Cancer

    SciTech Connect

    Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

    2014-11-01

    Purpose: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Methods and Materials: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. Results: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Conclusions: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment.

  7. Large-scale population-based metabolic phenotyping of thirteen genetic polymorphisms related to one-carbon metabolism.

    PubMed

    Fredriksen, Ase; Meyer, Klaus; Ueland, Per Magne; Vollset, Stein Emil; Grotmol, Tom; Schneede, Jrn

    2007-09-01

    Several polymorphisms of genes involved in one-carbon metabolism have been identified. The reported metabolic phenotypes are often based on small studies providing inconsistent results. This large-scale study of 10,601 population-based samples was carried out to investigate the association between a panel of biochemical parameters and genetics variants related to one-carbon metabolism. Concentrations of total homocysteine (tHcy), folate, vitamin B(12) (cobalamin), methylmalonic acid (MMA), vitamin B(2) (riboflavin), vitamin B(6) (PLP), choline, betaine, dimethylglycine (DMG), cystathionine, cysteine, methionine, and creatinine were determined in serum/plasma. All subjects were genotyped for 13 common polymorphisms: methylenetetrahydrofolate reductase (MTHFR) c.665C>T (known as 677C>T; p.Ala222Val) and c.1286A>C (known as 1298A>C; p.Glu429Ala); methionine synthase (MTR) c.2756A>G (p.Asp919Gly); methionine synthase reductase (MTRR) c.66A>G (p.Ile22Met); methylenetetrahydrofolate dehydrogenase (MTHFD1) c.1958G>A (p.Arg653Gln); betaine homocysteine methyltransferase (BHMT) c.716G>A (known as 742G>A; p.Arg239Gln); cystathionine beta-synthase (CBS) c.844_845ins68 and c.699C>T (p.Tyr233Tyr); transcobalamin-II (TCN2) c.67A>G (p.Ile23Val) and c.776C>G (p.Pro259Arg); reduced folate carrier-1 (SLC19A1) c.80G>A (p.Arg27His); and paraoxonase-1 (PON1) c.163T>A (p.Leu55Met) and c.575A>G (p.Gln192Arg). The metabolic profile in terms of the measured vitamins and metabolites were investigated for these 13 polymorphisms. We confirmed the strong associations of MTHFR c.665C>T with tHcy and folate, but also observed significant (P<0.01) changes in metabolite concentrations according to other gene polymorphisms. These include MTHFR c.1286A>C (associations with tHcy, folate and betaine), MTR c.2756A>G (tHcy), BHMT c.716G>A (DMG), CBS c.844_845ins68 (tHcy, betaine), CBS c.699C>T (tHcy, betaine, cystathionine) and TCN2 c.776C>G (MMA). No associations were observed for the other polymorphisms investigated. PMID:17436311

  8. Identification and genetic mapping of highly polymorphic microsatellite loci from an EST database of the septoria tritici blotch pathogen Mycosphaerella graminicola.

    PubMed

    Goodwin, Stephen B; van der Lee, Theo A J; Cavaletto, Jessica R; Te Lintel Hekkert, Bas; Crane, Charles F; Kema, Gert H J

    2007-05-01

    A database of 30,137 EST sequences from Mycosphaerella graminicola, the septoria tritici blotch fungus of wheat, was scanned with a custom software pipeline for di- and trinucleotide units repeated tandemly six or more times. The bioinformatics analysis identified 109 putative SSR loci, and for 99 of them, flanking primers were developed successfully and tested for amplification and polymorphism by PCR on five field isolates of diverse origin, including the parents of the standard M. graminicola mapping population. Seventy-seven of the 99 primer pairs generated an easily scored banding pattern and 51 were polymorphic, with up to four alleles per locus, among the isolates tested. Among these 51 loci, 23 were polymorphic between the parents of the mapping population. Twenty-one of these as well as two previously published microsatellite loci were positioned on the existing genetic linkage map of M. graminicola on 13 of the 24 linkage groups. Most (66%) of the primer pairs also amplified bands in the closely related barley pathogen Septoria passerinii, but only six were polymorphic among four isolates tested. A subset of the primer pairs also revealed polymorphisms when tested with DNA from the related banana black leaf streak (Black Sigatoka) pathogen, M. fijiensis. The EST database provided an excellent source of new, highly polymorphic microsatellite markers that can be multiplexed for high-throughput genetic analyses of M. graminicola and related species. PMID:17074520

  9. Biomarkers of susceptibility following benzene exposure: influence of genetic polymorphisms on benzene metabolism and health effects.

    PubMed

    Carbonari, Damiano; Chiarella, Pieranna; Mansi, Antonella; Pigini, Daniela; Iavicoli, Sergio; Tranfo, Giovanna

    2016-02-01

    Benzene is a ubiquitous occupational and environmental pollutant. Improved industrial hygiene allowed airborne concentrations close to the environmental context (1-1000 g/m(3)). Conversely, new limits for benzene levels in urban air were set (5 g/m(3)). The biomonitoring of exposure to such low benzene concentrations are performed measuring specific and sensitive biomarkers such as S-phenylmercapturic acid, trans, trans-muconic acid and urinary benzene: many studies referred high variability in the levels of these biomarkers, suggesting the involvement of polymorphic metabolic genes in the individual susceptibility to benzene toxicity. We reviewed the influence of metabolic polymorphisms on the biomarkers levels of benzene exposure and effect, in order to understand the real impact of benzene exposure on subjects with increased susceptibility. PMID:26764284

  10. Genetic polymorphisms and microRNAs: new direction in molecular epidemiology of solid cancer

    PubMed Central

    Slaby, Ondrej; Bienertova-Vasku, Julie; Svoboda, Marek; Vyzula, Rostislav

    2012-01-01

    Abstract MicroRNAs (miRNAs) are small non-coding RNAs, which regulate gene expression. Single nucleotide polymorphisms (SNPs) may occur in miRNA biogenesis pathway genes, primary miRNA, pre-miRNA or a mature miRNA sequence. Such polymorphisms may be functional with respect to biogenesis and actions of mature miRNA. Specific SNPs were identified in predicted miRNA target sites within 3? untranslated regions of mRNAs. These SNPs have a potential to affect the efficiency of miRNA binding to the target sites or can create or disrupt binding sites. Resulting gene dysregulation may involve changes in phenotype and may eventually prove critical for the susceptibility to cancer and its onset as well as for estimates of prognosis and therapy response. In this review, we provide a comprehensive list of potentially functional miRNA-related SNPs and summarize their importance as candidate cancer biomarkers. PMID:21692980

  11. The Associations between Two Vital GSTs Genetic Polymorphisms and Lung Cancer Risk in the Chinese Population: Evidence from 71 Studies

    PubMed Central

    Ma, Ting; Han, Liyuan; Mao, Guochuan; Chen, Jian; Yue, Xia; Wang, Huiqin; Zhang, Lu; Jin, Guixiu; Jiang, Jianmin; Zhao, Jinshun; Zou, Baobo

    2014-01-01

    Background The genetic polymorphisms of glutathione S-transferase (GSTs) have been suspected to be related to the development of lung cancer while the current results are conflicting, especially in the Chinese population. Methods Data on genetic polymorphisms of glutathione S-transferase Mu 1 (GSTM1) from 68 studies, glutathione S-transferase theta 1 (GSTT1) from 17 studies and GSTM1-GSTT1 from 8 studies in the Chinese population were reanalyzed on their association with lung cancer risk. Odds ratios (OR) were pooled using forest plots. 9 subgroups were all or partly performed in the subgroup analyses. The Galbraith plot was used to identify the heterogeneous records. Potential publication biases were detected by Begg's and Egger's tests. Results 71 eligible studies were identified after screening of 1608 articles. The increased association between two vital GSTs genetic polymorphisms and lung cancer risk was detected by random-effects model based on a comparable heterogeneity. Subgroup analysis showed a significant relationship between squamous carcinoma (SC), adenocarcinoma (AC) or small cell lung carcinoma (SCLC) and GSTM1 null genotype, as well as SC or AC and GSTT1 null genotype. Additionally, smokers with GSTM1 null genotype had a higher lung cancer risk than non-smokers. Our cumulative meta-analysis demonstrated a stable and reliable result of the relationship between GSTM1 null genotype and lung cancer risk. After the possible heterogeneous articles were omitted, the adjusted risk of GSTs and lung cancer susceptibility increased (fixed-effects model: ORGSTM1 = 1.23, 95% CI: 1.19 to 1.27, P<0.001; ORGSTT1 = 1.18, 95% CI: 1.10 to 1.26, P<0.001; ORGSTM1-GSTT1 = 1.33, 95% CI: 1.10 to 1.61, P = 0.004). Conclusions An increased risk of lung cancer with GSTM1 and GSTT1 null genotype, especially with dual null genotype, was found in the Chinese population. In addition, special histopathological classification of lung cancers and a wide range of gene-environment and gene-gene interaction analysis should be taken into consideration in future studies. PMID:25036724

  12. Genetic polymorphisms of interleukin 6 and interleukin 10 in Egyptian patients with systemic lupus eythematosus.

    PubMed

    Talaat, R M; Alrefaey, S A; Bassyouni, I H; Ashour, M E; Raouf, A A

    2016-03-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Cytokine gene polymorphisms play an important role in SLE. Thus, this study aimed to investigate the associations between interleukin 6 (IL-6) and interleukin 10 (IL-10) promoter single-nucleotide polymorphisms (SNPs) and their susceptibility to SLE and the implications for plasma levels. We genotyped IL-6-174G/C (rs1800795) using mutagenically separated polymerase chain reaction (MS-PCR) and IL-10-1082G/A (rs1800896) and -819C/T (rs1800871) using sequence specific primer polymerase chain reaction (SSP-PCR) in 100 Egyptian patients and 119 controls. The plasma levels of IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). There was significant increase in the frequency of IL-6 (-174) GG genotype (P?polymorphisms in SLE patients. In conclusion, our preliminary study indicated that bo