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Sample records for harbors genetic polymorphisms

  1. Genetic polymorphisms and disease prevention.

    PubMed

    Mahoney, Martin C

    2007-06-15

    Building upon the resources of traditional epidemiology, molecular epidemiology has extended our understanding that disease risk varies based not only upon acquired factors (e.g., exposures, behaviors, demographics), but also as a function of inherited factors (e.g., genetic polymorphisms). Individual susceptibility to cancer is influenced by polymorphisms in phase I enzymes (e.g., activation), phase 2 enzymes (e.g., detoxification), defects in the repair of DNA damage and other cancer susceptibility genes. Because tobacco use and nutrition represent behaviors/exposures which account for a significant number of cancer cases and deaths, these two factors are used to illustrate the relationship between genetic polymorphisms and disease prevention. Susceptibility to the health risks of smoking appears to be influenced by genetic factors that impact initiation, dependence, and nicotine metabolism. Nutrient metabolism also involves polymorphic enzyme pathways and gene-nutrient interactions may influence cancer risk. While the discipline of molecular epidemiology continues to face methodologic challenges related to the need to study large numbers of subjects, current knowledge can be applied to prevention activities. Genetic polymorphisms, and other molecular markers, can be used to develop clinical prevention studies targeted to unique subsets of persons at the highest risk of developing disease. Knowledge about the relationships between polymorphisms and disease outcomes can also be used for reinforcing healthy lifestyles, motivating positive behavior changes, helping to target medical therapy, and aiding in better focusing surveillance activities. PMID:17252563

  2. Genetics Home Reference: Floating-Harbor syndrome

    MedlinePlus

    ... Arpin S, Afenjar A, Dubern B, Toutain A, Cabrol S, Héron D. Floating-Harbor Syndrome: report on a case ... G, Whiteford ML, Quaio CR, Gomy I, Bertola DR, Albrecht B, Platzer K, McGillivray G, Zou R, ...

  3. Migraine and genetic polymorphisms: an overview.

    PubMed

    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), β-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.

  4. 59. Cold Spring Harbor symposium on quantitative biology: Molecular genetics of cancer

    SciTech Connect

    1994-12-31

    Investigation of the mechanistic aspects of cancer has its roots in the studies on tumor viruses and their effects on cell proliferation, function, and growth. This outstanding progress was well documented in previous Cold Spring Harbor Symposia on Quantitative Biology. In the early to mid 1980s, progress on the development of chromosome mapping strategies and the accumulation of DNA probes that identified polymorphisms, encouraged by the international Human Genome Project, enabled the identification of other genes that contributed to familial inheritance of high susceptibility to specific cancers. This approach was very successful and led to a degree of optimism that one aspect of cancer, the multistep genetic process from early neoplasia to metastatic tumors, was beginning to be understood. It therefore seemed appropriate that the 59th Symposium on Quantitative Biology focus attention on the Molecular Genetics of Cancer. The concept was to combine the exciting progress on the identification of new genetic alterations in human tumor cells with studies on the function of the cancer gene products and how they go awry in tumor cells.

  5. 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

  6. Genetic epidemiology of single-nucleotide polymorphisms.

    PubMed

    Collins, A; Lonjou, C; Morton, N E

    1999-12-21

    On the causal hypothesis, most genetic determinants of disease are single-nucleotide polymorphisms (SNPs) that are likely to be selected as markers for positional cloning. On the proximity hypothesis, most disease determinants will not be included among markers but may be detected through linkage disequilibrium with other SNPs. In that event, allelic association among SNPs is an essential factor in positional cloning. Recent simulation based on monotonic population expansion suggests that useful association does not usually extend beyond 3 kb. This is contradicted by significant disequilibrium at much greater distances, with corresponding reduction in the number of SNPs required for a cost-effective genome scan. A plausible explanation is that cyclical expansions follow population bottlenecks that establish new disequilibria. Data on more than 1,000 locus pairs indicate that most disequilibria trace to the Neolithic, with no apparent difference between haplotypes that are random or selected through a major disease gene. Short duration may be characteristic of alleles contributing to disease susceptibility and haplotypes characteristic of particular ethnic groups. Alleles that are highly polymorphic in all ethnic groups may be older, neutral, or advantageous, in weak disequilibrium with nearby markers, and therefore less useful for positional cloning of disease genes. Significant disequilibrium at large distance makes the number of suitably chosen SNPs required for genome screening as small as 30,000, or 1 per 100 kb, with greater density (including less common SNPs) reserved for candidate regions.

  7. Genetic Polymorphisms, Hormone Levels, and Hot Flashes in Midlife Women

    PubMed Central

    Schilling, Chrissy; Gallicchio, Lisa; Miller, Susan R.; Langenberg, Patricia; Zacur, Howard; Flaws, Jodi A.

    2007-01-01

    Objective Hot flashes disrupt the lives of millions of women each year. Although hot flashes are a public health concern, little is known about risk factors that predispose women to hot flashes. Thus, the objective of this study was to examine whether sex steroid hormone levels and genetic polymorphisms in hormone biosynthesis and degradation enzymes are associated with the risk of hot flashes. Methods In a cross-sectional study design, midlife women aged 45 to 54 years (n=639) were recruited from Baltimore and its surrounding counties. Participants completed a questionnaire and donated a blood sample for steroid hormone analysis and genotyping. The associations between genetic polymorphisms and hormone levels, as well as the associations between genetic polymorphisms, hormone levels, and hot flashes were examined using statistical models. Results A polymorphism in CYP1B1 was associated with lower dehydroepiandrosterone-sulfate (DHEA-S) and progesterone levels, while a polymorphism in CYP19 (aromatase) was associated with higher testosterone and DHEA-S levels. Lower progesterone and sex hormone binding globulin levels, lower free estradiol index, and a higher ratio of total androgens to total estrogens were associated with the experiencing of hot flashes. A polymorphism in CYP1B1 and a polymorphism in 3βHSD were both associated with hot flashes. Conclusion Some genetic polymorphisms may be associated with altered levels of hormones in midlife women. Further, selected genetic polymorphisms and altered hormone levels may be associated with the risk of hot flashes in midlife women. PMID:17187946

  8. Pharmacogenetic analysis of clinically relevant genetic polymorphisms.

    PubMed

    McLeod, Howard L

    2005-11-15

    The ascertainment of the human genome sequence has generated great enthusiasm for the use of gene-based approaches to improve virtually all aspects of medical care. Particular interest has focused on the field of pharmacogenetics--for example, the use of an individual's genetic profile to optimize drug prescription. This approach takes advantage of the presence of single-nucleotide polymorphisms (SNPs) or other genetic variants in every gene in the human genome. There are currently > 9 million SNPs in the human SNP database dbSNP, with an estimated 11 million variants ultimately to be found in the human population. To date, the preponderance of interest in this field has centered on the potential of applying this approach to subacute or chronic illnesses, such as cancer, cardiovascular disease, human immunodeficiency virus infection, or rheumatologic disorders. In contrast, little attention has been devoted to the potential utility of implementing the pharmacogenomic methodology for guiding drug selection for acutely ill patients in the critical care environment. Although such an approach has theoretical appeal as a means of enhancing quality and improving outcomes in this setting, several obstacles currently exist and slow the progress toward clinical application. PMID:16237646

  9. Genetics Home Reference: catecholaminergic polymorphic ventricular tachycardia

    MedlinePlus

    ... for This Page Cerrone M, Napolitano C, Priori SG. Catecholaminergic polymorphic ventricular tachycardia: A paradigm to understand ... on PubMed Central Liu N, Ruan Y, Priori SG. Catecholaminergic polymorphic ventricular tachycardia. Prog Cardiovasc Dis. 2008 ...

  10. Sexual selection and genetic colour polymorphisms in animals.

    PubMed

    Wellenreuther, Maren; Svensson, Erik I; Hansson, Bengt

    2014-11-01

    Genetic colour polymorphisms are widespread across animals and often subjected to complex selection regimes. Traditionally, colour morphs were used as simple visual markers to measure allele frequency changes in nature, selection, population divergence and speciation. With advances in sequencing technology and analysis methods, several model systems are emerging where the molecular targets of selection are being described. Here, we discuss recent studies on the genetics of sexually selected colour polymorphisms, aiming at (i) reviewing the evidence of sexual selection on colour polymorphisms, (ii) highlighting the genetic architecture, molecular and developmental basis underlying phenotypic colour diversification and (iii) discuss how the maintenance of such polymorphisms might be facilitated or constrained by these. Studies of the genetic architecture of colour polymorphism point towards the importance of tight clustering of colour loci with other trait loci, such as in the case of inversions and supergene structures. Other interesting findings include linkage between colour loci and mate preferences or sex determination, and the role of introgression and regulatory variation in fuelling polymorphisms. We highlight that more studies are needed that explicitly integrate fitness consequences of sexual selection on colour with the underlying molecular targets of colour to gain insights into the evolutionary consequences of sexual selection on polymorphism maintenance.

  11. Genetic Polymorphisms Influence Cognition in Patients Undergoing Carotid Interventions.

    PubMed

    Hitchner, Elizabeth; Morrison, Doug; Liao, Phoebe; Rosen, Allyson; Zhou, Wei

    2016-09-01

    While carotid interventions help decrease the risk of stroke, nearly 40% of patients experience cognitive deterioration. Genetic polymorphism in apolipoprotein E (ApoE) and brain-derived neurotrophic factor (BDNF) have been implicated in cognitive impairment; however, it is unclear whether they may influence cognitive changes in patients undergoing carotid intervention. In this study, we seek to assess the role of genetic polymorphisms in carotid intervention-related cognitive change. Polymorphisms related to cognitive function were chosen for this preliminary analysis. Over 2 years, patients undergoing carotid interventions were prospectively recruited. Patients underwent neuropsychological testing 2 weeks prior to and at 1 month following their procedure. Saliva samples were collected for genetic analysis. Logistic regressions were used to identify associations between polymorphisms and cognitive measures. A total of 91 patients were included; all were male with an average age of 70 years. The majority of patients exhibited hypertension (95%) and a history of smoking (81%). Presence of ApoE 4 allele was associated with depression (p= 0.047). After correcting for age and genetic polymorphisms in BDNF and serotonin transporter (5-HTT), ApoE 4 allele was associated with depression (p= 0.044) and showed a trend with baseline cognitive impairment (p= 0.10). Age ≥ 70 years was associated with baseline cognitive impairment after adjusting for the three genetic polymorphisms (p= 0.03). Patients with ApoE 4 and BDNF A polymorphisms performed less well on the visual and verbal memory measures, respectively. Polymorphisms in ApoE and BDNF may provide insight on cognition in patients undergoing carotid interventions; however, the mechanism of this relationship remains unclear. PMID:27574384

  12. Interleukin 28B genetic polymorphism and hepatitis B virus infection.

    PubMed

    Takahashi, Toru

    2014-09-14

    Interleukin (IL) 28B genetic polymorphism is significantly associated with the sustained virological response rate in patients with chronic hepatitis C treated with pegylated interferon-α (PEG-IFN) plus ribavirin and with spontaneous hepatitis C virus clearance. However, a consensus on the relationship between IL28B genetic polymorphism and the favorable outcome of chronic hepatitis B virus infection defined by hepatitis B e antigen seroconversion, and/or hepatitis B surface antigen seroclearance in patients treated with interferon or PEG-IFN has not been reached. Several reports failed to show a positive association, while some studies demonstrated a positive association in certain subject settings. More prospective studies including large cohorts are needed to determine the possible association between IL28B genetic polymorphism and the outcome of interferon or PEG-IFN treatment for chronic hepatitis B.

  13. 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

  14. A polymorphic DNA marker genetically linked to Huntington's disease.

    PubMed

    Gusella, J F; Wexler, N S; Conneally, P M; Naylor, S L; Anderson, M A; Tanzi, R E; Watkins, P C; Ottina, K; Wallace, M R; Sakaguchi, A Y

    Family studies show that the Huntington's disease gene is linked to a polymorphic DNA marker that maps to human chromosome 4. The chromosomal localization of the Huntington's disease gene is the first step in using recombinant DNA technology to identify the primary genetic defect in this disorder.

  15. 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.

  16. Mouse chromosome 11 harbors genetic determinants of hippocampal strain-specific nicotinic receptor expression.

    PubMed

    Rogers, Scott W; Weis, Janis J; Ma, Ying; Teuscher, Cory; Gahring, Lorise C

    2008-01-01

    Differences between isogenic mouse strains in cellular expression of the neuronal nicotinic acetylcholine (ACh) receptor subunit alpha 4 (nAChR alpha 4) by the dorsal hippocampus are well known. To investigate further the genetic basis of these variations, expression of the nAChR alpha 4 subunit was measured in congenic mouse lines derived from two strains exhibiting notable divergence in the expression of this subunit: C3H and C57BL/6. Congenic lines carrying reciprocally introgressed regions (quantitative trait loci; QTL) from chromosomes 4, 5, and 12 each retained the phenotype most closely associated with the parental strain. However, in congenic lines harboring the reciprocal transfer of a chromosome 11 QTL, a characteristic difference in the ratio of interneurons versus astrocytes expressing nAChR alpha 4 in the CA1 region is reversed relative to the parental strain. These finding suggest that this chromosomal segment harbors genes that regulate strain distinct hippocampal morphology that is revealed by nAChR alpha 4 expression.

  17. EFFECT OF CYTOKINE AND PHARMACOGENOMIC GENETIC POLYMORPHISMS IN TRANSPLANTATION

    PubMed Central

    Girnita, Diana M; Burckart, Gilbert; Zeevi, Adriana

    2008-01-01

    Purpose of review Recent investigations related to the polymorphism of genes that affect drug therapy and the polymorphisms of cytokines and growth factors that control immune responses have been associated with outcomes following solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). This review will provide a current update on the most recent findings and discuss the challenges for developing individualized therapeutic strategies based on clinical and genetic profiles. Recent Findings Single nucleotide polymorphisms (SNPs) of cytokine genes have been shown to have an impact in vitro or in vivo protein secretion, dividing the individuals into High, Low or Intermediate producers for a given molecule. Many studies have been performed to determine the contribution of single cytokine gene SNPs on SOT or HSCT outcomes and the reported results are still controversial. However, analysis of a combination of several cytokines and/or cytokine receptor polymorphisms adjusted for known clinical risk factors and ethnicity have resulted in significant clinical correlations. Furthermore, associations with gene polymorphisms that affect immunosuppressive drug therapy in solid organ transplantation have also been extensively studied. There is a continuous flow of new information regarding functional SNPs that may affect the immune response to the allograft or to drug therapy and their impact on clinical outcomes have yet to be validated in large cohorts SOT or HSCT Summary Consolidating the information that we have on pharmacogenetics and on cytokine genetics to produce patient-oriented individualized drug regimens is an important challenge in transplantation medicine. Using a multi-variant approach based on genetic profile and other relevant clinical factors a score system may be developed to predict the severity of rejection, infection or other complications associated with transplantation. The ultimate goal of these studies is to improve patient

  18. Genetic polymorphisms as a risk factor for dyslipidemia in children.

    PubMed

    Santos, Izabela R; Fernandes, Ana Paula; Sousa, Marinez O; Ferreira, Cláudia N; Gomes, Karina B

    2013-06-01

    Dyslipidemia is an important etiological factor for development of cardiovascular disease, which is the leading cause of deaths in adults. Given the growing global epidemic of dyslipidemia, lipoprotein metabolism disorders have become an important health problem not only in adulthood, but have also emerged as an increasingly risk factor in childhood. Although several genome-wide association studies in multiple large population-based cohorts of adults and meta-analyses have identified susceptibility genes or loci, especially in lipid-related traits, it is of great importance to evaluate genetic predisposition at an early age. Recent findings suggest that the identification of polymorphisms in the metabolism of lipids in childhood may help fight subclinical atherosclerosis and its progression to cardiovascular complications in adulthood. Therefore, the aim of this study was to review genetic polymorphisms as risk factors associated with dyslipidemia in children and adolescents. PMID:27625842

  19. Genetic polymorphisms as a risk factor for dyslipidemia in children

    PubMed Central

    Santos, Izabela R.; Fernandes, Ana Paula; Sousa, Marinez O.; Ferreira, Cláudia N.; Gomes, Karina B.

    2013-01-01

    Dyslipidemia is an important etiological factor for development of cardiovascular disease, which is the leading cause of deaths in adults. Given the growing global epidemic of dyslipidemia, lipoprotein metabolism disorders have become an important health problem not only in adulthood, but have also emerged as an increasingly risk factor in childhood. Although several genome-wide association studies in multiple large population-based cohorts of adults and meta-analyses have identified susceptibility genes or loci, especially in lipid-related traits, it is of great importance to evaluate genetic predisposition at an early age. Recent findings suggest that the identification of polymorphisms in the metabolism of lipids in childhood may help fight subclinical atherosclerosis and its progression to cardiovascular complications in adulthood. Therefore, the aim of this study was to review genetic polymorphisms as risk factors associated with dyslipidemia in children and adolescents. PMID:27625842

  20. 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.

  1. [Genetic polymorphism of hemoglobin, protein systems, blood enzymes and their relationship to reproducibility].

    PubMed

    Siratskiĭ, I Z

    1992-01-01

    The genetic polymorphism of haemoglobin, transferrin, amylase, alkaline phosphatase, ceruloplasmin, beta-lactoglobulins and casein were studied. The relationship between the level of the heterozygosity of the blood polymorphic protein and enzyme systems was determined.

  2. 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

  3. Genetic diversity and chemical polymorphism of some Thymus species.

    PubMed

    Rustaiee, Ali Reza; Yavari, Alireza; Nazeri, Vahideh; Shokrpour, Majid; Sefidkon, Fatemeh; Rasouli, Musa

    2013-06-01

    To ascertain whether there are chemical and genetic relationships among some Thymus species and also to determine correlation between these two sets of data, the essential-oil composition and genetic variability of six populations of Thymus including: T. daenensis ČELAK. (two populations), T. fallax FISCH. & C.A.MEY., T. fedtschenkoi RONNIGER, T. migricus KLOKOV & DES.-SHOST., and T. vulgaris L. were analyzed by GC and GC/MS, and also by randomly amplified polymorphic DNA (RAPD). Thus, 27 individuals were analyzed using 16 RAPD primers, which generated 264 polymorphic scorable bands and volatiles isolated by distillation extraction were subjected to GC and GC/MS analyses. The yields of oils ranged from 2.1 to 3.8% (v/w), and 34 components were identified, amounting to a total percentage of 97.8-99.9%. RAPD Markers allowed a perfect distinction between the different species based on their distinctive genetic background. However, they did not show identical clustering with the volatile-oil profiles. PMID:23776024

  4. 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.

  5. Random amplified polymorphic DNA analysis of genetically modified organisms.

    PubMed

    Yoke-Kqueen, Cheah; Radu, Son

    2006-12-15

    Randomly amplified polymorphic DNA (RAPD) was used to analyzed 78 samples comprises of certified reference materials (soya and maize powder), raw seeds (soybean and maize), processed food and animal feed. Combination assay of two arbitrary primers in the RAPD analysis enable to distinguish genetically modified organism (GMO) reference materials from the samples tested. Dendrogram analysis revealed 13 clusters at 45% similarity from the RAPD. RAPD analysis showed that the maize and soybean samples were clustered differently besides the GMO and non-GMO products.

  6. Random amplified polymorphic DNA analysis of genetically modified organisms.

    PubMed

    Yoke-Kqueen, Cheah; Radu, Son

    2006-12-15

    Randomly amplified polymorphic DNA (RAPD) was used to analyzed 78 samples comprises of certified reference materials (soya and maize powder), raw seeds (soybean and maize), processed food and animal feed. Combination assay of two arbitrary primers in the RAPD analysis enable to distinguish genetically modified organism (GMO) reference materials from the samples tested. Dendrogram analysis revealed 13 clusters at 45% similarity from the RAPD. RAPD analysis showed that the maize and soybean samples were clustered differently besides the GMO and non-GMO products. PMID:16860900

  7. Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity.

    PubMed

    Gidalevitz, Tali; Krupinski, Thomas; Garcia, Susana; Morimoto, Richard I

    2009-03-01

    Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS) cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation behavior and genetic interactions of mutant forms of SOD1. Expression of three structurally distinct SOD1 mutants in C. elegans muscle cells resulted in the appearance of heterogeneous populations of aggregates and was associated with only mild cellular dysfunction. However, introduction of destabilizing temperature-sensitive mutations into the genetic background strongly enhanced the toxicity of SOD1 mutants, resulting in exposure of several deleterious phenotypes at permissive conditions in a manner dependent on the specific SOD1 mutation. The nature of the observed phenotype was dependent on the temperature-sensitive mutation present, while its penetrance reflected the specific combination of temperature-sensitive and SOD1 mutations. Thus, the specific toxic phenotypes of conformational disease may not be simply due to misfolding/aggregation toxicity of the causative mutant proteins, but may be defined by their genetic interactions with cellular pathways harboring mildly destabilizing missense alleles. PMID:19266020

  8. Symposium overview: genetic polymorphisms in DNA repair and cancer risk.

    PubMed

    Hu, J J; Mohrenweiser, H W; Bell, D A; Leadon, S A; Miller, M S

    2002-11-15

    A symposium, Genetic Polymorphisms in DNA Repair and Cancer Risk, was presented at the 40th Annual Meeting of the Society of Toxicology, held in San Francisco, California, in March 2001. A brief report of the symposium was published (Kaiser, Science 292, 837-838, 2001). Molecular epidemiological studies have shown that polymorphic variants of genes involved in the metabolism and repair of carcinogens can act as cancer susceptibility genes. These variants of drug metabolic and DNA-repair enzymes either increase the activation of chemical carcinogens or decrease the cells' ability to detoxify/repair mutagenic damages. Although on an individual basis these variant alleles may only slightly change catalytic activity and increase cancer risk, their polymorphic frequency in the human population may contribute to a high proportion of cancer cases. Studies conducted over the past few years have identified variant alleles for a number of DNA-repair genes, some of which have been shown to change DNA-repair capacity. Identifying these genotypic alterations in DNA-repair enzymes and their association with cancer may help to elucidate the mechanisms of cancer etiology and to predict both disease risk and response to cancer therapy, since most antineoplastic treatments mediate their effects through DNA damage.

  9. Structure and genetic polymorphism of the mouse KCC1 gene.

    PubMed

    Shmukler, B E; Brugnara, C; Alper, S L

    2000-07-24

    The KCC1 K-Cl cotransporter is a major regulator of erythroid and non-erythroid cell volume, and the KCC1 gene is a candidate modifier gene for sickle cell disease and other hemoglobinopathies. We have cloned and sequenced the mouse KCC1 (mKCC1) gene, defined its intron-exon junctions, and analyzed (AC)/(TG) intragenic polymorphisms. A highly polymorphic (AC) repeat of mKCC1 intron 1 was characterized in musculus strains, and used to prove lack of linkage between the mKCC1 gene and the rol (resistant to osmotic lysis) locus. The intron 1 (AC) repeat in CAST/Ei and SPRET/Ei was not only more divergent in length but also underwent additional sequence variation. A dimorphic (TG) repeat in intron 2 distinguished CAST/Ei from other strains, and an intron 17 B1 Alu-like SINE present in all musculus strains was found to be absent from intron 17 in SPRET/Ei. These and additional described strain-specific polymorphisms will be useful mapping and genetic tools in the study of mouse models of sickle cell disease.

  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 polymorphism in pathogenesis of irritable bowel syndrome.

    PubMed

    Cheung, Cynthia K Y; Wu, Justin C Y

    2014-12-21

    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.

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

    PubMed Central

    Celec, Peter; Tretinárová, Denisa; Minárik, Gabriel; Ficek, Andrej; Szemes, Tomáš; Lakatošová, Silvia; Schmidtová, Eva; Turňa, Ján; Kádaši, Ľudevít; Ostatníková, 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

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

    PubMed

    Celec, Peter; Tretinárová, Denisa; Minárik, Gabriel; Ficek, Andrej; Szemes, Tomáš; Lakatošová, Silvia; Schmidtová, Eva; Turňa, Ján; Kádaši, Ľudevít; Ostatníková, 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.

  14. Genetics of complex traits: prediction of phenotype, identification of causal polymorphisms and genetic architecture.

    PubMed

    Goddard, M E; Kemper, K E; MacLeod, I M; Chamberlain, A J; Hayes, B J

    2016-07-27

    Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement. PMID:27440663

  15. Genetics of complex traits: prediction of phenotype, identification of causal polymorphisms and genetic architecture

    PubMed Central

    Goddard, M. E.; Kemper, K. E.; MacLeod, I. M.; Chamberlain, A. J.; Hayes, B. J.

    2016-01-01

    Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement. PMID:27440663

  16. 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

  17. [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

  18. Genetic polymorphism as a background of animal behavior.

    PubMed

    Inoue-Murayama, Miho

    2009-04-01

    Various studies have shown the associations between differences in human behavioral traits and genetic polymorphism of neurotransmitter-related proteins such as receptors, transporters and monoamine oxidase. To clarify the genetic background of animal behavior, corresponding regions in animals have been analyzed. The study has been especially focused on primates, as the evolutionally closest animal to humans, and on dogs, as the socially closest animal to humans. In primates, polymorphisms were discovered between or within species, and the functional effects on neural transmission were found to be different by alleles. Even in apes, the closest species to humans, function was different from that in humans. In dogs, allele distributions of several genes were different among breeds showing different behavioral traits, and genes associated with individual differences in aggressiveness and aptitude of working dogs were surveyed. The survey of behavior-related genes has also been carried out in other mammals such as horses and cetaceans. Genes controlling various behaviors in birds have also been reported. The marker genes for behavior will provide useful information for human evolution, welfare of zoo animals and effective selection of working dogs and industry animals. PMID:20163580

  19. Genetic Polymorphism and Expression of CXCR4 in Breast Cancer.

    PubMed

    Okuyama Kishima, Marina; Brajão 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

  20. Genetic Polymorphism and Expression of CXCR4 in Breast Cancer

    PubMed Central

    Okuyama Kishima, Marina; Brajão 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

  1. 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

  2. Genetic structure of Balearic honeybee populations based on microsatellite polymorphism

    PubMed Central

    De la Rúa, Pilar; Galián, José; Serrano, José; Moritz, Robin FA

    2003-01-01

    The genetic variation of honeybee colonies collected in 22 localities on the Balearic Islands (Spain) was analysed using eight polymorphic microsatellite loci. Previous studies have demonstrated that these colonies belong either to the African or west European evolutionary lineages. These populations display low variability estimated from both the number of alleles and heterozygosity values, as expected for the honeybee island populations. Although genetic differentiation within the islands is low, significant heterozygote deficiency is present, indicating a subpopulation genetic structure. According to the genetic differentiation test, the honeybee populations of the Balearic Islands cluster into two groups: Gimnesias (Mallorca and Menorca) and Pitiusas (Ibiza and Formentera), which agrees with the biogeography postulated for this archipelago. The phylogenetic analysis suggests an Iberian origin of the Balearic honeybees, thus confirming the postulated evolutionary scenario for Apis mellifera in the Mediterranean basin. The microsatellite data from Formentera, Ibiza and Menorca show that ancestral populations are threatened by queen importations, indicating that adequate conservation measures should be developed for protecting Balearic bees. PMID:12729553

  3. Association of cytotoxic T-lymphocyte antigen 4 genetic polymorphism, hepatitis C viral infection and B-cell non-Hodgkin lymphoma: an Egyptian study.

    PubMed

    Khorshied, Mervat Mamdooh; Gouda, Heba Mahmoud; Khorshid, Ola M Reda

    2014-05-01

    Abstract Genetic and environmental factors are involved in the pathogenesis of non-Hodgkin lymphoma (NHL). The present study aimed to investigate the association between cytotoxic T-lymphocyte antigen 4 (CTLA-4) genetic polymorphism, hepatitis C virus (HCV) infection and B-cell NHL risk in Egypt. Genotyping of CTLA-4 single nucleotide polymorphisms (SNPs) was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay for 181 adult patients with B-NHL and 200 controls. Our study revealed that CTLA-4 + 49 A/G polymorphism conferred increased risk of B-NHL (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.36-2.565). The prevalence of HCV infection in individuals harboring the mutant genotype + 49 A/G and - 318 C/T SNPs was higher in patients with B-NHL and was associated with increased risk of B-NHL (OR = 2.79, 95% CI = 1.24-6.93 for + 49 A/G and OR = 3.9, 95% CI = 1.01-15.98 for - 318 C/T). In conclusion, some SNPs of CTLA-4 are genetic risk factors for B-NHL. Moreover, this study identified an association of CTLA-4 + 49 A/G and - 318 C/T promoter polymorphisms with HCV infection.

  4. Microbial diversity in polluted harbor sediments II: Sulfate-reducing bacterial community assessment using terminal restriction fragment length polymorphism and clone library of dsrAB gene

    NASA Astrophysics Data System (ADS)

    Zhang, Wen; Song, Lin-sheng; Ki, Jang-Seu; Lau, Chun-Kwan; Li, Xiang-Dong; Qian, Pei-Yuan

    2008-02-01

    Sulfate-reducing bacteria (SRB) are important regulators of a variety of processes in coastal marine sediments regarding organic matter turnover, biodegradation of pollutants, and sulfur and carbon cycles. Yet their community compositions have not been investigated in polluted harbor sediments. This study described the diversity and spatial variation of SRB communities in surface sediments in Victoria Harbor, Hong Kong. The spatial variation of SRB communities was described by terminal restriction fragment length polymorphism (T-RFLP). The results showed that the most diversified terminal restriction fragments were found at polluted sites. In addition, cluster analysis indicated that although the SRB communities were different at the two polluted sites, they were still more similar to each other than to the two more distant reference sites. Based on a dsrAB clone library constructed at a polluted site, diversified SRB were found, represented by 30 Operational Taxonomic Units (OTUs). Upon comparisons among the SRB sequences detected from this study and those in the GenBank, five clades of SRB were found. Three clades belonged to the known families Desulfobacteraceae, Desulfobulbaceae, and Syntrophobacteriaceae. The majority of sequenced clones, which distantly related to sequences in the GenBank, constituted the remaining two unclassified groups, suggesting unique SRB members related to the polluted harbor environment. Statistical analyses indicated that estimated SRB richness correlated with environment factors such as sulfur content, acid volatile sulfate, and redox potential.

  5. 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.

  6. Polymorphic Alu insertions and genetic diversity among African populations.

    PubMed

    Terreros, Maria C; Martinez, Laisel; Herrera, Rene J

    2005-10-01

    Thorough assessment of modern genetic diversity and interpopulation affinities within the African continent is essential for understanding the processes that have been at work during the course of worldwide human evolution. Regardless of whether autosomal, Y-chromosome, or mtDNA markers are used, allele- or haplotype-frequency data from African populations are necessary in setting the framework for the construction of global population phylogenies. In the present study we analyze genetic differentiation and population structure in a data set of nine African populations using 12 polymorphic Alu insertions (PAls). Furthermore, to place our findings within a global context, we also examined an equal number of non-African groups. Frequency data from 456 individuals presented for the first time in this work plus additional data obtained from the literature indicate an overall pattern of higher intrapopulation diversity in sub-Saharan populations than in northern Africa, a prominent differentiation between these two locations, an appreciably high degree of transcontinental admixture in Egypt, and significant discontinuity between Morocco and the Iberian peninsula. Moreover, the topologies of our phylogenetic analyses suggest that out of the studied sub-Saharan groups, the southern Bantu population of Sotho/ Tswana presents the highest level of antiquity, perhaps as a result of ancestral or acquired Khoisan genetic signals. Close affinities of eastern sub-Saharan populations with Egypt in the phylogenetic trees may indicate the existence of gene flow along the Nile River.

  7. 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.

  8. [Molecular genetics of MTHFR: polymorphisms are not all benign].

    PubMed

    Leclerc, Daniel; Rozen, Rima

    2007-03-01

    Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in folate and homocysteine metabolism. Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia. Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia. Shortly thereafter, we identified the 677C-->T variant and showed that it encoded a thermolabile enzyme with reduced activity. Currently, a total of 41 rare but deleterious mutations in MTHFR, as well as about 60 polymorphisms have been reported. The 677C-->T (Ala222Val) variant has been particularly noteworthy since it has become recognized as the most common genetic cause of hyperhomocysteinemia. The disruption of homocysteine metabolism by this polymorphism influences risk for several complex disorders, including cardiovascular disease, neural tube defects and some cancers. We describe here the complex structure of the MTHFR gene, summarize the current state of knowledge on rare and common mutations in MTHFR and discuss some relevant findings in a mouse model for MTHFR deficiency.

  9. 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

  10. 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

  11. Genetic polymorphism of six plasma proteins in the domestic cat.

    PubMed

    Juneja, R K; Niini, T; Larsson, H E; Sandberg, K

    1991-01-01

    Phenotypes of cat plasma apolipoprotein A4 (APOA4), antithrombin 3 (AT3), alpha 1B-glycoprotein (A1BG), transferrin (TF), vitamin D-binding protein (GC), and an unidentified pretransferrin (PTF) were determined by using simple methods of horizontal, nondenaturing gel electrophoresis followed by protein staining. The cat proteins were identified by immunoblotting using antisera for human plasma proteins. Three alleles were reported for each of TF and PTF, and two alleles were reported for each of GC, APOA4, AT3, and A1BG. The mongrels and Persians showed a high degree of polymorphism at most of the loci whereas the Birmans exhibited much less variation. Genetic evidence indicating the occurrence of a monomeric and a dimeric form of APOA4 in cat plasma was reported. PMID:2013693

  12. Genetic polymorphism of matrix metalloproteinases in breast cancer.

    PubMed

    Wieczorek, E; Reszka, E; Gromadzinska, J; Wasowicz, W

    2012-01-01

    The family of human matrix metalloproteinases (MMPs) consists of 24 zinc- and calcium-dependent proteolytic enzymes. MMPs are divided into six subgroups, in terms of differences in the substrate specificity with structural domain architecture. These enzymes are involved in many physiological processes, such as skeletal development, wound healing, scar formation, as well as carcinogenesis. MMPs, fulfilling its function of degradation of extracellular matrix components, are involved in one of the stages of angiogenesis enabling the development, growth and spread of the primary tumor. Therefore, the search for the common polymorphic variants of MMPs, new genetic markers as prognostic factors in breast cancer progress seems to be understandable.The minireview presents the results of 19 case-control or prospective studies concerning the association of SNPs of genes encoding nine MMPs: MMP-1, -2, -3, -7, -8, -9, -12, -13, -21 with the breast cancer risk, progression and survival. PMID:22296495

  13. 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

    2015-12-22

    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.

  14. [Application of genetic polymorphisms in blood to forensic anthropology].

    PubMed

    Misawa, S

    1991-08-01

    1. The Ainu subjects and, as controls, Wajin subjects obtained in the District of Hokkaido, were studied for blood groups, serum groups and red cell enzyme groups. The high n gene and r" gene frequencies seem to be characteristic in the distribution of the Ainu. In considering the high frequencies of Fya and Agx genes, low incidence K gene and Rh negative type, and existence of Di (a+) type, it is conceivable that the distribution of these blood group in the Ainu are closer to those in Mongoloid than to those in Caucasoid. The results of genetic distance analysis were in full agreement with the genetic affinity of the Ainu to the Mongoloid racial stock. According to the phylogenetic tree constructed on the basis of 16 polymorphic loci, it may be concluded that the Ainu are derived from the common stock of Mongoloids, which in turn has common ancestry with American Indians. The Negritos which are thought to be oldest living aborigines of southeast Asia and the western pacific. We investigated for grouping some genetic polymorphic traits from Negrito blood samples collected in the Philippines. A total of more than 500 samples were examined for 20 genetic traits. The most outstanding features of Negritos were as follows: Di (a+) type was found and all individuals were Lu (a-b +) and K-k+ types. Mia, Wra and Jsa genes were absent and all samples were U+ type. The existence of Dia gene and absence of both Lua and K genes are thought to suggest that the distribution of Negritos is quite close to that of Mongoloid populations. Fy (a-b-) and Js (a+) types are not found in our study. These results do not suggest similarity between Negritos and African. 2. The tandem repeat of a 28-base-pair (bp) sequence downstream of the human c-Ha-ras-1 oncogene was studied as a probe for DNA fingerprinting. Multiple hypervariable patterns were observed by Southern hybridization at low stringency. The patterns were specific to individuals, indicating the availability of the 28-bp repeat

  15. Genetic polymorphisms in centrobin and Nek2 are associated with breast cancer susceptibility in a Chinese Han population.

    PubMed

    Wang, Hui; Xie, Yun-Tao; Han, Ji-Yuan; Ruan, Yuan; Song, Ai-Ping; Zheng, Li-Yuan; Zhang, Wei-Zao; Sajdik, Constantin; Li, Yan; Tian, Xin-Xia; Fang, Wei-Gang

    2012-11-01

    Centrosome aberrations have been suggested to cause chromosomal instability and aneuploidy, and eventually promote cancer development. The Centrobin and Nek2 proteins interact with each other and both are involved in centrosome duplication and chromosome segregation. This study aimed to investigate whether genetic polymorphisms in these two genes may affect breast cancer susceptibility in Chinese Han population using a haplotype-based analysis. Five single nucleotide polymorphisms (SNPs) in centrobin and four SNPs in Nek2 were genotyped in 1,215 cases of infiltrating ductal breast cancer and 1,215 age-matched cancer-free controls from Chinese Han population. The results showed that CATCG haplotype of centrobin was strongly associated with decreased breast cancer risk (adjusted OR = 0.14, 95 % CI = 0.09-0.22), which was mainly driven by the C allele of SNP rs11650083 (A>C, located in exon 12, resulting in Pro578Gln). None of the individual SNPs in Nek2 was associated with breast cancer risk. However, haplotype GTAT of Nek2 was associated with increased risk of breast cancer (adjusted OR = 1.56, 95 % CI = 1.18-2.06) and its risk was significantly elevated among women with both family history of cancer and a longer menarche-first full-term pregnancy (FFTP) interval (>11 years) (adjusted OR = 5.31, 95 % CI = 1.97-14.32). Furthermore, women harboring both at-risk haplotype GTAT of Nek2 and protective haplotype CATCG of centrobin were linked with decreased breast cancer risk, suggesting that the association between genetic variants of Nek2 and increased breast cancer risk was modified by genetic variants of centrobin. Our results indicate that genetic polymorphisms of centrobin and Nek2 are related to breast cancer susceptibility in Chinese Han women.

  16. 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

  17. Genetic diversity and structure of an estuarine fish (Fundulus heteroclitus) indigenous to sites associated with a highly contaminated urban harbor.

    PubMed

    McMillan, Amy M; Bagley, Mark J; Jackson, Suzanne A; Nacci, Diane E

    2006-08-01

    Intense selection on isolated populations can cause loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that polychlorinated biphenyls (PCBs), have acted as strong selective agents on populations of a non-migratory fish, Fundulus heteroclitus, indigenous to heavily contaminated sites. To evaluate population genetic structure and test for effects of intense, multi-generational PCB contamination on genetic diversity, we used AFLP analysis on fish collected from six sites along the east coast of North America that varied widely in PCB contamination. The sites included a heavily contaminated urban harbor (New Bedford, MA), an adjacent moderately contaminated sub-estuary (Buzzards Bay, MA), and an uncontaminated estuary 60 km away (Narragansett, RI). AFLP markers distinguished populations at moderate and small scales, suggesting genetic differentiation at distances of 2 km or less. Genetic diversity did not differ across the study sites. Genome-wide diversity may have been preserved because of large effective population sizes and/or because the mechanism for genetic adaptation to these contaminants affected only a small number of loci. Alternatively, loss in diversity may have been restored with moderate levels of migration and relatively short generation time for this species.

  18. Renal Function and Genetic Polymorphisms in Pediatric Heart Transplant Recipients

    PubMed Central

    Feingold, Brian; Brooks, Maria M; Zeevi, Adriana; Ohmann, Erin L.; Burckart, Gilbert J.; Ferrell, Robert E.; Chinnock, Richard; Canter, Charles; Addonizio, Linda; Bernstein, Daniel; Kirklin, James K.; Naftel, David C.; Webber, Steven A.

    2012-01-01

    Background Common genetic variations influence rejection, infection, drug metabolism, and side effect profiles after pediatric heart transplantation. Reports in adults suggest that genetic background may influence post-transplant renal function. In this multicenter study we investigated the association of genetic polymorphisms (GP) in a panel of candidate genes on renal function in 453 pediatric heart transplant recipients. Methods We performed genotyping for functional GPs in 19 candidate genes. Renal function was determined annually after transplantation by calculation of glomerular filtration rate (eGFR). Mixed effects and Cox proportional hazard models were used to assess recipient characteristics and the effect of GPs on longitudinal eGFR and time to eGFR <60 mL/min/1.73m2. Results Mean age at transplantation was 6.2 ± 6.1 years and mean follow-up was 5.1 ± 2.5 years. Older age at transplant and black race were independently associated with post-transplant renal dysfunction. In univariate analyses, FASL (C-843T) T allele (p=0.014) and HO-1 (A326G) G allele (p=0.0017) were associated with decreased renal function. After adjusting for age and race, these associations were attenuated [FASL (p=0.075), HO-1 (p=0.053)]. We found no associations of other GPs, including GPs in TGFβ1, CYP3A5, ABCB1, and ACE, with post-transplant renal function. Conclusions In this multicenter, large sample of pediatric heart transplant recipients we found no strong associations between GPs in 19 candidate genes and post-transplant renal function. Our findings contradict reported associations of CYP3A5 and TGFβ1 with renal function and suggest that genotyping for these GPs will not facilitate individualized immunosuppression for the purpose of protecting renal function after pediatric heart transplantation. PMID:22789135

  19. Integrated genetic map of Anopheles gambiae: use of RAPD polymorphisms for genetic, cytogenetic and STS landmarks.

    PubMed

    Dimopoulos, G; Zheng, L; Kumar, V; della Torre, A; Kafatos, F C; Louis, C

    1996-06-01

    Randomly amplified polymorphic DNA (RAPD) markers have been integrated in the genetic and cytogenetic maps of the malaria vector mosquito, Anopheles gambiae. Fifteen of these markers were mapped by recombination, relative to microsatellite markers that had been mapped previously. Thirty-four gel-purified RAPD bands were cloned and sequenced, generating sequence tagged sites (STSs) that can be used as entry points to the A. gambiae genome. Thirty one of these STSs were localized on nurse cell polytene chromosomes through their unique hybridization signal in in situ hybridization experiments. Five STSs map close to the breakpoints of polymorphic inversions, which are notable features of the Anopheles genome. The usefulness and limitations of this integrated mosquito map are discussed. PMID:8725241

  20. Genetic linkage between Huntington's disease and the DNA polymorphism G8 in South Wales families.

    PubMed

    Harper, P S; Youngman, S; Anderson, M A; Sarfarazi, M; Quarrell, O; Tanzi, R; Shaw, D; Wallace, P; Conneally, P M; Gusella, J F

    1985-12-01

    Analysis of the polymorphism shown by the DNA probe G8 in eight South Wales families with Huntington's disease has confirmed close genetic linkage between this marker and the disorder, the most likely genetic distance being two centimorgans (cM). The closeness of the linkage suggests that G8 may have clinical applications in genetic prediction for this condition.

  1. 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) ...

  2. 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

  3. [A comparative study on genetic polymorphism and genetic relationship of 13 SNPs in three Chinese populations].

    PubMed

    Wang, Rui-Heng; Liu, Li-Min; Zhao, Jin-Ling

    2009-03-01

    Using the fluorescence labeled capillary electrophoresis of multi-PCR technique, the single nucleotide polymorphism (SNP) typing system of fragment length discrepant allele specific fluorescence labeled multi-PCR technique is established based on the principle of allele-specific PCR. The typing of the 13 SNP loci can be completed simultaneously according to the length of PCR products and the number of product peaks. It appears a single product peak when the SNP is homozygous, and two product peaks with 4 bp differences will appear when it is heterozygous. By using this system, we conducted population census about allele frequencies for 13 autosomal SNP loci in Southern Liaoning Han samples, Mongolian samples in Inner Mongolia and Zhuang samples in Guangxi area, and got the allele frequencies of the 13 SNP loci in the three populations, then preliminarily discussed their genetic relationship by comparing their differences in allelic polymorphism. The results indicate that the allelic distributions of the 13 SNP loci in the three populations are polymorphic, and the difference is significant in some SNP loci (P< or =0.01). The sampling survey shows that the result is consistent with Hardy-Weinberg equilibrium, and Han population in southern Liaoning has relatively closer relationship with Mongolian in Inner Mongolia than with Zhuang population in Guangxi by origin. PMID:19273440

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

    PubMed

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

    2016-01-01

    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

  5. 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…

  6. N-acetyltransferase 2 genetic polymorphism: Effects of carcinogen and haplotype on urinary bladder cancer risk

    PubMed Central

    Hein, David W.

    2006-01-01

    A role for the N-acetyltransferase 2 (NAT2) genetic polymorphism in cancer risk has been the subject of numerous studies. Although comprehensive reviews of the NAT2 acetylation polymorphism have been published elsewhere, the objective of this paper is to briefly highlight some important features of the NAT2 acetylation polymorphism that are not universally accepted to better understand the role of NAT2 polymorphism in carcinogenic risk assessment. NAT2 slow acetylator phenotype(s) infer a consistent and robust increase in urinary bladder cancer risk following exposures to aromatic amine carcinogens. However, identification of specific carcinogens is important as the effect of NAT2 polymorphism on urinary bladder cancer differs dramatically between monoarylamines and aryldiamines. Misclassifications of carcinogen exposure and NAT2 genotype/phenotype confound evidence for a real biological effect. Functional understanding of the effects of NAT2 genetic polymorphisms on metabolism and genotoxicity, tissue-specific expression and the elucidation of the molecular mechanisms responsible are critical for interpretation of previous and future human molecular epidemiology investigations into the role of NAT2 polymorphism on cancer risk. Although associations have been reported for various cancers, this paper focuses on urinary bladder cancer, a cancer in which a role for NAT2 polymorphism was first proposed and for which evidence is accumulating that the effect is biologically significant with important public health implications. PMID:16550165

  7. eNOS Genetic Polymorphisms and Cancer Risk

    PubMed Central

    Gao, Xueren; Wang, Jie; Wang, Wenjun; Wang, Mingxi; Zhang, Jianqiong

    2015-01-01

    Abstract The association between endothelial nitric oxide synthase (eNOS) polymorphisms (intron 4a/b, -786T>C and 894G>T) and cancer risk remains elusive. In addition, no studies focused on their associations with the risk of breast cancer in Chinese Han population. Thus, a meta-analysis was conducted to determine the relationship between eNOS polymorphisms and cancer risk, and then a case–control study in Chinese Han population was performed to assess their associations with breast cancer susceptibility. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The pooled analysis indicated that eNOS intron 4a/b and -786T>C polymorphisms were significantly associated with an increased risk of overall cancer. In subgroup analyses based on cancer type, the significant association was found between eNOS intron 4a/b polymorphism and prostate cancer risk, eNOS -786T>C polymorphism and risk of prostate, bladder and breast cancers, and eNOS 894G>T polymorphism and breast cancer risk. In subgroup analyses based on ethnicity, eNOS intron 4a/b and -786T>C polymorphisms were associated with an increased risk of cancer in Caucasians. In consistent with our meta-analysis results, a case–control study in Chinese Han population showed significant associations of eNOS -786T>C and 894G>T polymorphisms with the increased risk of breast cancer. In addition, stratified analyses based on pathological type showed that eNOS 894G>T polymorphism was only associated with the risk of infiltrative ductal carcinoma. Stratified analyses by tumor stage showed that eNOS -786T>C polymorphism was only associated with the risk of tumor stage III and IV. In conclusion, our meta-analysis and case–control study suggest that eNOS -786T>C and 894G>T polymorphisms are associated with the increased risk of breast cancer. PMID:26131841

  8. Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia.

    PubMed

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Eskandarian, Narges; Etemad, Ali

    2016-01-01

    Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population. PMID:27413750

  9. Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia

    PubMed Central

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Eskandarian, Narges; Etemad, Ali

    2016-01-01

    Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population. PMID:27413750

  10. Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

    PubMed Central

    Drummond, M. Bradley; Hawkins, Gregory A.; Yang, Jenny; Chen, Ting-huei; Quibrera, Pedro Miguel; Anderson, Wayne; Barr, R. Graham; Bleecker, Eugene R.; Beaty, Terri; Casaburi, Richard; Castaldi, Peter; Cho, Michael H.; Comellas, Alejandro; Crapo, James D.; Criner, Gerard; Demeo, Dawn; Christenson, Stephanie A.; Couper, David J.; Doerschuk, Claire M.; Freeman, Christine M.; Gouskova, Natalia A.; Han, MeiLan K.; Hanania, Nicola A.; Hansel, Nadia N.; Hersh, Craig P.; Hoffman, Eric A.; Kaner, Robert J.; Kanner, Richard E.; Kleerup, Eric C.; Lutz, Sharon; Martinez, Fernando J.; Meyers, Deborah A.; Peters, Stephen P.; Regan, Elizabeth A.; Rennard, Stephen I.; Scholand, Mary Beth; Silverman, Edwin K.; Woodruff, Prescott G.; O’Neal, Wanda K.; Bowler, Russell P.

    2016-01-01

    Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In

  11. Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD.

    PubMed

    Sun, Wei; Kechris, Katerina; Jacobson, Sean; Drummond, M Bradley; Hawkins, Gregory A; Yang, Jenny; Chen, Ting-Huei; Quibrera, Pedro Miguel; Anderson, Wayne; Barr, R Graham; Basta, Patricia V; Bleecker, Eugene R; Beaty, Terri; Casaburi, Richard; Castaldi, Peter; Cho, Michael H; Comellas, Alejandro; Crapo, James D; Criner, Gerard; Demeo, Dawn; Christenson, Stephanie A; Couper, David J; Curtis, Jeffrey L; Doerschuk, Claire M; Freeman, Christine M; Gouskova, Natalia A; Han, MeiLan K; Hanania, Nicola A; Hansel, Nadia N; Hersh, Craig P; Hoffman, Eric A; Kaner, Robert J; Kanner, Richard E; Kleerup, Eric C; Lutz, Sharon; Martinez, Fernando J; Meyers, Deborah A; Peters, Stephen P; Regan, Elizabeth A; Rennard, Stephen I; Scholand, Mary Beth; Silverman, Edwin K; Woodruff, Prescott G; O'Neal, Wanda K; Bowler, Russell P

    2016-08-01

    Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10-10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10-392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In

  12. Ecosensitivity and genetic polymorphism of somatic traits in the perinatal development of twins.

    PubMed

    Waszak, Małgorzata; Cieślik, Krystyna; Skrzypczak-Zielińska, Marzena; Szalata, Marlena; Wielgus, Karolina; Kempiak, Joanna; Bręborowicz, Grzegorz; Słomski, Ryszard

    2016-04-01

    In view of criticism regarding the usefulness of heritability coefficients, the aim of this study was to analyze separately the information on genetic and environmental variability. Such an approach, based on the normalization of trait's variability for its value, is determined by the coefficients of genetic polymorphism (Pg) and ecosensitivity (De). The studied material included 1263 twin pairs of both sexes (among them 424 pairs of monozygotic twins and 839 pairs of dizygotic twins) born between the 22nd and 41st week of gestation. Variability of six somatic traits was analyzed. The zygosity of same-sex twins was determined based on the polymorphism of DNA from lymphocytes of the umbilical cord blood, obtained at birth. The coefficients of genetic polymorphism and ecosensitivity for analyzed traits of male and female twins born at various months of gestation were calculated. Our study revealed that a contribution of the genetic component predominated over that of the environmental component in determining the phenotypic variability of somatic traits of newborns from twin pregnancies. The genetically determined phenotypic variability in male twins was greater than in the females. The genetic polymorphism and ecosensitivity of somatic traits were relatively stable during the period of fetal ontogeny analyzed in this study. Only in the case of body weight, a slight increase in the genetic contribution of polygenes to the phenotypic variance could be observed with gestational age, along with a slight decrease in the influence of environmental factors.

  13. 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

  14. [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

  15. Association of AIRE polymorphisms with genetic susceptibility to rheumatoid arthritis in a Chinese population.

    PubMed

    Shao, Song; Li, Xing-Rui; Cen, Han; Yin, Zong-Sheng

    2014-04-01

    Recently, genetic polymorphisms within the autoimmune regulator (AIRE) have been implicated in the genetic susceptibility to rheumatoid arthritis (RA) in Japanese and Spanish. The aim of this case-control study involving 232 patients with RA and 313 ethnically matched control subjects was to investigate the association of AIRE rs2075876 and rs760426 polymorphisms with genetic predisposition to RA in a Chinese population. The genotypes of AIRE rs2075876 and rs760426 polymorphisms were determined by SNaPshot assay. A significant difference in the allele frequency of AIRE rs2075876 polymorphism between cases and controls was detected (A versus G, OR 1.33, 95 %CI 1.04-1.69, P = 0.02, P corrected (Bonferroni correction) Pc = 0.04). Significant evidence was found for the association between the minor allele A of AIRE rs2075876 polymorphism and the risk of RA under the recessive model (AA versus AG + GG, P = 7.15 × 10(-3), Pc = 1.43 × 10(-2)). The frequency of the minor allele G of AIRE rs760426 polymorphism was higher in patients compared with controls (47.8 % versus 42.1 %), and this deviation showed a trend towards significant level (P = 0.06, Pc = 0.12). The association between the minor allele G of AIRE rs760426 polymorphism with RA risk under the dominant model and the recessive model revealed that significant evidence was detected under the recessive model (GG versus GA + AA, P = 0.02, Pc = 0.04). Our results indicated that AIRE rs2075876 and rs760426 polymorphisms were involved in the genetic background of RA in the Chinese population.

  16. Protein Polymorphisms, Segregation in Genetic Crosses and Genetic Distances among Fishes of the Genus Xiphophorus (Poeciliidae)

    PubMed Central

    Morizot, Don C.; Siciliano, Michael J.

    1982-01-01

    The products of 49 protein-coding loci were examined by starch gel electrophoresis for populational variation in six species of Xiphophorus fishes and/or segregation in intra- and interspecific backcross and intercross hybrids. Electrophoretic variation was observed for 29 of the 35 locus products in a survey of 42 population samples. The highest frequency of polymorphic loci observed in noninbred populations was 0.143. After ten or more generations of inbreeding, all loci studied were monomorphic. Inbred strains generally exhibited the commonest electrophoretic alleles of the population from which they were derived. An assessment of genetic distances among Xiphophorus populations reflected classical systematic relationships and suggested incipient subspeciation between X. maculatus from different drainages as well as several species groups. Thirty-three loci were analyzed with respect to segregation in hybrids. The goodness of fit of segregations to Mendelian expectations at all loci analyzed (except loci in linkage group I) is interpreted as evidence for high genetic compatibility of the genomes of Xiphophorus species. It is anticipated that these data will result in a rapid expansion of the assignment of protein-coding loci to linkage groups in these lower vertebrate species. PMID:7173606

  17. CYP1A1 genetic polymorphisms in Ecuador, South America.

    PubMed

    Paz-y-Miño, César; Arévalo, Melissa; Muñoz G, María José; Leone, Paola E

    2005-01-01

    A total of 108 individuals from the Ecuadorian population from rural and urban places were analyzed for two CYP1A1 gene polymorphisms. The frequency of the val allele at codon 462 was 0.50, while the frequency of the Msp I restriction site, m2 allele at the T6235C position was 0.70. These polymorphisms in Ecuador have higher frequencies if we compare with others around the world, with the exception of some South American population in Brazil and Chile.

  18. Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis.

    PubMed

    Zhang, Ling Ling; Yang, Sen; Wei, Wei; Zhang, Xue Jun

    2014-11-01

    Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450 enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-α receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA.

  19. Genetic polymorphism of serotonin transporter 5-HTTLPR: involvement in smoking behaviour.

    PubMed

    Watanabe, Maria Angelica Ehara; Nunes, Sandra Odebrecht Vargas; Nunes, Sandra Odebrechet Vargas; Amarante, Marla Karine; Guembarovski, Roberta Losi; Oda, Julie Massayo Maeda; Lima, Kalil William Alves De; Fungaro, Maria Helena Pelegrinelli

    2011-04-01

    Data suggest that the serotonin (5-hydroxytryptamine, 5-HT) system is implicated in the pathogenesis of multiple neuropsychiatric disorders and may also be involved in smoking behaviour since nicotine increases brain serotonin secretion. It is known that smoking behaviour is influenced by both genetic and environmental factors. The present review examines the role of the serotonin transporter gene (5-HTT) in smoking behaviour and investigating studies that showed association of 5-HTT gene with smoking. This study discusses a polymorphism which has been investigated by many researchers, as the bi-allelic insertion/deletion polymorphism in the 5'- flanking promoter region (5-HTTLPR). This gene has received considerable attention in attempts to understand the molecular determinants of smoking. Therefore, in the present study, the relationship between genetic polymorphism of serotonin transporter in smoking behaviour is reviewed considering the interactive effect of genetic factors.

  20. Effect of multiple genetic polymorphisms on antigen presentation and susceptibility to Mycobacterium tuberculosis infection.

    PubMed

    Chang, Stewart T; Linderman, Jennifer J; Kirschner, Denise E

    2008-07-01

    Several molecules related to antigen presentation, including gamma interferon (IFN-gamma) and the major histocompatibility complex (MHC), are encoded by polymorphic genes. Some polymorphisms were found to affect susceptibility to tuberculosis (TB) when they were considered singly in epidemiological studies, but how multiple polymorphisms interact to determine susceptibility to TB in an individual remains an open question. We hypothesized that polymorphisms in some genes may counteract or intensify the effects of polymorphisms in other genes. For example, an increase in IFN-gamma expression may counteract the weak binding that a particular MHC variant displays for a peptide from Mycobacterium tuberculosis to establish the same T-cell response as another, more strongly binding MHC variant. To test this hypothesis, we developed a mathematical model of antigen presentation based on experimental data for the known effects of genetic polymorphisms and simulated time courses when multiple polymorphisms were present. We found that polymorphisms in different genes could affect antigen presentation to the same extent and therefore compensate for each other. Furthermore, we defined the conditions under which such relationships could exist. For example, increased IFN-gamma expression compensated for decreased peptide-MHC affinity in the model only above a certain threshold of expression. Below this threshold, changes in IFN-gamma expression were ineffectual compared to changes in peptide-MHC affinity. The finding that polymorphisms exhibit such relationships could explain discrepancies in the epidemiological literature, where some polymorphisms have been inconsistently associated with susceptibility to TB. Furthermore, the model allows polymorphisms to be ranked by effect, providing a new tool for designing association studies.

  1. [Genetic polymorphism of Gentiana lutea L. (Gentianaceae) populations from Chornohora Ridge of Ukrainian Carpathians].

    PubMed

    Mosula, M Z; Konvaliuk, I I; Mel'nyk, V M; Drobyk, N M; Tsaryk, I V; Nesteruk, Iu I; Kunakh, V A

    2014-01-01

    The features of genetic structure and level of diversity were investigated for G. lutea populations from Chornohora Ridge of Ukrainian Carpathians using RAPD- and ISSR-PCR. We have shown a high level of genetic diversity for investigated populations. The differences between populations account for 59-72% of the total genetic variation, whereas intrapopulation polymorphism makes up 28-41%. The relationships among genetic variability level and ecological-geographical conditions as well as biological features of the species were assumed to be possible. The obtained results indicate the genetic isolation of G. lutea Chornohora populations from Ukrainian Carpathians. Pozhyzhevska agropopulation was characterized by a high level of polymorphism that means the possibility to use artificial plantings of the investigated species for its conservation.

  2. Technologies for individual genotyping: detection of genetic polymorphisms in drug targets and disease genes.

    PubMed

    Shi, Michael M

    2002-01-01

    Genetic variations have been associated with a predisposition to common diseases and individual variations in drug responses. Identification and genotyping a vast number of genetic polymorphisms in large populations are increasingly important for disease gene identification and pharmacogenetics. Commonly used gel electrophoresis-based genotyping methods for known polymorphisms include polymerase chain reaction (PCR) coupled with restriction fragment-length polymorphism analysis, allele-specific amplification, and oligonucleotide ligation assay. Fluorescent dye-based DNA fragmentation has been extensively used for high-throughput microsatellite or short tandem-repeat genotyping. TaqMan and molecular beacon genotyping are commonly used homogeneous solution hybridization technologies. Because of the ease of experimental assay design, single nucleotide polymorphism (SNP) genotyping methods based on single-base extension are in rapid development, such as fluorescence homogenous assays, pyrosequencing and mass spectrometry. Non-PCR based genotyping assays such as Invader trade mark assays are promised to genotype directly from genomic DNA without the requirement of PCR amplification. The DNA microarray is a solid phase genotyping format that is rapidly developing for parallel genotyping of a large number of SNPs simultaneously. Advanced technologies to identify genetic polymorphisms rapidly, accurately, and cost effectively will fundamentally change the practice of medicine by allowing physicians to prescribe medicine based on a patient's genetic make-up.

  3. Huangshan population of Chinese Zacco platypus (Teleostei, Cyprinidae) harbors diverse matrilines and high genetic diversity

    PubMed Central

    ZHENG, Xin; ZHOU, Tian-Qi; WAN, Tao; PERDICES, Anabel; YANG, Jin-Quan; TANG, Xin-Sheng; WANG, Zheng-Ping; HUANG, Li-Qun; HUANG, Song; HE, Shun-Ping

    2016-01-01

    Six main mitochondrial DNA (mtDNA) lineages have been described in minnow (Zacco platypus) samples obtained from northern, western and southern China. Perdices et al. (2004) predicted that further sampling of other tributaries might discover more lineages of this species. In this study, we collected 26 Zacco platypus individuals in the Huangshan area of eastern China and determined the cytochrome b (cytb) sequence variations. Combined with reported data in GenBank, we identified ten matrilines (Zacco A-J) in a total of 169 samples, with relatively high molecular divergence found among them. The Huangshan population had the greatest genetic variation among all sampled regions and hosted six of the ten matrilines. Our results highlight the significance of the Huangshan area for the conservation of Zacco platypus. PMID:27029868

  4. Huangshan population of Chinese Zacco platypus (Teleostei, Cyprinidae) harbors diverse matrilines and high genetic diversity.

    PubMed

    Zheng, Xin; Zhou, Tian-Qi; Wan, Tao; Perdices, Anabel; Yang, Jin-Quan; Tang, Xin-Sheng; Wang, Zheng-Ping; Huang, Li-Qun; Huang, Song; He, Shun-Ping

    2016-03-18

    Six main mitochondrial DNA (mtDNA) lineages have been described in minnow (Zacco platypus) samples obtained from northern, western and southern China. Perdices et al. (2004) predicted that further sampling of other tributaries might discover more lineages of this species. In this study, we collected 26 Zacco platypus individuals in the Huangshan area of eastern China and determined the cytochrome b (cytb) sequence variations. Combined with reported data in GenBank, we identified ten matrilines (Zacco A-J) in a total of 169 samples, with relatively high molecular divergence found among them. The Huangshan population had the greatest genetic variation among all sampled regions and hosted six of the ten matrilines. Our results highlight the significance of the Huangshan area for the conservation of Zacco platypus. PMID:27029868

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

    ERIC Educational Resources Information Center

    Falteisek, Lukáš; Cerný, Jan; Janštová, 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…

  6. Interferon-gamma Genetic Polymorphism and Expression in Kawasaki Disease

    PubMed Central

    Huang, Ying-Hsien; Hsu, Yu-Wen; Lu, Hsing-Fang; Wong, Henry Sung-Ching; Yu, Hong-Ren; Kuo, Hsing-Chun; Huang, Fu-Chen; Chang, Wei-Chiao; Kuo, Ho-Chang

    2016-01-01

    Abstract Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. IFNG gene encoding interferon (IFN)-γ, produced by natural killer cells and T cells, has been suggested to play an important role in the immunopathogenesis of Kawasaki disease. The aim of this study was to examin the correlation of gene polymorphisms of the IFNG gene and plasma levels of IFN-γ in KD patients and their outcomes. A total of 950 subjects (381 KD and 569 controls) were recruited. Three tagging single-nucleotide polymorphisms (rs2069718, rs1861493, rs2069705) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL), coronary artery aneurysms (CAA) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. Plasma IFN-γ levels were also measured with an enzyme-linked immunosorbent assay. Polymorphisms of the IFNG gene were significantly different between the normal controls and KD patients. The G allele of rs1861493 conferred a better response to IVIG treatment in KD patients. AA allele frequencies of rs1861493 were also associated with a significantly higher risk of CAA in KD patients. Furthermore, the plasma IFN-γ level was lower in the AA allele than in the GG allele of rs1861493 both before and after IVIG treatment in KD patients. This study provides the first evidence supporting an association between IFNG gene polymorphisms, susceptibility of KD, IVIG responsiveness, and plasma IFN-γ levels in KD patients. PMID:27124053

  7. Detection of genetic polymorphism in the populations of brinjal shoot and fruit borer, Leucinodes orbonalis (Guenee).

    PubMed

    Karthikeyan, K A M; Vijayakumar, I; Murali, P; Suresh, P; Janarthanan, S

    2005-06-01

    In the present study six different populations of L. orbonalis were collected and subjected to analysis of genetic variability in terms of carboxylesterase isozyme pattern and DNA polymorphism using RAPD-PCR. Pattern of carboxylesterase revealed a similar isozyme cluster in the populations namely, sivaganga (population-3), dindigal (population-4), virudhunagar (population-5) and coimbatore (population-6). Similarly, the populations of L. orbonalis recorded 3 distinct randomly amplified polymorphic DNA markers in all populations grouped above. This pattern of genetic variability in the populations was also supported by the analysis of the similarity indices and UPGMA dendrogram. PMID:15991581

  8. The association between vascular endothelial growth factor (VEGF) +405G>C genetic polymorphism and endometriosis

    PubMed Central

    Gong, Lili; Wang, Xiaojuan; Zhang, Ling

    2015-01-01

    The vascular endothelial growth factor (VEGF) is one of the most important candidate genes for the development of endometriosis, and VEGF genetic polymorphisms might be potentially associated with endometriosis risk. However, the results still remain controversial. The objective of this study aimed to perform a comprehensive meta-analysis to explore a better understanding of the effects of VEGF +405G>C genetic polymorphism on the risk of endometriosis. A total of eleven eligible studies were eventually identified in this meta-analysis, including 2829 endometriosis cases and 2947 controls. In the overall analysis, no significant association between the VEGF +405G>C genetic polymorphism and the risk of endometriosis was detected in all genetic models (for homozygote comparison [CC versus vs. GG]: OR = 1.21, 95% CI 0.67–2.19, P = 0.537; for heterozygote comparison [CG vs. GG]: OR = 1.16, 95% CI 0.86–1.56, P = 0.348; for dominant comparison CC/CG vs. GG: OR = 1.10, 95% CI 0.93–1.30, P = 0.263; for recessive comparison [CC vs. CG/GG]: OR = 1.03, 95% CI 0.73–1.47, P = 0.857; allele comparison [C vs. G]: OR = 0.99, 95% CI 0.70–1.40, P = 0.962). In the subgroup analysis by ethnicities, there was no significant association between VEGF +405G>C genetic polymorphism and endometriosis risk in Asians and/or Caucasians under all genetic models (all P-values >0.05). No publication bias was observed in this study. This meta-analysis supports that the VEGF +405G>C genetic polymorphism is not significant associated with the risk of endometriosis. PMID:25573961

  9. The association between vascular endothelial growth factor (VEGF) +405G>C genetic polymorphism and endometriosis.

    PubMed

    Fang, Fang; Gong, Lili; Wang, Xiaojuan; Zhang, Ling

    2015-09-01

    The vascular endothelial growth factor (VEGF) is one of the most important candidate genes for the development of endometriosis, and VEGF genetic polymorphisms might be potentially associated with endometriosis risk. However, the results still remain controversial. The objective of this study aimed to perform a comprehensive meta-analysis to explore a better understanding of the effects of VEGF +405G>C genetic polymorphism on the risk of endometriosis. A total of eleven eligible studies were eventually identified in this meta-analysis, including 2829 endometriosis cases and 2947 controls. In the overall analysis, no significant association between the VEGF +405G>C genetic polymorphism and the risk of endometriosis was detected in all genetic models (for homozygote comparison [CC versus vs. GG]: OR = 1.21, 95% CI 0.67-2.19, P = 0.537; for heterozygote comparison [CG vs. GG]: OR = 1.16, 95% CI 0.86-1.56, P = 0.348; for dominant comparison CC/CG vs. GG: OR = 1.10, 95% CI 0.93-1.30, P = 0.263; for recessive comparison [CC vs. CG/GG]: OR = 1.03, 95% CI 0.73-1.47, P = 0.857; allele comparison [C vs. G]: OR = 0.99, 95% CI 0.70-1.40, P = 0.962). In the subgroup analysis by ethnicities, there was no significant association between VEGF +405G>C genetic polymorphism and endometriosis risk in Asians and/or Caucasians under all genetic models (all P-values >0.05). No publication bias was observed in this study. This meta-analysis supports that the VEGF +405G>C genetic polymorphism is not significant associated with the risk of endometriosis.

  10. Relationships of OPG Genetic Polymorphisms with Susceptibility to Cardiovascular Disease: A Meta-Analysis.

    PubMed

    Song, De-Hua; Zhou, Peng-Zhen; Xiu, Xiao-Lin; Zhou, Guang-Hui; Sun, Yu-Xia; Song, Chun

    2016-04-12

    BACKGROUND The aim of this meta-analysis was to determine whether genetic polymorphisms in the osteoprotegerin (OPG) gene contribute to increased risk of cardiovascular disease (CVD). MATERIAL AND METHODS Electronic databases were searched carefully without any language restriction. Analyses of data were conducted using STATA software. Odds ratios (OR) and 95% confidence intervals (95%CI) were also calculated. RESULTS Seven clinical case-control studies that enrolled 1170 CVD patients and 1194 healthy subjects were included. The results indicated that OPG gene polymorphism might be closely associated with susceptibility to CVD, especially for rs2073617 T>C and rs2073618 G>C polymorphisms. Ethnicity-stratified analysis indicated that genetic polymorphism in the OPG were closely related with the pathogenesis of CVD among Asians (all P<0.001), but no obvious relationship was found among Caucasians (all P>0.05). CONCLUSIONS Our meta-analysis provided quantitative evidence that OPG gene polymorphism may be closely related to an increased risk of CVD, especially for rs2073617 T>C and rs2073618 G>C polymorphisms.

  11. Levels of genetic polymorphism: marker loci versus quantitative traits.

    PubMed

    Butlin, R K; Tregenza, T

    1998-02-28

    Species are the units used to measure ecological diversity and alleles are the units of genetic diversity. Genetic variation within and among species has been documented most extensively using allozyme electrophoresis. This reveals wide differences in genetic variability within, and genetic distances among, species, demonstrating that species are not equivalent units of diversity. The extent to which the pattern observed for allozymes can be used to infer patterns of genetic variation in quantitative traits depends on the forces generating and maintaining variability. Allozyme variation is probably not strictly neutral but, nevertheless, heterozygosity is expected to be influenced by population size and genetic distance will be affected by time since divergence. The same is true for quantitative traits influenced by many genes and under weak stabilizing selection. However, the limited data available suggest that allozyme variability is a poor predictor of genetic variation in quantitative traits within populations. It is a better predictor of general phenotypic divergence and of postzygotic isolation between populations or species, but is only weakly correlated with prezygotic isolation. Studies of grasshopper and planthopper mating signal variation and assortative mating illustrate how these characters evolve independently of general genetic and morphological variation. The role of such traits in prezygotic isolation, and hence speciation, means that they will contribute significantly to the diversity of levels of genetic variation within and among species.

  12. Heparin-induced thrombocytopenia: the role of platelets genetic polymorphisms.

    PubMed

    Pamela, Scarparo; Anna Maria, Lombardi; Elena, Duner; Giovanni, Malerba; Emanuele, Allemand; Silvia, Vettore; Carmen, Blumentritt; Andreas, Greinacher; Fabrizio, Fabris

    2013-01-01

    Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy, characterized by thrombocytopenia and an increased risk for thrombotic complications secondary to the formation of IgG antibodies (Ab), recognizing a complex of heparin (H) and PF4. Using the 4T clinical score for HIT and the presence of heparin-associated Ab assayed by enzyme-linked immunosorbent assay and heparin-induced platelet aggregation, we define the phenotype of three groups of patients: 51 H/PF4/Ab patients with antibodies and without thrombocytopenia; 50 patients with thrombocytopenia (HIT) and 53 patients with thrombosis (HITT). In these patients we studied four polymorphisms: FcγRIIA-H131R, GpIIb/IIIa-HP-1, PECAM1-L125V (in linkage-disequilibrium with S563N and R670G), and FcγRIIIA-F158V, to understand if these variations may influence the different phenotypes of the patients. There were no difference in genotype or allele frequencies between controls and the three groups of patients. Afterward, we created a genotype score for multiple risk alleles for thrombosis considering as risk genotype FcγRIIA R/R131, HPA-1a/b, and PECAM1-V/V125. These polymorphisms were overrepresented in HITT patients, ascertained by a permutation test (10 000 replicates) p = 0.0198 for the two-single-nucleotide polymorphism (SNP) model and p = 0.0119 for the three-SNP model. The calculated odds ratio for thrombosis was 4.01[CI: 2.30-6.96] in the case of the presence of two at risk genotypes and 8.002 [CI: 4.59-13.93] if all the three at risk genotypes were present. In conclusion these polymorphisms could contribute to the risk of thrombotic complications in HIT.

  13. Genetic polymorphism of the LW blood group system.

    PubMed

    Sistonen, P; Green, C A; Lomas, C G; Tippett, P

    1983-10-01

    Family studies of rare LW(a-b+) propositi confirm the recent finding based on frequency studies that the LW blood groups are polymorphic in Finland (Sistonen & Tippett, 1982); they are controlled by two alleles LWa (0.97) and LWb (0.03) independent from most other common blood group loci. Lod scores for LW and the loci for 27 markers are presented. PMID:6418057

  14. 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

  15. Dopaminergic Genetic Polymorphisms Predict Rule-Based Category Learning

    PubMed Central

    Byrne, Kaileigh A.; Davis, Tyler; Worthy, Darrell A.

    2016-01-01

    Dopaminergic genes play an important role in cognitive function. DRD2 and DARPP-32 dopamine receptor gene polymorphisms affect striatal dopamine binding potential, while the Val158Met single nucleotide polymorphism of the COMT gene moderates dopamine availability in the prefrontal cortex. Our study assesses the role of these gene polymorphisms on performance in two rule-based category learning tasks. Participants completed unidimensional and conjunctive rule-based tasks. In the unidimensional task, a rule along a single stimulus dimension can be used to distinguish category members. In contrast, a conjunctive rule utilizes a combination of two dimensions to distinguish category members. DRD2 C957T TT homozygotes outperformed C allele carriers on both tasks, and DARPP-32 AA homozygotes outperformed G allele carriers on both tasks. However, we found an interaction between COMT and task-type where Met allele carriers outperformed Val homozygotes in the conjunctive rule task, but both groups performed equally well in the unidimensional task. Thus, striatal dopamine binding may play a critical role in both types of rule-based tasks, while prefrontal dopamine binding is important for learning more complex conjunctive rule tasks. Modeling results suggest that striatal dopaminergic genes influence selective attention processes while cortical genes mediate the ability to update complex rule-representations. PMID:26918585

  16. Double-stranded RNA viral infection of Trichomonas vaginalis and correlation with genetic polymorphism of isolates.

    PubMed

    Fraga, Jorge; Rojas, Lazara; Sariego, Idalia; Fernández-Calienes, Ayme

    2011-02-01

    Trichomonas vaginalis can be infected with double-stranded RNA (dsRNA) viruses known as T. vaginalis virus (TVV). This viral infection may have important implications for trichomonal virulence and disease pathogenesis. The objective of this study was to determine the possible correlation between the T. vaginalis genetic polymorphism and the isolate infection with TVV. The Random Amplified Polymorphic DNA (RAPD) technique was used to determine genetic differences among 37 isolates of T. vaginalis using a panel of 30 random primers and these genetic data were correlated with the infection of isolates with TVV. The trees drawn based on RAPD data showed significantly association with the presence of TVV (P = 0.028) demonstrating the existence of concordance between the genetic relatedness and the presence of TVV in T. vaginalis isolates. This result could point to a predisposition of T. vaginalis for the viral enters and/or survival. PMID:20875411

  17. Genetic Association Analysis of Dopamine DRD3 Ser9Gly Polymorphism and Schizophrenia in Malay Population

    PubMed Central

    Tee, SF; Tang, PY; Loh, HC

    2011-01-01

    Background: Molecular components of the dopamine receptor (DRD3) play an important role in the pathophysiology of schizophrenia (SCZ). Previous studies have demonstrated an association between the DRD3 Ser9Gly polymorphism and SCZ but the results have been inconclusive. Method: In this study, we investigated this controversial association between the Ser9Gly (A/G) polymorphism and SCZ using Malay cases-control (261 cases/157 controls) samples. PCR-RFLP was performed to genotype the distribution of the DRD3 Ser9Gly polymorphism. Results: Both healthy control and SCHZ patient groups were in of Hardy-Weinberg equilibrium for the analyzed genetic variability. There was a significant association between the genotype distribution DRD3 polymorphisms and SCZ (χ2= 9.359; df = 2; P = 0.009). Conclusion: We believe that further studies are required to examine the association between others dopamine-related genes and the behavioral phenotypes of SCZ. PMID:23113067

  18. 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.

  19. 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

    2014-09-26

    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.

  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

    2016-01-01

    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. The origins of extraversion: joint effects of facultative calibration and genetic polymorphism.

    PubMed

    Lukaszewski, Aaron W; Roney, James R

    2011-03-01

    The origins of variation in extraversion are largely mysterious. Recent theories and some findings suggest that personality variation can be orchestrated by specific genetic polymorphisms. Few studies, however, have examined an alternative hypothesis that personality traits are facultatively calibrated to variations in other phenotypic features, and none have considered how these distinct processes may interact in personality determination. Since physical strength and physical attractiveness likely predicted the reproductive payoffs of extraverted behavioral strategies over most of human history, it was theorized that extraversion is calibrated to variation in these characteristics. Confirming these predicted patterns, strength and attractiveness together explained a surprisingly large fraction of variance in extraversion across two studies--effects that were independent of variance explained by an androgen receptor gene polymorphism. These novel findings initially support an integrative model wherein facultative calibration and specific genetic polymorphisms operate in concert to determine personality variation.

  2. [Polymorphism of connexin 40 gene-- a novel genetic marker of the sick sinus node syndrome].

    PubMed

    Chernova, A A; Nikulina, S Iu; Shul'man, V A; Kukushkina, T S; Voevoda, M I; Maksimov, V N

    2011-01-01

    In this work we have demonstrated for the first time on the clinico-genetic material association between hereditary sick sinus node syndrome and connexin 40 gene polymorphism. We have revealed that heterozygous variant of connexin 40 gene variant is more frequent among patients with sick sinus node syndrome and their healthy relatives than in persons of control group.

  3. 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...

  4. 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

  5. Selection on a genetic polymorphism counteracts ecological speciation in a stick insect.

    PubMed

    Comeault, Aaron A; Flaxman, Samuel M; Riesch, Rüdiger; Curran, Emma; Soria-Carrasco, Víctor; Gompert, Zachariah; Farkas, Timothy E; Muschick, Moritz; Parchman, Thomas L; Schwander, Tanja; Slate, Jon; Nosil, Patrik

    2015-08-01

    The interplay between selection and aspects of the genetic architecture of traits (such as linkage, dominance, and epistasis) can either drive or constrain speciation [1-3]. Despite accumulating evidence that speciation can progress to "intermediate" stages-with populations evolving only partial reproductive isolation-studies describing selective mechanisms that impose constraints on speciation are more rare than those describing drivers. The stick insect Timema cristinae provides an example of a system in which partial reproductive isolation has evolved between populations adapted to different host plant environments, in part due to divergent selection acting on a pattern polymorphism [4, 5]. Here, we demonstrate how selection on a green/melanistic color polymorphism counteracts speciation in this system. Specifically, divergent selection between hosts does not occur on color phenotypes because melanistic T. cristinae are cryptic on the stems of both host species, are resistant to a fungal pathogen, and have a mating advantage. Using genetic crosses and genome-wide association mapping, we quantify the genetic architecture of both the pattern and color polymorphism, illustrating their simple genetic control. We use these empirical results to develop an individual-based model that shows how the melanistic phenotype acts as a "genetic bridge" that increases gene flow between populations living on different hosts. Our results demonstrate how variation in the nature of selection acting on traits, and aspects of trait genetic architecture, can impose constraints on both local adaptation and speciation.

  6. Impact of genetic polymorphisms on paediatric atopic dermatitis.

    PubMed

    Esposito, Susanna; Patria, Maria Francesca; Spena, Silvia; Codecà, Claudio; Tagliabue, Claudia; Zampiero, Alberto; Lelii, Mara; Montinaro, Valentina; Pelucchi, Claudio; Principi, Nicola

    2015-09-01

    In order to investigate whether polymorphisms of genes encoding some factors of innate and adaptive immunity play a role in the development of, or protection against atopic dermatitis (AD) and condition its severity, we genotyped 33 candidate genes and 47 single nucleotide polymorphisms (SNPs) using Custom TaqMan Array Microfluidic Cards and an ABI 7900HT analyser (Applied Biosystems, Foster City, CA, USA). The study involved 104 children with AD (29 with mild-to-moderate and 75 with severe disease; 42 girls; mean age ± SD, 5.8 ± 3.3 years) and 119 healthy controls (49 girls; mean age, 4.8 ± 3.0 years). IL10-rs1800872T, TG and MBL2-rs500737AG were all significantly more frequent among the children with AD (P = 0.015, P = 0.004 and P = 0.030), whereas IL10-rs1800896C and TC were more frequent in those without AD (P = 0.028 and P = 0.032). The VEGFA-rs2146326A and CTLA4-rs3087243AG SNPs were significantly more frequent in the children with mild/moderate AD than in those with severe AD (P = 0.048 andP = 0.036). IL10-rs1800872T and TG were significantly more frequent in the children with AD and other allergic diseases than in the controls (P = 0.014 and P = 0.007), whereas IL10-rs1800896TC and C were more frequent in the controls than in the children with AD and other allergic diseases (P = 0.0055 and P = 0.0034). These findings show that some of the polymorphisms involved in the immune response are also involved in some aspects of the development and course of AD and, although not conclusive, support the immunological hypothesis of the origin of the inflammatory lesions.

  7. 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

  8. Application of restriction site amplified polymorphism (RSAP) to genetic diversity in Saccharina japonica

    NASA Astrophysics Data System (ADS)

    Zhao, Cui; Liu, Cui; Li, Wei; Chi, Shan; Feng, Rongfang; Liu, Tao

    2013-07-01

    Restriction site amplified polymorphism (RSAP) was used, for the first time, to analyze the genetic structure and diversity of four, mainly cultivated, varieties of the brown alga, Saccharina japonica. Eighty-eight samples from varieties " Rongfu ", " Fujian ", " Ailunwan " and " Shengchanzhong " were used for the genetic analyses. One hundred and ninety-eight bands were obtained using eight combinations of primers. One hundred and ninety-one (96.46%) were polymorphic bands. Nei's genetic diversity was 0.360, and the coefficient of genetic differentiation was 0.357. No inbreeding-type recession was found in the four brown alga varieties and the results of the " Ailunwan " variety using samples from 2 years showed that the variety was becoming less diverse during the selection inherent in the breeding program. Genetic diversity and cluster analyses results were consistent with these genetic relationships. The results show the RSAP method is suitable for genetic analysis. Continuous inbreeding and selection could reduce the genetic diversity effectively; therefore periodical supervision is required.

  9. 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 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

  10. 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

  11. 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.

  12. 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

  13. AFLP genetic polymorphism in wild barley (Hordeum spontaneum) populations in Israel.

    PubMed

    Turpeinen, T; Vanhala, T; Nevo, E; Nissilä, E

    2003-05-01

    The genetic diversity produced by the amplified fragment length polymorphism (AFLP) method was studied in 94 genotypes of wild barley, Hordeum spontaneum (C. Koch) Thell., originating from ten ecologically and geographically different locations in Israel. Eight primer pairs produced 204 discernible loci of which 189 (93%) were polymorphic. Each genotype had a unique banding profile and the genetic similarity coefficient varied between 0.74 and 0.98. The phenogram generated from these similarities by the UPGMA method did not group genotypes strictly according to their geographical origin, which pattern was also seen in the principal coordinate (PCO) plot. Genetic diversity was larger within (69%) than among (31%) populations. Associations between ecogeographical variables and the mean gene diversity were found at one primer pair. The results are discussed and compared with data obtained by the simple sequence repeat (SSR) method. PMID:12748785

  14. TP53 Polymorphisms allow for genetic sub-grouping of the canine transmissible venereal tumor

    PubMed Central

    Sánchez-Servín, Abel; Córdova-Alarcon, Emilio; Fajardo, Raúl

    2009-01-01

    The canine transmissible venereal tumor (CTVT) is found mainly in dogs' sexual organs. Currently, it is widely accepted that all samples of CTVT show similar histopathological characteristics and share common genetic alterations. Despite the common genetic origin of CTVT, mutations in the P53 gene have been reported. In this study, we proposed that tumor samples can be genetically grouped using this gene. The presence of different subgroups of CTVT was determined in Mexican dogs using the TP53 gene sequence in CTVT samples. Four new polymorphisms were found and therefore, the CTVT samples were classified in five subgroups. PMID:19934603

  15. [ROLE OF GENETIC POLYMORPHISM AND DIFFERENCES IN THE DETOXIFICATION OF CHEMICAL SUBSTANCES IN THE HUMAN BODY].

    PubMed

    Mogilenkova, L A; Rembovskiy V R

    2016-01-01

    There are given modern views on the role of genetic polymorphism on the detoxification of chemical substances and individual sensitivity in workers to the development of diseases associated with xenobiotics metabolism disorders. In the search for genetic markers of occupationally caused diseases it is promising to study allelomorphs of genes responsible for the polyfunctional response of the human body, including genes involved in xenobiotic biotransformation. There is substantiated the expediency of compilation and introduction of genetic passports for stuff occupied at hazardous chemical enterprises. PMID:27266025

  16. [ROLE OF GENETIC POLYMORPHISM AND DIFFERENCES IN THE DETOXIFICATION OF CHEMICAL SUBSTANCES IN THE HUMAN BODY].

    PubMed

    Mogilenkova, L A; Rembovskiy V R

    2016-01-01

    There are given modern views on the role of genetic polymorphism on the detoxification of chemical substances and individual sensitivity in workers to the development of diseases associated with xenobiotics metabolism disorders. In the search for genetic markers of occupationally caused diseases it is promising to study allelomorphs of genes responsible for the polyfunctional response of the human body, including genes involved in xenobiotic biotransformation. There is substantiated the expediency of compilation and introduction of genetic passports for stuff occupied at hazardous chemical enterprises.

  17. Genetic markers for detection of Escherichia coli K-12 harboring ampicillin-resistance plasmid from an industrial wastewater treatment effluent pond.

    PubMed

    Simões, G A R; Xavier, M A S; Oliveira, D A; Menezes, E V; Magalhães, S S G; Gandra, J A C D; Xavier, A R E O

    2016-06-17

    Biotechnology industries that use recombinant DNA technology are potential sources for release of genetically modified organisms to the environment. Antibiotic-resistance marker genes are commonly used for recombinant bacteria selection. One example is the marker gene coding for β-lactamase (bla) in plasmids found in Escherichia coli K-12. The aim of this study was to provide an approach to develop a molecular method for genetic marker detection in E. coli K-12 harboring bla genes from an industrial wastewater treatment effluent pond (IWTEP). For the detection of bla and Achromobacter lyticus protease I (api) genes in samples from IWTEP, we employed multiplex polymerase chain reaction (PCR) using E. coli K-12 genetic marker detection primers, previously described in the literature, and primers designed in our laboratory. The microbiological screening method resulted in 22 bacterial colony-forming units isolated from three different IWTEP harvesting points. The multiplex PCR amplicons showed that five isolates were positive for the bla gene marker and negative for the E. coli K-12 and api genes. The 16S rRNA regions of positive microorganisms carrying the bla gene were genotyped by the MicroSeq®500 system. The bacteria found were Escherichia spp (3/5), Chromobacterium spp (1/5), and Aeromonas spp (1/5). None of the 22 isolated microorganisms presented the molecular pattern of E. coli K-12 harboring the bla gene. The presence of microorganisms positive for the bla gene and negative for E. coli K-12 harboring bla genes at IWTEP suggests that the ampicillin resistance found in the isolated bacteria could be from microorganisms other than the E. coli K-12 strain harboring plasmid.

  18. Genetic markers for detection of Escherichia coli K-12 harboring ampicillin-resistance plasmid from an industrial wastewater treatment effluent pond.

    PubMed

    Simões, G A R; Xavier, M A S; Oliveira, D A; Menezes, E V; Magalhães, S S G; Gandra, J A C D; Xavier, A R E O

    2016-01-01

    Biotechnology industries that use recombinant DNA technology are potential sources for release of genetically modified organisms to the environment. Antibiotic-resistance marker genes are commonly used for recombinant bacteria selection. One example is the marker gene coding for β-lactamase (bla) in plasmids found in Escherichia coli K-12. The aim of this study was to provide an approach to develop a molecular method for genetic marker detection in E. coli K-12 harboring bla genes from an industrial wastewater treatment effluent pond (IWTEP). For the detection of bla and Achromobacter lyticus protease I (api) genes in samples from IWTEP, we employed multiplex polymerase chain reaction (PCR) using E. coli K-12 genetic marker detection primers, previously described in the literature, and primers designed in our laboratory. The microbiological screening method resulted in 22 bacterial colony-forming units isolated from three different IWTEP harvesting points. The multiplex PCR amplicons showed that five isolates were positive for the bla gene marker and negative for the E. coli K-12 and api genes. The 16S rRNA regions of positive microorganisms carrying the bla gene were genotyped by the MicroSeq®500 system. The bacteria found were Escherichia spp (3/5), Chromobacterium spp (1/5), and Aeromonas spp (1/5). None of the 22 isolated microorganisms presented the molecular pattern of E. coli K-12 harboring the bla gene. The presence of microorganisms positive for the bla gene and negative for E. coli K-12 harboring bla genes at IWTEP suggests that the ampicillin resistance found in the isolated bacteria could be from microorganisms other than the E. coli K-12 strain harboring plasmid. PMID:27323199

  19. Genetic polymorphism and immune response to tuberculosis in indigenous populations: a brief review.

    PubMed

    Longhi, Renata Maronna Praça; Zembrzuski, Verônica Marques; Basta, Paulo Cesar; Croda, Julio

    2013-01-01

    We systematically reviewed studies of the immune response to tuberculosis and the genetic polymorphisms associated with Th1- or Th2-mediated cytokine expression in indigenous populations. A bibliographic search was performed on the Medline and ISI databases and included studies published between January 1980 and October 2011. The search terms were tuberculosis, American Indians, Amerindian, indigenous, Indians, native people, aboriginal, immun*, host immune, immune response, cytokine*, polymorphism*, and gene. Regardless of their design, studies that evaluated immunoglobulin, cytokine levels and genetic polymorphisms that altered cytokine expression were included. Thirteen studies met the inclusion criteria. The majority of studies were performed in Latin America, and five investigated the Warao ethnic group of Venezuela. Most of the investigations indirectly evaluated the immune response. Higher anergy to the tuberculin skin test, higher IgG4 and IgM levels, higher IL-5 production and lower TNF-α, IL-12p40 and IFN-γ production were found in the indigenous populations. The studies also reported a predominantly Th2-type response in these populations and a possibly higher susceptibility to tuberculosis. A better understanding of the relevant genetic polymorphisms and their role in immune regulation would help to clarify the immunogenetic mechanisms of TB infection in these populations. This information would be useful for identifying new treatments and preventing infection and progression to active disease. PMID:23665009

  20. Evaluation of genetic diversity in jackfruit (Artocarpus heterophyllus Lam.) based on amplified fragment length polymorphism markers.

    PubMed

    Shyamalamma, S; Chandra, S B C; Hegde, M; Naryanswamy, P

    2008-01-01

    Artocarpus heterophyllus Lam., commonly called jackfruit, is a medium-sized evergreen tree that bears high yields of the largest known edible fruit. Yet, it has been little explored commercially due to wide variation in fruit quality. The genetic diversity and genetic relatedness of 50 jackfruit accessions were studied using amplified fragment length polymorphism markers. Of 16 primer pairs evaluated, eight were selected for screening of genotypes based on the number and quality of polymorphic fragments produced. These primer combinations produced 5976 bands, 1267 (22%) of which were polymorphic. Among the jackfruit accessions, the similarity coefficient ranged from 0.137 to 0.978; the accessions also shared a large number of monomorphic fragments (78%). Cluster analysis and principal component analysis grouped all jackfruit genotypes into three major clusters. Cluster I included the genotypes grown in a jackfruit region of Karnataka, called Tamaka, with very dry conditions; cluster II contained the genotypes collected from locations having medium to heavy rainfall in Karnataka; cluster III grouped the genotypes in distant locations with different environmental conditions. Strong coincidence of these amplified fragment length polymorphism-based groupings with geographical localities as well as morphological characters was observed. We found moderate genetic diversity in these jackfruit accessions. This information should be useful for tree breeding programs, as part of our effort to popularize jackfruit as a commercial crop.

  1. Evaluation of genetic diversity in jackfruit (Artocarpus heterophyllus Lam.) based on amplified fragment length polymorphism markers.

    PubMed

    Shyamalamma, S; Chandra, S B C; Hegde, M; Naryanswamy, P

    2008-01-01

    Artocarpus heterophyllus Lam., commonly called jackfruit, is a medium-sized evergreen tree that bears high yields of the largest known edible fruit. Yet, it has been little explored commercially due to wide variation in fruit quality. The genetic diversity and genetic relatedness of 50 jackfruit accessions were studied using amplified fragment length polymorphism markers. Of 16 primer pairs evaluated, eight were selected for screening of genotypes based on the number and quality of polymorphic fragments produced. These primer combinations produced 5976 bands, 1267 (22%) of which were polymorphic. Among the jackfruit accessions, the similarity coefficient ranged from 0.137 to 0.978; the accessions also shared a large number of monomorphic fragments (78%). Cluster analysis and principal component analysis grouped all jackfruit genotypes into three major clusters. Cluster I included the genotypes grown in a jackfruit region of Karnataka, called Tamaka, with very dry conditions; cluster II contained the genotypes collected from locations having medium to heavy rainfall in Karnataka; cluster III grouped the genotypes in distant locations with different environmental conditions. Strong coincidence of these amplified fragment length polymorphism-based groupings with geographical localities as well as morphological characters was observed. We found moderate genetic diversity in these jackfruit accessions. This information should be useful for tree breeding programs, as part of our effort to popularize jackfruit as a commercial crop. PMID:18752192

  2. 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.

  3. 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

  4. Genetic polymorphism of MMP family and coronary disease susceptibility: a meta-analysis.

    PubMed

    Li, Min; Shi, Jingpu; Fu, Lingyu; Wang, Hailong; Zhou, Bo; Wu, Xiaomei

    2012-03-01

    The issue that genetic polymorphism of matrix metalloproteinase (MMP) family is in association with coronary disease is controversial. So we did a meta-analysis to clarify it clearly. We made a literature search of PubMed, the Web of Science, and Cochrane Collaboration's database to identify eligible reports. The methodological quality of each included studies was assessed. We calculated the pooled ORs with their 95%CI for each genetic polymorphism in STATA 11 software. Separate analysis was performed to address the consistency of results across the subgroup with different continents. A total of 39 studies were included, with a sample of 42269 individuals. This meta-analysis provided evidence that genetic polymorphism of MMP1-1607 1G/2G, MMP3-Gly45lys, MMP3-376 G/C, MMP3-1171 5A/6A, MMP9-1562 C/T and MMP9-R279Q have a small to medium effect on incidence of coronary disease. There was no evidence that MMP1-519 A/G, MMP1-340 T/C and MMP2-1306 C/T polymorphism could increase risk of coronary disease. Results from subgroup analysis supported a relation between MMP3-1711 5A allele, MMP9-1562 C allele and coronary disease especially in Asian population. The results provide moderate association between the six common genetic polymorphism of matrix metalloproteinase family and coronary disease. However, the challenge for researcher is identifying separate effect on different races.

  5. [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.

  6. Genetic polymorphisms in folate pathway enzymes, DRD4 and GSTM1 are related to temporomandibular disorder

    PubMed Central

    2011-01-01

    Background Temporomandibular disorder (TMD) is a multifactorial syndrome related to a critical period of human life. TMD has been associated with psychological dysfunctions, oxidative state and sexual dimorphism with coincidental occurrence along the pubertal development. In this work we study the association between TMD and genetic polymorphisms of folate metabolism, neurotransmission, oxidative and hormonal metabolism. Folate metabolism, which depends on genes variations and diet, is directly involved in genetic and epigenetic variations that can influence the changes of last growing period of development in human and the appearance of the TMD. Methods A case-control study was designed to evaluate the impact of genetic polymorphisms above described on TMD. A total of 229 individuals (69% women) were included at the study; 86 were patients with TMD and 143 were healthy control subjects. Subjects underwent to a clinical examination following the guidelines by the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Genotyping of 20 Single Nucleotide Polymorphisms (SNPs), divided in two groups, was performed by multiplex minisequencing preceded by multiplex PCR. Other seven genetic polymorphisms different from SNPs (deletions, insertions, tandem repeat, null genotype) were achieved by a multiplex-PCR. A chi-square test was performed to determine the differences in genotype and allelic frequencies between TMD patients and healthy subjects. To estimate TMD risk, in those polymorphisms that shown significant differences, odds ratio (OR) with a 95% of confidence interval were calculated. Results Six of the polymorphisms showed statistical associations with TMD. Four of them are related to enzymes of folates metabolism: Allele G of Serine Hydoxymethyltransferase 1 (SHMT1) rs1979277 (OR = 3.99; 95%CI 1.72, 9.25; p = 0.002), allele G of SHMT1 rs638416 (OR = 2.80; 95%CI 1.51, 5.21; p = 0.013), allele T of Methylentetrahydrofolate Dehydrogenase (MTHFD) rs

  7. 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

  8. 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

  9. 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

  10. Role of genetic polymorphisms and mutations in colorectal cancer therapy (Review).

    PubMed

    Aiello, Marco; Vella, Nadia; Cannavò, Calogero; Scalisi, Aurora; Spandidos, Demetrios A; Toffoli, Giuseppe; Buonadonna, Angela; Libra, Massimo; Stivala, Franca

    2011-01-01

    Gene polymorphisms and mutations in various types of cancer may predict clinical response to chemotherapy and related toxicity, since they may affect the metabolism of the drugs commonly used in combination chemotherapy treatments. However, conflicting data have been generated on this subject. To elucidate this issue, this review discusses the clinical applications of several genetic polymorphisms in colorectal cancer patients treated with the most common agents alone or in combination. UDP-glucuronosyltransferase (UGT)1A1 is a conjugating biotransformation enzyme that plays a role in maintaining the levels of endogenous compounds (e.g., bilirubin) and in handling exogenous compounds, including carcinogens. It has been demonstrated that the UGT1A1*28 polymorphism plays a predictive role in patients administered an irinotecan-containing regimen. Polymorphisms in XPD (Lys751Gln), a member of the nucleotide excision repair pathway, negatively affect response to therapy, with oxaliplatin/5FU reducing the survival of the patient. A similar reaction has also been observed in patients with the XRCC1 Arg399Gln polymorphism, while patients with the GSTP1 Ile105Val polymorphism have an improved response to oxaliplatin/5FU therapy. Treatment with biological compounds such as cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, has been shown to be effective only in colon cancer patients with wild-type K-Ras. Fc polymorphisms are associated with progression-free survival in patients treated with cetuximab. Another monoclonal antibody useful in the treatment of colon cancer is bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF); however, in some cases bevacizumab may cause deep vein thrombosis (DVP). In a related vein, our recent unpublished data show that the VEGF C936T polymorphism may increase the risk of DVP in cancer patients. In conclusion, this review indicates that certain polymorphisms increase the effectiveness of

  11. 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

    2015-11-19

    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.

  12. 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

  13. Correlations of IFN-γ genetic polymorphisms with susceptibility to breast cancer: a meta-analysis.

    PubMed

    Li, Chun-Jiang; Dai, Yue; Fu, Yan-Jun; Tian, Jia-Ming; Li, Jin-Lun; Lu, Hong-Jun; Duan, Feng; Li, Qing-Wang

    2014-07-01

    The meta-analysis was conducted to evaluate the correlations between common genetic polymorphisms in the IFN-γ gene and susceptibility to breast cancer. The following electronic databases were searched without language restrictions: MEDLINE (1966 ~ 2013), the Cochrane Library Database (issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013). Meta-analysis was performed with the use of the STATA statistical software. Odds ratios (OR) with their 95 % confidence intervals (95 % CIs) were calculated. Nine clinical case-control studies met all the inclusion criteria and were included in this meta-analysis. A total of 1,182 breast cancer patients and 1,525 healthy controls were involved in this meta-analysis. Three functional polymorphisms were assessed, including rs2069705 C>T, rs2430561 T>A, and CA repeats 2/X. Our meta-analysis results indicated that IFN-γ genetic polymorphisms might be significantly associated with an increased risk of breast cancer (allele model: OR = 1.37, 95 % CI = 1.03 ~ 1.83, P = 0.031; dominant model: OR = 1.55, 95 % CI = 1.01 ~ 2.37, P = 0.046; homozygous model: OR = 2.23, 95 % CI = 1.30 ~ 3.82, P = 0.004; respectively), especially the rs2430561 T>A polymorphism. Subgroup analysis based on ethnicity suggested that genetic polymorphisms in the IFN-γ gene were closely correlated with increased breast cancer risk among Asians (allele model: OR = 1.21, 95 % CI = 1.02 ~ 1.58, P = 0.017; dominant model: OR = 3.44, 95 % CI = 2.07 ~ 5.71, P < 0.001; recessive model: OR = 1.58, 95 % CI = 1.06 ~ 2.37, P = 0.025; homozygous model: OR = 1.83, 95 % CI = 1.19 ~ 2.80, P = 0.006; respectively), but not among Caucasians (all P > 0.05). Our meta-analysis supported the hypothesis that IFN-γ genetic polymorphisms may contribute to an increased risk of breast cancer, especially the rs2430561 T>A polymorphism among Asians.

  14. [Genetic analysis of microsatellite polymorphism in the Elliot's Pheasant (Syrmaticus ellioti) in China].

    PubMed

    Lin, Fang-Jun; Jiang, Ping-Ping; Ding, Ping

    2010-10-01

    In this study, we reported the population genetic analyses in the Elliot's Pheasant(Syrnaticus ellioti) using seven polymorphism microsatellite loci based on 105 individuals from 4 geographical populations. Departures from Hardy-Weinberg equilibrium were found in four geographical populations. The average number of alleles was 8.86, with a total of 62 alleles across 7 loci; observed heterozygosity (HO) was generally low and the average number was 0.504. For the seven microsatellite loci, the polymorphism information content ranged from 0.549 to 0.860, with an average number 0.712. Population bottlenecks of the four geographical populations were tested by infinite allele mutation model, step-wise mutation model and two-phase mutation model, which found that each population had experienced bottleneck effect during the recent period. Fst analysis across all geographical populations indicated that the genetic differentiaton between the Guizhou geographical population and the Hunan geographical population was highly significant (P<0.001), a finding supported by the far genetic relationship showed by the neighbor-joining tree of four geographical populations based on Nei's unbiased genetic distances. Using hierarchical analysis of molecular variance (Guizhou geographical population relative to all others pooled), we found a low level of the genetic variation among geographical populations and that between groups. However, differences among populations relative to the total sample explained most of the genetic variance (92.84%), which was significant.

  15. Genetic variation among world populations: inferences from 100 Alu insertion polymorphisms.

    PubMed

    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

    2003-07-01

    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). F(ST), 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 approximately 50 Alu polymorphisms are sufficient to obtain accurate and reliable genetic distance estimates. These analyses also demonstrate that markers with higher F(ST) values have greater resolving power and produce more consistent genetic distance estimates.

  16. [Clinical variations of chronic generalized periodontitis, genetic polymorphism and systemic production of inflammatory cytokines].

    PubMed

    Grigorovich, E Sh; Pomorgailo, E G; Khomutova, E Yu; Stepanov, S S

    2015-01-01

    Carriage of polymorphic alleles of genes of cytokines-interleukines IL-1β, IL-1RN, TNFα, IL-4 can be a specific feature of chronic periodontitis patients. Genetic tests can be used to predict the course of the disease at its early manifestations. Objective: To establish the relationship of clinical manifestations of periodontal disease, inflammatory cytokines gene polymorphism and systemic levels of cytokine production. Periodontal tissue assessment and cone-beam computed tomography (CBCT) were performed in 150 periodontitis patients. A molecular--genetic testing for the presence of polymorphic alleles of genes IL-1β -511 C>T and +3953 C>T, IL-1RN (VNTR intron 2), IL-4 (VNTR intron 3), TNFα-308 G>A; content determined IL-1β, TNFα, IL-4 in peripheral blood was carried out in 150 patients with periodontitis and 150 healthy donors. Based on the analysis of the speed and nature of the supporting bone resorption and clinical manifestations patients are divided in "aggressive", "moderately progressive" and "slowly progressive" periodontits course groups. Disease severity was associated with distribution of genotypes and alleles of polymorphic genes cytokine IL-1RN (VNTR intron 2), TNFα-308 G>A and IL-4 (VNTR intron 3); haplotype IL-1β-511 TIL-1β +3953 T/IL-1RN 2R. There was no statistically significant difference in systemic level of IL-1β, TNFα and IL-4 between periodontitis groups but the donor level of cytokines was 2-4 times less.

  17. 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

  18. Genetic polymorphisms of interleukin-6 modulate fibrosis progression in mild chronic hepatitis C.

    PubMed

    Falleti, Edmondo; Fabris, Carlo; Vandelli, Carmen; Colletta, Cosimo; Cussigh, Annarosa; Smirne, Carlo; Fontanini, Elisabetta; Cmet, Sara; Minisini, Rosalba; Bitetto, Davide; Toniutto, Pierluigi; Pirisi, Mario

    2010-10-01

    Genetic polymorphisms of interleukin-6 (IL-6) (-1363G>T, -597G>A, -572G>C, -174G>C, +2954G>C) may affect the outcomes of several diseases. This study was aimed to verify the role of these polymorphisms on the disease progression of patients with hepatitis C virus (HCV) infection and persistently normal transaminases (PNALT). A total of 121 PNALT patients did not receive any antiviral treatment but underwent periodic clinical monitoring, including repeat biopsies, for a median of 120 months. IL6-1363G>T, -597G>A, -572G>C, -174G>C, +2954G>C polymorphisms were related to histologic fibrosis progression. Among patients whose grading and staging scores increased at the end of the follow-up ≥2 Ishak points (N = 60 and N = 26, respectively), IL-6 -174G>C genotype frequencies were GG 37/66, GC 21/45, CC 2/10 (p = 0.041) and GG 18/66, GC 8/45, CC 0/10 (p = 0.040), respectively. The following frequencies were observed for the 572G>C polymorphism: GG 50/105, GC 10/16, CC 0/0, and GG 19/105, GC 7/16, CC 0/0, respectively. Grading progression was independently associated with carriage of the G allele in -174G>C polymorphism (oddd ratio = 5.07%, 95% confidence interval = 0.959-26.8, p = 0.023). Staging progression was independently associated with carriage of the C allele in -572G>C polymorphism (odd ratio = 4.60%, 95% confidence interval 1.42-14.8, p = 0.012). IL-6 polymorphisms influence histologic progression of HCV in patients with PNALT.

  19. Genetic Polymorphisms of the Bovine NOV Gene Are Significantly Associated with Carcass Traits in Korean Cattle

    PubMed Central

    Kim, B. S.; Kim, S. C.; Park, C. M.; Lee, S. H.; Cho, S. H.; Kim, N. K.; Jang, G. W.; Yoon, D. H.; Yang, B. S.; Hong, S. K.; Seong, H. H.; Choi, B. H.

    2013-01-01

    The objective of this study was to investigate single nucleotide polymorphisms (SNPs) in the bovine nephroblastoma overexpressed (NOV) gene and to evaluate whether these polymorphisms affect carcass traits in the Korean cattle population. We resequenced to detect SNPs from 24 unrelated individuals and identified 19 SNPs within the full 8.4-kb gene, including the 1.5-kb promoter region. Of these 19 SNPs, four were selected for genotyping based on linkage disequilibrium (LD). We genotyped 429 steers to assess the associations of these four SNPs with carcass traits. Statistical analysis revealed that g.7801T>C and g.8379A>C polymorphisms in the NOV gene were associated with carcass weight (p = 0.012 and 0.008, respectively), and the g.2005A>G polymorphism was associated with the back fat thickness (BF) trait (p = 0.0001). One haplotype of the four SNPs (GGTA) was significantly associated with BF (p = 0.0005). Our findings suggest that polymorphisms in the NOV gene may be among the important genetic factors affecting carcass yield in beef cattle. PMID:25049850

  20. [Genetic polymorphisms of five STR loci on chromosome 21 in Chinese Han population].

    PubMed

    Chen, Zhen-Bin; Zhu, Jin-Ling; Yan, Mei; Liang, Yan; Zhou, Yan; Tan, Shu-Zhen; Xiao, Bai; Liu, Jing-Zhong

    2004-07-01

    To elucidate the genetic polymorphisms of five STR loci on chromosome 21 in Chinese Han population and construct a preliminary database, EDTA-blood specimens were collected from unrelated individuals in Beijing. The DNAs were extracted with Chelex method and were amplified by PCR. The PCR products were analyzed by the PAG electrophoresis or by the approach of the automated fluorescent detection. The five STR loci consist of simple repeat motif and its distributions of genotypes are agreement with Hardy-Weinberg equation. Its polymorphism information content is all over 0.50. The obtained data can not only be used as evidences for genetic diagnosis of Down Syndrome, but also for calculating the probabilities in the paternity test and individual identification. PMID:15640034

  1. Genetic studies on the Senegal population. I. Mitochondrial DNA polymorphisms.

    PubMed Central

    Scozzari, R; Torroni, A; Semino, O; Sirugo, G; Brega, A; Santachiara-Benerecetti, A S

    1988-01-01

    The mtDNA of 186 Senegalese, mainly Wolof and Peuls, were analyzed by means of six restriction enzymes: HpaI, BamHI, HaeII, MspI, AvaII, and HincII. Two of the HpaI, one of the HaeII, two of the MspI, and one of the AvaII morphs had not been described before. The only enzymes which enabled Wolof and Peuls to be differentiated were HincII and, to a lesser extent, HaeII. Important differences emerge in the comparison of Senegalese with Bantu of South Africa and with Bushmen, the only other Africans who, as far as we know, were studied for the same genetic markers. Though Senegalese mtDNAs display typical African features (presence and frequency of HpaI morph 3 and high incidence of AvaII morph 3), the distribution of MspI and AvaII patterns markedly differentiates Senegalese from the others. The phylogeny of mtDNA types in Africa well portrays how the three African groups are clearly distinguishable genetic entities. Bushmen lie at one end of the range of variability, Senegalese being at the other end but still fairly closely related to Bantu. The information provided by individual restriction enzymes to the distinction among the three major ethnic groups is reviewed and discussed. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:2902791

  2. 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

    2015-12-28

    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.

  3. 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

  4. 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.

  5. Recombination within a Subclass of Restriction Fragment Length Polymorphisms May Help Link Classical and Molecular Genetics

    PubMed Central

    Meagher, R. B.; McLean, M. D.; Arnold, J.

    1988-01-01

    Restriction fragment length polymorphisms (RFLPs) are being used to construct complete linkage maps for many eukaryotic genomes. These RFLP maps can be used to predict the inheritance of important phenotypic loci and will assist in the molecular cloning of linked gene(s) which affect phenotypes of scientific, medical and agronomic importance. However, genetic linkage implies very little about the actual physical distances between loci. An assay is described which uses genetic recombinants to measure physical distance from a DNA probe to linked phenotypic loci. We have defined the subset of all RFLPs which have polymorphic restriction sites at both ends as class II RFLPs. The frequency of class II RFLPs is computed as a function of sequence divergence and total RFLP frequency for highly divergent genomes. Useful frequencies exist between organisms which differ by more than 7% in DNA sequence. Recombination within class II RFLPs will produce fragments of novel sizes which can be assayed by pulsed field electrophoresis to estimate physical distance in kilobase pairs between linked RFLP and phenotypic loci. This proposed assay should have particular applications to crop plants where highly divergent and polymorphic species are often genetically compatible and thus, where class II RFLPs will be most frequent. PMID:2906304

  6. 4P: fast computing of population genetics statistics from large DNA polymorphism panels.

    PubMed

    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.

  7. The association between serum ApoE genetic polymorphism and serum lipid level in hemodialysis patients.

    PubMed

    Zhang, Yong; Zhang, Linlin; Cao, Bo

    2015-02-01

    Growing evidence indicates that apolipoprotein E (ApoE) is one of the most important candidate genes for influencing the development of hemodialysis (HD). This study aims to detect the potential association between serum ApoE genetic polymorphism and serum lipid level in HD. A total of 485 subjects were enrolled in this case-control study. The created restriction site polymerase chain reaction and DNA sequencing methods were used to investigate ApoE c.109G>A genetic polymorphism. Our data suggested that there were significant differences in the distribution of allelic and genotypic frequencies between HD patients and healthy controls. The levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, ApoA-I, ApoB, ApoE, and lipoprotein (a) for genotype AA were different from genotype GG in HD patients and healthy controls. Our findings support that the ApoE c.109G>A genetic polymorphism might influence the development of HD and could be a risk factor for assessing HD.

  8. 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

  9. 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.

  10. Genetic polymorphism in Taenia solium metacestodes from different Brazilian geographic areas.

    PubMed

    Barcelos, Ivanildes Solange da Costa; Souza, Maria Aparecida; Pena, Janethe Deolinda de Oliveira; Machado, Gleyce Alves; Moura, Lísia Gomes Martins de; Costa-Cruz, Julia Maria

    2012-02-01

    The aim of the present study is to investigate genetic polymorphisms in Taenia solium metacestodes from different Brazilian geographical areas and to relate them to antibody recognition in serum samples of neurocysticercosis (NC) patients. Metacestodes were obtained from the Distrito Federal (DF), Bahia, Minas Gerais (MG) and São Paulo (SP) regions of Brazil. Samples of human sera from 49 individuals with NC, 68 individuals with other helminthiasis and 40 healthy volunteers were analysed (157 individuals in total). Antigens were prepared and used in enzyme-linked immunosorbent assay and western blotting assays to detect specific immunoglobulin G antibodies. Genetic distances between metacestode populations were analysed using random amplified polymorphic DNA (RAPD) analysis. Our results show that there was a higher frequency of reactivity in the DF region in the sera from NC patients (p < 0.05), while discrimination between active and inactive NC was seen only in extracts from the MG and SP regions (p < 0.05). Using RAPD, the sample from the DF region presented a greater increase compared to the other regions. A relationship between genetic polymorphisms among T. solium metacestodes from different areas in Brazil and the differences in antibody detection in patients with NC were established.

  11. 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

  12. A natural genetic polymorphism affects retroactive interference in Drosophila melanogaster

    PubMed Central

    Reaume, Christopher J.; Sokolowski, Marla B.; Mery, Frederic

    2011-01-01

    As environments change, animals update their internal representations of the external world. New information about the environment is learned and retained whereas outdated information is disregarded or forgotten. Retroactive interference (RI) occurs when the retrieval of previously learned information is less available owing to the acquisition of recently acquired information. Even though RI is thought to be a major cause of forgetting, its functional significance is still under debate. We find that natural allelic variants of the Drosophila melanogaster foraging gene known to affect rover and sitter behaviour differ in RI. More specifically, rovers who were previously shown to experience greater environmental heterogeneity while foraging display RI whereas sitters do not. Rover responses are biased towards more recent learning events. These results provide an ecological context to investigate the function of forgetting via RI and a suitable genetic model organism to address the evolutionary relevance of cognitive tasks. PMID:20667877

  13. Identification of trends in scientific publications related to genetic polymorphisms in gestational diabetes mellitus.

    PubMed

    Gomes, J S; Minasi, L B; da Cruz, A D; Rodrigues, F M

    2016-01-01

    Gestational diabetes is a genetic multifactorial systemic disease that has been extensively studied. Consequently, there is a large volume of scientific literature pertaining to genes associated with gestational diabetes. The aim of this study was to characterize the main trends in scientific publications focusing on the associations between genetic polymorphisms and gestational diabetes mellitus (GDM). The related articles were extracted from Scopus using the key words "genetic polymorphism" and "gestational diabetes mellitus"; the collected data focused on various fields (medical, biochemical, etc.) and included papers published within December 2013. One hundred and eighty-three relevant articles published between 1987 and 2013 were identified; we observed a significantly increasing trend in the number of publications pertaining to GDM. A majority of the articles focused on the medical (59.9%), biochemical, and genetics and molecular biological (29.6%) aspects of the disease. The genes coding for transcription factor 7-like 2 and glucokinase (TCF7L2, 29% and GCK, 28%) were predominantly studied and reported. This study helped quantify the growth in research pertaining to GDM; researchers from the USA have published a majority of the publications related to GDM. Several candidate genes have been linked to diabetes; however, the specific gene locus responsible for GDM has not yet been identified. The results of this study could help determine the orientation of future research on genetic factors associated with GDM. PMID:27173344

  14. Evolution of genetic polymorphisms of Plasmodium falciparum merozoite surface protein (PfMSP) in Thailand.

    PubMed

    Kuesap, Jiraporn; Chaijaroenkul, Wanna; Ketprathum, Kanchanok; Tattiyapong, Puntanat; Na-Bangchang, Kesara

    2014-02-01

    Plasmodium falciparum malaria is a major public health problem in Thailand due to the emergence of multidrug resistance. The understanding of genetic diversity of malaria parasites is essential for developing effective drugs and vaccines. The genetic diversity of the merozoite surface protein-1 (PfMSP-1) and merozoite surface protein-2 (PfMSP-2) genes was investigated in a total of 145 P. falciparum isolates collected from Mae Sot District, Tak Province, Thailand during 3 different periods (1997-1999, 2005-2007, and 2009-2010). Analysis of genetic polymorphisms was performed to track the evolution of genetic change of P. falciparum using PCR. Both individual genes and their combination patterns showed marked genetic diversity during the 3 study periods. The results strongly support that P. falciparum isolates in Thailand are markedly diverse and patterns changed with time. These 2 polymorphic genes could be used as molecular markers to detect multiple clone infections and differentiate recrudescence from reinfection in P. falciparum isolates in Thailand.

  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.

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

    PubMed

    Verdejo-García, Antonio; Fagundo, Ana Beatriz; Cuenca, Aida; Rodriguez, Joan; Cuyás, Elisabet; Langohr, Klaus; de Sola Llopis, Susana; Civit, Ester; Farré, Magí; Peña-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 Δ9-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.

  17. Association between ABCB1 genetic polymorphism and the effect on epilepsy following phenytoin treatment

    PubMed Central

    Sun, Fei; Cao, Bo-Qiang; Wang, Bo; Wu, Shi-Qiang; Jiang, De-Hua

    2016-01-01

    The aim of the study was to analyze the effect of ABCB1 genetic polymorphisms on the efficacy of phenytoin (PHT) treatment in epilepsy patients. In total, 200 epilepsy patients who were administered PHT were divided into the responsive and pharmaco-resistance groups depending on the clinical data of PHT treatment in epilepsy patients. The serum concentration of PHT was detected by high-performance liquid chromatography (HPLC). ABCB1 polymorphisms were analyzed by the polymerase chain reaction restriction-fragment length polymorphism method. The C1236T, C3435T and G2677T/A haplotypes were reconstructed for the ABCB1 gene using SHEsis programs. One-way analysis of variance was used for data analysis. In ABCB1 C1236T, the rate of the CC genotype in pharmaco-resistance (17.5%) was higher than that of the responsive group (2.1%), while the rate of the TT genotype in pharmaco-resistance (41.6%) was lower than that of the responsive group (55.4%) (P<0.05). In ABCB1 G2677T/A, the rate of the GG genotype in pharmaco-resistance (29.6%) was higher than that of the responsive group (9.7%), while the rate of the TT genotype in pharmaco-resistance (4.6%) was lower than that of the responsive group (30.4%) (P<0.05). The rate of the TTC haploid in pharmaco-resistance (24.1%) was higher than that of the responsive group (8.8%) (P<0.05). The PHT serum concentration had no statistical significance in the patients with different genotypes. In conclusion, there was no association between ABCB1 genetic polymorphism and PHT serum concentration, although the polymorphisms affected the efficacy of PHT treatment in patients with epilepsy. PMID:27602091

  18. Association between ABCB1 genetic polymorphism and the effect on epilepsy following phenytoin treatment

    PubMed Central

    Sun, Fei; Cao, Bo-Qiang; Wang, Bo; Wu, Shi-Qiang; Jiang, De-Hua

    2016-01-01

    The aim of the study was to analyze the effect of ABCB1 genetic polymorphisms on the efficacy of phenytoin (PHT) treatment in epilepsy patients. In total, 200 epilepsy patients who were administered PHT were divided into the responsive and pharmaco-resistance groups depending on the clinical data of PHT treatment in epilepsy patients. The serum concentration of PHT was detected by high-performance liquid chromatography (HPLC). ABCB1 polymorphisms were analyzed by the polymerase chain reaction restriction-fragment length polymorphism method. The C1236T, C3435T and G2677T/A haplotypes were reconstructed for the ABCB1 gene using SHEsis programs. One-way analysis of variance was used for data analysis. In ABCB1 C1236T, the rate of the CC genotype in pharmaco-resistance (17.5%) was higher than that of the responsive group (2.1%), while the rate of the TT genotype in pharmaco-resistance (41.6%) was lower than that of the responsive group (55.4%) (P<0.05). In ABCB1 G2677T/A, the rate of the GG genotype in pharmaco-resistance (29.6%) was higher than that of the responsive group (9.7%), while the rate of the TT genotype in pharmaco-resistance (4.6%) was lower than that of the responsive group (30.4%) (P<0.05). The rate of the TTC haploid in pharmaco-resistance (24.1%) was higher than that of the responsive group (8.8%) (P<0.05). The PHT serum concentration had no statistical significance in the patients with different genotypes. In conclusion, there was no association between ABCB1 genetic polymorphism and PHT serum concentration, although the polymorphisms affected the efficacy of PHT treatment in patients with epilepsy.

  19. 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

  20. Genetic variability of the stable fly assessed on a global scale using amplified fragment length polymorphism.

    PubMed

    Kneeland, Kathleen M; Skoda, Steven R; Foster, John E

    2016-10-01

    The stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae), is a blood-feeding, economically important pest of animals and humans worldwide. Improved management strategies are essential and their development would benefit from studies on genetic diversity of stable flies. Especially if done on a global scale, such research could generate information necessary for the development and application of more efficient control methods. Herein we report on a genetic study of stable flies using amplified fragment length polymorphism, with samples of 10-40 individuals acquired from a total of 25 locations in the Nearctic, Neotropic, Palearctic, Afrotropic and Australasian biogeographical regions. We hypothesized that genetic differentiation would exist across geographical barriers. Although FST (0.33) was moderately high, the GST (0.05; representing genetic diversity between individuals) was very low; Nm values (representing gene flow) were high (9.36). The mismatch distribution and tests of neutrality suggested population expansion, with no genetic differentiation between locations. The analysis of molecular variance (AMOVA) results showed the majority of genetic diversity was within groups. The mantel test showed no correlation between geographic and genetic distance; this strongly supports the AMOVA results. These results suggest that stable flies did not show genetic differentiation but are panmictic, with no evidence of isolation by distance or across geographical barriers. PMID:25788399

  1. 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

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

    PubMed

    Barnea, Teodora Virginia; Sava, Anca; Gentimir, Carmen; Goriuc, Ancuţa; Boişteanu, Otilia; Chelaru, Liliana; Iancu, Roxana Irina; Avram, Cătălina Anda; Acatrinei, Dragoş Daniel; Bogza, Elena Geanina; Răducanu, 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 μg/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

  3. Genetic polymorphisms in peroxisome proliferator-activated receptor delta associated with obesity.

    PubMed

    Shin, Hyoung Doo; Park, Byung Lae; Kim, Lyoung Hyo; Jung, Hye Seung; Cho, Young Min; Moon, Min Kyong; Park, Young Joo; Lee, Hong Kyu; Park, Kyong Soo

    2004-03-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors regulating the expression of genes involved in lipid and glucose metabolism. Three different PPARs, PPAR-alpha, -gamma, and -delta, have been characterized, and they are distinguished from each other by tissue distribution and cell activation. All PPARs are, to different extents, activated by fatty acids and derivatives. Recently, it has been shown that PPAR-delta serves as a widespread regulator of fat burning, suggesting that it might be a potential target in the treatment of obesity and type 2 diabetes. In an effort to identify polymorphic markers in potential candidate genes for type 2 diabetes, we have sequenced PPAR-delta, including -1,500 bp of the 5' flanking region. Nine polymorphisms were identified in PPAR-delta: four in the intron, one in the 5' untranslated region (UTR), and four in the 3' UTR. Among identified polymorphisms, five common sites, including c.-13454G>T, c.-87T>C, c.2022+12G>A, c.2629T>C, and c.2806C>G, were genotyped in subjects with type 2 diabetes and normal control subjects (n = 702). The genetic associations with the risk of type 2 diabetes and metabolic phenotype were analyzed. No significant associations with the risk of type 2 diabetes were detected. However, several positive associations of PPAR-delta polymorphisms with fasting plasma glucose and BMI were detected in nondiabetic control subjects. The genetic information about PPAR-delta from this study would be useful for further genetic study of obesity, diabetes, and other metabolic diseases. PMID:14988273

  4. A web-based genetic polymorphism learning approach for high school students and science teachers*.

    PubMed

    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 freely available bioinformatics tools on the Internet to detect single nucleotide polymorphisms in genomic DNA and gene-based sequences to evaluate variation or polymorphism. Similar tools were also used to show the functional effect, if any, of the single nucleotide polymorphisms. A total of 25 science teachers and 60 students from high schools in Alabama and Virginia participated in the program that ranged from 2 to 4 weeks. Seventy percent of the teachers have now developed a web-based module to teach at least two lessons involving DNA variation and how it influences other disciplines, including evolution. Among former high school students, five are in Ph.D. programs in genetics or related subjects, and 80% are in medical school or in college in a biology or pre-med major. The exercise is simple to implement, and the cost is relatively low, requiring only a computer with an Internet connection. It also provides a foundation for introducing students to the theory of evolution, a concept that remains controversial in high school science curricula. Similar programs, if properly implemented, may result in fostering more interest in the biological sciences among prospective college students and ensure a good foundation in the pipeline for career biologists and scientists.

  5. Haptoglobin polymorphism and schizophrenia: genetic variation on chromosome 16.

    PubMed

    Maes, M; Delanghe, J; Bocchio Chiavetto, L; Bignotti, S; Tura, G B; Pioli, R; Zanardini, R; Altamura, C A

    2001-10-10

    Recently, it was shown that schizophrenia is accompanied by an activation of the inflammatory response system with signs of an acute phase response, such as increased plasma haptoglobin (Hp) concentrations. Hp is characterized by a molecular variation with three known phenotypes, i.e. Hp 1-1, Hp 2-1 and Hp 2-2. The aim of the present study was to examine Hp phenotypic and genotypic frequencies in schizophrenic patients. Hp phenotyping was carried out in 98 Northwestern Italian schizophrenic patients and the phenotypic and genotypic distributions were compared with the distributions established in the Northwestern Italian population. Plasma Hp concentrations were determined by means of a laser nephelometric method. The allele frequency of the Hp phenotypes in schizophrenia, i.e. Hp 1-1 (9.2%), Hp 2-1 (38.8%) and Hp 2-2 (52.0%), was significantly different from that in the Northwestern Italian population, i.e. Hp 1-1 (17.0%), Hp 2-1 (51.3%) and Hp 2-2 (38.5%). The frequency of the Hp-2 gene was significantly higher in schizophrenic patients (71.7%) as compared with the observed frequency in the Northwestern Italian population (62.5%). The alterations in Hp phenotypic and genotypic distribution were more pronounced in the schizo-affective, disorganized, undifferentiated and residual schizophrenic patients than in paranoid schizophrenic patients. More than a third (35.7%) of the schizophrenic patients showed plasma Hp concentrations which were higher than the upper limits of normality. Schizophrenia is accompanied by an altered distribution of the Hp phenotypes and genotypes, suggesting that genetic variation on chromosome 16 may be associated with schizophrenia.

  6. Random amplified polymorphic markers as indicator for genetic conservation program in Iranian pheasant (Phasianus colchicus).

    PubMed

    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.

  7. Mycoplasma hominis in Cuban Trichomonas vaginalis isolates: association with parasite genetic polymorphism.

    PubMed

    Fraga, Jorge; Rodríguez, Nadia; Fernández, Carmen; Mondeja, Brian; Sariego, Idalia; Fernández-Calienes, Aymé; Rojas, Lazara

    2012-07-01

    Trichomonas vaginalis can be naturally infected with intracellular Mycoplasma hominis. This bacterial infection may have implications for trichomonal virulence and disease pathogenesis. The objective of the study was to report the presence of M. hominis in Cuban T. vaginalis isolates and to describe the association between the phenotype M. hominis infected with RAPD genetic polymorphism of T. vaginalis. The Random Amplified Polymorphic DNA (RAPD) technique was used to determine genetic differences among 40 isolates of T. vaginalis using a panel of 30 random primers and these genetic data were correlated with the infection of isolates with M. hominis. The trees drawn based on RAPD data showed no relations with metronidazole susceptibility and significantly association with the presence of M. hominis (P=0.043), which demonstrates the existence of concordance between the genetic relatedness and the presence of M. hominis in T. vaginalis isolates. This result could point to a predisposition of T. vaginalis for the bacterial enters and/or survival. PMID:22584035

  8. Genetic polymorphisms in the carbonic anhydrase VI gene and dental caries susceptibility.

    PubMed

    Li, Z-Q; Hu, X-P; Zhou, J-Y; Xie, X-D; Zhang, J-M

    2015-06-01

    We investigated the role of 7 single nucleotide polymorphisms in the carbonic anhydrase (CA) VI gene (rs2274328, rs17032907, rs11576766, rs2274333, rs10864376, rs3765964, and rs6680186) and the possible association between these polymorphisms and dental caries susceptibility in a Northwestern Chinese population. We collected samples from 164 high caries experience and 191 very low caries experience and conducted a case-control study according to the number of decayed, missing, and filled teeth index and genotyped the 7 polymorphisms using a 384-well plate format with the Sequenom MassARRAY platform. Individuals carrying the rs17032907 TT genotype were more likely to have an increased risk of dental caries compared with carriers of the C/C genotype in the co-dominant model, with an odds ratio (95% confidence interval) of 2.144 (1.096-4.195). We also found that the haplotype (ACA) (rs2274328, rs17032907 and rs11576766) was associated with a low number of decayed, missing, and filled teeth index with an odds ratio (95% confidence interval) of 0.635 (0.440-0.918). However, we found no association between dental caries susceptibility and the rs2274328, rs11576766, rs2274333, rs10864376, rs3765964, and rs6680186 polymorphisms and other haplotypes. The rs17032907 genetic variant and the haplotype (ACA) of CA VI may be associated with dental caries susceptibility.

  9. Correlation of genetic polymorphism of vascular endothelial growth factor gene with susceptibility to lung cancer.

    PubMed

    Liu, C; Zhou, X; Gao, F; Qi, Z; Zhang, Z; Guo, Y

    2015-06-01

    The aim of the study is to study the correlation of genetic polymorphism of vascular endothelial growth factor (VEGF) gene with susceptibility to primary lung cancer. A total of 414 patients with primary lung cancer and 338 healthy volunteers were enrolled in this case-control study from September 2008 to October 2011. Gene identification with PCR-RFLP (polymerase chain reaction-based restriction fragment length polymorphism) was used to detect in white blood cells from the subjects the single-nucleotide polymorphisms (SNP) of VEGF gene, including +405G/C, -460 T/C, -1154G/A, -2578C/A sites. Association of genotypes or haplotypes with susceptibility of lung cancer was analyzed with unconditional logistic regression adjusted by gender and age. Smoking was significantly associated with increased risk of lung cancer. Gene phenotypic analysis demonstrated that C allele of +405G/C in VEGF gene was significantly associated increased risk of lung cancer in males (P=0.0094, odds ratio=1.634.3), as that with carrying GCTC haplotype (odds ratio=1.349), whereas carrying GACG had decreased risk for lung cancer (odds ratio=0.044). No relationship existed between 460 T/C, -1154G/A, -2578C/A alleles of VEGF gene and risk of lung cancer. VEGF gene polymorphism may have a role in the development of lung cancer.

  10. 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, Érika 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

  11. Association of the Genetic Polymorphisms RRM1 -756T>C and -269C>A With Cervical Neoplasia.

    PubMed

    Chang, Ching-Wen; Yang, Shun-Fa; Wang, Po-Hui; Chang, Hsiu-Ju; Liu, Wen-Chi; Tsai, Hsiu-Ting

    2016-10-01

    Cervical neoplasia is one of the most prevalent malignant neoplasms worldwide. Ribonucleotide reductase 1 (RRM1) is thought to play an essential role in modulating the development and progression of cervical neoplasia. Two novel genetic polymorphisms, RRM1 -756T>C and -269 C>A, are significantly correlated with RRM1 expression. Some epidemiological studies have demonstrated that genetic variants play a crucial role in susceptibility to cervical cancer. The present study aimed to identify the genetic polymorphisms RRM1 -756T>C and -269 C>A in patients with cervical neoplasia and healthy controls. In total, 493 subjects, comprising 324 healthy controls and 169 patients with cervical neoplasia, were enrolled for this study. The allelic discrimination of the RRM1 -756T>C (rs11030918) and -269C>A (rs12806698) polymorphisms was assessed using the ABI StepOne™ real-time polymerase chain reaction system and analyzed using Software Design Specification (SDS), Version 3.0, software with TaqMan assays. The risk of cervical cancer was examined, revealing adjusted odds ratios and 95% confidence intervals of 1.25 [0.51, 3.08] and 1.09 [0.43, 2.78] for individuals with CC alleles of RRM1 -756T>C and for individuals with AA alleles of RRM1 -269C>A genetic polymorphisms, respectively, compared to individuals with wild-type RRM1 genetic polymorphisms. No significant genetic interaction effect was observed in susceptibility to cervical neoplasia, and no association was found between genetic polymorphisms and clinical statuses of invasive cervical cancer. The genetic polymorphisms RRM1 -756T>C and -269C>A may not be a factor for susceptibility to cervical neoplasia.

  12. [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…

  13. Color polymorphism and genetic structure in the sea star Pisaster ochraceus.

    PubMed

    Harley, C D G; Pankey, M S; Wares, J P; Grosberg, R K; Wonham, M J

    2006-12-01

    The sea star Pisaster ochraceus is one of the more striking species on the rocky shores of the Northeast Pacific, in part due to the dramatic color polymorphism of the adults. Along the open Pacific coast, Pisaster populations are 6%-28% orange, with a small percentage of brilliant purple stars and a large percentage of reddish-brown to dull purple ones. However, populations in the San Juan Island Archipelago (Washington, USA) and the southern Strait of Georgia (British Columbia, Canada) are almost entirely brilliant purple. The factors that maintain the color polymorphism, and those that contribute to among-site variation in color frequencies, remain unknown. We examined the relationships between color frequencies and several ecological and morphological variables, and conducted a large-scale phylogeographic survey of Pisaster populations. We found very low population genetic structure, suggesting that gene flow is high and geographic variation in color frequencies is not a vestige of Pleistocene glacial refugia. Color frequencies are also unrelated to adult size and to the frequency of injury within a population. However, there are suggestive relationships between color frequency and diet, and with areas of potentially low salinity. We propose that, although the color polymorphism may have an underlying genetic component, the regional-scale variation in color frequency is ecologically controlled.

  14. 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

  15. [Relationship between Arsenic (+3 Oxidation State) Methyltransferase Genetic Polymorphisms and Methylation Capacity of Inorganic Arsenic].

    PubMed

    Agusa, Tetsuro; Kunito, Takashi; Minh Tue, Nguyen; Thi Mai Lan, Vi; Binh Minh, Tu; Thi Kim Trang, Pham; Fujihara, Junko; Takeshita, Haruo; Takahashi, Shin; Hung Viet, Pham; Tanabe, Shinsuke; Iwata, Hisato

    2015-01-01

    Arsenic metabolism affects the susceptibility of humans to arsenic toxicity; therefore, clarification of the factors associated with individual variations in arsenic metabolism is an important task. Genetic polymorphisms such as single nucleotide polymorphisms (SNPs) in arsenic (+3 oxidation state) methyltransferase (AS3MT), which can methylate arsenic compounds using S-adenosyl-l-methionine (AdoMet), have been reported to modify arsenic methylation. In this review, we summarize studies conducted by us in Vietnam and by others on the association of AS3MT genetic polymorphisms with arsenic metabolism as well as human health effects. Most of the SNPs in AS3MT showed inconsistent results in terms of genotype-dependent differences in arsenic metabolism among the studies. However, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the study population: AS3MT 12390 (rs3740393) affected the second step of methylation of arsenic, whereas 14458 (rs11191439) affected the first methylation step.

  16. Hodgkin Lymphoma Risk: Role of Genetic Polymorphisms and Gene-Gene Interactions in DNA repair pathways

    PubMed Central

    Monroy, Claudia M.; Cortes, Andrea C.; Lopez, Mirtha; Rourke, Elizabeth; Etzel, Carol J.; Younes, Anas; Strom, Sara S.; El-Zein, Randa

    2011-01-01

    DNA repair variants may play a potentially important role in an individual’s susceptibility to developing cancer. Numerous studies have reported the association between genetic single nucleotide polymorphisms (SNPs) in DNA repair genes and different types of hematologic cancers. However, to date, the effects of such SNPs on modulating Hodgkin Lymphoma (HL) risk have not yet been investigated. We hypothesized that gene-gene interaction between candidate genes in Direct Reversal, Nucleotide excision repair (NER), Base excision repair (BER) and Double strand break (DSB) pathways may contribute to susceptibility to HL. To test this hypothesis, we conducted a study on 200 HL cases and 220 controls to assess associations between HL risk and 21 functional SNPs in DNA repair genes. We evaluated potential gene-gene interactions and the association of multiple polymorphisms in a chromosome region using a multi-analytic strategy combining logistic regression, multi-factor dimensionality reduction and classification and regression tree approaches. We observed that, in combination, allelic variants in the XPC Ala499Val, NBN Glu185Gln, XRCC3 Thr241Me, XRCC1 Arg194Trp and XRCC1 399Gln polymorphisms modify the risk for developing HL. Moreover, the cumulative genetic risk score revealed a significant trend where the risk for developing HL increases as the number of adverse alleles in BER and DSB genes increase. These findings suggest that DNA repair variants in BER and DSB pathways may play an important role in the development of HL. PMID:21374732

  17. Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population

    PubMed Central

    Al-Mahruqi, Samira H.; Zadjali, Fahad; Beja-Pereira, Albano; Koh, Crystal Y.; Balkhair, Abdullah; Al-Jabri, Ali A.

    2014-01-01

    Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Ocean. In this study, we examined the CCR2-CCR5 haplotypes in Omanis and compared the patterns of genetic diversity with those of other populations. Blood samples were collected from 115 Omani adults and genomic DNA was screened to identify the polymorphic sites in the CCR5 gene and the CCR2V64I mutation. Four minor alleles were common: CCR5-2554T and CCR5-2086G showed frequencies of 49% and 46%, respectively, whereas CCR5-2459A and CCR5-2135C both had a frequency of 36%. These alleles showed moderate levels of heterozygosity, indicating that they were under balancing selection. However, the well-known allele CCR5Δ32 was relatively rare. Eleven haplotypes were identified, four of which were common: HHC (46%), HHE (20%), HHA (14%) and HHF*2 (12%). PMID:24688285

  18. [Relationship between Arsenic (+3 Oxidation State) Methyltransferase Genetic Polymorphisms and Methylation Capacity of Inorganic Arsenic].

    PubMed

    Agusa, Tetsuro; Kunito, Takashi; Minh Tue, Nguyen; Thi Mai Lan, Vi; Binh Minh, Tu; Thi Kim Trang, Pham; Fujihara, Junko; Takeshita, Haruo; Takahashi, Shin; Hung Viet, Pham; Tanabe, Shinsuke; Iwata, Hisato

    2015-01-01

    Arsenic metabolism affects the susceptibility of humans to arsenic toxicity; therefore, clarification of the factors associated with individual variations in arsenic metabolism is an important task. Genetic polymorphisms such as single nucleotide polymorphisms (SNPs) in arsenic (+3 oxidation state) methyltransferase (AS3MT), which can methylate arsenic compounds using S-adenosyl-l-methionine (AdoMet), have been reported to modify arsenic methylation. In this review, we summarize studies conducted by us in Vietnam and by others on the association of AS3MT genetic polymorphisms with arsenic metabolism as well as human health effects. Most of the SNPs in AS3MT showed inconsistent results in terms of genotype-dependent differences in arsenic metabolism among the studies. However, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the study population: AS3MT 12390 (rs3740393) affected the second step of methylation of arsenic, whereas 14458 (rs11191439) affected the first methylation step. PMID:26411936

  19. [The role of genetic polymorphisms of interleukins in chronic lymphocytic leukemia in patients of different ages].

    PubMed

    Sirotina, S S; Tikunova, T S; Proshchaev, K I; Efremova, O A; Batlutskaia, I V; Iakunchenko, T I; Sobianin, F I; Churnosov, M I; Alekseev, S M

    2014-01-01

    Chronic lymphocytic leukemia (CLL) is a multifactorial disease, in which development the important role played the cytokine genes, in particular interleukins. This type of leukemia is more common in the elderly. The purpose of the study was to evaluate the association of genetic polymorphisms of interleukin with the development of chronic lymphocytic leukemia among residents of the Central Chernozem region of Russia. Genotyping of the -889C/T IL-1A, -590C/T IL-4 and VNTR IL-1 Ra was conducted in 206 patients with CLL and 307 individuals of the control group. The study found that the genetic risk factor for the development of CLL is allele -590T IL-4 (OR=-1,45). The development of thrombocytopenia in patients with CLL is associated with genetic variants -889T IL-1A (OR=1,95), -889TT IL-1A (OR=6,2) and IL-1Ra*1 (OR=-2,32).

  20. Direct fluorescence analysis of genetic polymorphisms by hybridization with oligonucleotide arrays on glass supports.

    PubMed Central

    Guo, Z; Guilfoyle, R A; Thiel, A J; Wang, R; Smith, L M

    1994-01-01

    A simple and rapid method for the analysis of genetic polymorphisms has been developed using allele-specific oligonucleotide arrays bound to glass supports. Allele-specific oligonucleotides are covalently immobilized on glass slides in arrays of 3 mm spots. Genomic DNA is amplified by PCR using one fluorescently tagged primer oligonucleotide and one biotinylated primer oligonucleotide. The two complementary DNA strands are separated, the fluorescently tagged strand is hybridized to the support-bound oligonucleotide array, and the hybridization pattern is detected by fluorescence scanning. Multiple polymorphisms present in the PCR product may be detected in parallel. The effect of spacer length, surface density and hybridization conditions were evaluated, as was the relative efficacy of hybridization with single or double-stranded PCR products. The utility of the method was demonstrated in the parallel analysis of 5 point mutations from exon 4 of the human tyrosinase gene. Images PMID:7816638

  1. Extensive genetic polymorphism in the human tumor necrosis factor region and relation to extended HLA haplotypes.

    PubMed Central

    Jongeneel, C V; Briant, L; Udalova, I A; Sevin, A; Nedospasov, S A; Cambon-Thomsen, A

    1991-01-01

    We have identified three polymorphic microsatellites (which we call TNFa, TNFb, and TNFc) within a 12-kilobase region of the human major histocompatibility complex (MHC) that includes the tumor necrosis factor (TNF) locus. TNFc is located within the first intron of the TNF-beta gene and has only 2 alleles. TNFa and TNFb are 3.5 kilobases upstream (telomeric) of the TNF-beta gene and have at least 13 and 7 alleles, respectively. TNFa, -b, and -c alleles are in linkage disequilibrium with alleles at other loci within the MHC, including class I, class II, and class III. TNFa, -b, and -c alleles are also associated with extended HLA haplotypes. These TNF polymorphisms will allow a thorough genetic analysis of the involvement of TNF in MHC-linked pathologies. Images PMID:1946393

  2. 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.

  3. MTHFR Genetic Polymorphism As a Risk Factor in Egyptian Mothers with Down Syndrome Children

    PubMed Central

    Meguid, Nagwa A.; Dardir, Ahmed A.; Khass, Mohamed; Hossieny, Lamia El; Ezzat, Afaf; Awady, Mostafa K. El

    2008-01-01

    Recent reports linking Down syndrome (DS) to maternal polymorphisms at the methylenetetrahydrofolate reductase (MTHFR) gene locus have generated great interest among investigators in the field. The present study aimed at evaluation of MTHFR 677C/T and 1298A/C polymorphisms in the MTHFR gene as maternal risk factors for DS. Forty two mothers of proven DS outcomes and forty eight control mothers with normal offspring were included. Complete medical and nutritional histories for all mothers were taken with special emphasis on folate intake. Folic acid intake from food or vitamin supplements was significantly low (below the Recommended Daily Allowance) in the group of case mothers compared to control mothers. Frequencies of MTHFR 677T and MTHFR 1298C alleles were significantly higher among case mothers (32.1% and 57.1%, respectively) compared to control mothers (18.7% and 32.3%, respectively). Heterozygous and homozygous genotype frequencies of MTHFR at position 677 (CT and TT) were higher among case mothers than controls (40.5% versus 25% and 11.9% versus 6.2%, respectively) with an odds ratio of 2.34 (95% confidence interval [CI] 0.93–5.89) and 2.75 (95% CI 0.95–12.77), respectively. Interestingly, the homozygous genotype frequency (CC) at position 1298 was significantly higher in case mothers than in controls (33.3% versus 2.1% respectively) with an odds ratio of 31.5 (95% CI 3.51 to 282.33) indicating that this polymorphism may have more genetic impact than 677 polymorphism. Heterozygous genotype (AC) did not show significant difference between the two groups. We here report on the first pilot study of the possible genetic association between DS and MTHFR 1298A/C genotypes among Egyptians. Further extended studies are recommended to confirm the present work. PMID:18057532

  4. MTHFR genetic polymorphism as a risk factor in Egyptian mothers with Down syndrome children.

    PubMed

    Meguid, Nagwa A; Dardir, Ahmed A; Khass, Mohamed; Hossieny, Lamia El; Ezzat, Afaf; El Awady, Mostafa K

    2008-01-01

    Recent reports linking Down syndrome (DS) to maternal polymorphisms at the methylenetetrahydrofolate reductase (MTHFR) gene locus have generated great interest among investigators in the field. The present study aimed at evaluation of MTHFR 677C/T and 1298A/C polymorphisms in the MTHFR gene as maternal risk factors for DS. Forty two mothers of proven DS outcomes and forty eight control mothers with normal offspring were included. Complete medical and nutritional histories for all mothers were taken with special emphasis on folate intake. Folic acid intake from food or vitamin supplements was significantly low (below the Recommended Daily Allowance) in the group of case mothers compared to control mothers. Frequencies of MTHFR 677T and MTHFR 1298C alleles were significantly higher among case mothers (32.1% and 57.1%, respectively) compared to control mothers (18.7% and 32.3%, respectively). Heterozygous and homozygous genotype frequencies of MTHFR at position 677 (CT and TT) were higher among case mothers than controls (40.5% versus 25% and 11.9% versus 6.2%, respectively) with an odds ratio of 2.34 (95% confidence interval [CI] 0.93-5.89) and 2.75 (95% CI 0.95-12.77), respectively. Interestingly, the homozygous genotype frequency (CC) at position 1298 was significantly higher in case mothers than in controls (33.3% versus 2.1% respectively) with an odds ratio of 31.5 (95% CI 3.51 to 282.33) indicating that this polymorphism may have more genetic impact than 677 polymorphism. Heterozygous genotype (AC) did not show significant difference between the two groups. We here report on the first pilot study of the possible genetic association between DS and MTHFR 1298A/C genotypes among Egyptians. Further extended studies are recommended to confirm the present work.

  5. 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

    2015-03-20

    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.

  6. IL-6 gene promoter polymorphisms: genetic susceptibility to recurrent pregnancy loss.

    PubMed

    Demirturk, F; Ates, O; Gunal, O; Bozkurt, N; Aysal, T; Nacar, M C

    2014-01-01

    Recurrent pregnancy loss (RPL) is defined as three or more pregnancy losses before 20 weeks. RPL is a multifactorial condition with several etiologic factors including genetic abnormalities of the parents, anatomical, endocrinological, hematologic and immunologic abnormalities, infections, nutritional and environmental factors. The causes of pregnancy loss in about half of the women with RPL even after extensive investigations remain unknown. We analyzed IL-6 -174 G/C, -572 G/C, -597 G/A, -1363 G/T, -2954 G/C promoter region polymorphisms in 113 RPL patients and 113 healthy subjects by using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay. The -174G/C genotypic and -174C allelic frequency and the -2954G/C genotypic and -2954C allelic frequency of IL-6 was higher in RPL patients than healthy controls and a significant association was found between RPL and -174G/C, -2954G/C polymorphisms (p < 0.0001, OR: 0.28, 95% CI: 0.15-0.51, p < 0.034, OR: 0.16, 95% CI: 0.01-1.12 respectively). We found remarkably similar frequencies in RPL patients compared to controls for IL-6 -572G/C,-597G/A and -1363G/T genotypes/alleles and no association was observed between RPL and these polymorphisms. Our study supported that IL-6 -174G/C and -2954G/C polymorphisms were associated with an increased risk of RPL in Turkish patients (Tab. 3, Ref. 24). PMID:25246282

  7. 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

  8. Functional effects of genetic polymorphism in inflammatory genes in subjective memory complainers.

    PubMed

    Lau, Simon; Bates, Kristyn Alissa; Sohrabi, Hamid R; Rodrigues, Mark; Martins, Georgia; Dhaliwal, Satvinder S; Taddei, Kevin; Laws, Simon M; Martins, Ian J; Mastaglia, Francis L; Foster, Jonathan K; Phillips, Jacqueline K; Martins, Ralph N

    2012-06-01

    A number of genetic risk factors have been identified for Alzheimer's disease (AD) including genes involved in the inflammatory response (interleukin 1A, [IL-1α (-889)], interleukin 1B (IL-1β [+3953]), and tumor necrosis factor (TNF [-308 and -850]). We investigated the prevalence and functional consequences (baseline cognitive performance, plasma cytokine levels) of possession of these putative genetic risk factors within a group of subjective memory complainers (SMC, n = 226) and age and sex matched noncomplainers (NMC, n = 167). We observed no effect of any of the genetic factors investigated on cognitive performance. Further, there was no difference in the frequency of the disease-associated alleles, or cytokine levels between subjective memory complainers and noncomplainer participants. There was no relationship between TNF polymorphisms and TNF levels. There was a significant increase in plasma IL-1β levels in those homozygous for the disease-associated allele (i.e., IL-1β +3953 TT). Follow-up longitudinal assessments on this cohort will provide insight as to how these polymorphisms may affect the risk of cognitive decline over time.

  9. 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.

  10. Genetic polymorphism of toll-like receptors 4 gene by polymerase chain reaction-restriction fragment length polymorphisms, polymerase chain reaction-single-strand conformational polymorphism to correlate with mastitic cows

    PubMed Central

    Gupta, Pooja H.; Patel, Nirmal A.; Rank, D. N.; Joshi, C. G.

    2015-01-01

    Aim: An attempt has been made to study the toll-like receptors 4 (TLR4) gene polymorphism from cattle DNA to correlate with mastitis cows. Materials and Methods: In present investigation, two fragments of TLR4 gene named T4CRBR1 and T4CRBR2 of a 316 bp and 382 bp were amplified by polymerase chain reaction (PCR), respectively from Kankrej (22) and Triple cross (24) cattle. The genetic polymorphisms in the two populations were detected by a single-strand conformational polymorphism in the first locus and by digesting the fragments with restriction endonuclease Alu I in the second one. Results: Results showed that both alleles (A and B) of two loci were found in all the two populations and the value of polymorphism information content indicated that these were highly polymorphic. Statistical results of χ2 test indicated that two polymorphism sites in the two populations fit with Hardy–Weinberg equilibrium (p<0.05). Meanwhile, the effect of polymorphism of TLR4 gene on the somatic cell score (SCS) indicated the cattle with allele a in T4CRBR1 showed lower SCS than that of allele B (p<0.05). Thus, the allele A might play an important role in mastitis resistance in cows. Conclusion: The relationship between the bovine mastitis trait and the polymorphism of TLR4 gene indicated that the bovine TLR4 gene may play an important role in mastitis resistance. PMID:27047144

  11. MMP7 and MMP8 genetic polymorphisms in bladder cancer patients

    PubMed Central

    Reszka, Edyta; Wasowicz, Wojciech; Grzegorczyk, Adam; Konecki, Tomasz; Sosnowski, Marek; Jablonowski, Zbigniew

    2013-01-01

    Introduction Breakdown of the extracellular matrix by matrix metalloproteinases (MMPs), as we know, is one of mechanisms involved and required in tumor invasion. MMP7 is a negative prognostic factor of various malignances, while MMP8 exhibits an inhibitory effect on tumorigenesis and metastasis. We evaluated the potential association of functional polymorphisms in the promoter of the MMP7 (rs11568818) and MMP8 (rs11225395) genes and bladder cancer (BCa) risk. Materials and methods The study included 241 BCa cases and 199 healthy population controls that were collected at the First Department of Urology, Medical University (Łódź, Poland) and at the Nofer Institute of Occupational Medicine (Łódź, Poland). Genomic DNA samples were isolated from venous blood and genetic polymorphisms were analyzed by real–time polymerase chain reaction using TaqMan fluorescent probes. Associations between genotype and allele status were estimated by logistic regression models adjusted for classic risk factors (e.g. age, gender and cigarette smoking). Results MMP7 and MMP8 genotypes were distributed similarly in BCa patients and in controls and at least one variant allele was not associated with BCa cancer risk (OR, 0.91; 95% CI, 0.60–1.39; p = 0.662 for MMP7 and OR, 0.96; 95% CI, 0.63–1.46; p = 0.836 for MMP8). We observed higher prevalence of MMP7 GG genotypes among BCa patients than in controls (OR, 1.54; 95% CI, 0.93–2.55; p = 0.093). Additionally, genetic polymorphisms in the MMP7 and MMP8 were not associated with the tumor grade or stage. Conclusions Our results suggest that genetic variations in two genes encoding members of the MMP7 and MMP8 are not associated with a risk of BCa in the Caucasian population. PMID:24757528

  12. Embryo genome profiling by single-cell sequencing for successful preimplantation genetic diagnosis in a family harboring COL4A1 c.1537G>A; p.G513S mutation

    PubMed Central

    Patel, Nayana H.; Bhadarka, Harsha K.; Patel, Kruti B.; Vaniawala, Salil N.; Acharya, Arpan; Mukhopadhyaya, Pratap N.; Sodagar, Nilofar R.

    2016-01-01

    CONTEXT: Genetic profiling of embryos (also known as preimplantation genetic diagnosis) before implantation has dramatically enhanced the success quotient of in vitro fertilization (IVF) in recent times. The technology helps in avoiding selective pregnancy termination since the baby is likely to be free of the disease under consideration. AIM: Screening of embryos free from c.1537G>A; p.G513S mutation within the COL4A1 gene for which the father was known in before be in heterozygous condition. SUBJECTS AND METHODS: Processing of trophectoderm biopsies was done from twelve embryos for c.1537G>A; p.G513S mutation within the COL4A1 gene. DNA extracted from isolated cells were subjected to whole genome amplification using an isothermal amplification and strand displacement technology. Oligonucleotide primers bracketing the mutation were synthesized and used to amplify 162 base pairs (bp) polymerase chain reaction amplicons originating from each embryo which were subsequently sequenced to detect the presence or absence of the single base polymorphism. RESULTS: Three out of 12 embryos interrogated in this study were found to be normal while 9 were found to harbor the mutation in heterozygous condition. Implantation of one of the normal embryos following by chorionic villus sampling at 11th week of pregnancy indicated that the baby was free from c.1537G>A; p.G513S mutation within the COL4A1 gene. CONCLUSIONS: Single-cell sequencing is a helpful tool for preimplantation embryo profiling. This is the first report from India describing the birth of a normal child through IVF procedure where a potential pathogenic COL4A1 allele was avoided using this technology. PMID:27803589

  13. 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

    2013-04-12

    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.

  14. Closure of a genetic linkage map of human chromosome 7q with centromere and telomere polymorphisms

    SciTech Connect

    Helms, C.; Mishra, S.K.; Burgess, A.K.; Ramachandra, S.; Tierney, C.; Dorsey, D.; Donis-Keller, H. ); Riethman, H. )

    1992-12-01

    The authors have constructed a 2.4-cM resolution genetic linkage map for chromosome 7q that is bounded by centromere and telomere polymorphisms and contains 66 loci (88 polymorphic systems), 38 of which are uniquely placed with odds for order of at least 1000:1. Ten genes are included in the map and 11 markers have heterozygosities of at least 70%. This map is the first to incorporate several highly informative markers derived from a telomere YAC clone HTY146 (locus D7S427), including HTY146c3 (HET 92%). The telomere locus markers span at least 200 kb of the 7q terminus and no crossovers within the physical confines of the locus were observed in approximately 240 jointly informative meioses. The sex-equal map length is 158 cM and the largest genetic interval between uniquely localized markers in this map is 11 cM. The female and male map lengths are 181 and 133 cM, respectively. The map is based on the CEPH reference pedigrees and includes over 4000 new genotypes, the previously reported data plus 29 allele systems from the published CEPH version 5 database, and was constructed using the program package CRI-MAP. This genetic linkage map can be considered a baseline map for 7q, and will be useful for defining the extent of chromosome deletions previously reported for breast and prostate cancers, for developing additional genetic maps such as index marker and 1-cM maps, and ultimately for developing a fully integrated genetic and physical map for this chromosome. 63 refs., 4 figs., 1 tab.

  15. The Significance of Genetic Polymorphisms within and between Founder Populations of Ceratitis capitata (Wied.) from Argentina

    PubMed Central

    Basso, Alicia; Martinez, Laura; Manso, Fanny

    2009-01-01

    Background The Mediterranean fruit fly Ceratitis Capitata (DIPTERA: Tephritidae) is a major agricultural pest in Argentina. One main cause for the success of non-contaminant control programs based on genetic strategies is compatibility between natural and laboratory germplasms. A comprehensive characterization of the fruit fly based on genetic studies and compatibility analysis was undertaken on two founder populations from the provinces of Buenos Aires and Mendoza, used in pioneering sterile male technique control programmes in our country. The locations are 1,000 km apart from each other. Methodology/Principal Findings We compared the genetic composition of both populations based on cytological, physiological and morphological characterization. Compatibility studies were performed in order to determine the presence of isolation barriers. Results indicate that the Buenos Aires germplasm described previously is partially different from that of the Mendoza population. Both laboratory colonies are a reservoir of mutational and cytological polymorphisms. Some sexual chromosome variants such as the XL and the YL resulting from attachment of a B-chromosome to the X-chromosome or Y-chromosome behave as a lethal sex-linked factor. Our results also show incompatibility between both germplasms and pre-zygotic isolation barriers between them. Our evidence is consistent with the fact that polymorphisms are responsible for the lack of compatibility. Conclusions The genetic control mechanism should be directly produced in the germplasm of the target population in order to favour mating conditions. This is an additional requirement for the biological as well as economic success of control programs based on genetic strategies such as the sterile insect technique. The analysis of representative samples also revealed natural auto-control mechanisms which could be used in modifying pest population dynamics. PMID:19252742

  16. 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

  17. Association of the g.27563G>A osteoprotegerin genetic polymorphism with bone mineral density in Chinese women.

    PubMed

    Liu, Y P; Zhao, D W; Wang, W M; Wang, B J; Zhang, Y; Li, Z G

    2014-02-14

    Osteoporosis is a common multifactorial disease in postmenopausal women. This study aimed to investigate the association of the g.27563G>A osteoprotegerin (OPG) genetic polymorphism with bone mineral density (BMD) and osteoporosis. A case-control study was carried out with 435 osteoporosis postmenopausal women cases and 442 age-matched healthy controls. The BMD at the femoral neck hip, lumbar spine (L₂₋₄), and total hip were assessed by Norland XR-46 dual-energy X-ray absorptiometry. The genotypes of the g.27563G>A genetic polymorphism were detected by created restriction site-polymerase chain reaction and verified by DNA sequencing methods. We detected that the g.27563G>A genetic polymorphism was a non-synonymous mutation that resulted in an arginine (Arg) to glutamine (Gln) amino acid replacement (p.Arg333Gln). Significant differences were found in the BMD of the femoral neck hip, lumbar spine (L₂₋₄), and total hip among different genotypes of the g.27563G>A genetic polymorphism. Subjects with the genotype GG had significantly higher BMD values than those with genotypes GA and AA (P < 0.05). Our data indicated that the A allele of the g.27563G>A genetic polymorphism in OPG could be associated with lower BMD values in the Chinese postmenopausal women evaluated, and that it might be an increased risk factor for osteoporosis.

  18. Investigation on XRCC1 genetic polymorphism and its relationship with breast cancer risk factors in Chinese women.

    PubMed

    Zheng, Luming; Yang, Feng; Zhang, Xukui; Zhu, Jian; Zhou, Pen; Yu, Fang; Hou, Lei; Zhao, Guowei; He, Qingqing; Wang, Baocheng

    2013-12-01

    Breast cancer (BC) remains one of the most common cancers among women. The human X-ray repair cross-complementing 1 (XRCC1) gene plays key roles in base excision repair, and genetic polymorphisms of XRCC1 may be associated with the susceptibility to BC. This study aimed to evaluate the relationship between the XRCC1 genetic polymorphisms and BC susceptibility. A total of 354 BC patients and 366 cancer-free controls were enrolled in this study. Data about the risk factors of BC were collected using questionnaires. The XRCC1 genetic polymorphism was determined using created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. No significant differences in the allelic and genotypic frequencies of c.1804C>A genetic polymorphism were detected between cases and controls. The distributions of BC patients' risk factors were not significantly different between CC, CA, and AA genotypes. These findings indicate that the c.1804C>A genetic polymorphism of XRCC1 gene is not significantly associated with BC susceptibility in the Chinese women.

  19. Association of the XRCC1 c.1178G>A genetic polymorphism with lung cancer risk in Chinese.

    PubMed

    Wang, Lei; Lin, Yong; Qi, Cong-Cong; Sheng, Bao-Wei; Fu, Tian

    2014-01-01

    The X-ray repair cross-complementing group 1 protein (XRCC1) plays important roles in the DNA base excision repair pathway which may influence the development of lung cancer. This study aimed to evaluate the potential association of the XRCC1 c.1178G>A genetic polymorphism with lung cancer risk. The created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods were utilized to evaluate the XRCC1 c.1178G>A genetic polymorphism among 376 lung cancer patients and 379 controls. Associations between the genetic polymorphism and lung cancer risk were determined with an unconditional logistic regression model. Our data suggested that the distribution of allele and genotype in lung cancer patients was significantly different from that of controls. The XRCC1 c.1178G>A genetic polymorphism was associated with an increased risk of lung cancer (AA vs GG: OR=2.91, 95%CI 1.70-4.98, p<0.001; A vs G: OR=1.52, 95%CI 1.22-1.90, p<0.001). The allele A and genotype AA may contribute to risk of lung cancer. These preliminary results suggested that the XRCC1 c.1178G>A genetic polymorphism is statistically associated with lung cancer risk in the Chinese population.

  20. Association between genetic polymorphisms in the serotonergic system and comorbid personality disorders among patients with first-episode depression.

    PubMed

    Bukh, Jens D; Bock, Camilla; Kessing, Lars V

    2014-06-01

    Studies on the association between genetic polymorphisms and personality disorders have provided inconsistent results. Using the "enriched sample method," the authors of the present study aimed to assess the association between polymorphisms in the serotonergic transmitter system and comorbid personality disorders in patients recently diagnosed with first-episode depression. A total of 290 participants were systematically recruited via the Danish Psychiatric Central Research Register. Diagnoses of personality disorders were assessed by a SCID-II interview, and polymorphisms in the genes encoding the serotonin transporter, serotonin receptors 1A, 2A, 2C, and tryptophan hydroxylase 1 were genotyped. The authors found a significant effect of the length polymorphism in the serotonin transporter gene (5-HTTLPR) on cluster B personality disorder (mainly borderline disorder), but no influence on cluster C personality disorder, and no associations between other polymorphisms and personality disorders. The study adds evidence to the effect of the serotonin transporter gene specifically on cluster B personality disorders.

  1. Genome-wide patterns of genetic polymorphism and signatures of selection in Plasmodium vivax.

    PubMed

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

    2014-12-17

    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.

  2. NIG_MoG: a mouse genome navigator for exploring intersubspecific genetic polymorphisms.

    PubMed

    Takada, Toyoyuki; Yoshiki, Atsushi; Obata, Yuichi; Yamazaki, Yukiko; Shiroishi, Toshihiko

    2015-08-01

    The National Institute of Genetics Mouse Genome database (NIG_MoG; http://molossinus.lab.nig.ac.jp/msmdb/) primarily comprises the whole-genome sequence data of two inbred mouse strains, MSM/Ms and JF1/Ms. These strains were established at NIG and originated from the Japanese subspecies Mus musculus molossinus. NIG_MoG provides visualized genome polymorphism information, browsing single-nucleotide polymorphisms and short insertions and deletions in the genomes of MSM/Ms and JF1/Ms with respect to C57BL/6J (whose genome is predominantly derived from the West European subspecies M. m. domesticus). This allows users, especially wet-lab biologists, to intuitively recognize intersubspecific genome divergence in these mouse strains using visual data. The database also supports the in silico screening of bacterial artificial chromosome (BAC) clones that contain genomic DNA from MSM/Ms and the standard classical laboratory strain C57BL/6N. NIG_MoG is thus a valuable navigator for exploring mouse genome polymorphisms and BAC clones that are useful for studies of gene function and regulation based on intersubspecific genome divergence.

  3. 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

  4. Computer-aided identification of polymorphism sets diagnostic for groups of bacterial and viral genetic variants

    PubMed Central

    Price, Erin P; Inman-Bamber, John; Thiruvenkataswamy, Venugopal; Huygens, Flavia; Giffard, Philip M

    2007-01-01

    Background Single nucleotide polymorphisms (SNPs) and genes that exhibit presence/absence variation have provided informative marker sets for bacterial and viral genotyping. Identification of marker sets optimised for these purposes has been based on maximal generalized discriminatory power as measured by Simpson's Index of Diversity, or on the ability to identify specific variants. Here we describe the Not-N algorithm, which is designed to identify small sets of genetic markers diagnostic for user-specified subsets of known genetic variants. The algorithm does not treat the user-specified subset and the remaining genetic variants equally. Rather Not-N analysis is designed to underpin assays that provide 0% false negatives, which is very important for e.g. diagnostic procedures for clinically significant subgroups within microbial species. Results The Not-N algorithm has been incorporated into the "Minimum SNPs" computer program and used to derive genetic markers diagnostic for multilocus sequence typing-defined clonal complexes, hepatitis C virus (HCV) subtypes, and phylogenetic clades defined by comparative genome hybridization (CGH) data for Campylobacter jejuni, Yersinia enterocolitica and Clostridium difficile. Conclusion Not-N analysis is effective for identifying small sets of genetic markers diagnostic for microbial sub-groups. The best results to date have been obtained with CGH data from several bacterial species, and HCV sequence data. PMID:17672919

  5. Association of FCRL3 Genetic Polymorphisms With Endometriosis-Related Infertility Risk

    PubMed Central

    Zhang, Haiyan; Zhang, Zhen; Li, Guang; Wang, Surong; Zhang, Shiqian; Xie, Beibei

    2015-01-01

    Abstract The Fc receptor-like 3 (FCRL3) gene was reported to be linked to a variety of autoimmune diseases, including endometriosis-related infertility. However, this linkage has not been studied in Chinese population and there has been no meta-analysis on the interrelationship of FCRL3 gene and endometriosis-related infertility. The aim of the study was to investigate the association between FCRL3 genetic polymorphisms and the risk of endometriosis-related infertility in Han Chinese, and a further meta-analysis was conducted to confirm our results. Four single nucleotide polymorphisms (SNPs) (rs7528684 [FCRL3_3], rs11264799 [FCRL3_4], rs945635 [FCRL3_5], and rs3761959 [FCRL3_6]) on FCRL3 gene were genotyped in a case–control cohort composed of 217 patients suffering from endometriosis-related infertility and 220 healthy controls using cleaved amplification polymorphism sequence-tagged sites (polymerase chain reaction–restriction fragment length polymorphism, PCR–RFLP). Odds ratio (OR) and its 95% confidence interval (CI) was used to evaluate the association quantitatively. Furthermore, a meta-analysis of previous studies including the present study was implemented through Stata 11.0 (Stata Corporation, College Station, TX). We found an approximately 1.4-fold significantly increased frequency of the FCRL3_3 variant in women with endometriosis-related infertility over the controls (OR = 1.41 [95% CI = 1.08–1.84], P = 0.013). However, no significant difference was found between women with endometriosis-related infertility and controls for FCRL3_4, FCRL3_5, and FCRL3_6. Regardless of the symptoms and the revised classification of the American Society of Reproductive Medicine (rASRM) stage of endometriosis, there was a significant association between FCRL3_3 variant and an increased risk of endometriosis-related infertility. Meta-analysis of previous studies combined with the present study further confirmed the association between FCRL3_3 and the

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

    PubMed

    Barillet, Francis; Arranz, Juan-José; Carta, Antonello

    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 alphas1-casein and beta-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.

  7. Genetic polymorphism of beta-lactoglobulin gene in native Turkish sheep breeds.

    PubMed

    Elmaci, Cengiz; Oner, Yasemin; Balcioglu, M Soner

    2006-10-01

    The genetic polymorphism of the beta-lactoglobulin gene was investigated in three native Turkish sheep breeds. The study was carried out on 108 sheep (29 Kivircik, 38 Gökçeada, and 41 Sakiz) by means of PCR-RFLP methods. Two genetic variants (A and B) and three genotypes (AA, AB, and BB) of beta-lactoglobulin have been identified. The gene frequencies of beta-LG A and B were 0.7759 and 0.2241 in Kivircik, 0.7632 and 0.2368 in Gökçeada, and 0.9756 and 0.0244 in Sakiz breeds, respectively. The populations were in Hardy-Weinberg equilibrium in all samples from the three breeds.

  8. Genetic association of cytokines polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese

    PubMed Central

    Fan, Lie-Ying; Tu, Xiao-Qing; Zhu, Ye; Pfeiffer, Thomas; Feltens, Ralph; Stoecker, Winfried; Zhong, Ren-Qian

    2005-01-01

    AIM: To characterize gene polymorphism of several cytokine gene in-patients with AIH and PBC and to analyze the difference of the polymorphism distribution between Chinese patients and healthy controls. METHODS: The study population consisted of 62 patients with AIH, and 77 patients with PBC. The genetic profile of four cytokines was analyzed by restriction fragment length polymorphism after specific PCR amplification (PCR-RFLP) or sequence-specific primers PCR (SSP-PCR). The analyzed gene polymorphism included interleukin-1 (IL-1) (at position +3 953 and IL-1RN intron 2), IL-6 (at position -174), IL-10 promoter (at position -1082, -819, and -592). The control group consisted of 160 healthy blood donors. RESULTS: The majority of Chinese people including patients and healthy controls exhibited IL-1B 1,1 genotype, and there was no significant difference in AIH, PBC patients and controls. There were highly statistically significant differences in the distribution of the IL-1RN gene polymorphism between the patients with PBC compared with controls. The frequency of IL-1RN 1,1 was significantly higher (90.9% vs 79.4%, P = 0.03) and the frequency of IL-1RN 1,2 was significantly lower in PBC patients (6.5% vs 17.5%, P = 0.01). No statistical difference was observed between AIH patients and controls. All of the 160 healthy controls and 62 cases of AIH patients exhibited IL-6-174GG genotype, and there were four cases, which expressed IL-6-174GC genotype in 77 cases of PBC patients. The frequency of IL-6-174GC was markedly significantly higher in PBC patients compared with controls (5.2% vs 0%, P = 0.004). No statistically significant difference was found in the distribution of IL-10 promoter genotype in AIH and PBC patients compared with controls. CONCLUSION: The polymorphisms of IL-1RN and IL-6 -174G/C appear to be associated with PBC in Chinese patients. PMID:15884119

  9. Genetic Polymorphisms in DNA Repair Genes as Modulators of Hodgkin Disease Risk

    PubMed Central

    El-Zein, Randa; Monroy, Claudia M.; Etzel, Carol J.; Cortes, Andrea C.; Xing, Yun; Collier, Amanda L.; Strom, Sara S.

    2009-01-01

    BACKGROUND Although the pathogenesis of Hodgkin disease (HD) remains unknown, the results of epidemiologic studies suggest that heritable factors are important in terms of susceptibility. Polymorphisms in DNA repair genes may contribute to individual susceptibility for development of different cancers. However, to the authors’ knowledge, few studies to date have investigated the role of such polymorphisms as risk factors for development of HD. METHODS The authors evaluated the relation between polymorphisms in 3 nucleotide excision repair pathway genes (XPD [Lys751Gln], XPC [Lys939Gln], and XPG [Asp1104His]), the base excision repair XRCC1 (Arg399Gln), and double-strand break repair XRCC3 (Thr241Met) in a population of 200 HD cases and 220 matched controls. Variants were investigated independently and in combination; odd ratios (OR) were calculated. RESULTS A positive association was found for XRCC1 gene polymorphism Arg399Gln (OR, 1.77; 95% confidence interval [95% CI], 1.16−2.71) and risk of HD. The combined analysis demonstrated that XRCC1/XRCC3 and XRCC1/XPC polymorphisms were associated with a significant increase in HD risk. XRCC1 Arg/Arg and XRCC3 Thr/Met genotypes combined were associated with an OR of 2.38 (95% CI, 1.24−4.55). The XRCC1 Arg/Gln and XRCC3 Thr/Thr, Thr/Met, and Met/Met genotypes had ORs of 1.88 (95% CI, 1.02−4.10), 1.97 (95% CI, 1.05−3.73), and 4.13 (95% CI, 1.50−11.33), respectively. XRCC1 Gln/Gln and XRCC3 Thr/Thr variant led to a significant increase in risk, with ORs of 3.00 (95% CI, 1.15−7.80). Similarly, XRCC1 Arg/Gln together with XPC Lys/Lys was found to significantly increase the risk of HD (OR, 2.14; 95% CI, 1.09−4.23). CONCLUSIONS These data suggest that genetic polymorphisms in DNA repair genes may modify the risk of HD, especially when interactions between the pathways are considered. PMID:19280628

  10. The danger within: the role of genetic, behavioural and ecological factors in population persistence of colour polymorphic species.

    PubMed

    Bolton, Peri E; Rollins, Lee A; Griffith, Simon C

    2015-06-01

    Polymorphic species have been the focus of important work in evolutionary biology. It has been suggested that colour polymorphic species have specific evolutionary and population dynamics that enable them to persist through environmental changes better than less variable species. We suggest that recent empirical and theoretical work indicates that polymorphic species may be more vulnerable to extinction than previously thought. This vulnerability arises because these species often have a number of correlated sexual, behavioural, life history and ecological traits, which can have a simple genetic underpinning. When exacerbated by environmental change, these alternate strategies can lead to conflict between morphs at the genomic and population levels, which can directly or indirectly affect population and evolutionary dynamics. In this perspective, we identify a number of ways in which the nature of the correlated traits, their underpinning genetic architecture, and the inevitable interactions between colour morphs can result in a reduction in population fitness. The principles illustrated here apply to all kinds of discrete polymorphism (e.g. behavioural syndromes), but we focus primarily on colour polymorphism because they are well studied. We urge further empirical investigation of the genetic architecture and interactions in polymorphic species to elucidate the impact on population fitness.

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

    PubMed Central

    Tardin, Oziel Marcio Araujo; Pereira, Sabrina Bernardez; Velloso, Monica Wanderley Monçores; 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

  12. 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 (1.50–2.84)). 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 significantly 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

  13. 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 = 1.01–8.83; 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

  14. 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

  15. Investigating the genetic basis of altruism: the role of the COMT Val158Met polymorphism

    PubMed Central

    Frenzel, Clemens; Walter, Nora T.; Markett, Sebastian; Montag, Christian

    2011-01-01

    Findings from twin studies yield heritability estimates of 0.50 for prosocial behaviours like empathy, cooperativeness and altruism. First molecular genetic studies underline the influence of polymorphisms located on genes coding for the receptors of the neuropeptides, oxytocin and vasopressin. However, the proportion of variance explained by these gene loci is rather low indicating that additional genetic variants must be involved. Pharmacological studies show that the dopaminergic system interacts with oxytocin and vasopressin. The present experimental study tests a dopaminergic candidate polymorphism for altruistic behaviour, the functional COMT Val158Met SNP. N = 101 healthy Caucasian subjects participated in the study. Altruism was assessed by the amount of money donated to a poor child in a developing country, after having earned money by participating in two straining computer experiments. Construct validity of the experimental data was given: the highest correlation between the amount of donations and personality was observed for cooperativeness (r = 0.32, P ≤ 0.001). Carriers of at least one Val allele donated about twice as much money as compared with those participants without a Val allele (P = 0.01). Cooperativeness and the Val allele of COMT additively explained 14.6% of the variance in donation behaviour. Results indicate that the Val allele representing strong catabolism of dopamine is related to altruism. PMID:21030481

  16. Genetic variation of polymorphic NOS STR locus in ten Indian population groups.

    PubMed

    Shazia, A; Nithya, P; Seshadri, M

    2009-02-01

    The genotyping of 313 random individuals belonging to ten different population groups from three different states of India was performed for polymorphic pentanucleotide repeat present in the 5'-flanking region of nitric oxide synthase gene (NOS2A) to study the effect of geographical and linguistic affiliations on the genetic affinities among these groups. Likelihood ratio tests showed that all the ten populations for this locus were in Hardy Weinberg equilibrium. Eleven different alleles ranging from 7 repeat to 17 repeats and 46 different genotypes were observed. The observed and the expected heterozygosity ranged from 0.72-0.94 and 0.84-0.89, respectively. The discriminating power of this locus is > or = 0.86 and the polymorphism information content of this locus in ten population groups ranged from 0.80 to 0.85. High PIC, PD and PE value of this STR showed this marker to be informative and can be used for DNA typing and population studies. The eight populations from Kerala showed a lower GST value of 0.016 compared to the GST of ten populations (G(ST) = 0.019), thereby showing that the populations from the same state showed higher genetic proximity probably due to linguistic and geographical proximity between them.

  17. 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

  18. 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

  19. Investigation of the relationship between serum creatine kinase and genetic polymorphisms in military recruits.

    PubMed

    Landau, Mark E; Kenney, Kimbra; Deuster, Patricia; Gonzalez, Rodney S; Contreras-Sesvold, Carmen; Sambuughin, Nyamkhishig; O'Connor, Francis G; Campbell, William W

    2012-11-01

    Genetic polymorphisms may explain why certain individuals will develop exertional rhabdomyolysis (ER) or markedly elevated serum creatine kinase (CK) levels following exertion, while others in the same environment, performing the same exertion, do not. Prospectively, 499 recruits were evaluated during the initial fortnight of Army basic training. Serum CK levels were determined before and during that time. Eleven candidate genetic polymorphisms were studied and compared to CK levels. No subjects developed ER. Baseline CK was significantly greater in interleukin-6 G174C GG and myosin light chain kinase 2 (MLCK 2) AA subjects. Intertraining levels were significantly greater in angiotensin I-converting enzyme D/D and interleukin-6 GG subjects. Among African-Americans, those with MLCK2 AA had greater baseline CK (1,352 +/- 1,102.8 IU/L) than AC and CC genotypes (536.9 +/- 500.6). African-American men have the highest baseline levels and are more likely to have MLCK AA genotype. Whether this finding is associated with an increased incidence of ER requires further study.

  20. Heredity mode of genetic polymorphism in aldehyde oxidase activity in Donryu strain rats.

    PubMed

    Adachi, M; Itoh, K; Abe, H; Tanaka, Y

    2008-01-01

    Donryu strain rats show genetic polymorphisms in the aldehyde oxidase gene, resulting in the phenotypic expression of ultrarapid metabolizers with homozygous nucleotide sequences (337G, 2604C), extensive metabolizers with heterozygous nucleotide sequences (377G/A, 2604C/T), and poor metabolizers with homozygous nucleotide sequences (377A, 2604T). In the mating experiments the ratio of the number of ultrarapid metabolizers, extensive metabolizers, and poor metabolizers rats in the F1 generation from the heterozygous F0 extensive metabolizers male and female rats was roughly 0.6 : 1.5 : 1, and the ratio converged to approximately 1 : 2 : 1 in the F2 generation from the heterozygous F1 extensive metabolizers male and female rats. On the contrary, all the F2 generation from homozygous F1 ultrarapid metabolizers male and female rats or from homozygous F1 poor metabolizers male and female rats had the ultrarapid metabolizers or the poor metabolizers genotypes and phenotypes. The genotypes completely agreed with the phenotypes in all individuals of F0, F1, and F2 generations. The results indicate that the genetic polymorphism of aldehyde oxidase in Donryu strain rats obeys Mendelian heredity. The reason for a low ratio of the ultrarapid metabolizers rats in the commercially available Donryu strain rats - not more than several per cent - compared with the ratio expected from the Mendelian rule is unknown.

  1. 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.

  2. Neanderthal and Denisova genetic affinities with contemporary humans: introgression versus common ancestral polymorphisms.

    PubMed

    Lowery, Robert K; Uribe, Gabriel; Jimenez, Eric B; Weiss, Mark A; Herrera, Kristian J; Regueiro, Maria; Herrera, Rene J

    2013-11-01

    Analyses of the genetic relationships among modern humans, Neanderthals and Denisovans have suggested that 1-4% of the non-Sub-Saharan African gene pool may be Neanderthal derived, while 6-8% of the Melanesian gene pool may be the product of admixture between the Denisovans and the direct ancestors of Melanesians. In the present study, we analyzed single nucleotide polymorphism (SNP) diversity among a worldwide collection of contemporary human populations with respect to the genetic constitution of these two archaic hominins and Pan troglodytes (chimpanzee). We partitioned SNPs into subsets, including those that are derived in both archaic lineages, those that are ancestral in both archaic lineages and those that are only derived in one archaic lineage. By doing this, we have conducted separate examinations of subsets of mutations with higher probabilities of divergent phylogenetic origins. While previous investigations have excluded SNPs from common ancestors in principal component analyses, we included common ancestral SNPs in our analyses to visualize the relative placement of the Neanderthal and Denisova among human populations. To assess the genetic similarities among the various hominin lineages, we performed genetic structure analyses to provide a comparison of genetic patterns found within contemporary human genomes that may have archaic or common ancestral roots. Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe. Our results suggest that Neanderthal genetic associations with contemporary non-Sub-Saharan African populations, as well as the genetic affinities observed between Denisovans and Melanesians most likely result from the retention of ancient mutations in these populations. PMID:23872234

  3. Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson’s 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 Parkinson’s 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 χ2 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

  4. Exploiting the extraordinary genetic polymorphism of ciona for developmental genetics with whole genome sequencing.

    PubMed

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

    2014-05-01

    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 Ca(2+) 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.

  5. 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

    2014-02-14

    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.

  6. 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

  7. 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...

  8. 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...

  9. Twin pregnancy with complete hydatidiform mole (46,XX) and fetus (46,XY): genetic origin proved by analysis of chromosome polymorphisms.

    PubMed Central

    Fisher, R A; Sheppard, D M; Lawler, S D

    1982-01-01

    In a case of complete hydatidiform mole with fetus the genetic origins were defined by the use of chromosomal polymorphisms. The fetus had a normal 46,XY karyotype with evidence of the presence of both maternal and paternal chromosomes. The mole was 46,XX and of androgenetic origin. There was no evidence of a maternal contribution, and duplication of paternal chromosomes was shown. In such atypical molar pregnancies examining genetic polymorphisms yields much more information than do sex chromosome studies and karyotyping, particularly in confirming the diagnosis and defining the origin and aetiology of the condition. Images FIG 1 FIG 2 PMID:6803908

  10. Microsatellite polymorphism in the sexually transmitted human pathogen Trichomonas vaginalis indicates a genetically diverse parasite.

    PubMed

    Conrad, Melissa; Zubacova, Zuzana; Dunn, Linda A; Upcroft, Jacqui; Sullivan, Steven A; Tachezy, Jan; Carlton, Jane M

    2011-01-01

    Given the growing appreciation of serious health sequelae from widespread Trichomonas vaginalis infection, new tools are needed to study the parasite's genetic diversity. To this end we have identified and characterized a panel of 21 microsatellites and six single-copy genes from the T. vaginalis genome, using seven laboratory strains of diverse origin. We have (1) adapted our microsatellite typing method to incorporate affordable fluorescent labeling, (2) determined that the microsatellite loci remain stable in parasites continuously cultured for up to 17 months, and (3) evaluated microsatellite marker coverage of the six chromosomes that comprise the T. vaginalis genome, using fluorescent in situ hybridization (FISH). We have used the markers to show that T. vaginalis is a genetically diverse parasite in a population of commonly used laboratory strains. In addition, we have used phylogenetic methods to infer evolutionary relationships from our markers in order to validate their utility in future population analyses. Our panel is the first series of robust polymorphic genetic markers for T. vaginalis that can be used to classify and monitor lab strains, as well as provide a means to measure the genetic diversity and population structure of extant and future T. vaginalis isolates. PMID:20813140

  11. Microsatellite polymorphism in the sexually transmitted human pathogen Trichomonas vaginalis indicates a genetically diverse parasite.

    PubMed

    Conrad, Melissa; Zubacova, Zuzana; Dunn, Linda A; Upcroft, Jacqui; Sullivan, Steven A; Tachezy, Jan; Carlton, Jane M

    2011-01-01

    Given the growing appreciation of serious health sequelae from widespread Trichomonas vaginalis infection, new tools are needed to study the parasite's genetic diversity. To this end we have identified and characterized a panel of 21 microsatellites and six single-copy genes from the T. vaginalis genome, using seven laboratory strains of diverse origin. We have (1) adapted our microsatellite typing method to incorporate affordable fluorescent labeling, (2) determined that the microsatellite loci remain stable in parasites continuously cultured for up to 17 months, and (3) evaluated microsatellite marker coverage of the six chromosomes that comprise the T. vaginalis genome, using fluorescent in situ hybridization (FISH). We have used the markers to show that T. vaginalis is a genetically diverse parasite in a population of commonly used laboratory strains. In addition, we have used phylogenetic methods to infer evolutionary relationships from our markers in order to validate their utility in future population analyses. Our panel is the first series of robust polymorphic genetic markers for T. vaginalis that can be used to classify and monitor lab strains, as well as provide a means to measure the genetic diversity and population structure of extant and future T. vaginalis isolates.

  12. Clinical and genetic characteristics and effects of long-term growth hormone therapy in a girl with Floating-Harbor syndrome.

    PubMed

    García, Roberto J; Kant, Sarina G; Wit, Jan M; Mericq, Verónica

    2012-01-01

    The established facts to date relating to Floating-Harbor syndrome (FHS) are its characteristic typical triangular facies with bulbous nose and thin lips, short stature, delayed bone age, and mild mental retardation with delay in expressive speech; its sporadic occurrence without Mendelian inheritance; and its unknown cause. Little is known about the growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis and the effect of GH treatment in children with this syndrome. We report on a 9-year-old girl born small for gestational age (SGA, birth length -2.2 standard deviation score) with persistent short stature who has been treated with GH from 3.5 years onward with a modest growth response. Revision of the case led to the diagnosis of FHS. No abnormalities were found in the sequence or copy number of IGF-1 receptor or in the genomic single-nucleotide polymorphism array. GH treatment led to an increase in serum IGF-1 in the upper normal range, but the growth response was modest, suggesting a defect in IGF-1 signaling. Early recognition of this entity is important, as it enables specific diagnostic tests targeted at other abnormalities associated with FHS. PMID:22570979

  13. 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 < 0.01) between similarity matrix obtained by SCoT and CDDP. Three different marker techniques showed relatively same pattern of diversity across genotypes and using each marker technique it's obvious that diversity pattern and 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.

  14. 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

  15. 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 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

  16. 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.

  17. Genetic Polymorphisms of the TYMS Gene Are Not Associated with Congenital Cardiac Septal Defects in a Han Chinese Population

    PubMed Central

    Wang, Jue; Wang, Er-Li; Yang, Xue-Yan; Qiao, Bin; Duan, Wen-Yuan; Huang, Guo-Ying; Wang, Hong-Yan

    2012-01-01

    Background Clinical research indicates that periconceptional administration of folic acid can reduce the occurrence of congenital cardiac septal defects (CCSDs). The vital roles of folate exhibits in three ways: the unique methyl donor for DNA expression regulation, the de novo biosynthesis of purine and pyrimidine for DNA construction, and the serum homocysteine removal. Thymidylate synthase (TYMS) is the solo catalysis enzyme for the de novo synthesis of dTMP, which is the essential precursor of DNA biosynthesis and repair process. To examine the role of TYMS in Congenital Cardiac Septal Defects (CCSDs) risk, we investigated whether genetic polymorphisms in the TYMS gene associated with the CCSDs in a Han Chinese population. Method Polymorphisms in the noncoding region of TYMS were identified via direct sequencing in 32 unrelated individuals composed of half CCSDs and half control subjects. Nine SNPs and two insertion/deletion polymorphisms were genotyped from two independent case-control studies involving a total of 529 CCSDs patients and 876 healthy control participants. The associations were examined by both single polymorphism and haplotype tests using logistic regression. Result We found that TYMS polymorphisms were not related to the altered CCSDs risk, and even to the changed risk of VSDs subgroup, when tested in both studied groups separately or in combination. In the haplotype analysis, there were no haplotypes significantly associated with risks for CCSDs either. Conclusion Our results show no association between common genetic polymorphisms of the regulatory region of the TYMS gene and CCSDs in the Han Chinese population. PMID:22384047

  18. 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

  19. Genetic polymorphism of microsatellite dna in two populations of northern sheatfish (Silurus soldatovi).

    PubMed

    Quan, Ying-Chun; Sun, Xiao-Wen; Liang, Li-Qun

    2006-10-01

    In this article, population variations and genetic structures of two populations of northern sheatfish (Silurus soldatovi) were analyzed using 24 microsatellite loci enriched from southern catfish (S. meriaionalis Chen) by magnetic beads. Gene frequency (P), observed heterozygosity (Ho), expected heterozygosity (He), polymorphism information contents (PIC), and number of effective alleles (Ne) were determined. One population was wild, ripe individuals collected from Heilongjiang River (HNS); the other was cultured fry collected from Songhuajiang River (SNS). The Hardy-Weinberg equilibrium (HWE) was tested by the genetic departure index (d). The coefficient of gene differentiation G(ST) and Phi(ST) by AMOVA (Analysis of Molecular Variety) was imputed using Arlequin software in this study. In addition, a phylogenetic tree was constructed by UPGMA method based on the pairwise Nei's standard distances using PHYLIP. A total of 1,357 fragments with sizes ranging between 102 bp and 385 bp were acquired by PCR amplifications. The average number of alleles of the two populations was 8.875. Results indicated that these microsatellite loci were highly polymorphic and could be used as genetic markers. The mean values of the parameters P, Ho, He, PIC, and Ne were 0.165, 0.435, 0.758, 0.742, and 5.019 for HNS and 0.147, 0.299, 0.847, 0.764, and 5.944 for SNS, respectively. Although there were differences, there were no significant differentiations except for the locus HLJcf37. These populations to a certain extent deviated from HWE, such as excessive and deficient heterozygote numbers. The value of G(ST) was 0.078 and above 98% of the variation were differences among individuals within the population, so the variation between populations was insignificant. Cluster analysis also showed that the relationships among individuals were very close. In conclusion, the microsatellite markers that were developed through this study are useful for genetic analysis and the genetic culture

  20. Analysis of genetic polymorphisms associated with leukoaraiosis in the southern Chinese population

    PubMed Central

    Huang, Wen-Qing; Ye, Hui-Ming; Li, Fang-Fang; Yi, Ke-Hui; Zhang, Ya; Cai, Liang-Liang; Lin, Hui-Nuan; Lin, Qing; Tzeng, Chi-Meng

    2016-01-01

    Abstract Leukoaraiosis (LA) is a frequent neuroimaging finding commonly observed on brain MRIs of elderly people with prevalence ranging from 50% to 100%. Multiple susceptibility genes or genetic risk factors for LA have been identified in subjects of European descent. Here, we report the first replication study on several common and novel genetic variations in the Chinese population. In this study, a total of 244 subjects (201 LA patients and 43 controls) were enrolled according to our new and strict definition for LA. Subsequently, 6 genetic variants at 5 genes, rs3744028 in TRIM65, rs1055129 in TRIM47, rs1135889 in FBF1, rs1052053 in PMF1, and rs1801133 (C677T) and rs1801131(A1298C) in MTHFR, were selected for genotyping using polymerase chain reaction (PCR)-based pyrosequencing and restriction fragment length polymorphism (RFLP) together with capillary electrophoresis (CE) and agarose gel electrophoresis. Finally, Pearson's χ2 and multivariate logistic regression tests were used to examine the associations between the genotypes and LA. Among these candidate polymorphisms, except for rs1052053 and rs1801131, rs1135889 (P = 0.012) showed significant associations with LA in the dominant model, and the other 3 SNPs, rs3744028 (P = 0.043), rs1055129 (P = 0.038), and rs1801133 (P = 0.027), showed significant associations with LA in the recessive model. However, these differences no longer remained significant after adjusting for age, gender, hypertension, and diabetes mellitus and applying Bonferroni correction or Sidak correction for multiple testing. These results suggest that the above-mentioned genetic variants are not associated with LA risk. In summary, the study did not replicate the susceptibility of rs3744028, rs1055129, and rs1135889 at the Chr17q25 locus for LA nor did it find any other significant results for rs1052053, rs1801133, and rs1801131 in the Chinese population. It strongly indicated the ethnic differences in the genetics of LA

  1. Genetic polymorphisms in the MMP-7 gene and breast cancer survival

    PubMed Central

    Beeghly-Fadiel, Alicia; Shu, Xiao-ou; Long, Jirong; Li, Chun; Cai, Qiuyin; Cai, Hui; Gao, Yu-Tang; Zheng, Wei

    2008-01-01

    Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with broad substrate specificity. Its expression has been shown to be associated with tumor invasion, metastasis, and survival for a variety of cancers. We systematically evaluated single nucleotide polymorphisms (SNPs) in this gene in relation to breast cancer survival in a large follow-up study. This study included 1,079 breast cancer patients, recruited from 1996 to 1998, that were followed for a median of 7.1 years as part of the Shanghai Breast Cancer Study (SBCS). Eleven SNPs, including two known functional promoter SNPs, were analyzed using the Affymetrix Targeted Genotyping System. Associations with survival were evaluated by Cox proportional hazards regression and Kaplan-Meier functions. Statistically significant associations with disease-free (DFS) and/or overall survival (OS) were found for 5 polymorphisms; these associations were explained primarily by two SNPs (rs11568818 and rs11225297) that were in high linkage disequilibrium (LD) with the others. Patients homozygous for the rs11568818 rare allele (G) had a significantly worse prognosis (OS HR: 6.7, 95% CI: 2.4–18.6) than patients homozygous for the common allele (A). Significantly improved survival was seen for patients with the rs11225297 T allele, and this association occurred in a dose-response manner; patients with AT (OS HR: 0.7, 95% CI: 0.5–0.9) and TT (OS HR: 0.3, 95% CI: 0.1–0.8) fared better than patients with AA (p-value for trend: 0.001). Thus, common MMP-7 genetic polymorphisms were found to be significant determinants of survival among Chinese women with breast cancer. PMID:18798254

  2. Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients

    PubMed Central

    2012-01-01

    Background The enzymes of the cytochrome P450 family (CYPs) play an important role in the metabolism of a great variety of anticancer agents; therefore, polymorphisms in genes encoding for metabolizing enzymes and drugs transporters can affect drug efficacy and toxicity. Methods The genetic polymorphisms of cytochrome P450 were studied in 395 patients with breast cancer by RLFP analysis. Results Here, we studied the association of functionally significant variant alleles of CYP3A4, CYP3A5, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 with the clinical response to neoadjuvant chemotherapy in breast cancer patients. A significant correlation was observed between the CYP2C9*2 polymorphism and chemotherapy resistance (OR = 4.64; CI 95% = 1.01 – 20.91), as well as between CYP2C9*2 heterozygotes and chemotherapy resistance in women with nodal forms of breast cancer and a cancer hereditary load (OR = 15.50; CI 95% = 1.08 – 826.12) when the potential combined effects were examined. No significant association between chemotherapy resistance and the other examined genotypes and the potential combined clinical and tumour-related parameters were discovered. Conclusion In conclusion, CYP2C9*2 was associated with neoadjuvant chemotherapy resistance (OR = 4.64; CI 95% = 1.01 – 20.91) in the population of interest. PMID:22702493

  3. 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

  4. Additive Genetic Risk from Five Serotonin System Polymorphisms Interacts with Interpersonal Stress to Predict Depression

    PubMed Central

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

    2016-01-01

    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 (GxE). 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 GxE predicting depression, we created an additive multilocus profile score from five serotonin system polymorphisms (one each in the genes HTR1A, HTR2A, HTR2C, and two in TPH2). Analyses focused on two forms of interpersonal stress as environmental risk factors. Using five 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 (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 GxE 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 GxE 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

  5. Analysis of Polymorphisms and Haplotype Structure of the Human Thymidylate Synthase Genetic Region: A Tool for Pharmacogenetic Studies

    PubMed Central

    Ghosh, Soma; Hossain, M. Zulfiquer; Borges, Michael; Goggins, Michael G.; Ingersoll, Roxann G.; Eshleman, James R.; Klein, Alison P.; Kern, Scott E.

    2012-01-01

    5-fluorouracil (5FU), a widely used chemotherapeutic drug, inhibits the DNA replicative enzyme, thymidylate synthase (Tyms). Prior studies implicated a VNTR (variable numbers of tandem repeats) polymorphism in the 5′-untranslated region (5′-UTR) of the TYMS gene as a determinant of Tyms expression in tumors and normal tissues and proposed that these VNTR genotypes could help decide fluoropyrimidine dosing. Clinical associations between 5FU-related toxicity and the TYMS VNTR were reported, however, results were inconsistent, suggesting that additional genetic variation in the TYMS gene might influence Tyms expression. We thus conducted a detailed genetic analysis of this region, defining new polymorphisms in this gene including mononucleotide (poly A:T) repeats and novel single nucleotide polymorphisms (SNPs) flanking the VNTR in the TYMS genetic region. Our haplotype analysis of this region used data from both established and novel genetic variants and found nine SNP haplotypes accounting for more than 90% of the studied population. We observed non-exclusive relationships between the VNTR and adjacent SNP haplotypes, such that each type of VNTR commonly occurred on several haplotype backgrounds. Our results confirmed the expectation that the VNTR alleles exhibit homoplasy and lack the common ancestry required for a reliable marker of a linked adjacent locus that might govern toxicity. We propose that it may be necessary in a clinical trial to assay multiple types of genetic polymorphisms in the TYMS region to meaningfully model linkage of genetic markers to 5FU-related toxicity. The presence of multiple long (up to 26 nt), polymorphic monothymidine repeats in the promoter region of the sole human thymidylate synthetic enzyme is intriguing. PMID:22496803

  6. Evolution of a genetic polymorphism with climate change in a Mediterranean landscape

    PubMed Central

    Thompson, John; Charpentier, Anne; Bouguet, Guillaume; Charmasson, Faustine; Roset, Stephanie; Buatois, Bruno; Vernet, Philippe; Gouyon, Pierre-Henri

    2013-01-01

    Many species show changes in distribution and phenotypic trait variation in response to climatic warming. Evidence of genetically based trait responses to climate change is, however, less common. Here, we detected evolutionary variation in the landscape-scale distribution of a genetically based chemical polymorphism in Mediterranean wild thyme (Thymus vulgaris) in association with modified extreme winter freezing events. By comparing current data on morph distribution with that observed in the early 1970s, we detected a significant increase in the proportion of morphs that are sensitive to winter freezing. This increase in frequency was observed in 17 of the 24 populations in which, since the 1970s, annual extreme winter freezing temperatures have risen above the thresholds that cause mortality of freezing-sensitive morphs. Our results provide an original example of rapid ongoing evolutionary change associated with relaxed selection (less extreme freezing events) on a local landscape scale. In species whose distribution and genetic variability are shaped by strong selection gradients, there may be little time lag associated with their ecological and evolutionary response to long-term environmental change. PMID:23382198

  7. Investigation of the genetic diversity among native Turkish sheep breeds using mtDNA polymorphisms.

    PubMed

    Oner, Yasemin; Calvo, Jorge Hugo; Elmaci, Cengiz

    2013-04-01

    A total of 135 unrelated sheep from nine Turkish native sheep breeds (Daglıc, Kivircik, Imroz, Chios, Morkaraman, Ivesi, Hemsin, Karayaka and Akkaraman) were investigated to determinate the maternal genetic diversity using a sequence of a 531-bp segment of the mtDNA control region. Analysis of the mtDNA control region sequence revealed 63 haplotypes and 53 polymorphic sites. Haplotype diversity, nucleotide diversity and the average number of nucleotide differences were estimated to be 0.9496 ± 0.011, 0.01407 ± 0.00060 and 7.456, respectively. The sequence analysis also revealed high level of genetic diversity among the native Turkish breeds. These breeds were grouped into three major maternal haplogroups: A, B and C, with one animal belonging from the Akkaraman breed to the rare haplogroup E. Irregular shape of mismatch distribution of haplogroup C could be an indicator that haplogroup C may represent different haplogroups. Contrarily to previous studies carried out on Turkish native breeds, majority of animals grouped in haplogroup A in the present study. This result and the irregular shape of mismatch curve of haplogroup C indicate that genetic structure of Turkish native sheep breeds could be more complicated than it is thought.

  8. Genetic Polymorphisms at TIMP3 Are Associated with Survival of Adenocarcinoma of the Gastroesophageal Junction

    PubMed Central

    Bashash, Morteza; Shah, Amil; Hislop, Greg; Treml, Martin; Bretherick, Karla; Janoo-Gilani, Rozmin; Leach, Stephen; Le, Nhu

    2013-01-01

    The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ) makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs) at four TIMP (TIMP1-4) and three MMP genes (MMP2, MMP7 and MMP9) were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312) were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients. PMID:23527119

  9. Genetic relationships among Aedes aegypti (Diptera: Culicidae) populations from Argentina using random amplified polymorphic DNA polymerase chain reaction markers.

    PubMed

    de Sousa, G B; Blanco, A; Gardenal, C N

    2001-05-01

    Random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) polymorphism was analyzed in five Aedes aegypti (L.) populations from Argentina and one from Puerto Rico to estimate levels of intraspecific polymorphism and genetic relatedness. Allele frequencies were estimated assuming that RAPD products segregate as dominants and that genotype frequencies at those loci are in Hardy-Weinberg equilibrium. Mean expected heterozygosity (He) was 0.350; F(ST) values were significant at all loci except one, supporting the usefulness of the fragments used here to discriminate among populations. Rogers' genetic similarity between samples ranged from 0.806 to 0.621. The population from Puerto Rico was the most different from the Argentina populations. Considering that Ae. aegypti eggs, larvae, and pupae can be transported easily, relationships among the Argentinian populations may reflect the routes and intensity of commercial transit. PMID:11372960

  10. 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

    2014-12-04

    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.

  11. Integrating Monitoring and Genetic Methods To Infer Historical Risks of PCBs and DDE to Common and Roseate Terns Nesting Near the New Bedford Harbor Superfund Site (Massachusetts, USA).

    PubMed

    Nacci, Diane E; Hahn, Mark E; Karchner, Sibel I; Jayaraman, Saro; Mostello, Carolyn; Miller, Kenneth M; Blackwell, Carma Gilchrist; Nisbet, Ian C T

    2016-09-20

    Common and roseate terns are migratory piscivorous seabirds with major breeding colonies within feeding range of the polychlorinated biphenyl (PCB)-contaminated New Bedford Harbor (NBH, MA, USA) Superfund site. Our longitudinal study shows that before PCB discharges into NBH ceased (late 1970s), tern eggs had very high but variable PCB concentrations. However, egg concentrations of PCBs as well as DDE (1,1-bis(p-chlorophenyl)-2,2-dichloroethene), the degradation product of the ubiquitous global contaminant DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane), have since declined. Rate constants for temporal decline of PCB congeners in tern eggs varied inversely with log10KOW (n-octanol-water partition coefficient), shifting egg congener patterns away from those characterizing NBH sediment. To estimate the toxic effects on tern eggs of PCB dioxin-like congener (DLC) exposures, we extrapolated published laboratory data on common terns to roseate terns by characterizing genetic and functional similarities in species aryl hydrocarbon receptors (AHRs), which mediate DLC sensitivity. Our assessment of contaminant risks suggests that terns breeding near NBH were exposed historically to toxic levels of PCBs and DDE; however, acute effects on tern egg development have become less likely since the 1970s. Our approach demonstrates how comparative genetics at target loci can effectively increase the range of inference for chemical risk assessments from tested to untested and untestable species. PMID:27564328

  12. Genetic Association of PTPN22 Polymorphisms with Autoimmune Hepatitis and Primary Biliary Cholangitis in Japan

    PubMed Central

    Umemura, Takeji; Joshita, Satoru; Yamazaki, Tomoo; Komatsu, Michiharu; Katsuyama, Yoshihiko; Yoshizawa, Kaname; Tanaka, Eiji; Ota, Masao

    2016-01-01

    Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are liver-specific autoimmune conditions that are characterized by chronic hepatic damage and often lead to cirrhosis and hepatic failure. Specifically, the protein tyrosine phosphatase N22 (PTPN22) gene encodes the lymphoid protein tyrosine phosphatase, which acts as a negative regulator of T-cell receptor signaling. A missense single nucleotide polymorphism (SNP) (rs2476601) in PTPN22 has been linked to numerous autoimmune diseases in Caucasians. In the present series, nine SNPs in the PTPN22 gene were analyzed in 166 patients with AIH, 262 patients with PBC, and 322 healthy controls in the Japanese population using TaqMan assays. Although the functional rs3996649 and rs2476601 were non-polymorphic in all subject groups, the frequencies of the minor alleles at rs1217412, rs1217388, rs1217407, and rs2488458 were significantly decreased in AIH patients as compared with controls (all Pc < 0.05). There were no significant relationships with PTPN22 SNPs in PBC patients. Interestingly, the AAGTCCC haplotype was significantly associated with resistance to both AIH (odds ratio [OR] = 0.58, P = 0.0067) and PBC (OR = 0.58, P = 0.0048). SNPs in the PTPN22 gene may therefore play key roles in the genetic resistance to autoimmune liver disease in the Japanese. PMID:27406031

  13. Single-strand conformation polymorphism analysis of genetic variation in Labiostrongylus longispicularis from kangaroos.

    PubMed

    Huby-Chilton, F; Beveridge, I; Gasser, R B; Chilton, N B

    2001-06-01

    Single-strand conformation polymorphism (SSCP) analysis was employed to screen for sequence heterogeneity in the second internal transcribed spacer (ITS-2) of ribosomal (r) DNA of Labiostrongylus longispicularis, a parasitic strongylid nematode occuring in some species of kangaroo in different geographical regions of Australia. The results showed that most of the nematodes screened had different SSCP profiles, which were subsequently shown to correspond to polymorphisms and/or an indel in the ITS-2 sequence. These variable sites related mainly to unpaired regions of the predicted secondary structure of the precursor rRNA molecule. SSCP profiles could be used to distinguish L. longispicularis in Macropus robustus robustus (New South Wales) from L. longispicularis in Macropus robustus erubescens and Macropus rufus (South Australia). This difference corresponded to a transversional change in the ITS-2 sequence at alignment position 82. The study demonstrated clearly the effectiveness of SSCP analysis for future large-scale population genetic studies of L. longispicularis in order to test the hypothesis that L. longispicularis from different geographical regions represents multiple sibling species.

  14. 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

  15. Genetic polymorphisms of the RAS-cytokine pathway and chronic kidney disease

    PubMed Central

    Kanetsky, Peter; Raj, Dominic

    2008-01-01

    Chronic kidney disease (CKD) in children is irreversible. It is associated with renal failure progression and atherosclerotic cardiovascular (CV) abnormalities. Nearly 60% of children with CKD are affected since birth with congenital or inherited kidney disorders. Preliminary evidence primarily from adult CKD studies indicates common genetic risk factors for CKD and atherosclerotic CV disease. Although multiple physiologic pathways share common genes for CKD and CV disease, substantial evidence supports our attention to the renin angiotensin system (RAS) and the interlinked inflammatory cascade because they modulate the progressions of renal and CV disease. Gene polymorphisms in the RAS-cytokine pathway, through altered gene expression of inflammatory cytokines, are potential factors that modulate the rate of CKD progression and CV abnormalities in patients with CKD. For studying such hypotheses, the cooperative efforts among scientific groups and the availability of robust and affordable technologies to genotype thousands of single nucleotide polymorphisms (SNPs) across the genome make genome-wide association studies an attractive paradigm for studying polygenic diseases such as CKD. Although attractive, such studies should be interpreted carefully, with a fundamental understanding of their potential weaknesses. Nevertheless, whole-genome association studies for diabetic nephropathy and future studies pertaining to other types of CKD will offer further insight for the development of targeted interventions to treat CKD and associated atherosclerotic CV abnormalities in the pediatric CKD population. PMID:18481112

  16. Genetic polymorphisms of CYP2D6 oxidation in patients with systemic lupus erythematosus

    PubMed Central

    Skrętkowicz, Jadwiga; Barańska, Małgorzata; Kaczorowska, Anna; Rychlik-Sych, Mariola

    2011-01-01

    Introduction Systemic lupus erythematosus (SLE) is a complex, multifactor autoimmune disease. The studies on aetiopathogenesis of autoimmune diseases focus on the impact the genetically conditioned impairment of xenobiotic metabolism may exert. The knowledge of oxidation polymorphism in the course of SLE may be helpful in choosing more efficient and safer therapy. We determined whether there was an association between susceptibility to SLE and particularly to CYP2D6 genotypes. Material and methods The study was carried out in 60 patients with SLE and 129 healthy volunteers and all the subjects were of Polish origin. The samples were analysed for two major defective alles for CYP2D6 – CYP2D6*3 and CYP2D6*4 and one wild -type allele CYP2D6*1-by the polymerase chain reaction fragment length polymorphism (PCR-RFLP) metod with DNA extracted from peripheral blood. Results No statistically significant differences in the incidence of CYP2D6 genotypes between the studied groups were found (p = 0.615). Risk (OR) of SLE development was 1.03 for the carriers of CYP2D6*3 allele and 1.48 for the subjects with CYP2D6*4 allele; but it was not statistically significant. Conclusions Increased occurrence of mutant alleles of the CYP2D6 gene in SLE patients and the calculated OR values could suggest the effect of these mutations on increased SLE development. PMID:22291833

  17. Investigating the genetic polymorphism of sheep milk proteins: a useful tool for dairy production.

    PubMed

    Selvaggi, Maria; Laudadio, Vito; Dario, Cataldo; Tufarelli, Vincenzo

    2014-12-01

    Sheep is the second most important dairy species after cow worldwide, and especially in the Mediterranean and Middle East regions. In some countries, the difficult environmental conditions require a peculiar adaptation and, in these contexts, sheep are able to provide higher quality protein than cattle. In the least-developed countries, the amount of dairy sheep and ovine milk production is progressively increasing. In order to improve dairy productions, in particular those with local connotations, it is necessary to obtain in-depth information regarding milk quality and rheological properties. The genetic polymorphisms of milk proteins are often associated with quantitative and qualitative parameters in milk and are potential candidate markers that should be included in breeding strategies similar to those already available for cattle. Due to the current and growing interest in this topic and considering the large amount of new information, the aim of this study was to review the literature on sheep milk protein polymorphisms with a particular emphasis on recent findings in order to give scientists useful support. Moreover, the effects of different protein variants on milk yield and composition are discussed.

  18. Structure and population genetics of the breakpoints of a polymorphic inversion in Drosophila subobscura.

    PubMed

    Papaceit, Montserrat; Segarra, Carmen; Aguadé, Montserrat

    2013-01-01

    Drosophila subobscura is a paleartic species of the obscura group with a rich chromosomal polymorphism. To further our understanding on the origin of inversions and on how they regain variation, we have identified and sequenced the two breakpoints of a polymorphic inversion of D. subobscura--inversion 3 of the O chromosome--in a population sample. The breakpoints could be identified as two rather short fragments (∼300 bp and 60 bp long) with no similarity to any known transposable element family or repetitive sequence. The presence of the ∼300-bp fragment at the two breakpoints of inverted chromosomes implies its duplication, an indication of the inversion origin via staggered double-strand breaks. Present results and previous findings support that the mode of origin of inversions is neither related to the inversion age nor species-group specific. The breakpoint regions do not consistently exhibit the lower level of variation within and stronger genetic differentiation between arrangements than more internal regions that would be expected, even in moderately small inversions, if gene conversion were greatly restricted at inversion breakpoints. Comparison of the proximal breakpoint region in species of the obscura group shows that this breakpoint lies in a small high-turnover fragment within a long collinear region (∼300 kb).

  19. 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

  20. 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 ...

  1. Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX

    PubMed Central

    Kim, Mi-Jung; Han, Sae-Won; Lee, Dae-Won; Cha, Yongjun; Lee, Kyung-Hun; Kim, Tae-Yong; Oh, Do-Youn; Kim, Se Hyung; Im, Seock-Ah; Bang, Yung-Jue; Kim, Tae-You

    2016-01-01

    Purpose Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. Materials and Methods Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. Results Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, –42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. Conclusion Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly. PMID:26790967

  2. 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 ...

  3. The association between interleukin-4 -590C/T genetic polymorphism, IL-4 serum level, and advanced endometriosis

    PubMed Central

    Malutan, Andrei M.; Drugan, Tudor; Ciortea, Razvan; Mihu, Dan

    2016-01-01

    Aim of the study Aim of the study was to investigate interleukin (IL)-4 serum levels in patients with advanced endometriosis and whether IL-4 promoter region (-590C/T) genetic polymorphism is involved in genetic susceptibility to endometriosis. Material and methods IL-4 serum levels and IL-4 -590C/T genetic polymorphism were determined for 80 patients with advanced endometriosis and 85 healthy fertile women using a multiplex cytokine kit, with a Luminex 200 system; high molecular weight genomic DNA was extracted from peripheral blood leukocytes, and further analyzed by PCR amplification and restriction fragment length polymorphism (PCR-PFLP). The relationship between IL-4 serum levels, genotypes and haplotypes and the presence of endometriosis was explored. Results Interleukin 4 serum levels were significantly higher in the endometriosis group compared to controls (138,459 compared to 84,710, p < 0.001). No significant difference was observed in IL-4 serum levels between genotypes. There were no differences in IL-4 -590C/T genotypes and allele frequencies between control women and patients with endometriosis (χ2 = 0.496, and χ2 = 0.928, OR = 1.3636, CI: 0.725-2.564). Conclusions The results suggest that in patients with advanced stages of endometriosis there is a higher serum level of IL-4, and that this value, or the presence of the disease, is not influenced by the presence of IL-4 -590C/T genetic polymorphism. PMID:27536203

  4. 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.

  5. Estimating the genetic variance of major depressive disorder due to all single nucleotide polymorphisms.

    PubMed

    Lubke, Gitta H; Hottenga, Jouke Jan; Walters, Raymond; Laurin, Charles; de Geus, Eco J C; Willemsen, Gonneke; Smit, Jan H; Middeldorp, Christel M; Penninx, Brenda W J H; Vink, Jacqueline M; Boomsma, Dorret I

    2012-10-15

    Genome-wide association studies of psychiatric disorders have been criticized for their lack of explaining a considerable proportion of the heritability established in twin and family studies. Genome-wide association studies of major depressive disorder in particular have so far been unsuccessful in detecting genome-wide significant single nucleotide polymorphisms (SNPs). Using two recently proposed methods designed to estimate the heritability of a phenotype that is attributable to genome-wide SNPs, we show that SNPs on current platforms contain substantial information concerning the additive genetic variance of major depressive disorder. To assess the consistency of these two methods, we analyzed four other complex phenotypes from different domains. The pattern of results is consistent with estimates of heritability obtained in twin studies carried out in the same population.

  6. 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.

  7. 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

  8. Catecholamine Storage Vesicles: Role of Core Protein Genetic Polymorphisms in Hypertension

    PubMed Central

    Zhang, Kuixing; Chen, Yuqing; Wen, Gen; Mahata, Manjula; Rao, Fangwen; Fung, Maple M.; Vaingankar, Sucheta; Biswas, Nilima; Gayen, Jiaur R.; Friese, Ryan S.; Mahata, Sushil K.; Hamilton, Bruce A.

    2010-01-01

    Hypertension is a complex trait with deranged autonomic control of the circulation. The sympathoadrenal system exerts minute-to-minute control over cardiac output and vascular tone. Catecholamine storage vesicles (or chromaffin granules) of the adrenal medulla contain remarkably high concentrations of chromogranins/secretogranins (or “granins”), catecholamines, neuropeptide Y, adenosine triphosphate (ATP), and Ca2+. Within secretory granules, granins are co-stored with catecholamine neurotransmitters and co-released upon stimulation of the regulated secretory pathway. The principal granin family members, chromogranin A (CHGA), chromogranin B (CHGB), and secretogranin II (SCG2), may have evolved from shared ancestral exons by gene duplication. This article reviews human genetic variation at loci encoding the major granins and probes the effects of such polymorphisms on blood pressure, using twin pairs to probe heritability and individuals with the most extreme blood pressure values in the population to study hypertension. PMID:21104344

  9. 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 virus–host relationship. PMID:21896819

  10. Genetic polymorphisms in obesity-related genes and endometrial cancer risk

    PubMed Central

    Chen, Xiaoli; Xiang, Yong-Bing; Long, Ji-Rong; Cai, Hui; Cai, Qiuyin; Cheng, Jiarong; Wen, Wanqing; Gao, Yu-Tang; Zheng, Wei; Shu, Xiao-Ou

    2011-01-01

    Background Obesity is associated with circulating levels of adiponectin and leptin and endometrial cancer risk. Little is known about whether single nucleotide polymorphisms (SNPs) in the genes that encode adiponectin (ADIPOQ), leptin (LEP), adiponectin receptor 1 (ADIPOR1), adiponectin receptor 2 (ADIPOR2), and leptin receptor (LEPR) are associated with endometrial cancer. Methods We selected 87 tagging SNPs to capture common genetic variants in these five genes. These SNPs were evaluated in 1,028 endometrial cancer cases and 1,932 community controls recruited from Chinese women. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Three of the 10 SNPs evaluated in the ADIPOQ gene were significantly associated with reduced cancer risk. The OR for women homozygous for the minor allele (A/A) for rs3774262 was 0.68 (95% CI: 0.48-0.97) compared with women homozygous for the major allele (G/G). Similar results were found for SNPs rs1063539 and rs12629945 in ADIPOQ, which were in linkage disequilibrium with rs3774262. These associations became non-significant after Bonferroni correction was applied. Controls with the minor allele A at rs3774262 had lower weight, waist circumference, hip circumference, and BMI than controls with the major allele G (all P<0.05). Women homozygous for the minor allele (T/T) of rs2071045 in the LEP gene also had significantly lower risk (OR=0.70 (0.54-0.90)) than women homozygous for the major allele (C/C). No other SNPs in the LEP, ADIPOR1, ADIPOR2, or LEPR genes were found to be associated with cancer risk. Conclusions Although a chance finding cannot be ruled out, the consistency of findings for gene-endometrial cancer risk and gene-obesity measurements suggests that genetic polymorphisms in the ADIPOQ genes may play a role in endometrial cancer development. PMID:22038736

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

    PubMed

    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

  12. 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

  13. Genetic polymorphisms of the interleukin-1 gene and early marginal bone loss around endosseous dental implants.

    PubMed

    Shimpuku, Hitomi; Nosaka, Yasuhiro; Kawamura, Tatsuya; Tachi, Yoichi; Shinohara, Mitsuko; Ohura, Kiyoshi

    2003-08-01

    Dental implant surgery commonly proceeds in two stages. It is generally accepted that bone loss around implants does not occur at stage-II surgery because implants do not receive mechanical loading. However, early marginal bone loss around implants occasionally does occur during the healing period. Genetic polymorphisms in the interleukin-1 (IL-1) gene have been reported to be important for bone homeostasis and susceptibility to bone disease. We therefore investigated whether the idiopathic early marginal bone loss around implants is related to polymorphisms in the IL-1 gene. We performed a case-control study. Patients demonstrating marginal bone loss around implants at stage-II surgery were designated as the 'marginal bone loss (+)' group and those without bone loss as the 'marginal bone loss (-)' group. Polymorphisms of the IL-1alpha and IL-1beta genes (IL-1A-889, IL-1B-511 and IL-1B+3954) were detected by restriction fragment length polymorphism using NcoI, AvaI and TaqI after polymerase chain reactions. A total of 251 implants were placed in 39 patients. Marginal bone loss was observed in 36 implants. The patients with IL-1B-511 2/2 genotype exhibited a significantly higher occurrence of marginal bone loss than those with IL-1B-511 1/1 or 1/2 genotypes (OR=5.63; 95% CI=1.20-26.42; P=0.033). Multiple logistic regression analyses showed a markedly increased odds ratio (OR=10.86; 95% CI=1.64-71.90) in IL-1B-511 2/2 genotype carriers, while ORs of the other risk factors for bone loss, such as age, smoking status, post-menopausal women and bone quality, remained between 0.44 and 6.20. There was no significant difference in the distributions of the IL-1B+3954 and IL-1 A-889 genotypes between cases and controls. These data suggest that the IL-1B-511 2/2 genotype has a significant association with the incidence of early marginal bone loss around endosseous implants. PMID:12869004

  14. Association of genetic polymorphisms of GALNT3 and VDR with osteoporosis in postmenopausal women

    PubMed Central

    Wang, Guorong; Yang, Junhua; Zheng, Xun; Zhu, Jiahua; Shi, Wangqing; Chen, Aimin; Chen, Guoxian; Zhou, Fangye

    2016-01-01

    The correlation of genetic polymorphisms of GALNT3 and vitamin D receptor (VDR) with osteoporosis in postmenopausal women was investigated. A total of 1,212 cases of postmenopausal patients diagnosed with osteoporosis (observation group) and 404 cases of postmenopausal women without osteoporosis (control group) were selected. Dual-energy X-ray absorptiometry was used for measurement of bone mineral density (BMD) of lumbar vertebrae L2–4, proximal femoral neck and total hip, and classifications were made. TaqMan genotyping technology was employed to examine tag single-nucleotide polymorphism (tagSNP) of GALNT3 and VDR and the correlation of tagSNP with bone turnover markers (BTMs) and serum calcium and phosphorous levels was analyzed. The multiple logistic regression analysis was used to screen risk factors for osteoporosis. A comparison of age and menopause time of the two groups, yielded no statistical significance difference (P>0.05). BMD and T values of the lumbar vertebrae, femoral neck and total hip in the observation group were significantly lower than those in the control group, and the differences were statistically significant (P<0.05). A comparison of the degree of osteoporosis, yielded statistically significant differences (P<0.05). The proportion of tagSNP of 5 loci in GALNT3 and 3 loci in VDR in the observation group was significantly higher than that in the control group, and the differences were of statistical significance (P<0.05). Levels of 25-OHD3, β-CTX, P1NP and serum calcium in the observation group were lower than those in the control group and the level of serum phosphorus in the observation group was higher than that in the control group, and all of these results were statistically significant (P<0.05). The result of the correlation analysis revealed that rs1425000 and rs757343 were negatively correlated with BTM and serum calcium and phosphorus levels (P<0.05). The result of the regression analysis revealed that 8 tagSNPs were

  15. Association of genetic polymorphisms of GALNT3 and VDR with osteoporosis in postmenopausal women

    PubMed Central

    Wang, Guorong; Yang, Junhua; Zheng, Xun; Zhu, Jiahua; Shi, Wangqing; Chen, Aimin; Chen, Guoxian; Zhou, Fangye

    2016-01-01

    The correlation of genetic polymorphisms of GALNT3 and vitamin D receptor (VDR) with osteoporosis in postmenopausal women was investigated. A total of 1,212 cases of postmenopausal patients diagnosed with osteoporosis (observation group) and 404 cases of postmenopausal women without osteoporosis (control group) were selected. Dual-energy X-ray absorptiometry was used for measurement of bone mineral density (BMD) of lumbar vertebrae L2–4, proximal femoral neck and total hip, and classifications were made. TaqMan genotyping technology was employed to examine tag single-nucleotide polymorphism (tagSNP) of GALNT3 and VDR and the correlation of tagSNP with bone turnover markers (BTMs) and serum calcium and phosphorous levels was analyzed. The multiple logistic regression analysis was used to screen risk factors for osteoporosis. A comparison of age and menopause time of the two groups, yielded no statistical significance difference (P>0.05). BMD and T values of the lumbar vertebrae, femoral neck and total hip in the observation group were significantly lower than those in the control group, and the differences were statistically significant (P<0.05). A comparison of the degree of osteoporosis, yielded statistically significant differences (P<0.05). The proportion of tagSNP of 5 loci in GALNT3 and 3 loci in VDR in the observation group was significantly higher than that in the control group, and the differences were of statistical significance (P<0.05). Levels of 25-OHD3, β-CTX, P1NP and serum calcium in the observation group were lower than those in the control group and the level of serum phosphorus in the observation group was higher than that in the control group, and all of these results were statistically significant (P<0.05). The result of the correlation analysis revealed that rs1425000 and rs757343 were negatively correlated with BTM and serum calcium and phosphorus levels (P<0.05). The result of the regression analysis revealed that 8 tagSNPs were

  16. 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.; Pérez-Salas, Santiago

    1974-01-01

    We have studied genetic variation at 30–32 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

  17. 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

  18. 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

  19. Marine Oxygen-Deficient Zones Harbor Depauperate Denitrifying Communities Compared to Novel Genetic Diversity in Coastal Sediments.

    PubMed

    Bowen, Jennifer L; Weisman, David; Yasuda, Michie; Jayakumar, Amal; Morrison, Hilary G; Ward, Bess B

    2015-08-01

    Denitrification is a critically important biogeochemical pathway that removes fixed nitrogen from ecosystems and thus ultimately controls the rate of primary production in nitrogen-limited systems. We examined the community structure of bacteria containing the nirS gene, a signature gene in the denitrification pathway, from estuarine and salt marsh sediments and from the water column of two of the world's largest marine oxygen-deficient zones (ODZs). We generated over 125,000 nirS gene sequences, revealing a large degree of genetic diversity including 1,815 unique taxa, the vast majority of which formed clades that contain no cultured representatives. These results underscore how little we know about the genetic diversity of metabolisms underlying this critical biogeochemical pathway. Marine sediments yielded 1,776 unique taxa when clustered at 95 % sequence identity, and there was no single nirS denitrifier that was a competitive dominant; different samples had different highly abundant taxa. By contrast, there were only 39 unique taxa identified in samples from the two ODZs, and 99 % of the sequences belonged to 5 or fewer taxa. The ODZ samples were often dominated by nirS sequences that shared a 92 % sequence identity to a nirS found in the anaerobic ammonium-oxidizing (anammox) genus Scalindua. This sequence was abundant in both ODZs, accounting for 38 and 59 % of all sequences, but it was virtually absent in marine sediments. Our data indicate that ODZs are remarkably depauperate in nirS genes compared to the remarkable genetic richness found in coastal sediments.

  20. Association of BCL2-938C>A genetic polymorphism with glioma risk in Chinese Han population.

    PubMed

    Li, Wei; Qian, Chunfa; Wang, Linxiong; Teng, Hong; Zhang, Li

    2014-03-01

    Glioma is the most common type of primary brain malignancy in adults. The anti-apoptotic protein B-cell lymphoma 2 (BCL2) has been implicated in the pathogenesis of glioma. This study aimed to evaluate the potential association between BCL2-938C>A genetic polymorphism and glioma susceptibility. This case-control study was conducted in Chinese Han populations consisting of 248 glioma cases and 252 cancer-free controls. The BCL2-938C>A genetic polymorphism was detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and verified using DNA sequencing methods. Our data suggested that the genotype/allele of BCL2-938C>A polymorphism were statistically associated with the increased risk of glioma where the risk of glioma for genotype AA or allele A is significantly higher than wild genotype CC (odds ratio (OR) = 2.23, 95% confidence interval (CI) 1.21-4.10, p = 0.009) or allele C (OR = 1.39, 95% CI 1.06-1.82, p = 0.016), respectively. In addition, the BCL2-938AA genotype was significantly more common in patients with glioblastoma and in patients with grade IV glioma. Our findings indicate that the BCL2-938C>A polymorphism is associated with the susceptibility to glioma in Chinese Han populations and might be used as molecular markers for evaluating glioma risk.

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

    PubMed

    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

  2. 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

  3. [Genetic polymorphism of FIBRA,DHFRP2 and ACTBP2 and their forensic application in Yunnan Han population].

    PubMed

    Jing, Qiang; Nie, Sheng-Jie

    2002-09-01

    To investigate the genetic polymorphism of FIBRA,DHFRP2 and ACTBP2 in Yunnan Han population as well as their application in forensic science, EDTA-blood specimens were collected from 200 healthy individuals. The DNA were extracted either by the Chloro form, phenol method or by the Chelex-100 method. The PCR products were analyzed by PAG vertical electrophoresis,following by silver staining. All gene frequencies, discrimination power (DP), exclusion of paternity probability (EPP), heterozygosity (H),polymorphisms information content (PIC),matching probability (PM) as well as the Hardy-Weinberg test were calculated. The obtained data are beneficial in the understanding of population genetics of the three STR loci in Yunnan Han population and the results suggest that these loci are valuable genetic markers for paternity testing and personal identification in forensic science practice.

  4. Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma.

    PubMed

    Giannitrapani, Lydia; Soresi, Maurizio; Balasus, Daniele; Licata, Anna; Montalto, Giuseppe

    2013-04-28

    Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellular carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV co-infected patients show a higher prevalence of the low-producer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC.

  5. 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.

  6. A genetic and biochemical analysis of a polymorphism of bovine alpha S2-casein.

    PubMed

    Grosclaude, F; Joudrier, P; Mahé, M F

    1979-04-01

    Using gel electrophoresis a genetic polymorphism of alpha S2-casein (Cn) was discovered in individual milk samples from 2 bovine breeds of the eastern part of France (Vosgienne and Montbéliarde). The 3 observed phenotypes (Plate 1) are determined by 2 co-dominant alleles at an autosomal locus. The alpha S2-Cn A variant was the only one known up to now in European breeds (reference variant) and alpha S2-Cn D is a new variant, whose bands overlap the beta-casein A band at pH 8.6, and migrate faster than alpha S2-Cn A at pH 3.0. The sequence of the polypeptide chain alpha S2-Cn D differs from that of alpha S2-Cn A by the deletion of a very acidic nonapeptide, which includes a cluster of 3 phosphoseryl residues. Due to the characteristics of the reference sequence, this deletion cannot be exactly located but it involves residues 50-58, or 51-59, or 52-60. A genetic analysis shows that locus alpha S2-Cn is closely linked to the cluster alpha S1-Cn--beta-Cn--kappa-Cn. The 4 casein species are thus synthesized by 4 closely linked loci.

  7. 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

    2016-03-01

    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

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

    PubMed Central

    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

  9. Genetic polymorphism of 14 non-CODIS STR loci for forensic use in southeast China population.

    PubMed

    Shi, Meisen; Yu, Xiaojun; Bai, Rufeng; Shu, Xiji; Zhu, Guanghui; Lv, Junyao; Tu, Youhua

    2008-01-15

    We investigated 14 polymorphic STR loci (D1S2142, D2S1360, D3S1545, D7S1517, D10S2325, D12S391, D13S1492, D14S306, D15S659, D16S3253, D18S1270, D19S253, D20S470, D21S1437) which are not included in the standard sets of forensic loci (CODIS) in a sample of 216 unrelated healthy southeast Chinese individuals. The studied loci were highly informative and did not show departures from Hardy-Weinberg equilibrium. The accumulated powers of discrimination and power of exclusion for the 14 loci were 99.9999999999 and 99.999998%, respectively. No linkage was observed between the 14 loci and the traditional set of STR markers included in commercially available kits (the AmpFLSTR IdentifilerTM 15 System loci). We thus considered the studied 14 STRs are informative and when necessary, can be used as the candidate genetic markers in the study and application in genetics and forensic practice.

  10. Single nucleotide polymorphism array analysis defines a specific genetic fingerprint for well-differentiated cutaneous SCCs.

    PubMed

    Purdie, Karin J; Harwood, Catherine A; Gulati, Abha; Chaplin, Tracy; Lambert, Sally R; Cerio, Rino; Kelly, Gavin P; Cazier, Jean-Baptiste; Young, Bryan D; Leigh, Irene M; Proby, Charlotte M

    2009-06-01

    Cutaneous squamous cell carcinomas (cSCCs) are the second most frequent cancers in fair-skinned populations; yet, because of their genetic heterogeneity, the key molecular events in cSCC tumorigenesis remain poorly defined. We have used single nucleotide polymorphism microarray analysis to examine genome-wide allelic imbalance in 60 cSCCs using paired non-tumor samples. The most frequent recurrent aberrations were loss of heterozygosity at 3p and 9p, observed in 39 (65%) and 45 (75%) tumors, respectively. Microdeletions at 9p23 within the protein tyrosine phosphatase receptor type D (PTPRD) locus were identified in 9 (15%) samples, supporting a tumor suppressor role for PTPRD in cSCC. In addition, microdeletions at 3p14.2 were detected in 3 (5%) cSCCs, implicating the fragile histidine triad (FHIT) gene as a possible target for inactivation. Statistical analysis revealed that well-differentiated cSCCs demonstrated significantly fewer aberrations than moderately and poorly differentiated cSCCs; yet, despite a lower rate of allelic imbalance, some specific aberrations were observed equally frequently in both groups. No correlation was established between the frequency of chromosomal aberrations and immune or human papillomavirus status. Our data suggest that well-differentiated tumors are a genetically distinct subpopulation of cSCC.

  11. Relationship between genetic polymorphisms in the DRD5 gene and paranoid schizophrenia in northern Han Chinese.

    PubMed

    Zhao, Y; Ding, M; Pang, H; Xu, X M; Wang, B J

    2014-03-12

    Dopamine (DA) has been implicated in the pathophysiol-ogy of several psychiatric disorders, including schizophrenia. Thus, genes related to the dopaminergic (DAergic) system are good candidate genes for schizophrenia. One of receptors of the DA receptor system is dopa-mine receptor 5 (DRD5). Single nucleotide polymorphisms (SNPs) in the regulatory regions of DRD5 gene may affect gene expression, influence biosynthesis of DA and underlie various neuropsychiatric disorders re-lated to DA dysfunction. The present study explored the association of SNPs within the DRD5 gene with paranoid schizophrenia in Han Chinese. A total of 176 patients with schizophrenia and 206 healthy controls were genotyped for four DRD5 SNPs (rs77434921, rs2076907, rs6283, and rs1800762). Significant group differences were observed in the allele and genotype frequencies of rs77434921 and rs1800762 and in the frequen-cies of GC haplotypes corresponding to rs77434921-rs1800762. Our find-ings suggest that common genetic variations of DRD5 are likely to con-tribute to genetic susceptibility to paranoid schizophrenia in Han Chinese. Further studies in larger samples are needed to replicate this association.

  12. Inference of Selection Based on Temporal Genetic Differentiation in the Study of Highly Polymorphic Multigene Families

    PubMed Central

    McMullan, Mark; van Oosterhout, Cock

    2012-01-01

    The co-evolutionary arms race between host immune genes and parasite virulence genes is known as Red Queen dynamics. Temporal fluctuations in allele frequencies, or the ‘turnover’ of alleles at immune genes, are concordant with predictions of the Red Queen hypothesis. Such observations are often taken as evidence of host-parasite co-evolution. Here, we use computer simulations of the Major Histocompatibility Complex (MHC) of guppies (Poecilia reticulata) to study the turnover rate of alleles (temporal genetic differentiation, G'ST). Temporal fluctuations in MHC allele frequencies can be ≥≤order of magnitude larger than changes observed at neutral loci. Although such large fluctuations in the MHC are consistent with Red Queen dynamics, simulations show that other demographic and population genetic processes can account for this observation, these include: (1) overdominant selection, (2) fluctuating population size within a metapopulation, and (3) the number of novel MHC alleles introduced by immigrants when there are multiple duplicated genes. Synergy between these forces combined with migration rate and the effective population size can drive the rapid turnover in MHC alleles. We posit that rapid allelic turnover is an inherent property of highly polymorphic multigene families and that it cannot be taken as evidence of Red Queen dynamics. Furthermore, combining temporal samples in spatial FST outlier analysis may obscure the signal of selection. PMID:22900006

  13. Genetic analysis of the fragile-X mental retardation syndrome with two flanking polymorphic DNA markers

    SciTech Connect

    Oberle, I.; Heilig, R.; Moisan, J.P.; Kloepfer, C.; Mattei, M.G.; Mattei, J.F.; Boue, J.; Froster-Iskenius, U.; Jacobs, P.A.; Lathrop, G.M.; Lalouel, J.M.

    1986-02-01

    The fragile-X mental retardation syndrome, one of the most prevalent chromosome X-linked diseases (approx. = 1 of 2000 newborn males), is characterized by the presence in affected males and in a portion of carrier females of a fragile site at chromosome band Xq27. The authors have performed a linkage analysis in 16 families between the locus for the fragile-X syndrome, FRAXQ27, and two polymorphic DNA markers that correspond to the anonymous probe St14 and to the coagulation factor IX gene F9. The results indicate that the order of loci is centromere-F9-FRAXQ27-St14-Xqter. The estimate of the recombination fraction for the linkage F9-FRAXQ27 is 0.12 and 0.10 for FRAXQ27-St14. Recombination between St14 and F9 does not appear to be significantly different in normal and fragile-X families. The two flanking probes were used for diagnosis of the carrier state and for detection of transmission of the disease through phenotypically normal males. They should also allow first-trimester diagnosis with a reliability of about 98% in 40% of the families. Used in conjunction with the cytogenetic analysis, the segregation studies with both probes should improve the genetic counseling for the fragile-X syndrome and should be useful for the formal genetic analysis of this unique disease.

  14. Genetic polymorphism of the iron-regulatory protein-1 and -2 genes in age-related macular degeneration.

    PubMed

    Synowiec, Ewelina; Pogorzelska, Magdalena; Blasiak, Janusz; Szaflik, Jerzy; Szaflik, Jacek Pawel

    2012-06-01

    Iron can be involved in the pathogenesis of AMD through the oxidative stress because it may catalyze the Haber-Weiss and Fenton reactions converting hydrogen peroxide to free radicals, which can induce cellular damage. We hypothesized that genetic polymorphism in genes related to iron metabolism may predispose individuals to the development of AMD and therefore we checked for an association between the g.32373708 G>A polymorphism (rs867469) of the IRP1 gene and the g.49520870 G>A (rs17483548) polymorphism of the IRP2 gene and AMD risk as well as the modulation of this association by some environmental and life-style factors. Genotypes were determined in DNA from blood of 269 AMD patients and 116 controls by the allele-specific oligonucleotide-restriction fragment length polymorphism and the polymerase chain reaction-restriction fragment length polymorphism. An association between AMD, dry and wet forms of AMD and the G/G genotype of the g.32373708 G>A-IRP1 polymorphism was found (OR 3.40, 4.15, and 2.75). On the other hand, the G/A genotype reduced the risk of AMD as well as its dry or wet form (OR 0.23, 0.21, 0.26). Moreover, the G allele of the g.49520870 G>A-IRP2 polymorphism increased the risk of the dry form of the disease (OR 1.51) and the A/A genotype and the A allele decreased such risk (OR 0.43 and 0.66). Our data suggest that the g.32373708 G>A-IRP1 and g.49520870 G>A-IRP2 polymorphisms may be associated with increased risk for AMD.

  15. Evaluation of the potential for lymph node metastasis using CRP 1846C>T genetic polymorphism in invasive breast cancer.

    PubMed

    Terata, Kaori; Motoyama, Satoru; Kamata, Shuichi; Hinai, Yudai; Miura, Masatomo; Sato, Yusuke; Yoshino, Kei; Ito, Aki; Imai, Kazuhiro; Saito, Hajime; Minamiya, Yoshihiro

    2014-06-01

    Lymph node status is a key indicator of the best approach to treatment of invasive breast cancer. However, the accuracy with which lymph node metastasis is diagnosed is not currently satisfactory. New and more reliable methods that enable one to know who has a greater potential for lymph node metastasis would be highly desirable. We previously reported that lymph node involvement in esophageal and lung cancer may have a genetic component: C-reactive protein (CRP) 1846C>T genetic polymorphism. Here we examined the diagnostic value of CRP 1846C>T polymorphism for assessing the risk of lymph node metastasis in cases of invasive breast cancer. The study participants were 185 women with invasive breast cancer who underwent curative surgery with lymph node dissection. Using DNA from blood samples and polymerase chain reaction-restriction fragment length polymorphism, the utility of CRP genetic 1846C>T polymorphism (rs1205) for assessing the risk of lymph node metastasis was evaluated. Fifty-two (28 %) patients had lymph node metastasis. After the patients were divided into two groups based on their CRP 1846 genotypes (C/C+C/T and T/T), the clinical characteristics did not differ between the groups, but there was a significantly greater incidence of lymph node metastasis among patients in the T/T group. Moreover, the odds ratio for lymph node involvement in patients carrying the 1846 T/T genotype was more than 2.2 in multivariate logistic regression models. CRP genetic polymorphism may be a novel predictor of the risk of lymph node metastasis in invasive breast cancer.

  16. Different portions of the maize root system host Burkholderia cepacia populations with different degrees of genetic polymorphism.

    PubMed

    Chiarini, L; Giovannelli, V; Bevivino, A; Dalmastri, C; Tabacchioni, S

    2000-02-01

    In order to acquire a better understanding of the spatial and temporal variations of genetic diversity of Burkholderia cepacia populations in the rhizosphere of Zea mays, 161 strains were isolated from three portions of the maize root system at different soil depths and at three distinct plant growth stages. The genetic diversity among B. cepacia isolates was analysed by means of the random amplified polymorphic DNA (RAPD) technique. A number of diversity indices (richness, Shannon diversity, evenness and mean genetic distance) were calculated for each bacterial population isolated from the different root system portions. Moreover, the analysis of molecular variance (AMOVA) method was applied to estimate the genetic differences among the various bacterial populations. Our results showed that, in young plants, B. cepacia colonized preferentially the upper part of the root system, whereas in mature plants, B. cepacia was mostly recovered from the terminal part of the root system. This uneven distribution of B. cepacia cells among different root system portions partially reflected marked genetic differences among the B. cepacia populations isolated along maize roots on three distinct sampling occasions. In fact, all the diversity indices calculated indicated that genetic diversity increased during plant development and that the highest diversity values were found in mature maize plants, in particular in the middle and terminal portions of the root system. Moreover, the analysis of RAPD patterns by means of the AMOVA method revealed highly significant divergences in the degree of genetic polymorphism among the various B. cepacia populations. PMID:11243257

  17. Alternative genetic foundations for a key social polymorphism in fire ants.

    PubMed

    Ross, Kenneth G; Krieger, Michael J B; Shoemaker, D DeWayne

    2003-12-01

    Little is known about the genetic foundations of colony social organization. One rare example in which a single major gene is implicated in the expression of alternative social organizations involves the presumed odorant-binding protein gene Gp-9 in fire ants. Specific amino acid substitutions in this gene invariably are associated with the expression of monogyny (single queen per colony) or polygyny (multiple queens per colony) in fire ant species of the Solenopsis richteri clade. These substitutions are hypothesized to alter the abilities of workers to recognize queens and thereby regulate their numbers in a colony. We examined whether these same substitutions underlie the monogyny/polygyny social polymorphism in the distantly related fire ant S. geminata. We found that Gp-9 coding region sequences are identical in the polygyne and monogyne forms of this species, disproving our hypothesis that one or a few specific amino acid replacements in the protein are necessary to induce transitions in social organization in fire ants. On the other hand, polygyne S. geminata differs genetically from the monogyne form in ways not mirrored in the two forms of S. invicta, a well-studied member of the S. richteri clade, supporting the conclusion that polygyny did not evolve via analogous routes in the two lineages. Specifically, polygyne S. geminata has lower genetic diversity and different gene frequencies than the monogyne form, suggesting that the polygyne form originated via a founder event from a local monogyne population. These comparative data suggest an alternative route to polygyny in S. geminata in which loss of allelic variation at genes encoding recognition cues has led to a breakdown in discrimination abilities and the consequent acceptance of multiple queens in colonies.

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

    PubMed

    Zhou, Zheng; Li, Xinde; 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.

  19. Genetic scores based on risk-associated single nucleotide polymorphisms (SNPs) can reveal inherited risk of renal cell carcinoma.

    PubMed

    Wu, Yishuo; Zhang, Ning; Li, Kaiwen; Chen, Haitao; Lin, Xiaolin; Yu, Yang; Gou, Yuancheng; Hou, Jiangang; Jiang, Deke; Na, Rong; Wang, Xiang; Ding, Qiang; Xu, Jianfeng

    2016-04-01

    The objective of this study was to evaluate whether renal cell carcinoma (RCC) risk-associated single nucleotide polymorphisms (SNPs) could reflect the individual inherited risks of RCC. A total of 346 RCC patients and 1,130 controls were recruited in this case-control study. Genetic scores were calculated for each individual based on the odds ratios and frequencies of risk-associated SNPs. Four SNPs were significantly associated with RCC in Chinese population. Two genetic score models were established, genetic score 1 (rs10054504, rs7023329 and rs718314) and genetic score 2 (rs10054504, rs7023329 and rs1049380). For genetic score 1, the individual likelihood of RCC with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 1 was 15.61%, 22.25% and 33.92% respectively (P-trend=6.88×10(-7)). For genetic score 2, individual with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 2 would have likelihood of RCC as 14.39%, 24.54% and 36.48%, respectively (P-trend=1.27×10(-10)). The area under the receiver operating curve (AUC) of genetic score 1 was 0.626, and AUC of genetic score 2 was 0.658. We concluded that genetic score can reveal personal risk and inherited risk of RCC, especially when family history is not available.

  20. Genetic scores based on risk-associated single nucleotide polymorphisms (SNPs) can reveal inherited risk of renal cell carcinoma

    PubMed Central

    Chen, Haitao; Lin, Xiaolin; Yu, Yang; Gou, Yuancheng; Hou, Jiangang; Jiang, Deke; Na, Rong; Wang, Xiang; Ding, Qiang; Xu, Jianfeng

    2016-01-01

    The objective of this study was to evaluate whether renal cell carcinoma (RCC) risk-associated single nucleotide polymorphisms (SNPs) could reflect the individual inherited risks of RCC. A total of 346 RCC patients and 1,130 controls were recruited in this case-control study. Genetic scores were calculated for each individual based on the odds ratios and frequencies of risk-associated SNPs. Four SNPs were significantly associated with RCC in Chinese population. Two genetic score models were established, genetic score 1 (rs10054504, rs7023329 and rs718314) and genetic score 2 (rs10054504, rs7023329 and rs1049380). For genetic score 1, the individual likelihood of RCC with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 1 was 15.61%, 22.25% and 33.92% respectively (P-trend=6.88×10−7). For genetic score 2, individual with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 2 would have likelihood of RCC as 14.39%, 24.54% and 36.48%, respectively (P-trend=1.27×10−10). The area under the receiver operating curve (AUC) of genetic score 1 was 0.626, and AUC of genetic score 2 was 0.658. We concluded that genetic score can reveal personal risk and inherited risk of RCC, especially when family history is not available. PMID:27229762

  1. 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

  2. Genetic polymorphisms in three Iranian populations with different risks of esophageal cancer, an ecologic comparison.

    PubMed

    Sepehr, Alireza; Kamangar, Farin; Abnet, Christian C; Fahimi, Saman; Pourshams, Akram; Poustchi, Hossein; Zeinali, Sirous; Sotoudeh, Masood; Islami, Farhad; Nasrollahzadeh, Dariush; Malekzadeh, Reza; Taylor, Philip R; Dawsey, Sanford M

    2004-09-30

    The age-standardized incidence of esophageal cancer (EC) varies from 3 to >100/100,000 per year in different provinces of Iran. This striking variation of incidence is associated with differences in ethnic backgrounds, raising the possibility that genetic factors are involved in the pathogenesis of EC. We compared the frequencies of polymorphisms in ten genes that have been hypothesized to have a role in risk of EC (CYP1A1, CYP2A6, CYP2E1, GSTM1, GSTP1, GSTT1, ADH2, ADH3, ALDH2, and O6-MGMT) among three Iranian ethnic groups with highly varying rates of EC. These three groups included high-risk Turkomans, medium-risk Turks, and low-risk Zoroastrian Persians. Compared to Zoroastrians, Turkomans had higher frequency of four alleles that are speculated to favor carcinogenesis (CYP1A1 m1, CYP1A1 m2, CYP2A6*9, and ADH2*1); these results are consistent with an influence of these allele variants on the population risk of EC. However, none of these four alleles had a high enough prevalence in Turkomans to explain the high rates of EC in this group. Three of these four alleles (CYP1A1 m1, CYP1A1 m2, CYP2A6*9) were less frequent among Turkomans than in some Asian populations with lower risks of EC. We conclude that it is unlikely that variations in these polymorphic genes are major contributors to the high incidence of EC among Turkomans in Iran. PMID:15327835

  3. 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

  4. 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

  5. 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.

  6. 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 χ2 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

  7. 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

  8. Genetic association of complement component 2 polymorphism with systemic lupus erythematosus.

    PubMed

    Chen, H-H; Tsai, L-J; Lee, K-R; Chen, Y-M; Hung, W-T; Chen, D-Y

    2015-08-01

    Complement component 2 (C2), an early member of the classical pathway, mainly participates in apoptotic cell clearance. We hypothesize that C2 polymorphism may confer genetic susceptibility to complement dysfunction in systemic lupus erythematosus (SLE). The major aim of our study was to investigate the clinical and serological associations of C2 variants in Chinese patients with SLE. The single-nucleotide polymorphism (rs2844455, G/A SNP) located in the intron region of C2 gene was genotyped by direct sequencing in 95 SLE patients and 95 matched normal control subjects. The gene expression profiles were generated by quantitative real-time polymerase chain reaction (PCR) and reverse transcription PCR. Our results showed that the AA genotype was observed more frequently in SLE patients than in normal control subjects (22.1% vs 9.5%, P < 0.05). The A allele was strongly associated with the occurrence of hair loss, photosensitivity and anti-cardiolipin antibodies; whereas, the G allele was associated with lower frequencies of these clinical presentations. Relative expression levels were significantly lower in patients with the AA genotype [median: 18.86, interquartile range (IQR) 11.36-22.43, P = 0.002] than in those with the GG genotype (35.76, IQR: 19.33-49.71). As expected, we confirmed the A allele as a risk factor for SLE development in a Chinese population, in contrast, the G allele might be a protective factor against the pathogenic autoantibody formation and cutaneous manifestations in SLE patients.

  9. 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

  10. 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

  11. 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

  12. [Influence of genetic polymorphisms (IL-10/CXCL8/CXCR2/NFκB) on the susceptibility of autoimmune rheumatic diseases].

    PubMed

    Salim, Patricia Hartstein; Xavier, Ricardo Machado

    2014-01-01

    The autoimmune rheumatologic disorders mostly have a common genetic path to the autoimmunity. Several genes have been associated with rheumatologic disorders; therefore, we are analyzing just the ones in those containing several evidences of the existence of association with the risk or protection from autoimmune disorder. The nuclear factor kappa beta (NF-kappa B), which regulates the autoimmune and anti-inflammatory responses, is associated with systemic sclerosis (SS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), just as the CXCR2 e CXCL8 genes. On the other hand, the interleukin-10 (IL-10), which is an anti-inflammatory cytokine, is associated with almost all rheumatologic disorders. In this article, we are reviewing the potential roles of these genes in the immune system and in several rheumatologic disorders. In relation to IL-10, several studies have been carried out, but most of them are controversial - some detected the absence of association, and others found association in different genetic polymorphisms. Conversely, in relation to NF-kappa B, it was studied just in RA and SLE, and no relevant significant analyses were observed. The genetic polymorphisms of the CXCR2 gene were associated with SS, but not with RA e SLE. On the other side, the genetic polymorphisms of the CXCL8 gene are not associated with SS, but with RA.

  13. Short communication: Fc gamma receptors IIa and IIIa genetic polymorphisms do not predict HIV-1 disease progression in Kenyan women.

    PubMed

    Weis, Julie F; McClelland, R Scott; Jaoko, Walter; Mandaliya, Kishor N; Overbaugh, Julie; Graham, Susan M

    2015-03-01

    Genetic polymorphisms of the Fc gamma receptors (FcγR) IIa and IIIa have been implicated in the rate of HIV-1 disease progression, but results are inconsistent. We aimed to determine the association between these polymorphisms and disease progression in a cohort of HIV-1 seroconverters from Mombasa, Kenya. Neither FcγRIIa nor FcγRIIIa genotypes were predictive of set point viral load, viral load increase, CD4 decline, or HIV-1 disease progression (time to CD4 count <200 cells/mm(3), death, or treatment initiation). Our results suggest that FcγR polymorphisms might not be an important indicator of viral control and disease progression in this population.

  14. 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

  15. Effects of selected genetic polymorphisms in xeroderma pigmentosum complementary group D on gastric cancer.

    PubMed

    Chen, Ziping; Zhang, Chuanzhen; Xu, Changqing; Li, Kun; Hou, Ruiping; Li, Danping; Cheng, Xiaoli

    2011-03-01

    DNA repair capacity (DRC) can be altered based on sequence variations in DNA repair genes, which may result in cancer susceptibility. The current study was to evaluate the association between genetic polymorphisms, including associated haplotypes of xeroderma pigmentosum complementary group D (XPD), and individual susceptibility to gastric cancer. Two-hundred-eight patients with gastric cancer and 339 healthy controls were enrolled in this study. Their genomic DNA was extracted from peripheral blood leukocytes. The genotypes at exon 6, 10 and 23 were identified by polymerase chain reaction (PCR). Unconditional logistic regression model was used to analyze the effects of the polymorphisms, including the corresponding haplotypes, on the susceptibility to develop gastric cancer. The proportion of genotypes GA or AA at exon 10 in cases was showed to be significantly higher than that in controls (P < 0.01, P < 0.01, respectively). The risk of genotype GA or AA carriers to develop gastric cancer was simultaneously much higher (OR = 3.38, 95% CI 2.30-4.95; OR = 6.13, 95% CI 2.45-15.31, respectively). The allele A at exon 10 was also observed to manifest a substantially higher frequency in cases compared to controls (P < 0.01), which might indicate an increased tendency to gastric cancer (OR = 2.40, 95% CI 1.81-3.17). No significant differences were found in the distribution of genotypes at exon 6 or 23 between the two groups (P = 0.23, P = 0.52; P = 0.44, P = 0.56, respectively). By haplotype analysis, haplotype AAA could individually increase incidence of gastric cancer (P < 0.01, OR = 3.39, 95% CI 2.21-5.21). In contrast, haplotypes CGA and AGA were showed a decline in gastric cancer susceptibility (OR = 0.67, 95% CI 0.46-0.97; OR = 0.58, 95% CI 0.41-0.83, respectively). The rest of haplotypes made no statistically significant difference between cases and controls. Taken together, this study demonstrates that the genetic variation at exon 10 and haplotype AAA may be

  16. 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-1β (IL-1β), IL-6 (IL-6), and tumor necrosis factor-α (TNF-α) 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-1β C3953T (CC vs. CT+TT: OR, 1.61; 95% CI, 1.18-2.20), and TNF-α 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.

  17. Genetic divergence between Mexican Opuntia accessions inferred by polymerase chain reaction-restriction fragment length polymorphism analysis.

    PubMed

    Samah, S; Valadez-Moctezuma, E; Peláez-Luna, K S; Morales-Manzano, S; Meza-Carrera, P; Cid-Contreras, R C

    2016-01-01

    Molecular methods are powerful tools in characterizing and determining relationships between plants. The aim of this study was to study genetic divergence between 103 accessions of Mexican Opuntia. To accomplish this, polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis of three chloroplast intergenic spacers (atpB-rbcL, trnL-trnF, and psbA-trnH), one chloroplast gene (ycf1), two nuclear genes (ppc and PhyC), and one mitochondrial gene (cox3) was conducted. The amplified products from all the samples had very similar molecular sizes, and there were only very small differences between the undigested PCR amplicons for all regions, with the exception of ppc. We obtained 5850 bp from the seven regions, and 136 fragments were detected with eight enzymes, 37 of which (27.2%) were polymorphic. We found that 40% of the fragments from the chloroplast regions were polymorphic, 9.8% of the bands detected in the nuclear genes were polymorphic, and 20% of the bands in the mitochondrial locus were polymorphic. trnL-trnF and psbA-trnH were the most variable regions. The Nei and Li/Dice distance was very short, and ranged from 0 to 0.12; indeed, 77 of the 103 genotypes had the same genetic profile. All the xoconostle accessions (acidic fruits) were grouped together without being separated from three genotypes of prickly pear (sweet fruits). We assume that the genetic divergence between prickly pears and xoconostles is very low, and question the number of Opuntia species currently considered in Mexico. PMID:27323120

  18. Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease.

    PubMed

    Fedele, Francesco; Mancone, Massimo; Chilian, William M; Severino, Paolo; Canali, Emanuele; Logan, Suzanna; De Marchis, Maria Laura; Volterrani, Maurizio; Palmirotta, Raffaele; Guadagni, Fiorella

    2013-11-01

    Conventionally, ischemic heart disease (IHD) is equated with large vessel coronary disease. However, recent evidence has suggested a role of compromised microvascular regulation in the etiology of IHD. Because regulation of coronary blood flow likely involves activity of specific ion channels, and key factors involved in endothelium-dependent dilation, we proposed that genetic anomalies of ion channels or specific endothelial regulators may underlie coronary microvascular disease. We aimed to evaluate the clinical impact of single-nucleotide polymorphisms in genes encoding for ion channels expressed in the coronary vasculature and the possible correlation with IHD resulting from microvascular dysfunction. 242 consecutive patients who were candidates for coronary angiography were enrolled. A prospective, observational, single-center study was conducted, analyzing genetic polymorphisms relative to (1) NOS3 encoding for endothelial nitric oxide synthase (eNOS); (2) ATP2A2 encoding for the Ca²⁺/H⁺-ATPase pump (SERCA); (3) SCN5A encoding for the voltage-dependent Na⁺ channel (Nav1.5); (4) KCNJ8 and KCNJ11 encoding for the Kir6.1 and Kir6.2 subunits of K-ATP channels, respectively; and (5) KCN5A encoding for the voltage-gated K⁺ channel (Kv1.5). No significant associations between clinical IHD manifestations and polymorphisms for SERCA, Kir6.1, and Kv1.5 were observed (p > 0.05), whereas specific polymorphisms detected in eNOS, as well as in Kir6.2 and Nav1.5 were found to be correlated with IHD and microvascular dysfunction. Interestingly, genetic polymorphisms for ion channels seem to have an important clinical impact influencing the susceptibility for microvascular dysfunction and IHD, independent of the presence of classic cardiovascular risk factors.

  19. Genetic divergence between Mexican Opuntia accessions inferred by polymerase chain reaction-restriction fragment length polymorphism analysis.

    PubMed

    Samah, S; Valadez-Moctezuma, E; Peláez-Luna, K S; Morales-Manzano, S; Meza-Carrera, P; Cid-Contreras, R C

    2016-06-03

    Molecular methods are powerful tools in characterizing and determining relationships between plants. The aim of this study was to study genetic divergence between 103 accessions of Mexican Opuntia. To accomplish this, polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis of three chloroplast intergenic spacers (atpB-rbcL, trnL-trnF, and psbA-trnH), one chloroplast gene (ycf1), two nuclear genes (ppc and PhyC), and one mitochondrial gene (cox3) was conducted. The amplified products from all the samples had very similar molecular sizes, and there were only very small differences between the undigested PCR amplicons for all regions, with the exception of ppc. We obtained 5850 bp from the seven regions, and 136 fragments were detected with eight enzymes, 37 of which (27.2%) were polymorphic. We found that 40% of the fragments from the chloroplast regions were polymorphic, 9.8% of the bands detected in the nuclear genes were polymorphic, and 20% of the bands in the mitochondrial locus were polymorphic. trnL-trnF and psbA-trnH were the most variable regions. The Nei and Li/Dice distance was very short, and ranged from 0 to 0.12; indeed, 77 of the 103 genotypes had the same genetic profile. All the xoconostle accessions (acidic fruits) were grouped together without being separated from three genotypes of prickly pear (sweet fruits). We assume that the genetic divergence between prickly pears and xoconostles is very low, and question the number of Opuntia species currently considered in Mexico.

  20. Genetic Association between Presenilin 2 Polymorphisms and Alzheimer's Disease and Dementia of Lewy Body Type in a Japanese Population

    PubMed Central

    Suzuki, Ayako; Shibata, Nobuto; Kasanuki, Koji; Nagata, Tomoyuki; Shinagawa, Shunichiro; Kobayashi, Nobuyuki; Ohnuma, Tohru; Takeshita, Yoshihide; Kawai, Eri; Takayama, Toshiki; Nishioka, Kenya; Motoi, Yumiko; Hattori, Nobutaka; Nakayama, Kazuhiko; Yamada, Hisashi; Arai, Heii

    2016-01-01

    Background/Aims Mutations in the presenilin 2 (PSEN2) gene cause familial Alzheimer's disease (AD). Common polymorphisms affect gene activity and increase the risk of AD. Nonsynonymous polymorphisms in the PSEN2 gene showed Lewy body dementia (LBD) phenotypes clinically. Therefore, we aimed to investigate whether PSEN2 gene polymorphisms were associated with AD or LBD. Methods Seven single nucleotide polymorphisms (SNPs) of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBD patients, and 105 age-matched controls. Results Linkage disequilibrium (LD) examination showed strong LD from rs1295645 to rs8383 on the gene in our cases from Japan. There were no associations between the SNPs studied here and AD onset, and haplotypic analyses did not detect genetic associations between AD and the PSEN2 gene. Although the number of the cases was small, the SNPs studied did not modify the risk of developing LBD in a Japanese population. Conclusion The common SNPs of the PSEN2 gene did not affect the risk of AD or LBD in a Japanese population. Because genetic variability of the PSEN2 gene is associated with behavioral and psychological symptoms of dementia (BPSD) in AD and LBD, further detailed analyses considering BPSD of both diseases would be required. PMID:27065294

  1. 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. PMID:27019828

  2. Glutathione S-transferase T1, M1 and P1 Genetic Polymorphisms and Susceptibility to Colorectal Cancer in Turkey.

    PubMed

    Gorukmez, Ozlem; Yakut, Tahsin; Gorukmez, Orhan; Sag, Sebnem Ozemri; Topak, Ali; Sahinturk, Serdar; Kanat, Ozkan

    2016-01-01

    Colorectal cancer (CRC) is reported to be the third most common cancer worldwide and the fourth most common cause of cancer related deaths. CRC is considered to be a multifactorial disease whose risk varies due to the complex interaction between individual genetic basis and exposure to multiple endogenous factors. Glutathione S-transferases are pro-carcinogenic in CRC and are required for the conjugation between chemotherapeutics and broad spectrum xenobiotics. One hundred and eleven patients with CRC and 128 control subjects without any cancer history were enrolled in this study. Multiplex PCR was applied to determine polymorphisms for the GSTT1 and M1 genes, and PCR-RFLP was applied for the GSTP1 (Ile105Val) gene polymorphism. Values <0.05 were defined as statistically significant. We detected a significant high correlation between predisposition for CRC and presence of the Ile/Ile genotype of the GSTP1 (IIe105Val) gene polymorphism, but we did not find a significant relationship between predisposition for CRC and GSTT1 and M1 deletion polymorphisms. In addition, we did not determine a relationship between GSTT1, M1 and P1 gene polymorphisms and any clinicopathological features of CRC. GSTT1 null/GSTM1 positive and GSTT1 null/GSTM1 positive/GSTP1 Ile/ Ile genotypes were significantly higher in the patient group. Our results revealed that there is no relationship among CRC, its clinicopathologic features, and GSTT1 M1 gene polymorphisms. However, there was a significant correlation between CRC and the GSTP1 Ile/Ile genotype. Further studies with larger patient groups are required to delineate the relationships between GST gene polymorphisms and the clinicopathologic features of CRC in Turkey. PMID:27644629

  3. Genetic polymorphisms of interleukin-1 alpha and the vitamin d receptor in mexican mestizo patients with intervertebral disc degeneration.

    PubMed

    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.

  4. 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

  5. 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

  6. SOCS3 Genetic Polymorphism Is Associated With Clinical Features and Prognosis of Hepatocellular Carcinoma Patients Receiving Hepatectomy.

    PubMed

    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

    2015-10-01

    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.

  7. 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

  8. 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

  9. Preliminary genetic imaging study of the association between estrogen receptor-α gene polymorphisms and harsh human maternal parenting.

    PubMed

    Lahey, Benjamin B; Michalska, Kalina J; Liu, Chunyu; Chen, Qi; Hipwell, Alison E; Chronis-Tuscano, Andrea; Waldman, Irwin D; Decety, Jean

    2012-09-01

    A failure of neural changes initiated by the estrogen surge in late pregnancy to reverse the valence of infant stimuli from aversive to rewarding is associated with dysfunctional maternal behavior in nonhuman mammals. Estrogen receptor-α plays the crucial role in mediating these neural effects of estrogen priming. This preliminary study examines associations between estrogen receptor-α gene polymorphisms and human maternal behavior. Two polymorphisms were associated with human negative maternal parenting. Furthermore, hemodynamic responses in functional magnetic resonance imaging to child stimuli in neural regions associated with social cognition fully mediated the association between genetic variation and negative parenting. This suggests testable hypotheses regarding a biological pathway between genetic variants and dysfunctional human maternal parenting.

  10. 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.

  11. Milk protein polymorphism in Danish dairy cattle and the influence of genetic variants on milk yield.

    PubMed

    Bech, A M; Kristiansen, K R

    1990-02-01

    In milk samples from 549 cows of the breeds Danish Jersey, Red Danish Dairy Cattle (RDM), and Black and White Danish Dairy Cattle (SDM) the genetic polymorphisms of the alpha-s1, beta and k-casein and beta=lactoglobulin (beta-Lg) loci were determined by isoelectric focusing in agarose gels. The results of the screening were compared with results obtained by Larsen and Thymann. In addition, the genetic linkage of the three casein loci was studied , and the association between milk protein genotypes and yields in first and second lactations of milk, fat and protein were investigated. The distribution of genotypes of all four milk protein systems was different from breed to breed. For Jersey cows, significant differences in the gene frequencies from the results of the 1966 investigation were found for alpha-s1 and k-casein and beta-Lg. For SDM cows a change in the k-casein frequency had occurred whereas for RDM cows no changes were found. Linkage between some of the casein loci was found within all three breeds. For the RDM breed the possible linkage between alpha-s1-casein and the other caseins could not be tested because nearly all the cows were homozygous for the alpha-s1-casein-B genotypes. beta-Casein genotypes were associated with yield parameters in all breeds. The A2A2 genotype of this protein gave higher yields of milk, fat, and protein in the second lactation than the A1A1 genotype.

  12. Common Genetic Polymorphisms within NFκB-Related Genes and the Risk of Developing Invasive Aspergillosis.

    PubMed

    Lupiañez, Carmen B; Villaescusa, María T; Carvalho, Agostinho; Springer, Jan; Lackner, Michaela; Sánchez-Maldonado, José M; Canet, Luz M; Cunha, Cristina; Segura-Catena, Juana; Alcazar-Fuoli, Laura; Solano, Carlos; Fianchi, Luana; Pagano, Livio; Potenza, Leonardo; Aguado, José M; Luppi, Mario; Cuenca-Estrella, Manuel; Lass-Flörl, Cornelia; Einsele, Hermann; Vázquez, Lourdes; Ríos-Tamayo, Rafael; Loeffler, Jurgen; Jurado, Manuel; Sainz, Juan

    2016-01-01

    Invasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mold. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NFκB1, NFκB2, RelA, RelB, Rel, and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non-IA) recruited through a collaborative effort involving the aspBIOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT)-stratified analysis revealed that carriers of the IRF4 rs12203592T/T genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (ORREC = 6.24, 95%CI 1.25-31.2, P = 0.026), the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4AATC and IRF4GGTC haplotypes (not including the IRF4 rs12203592T risk allele) with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4 rs12203592 SNP. Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA. PMID:27570521

  13. Influence of physical inactivity on associations between single nucleotide polymorphisms and genetic predisposition to childhood obesity.

    PubMed

    Xi, Bo; Wang, Chunyu; Wu, Lijun; Zhang, Meixian; Shen, Yue; Zhao, Xiaoyuan; Wang, Xingyu; Mi, Jie

    2011-06-01

    Childhood obesity is a complex disease that is influenced by both genetic and environmental factors. The authors' aim was to determine whether sedentary behavior and physical activity modulate the association between single nucleotide polymorphisms (SNPs) and obesity risk in Chinese children. A population-based study was carried out in 2,848 children (6-18 years of age) in Beijing, China, in 2004. It included 1,229 obese cases and 1,619 normal-weight controls. Lifestyle information was collected through the use of a validated questionnaire, and 6 SNPs were genotyped. The association between the 6 SNPs and obesity risk was modulated by sedentary behavior and physical activity. A higher risk of obesity was observed in children who carried the high-risk alleles of the 6 SNPs and engaged in sedentary behavior ≥2 hours/day outside of school or participated in low or moderate physical activity. Most notably, the association between 5 SNPs (Fas apoptotic inhibitory molecule 2 rs7138803, Niemann-Pick disease, type C1 rs1805081, fat mass- and obesity-associated gene rs6499640, melanocortin 4 receptor gene rs17782313, and brain-derived neurotrophic factor rs6265) and obesity risk was only observed in children who had moderate-to-low physical activity levels or engaged in sedentary behavior, regardless of which risk alleles they carried. The results indicated that encouraging less sedentary behavior and higher levels of physical activity could alleviate the influence of risk alleles on genetic predisposition to childhood obesity, thereby serving as a promising prevention strategy.

  14. Common Genetic Polymorphisms within NFκB-Related Genes and the Risk of Developing Invasive Aspergillosis

    PubMed Central

    Lupiañez, Carmen B.; Villaescusa, María T.; Carvalho, Agostinho; Springer, Jan; Lackner, Michaela; Sánchez-Maldonado, José M.; Canet, Luz M.; Cunha, Cristina; Segura-Catena, Juana; Alcazar-Fuoli, Laura; Solano, Carlos; Fianchi, Luana; Pagano, Livio; Potenza, Leonardo; Aguado, José M.; Luppi, Mario; Cuenca-Estrella, Manuel; Lass-Flörl, Cornelia; Einsele, Hermann; Vázquez, Lourdes; Ríos-Tamayo, Rafael; Loeffler, Jurgen; Jurado, Manuel; Sainz, Juan

    2016-01-01

    Invasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mold. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NFκB1, NFκB2, RelA, RelB, Rel, and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non-IA) recruited through a collaborative effort involving the aspBIOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT)-stratified analysis revealed that carriers of the IRF4rs12203592T/T genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (ORREC = 6.24, 95%CI 1.25–31.2, P = 0.026), the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4AATC and IRF4GGTC haplotypes (not including the IRF4rs12203592T risk allele) with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4rs12203592 SNP. Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA. PMID:27570521

  15. Prospective Analysis of Genetic Polymorphisms and Risk of Recurrence in Renal Cell Cancer

    PubMed Central

    Schutz, Fabio A. B.; Pomerantz, Mark M.; Gray, Kathryn P.; Atkins, Prof Michael B.; Rosenberg, Jonathan E.; Hirsch, Michelle S.; McDermott, David F.; Lampron, Megan E.; Lee, Gwo-Shu Mary; Signoretti, Sabina; Kantoff, Prof Philip W.; Freedman, Matthew L.; Choueiri, Toni K.

    2013-01-01

    Summary Background Germline genetic polymorphisms may affect the risk of recurrence in patients with localized renal cell carcinoma (RCC). Our aim was to investigate the association of genetic polymorphisms with RCC recurrence. Patients and Methods We analyzed germline DNA samples extracted from 554 (discovery cohort of 403 and an independent validation cohort of 151) patients with localized RCC treated at Dana-Farber/Harvard Cancer Center (DF/HCC) and of European-American ancestry (Caucasians). The discovery cohort was selected from a prospective database at Dana-Farber/Harvard Cancer Center and the validation cohort was identified from the Brigham and Women’s Hospital surgery and pathology department records. Single nucleotide polymorphims (SNPs) residing in 70 genes involved in RCC pathogenesis including the VHL/HIF/VEGF, PI3K/AKT/mTOR pathways, and genes involved in immune regulation and metabolism were genotyped for the discovery cohort (total 285 SNPs successfully genotyped and assessable for analysis). The analyses of genotype associations with recurrence free survival (RFS) were assessed using Cox proportional hazards model, Kaplan-Meier method and logrank test. False discovery rate (FDR) q-value was used to adjust for multiple comparisons in selecting potential SNPs with RFS association. The finding from the discovery cohort was validated in an external independent cohort. Findings We report the significant association between genotype variants of SNP rs11762213 (c.144G>A; p.Ala48Ala, located in exon two c-MET) and primary analysis endpoint of RFS using both univariate and multivariable analysis. Specifically, patients carrying one or two copies of the minor (risk) allele had an increased risk of recurrence or death (hazard ratio (HR) =1·86, 95% confidence interval (CI), 1·17,2·95; p=0·0084) in the multivariate analysis adjusted for clinical and pathological factors. The median RFS for carriers of the risk allele was 19 months (95%CI: 9,*) compared

  16. 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

  17. 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.

  18. 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

  19. Genetic influences on insight problem solving: the role of catechol-O-methyltransferase (COMT) gene polymorphisms.

    PubMed

    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.

  20. Genetic structure of the genus Lemna L. (Lemnaceae) as revealed by amplified fragment length polymorphism.

    PubMed

    Bog, Manuela; Baumbach, Henryk; Schween, Ulrike; Hellwig, Frank; Landolt, Elias; Appenroth, Klaus-J

    2010-08-01

    Duckweeds (Lemnaceae) are extremely reduced in morphology, which made their taxonomy a challenge for a long time. The amplified fragment length polymorphism (AFLP) marker technique was applied to solve this problem. 84 clones of the genus Lemna were investigated representing all 13 accepted Lemna species. By neighbour-joining (NJ) analysis, 10 out of these 13 species were clearly recognized: L. minor, L. obscura, L. turionifera, L. japonica, L. disperma, L. aequinoctialis, L. perpusilla, L. trisulca, L. tenera, and L. minuta. However, L. valdiviana and L. yungensis could be distinguished neither by NJ cluster analysis nor by structure analysis. Moreover, the 16 analysed clones of L. gibba were assembled into four genetically differentiated groups. Only one of these groups, which includes the standard clones 7107 (G1) and 7741 (G3), represents obviously the "true" L. gibba. At least four of the clones investigated, so far considered as L. gibba (clones 8655a, 9481, 9436b, and Tra05-L), represent evidently close relatives to L. turionifera but do not form turions under any of the conditions tested. Another group of clones (6745, 6751, and 7922) corresponds to putative hybrids and may be identical with L. parodiana, a species not accepted until now because of the difficulties of delineation on morphology alone. In conclusion, AFLP analysis offers a solid base for the identification of Lemna clones, which is particularly important in view of Lemnaceae application in biomonitoring.

  1. Genetic structure of the genus Lemna L. (Lemnaceae) as revealed by amplified fragment length polymorphism.

    PubMed

    Bog, Manuela; Baumbach, Henryk; Schween, Ulrike; Hellwig, Frank; Landolt, Elias; Appenroth, Klaus-J

    2010-08-01

    Duckweeds (Lemnaceae) are extremely reduced in morphology, which made their taxonomy a challenge for a long time. The amplified fragment length polymorphism (AFLP) marker technique was applied to solve this problem. 84 clones of the genus Lemna were investigated representing all 13 accepted Lemna species. By neighbour-joining (NJ) analysis, 10 out of these 13 species were clearly recognized: L. minor, L. obscura, L. turionifera, L. japonica, L. disperma, L. aequinoctialis, L. perpusilla, L. trisulca, L. tenera, and L. minuta. However, L. valdiviana and L. yungensis could be distinguished neither by NJ cluster analysis nor by structure analysis. Moreover, the 16 analysed clones of L. gibba were assembled into four genetically differentiated groups. Only one of these groups, which includes the standard clones 7107 (G1) and 7741 (G3), represents obviously the "true" L. gibba. At least four of the clones investigated, so far considered as L. gibba (clones 8655a, 9481, 9436b, and Tra05-L), represent evidently close relatives to L. turionifera but do not form turions under any of the conditions tested. Another group of clones (6745, 6751, and 7922) corresponds to putative hybrids and may be identical with L. parodiana, a species not accepted until now because of the difficulties of delineation on morphology alone. In conclusion, AFLP analysis offers a solid base for the identification of Lemna clones, which is particularly important in view of Lemnaceae application in biomonitoring. PMID:20526614

  2. GENETIC POLYMORPHISM OF TOXOPLASMA GONDII FROM RECENTLY INFECTED ABORTED EGYPTIAN WOMEN.

    PubMed

    Badr, Mohamed S; Attia, Samar S; El-Sherbiny, Walid S; Abd-Allah M A, El Ebidi; Hefny, Hesham M; Salem, Ahmed N M

    2016-04-01

    Toxoplasmosis caused by Toxoplasma gondii is one of the most prevalent parasitic diseases in human beings. Human toxoplasmosis can be associated with serious clinical manifestations, particularly in developing fetus. The aim of the current study was to identify the possible lineage type of Toxoplasma gondii, molecularly detected in placental samples of women whose pregnancies were spontaneously terminated in the first trimester. Preliminary detection of Toxoplasma genomic materials was done by a SYBR green qPCR technology. Subsequent identification of Toxoplasma strain was done for the positive samples using PCR-restriction fragment length polymorphism (RFLP) at the SAG2 loci of T. gondii using restriction enzymes HhaI and Sau3AI. Out of 72 tested samples, Toxoplasma B1 gene was detected in 9 cases. Toxoplasma genotypes I and II in addition to unknown type were identified in 4, 3 and 2 cases respectively, while type III was not detected in our samples, hence excluded as a leading cause of abortion in humans in our preliminary study. Nevertheless, it remains uncertain to what extent the genotype of the parasite directly contributes to the clinical severity of human toxoplasmosis. Certainly, advanced molecular techniques targeting different Toxoplasma strains are crucial for better understanding of human toxoplasmosis. For more elucidation, additional studies are recommended intended for genetic characterization of such serious parasitic infection using larger number of samples. PMID:27363040

  3. [Influence of salt stress on the genetically polymorphic system of Sinorhizobium meliloti-Medicago truncatula].

    PubMed

    Kurchak, O N; Provorov, N A; Onishchuk, O P; Vorobyov, N I; Roumiantseva, M L; Simarov, B V

    2014-07-01

    The impacts of salt stress (75 mM NaC1) on the ecological efficiency of the genetically polymorphic Sinorhizobium meliloti-Medicago truncatula system were studied. Its impact on a symbiotic system results in an increase of the partners' variability for symbiotic traits and of the symbiosis integrity as indicated by: a) the specificity of the partners' interactions--the nonadditive inputs of their genotypes into the variation of symbiotic parameters; and b) the correlative links between these parameters. The structure of the nodDI locus and the content correlates to the efficiency of the symbiosis between S. meliloti and M. truncatula genotypes under stress conditions more sufficiently than in the absence of stress. Correlations between the symbiotic efficiency of rhizobia strains and their growth rate outside symbiosis are expressed under stress conditions, not in the absence of stress. Under salt stress symbiotic effectiveness was decreased for M. truncatula line F83005.5, which was salt sensitive for mineral nutrition. The inhibition of symbiotic activity for this line is linked with decreased nodule formation, whereas for Jemalong 6 and DZA315.16 lines it is associated with repressed N2-fixation. It was demonstrated for the first time that salt stress impairs the M. truncatula habitus (the mass : height ratio increased 2- to 6-fold), which in the salt-resistant cultivar Jemalong 6 is normalized as the result of rhizobia inoculation.

  4. Autoimmune Hepatitis in Brazilian Children: IgE and Genetic Polymorphisms in Associated Genes

    PubMed Central

    de Oliveira, Léa 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 1–14 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

  5. Genetic Polymorphism, Telomere Biology and Non-Small Lung Cancer Risk.

    PubMed

    Wei, Rongrong; DeVilbiss, Frank T; Liu, Wanqing

    2015-10-20

    Recent genome-wide association studies (GWAS) have identified a number of chromosomal regions associated with the risk of lung cancer. Of these regions, single-nucleotide polymorphisms (SNPs), especially rs2736100 located in the telomerase reverse transcriptase (TERT) gene show unique and significant association with non-small cell lung cancer (NSCLC) in a few subpopulations including women, nonsmokers, East Asians and those with adenocarcinoma. Recent studies have also linked rs2736100 with a longer telomere length and lung cancer risk. In this review, we seek to summarize the relationship between these factors and to further link the underlying telomere biology to lung cancer etiology. We conclude that genetic alleles combined with environmental (e.g., less-smoking) and physiological factors (gender and age) that confer longer telomere length are strong risk factors for NSCLC. This linkage may be particularly relevant in lung adenocarcinoma driven by epidermal growth factor receptor (EGFR) mutations, as these mutations have also been strongly linked to female gender, less-smoking history, adenocarcinoma histology and East Asian ethnicity. By establishing this connection, a strong argument is made for further investigating of the involvement of these entities during the tumorigenesis of NSCLC.

  6. Genetic Diversity of mtDNA D-loop Polymorphisms in Laotian Native Fowl Populations

    PubMed Central

    Kawabe, K.; Worawut, R.; Taura, S.; Shimogiri, T.; Nishida, T.; Okamoto, S.

    2014-01-01

    Here, we studied the genetic diversity of native fowls in Laos by analyzing a mitochondrial DNA (mtDNA) sequence polymorphism. A 546-bp fragment of the mtDNA D-loop region was sequenced in 129 chickens from the areas of Vientiane, Luang Prabang and Pakse. In total, 29 haplotypes were identified and formed five clades. Haplotype diversity and nucleotide diversity of the native fowls in Laos were 0.85536±0.0172 and 0.010158±0.005555, respectively. Although the Laotian native fowls were distributed across five clades, most of them were clustered in two main clades (A and B), which were originated in China. The other haplotypes were contained in clades D, F, and I, which originated from continental southeast Asia. These results suggest that multiple maternal lineages were involved in the origin of domestic chicken in Laos. Moreover, there appear to be at least two maternal lineages, one from China and the other from the southeast Asian continent. PMID:25049921

  7. Genetic polymorphisms of Echinococcus tapeworms in China as determined by mitochondrial and nuclear DNA sequences ✩

    PubMed Central

    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

    2009-01-01

    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 colonizing alpine mammals and its mitochondrial locus has evolved without bottleneck effects. PMID:19800346

  8. 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

    2015-01-01

    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.

  9. Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain.

    PubMed

    Miksys, Sharon; Lerman, Caryn; Shields, Peter G; Mash, Deborah C; Tyndale, Rachel F

    2003-07-01

    CYP2B6 metabolizes drugs such as nicotine and bupropion, and many toxins and carcinogens. Nicotine induces CYP2B1 in rat brain and in humans polymorphic variation in CYP2B6 affects smoking cessation rates. The aim of this study was to compare CYP2B6 expression in brains of human smokers and non-smokers and alcoholics and non-alcoholics (n=26). CYP2B6 expression was brain region-specific, and was observed in both neurons and astrocytes. CYP2B6 levels were higher in brains of smokers and alcoholics, particularly in cerebellar Purkinje cells and hippocampal pyramidal neurons, cells known to be damaged in alcoholics. Significantly more (p<0.05) CYP2B6 protein was seen in four brain regions of smoking alcoholics compared to non-smoking non-alcoholics: hippocampus (5.8-fold), caudate nucleus (3.3-fold), putamen (3.0-fold) and cerebellar hemisphere (1.6-fold). The genetic variant C1459T (R487C) has been associated with reduced hepatic enzyme levels, stability and activity. Preliminary genotyping of this small sample (n=24) suggested that individuals with the CC genotype had higher brain CYP2B6 than those with the CT or TT genotype. Higher brain CYP2B6 activity in smokers and alcoholics may cause altered sensitivity to centrally acting drugs, increased susceptibility to neurotoxins and carcinogenic xenobiotics and contribute to central tolerance to nicotine.

  10. Genetic heterogeneity in Leber hereditary optic neuroretinopathy revealed by mitochondrial DNA polymorphism.

    PubMed

    Vilkki, J; Savontaus, M L; Nikoskelainen, E K

    1989-08-01

    The presence or absence of a recently observed mitochondrial DNA (mtDNA) mutation associated with Leber hereditary optic neuroretinopathy (LHON) was tested in 19 Finnish families with cases of LHON. Leukocyte and muscle DNA from individuals with optic atrophy, microangiopathy, or normal fundi from maternal lineages were studied by Southern blot analysis, using mouse mtDNA as a hybridization probe. The mtDNA mutation, detected as SfaNI site polymorphism, was seen in 10 of the 19 families. In one family, the mutation was seen only in the two affected individuals, indicating recent origin for the mutation. Nine families and 28 maternally unrelated controls did not show the mutation. The results imply that alternative mtDNA mutations are associated with LHON and that this genetic heterogeneity may be the cause of the interfamilial variation in the clinical expression of LHON. In the families showing the SfaNI site mutation, the mutation was homoplasmic in all individuals irrespective of their disease status, suggesting that the intrafamilial variation in the clinical expression is not due to different ratios of mutant versus normal mtDNA. PMID:2757028

  11. Effect of CYP2D6 genetic polymorphism on the metabolism of citalopram in vitro.

    PubMed

    Hu, Xiao-Xia; Yuan, Ling-Jing; Fang, Ping; Mao, Yong-Hui; Zhan, Yun-Yun; Li, Xiang-Yu; Dai, Da-Peng; Cai, Jian-Ping; Hu, Guo-Xin

    2016-04-01

    Genetic polymorphisms of CYP2D6 significantly influence the efficacy and safety of some drugs, which might cause adverse effects and therapeutic failure. We aimed at investigating the role of CYP2D6 in the metabolism of citalopram and identifying the effect of 24 CYP2D6 allelic variants we found in Chinese Han population on the metabolism of citalopram in vitro. These CYP2D6 variants expressed by insect cells system were incubated with 10-1000 μM citalopram for 30 min at 37 °C and the reaction was terminated by cooling to -80 °C immediately. Citalopram and its metabolites were analyzed by high-performance liquid chromatography (HPLC). The intrinsic clearance (Vmax/Km) values of the variants toward citalopram metabolites were significantly altered, 38-129% for demethylcitalopram and 13-138% for citalopram N-oxide when compared with CYP2D6*1. Most of the tested rare alleles exhibited significantly decreased values due to increased Km and/or decreased Vmax values. We conclude that recombinant system could be used to investigate the enzymes involved in drug metabolism and these findings suggest that more attention should be paid to subjects carrying these CYP2D6 alleles when administering citalopram in the clinic. PMID:27016952

  12. Genetic diversity and relationships in olive ( Olea europaea L.) germplasm collections as determined by randomly amplified polymorphic DNA.

    PubMed

    Belaj, A.; Satovic, Z.; Rallo, L.; Trujillo, I.

    2002-09-01

    Genetic diversity studies using the RAPD technique were carried out in a set of 103 olive cultivars from the World Germplasm Bank of the Centro de Investigación y Formación Agraria (CIFA) "Alameda del Obispo" in Cordoba (Spain). A total of 126 polymorphisms (6.0 polymorphic markers per primer) out of 135 reproducible products (6.4 fragments per primer) were obtained from the 21 primers used. The number of bands per primer ranged from 4 to 11, whereas the number of polymorphic bands ranged from 3 to 10, corresponding to 83% of the amplification products. The dendrogram based on unweighted pair-group cluster analysis using Jaccard's index includes three major groups according to their origin: (1) cultivars from the Eastern and Central Mediterranean areas, (2) some Italian and Spanish cultivars, and (3) cultivars from the Western Mediterranean zone. The pattern of genetic variation among olive cultivars from three different Mediterranean zones (West, Centre and East) was analysed by means of the analysis of molecular variance (AMOVA). Although most of the genetic diversity was attributable to differences of cultivars within Mediterranean zones (96.86%) significant phi-values among zones (phi(st) = 0.031; p < 0.001) suggested the existence of phenotypic differentiation. Furthermore, the AMOVA analysis was used to partition the phenotypic variation of Spain, Italy (Western region), Greece and Turkey (Eastern region) into four categories: among regions, among countries (within regions), within countries, and among and within countries of each region. Most of the genetic diversity was attributable to differences among genotypes within a country. These results are consistent with the predominantly allogamous nature of Olea europaea L. species. This paper indicates the importance of the study of the amount and distribution of genetic diversity for a better exploration of olive genetic resources and the design of plant breeding programmes.

  13. Genetic Polymorphism in the Promoter Region of Serotonin Transporter: Implications for Ethanol Abuse in Children and Adolescents

    PubMed Central

    de Oliveira, Carlos Eduardo Coral; Oda, Julie Massayo Maeda; Ariza, Carolina Batista; Guembarovski, Roberta Losi; Hirata, Bruna Karina Banin; de Almeida, Felipe Campos; André, Nayara Delgado; Fungaro, Maria Helena Pelegrinelli; Watanabe, Maria Angelica Ehara

    2016-01-01

    Objectives: To provide a review of published literature regarding genetic polymorphism of serotonin transporter gene, named as 5-HTTLPR, and its potential role as a susceptibility marker for ethanol abuse in childhood and adolescence. Methods: A literature review of several databases was conducted with the following keywords: 5-HTTLPR, children or adolescents or teenagers, susceptibility, alcohol or ethanol, abuse or misuse. Results: Alcohol interacts with serotonergic synaptic transmission in several ways, and the reduced availability of serotonin transporters might foster brain dysfunction, driving to alcohol abuse. The initial use of ethanol in children and adolescents is determined primarily by environmental influences, whereas the establishment of drinking patterns is strongly controlled by genetic factors. Functional polymorphic variants in the promoter region of the 5-HTTLPR gene have age-dependent effects in alcohol abuse. This polymorphism, mapped to the 5′ region of the SLC6A4, is a variable number of tandem repeats (VNTR) and involves a direct repeat of 20–23 base pairs GC-rich sequences, comprising a short (S) allele, consisting of 14 repeats, and a long (L) allele, with 16 repeats. Additional variants have been described, although their influences on childhood and adolescence ethanol use are not clear. Conclusion: The influence of the 5-HTTLPR allelic variants in children and adolescent misuse of alcohol might be considered for clinical management, preventing long-term behavior problem. Identifying genetic markers associated to the potential alcohol misuse or abuse could be useful in guiding management and formulating effective coping strategies. PMID:27047556

  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

    2015-02-13

    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.

  15. High throughput screening of genetic polymorphisms by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

    PubMed

    Corona, Giuseppe; Toffoli, Giuseppe

    2004-12-01

    In the post genomic era, the screening of many different genetic polymorphisms in large populations represents a major goal that will facilitate the understanding of individual genetic variability in the development of multi factor diseases and in drug response and toxicities. The increasing interest in these pathogenetic and pharmacogenomic studies by both academic and pharmaceutical industry researchers has increased the demand for broad genome association studies. This demand has produced a boom in the development of new and robust high throughput screening methods for genotype analysis. Matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) represents an emerging and powerful technique for DNA analysis because of its high speed, accuracy, no label requirement, and cost-effectiveness. So far, many MALDI-TOF MS approaches have been developed for rapid screening of single nucleotide polymorphisms (SNPs), variable sequences repeat, epigenotype analysis, quantitative allele studies, and for the discovery of new genetic polymorphisms. The more established methods are based on single base primer extension and minisequencing implemented with new chemical features to overcome the limitations associated with DNA analysis using MALDI-TOF MS. These new promising methods of genotyping include both photochemical and other different chemical and enzyme cleavage strategies that facilitate sample automation and MS analysis for both real-time genotyping and resequencing screening. In this review, we analyze and discuss in depth the advantages and the limitations of the more recent developments in MALDI-TOF MS analysis for large-scale genomic studies applications.

  16. 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

  17. 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

  18. 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

    2015-12-02

    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.

  19. Genetic Polymorphisms Associated to Folate Transport as Predictors of Increased Risk for Acute Lymphoblastic Leukemia in Mexican Children.

    PubMed

    Zaruma-Torres, Fausto; Lares-Asseff, Ismael; Lima, Aurea; Reyes-Espinoza, Aarón; Loera-Castañeda, Verónica; Sosa-Macías, Martha; Galaviz-Hernández, Carlos; Arias-Peláez, María C; Reyes-López, Miguel A; Quiñones, Luis A

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is a frequent neoplasia occurring in children. The most commonly used drug for the treatment of ALL is methotrexate (MTX), an anti-folate agent. Previous studies suggest that folate transporters play a role in ALL prognosis and that genetic polymorphism of genes encoding folate transporters may increase the risk of ALL. Therefore, the main goal of this study was to determine the associations among six genetic polymorphisms in four genes related with the folate transporter pathway to determine a relationship with the occurrence of ALL in Mexican children. A case-control study was performed in 73 ALL children and 133 healthy children from Northern and Northwestern Mexico. COL18A1 (rs2274808), SLC19A1 (rs2838956), ABCB1 (rs1045642 and rs1128503), and ABCC5 (rs9838667 and rs3792585). Polymorphisms were assayed through qPCR. Our results showed an increased ALL risk in children carrying CT genotype (OR = 2.55, CI 95% 1.11-5.83, p = 0.0001) and TT genotype (OR = 21.05, CI 95% 5.62-78.87, p < 0.0001) of COL18A1 rs2274808; in SLC19A1 rs2838956 AG carriers (OR = 44.69, CI 95% 10.42-191.63, p = 0.0001); in ABCB1 rs1045642 TT carriers (OR = 13.76, CI 95% 5.94-31.88, p = 0.0001); in ABCC5 rs9838667 AC carriers (OR = 2.61, CI 95% 1.05-6.48, p < 0.05); and in ABCC5 rs3792585 CC carriers (OR = 9.99, CI 95% 3.19-31.28, p = 0.004). Moreover, several combinations of genetic polymorphisms were found to be significantly associated with a risk for ALL. Finally, two combinations of ABCC5 polymorphisms resulted in protection from this neoplasia. In conclusion, certain genetic polymorphisms related to the folate transport pathway, particularly COL18A1 rs2274808, SLC19A1 rs2838956, ABCB1 rs1045642, and ABCC5 rs3792585, were associated with an increased risk for ALL in Mexican children. PMID:27547186

  20. Genetic Polymorphisms Associated to Folate Transport as Predictors of Increased Risk for Acute Lymphoblastic Leukemia in Mexican Children

    PubMed Central

    Zaruma-Torres, Fausto; Lares-Asseff, Ismael; Lima, Aurea; Reyes-Espinoza, Aarón; Loera-Castañeda, Verónica; Sosa-Macías, Martha; Galaviz-Hernández, Carlos; Arias-Peláez, María C.; Reyes-López, Miguel A.; Quiñones, Luis A.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is a frequent neoplasia occurring in children. The most commonly used drug for the treatment of ALL is methotrexate (MTX), an anti-folate agent. Previous studies suggest that folate transporters play a role in ALL prognosis and that genetic polymorphism of genes encoding folate transporters may increase the risk of ALL. Therefore, the main goal of this study was to determine the associations among six genetic polymorphisms in four genes related with the folate transporter pathway to determine a relationship with the occurrence of ALL in Mexican children. A case-control study was performed in 73 ALL children and 133 healthy children from Northern and Northwestern Mexico. COL18A1 (rs2274808), SLC19A1 (rs2838956), ABCB1 (rs1045642 and rs1128503), and ABCC5 (rs9838667 and rs3792585). Polymorphisms were assayed through qPCR. Our results showed an increased ALL risk in children carrying CT genotype (OR = 2.55, CI 95% 1.11–5.83, p = 0.0001) and TT genotype (OR = 21.05, CI 95% 5.62–78.87, p < 0.0001) of COL18A1 rs2274808; in SLC19A1 rs2838956 AG carriers (OR = 44.69, CI 95% 10.42–191.63, p = 0.0001); in ABCB1 rs1045642 TT carriers (OR = 13.76, CI 95% 5.94–31.88, p = 0.0001); in ABCC5 rs9838667 AC carriers (OR = 2.61, CI 95% 1.05–6.48, p < 0.05); and in ABCC5 rs3792585 CC carriers (OR = 9.99, CI 95% 3.19–31.28, p = 0.004). Moreover, several combinations of genetic polymorphisms were found to be significantly associated with a risk for ALL. Finally, two combinations of ABCC5 polymorphisms resulted in protection from this neoplasia. In conclusion, certain genetic polymorphisms related to the folate transport pathway, particularly COL18A1 rs2274808, SLC19A1 rs2838956, ABCB1 rs1045642, and ABCC5 rs3792585, were associated with an increased risk for ALL in Mexican children. PMID:27547186

  1. Modular genetic architecture of the toxigenic plasmid pIS56-63 harboring cry1Ab21 in Bacillus thuringiensis subsp. thuringiensis strain IS5056.

    PubMed

    Murawska, Emilia; Fiedoruk, Krzysztof; Swiecicka, Izabela

    2014-01-01

    Bacillus thuringiensis subsp. thuringiensis IS5056, a strain highly toxic to Trichoplusia ni larvae, produces the newly described Cry1Ab21 delta-endotoxin encoded by a gene located in the 63.8 kb pIS56-63 plasmid. In this report we present the structure and functional similarity of this plasmid to other B. thuringiensis large toxigenic plasmids with particular interest focused on its modular architecture. The 61 open reading frames (ORFs) of the plasmid made four functional modules: (i) M1-mic, the mobile insertion cassette harboring cry1Ab21; (ii) M2-tra, the putative conjugative element; (iii) M3-reg, regulation sequence; and (iv) M4-rep, the ori44 replicon. These modules display similarity to corresponding sequences in distinct B. thuringiensis plasmids, but, in general, not to plasmid of other Bacillus cereus sensu lato. The nucleotide sequence and organization of genes in pIS56-63 were highly similar (80-100%) to those in pHT73 of B. thuringiensis HT73, and in p03 of B. thuringiensis HD771, particularly within the M3-reg and M4-rep modules, and slightly less in M2-tra, the latter of which is composed of two segments exhibiting homology to sequences in pBMB28, pAH187_45, pCT83, and pIS56-85 or to pCT72, pBMB67, p04, and pIS56-68. The tetrapartite structure of the toxigenic pIS56-63 plasmid strongly suggests that its hybrid nature is a result of recombination of various genetic elements originating from different extrachromosomal and chromosomal sources in B. thuringiensis. The presence of cry1Ab21 in the mobile cassette suggests that its occurrence on pIS56-63 resulted from recombination and transposition events during the evolution of the plasmid.

  2. Transferable EST-SSR markers for the study of polymorphism and genetic diversity in bread wheat.

    PubMed

    Gupta, P K; Rustgi, S; Sharma, S; Singh, R; Kumar, N; Balyan, H S

    2003-12-01

    Nearly 900 SSRs (simple sequence repeats) were identified among 15,000 ESTs (expressed sequence tags) belonging to bread wheat ( Triticum aestivumL.). The SSRs were defined by their minimum length, which ranged from 14 to 21 bp. The maximum length ranged from 24 to 87 bp depending upon the length of the repeat unit itself (1-7 bp). The average density of SSRs was one SSR per 9.2 kb of EST sequence screened. The trinucleotide repeats were the most abundant SSRs detected. As a representative sample, 78 primer pairs were designed, which were also used to screen the dbEST entries for Hordeum vulgare and Triticum tauschii (donor of the D-genome of cultivated wheat) using a cut-off E (expectation) value of 0.01. On the basis of in silico analysis, up to 55.12% of the primer pairs exhibited transferability from Triticum to Hordeum, indicating that the sequences flanking the SSRs are not only conserved within a single genus but also between related genera in Poaceae. Primer pairs for the 78 SSRs were synthesized and used successfully for the study of (1) their transferability to 18 related wild species and five cereal species (barley, oat, rye, rice and maize); and (2) polymorphism between the parents of four mapping populations available with us. A subset of 20 EST-SSR primers was also used to assess genetic diversity in a collection of 52 elite exotic wheat genotypes. This was done with a view to compare their utility relative to other molecular markers (gSSRs, AFLPs, and SAMPL) previously used by us for the same purpose with the same set of 52 bread wheat genotypes. Although only a low level of polymorphism was detected, relative to that observed with genomic SSRs, the study suggested that EST-SSRs can be successfully used for a variety of purposes, and may actually prove superior to SSR markers extracted from genomic libraries for diversity estimation and transferability. PMID:14508680

  3. Genetic variation and genetic structure of the endangered species Sinowilsonia henryi Hemsi. (Hamamelidaceae) revealed by amplified fragment length polymorphism (AFLP) markers.

    PubMed

    Zhang, H; Ji, W L; Li, M; Zhou, L Y

    2015-10-14

    Comprehensive research of genetic variation is crucial in designing conservation strategies for endangered and threatened species. Sinowilsonia henryi Hemsi. is a tertiary relic with a limited geographical distribution in the central and western areas of China. It is endangered because of climate change and habitat fragmentation over the last thousands of years. In this study, amplified fragment length polymorphism markers were utilized to estimate genetic diversity and genetic structure in and among S. henryi. In this study, Nei's genetic diversity and Shannon's information index were found to be 0.192 and 0.325 respectively, indicating a moderate-to-high genetic diversity in species. According to analysis of molecular variation results, 32% of the genetic variation was shown to be partitioned among populations, demonstrating a relatively high genetic divergence; this was supported by principal coordinate analysis and unweighted pair-group method with arithmetic average analysis. Moreover, the Mantel test showed that there was no significant correlation between genetic and geographical distances. The above results can be explained by the effects of habitat fragmentation, history traits, and gene drift. Based on the results, several implications were indicated and suggestions proposed for preservation strategies for this species.

  4. The study of genetic polymorphisms related to serotonin in Alzheimer's disease: a new perspective in a heterogenic disorder.

    PubMed

    Oliveira, J R; Zatz, M

    1999-04-01

    Genetic and environmental factors have been implicated in the development of Alzheimer's disease (AD), the most common form of dementia in the elderly. Mutations in 3 genes mapped on chromosomes 21, 14 and 1 are related to the rare early onset forms of AD while the epsilon 4 allele of the apolipoprotein E (APOE) gene (on chromosome 19) is the major susceptibility locus for the most common late onset AD (LOAD). Serotonin (5-hydroxytryptamine or 5-HT) is a key neurotransmitter implicated in the control of mood, sleep, appetite and a variety of traits and behaviors. Recently, a polymorphism in the transcriptional control region upstream of the 5-HT transporter (5-HTT) gene has been studied in several psychiatric diseases and personality traits. It has been demonstrated that the short variant(s) of this 5-HTT gene-linked polymorphic region (5-HTTLPR) is associated with a different transcriptional efficiency of the 5-HTT gene promoter resulting in decreased 5-HTT expression and 5-HT uptake in lymphocytes. An increased frequency of this 5-HTTLPR short variant polymorphism in LOAD was recently reported. In addition, another common polymorphic variation in the 5-HT2A and 5-HT2C serotonin receptor genes previously analyzed in schizophrenic patients was associated with auditory and visual hallucinations in AD. These observations suggest that the involvement of the serotonin pathway might provide an explanation for some aspects of the affective symptoms commonly observed in AD patients. In summary, research on genetic polymorphisms related to AD and involved in receptors, transporter proteins and the enzymatic machinery of serotonin might enhance our understanding of this devastating neurodegenerative disorder.

  5. 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:1.30–1.78). Additionally, the subgroup analysis also showed that the associations were still significant in case number more than 500 (OR=1.38, 95% CI: 1.04–1.83), while in the case number less than 500 was OR=1.55, 95% CI: 1.39–1.72. Conclusions: SNPs of PTPN22 (1858C>T) showed an increased risk of developing JIA. PMID:26587490

  6. Genetic Association of CHAT rs3810950 and rs2177369 Polymorphisms with the Risk of Alzheimer's Disease: A Meta-Analysis.

    PubMed

    Liu, Yong; Chen, Qicong; Liu, Xu; Dou, Mengmeng; Li, Silu; Zhou, Jiahui; Liu, Hong; Wu, Yongfu; Huang, Zunnan

    2016-01-01

    Choline acetyltransferase (CHAT) rs3810950 and rs2177369 polymorphisms have been implicated in susceptibility to Alzheimer's disease (AD). Due to the inconsistent results from previous studies, a meta-analysis was performed to estimate the association between these polymorphisms and AD risk more precisely. Pooled results of our meta-analysis indicated CHAT rs2177369 polymorphism was correlated with decreasing AD risk in one of five genetic models (dominant: OR = 0.77, 95% CI: 0.62-0.96), while rs3810950 mutant was associated with AD development in three models (allelic: OR = 1.18, 95% CI: 1.01-1.37, homozygous: OR = 1.63, 95% CI: 1.09-2.42, and recessive: OR = 1.65, 95% CI: 1.20-2.26). In subgroup analysis by ethnicity, the association between CHAT rs3810950 polymorphism and AD risk was just found in the recessive model (OR = 1.47, 95% CI: 1.05-2.07) among Caucasians, while four genetic models (allelic: OR = 1.23, 95% CI: 1.01-1.48; homozygous: OR = 2.24, 95% CI: 1.48-3.39; dominant: OR = 1.21, 95% CI: 1.06-1.40; and recessive: OR = 2.18, 95% CI: 1.45-3.29) assumed this association in Asians. In conclusion, our meta-analysis indicated CHAT rs2177369 polymorphism might play a protective role in AD, while rs3810950 variant was a risk factor for AD but its single heterozygous mutations might not influence susceptibility to AD. PMID:27597977

  7. Genetic Association of CHAT rs3810950 and rs2177369 Polymorphisms with the Risk of Alzheimer's Disease: A Meta-Analysis

    PubMed Central

    Liu, Yong; Chen, Qicong; Liu, Xu; Dou, Mengmeng; Li, Silu; Zhou, Jiahui; Liu, Hong

    2016-01-01

    Choline acetyltransferase (CHAT) rs3810950 and rs2177369 polymorphisms have been implicated in susceptibility to Alzheimer's disease (AD). Due to the inconsistent results from previous studies, a meta-analysis was performed to estimate the association between these polymorphisms and AD risk more precisely. Pooled results of our meta-analysis indicated CHAT rs2177369 polymorphism was correlated with decreasing AD risk in one of five genetic models (dominant: OR = 0.77, 95% CI: 0.62–0.96), while rs3810950 mutant was associated with AD development in three models (allelic: OR = 1.18, 95% CI: 1.01–1.37, homozygous: OR = 1.63, 95% CI: 1.09–2.42, and recessive: OR = 1.65, 95% CI: 1.20–2.26). In subgroup analysis by ethnicity, the association between CHAT rs3810950 polymorphism and AD risk was just found in the recessive model (OR = 1.47, 95% CI: 1.05–2.07) among Caucasians, while four genetic models (allelic: OR = 1.23, 95% CI: 1.01–1.48; homozygous: OR = 2.24, 95% CI: 1.48–3.39; dominant: OR = 1.21, 95% CI: 1.06–1.40; and recessive: OR = 2.18, 95% CI: 1.45–3.29) assumed this association in Asians. In conclusion, our meta-analysis indicated CHAT rs2177369 polymorphism might play a protective role in AD, while rs3810950 variant was a risk factor for AD but its single heterozygous mutations might not influence susceptibility to AD. PMID:27597977

  8. Genetic Association of CHAT rs3810950 and rs2177369 Polymorphisms with the Risk of Alzheimer's Disease: A Meta-Analysis

    PubMed Central

    Liu, Yong; Chen, Qicong; Liu, Xu; Dou, Mengmeng; Li, Silu; Zhou, Jiahui; Liu, Hong

    2016-01-01

    Choline acetyltransferase (CHAT) rs3810950 and rs2177369 polymorphisms have been implicated in susceptibility to Alzheimer's disease (AD). Due to the inconsistent results from previous studies, a meta-analysis was performed to estimate the association between these polymorphisms and AD risk more precisely. Pooled results of our meta-analysis indicated CHAT rs2177369 polymorphism was correlated with decreasing AD risk in one of five genetic models (dominant: OR = 0.77, 95% CI: 0.62–0.96), while rs3810950 mutant was associated with AD development in three models (allelic: OR = 1.18, 95% CI: 1.01–1.37, homozygous: OR = 1.63, 95% CI: 1.09–2.42, and recessive: OR = 1.65, 95% CI: 1.20–2.26). In subgroup analysis by ethnicity, the association between CHAT rs3810950 polymorphism and AD risk was just found in the recessive model (OR = 1.47, 95% CI: 1.05–2.07) among Caucasians, while four genetic models (allelic: OR = 1.23, 95% CI: 1.01–1.48; homozygous: OR = 2.24, 95% CI: 1.48–3.39; dominant: OR = 1.21, 95% CI: 1.06–1.40; and recessive: OR = 2.18, 95% CI: 1.45–3.29) assumed this association in Asians. In conclusion, our meta-analysis indicated CHAT rs2177369 polymorphism might play a protective role in AD, while rs3810950 variant was a risk factor for AD but its single heterozygous mutations might not influence susceptibility to AD.

  9. Estimating Additive and Non-Additive Genetic Variances and Predicting Genetic Merits Using Genome-Wide Dense Single Nucleotide Polymorphism Markers

    PubMed Central

    Su, Guosheng; Christensen, Ole F.; Ostersen, Tage; Henryon, Mark; Lund, Mogens S.

    2012-01-01

    Non-additive genetic variation is usually ignored when genome-wide markers are used to study the genetic architecture and genomic prediction of complex traits in human, wild life, model organisms or farm animals. However, non-additive genetic effects may have an important contribution to total genetic variation of complex traits. This study presented a genomic BLUP model including additive and non-additive genetic effects, in which additive and non-additive genetic relation matrices were constructed from information of genome-wide dense single nucleotide polymorphism (SNP) markers. In addition, this study for the first time proposed a method to construct dominance relationship matrix using SNP markers and demonstrated it in detail. The proposed model was implemented to investigate the amounts of additive genetic, dominance and epistatic variations, and assessed the accuracy and unbiasedness of genomic predictions for daily gain in pigs. In the analysis of daily gain, four linear models were used: 1) a simple additive genetic model (MA), 2) a model including both additive and additive by additive epistatic genetic effects (MAE), 3) a model including both additive and dominance genetic effects (MAD), and 4) a full model including all three genetic components (MAED). Estimates of narrow-sense heritability were 0.397, 0.373, 0.379 and 0.357 for models MA, MAE, MAD and MAED, respectively. Estimated dominance variance and additive by additive epistatic variance accounted for 5.6% and 9.5% of the total phenotypic variance, respectively. Based on model MAED, the estimate of broad-sense heritability was 0.506. Reliabilities of genomic predicted breeding values for the animals without performance records were 28.5%, 28.8%, 29.2% and 29.5% for models MA, MAE, MAD and MAED, respectively. In addition, models including non-additive genetic effects improved unbiasedness of genomic predictions. PMID:23028912

  10. Integrating Monitoring and Genetic Methods To Infer Historical Risks of PCBs and DDE to Common and Roseate Terns Nesting Near the New Bedford Harbor Superfund Site (Massachusetts, USA)

    EPA Science Inventory

    Common and roseate terns are migratory piscivorous seabirds with major breeding colonies within feeding range of thepolychlorinated biphenyl (PCB)-contaminated New Bedford Harbor (NBH, MA, USA) Superfund site. Our longitudinal study shows that before PCB discharges into NBH cease...

  11. Genetic polymorphism of β-fibrinogen gene-455G/A can contribute to the risk of ischemic stroke.

    PubMed

    Gu, Lian; Wu, Guangliang; Su, Li; Yan, Yan; Long, Jianxiong; Tan, Jinjing; Liang, Baoyun; Guo, Xiaojing; Huang, Guihua

    2014-02-01

    Many studies have investigated the association between the β-fibrinogen gene-455G/A (FGβ-455G/A) polymorphism and the risk of ischemic stroke. However, these evidences were inadequate to provide stronger conclusions because most studies were generally small. To shed light on these inconclusive findings, we conducted a large sample size meta-analysis of studies relating to the FGβ-455G/A polymorphism and the risk of ischemic stroke. Odds ratios with a 95 % confidence interval were used to investigate the association between FGβ-455G/A polymorphism and ischemic stroke. Publication bias was tested by Egger's test and funnel plot. Inconsistency index and Cochran's Q statistic were used to check heterogeneity. Cumulative and recursive cumulative meta-analyses were performed to provide a framework for updating a genetic effect from all of the included studies. Twenty-six independent publications with 4,070 cases and 4,649 controls were included in this meta-analysis. Results showed that the β-fibrinogen-455G/A polymorphism was significantly associated with the risk of ischemic stroke. The FGβ-455G/A polymorphism was found to be a risk factor for ischemic stroke in Asians and adults, while association was not observed for Caucasians and juveniles based on the small size and it may be necessary to conduct larger studies on them to investigate the association in the future. The cumulative meta-analysis indicated a decline from 1998 to 2003, and the results remained stable during the period 2004-2012. The results indicate that FGβ-455G/A polymorphism may be a susceptible predictor of ischemic stroke. More studies are needed to elucidate the relationship further.

  12. Glutathione S-transferase genetic polymorphisms (GSTM1, GSTT1 and GSTO2) in three Iranian populations.

    PubMed

    Rafiee, Laleh; Saadat, Iraj; Saadat, Mostafa

    2010-01-01

    Genetic polymorphisms in genes encoding glutathione S-transferases M1 (GSTM1; a member of class mu), T1 (GSTT1; a member of class theta) and O2 (GSTO2; a member of class omega) have been defined previously. Studies have revealed that there were significant differences between populations for allelic frequencies of GSTT1, GSTM1 and GSTO2 N412D polymorphisms. To get more insight into the genetic structure of Iranian populations the present study was done on Iranian Georgians living in Frydoonshahr (Isfahan province) and two Persian populations who living in Shiraz (Fars province) and Frydoonshahr. Study subjects consisted of 401 unrelated healthy individuals. From these 121 were Georgians. The remaining subjects were Persians from either Frydoonshahr (n = 34) or Shiraz (n = 246). The genetic polymorphism of GSTT1, GSTM1 and GSTO2 N412D was detected by PCR-based method. The frequency of GSTT1 null genotype in Georgian and Persians of Frydoonshahr and Shiraz was 15.7, 35.2 and 24.8%, respectively. There was significant difference between these populations for the distributions of the GSTT1 genotypes (chi(2) = 7.00, df = 2, P = 0.030). No significant difference was observed between these populations for polymorphisms of GSTM1 (chi(2) = 1.682, df = 2, P = 0.431) and GSTO N142D (chi(2) = 4.622, df = 4, P = 0.328). The prevalence of GSTT1 null genotype in Iranian Georgians showed significant difference with Persians and other Asian countries, but it seems to be similar with the frequency which was reported from European populations. PMID:19430957

  13. Novel Primate Model of Serotonin Transporter Genetic Polymorphisms Associated with Gene Expression, Anxiety and Sensitivity to Antidepressants.

    PubMed

    Santangelo, Andrea M; Ito, Mitsuteru; Shiba, Yoshiro; Clarke, Hannah F; Schut, Evelien Hs; Cockcroft, Gemma; Ferguson-Smith, Anne C; Roberts, Angela C

    2016-08-01

    Genetic polymorphisms in the repeat upstream region of the serotonin transporter gene (SLC6A4) are associated with individual differences in stress reactivity, vulnerability to affective disorders, and response to pharmacotherapy. However, the molecular, neurodevelopmental and psychopharmacological mechanisms underlying the link between SLC6A4 polymorphisms and the emotionally vulnerable phenotype are not fully understood. Thus, using the marmoset monkey Callithrix jacchus we characterize here a new neurobiological model to help to address these questions. We first sequenced the marmoset SLC6A4 promoter and identified a double nucleotide polymorphism (-2053AC/CT) and two single-nucleotide polymorphisms (-2022C/T and -1592G/C) within the repeat upstream region. We showed their association with gene expression using in vivo quantitative PCR and with affective behavior using a primate test of anxiety (human intruder test). The low-expressing haplotype (AC/C/G) was linked with high anxiety while the high-expressing one (CT/T/C) was associated with an active coping strategy in response to threat. Pharmacological challenge with an acute dose of the selective serotonin reuptake inhibitor, citalopram, revealed a genotype-dependent behavioral response. While individuals homozygous for the high anxiety-related haplotype AC/C/G exhibited a dose-dependent, anxiogenic response, individuals homozygous for the low anxiety-related haplotype CT/T/C showed an opposing, dose-dependent anxiolytic effect. These findings provide a novel genetic and behavioral primate model to study the molecular, neurodevelopmental, and psychopharmacological mechanisms that underlie genetic variation-associated complex behaviors, with specific implications for the understanding of normal and abnormal serotonin actions and the development of personalized pharmacological treatments for psychiatric disorders. PMID:26997299

  14. Novel Primate Model of Serotonin Transporter Genetic Polymorphisms Associated with Gene Expression, Anxiety and Sensitivity to Antidepressants

    PubMed Central

    Santangelo, Andrea M; Ito, Mitsuteru; Shiba, Yoshiro; Clarke, Hannah F; Schut, Evelien HS; Cockcroft, Gemma; Ferguson-Smith, Anne C; Roberts, Angela C

    2016-01-01

    Genetic polymorphisms in the repeat upstream region of the serotonin transporter gene (SLC6A4) are associated with individual differences in stress reactivity, vulnerability to affective disorders, and response to pharmacotherapy. However, the molecular, neurodevelopmental and psychopharmacological mechanisms underlying the link between SLC6A4 polymorphisms and the emotionally vulnerable phenotype are not fully understood. Thus, using the marmoset monkey Callithrix jacchus we characterize here a new neurobiological model to help to address these questions. We first sequenced the marmoset SLC6A4 promoter and identified a double nucleotide polymorphism (−2053AC/CT) and two single-nucleotide polymorphisms (−2022C/T and −1592G/C) within the repeat upstream region. We showed their association with gene expression using in vivo quantitative PCR and with affective behavior using a primate test of anxiety (human intruder test). The low-expressing haplotype (AC/C/G) was linked with high anxiety while the high-expressing one (CT/T/C) was associated with an active coping strategy in response to threat. Pharmacological challenge with an acute dose of the selective serotonin reuptake inhibitor, citalopram, revealed a genotype-dependent behavioral response. While individuals homozygous for the high anxiety-related haplotype AC/C/G exhibited a dose-dependent, anxiogenic response, individuals homozygous for the low anxiety-related haplotype CT/T/C showed an opposing, dose-dependent anxiolytic effect. These findings provide a novel genetic and behavioral primate model to study the molecular, neurodevelopmental, and psychopharmacological mechanisms that underlie genetic variation-associated complex behaviors, with specific implications for the understanding of normal and abnormal serotonin actions and the development of personalized pharmacological treatments for psychiatric disorders. PMID:26997299

  15. An Association Study Between Genetic Polymorphisms in Functional Regions of Five Genes and the Risk of Schizophrenia.

    PubMed

    Yan, Peng; Qiao, Xiaomeng; Wu, Hua; Yin, Fangyuan; Zhang, Jing; Ji, Yuanyuan; Wei, Shuguang; Lai, Jianghua

    2016-07-01

    Schizophrenia is a severe mental disorder that is likely to be strongly determined by genetic factors. To identify markers of disks, large homolog 2 (DLG2), FAT atypical cadherin 3 (FAT3), kinectin1 (KTN1), deleted in colorectal carcinoma (DCC), and glycogen synthase kinase-3β (GSK3β) that contribute to the genetic susceptibility to schizophrenia, we systematically screened for polymorphisms in the functional regions of these genes. A total of 22 functional single-nucleotide polymorphisms (SNPs) in 940 Chinese subjects were genotyped using SNaPshot. The results first suggested that the allelic and genotypic frequencies of the DCC polymorphism rs2229080 were nominally associated with schizophrenia. The patients were significantly less likely to be CC homozygous (P = 0.005, odds ratio [OR] = 0.635, 95 % confidence interval [95 % CI] = 0.462-0.873), and the schizophrenia subjects exhibited lower frequency of the C allele (P = 0.024, OR = 0.811, 95 % CI = 0.676-0.972). Regarding GSK3β, there was a significant difference in genotype distribution of rs3755557 between schizophrenia and healthy control subjects (P = 0.009). The patients exhibited a significantly lower frequency of the T allele of rs3755557 (P = 0.002, OR = 0.654, 95 % CI = 0.498-0.860). Our results point to the polymorphisms of DCC and GSK3β as contributors to the genetic basis of individual differences in the susceptibility to schizophrenia.

  16. 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

  17. 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...

  18. [Polymorphism of 17 Y-STR loci in She ethnic population in Fujian and genetic relationship with 11 populations].

    PubMed

    Bai, Ru-Feng; Yang, Li-Hai; Yuan, Li; Liang, Quan-Zeng; Lu, Di; Yang, Xue; Shi, Mei-Sen

    2012-08-01

    To investigate the genetic polymorphisms of 17 Y-chromosomal short tandem repeats(Y-STR) loci in She ethnic population from Fujian province, and to evaluate their forensic application values and genetic relationship with other 11 populations, 152 unrelated male individuals of She ethnic population in Fujian were used to determine the distribution of allele frequencies and haplotypes by using Y-filerTM System. Cluster analysis and phylogenic trees were applied to show the genetic distance among the populations. As a result, 50 haplotypes were found in DYS385a/b loci, and 3~11 alleles were found in the rest 15 Y-STR loci. The GD value was from 0.4037(DYS391) to 0. 9725(DYS385a/b). This study has also revealed "off-ladder" alleles at several Y-loci, namely DYS448, DYS393, DYS458 and DYS635, and several occurrences of duplications at the DYS385a/b, DYS19 and DYS390 loci. One hundred and forty-four haplotypes were found in 17 Y-STR loci, of which 138 were unique, 5 were found in 2 individuals, 1 was found in 4 individuals, and the observed haplotypes diversity value was 0.9990. Comparing with 11 populations, the genetic distance between She ethnic and Han population in Zhejiang was the smallest (0.0042), while it was the largest between She ethnic and Tibet ethnic population (0.2380). Cluster analysis and phylogenetic tree both demonstrated that genetic distance between She ethnic and several south Han populations is closer than between She ethnic and non-Han populations. Multiplex detection of the 17 Y-STR loci revealed a highly polymorphic genetic distribution, which would be very powerful for establishing a Y-STR database, for population genetics and forensic practice.

  19. Reliable in silico identification of sequence polymorphisms and their application for extending the genetic map of sugar beet (Beta vulgaris).

    PubMed

    Holtgräwe, Daniela; Sörensen, Thomas Rosleff; Viehöver, 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.

  20. 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.

  1. Reliable In Silico Identification of Sequence Polymorphisms and Their Application for Extending the Genetic Map of Sugar Beet (Beta vulgaris)

    PubMed Central

    Holtgräwe, Daniela; Sörensen, Thomas Rosleff; Viehöver, 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

  2. Applicability of genetic polymorphism analysis for the diagnosis of Angelman syndrome and the correlation between language difficulties and disease phenotype.

    PubMed

    Wang, K; Li, Y T; Hou, M

    2016-01-01

    Angelman syndrome (AS) is a neurogenetic disorder caused by a defect in the expression of the maternally inherited ubiquitin protein ligase E3A (UBE3A) gene in chromosome 15. The most common genetic defects include maternal deletions in chromosome 15q11-13; however, paternal uniparental disomy and imprinting defects allow for the identification of mutations in UBE3A in 10% of patients with AS. The aim of this study was to validate the clinical features and genetic polymorphisms of AS, and to discuss the relationship between functional language lateralization and the arcuate fasciculus in the Broca's and Wernicke's areas. Six children with AS (mean age = 32.57 months) presenting characteristic behavioral patterns of AS (frequent laughter and happy demeanor, hand flapping, and hypermotor behavior) were recruited to this study. The patients underwent a clinical evaluation (clinical history, dysmorphological and neurological examinations, and psychological evaluations) and paraclinical investigations [genetic tests (fluorescence in situ hybridization and methylation polymerase chain reaction), electroencephalogram, and magnetic resonance imaging]. We conclude that AS diagnosis cannot rely solely on genetic testing for polymorphisms in UBE3A and must consider its clinical characteristics. Moreover, functional language lateralization and the arcuate fasciculus in the Broca's and Wernicke's areas were found to be closely correlated. Therefore, UBE3A gene mutation analysis combined with comprehensive clinical evaluations may be suitable for the diagnosis of AS. PMID:27323188

  3. 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

  4. An approach for the quantitative consideration of genetic polymorphism data in chemical risk assessment: examples with warfarin and parathion.

    PubMed

    Gentry, P Robinan; Hack, C Eric; Haber, Lynne; Maier, Andrew; Clewell, Harvey J

    2002-11-01

    In recent years, a great deal of research has been conducted to identify genetic polymorphisms. One focus has been to characterize variability in metabolic enzyme systems that could impact internal doses of pharmaceuticals or environmental pollutants. Methods are needed for using this metabolic information to estimate the resulting variability in tissue doses associated with chemical exposure. We demonstrate here the use of physiologically based pharmacokinetic (PBPK) modeling in combination with Monte Carlo analysis to incorporate information on polymorphisms into the analysis of toxicokinetic variability. Warfarin and parathion were used as case studies to demonstrate this approach. Our results suggest that polymorphisms in the PON1 gene, that give rise to allelic variants of paraoxonase, which is involved in the metabolism of paraoxon (a metabolite of parathion), make only a minor contribution to the overall variability in paraoxon tissue dose, while polymorphisms in the CYP2C9 gene, which gives rise to allelic variants of the major metabolic enzyme for warfarin, account for a significant portion of the overall variability in (S)-warfarin tissue dose. These analyses were used to estimate chemical-specific adjustment factors (CSAFs) for the human variability in toxicokinetics for both parathion and warfarin. Implications of alternatives in the calculation of CSAFs are explored. Key decision points for applying the PBPK-Monte Carlo approach to evaluate toxicokinetic variability for other chemicals are also discussed.

  5. Genetic distribution and association analysis of DRD2 gene polymorphisms with major depressive disorder in the Chinese Han population.

    PubMed

    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.

  6. Genetic association analysis of TAP1 and TAP2 polymorphisms with aspirin exacerbated respiratory disease and its FEV1 decline.

    PubMed

    Kim, Jeong-Hyun; Park, Byung-Lae; Pasaje, Charisse Flerida A; Bae, Joon Seol; Park, Jong Sook; Park, Sung Woo; Uh, Soo-Taek; Kim, Mi-Kyeong; Choi, Inseon S; Cho, Sang Heon; Choi, Byoung Whui; Park, Choon-Sik; Shin, Hyoung Doo

    2011-09-01

    Aspirin exacerbated respiratory disease (AERD) induces bronchoconstriction in asthmatic patients characterized with a clinical condition of severe decline in forced expiratory volume in one second (FEV1) after ingestion of aspirin. Two genes consisting a heterodimer, transporter 1 and 2, ATP-binding cassette, sub-family B (MDR/TAP) (TAP1 and TAP2) within the major histocompatibility complex (MHC) region, have been implicated in immunodeficiency and bronchiectasis development. To investigate the associations of TAP1 and TAP2 genetic polymorphisms with AERD and phenotypic FEV1 decline, a total of 43 common single-nucleotide polymorphisms (SNPs) including 12 SNPs of TAP1 and 31 SNPs of TAP2 were genotyped in 93 AERD patients and 96 aspirin-tolerant asthma controls. Interestingly, regression analysis revealed that polymorphisms and haplotypes of TAP2 were associated with FEV1 decline by aspirin provocation (P=0.002-0.04), with about twofold decline rate of FEV1 in most of minor homozygotes compared with major homozygotes. In addition, nominal evidences of association between TAP2 and AERD development were observed (P=0.02-0.04). However, TAP1 polymorphisms showed no relations to both AERD and FEV1 decline after aspirin challenge (P>0.05). Although further functional evaluations and replications are required, our preliminary findings provide supporting information that variants of TAP2 might be predisposing factors for FEV1 decline-related symptoms.

  7. Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population

    PubMed Central

    2010-01-01

    Background The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed TP53 72Arg>Pro and MDM2 309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored. Methods In this study, we performed a case-control study between 522 NPC patients and 722 healthy controls in a Chinese population by using PCR-RFLP. Results We found an increased NPC risk associated with the MDM2 GG (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 2.08-3.96) and TG (OR = 1.49, 95% CI = 1.16-2.06) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.22, 95% CI = 1.58-3.10) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased adult NPC risk in a more than multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.75, 95% CI = 3.53-17.58). Conclusion The findings suggest that polymorphisms of MDM2 and TP53 genes may be genetic modifier for developing NPC. PMID:20398418

  8. An approach for the quantitative consideration of genetic polymorphism data in chemical risk assessment: examples with warfarin and parathion.

    PubMed

    Gentry, P Robinan; Hack, C Eric; Haber, Lynne; Maier, Andrew; Clewell, Harvey J

    2002-11-01

    In recent years, a great deal of research has been conducted to identify genetic polymorphisms. One focus has been to characterize variability in metabolic enzyme systems that could impact internal doses of pharmaceuticals or environmental pollutants. Methods are needed for using this metabolic information to estimate the resulting variability in tissue doses associated with chemical exposure. We demonstrate here the use of physiologically based pharmacokinetic (PBPK) modeling in combination with Monte Carlo analysis to incorporate information on polymorphisms into the analysis of toxicokinetic variability. Warfarin and parathion were used as case studies to demonstrate this approach. Our results suggest that polymorphisms in the PON1 gene, that give rise to allelic variants of paraoxonase, which is involved in the metabolism of paraoxon (a metabolite of parathion), make only a minor contribution to the overall variability in paraoxon tissue dose, while polymorphisms in the CYP2C9 gene, which gives rise to allelic variants of the major metabolic enzyme for warfarin, account for a significant portion of the overall variability in (S)-warfarin tissue dose. These analyses were used to estimate chemical-specific adjustment factors (CSAFs) for the human variability in toxicokinetics for both parathion and warfarin. Implications of alternatives in the calculation of CSAFs are explored. Key decision points for applying the PBPK-Monte Carlo approach to evaluate toxicokinetic variability for other chemicals are also discussed. PMID:12388841

  9. Genetic polymorphism directs IL-6 expression in fibroblasts but not selected other cell types.

    PubMed

    Noss, Erika H; Nguyen, Hung N; Chang, Sook Kyung; Watts, Gerald F M; Brenner, Michael B

    2015-12-01

    Interleukin (IL)-6 blockade is an effective treatment for rheumatoid arthritis (RA), and synovial fibroblasts are a major IL-6 producer in the inflamed joint. We found that human RA and osteoarthritis (OA) synovial fibroblasts derived from independent donors reproducibly segregated into low, medium, and high IL-6 producers, independent of stimulus, cell passage, or disease state. IL-6 expression pattern correlated strongly with total mRNA expression, not mRNA stability, suggesting transcriptional rather than posttranscriptional regulation. High-fibroblast IL-6 expression was significantly associated with the IL-6 proximal promoter single nucleotide polymorphism (SNP) rs1800795 minor allele (CC) genotype. In contrast, no association between this SNP and IL-6 production was detected in CD14(+) monocytes, another major producer of synovial IL-6. Luciferase expression assays confirmed that this SNP was associated with differential IL-6 expression in fibroblasts. To date, several association studies examining rs1800795 allele frequency and disease risk have reported seemingly conflicting results ranging from no association to association with either the major or minor allele across a spectrum of conditions, including cancer and autoimmune, cardiovascular, infectious, and metabolic diseases. This study points to a prominent contribution from promoter genetic variation in fibroblast IL-6 regulation, but not in other IL-6-producing cell types. We propose that some of the heterogeneity in these clinical studies likely reflects the cellular source of IL-6 in specific diseases, much of which may be produced by nonhematopoietic cells. These results highlight that functional analysis of disease-associated SNPs on gene expression and pathologic processes must consider variation in diverse cell types.

  10. Genetic Polymorphisms Affect Mouse and Human Trace Amine-Associated Receptor 1 Function.

    PubMed

    Shi, Xiao; Walter, Nicole A R; Harkness, John H; Neve, Kim A; Williams, Robert W; Lu, Lu; Belknap, John K; Eshleman, Amy J; Phillips, Tamara J; Janowsky, Aaron

    2016-01-01

    Methamphetamine (MA) and neurotransmitter precursors and metabolites such as tyramine, octopamine, and β-phenethylamine stimulate the G protein-coupled trace amine-associated receptor 1 (TAAR1). TAAR1 has been implicated in human conditions including obesity, schizophrenia, depression, fibromyalgia, migraine, and addiction. Additionally TAAR1 is expressed on lymphocytes and astrocytes involved in inflammation and response to infection. In brain, TAAR1 stimulation reduces synaptic dopamine availability and alters glutamatergic function. TAAR1 is also expressed at low levels in heart, and may regulate cardiovascular tone. Taar1 knockout mice orally self-administer more MA than wild type and are insensitive to its aversive effects. DBA/2J (D2) mice express a non-synonymous single nucleotide polymorphism (SNP) in Taar1 that does not respond to MA, and D2 mice are predisposed to high MA intake, compared to C57BL/6 (B6) mice. Here we demonstrate that endogenous agonists stimulate the recombinant B6 mouse TAAR1, but do not activate the D2 mouse receptor. Progeny of the B6XD2 (BxD) family of recombinant inbred (RI) strains have been used to characterize the genetic etiology of diseases, but contrary to expectations, BXDs derived 30-40 years ago express only the functional B6 Taar1 allele whereas some more recently derived BXD RI strains express the D2 allele. Data indicate that the D2 mutation arose subsequent to derivation of the original RIs. Finally, we demonstrate that SNPs in human TAAR1 alter its function, resulting in expressed, but functional, sub-functional and non-functional receptors. Our findings are important for identifying a predisposition to human diseases, as well as for developing personalized treatment options. PMID:27031617

  11. Genetic Polymorphisms Affect Mouse and Human Trace Amine-Associated Receptor 1 Function

    PubMed Central

    Shi, Xiao; Walter, Nicole A. R.; Harkness, John H.; Neve, Kim A.; Williams, Robert W.; Lu, Lu; Belknap, John K.; Eshleman, Amy J.; Phillips, Tamara J.; Janowsky, Aaron

    2016-01-01

    Methamphetamine (MA) and neurotransmitter precursors and metabolites such as tyramine, octopamine, and β-phenethylamine stimulate the G protein-coupled trace amine-associated receptor 1 (TAAR1). TAAR1 has been implicated in human conditions including obesity, schizophrenia, depression, fibromyalgia, migraine, and addiction. Additionally TAAR1 is expressed on lymphocytes and astrocytes involved in inflammation and response to infection. In brain, TAAR1 stimulation reduces synaptic dopamine availability and alters glutamatergic function. TAAR1 is also expressed at low levels in heart, and may regulate cardiovascular tone. Taar1 knockout mice orally self-administer more MA than wild type and are insensitive to its aversive effects. DBA/2J (D2) mice express a non-synonymous single nucleotide polymorphism (SNP) in Taar1 that does not respond to MA, and D2 mice are predisposed to high MA intake, compared to C57BL/6 (B6) mice. Here we demonstrate that endogenous agonists stimulate the recombinant B6 mouse TAAR1, but do not activate the D2 mouse receptor. Progeny of the B6XD2 (BxD) family of recombinant inbred (RI) strains have been used to characterize the genetic etiology of diseases, but contrary to expectations, BXDs derived 30–40 years ago express only the functional B6 Taar1 allele whereas some more recently derived BXD RI strains express the D2 allele. Data indicate that the D2 mutation arose subsequent to derivation of the original RIs. Finally, we demonstrate that SNPs in human TAAR1 alter its function, resulting in expressed, but functional, sub-functional and non-functional receptors. Our findings are important for identifying a predisposition to human diseases, as well as for developing personalized treatment options. PMID:27031617

  12. Sequencing based typing for genetic polymorphisms in exons, 2, 3 and 4 of the MICA gene.

    PubMed

    Katsuyama, Y; Ota, M; Ando, H; Saito, S; Mizuki, N; Kera, J; Bahram, S; Nose, Y; Inoko, H

    1999-08-01

    We have established a sequencing based typing (SBT) method for detection of genetic polymorphism in the exon 2 to 4 domains of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) and applied it to allele typing of 130 healthy Japanese individuals. A 2.2-kb segment including exons 2, 3 and 4 of the MICA gene was amplified by a pair of generic primers followed by cycle sequencing using exon-specific nested primers. In total, 8 alleles were observed in a Japanese population and the most frequent allele was MICA008 with the gene frequency of 30.8%. MICA009 was the second most frequent (16.5%), while the rarest one was MICA007 (1.2%). MICA alleles displayed strong linkage equilibria with HLA-B antigens (i.e. MICA008 with B7, B48, B60 and B61; MICA009 with B51 and B52; MICA002 with B35, B39, B58 and B67; MICA004 with B44, MICA007 with B13 and B27; MICA010 with B46, B62 and B48, MICA012 with B54, B55, B56 and B59; MICA019 and B70, B71 and B62). Recently, the B48 haplotype has been reported to lack the entire MICA gene by a large-scale deletion in a Japanese population. Among 8 serologically B48 homozygous individuals, 4 were found to represent this MICA null allele as assessed by no polymerase chain reaction (PCR) amplification using MICA-specific primers, while the remaining four possessed the intact MICA gene with MICA008 or MICA010.

  13. Impact of genetic polymorphisms and drug-drug interactions on clopidogrel and prasugrel response variability.

    PubMed

    Ancrenaz, V; Daali, Y; Fontana, P; Besson, M; Samer, C; Dayer, P; Desmeules, J

    2010-10-01

    Thienopyridine antiaggregating platelet agents (clopidogrel and prasugrel) act as irreversible P2Y12 receptor inhibitors. They are used with aspirin to prevent thrombotic complications after an acute coronary syndrome or percutaneous coronary intervention. A large interindividual variability in response to clopidogrel and to a lesser extent to prasugrel is observed and may be related to their metabolism. Clopidogrel and prasugrel are indeed prodrugs converted into their respective active metabolites by several cytochromes P450 (CYPs). Besides clopidogrel inactivation (85%) by esterases to the carboxylic acid, clopidogrel is metabolized by CYPs to 2-oxo-clopidogrel (15%) and further metabolized to an unstable but potent platelet-aggregating inhibitor. Prasugrel is more potent than clopidogrel with a better bioavailability and lower pharmacodynamic variability. Prasugrel is completely converted by esterases to an intermediate oxo-metabolite (R-95913) further bioactivated by CYPs. Numerous clinical studies have shown the influence of CYP2C19 polymorphism on clopidogrel antiplatelet activity. Moreover, unwanted drug-drug pharmacokinetic interactions influencing CYP2C19 activity and clopidogrel bioactivation such as with proton pump inhibitors remain a matter of intense controversy. Several studies have also demonstrated that CYP3A4/5 and CYP1A2 are important in clopidogrel bioactivation and should also be considered as potential targets for unwanted drug-drug interactions. Prasugrel bioactivation is mainly related to CYP3A4 and 2B6 activity and therefore the question of the effect of drug-drug interaction on its activity is open. The purpose of this review is to critically examine the current literature evaluating the influence of genetic and environmental factors such as unwanted drug-drug interaction affecting clopidogrel and prasugrel antiplatelet activity. PMID:20942779

  14. Genetic Polymorphisms Affect Mouse and Human Trace Amine-Associated Receptor 1 Function.

    PubMed

    Shi, Xiao; Walter, Nicole A R; Harkness, John H; Neve, Kim A; Williams, Robert W; Lu, Lu; Belknap, John K; Eshleman, Amy J; Phillips, Tamara J; Janowsky, Aaron

    2016-01-01

    Methamphetamine (MA) and neurotransmitter precursors and metabolites such as tyramine, octopamine, and β-phenethylamine stimulate the G protein-coupled trace amine-associated receptor 1 (TAAR1). TAAR1 has been implicated in human conditions including obesity, schizophrenia, depression, fibromyalgia, migraine, and addiction. Additionally TAAR1 is expressed on lymphocytes and astrocytes involved in inflammation and response to infection. In brain, TAAR1 stimulation reduces synaptic dopamine availability and alters glutamatergic function. TAAR1 is also expressed at low levels in heart, and may regulate cardiovascular tone. Taar1 knockout mice orally self-administer more MA than wild type and are insensitive to its aversive effects. DBA/2J (D2) mice express a non-synonymous single nucleotide polymorphism (SNP) in Taar1 that does not respond to MA, and D2 mice are predisposed to high MA intake, compared to C57BL/6 (B6) mice. Here we demonstrate that endogenous agonists stimulate the recombinant B6 mouse TAAR1, but do not activate the D2 mouse receptor. Progeny of the B6XD2 (BxD) family of recombinant inbred (RI) strains have been used to characterize the genetic etiology of diseases, but contrary to expectations, BXDs derived 30-40 years ago express only the functional B6 Taar1 allele whereas some more recently derived BXD RI strains express the D2 allele. Data indicate that the D2 mutation arose subsequent to derivation of the original RIs. Finally, we demonstrate that SNPs in human TAAR1 alter its function, resulting in expressed, but functional, sub-functional and non-functional receptors. Our findings are important for identifying a predisposition to human diseases, as well as for developing personalized treatment options.

  15. Genetic polymorphisms in arginase I and II and childhood asthma and atopy

    PubMed Central

    Li, Huiling; Romieu, Isabelle; Sienra-Monge, Juan-Jose; Ramirez-Aguilar, Matiana; Rio-Navarro, Blanca Estela del; Kistner, Emily O.; Gjessing, Håkon K.; Lara-Sanchez, Irma del Carmen; Chiu, Grace Y.; London MD, Stephanie J.

    2006-01-01

    Background A recent microarray study implicated arginase I (ARG1) and arginase II (ARG2) in mouse allergic asthma models and human asthma. Objectives To examine the association between genetic variation in ARG1 and ARG2 and childhood asthma and atopy risk. Methods We enrolled 433 case-parent triads, consisting of asthmatics 4 to 17 years and their biologic parents, from the allergy clinic of a public hospital in Mexico City between 1998 and 2003. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped 4 single nucleotide polymorphisms (SNPs) of ARG1 and 4 SNPs of ARG2 with minor allele frequencies over 10% using the TaqMan assay. Results ARG1 SNPs and haplotypes were not associated with asthma but all four ARG1 SNPs were associated with the number of positive skin tests (P = 0.007 to 0.018). Carrying two copies of minor alleles for either of two highly associated ARG2 SNPs was associated with a statistically significant increased relative risk (RR) of asthma [1.5, 95% confidence interval (CI) 1.1–2.1 for arg2s1; RR = 1.6, 95% CI = 1.1–2.3 for arg2s2]. The association was slightly stronger among children with a smoking parent (arg2s1 RR = 2.1, 95% CI = 1.2 – 3.9 with a smoking parent; RR =1.2, 95% CI = 0.8–1.9 without, interaction P = 0.025). Haplotype analyses reduced the sample size but supported the single SNP results. One ARG2 SNP was related to the number of positive skin tests (P = 0.027). Conclusions Variation in arginase genes may contribute to asthma and atopy in children. PMID:16387594

  16. Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy

    PubMed Central

    Li, Huiling; Romieu, Isabelle; Wu, Hao; Sienra-Monge, Juan-Jose; Ramírez-Aguilar, Matiana; del Río-Navarro, Blanca Estela; Lara-Sánchez, Irma del Carmen; Kistner, Emily O.; Gjessing, Håkon K.; London, Stephanie J.

    2007-01-01

    Transforming growth factor beta-1 (TGFB1) may influence asthma by modulating allergic airway inflammation and airway remodeling. The role of single nucleotide polymorphisms (SNPs) of TGFB1 in asthma remains inconclusive. We examined TGFB1 SNPs in relation to asthma risk and degree of atopy among 546 case-parent triads, consisting of asthmatics aged 4 to 17 years and their parents in Mexico City. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped five TGFB1 SNPs, including two known functional SNPs [C-509T (rs1800469), T869C (rs1982073)] and three others (rs7258445, rs1800472, rs8179181), using TaqMan and Masscode assays. We analyzed the data using log-linear and polytomous logistic methods. Three associated SNPs, including the two known functional SNPs, were statistically significantly related to asthma risk. Individuals carrying the T allele of C-509T had an increased risk of asthma [relative risk (RR) = 1.42, 95% confidence interval (CI) = 1.08–1.87 for one copy; RR (95%CI) = 1.95 (1.36–2.78) for two copies]. For T869C, the RRs (95%CI) were 1.47 (1.09–1.98) for one and 2.00 (1.38–2.90) for two copies of the C allele. Similar results were found for rs7258445. The haplotype containing all three risk alleles conferred an increased risk of asthma (RR = 1.48, 95% CI = 1.11–1.95 for one copy; RR = 1.77, 95% CI = 1.22–2.57 for two copies). These three SNPs were also related to the degree of atopy. This largest study to date of genetic variation in TGFB1 and asthma and atopy adds to increasing evidence for a role in these disorders. PMID:17333284

  17. Genetic polymorphisms of 26 Y-STR loci in the Mongolian minority from Horqin district, China.

    PubMed

    Fu, Xiaoliang; Fu, Yong; Liu, Ying; Guo, Juanjuan; Liu, Yanfang; Guo, Yadong; Yan, Jie; Cai, Jifeng; Liu, Jinshan; Zha, Lagabaiyila

    2016-07-01

    To study the population data of Y chromosome STR (Y-STRs) of the Mongolian minority population residing in the Horqin district, we analyzed haplotypes of 26 Y-STRs (DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS481, DYS533, DYS549, DYS570, DYS576, DYS635, DYS643, DYS388, DYS449, DYS460, and YGATAH4) in 298 unrelated Chinese Mongolian individuals using the commercially available Goldeneye® DNA ID 26Y system. We also investigated blood stains, saliva spots, semen spots, hair follicles, fingernails, and sweat latent fingerprints from ten healthy males for testing the efficiency of direct amplification of this new Y-STRs system. The calculated average gene diversity values of the Mongolian population ranged from 0.3024 to 0.9510 for the DYS389I and DYS385a/b loci, respectively. The discriminatory capacity was 92.95 % with 277 observed haplotypes using 23 Y-STR loci (DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS481, DYS533, DYS549, DYS570, DYS576, DYS635, DYS643, and YGATAH4). By adding three more Y-STRs (DYS388, DYS449, and DYS460) to the 26Y system, the discriminatory capacity was increased to 94.63 % with a total of 282 observed haplotypes. Population relationships were calculated and compared with seven populations available from the Y chromosome haplotype reference database and data from ten Asian populations published previously. The Mongolian minority population residing in Horqin district is significantly different from other populations. Our results indicated that these 26 Y-STRs were highly genetically polymorphic in the Mongolian group and this contributes greatly to existing Chinese ethnic genetic information. As a result of direct amplification, we have obtained full profile from all blood stains, saliva spots, hair follicles, and fingernails; six semen spots; and one sweat latent fingerprint. It revealed

  18. Genetic polymorphisms of 26 Y-STR loci in the Mongolian minority from Horqin district, China.

    PubMed

    Fu, Xiaoliang; Fu, Yong; Liu, Ying; Guo, Juanjuan; Liu, Yanfang; Guo, Yadong; Yan, Jie; Cai, Jifeng; Liu, Jinshan; Zha, Lagabaiyila

    2016-07-01

    To study the population data of Y chromosome STR (Y-STRs) of the Mongolian minority population residing in the Horqin district, we analyzed haplotypes of 26 Y-STRs (DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS481, DYS533, DYS549, DYS570, DYS576, DYS635, DYS643, DYS388, DYS449, DYS460, and YGATAH4) in 298 unrelated Chinese Mongolian individuals using the commercially available Goldeneye® DNA ID 26Y system. We also investigated blood stains, saliva spots, semen spots, hair follicles, fingernails, and sweat latent fingerprints from ten healthy males for testing the efficiency of direct amplification of this new Y-STRs system. The calculated average gene diversity values of the Mongolian population ranged from 0.3024 to 0.9510 for the DYS389I and DYS385a/b loci, respectively. The discriminatory capacity was 92.95 % with 277 observed haplotypes using 23 Y-STR loci (DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS481, DYS533, DYS549, DYS570, DYS576, DYS635, DYS643, and YGATAH4). By adding three more Y-STRs (DYS388, DYS449, and DYS460) to the 26Y system, the discriminatory capacity was increased to 94.63 % with a total of 282 observed haplotypes. Population relationships were calculated and compared with seven populations available from the Y chromosome haplotype reference database and data from ten Asian populations published previously. The Mongolian minority population residing in Horqin district is significantly different from other populations. Our results indicated that these 26 Y-STRs were highly genetically polymorphic in the Mongolian group and this contributes greatly to existing Chinese ethnic genetic information. As a result of direct amplification, we have obtained full profile from all blood stains, saliva spots, hair follicles, and fingernails; six semen spots; and one sweat latent fingerprint. It revealed

  19. Impact of CYP2C9 genetic polymorphism on warfarin dose requirements in Pakistani population.

    PubMed

    Siddiqi, Aisha; Khan, Dilshad Ahmad; Khan, Farooq Ahmed; Naveed, Abdul Khaliq

    2010-10-01

    Variations of cytochrome-P450 enzyme system (CYP2CP) are associated with impaired metabolism of warfarin. The objective of our study was to estimate the frequency of genetic and allelic variants of CYP2C9 in Punjabi population of Pakistan and their effects on warfarin dose requirement. One hundred and twenty unrelated Pakistani subjects belong to Punjab province, were randomly included from the registry of National Institute of Heart Disease Rawalpindi, Pakistan. The patients had stable international normalized ratio (INR) of 2 to 3 for last 3 months with warfarin therapy after heart valves replacement. The detection of CYP2C9 variant was done on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Total 120 patients (73 males; 47 females) of mean age of 37 years participated in the study. Nine patients had mutant allele CYP2C9*3 (7.5%), one CYP2C9*2 (0.8%) and 110 patients exhibited wild type CYP2C9*1 (91.7%). The frequency of CYP2C9 genotype was *1/*1 (0.858) ; *1/*3 (0.117) ; 2/*20 (0.08 ) and *3/*3 (0.017) in our study population. A high dose of warfarin (42.2+9.56) mg/week is required for patients with *1/*1 genotype as compared to patients with *2/*2 (17.5+1.9) and *1/*3 (16.6+2.3) allele (p<0.001). Individuals with CYP2C9*3/3* need lowest (8.75±1.76 mg/week) daily warfarin dose. In conclusion, the genetic variations in the CYP2C9 occur in 14% of Punjabi ethnic group in Pakistan. Presence of CYP2C9*2 or *3 variants is an independent predictor of low warfarin dose requirement in our patients. CYP2C9 variants assay may be used in high risk groups for appropriate dose adjustment to avoid complications on long term basis.

  20. Identification of Pyrus single nucleotide polymorphisms (SNPs) and evaluation for genetic mapping in European pear and interspecific Pyrus hybrids.

    PubMed

    Montanari, Sara; Saeed, Munazza; Knäbel, Mareike; Kim, YoonKyeong; 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; Chagné, 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 Home'×'Louise 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.

  1. Genetic polymorphisms and haplotypes of TRAIL gene correlate with NSCLC susceptibility in a group of Chinese patients.

    PubMed

    Luo, Jun; Xiong, Jinmeng; Wu, Jianghua; Ye, Xujun

    2015-01-01

    The association between genetic polymorphisms and haplotypes of TNF-related apoptosis-inducing ligand (TRAIL) and the NSCLC development was investigated in 592 Chinese patients and the prevalence of G1525A, G1588A, and C1595T gene polymorphisms compared between the NSCLC patients and control group in this study. It was found that the frequencies of variant allele A and genotype GA+AA of G1525A were significantly lower and those of variant alleles A and T of G1588A and C1595T significantly higher in the NSCLC patients compared with those in control. The frequencies of variant allele T and genotype CT+TT of C1595T were significantly higher in stage III and IV than in stage I and II of the patients. Moreover, the frequencies of variant allele A and genotype GA+AA of G1525A were significantly higher in stage III and IV than in stage I and II of the patients. In addition, TRAIL gene variants G1525A/G1588A/C1595T were found to be in complete linkage disequilibrium in all patients. Compared with the healthy people, the frequency of AAT haplotype was significantly lower whereas that of GAT haplotype significantly higher in NSCLC patients. The results indicated that the genetic polymorphisms and haplotypes of TRAIL gene correlated significantly with the NSCLC susceptibility in the group of Chinese patients. PMID:26629137

  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. Clinical hallmarks and genetic polymorphisms in the CFTR gene contribute to the disclosure of the A1006E mutation.

    PubMed

    Tomaiuolo, Anna Cristina; Alghisi, Federico; Petrocchi, Stefano; Surace, Cecilia; Roberti, Maria Cristina; Bella, Sergio; Lucidi, Vincenzina; Angioni, Adriano

    2010-08-01

    Since the identification of the Cystic Fibrosis transmembrane conductance regulator (CFTR) gene in 1989, many genetic mutations have been found in cystic fibrosis (CF) patients. Dysfunctions of the CFTR gene are responsible for the highly variable clinical presentation ranging from severe CF, disseminated bronchiectasis, idiopathic chronic pancreatitis and congenital bilateral absence of vas deferens (CBAVD). Linkage disequilibrium studies have shown that some mutations are stringently coupled with polymorphisms in a genetic complex called haplotype. From a familial study of a patient with CBAVD, carrier of the A1006E mutation, we have observed its strict association with the polymorphism 5T-TG11. In order to speed up the genetic diagnosis and to correlate the clinical setting to this genetic feature, we have directly investigated the exon 17a, where the A1006E mutation is located, of five cystic fibrosis patients belonging to two unrelated families. All patients had the 5T-TG11 tract, F508del and one unknown mutation. One more family with two affected individuals carrying the Q220X/A1006E mutations was investigated for the poly-T polymorphism. All the members were found to have the A1006E mutation and the 5T-TG11 in the same DNA strand, demonstrating that this strategy is a reliable and inexpensive method for genotyping the CFTR gene. A detailed description of the clinical presentation and follow-up are provided in order to highlight common phenotypic features useful to improve the management of cystic fibrosis patients.

  4. Genetic polymorphism of morphological and biochemical characters in a Natal, Brazil, population of Lutzomyia longipalpis (Diptera: Psychodidae).

    PubMed

    Mukhopadhyay, J; Ghosh, K; Azevedo, A C; Rangel, E F; Munstermann, L E

    1998-09-01

    The phlebotomine sand fly, Lutzomyia longipalpis, is the vector of visceral leishmaniasis in the New World. Variability in its tergal spot morphology has led to conflicting interpretations of the species status of the various forms. An L. longipalpis field population from eastern Brazil was found with three co-occurring morphological variations--1-spot, 2-spot, and an intermediate form. Genetic profiles were established for each form. Fifteen isoenzyme loci provided the data matrix for comparison of genetic variation among the forms. Spot patterns and isoenzyme frequencies fit Hardy-Weinberg expectations, and no significant differences in isoenzyme frequencies were associated with morphological phenotype. The spot phenotype appears to be a polymorphic character not related to genetic isolation or differentiation at the species level. PMID:9813825

  5. The suitability of restriction fragment length polymorphism markers for evaluating genetic diversity among and synteny between mosquito species.

    PubMed

    Severson, D W; Mori, A; Zhang, Y; Christensen, B M

    1994-04-01

    Restriction fragment length polymorphism (RFLP) markers derived from the yellow fever mosquito, Aedes aegypti, were used in hybridizations to genomic DNA of the following mosquito species: Ae. albopictus, Ae. togoi, Armigeres subalbatus, Culex pipiens, and Anopheles gambiae. Interspecific hybridization with Ae. aegypti probes varied from 50% (An. gambiae) to 100% (Ae. albopictus) under high stringency conditions. We demonstrated the usefulness of using RFLP profiles to examine genetic diversity between mosquito populations; Ae. aegypti RFLP markers were used to examine genetic relatedness between 10 laboratory strains of Ae. aegypti as well as between nine populations representing four Cx. pipiens subspecies. These results indicate that many Ae. aegypti RFLP markers should have direct applicability in gaining a better understanding of genome structure in other mosquito species, including RFLP linkage mapping and determinations of genetic relatedness among field populations. PMID:7909414

  6. 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

  7. Genetic studies of human apolipoproteins. XX. Genetic polymorphism of apolipoprotein J and its impact on quantitative lipid traits in normolipidemic subjects.

    PubMed Central

    Kamboh, M I; Harmony, J A; Sepehrnia, B; Nwankwo, M; Ferrell, R E

    1991-01-01

    Apolipoprotein J (apo J) is a newly identified member of a growing family of proteins associated with various lipoprotein particles. Apo J is a glycoprotein which exists in the plasma associated with high-density lipoprotein subfractions which also contain apo A-I and cholesteryl ester transfer protein (CETP). We have investigated the possible existence of genetic polymorphism at the apo J structural locus and have evaluated its role in lipid metabolism. By employing isoelectric focusing and immunoblotting techniques, we have screened plasma or serum samples from six population groups: U.S. whites, Amerindians, Eskimos, New Guineans, U.S. blacks, and Nigerian blacks. Apo J revealed a common two-allele polymorphism only in populations with African ancestry and was found to be monomorphic in all other population groups tested. The genetic basis of the two alleles designated--APO J*1 and APO J*2, at a single structural locus, apo J-- was confirmed in a large number of segregating families. In the U.S. blacks, the frequencies of the APO J*1 and APO J*2 alleles were .76 and .24, respectively, and in the Nigerian blacks these values were .72 and .28, respectively. In addition, a single example of a rare allele designated APO J*3 was also encountered in the U.S. black sample. In Nigerian blacks, the apo J polymorphism's impact on seven quantitative lipid traits--total cholesterol, LDL-cholesterol, HDL-cholesterol, HDL3-cholesterol, HDL2-cholesterol, VLDL-cholesterol, and triglycerides--was investigated. No significant impact of the apo J polymorphism was observed for any of these lipid traits. Images Figure 1 Figure 2 PMID:1746550

  8. The role of CYBA (p22phox) and catalase genetic polymorphisms and their possible epistatic interaction in cervical cancer.

    PubMed

    Castaldo, Stephanie Anais; da Silva, Alda Pereira; Matos, Andreia; Inácio, Ângela; Bicho, Manuel; Medeiros, Rui; Alho, Irina; Bicho, Maria Clara

    2015-02-01

    Human papillomavirus (HPV) infection is necessary but not a sufficient cause for the development of invasive cervical cancer (ICC). Epithelial tissues, target for HPV, are exposed to reactive oxygen species (ROS) associated with tumor initiation and progression. The NADPH oxidase (NOX) and catalase (CAT) are involved in hydrogen peroxide (H2O2) production and inactivation, respectively. P22phox is the NOX subunit encoded by the CYBA gene that has a functional polymorphism (C-242T). This protein is involved in the regulation of electron transfer to oxygen. CAT is a hemic enzyme that plays a role in regulating H2O2 concentration, with a functional polymorphism (C-262T) in its gene. We evaluated CYBA C-242T and CAT C262T genetic polymorphisms and their interaction in 132 women with ICC. We found that CYBA C-242T and CAT C262T genotype frequencies were significantly different between ICC and controls (χ (2) test, p = 0.017 and p = 0.009, respectively). Women with the C/T CYBA-242 genotype had a lower risk for ICC development (odds ratio (OR) = 0.515, 95% confidence interval (CI) 0.291-0.914, p = 0.023) whereas T/T CAT-262 genotype carriers present an increased risk for ICC (OR = 3.034, 95% CI 1.462-6.298, p = 0.003). Women with C/C genotype for CYBA and T/T genotype for CAT had an increased risk to develop ICC comparing with the interaction of the other possible genotypes of both genes (OR = 3.952, 95% CI 1.075-14.521, p = 0.032). The CYBA C-242T and CAT C-262T genetic polymorphisms and their epistatic interactions can be associated with ICC through mechanisms related with the role of ROS in cell proliferation and apoptosis.

  9. Genetic polymorphisms in the aryl hydrocarbon receptor–signaling pathway and sleep disturbances in middle-aged women

    PubMed Central

    Ziv-Gal, Ayelet; Flaws, Jodi A.; Mahoney, Megan M.; Miller, Susan R.; Zacur, Howard A.; Gallicchio, Lisa

    2013-01-01

    Objective We aimed to determine if selected genetic polymorphisms in the aryl hydrocarbon receptor (AHR)–signaling pathway and circadian locomotor output cycles kaput (CLOCK) are associated with insomnia and early awakening in middle-aged women. Methods Women aged 45 to 54 years (n=639) were recruited into a middle-aged health study and agreed to complete questionnaires and donate blood samples. Questionnaires were used to assess sleep outcomes. Blood samples were processed for genotyping the selected polymorphisms: AHR (rs2066853), AHR repressor (AHRR) (rs2292596), aryl hydrocarbon nuclear translocator (ARNT) (rs2228099), and circadian locomotor output cycles kaput (CLOCK) (rs1801260). Data were analyzed using multivariable logistic regression. Results Women heterozygous for the AHRR alleles (GC) had decreased odds of insomnia compared to women homozygous for the AHRR_C allele (adjusted odds ratio [aOR], 0.69; 95% confidence interval [CI], 0.49–0.96). Women with at least one of the AHRR_G or CLOCK_C alleles had significantly decreased odds of insomnia compared to women homozygous for the AHRR_C and CLOCK_T alleles (aOR, 0.64; 95% CI, 0.43–0.96). Additionally, women homozygous for the AHRR_G and CLOCK_C alleles had significantly decreased odds of insomnia compared to women homozygous for the AHRR_C and CLOCK_T alleles (aOR, 0.56; 95% CI, 0.35–0.89). None of the selected single nucleotide polymorphisms (SNPs) or combinations of SNPs were significantly associated with early awakening. Conclusions Selected genetic polymorphisms in the AHR-signaling pathway (i.e., AHRR) and CLOCK may play a role in decreasing the risk for experiencing insomnia during the menopausal transition. PMID:23768840

  10. 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

  11. Genetic polymorphism of interleukin 1β -511C/T and susceptibility to sporadic Alzheimer's disease: a meta-analysis.

    PubMed

    Yuan, Hai; Xia, Qing; Ge, Pingping; Wu, Shaowei

    2013-02-01

    A large number of epidemiological studies have been performed to investigate the association between Alzheimer's disease (AD) risk and interleukin-1β -511C/T genetic polymorphism, however, inconsistent results have been reported. The effect of the IL-1β -511C/T polymorphism on AD susceptibility was evaluated by a meta-analysis. Series of databases were researched. 14 studies involving 2640 AD case and 3493 control subjects were identified. The pooled results showed there were no statistical associations of interleukin-1β -511C/T genetic polymorphism with susceptibility to AD for five analysis models in all subjects. However, obvious heterogeneity among studies was detected. When stratifying for age at onset, ethnicity and geographic distribution of population to explore the original source of heterogeneity, the meta-analysis results based on geographic distribution of population showed the significant difference (CC vs CT, OR 1.26, 95 % CI: 1.03, 1.54, z = 2.25, P = 0.025; CC vs CT+TT, OR 1.24, 95 % CI: 1.03, 1.50, z = 2.24, P = 0.025) only in non-Europe. These findings indicate that the IL-1β -511C/T polymorphism might be associated with AD risk, and individuals with IL-1β -511C/C genotype might be at higher risk of AD in non-Europe. Further larger sample research would be warranted to confirm these conclusions.

  12. Interaction between use of non-steroidal anti-inflammatory drugs and selected genetic polymorphisms in ovarian cancer risk

    PubMed Central

    Pinheiro, Simone P; Gates, Margaret A; DeVivo, Immaculata; Rosner, Bernard A; Tworoger, Shelley S; Titus-Ernstoff, Linda; Hankinson, Susan E; Cramer, Daniel W

    2010-01-01

    Inflammation and non-steroidal anti-inflammatory agents (NSAIDs) may play important role in ovarian cancer. However, epidemiologic data are inconsistent, possibly reflecting inter-individual genetic differences affecting the metabolism of NSAIDs. We examined whether common polymorphisms affecting the metabolism of NSAIDs modify the association between NSAIDs and ovarian cancer risk. We genotyped 1,353 DNA samples from women who developed ovarian cancer and 1,823 samples from matched controls participating in the New England Case-Control study and the Nurses' Health Studies. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) associated with regular use of NSAIDs and with relevant polymorphisms on ovarian cancer risk. Multivariable unconditional logistic regression estimated the association of NSAID use across stratum of each genotype. Regular use of NSAIDs was not associated with ovarian cancer risk. Multivariable OR (95% CI) associated with use NSAIDs was 0.85 (95% CI: 0.71-1.02). Associations between NSAID use and ovarian cancer risk did not differ significantly across strata of genotypes. None of the studied polymorphisms was associated with ovarian cancer risk. The multivariable ORs (95% CI) associated with CYP2C9 and UGT1A6 variant genotypes were 0.99 (0.90-1.08) and 0.93 (0.82-1.05), respectively. The multivariable ORs (95% CI) associated with PPAR-γ, COX-2 -765G>C, and COX-2 Ex10+837T>C polymorphisms were 1.02 (0.87-1.20), 0.87 (0.75-1.00), and 0.97 (0.87-1.09), respectively. In this relatively large study, we found no convincing evidence supporting an association between NSAIDs use and ovarian cancer risk. Furthermore, data did not suggest interaction between selected polymorphisms and use of NSAIDs in relation to ovarian cancer risk. PMID:21532843

  13. 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

    outcomes. Studies of these and related genetic polymorphisms are warranted to advance understanding of RVF pathogenesis. PMID:25756647

  14. 5-HTR1A and 5-HTR2A genetic polymorphisms and SSRI antidepressant response in depressive Chinese patients

    PubMed Central

    Dong, Zai-Quan; Li, Xi-Rong; He, Lin; He, Guang; Yu, Tao; Sun, Xue-Li

    2016-01-01

    Objective Genetic variabilities within the serotoninergic system may predict response or remission to antidepressant drugs. Several serotonin receptor (5-HTR) gene polymorphisms have been associated with susceptibility to psychiatric diseases. In this study, we analyzed the correlation between 5-HTR1A and 5-HTR2A polymorphisms and response or remission to selective serotonin reuptake inhibitors (SSRIs) drugs. Methods Two hundred and ninety patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder were involved in this study. SSRIs (fluoxetine, paroxetine, citalopram, or sertraline) were selected randomly for treatment. The Hamilton Rating Scale for Depression was used to evaluate the antidepressant effect. To assess 5-HTR gene variabilities, two single-nucleotide polymorphisms in 5-HTR1A (rs1364043 and rs10042486) and three in 5-HTR2A (rs6311, rs6313, and rs17289304) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the Sequenom MassARRAY Analyzer 4 system. Results There were 220 responders and 70 nonresponders (120 remissioners and 170 nonremissioners) after 6 weeks of treatment. We found no association between any of the five 5-HTR1A and 5-HTR2A gene polymorphisms and antidepressant drug response or remission (P>0.05). It is worth mentioning that TT genotype frequency of rs10042486 was significantly different from the CT genotype frequency between responders and nonresponders, although the significance was not maintained after correcting for multiple testing. Conclusion Thus, 5-HTR1A and 5-HTR2A gene polymorphisms may not play an important role in antidepressant drug response or remission. PMID:27445478

  15. Genetic relationship of 32 cell lines of Euplotes octocarinatus species complex revealed by random amplified polymorphic DNA (RAPD) fingerprinting.

    PubMed

    Möllenbeck, M

    1999-12-01

    Random amplified polymorphic DNA (RAPD) fingerprinting was used in this study to determine the genetic relationship of different cell lines of the hypotrichous ciliate Euplotes octocarinatus. Stocks isolated from different habitats in the USA, and from a group of genetically recombined laboratory strains, were characterized. Band-sharing indices (D) for all possible pairwise comparisons revealed a remarkable genetic diversity between the different cell lines. Investigation of the genetic structure in natural populations found diversity--although to a different extent--in all populations investigated. No clonal structure could be observed, as proposed for several protozoa and recently shown for E. daidaleos. These findings suggest frequent conjugation in the population of E. octocarinatus. No correlation between the genetic relationship of cell lines from different habitats and the distance between the corresponding sampling locations was found. Once separated geographically, the exchange of genetic material between populations appears to be nearly impossible. Therefore, these groups tend to separate into sibling species. The data generally support the occurrence of different syngens in the E. octocarinatus species complex. This finding is in accordance with our observation that the morphological 'species' of E. octocarinatus consists of several syngens or sibling species, similar to findings for the Paramecium aurelia-, Tetrahymena pyriformis- and E. vannus- species complexes. PMID:10722304

  16. Makeup of the genetic correlation between milk production traits using genome-wide single nucleotide polymorphism information.

    PubMed

    van Binsbergen, R; Veerkamp, R F; Calus, M P L

    2012-04-01

    The correlated responses between traits may differ depending on the makeup of genetic covariances, and may differ from the predictions of polygenic covariances. Therefore, the objective of the present study was to investigate the makeup of the genetic covariances between the well-studied traits: milk yield, fat yield, protein yield, and their percentages in more detail. Phenotypic records of 1,737 heifers of research farms in 4 different countries were used after homogenizing and adjusting for management effects. All cows had a genotype for 37,590 single nucleotide polymorphisms (SNP). A bayesian stochastic search variable selection model was used to estimate the SNP effects for each trait. About 0.5 to 1.0% of the SNP had a significant effect on 1 or more traits; however, the SNP without a significant effect explained most of the genetic variances and covariances of the traits. Single nucleotide polymorphism correlations differed from the polygenic correlations, but only 10 regions were found with an effect on multiple traits; in 1 of these regions the DGAT1 gene was previously reported with an effect on multiple traits. This region explained up to 41% of the variances of 4 traits and explained a major part of the correlation between fat yield and fat percentage and contributes to asymmetry in correlated response between fat yield and fat percentage. Overall, for the traits in this study, the infinitesimal model is expected to be sufficient for the estimation of the variances and covariances.

  17. 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

  18. [The genetic polymorphism of the blood proteins in RID-positive reacting cows].

    PubMed

    Kivan, M

    1991-01-01

    Cattle herd of Black-and-White, Red and Simmental breeds having positive or negative RID-reaction to leucosis was studied as to the polymorphism of serum blood proteins in three loci: Tf, Am and Cp. One system of polymorphic proteins has been determined as having a higher concentration of homozygotes (Tf) and another one as having a higher concentration of heterozygotes (Am) within one and the same herd among animals with the positive RID-reaction. PMID:1796504

  19. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients.

    PubMed

    do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; 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.

  20. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients

    PubMed Central

    do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; 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 1.45–4.55, 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

  1. Genetic polymorphisms of the human cytomegalovirus UL144 gene in colorectal cancer and its association with clinical outcome.

    PubMed

    Chen, Hsin-Pai; Jiang, Jeng-Kai; Chan, Chia-Hao; Teo, Wan-Huai; Yang, Chih-Yung; Chen, Yen-Chung; Chou, Teh-Ying; Lin, Chi-Hung; Chan, Yu-Jiun

    2015-12-01

    Human cytomegalovirus (HCMV) has been increasingly detected in colorectal cancer (CRC), and genetic polymorphisms in HCMV affect its pathogenesis. This study aimed to investigate HCMV genetic polymorphisms in CRC and its correlation with the clinical outcomes. We performed PCR and sequencing of a viral immunomodulatory gene, UL144, in clinical isolates and CRC specimens. The nucleotide and amino acid sequences were aligned, and a phylogenetic tree was constructed. The clinical, pathological and survival data were compared among tumours with different UL144 genotypes. HCMV was detected in 49 (47.8 %) of the tumour specimens. Genotype A predominated in 43 samples (22/43; 51.2 %) with successful sequencing, followed by genotype B (13/43; 30.2 %) and genotype C (8/43; 18.6 %). The genotypic distribution was similar to that of the clinical isolates and those reported in other Asian populations. The amino acid sequence of genotype B was the most conserved. For stage II and III CRC patients with HCMV-positive tumours, disease-free survival (DFS) varied among the three major genotypes (P50.0046). The presence of genotype B virus in the tumours was associated with a shorter DFS and independently predicted tumour recurrence in a multivariate Cox proportional hazards model (hazard ratio, 5.79; 95 % confidence interval, 1.30–25.81; P50.021). By reverse transcription PCR, tumour samples with genotype B viruses had the highest rate of UL144 expression. Our results suggest that genetic polymorphisms of HCMV UL144 are associated with clinical outcome in CRC and that HCMV may play an immunomodulatory role in the tumour microenvironment of CRC. PMID:26450180

  2. 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

  3. Genetic polymorphisms and phenotypic analysis of drug-metabolizing enzyme CYP2C19 in a Li Chinese population.

    PubMed

    Ding, Yipeng; Xu, Dongchuan; Zhang, Xiyang; Yang, Hua; Geng, Tingting; He, Ping; Yao, Jinjian; Yi, Shengyang; Xu, Heping; Wu, Duoyi; Wang, Xiang; Jin, Tianbo

    2015-01-01

    CYP2C19 is a highly polymorphic gene and CYP2C19 enzyme results in broad inter-individual variability in response to certain clinical drugs, while little is known about the genetic variation of CYP2C19 in Li Chinese population. The aim of this study was to identify different CYP2C19 mutant alleles and determine their frequencies, along with genotype frequencies, in the Li Chinese population. We used DNA sequencing to investigate promoter, exons, introns, and 3'UTR of the CYP2C19 gene in 100 unrelated healthy Li individuals from Hainan Province, China. We also used SIFT and PolyPhen-2 to predict the protein function of the non-synonymous mutation in CYP2C19 coding regions. We identified 22 different CYP2C19 polymorphisms in the Li Chinese population, including three novel variants (-254A > G, 17807T > C and 58025C > T). The allele frequencies of CYP2C19*1A, *1B, *2A and *3A were 50%, 24%, 24.5%, and 1.5%, respectively. The most common genotype combinations were *1A/*1B (48%) and *1A/*2A (49%). Additionally, the mutation Ala161Pro was predicted to be intolerant and possibly damaging by SIFT and PolyPhen-2, respectively. Our results shed new light on CYP2C19 polymorphisms in Li individuals, which may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group.

  4. Genetic diversity in potato field populations of Thanatephorus cucumeris AG-3, revealed by ITS polymorphism and RAPD markers.

    PubMed

    Justesen, Annemarie Fejer; Yohalem, David; Bay, Anne; Nicolaisen, Mogens

    2003-11-01

    DNA sequence analysis of the internal transcribed spacer region 1 (ITS1) and random amplified polymorphic DNA (RAPD) markers were used to survey genetic variability in relation to agronomic and regional factors among 60 isolates of Thanatephorus cucumeris (anamorph Rhizoctonia solani) collected from lesions on potato stems or sclerotia of potato tubers. Based on comparative sequence analysis it was shown that all isolates belonged to anastomosis group 3 subgroup Potato Type (AG-3 PT). ITS1 sequence polymorphisms were found within 45 of the 60 isolates showing that different types of the ITS-region are present in individual isolates. Cloning and sequence analysis of the ITS1 region from three selected isolates with sequence polymorphism showed that two different ITS1-types were present in each isolate. RAPD analysis identified 51 RAPD-phenotypes among the 60 investigated isolates indicating a high level of diversity within the subgroup AG-3 PT. Putative clonal isolates with identical RAPD- and ITS1-types were identified within fields, and in one case the same phenotype was found in two different fields separated by several hundred kilometers. Population subdivision analysis based on phenotypic as well as genotypic diversities showed differentiation among populations from different fields when isolates were sampled from tubers, indicating restricted gene flow among soil populations. Low differentiation was seen among field populations sampled from stems, indicating that gene flow is taking place. The population structure was not influenced by the previous crop in the rotation nor by the two cultivars 'Sava' and 'Bintje'.

  5. The association of the HOPA(12bp) polymorphism with schizophrenia in the NIMH Genetics Initiative for Schizophrenia sample.

    PubMed

    Philibert, Robert A; Bohle, Phil; Secrest, Dianna; Deaderick, Jessica; Sandhu, Harinder; Crowe, Raymond; Black, Donald W

    2007-09-01

    HOPA (MED12) is an X-chromosome gene that codes for a critical member of the Mediator Complex, a group of proteins that regulates transcription via the nuclear receptor, Wnt and Receptor Tyrosine Kinase pathways. In prior association and meta-analyses, we have shown that the presence of an evolutionarily conserved, 12 bp (4 amino acid) insertional polymorphism in exon 43 of this gene is associated with increased risk for an endophenotype of schizophrenia. In this communication, we describe the results of our work with subjects and data from the National Institutes of Mental Health (NIMH) Genetics Initiative for Schizophrenia. We report that the presence of the HOPA(12bp) polymorphism is associated with increased risk for schizophrenia in subjects of European ancestry. In the light of this new study and the prior wealth of clinical and basic science data, we conclude that the HOPA(12bp) allele is a risk factor for schizophrenia in subjects of European ancestry and suggest that further studies to define the endophenotype and mechanisms of illness associated with this polymorphism are indicated.

  6. Assessment of genetic diversity in Mucuna species of India using randomly amplified polymorphic DNA and inter simple sequence repeat markers.

    PubMed

    Patil, Ravishankar R; Pawar, Kiran D; Rane, Manali R; Yadav, Shrirang R; Bapat, Vishwas A; Jadhav, Jyoti P

    2016-04-01

    Genus Mucuna which is native to China and Eastern India comprises of perennial climbing legume with long slender branches, trifoliate leaves and bear green or brown pod covered with soft or rigid hairs that cause intense irritation. The plants of this genus are agronomically and economically important and commercially cultivated in India, China and other regions of the world. The high degrees of taxonomical confusions exist in Mucuna species that make authentic identification and classification difficult. In the present study, the genetic diversity among the 59 accessions of six species and three varieties of M. pruriens has been assessed using DNA fingerprinting based molecular markers techniques namely randomly amplified polymorphic DNA (RAPD), inter simple sequence repeats (ISSR) and combined dataset of RAPD and ISSR. Also, genetic relationship among two endemic species of Mucuna namely M. imbricata and M. macrocarpa and two varieties namely IIHR hybrid (MHR) and Dhanwantari (MD) with other species under study was investigated by using cluster analysis and principal coordinate analysis. The cluster analysis of RAPD, ISSR and combined dataset of RAPD and ISSR clearly demonstrated the existence of high interspecific variation than intra-specific variation in genus Mucuna. The utility and efficacy of RAPD and ISSR for the study of intra species and interspecies genetic diversity was evident from AMOVA and PCoA analysis. This study demonstrates the genetic diversity in Mucuna species and indicates that these markers could be successfully used to assess genetic variation among the accessions of Mucuna species. PMID:27436912

  7. 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

  8. Expression of STK39 in peripheral blood of hypertension patients and the relationship between its genetic polymorphism and blood pressure.

    PubMed

    Li, B; Yang, M; Liu, J W

    2015-12-09

    This study investigated the STK39 expression in peripheral blood of hypertension patients and the relation between its genetic polymorphism and blood pressure. The observation group comprised of 42 primary hypertension patients admitted to our hospital, and the control group comprised of 30 healthy individuals who underwent physical examination in our hospital during the same period. Fasting venous blood was collected from both groups in the morning to determine the STK39 mRNA and protein levels in peripheral blood using quantitative real-time PCR and western blot. STK39 gene SNP (rs6433027) was sequenced using PCR and its genetic variation was analyzed. The relationship between STK39 protein level, genetic variation, and diastolic and systolic blood pressure was also analyzed. The observation group showed increased STK39 mRNA and protein levels in peripheral blood compared to the control group, and the difference was statistically significant (P < 0.05), suggesting C/T mutation in STK39 gene SNP (rs6433027). Correlation analysis showed positive association between STK39 protein level and diastolic and systolic blood pressure (P < 0.05), indicating a positive association between C/T genetic mutation and diastolic and systolic blood pressure (P < 0.05). In conclusion, STK39 mRNA and protein express abnormally in primary hypertension patients with genetic variation, which is related to the blood pressure.

  9. Genetic Polymorphism of SUMO-Specific Cysteine Proteases - SENP1 and SENP2 in Breast Cancer.

    PubMed

    Mirecka, Alicja; Morawiec, Zbigniew; Wozniak, Katarzyna

    2016-10-01

    SENP proteases take part in post-translational modification of proteins known as sumoylation. They catalyze three distinct processes during sumoylation: processing of SUMO protein, deconjugation of SUMO from the target protein, and chain editing which mentions to the dismantling of SUMO chain. Many proteins that are involved in the basic processes of cells, such as regulation of transcription, DNA repair or cell cycle control, are sumoylated. The aim of these studies was to investigate an association between polymorphic variants (SNPs) of the SENP1 gene (c.1691 + 36C > T, rs12297820) and SENP2 gene (c.902C > A, p.Thr301Lys, rs6762208) and a risk of breast cancer occurrence. We performed a case-control study in 324 breast cancer cases and 335 controls using PCR-RLFP. In the case of the SENP1 gene polymorphism we did not find any association between this polymorphism and breast cancer risk. In the case of SENP2 gene polymorphism we observed higher risk of breast cancer for carriers of the A allele (OR =1.33; 95 % CI 1.04-1.69). Our analysis also showed the genotype C/C (OR =0.67, 95 % CI 0.48-0.93) and the allele C (OR =0.75, 95 % CI 0.59-0.69) of this polymorphism decrease a risk of breast cancer. We also checked the distribution of genotypes and frequency of alleles of the SENP1 and SENP2 genes polymorphisms in groups of patients with different hormone receptor status, patients with positive and negative lymph node status and patients with different tumor grade. Odds ratio analysis showed a higher risk of metastases in women with the genotype C/C (OR =2.07, 95 % CI 1.06-4.05) and allele C (OR =2.10 95 % CI 1.10-4.01) of the c.1691 + 36C > T SENP1 gene polymorphism. Moreover, we observed reduced risk in women with the allele T (OR =0.48, 95 % CI 0.25-0.91) in this polymorphic site. In the case of SENP2 gene polymorphism we observed that the A/A genotype correlated with the lack of estrogen receptor (OR =1.94, 95 % CI 1.04-3.62). Our results suggest

  10. Description of the data from the Collaborative Study on the Genetics of Alcoholism (COGA) and single-nucleotide polymorphism genotyping for Genetic Analysis Workshop 14.

    PubMed

    Edenberg, Howard J; Bierut, Laura J; Boyce, Paul; Cao, Manqiu; Cawley, Simon; Chiles, Richard; Doheny, Kimberly F; Hansen, Mark; Hinrichs, Tony; Jones, Kevin; Kelleher, Mark; Kennedy, Giulia C; Liu, Guoying; Marcus, Gregory; McBride, Celeste; Murray, Sarah Shaw; Oliphant, Arnold; Pettengill, James; Porjesz, Bernice; Pugh, Elizabeth W; Rice, John P; Rubano, Todd; Shannon, Stu; Steeke, Rhoberta; Tischfield, Jay A; Tsai, Ya Yu; Zhang, Chun; Begleiter, Henri

    2005-01-01

    The data provided to the Genetic Analysis Workshop 14 (GAW 14) was the result of a collaboration among several different groups, catalyzed by Elizabeth Pugh from The Center for Inherited Disease Research (CIDR) and the organizers of GAW 14, Jean MacCluer and Laura Almasy. The DNA, phenotypic characterization, and microsatellite genomic survey were provided by the Collaborative Study on the Genetics of Alcoholism (COGA), a nine-site national collaboration funded by the National Institute of Alcohol and Alcoholism (NIAAA) and the National Institute of Drug Abuse (NIDA) with the overarching goal of identifying and characterizing genes that affect the susceptibility to develop alcohol dependence and related phenotypes. CIDR, Affymetrix, and Illumina provided single-nucleotide polymorphism genotyping of a large subset of the COGA subjects. This article briefly describes the dataset that was provided.

  11. 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

  12. Association of FCRL3 Genetic Polymorphisms With Endometriosis-Related Infertility Risk: An Independent Study in Han Chinese.

    PubMed

    Zhang, Haiyan; Zhang, Zhen; Li, Guang; Wang, Surong; Zhang, Shiqian; Xie, Beibei

    2015-09-01

    The Fc receptor-like 3 (FCRL3) gene was reported to be linked to a variety of autoimmune diseases, including endometriosis-related infertility. However, this linkage has not been studied in Chinese population and there has been no meta-analysis on the interrelationship of FCRL3 gene and endometriosis-related infertility. The aim of the study was to investigate the association between FCRL3 genetic polymorphisms and the risk of endometriosis-related infertility in Han Chinese, and a further meta-analysis was conducted to confirm our results.Four single nucleotide polymorphisms (SNPs) (rs7528684 [FCRL3_3], rs11264799 [FCRL3_4], rs945635 [FCRL3_5], and rs3761959 [FCRL3_6]) on FCRL3 gene were genotyped in a case-control cohort composed of 217 patients suffering from endometriosis-related infertility and 220 healthy controls using cleaved amplification polymorphism sequence-tagged sites (polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP). Odds ratio (OR) and its 95% confidence interval (CI) was used to evaluate the association quantitatively. Furthermore, a meta-analysis of previous studies including the present study was implemented through Stata 11.0 (Stata Corporation, College Station, TX).We found an approximately 1.4-fold significantly increased frequency of the FCRL3_3 variant in women with endometriosis-related infertility over the controls (OR = 1.41 [95% CI = 1.08-1.84], P = 0.013). However, no significant difference was found between women with endometriosis-related infertility and controls for FCRL3_4, FCRL3_5, and FCRL3_6. Regardless of the symptoms and the revised classification of the American Society of Reproductive Medicine (rASRM) stage of endometriosis, there was a significant association between FCRL3_3 variant and an increased risk of endometriosis-related infertility. Meta-analysis of previous studies combined with the present study further confirmed the association between FCRL3_3 and the risk of endometriosis

  13. 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, Ilíada 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, Lídia; 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

  14. A Simple Sequence Repeat- and Single-Nucleotide Polymorphism-Based Genetic Linkage Map of the Brown Planthopper, Nilaparvata lugens

    PubMed Central

    Jairin, Jirapong; Kobayashi, Tetsuya; Yamagata, Yoshiyuki; Sanada-Morimura, Sachiyo; Mori, Kazuki; Tashiro, Kosuke; Kuhara, Satoru; Kuwazaki, Seigo; Urio, Masahiro; Suetsugu, Yoshitaka; Yamamoto, Kimiko; Matsumura, Masaya; Yasui, Hideshi

    2013-01-01

    In this study, we developed the first genetic linkage map for the major rice insect pest, the brown planthopper (BPH, Nilaparvata lugens). The linkage map was constructed by integrating linkage data from two backcross populations derived from three inbred BPH strains. The consensus map consists of 474 simple sequence repeats, 43 single-nucleotide polymorphisms, and 1 sequence-tagged site, for a total of 518 markers at 472 unique positions in 17 linkage groups. The linkage groups cover 1093.9 cM, with an average distance of 2.3 cM between loci. The average number of marker loci per linkage group was 27.8. The sex-linkage group was identified by exploiting X-linked and Y-specific markers. Our linkage map and the newly developed markers used to create it constitute an essential resource and a useful framework for future genetic analyses in BPH. PMID:23204257

  15. 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, Ilíada 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, Lídia; 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.

  16. [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

  17. Presence and genetic polymorphism of an epithelial mucin in milk of the goat (Capra hircus).

    PubMed

    Campana, W M; Josephson, R V; Patton, S

    1992-09-01

    1. Analysis of individual samples of goat's milk by SDS-PAGE confirmed that they contain a polymorphic, high molecular weight (M(r) greater than 205 kDa) glycoprotein. 2. On SDS-gels, the polymorphism takes the form of two bands of variable mobility which usually stain with equal intensity. This polymorphism resembles that detected in milk mucins of other species and is best explained by an expression of codominant genes containing variable numbers of a tandemly repeated 60-base segment. 3. Analysis of milk fractions provided evidence that the goat mucin is exclusively a membrane protein, and that it can be purified from other fat globule proteins by gel filtration and peanut lectin affinity chromatography. 4. Among proteins in the goat milk fat globule, the mucin appears to be a strong immunogen but the resulting antibodies applied to Western blots only stained the cow's milk mucin mildly and the guinea pig and human milk mucins not at all.

  18. 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

  19. Genetic Polymorphism of DNA Methyltransferase 3A rs1550117 A>G and Risk of Cancer: A Meta-analysis.

    PubMed

    Zhang, Wenbo; Xu, Ying; Ma, Gui; Qi, Weidong; Gu, Haiyong; Jiang, Pengcheng

    2015-01-01

    Numerous studies have investigated the association between DNMT3A rs1550117 A>G polymorphism and cancer risk, but the results are inconsistent. To obtain a more precise evaluation of the relationship, we performed a meta-analysis of 10 case-control studies involving a total of 2184 cancer cases and 3420 controls. Our findings demonstrated a significant association between DNMT3A rs1550117 A>G polymorphism and increased risk of cancer in three genetic models: AA vs. AG + GG (OR, 1.79; 95% CI, 1.12-2.88; p = 0.015), AA vs. GG (OR, 1.81; 95% CI, 1.11-2.95; p = 0.018) and AA vs. AG (OR 1.77; 95% CI 1.13-2.79; p = 0.013). In a stratified analysis by cancer type, significant association between DNMT3A rs1550117 A>G polymorphism and increased risk of colorectal cancer was identified in four genetic models: AA vs. AG + GG (OR, 3.07; 95% CI, 1.56-6.06; p = 0.001), AA vs. GG (OR, 3.16; 95% CI, 1.58-6.29; p = 0.001), AA vs. AG (OR, 2.87; 95% CI, 1.41-5.84; p = 0.004), A vs. G (OR, 1.43; 95% CI, 1.11-1.83; p = 0.005). Furthermore, a stratified analysis by ethnicity, significant increased risk of cancer was found among Asians in three genetic models: AA vs. AG + GG (OR, 1.77; 95% CI, 1.09-2.88; p = 0.022), AA vs. GG (OR, 1.78; 95% CI, 1.08-2.96; p = 0.025), AA vs. AG (OR, 1.75; 95% CI, 1.10-2.79; p = 0.019). No significant publication bias was revealed for the meta-analysis. Sensitivity analysis suggested the reliability of our findings. In conclusion, this meta-analysis suggests that DNMT3A rs1550117 A>G polymorphism may be associated with cancer susceptibility.

  20. 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

  1. PRELIMINARY REPORT ON THE PUTATIVE ASSOCIATION OF IL10 -3575 T/A GENETIC POLYMORPHISM WITH MALARIA SYMPTOMS

    PubMed Central

    DOMINGUES, Wilson; KANUNFRE, Kelly Aparecida; RODRIGUES, Jonatas Cristian; TEIXEIRA, Leandro Emidio; YAMAMOTO, Lidia; OKAY, Thelma Suely

    2016-01-01

    Only a small percentage of individuals living in endemic areas develop severe malaria suggesting that host genetic factors may play a key role. This study has determined the frequency of single nucleotide polymorphisms (SNPs) in some pro and anti-inflammatory cytokine gene sequences: IL6 (-174; rs1800795), IL12p40 (+1188; rs3212227), IL4 (+33; rs2070874), IL10 (-3575; rs1800890) and TGFb1 (+869; rs1800470), by means of PCR-RFLP. Blood samples were collected from 104 symptomatic and 37 asymptomatic subjects. Laboratory diagnosis was assessed by the thick blood smear test and nested-PCR. No association was found between IL6 (-174), IL12p40 (+1188), IL4 (+33), IL10 (- 3575), TGFb1 (+869) SNPs and malaria symptoms. However, regarding the IL10 -3575 T/A SNP, there were significantly more AA and AT subjects, carrying the polymorphic allele A, in the symptomatic group (c2 = 4.54, p = 0.01, OR = 0.40 [95% CI - 0.17- 0.94]). When the analysis was performed by allele, the frequency of the polymorphic allele A was also significantly higher in the symptomatic group (c2 = 4.50, p = 0.01, OR = 0.45 [95% CI - 0.21-0.95]). In conclusion, this study has suggested the possibility that the IL10 - 3575 T/A SNP might be associated with the presence and maintenance of malaria symptoms in individuals living in endemic areas. Taking into account that this polymorphism is related to decreased IL10 production, a possible role of this SNP in the pathophysiology of malaria is also suggested, but replication studies with a higher number of patients and evaluation of IL10 levels are needed for confirmation. PMID:27074324

  2. Influence of genetic polymorphisms in the folate pathway on toxicity after high-dose methotrexate treatment in pediatric osteosarcoma

    PubMed Central

    Park, Jeong A

    2016-01-01

    Background Methotrexate (MTX), one of the main drugs used to treat osteosarcoma, is a representative folic acid antagonist. Polymorphisms of various enzymes involved in the metabolism of MTX could contribute to differences in response to MTX in pediatric osteosarcoma patients. Methods Blood and tissue samples were obtained from 37 pediatric osteosarcoma patients who were treated with high-dose MTX therapy. The following 4 single nucleotide polymorphisms (SNPs) were analyzed: ATIC 347C>G, MTHFR 677C>T, MTHFR 1298A>C and SLC19A1 80G>A. Serial plasma MTX concentrations after high-dose MTX therapy and MTX-induced toxicities were evaluated. Correlations among polymorphisms, MTX concentrations and treatment-induced toxicities were assessed. Results Plasma MTX levels at 48 hours after high-dose MTX infusion were significantly associated with SLC19A1 80G>A (P=0.031). Higher plasma levels of MTX at 48 and 72 hours were significantly associated with MTX-induced mucositis (P=0.007 and P=0.046) and renal toxicity (P=0.002), respectively. SNP of SLC19A1 gene was associated with development of severe mucositis (P=0.026). Conclusion This study suggests that plasma levels of MTX are associated with GI and renal toxicities after high-dose MTX therapy, and genetic polymorphisms that affect the metabolism of MTX may influence drug concentrations and development of significant side effects in pediatric patients treated with high-dose MTX. PMID:27104192

  3. 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.

  4. 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.

  5. Sulfation of ritodrine by the human cytosolic sulfotransferases (SULTs): Effects of SULT1A3 genetic polymorphism.

    PubMed

    Hui, Ying; Liu, Ming-Cheh

    2015-08-15

    Previous studies have demonstrated the metabolism of ritodrine through sulfation. The current study was designed to identify the human SULTs that are capable of sulfating ritodrine and to investigate how genetic polymorphism of the major ritodrine-sulfating SULT, SULT1A3, may affect its sulfating activity. A systematic analysis revealed that of the 13 known human SULTs, SULT1A1, SULT1A3, and SULT1C4, were capable of mediating the sulfation of ritodrine, with SULT1A3 displaying the strongest sulfating activity. Effects of genetic polymorphism on the sulfating activity of SULT1A3 were examined. By employing site-directed mutagenesis, 4 SULT1A3 allozymes were generated, expressed, and purified. Purified SULT1A3 allozymes were shown to exhibit differential sulfating activity toward ritodrine. Kinetic studies further demonstrated differential substrate affinity and catalytic efficiency among the SULT1A3 allozymes. Collectively, these results provided useful information concerning the differential metabolism of ritodrine through sulfation in different individuals.

  6. Effects of UGT1A4 genetic polymorphisms on serum lamotrigine concentrations in Chinese children with epilepsy.

    PubMed

    Wang, Qiuning; Liang, Min; Dong, Yang; Yun, Wenting; Qiu, Feng; Zhao, Limei; Guo, Yingjie

    2015-06-01

    Lamotrigine (LTG) is widely used in the treatment of children with epilepsy. Genetic polymorphisms in genes encoding drug-metabolizing enzymes may be an important source of interindividual variability in LTG metabolism. The aim of this study was to evaluate the effects of genetic polymorphisms of uridine diphosphate glucuronosyltransferase (UGT) 1A4 (UGT1A4) gene on LTG serum concentrations in children with epilepsy. The UGT1A4 142T > G in the coding regions and -219C > T/-163G > A in the 5'-upstream regions were genotyped using polymerase chain reaction amplification followed by direct automated DNA sequencing in 148 patients treated with polytherapy with LTG and valproic acid (VPA). Our data showed that patients carrying the variant UGT1A4 -219C > T/-163G > A genotypes or alleles had significantly higher adjusted LTG concentrations than those carrying the wild-type genotypes or alleles. However, the significant association was abrogated after adjusted by age, body weight, and adjusted VPA concentration. No associations were detected between the UGT1A4 142T > G genotypes or alleles and adjusted LTG concentrations. Taken together, these results suggest that the -219C > T/-163G > A mutations in the 5'-upstream regions of the UGT1A4 gene affect LTG pharmacokinetics, with which is potentially interfered by age, body weight, and concomitant VPA administration. PMID:25922177

  7. 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

    2015-11-26

    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.

  8. A pilot genetic study of the continuum between compulsivity and impulsivity in females: the serotonin transporter promoter polymorphism.

    PubMed

    Baca-García, Enrique; Salgado, Beatríz Rodríguez; Segal, Helen Dolengevich; Lorenzo, Concepción Vaquero; Acosta, Mercedes Navio; Romero, Manuel Arrojo; Hernández, Montserrat Díaz; Saiz-Ruiz, Jeronimo; Fernandez Piqueras, Jose; de Leon, Jose

    2005-06-01

    According to some authors the obsessive-compulsive (OC) spectrum includes on one extreme, the Obsessive-Compulsive Disorder (OCD) and on the other extreme the most impulsive behaviors. This is a controversial idea and other authors define the OC spectrum in different ways. The serotonin transporter (5-HTT) gene is one of the main genes that control serotonergic function. A polymorphism in the promoter area of this gene classifies subjects with low expression as S individuals (s/s or s/l) and subjects with high expression as L individuals (l/l). This polymorphism was studied in female OCD patients (n = 24), non-impulsive controls (n = 112) and impulsive suicidal patients (n = 118) to support the OC spectrum hypothesis from a genetic perspective. A linear association exists among the serotonin transporter promoter functional genotypes (S versus L individuals) (chi2 linear by linear association = 8.9; df = 1; p = 0.003). The frequency of S individuals (s/l or s/s) was lowest in OCD (54%, 13/24); intermediate in non-impulsive controls (71%, 80/112) and highest in impulsive suicide attempters (82%, 96/117). More importantly, future studies need to consider that genetics may be related to behavioral dimensions (compulsivity to impulsivity) instead of to specific psychiatric disorders defined in clinical terms.

  9. Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case–control study

    PubMed Central

    Reszka, Edyta; Gromadzinska, Jolanta

    2007-01-01

    Oxidative stress and xenobiotic metabolizing enzymes are suspected to be related to carcinogenesis by different cellular mechanisms. Hence, our study aimed at identifying potential relationships between antioxidant defense parameters measured in blood and glutathione S-transferase (GST) genetic polymorphisms of four GST izoenzymes in lung cancer patients and reference individuals. The case–control study included 404 lung cancer patients and 410 non-cancer subjects as controls, matched by age, gender and place of living (central Poland). In control subjects with GSTM3*A/*A, GSTT1 null, GSTM1 null + GSTT1 null, GSTM3*A/*A + GSTT1 null genotype, glutathione peroxidase activity was significantly higher (P < 0.05) than in controls possessing respective potential protective GST genotypes. Controls with GSTM3*A/*A + GSTP1*B genotype presented significantly higher ceruloplasmin activity (P < 0.05) than GSTM3*B + GSTP1*A/*A carriers. Zinc level was significantly higher (P < 0.05) in controls and cases with GSTP1*B + GSTT1 null genotype and in cases with GSTM1 null + GSTP1*B genotype, when compared with respective potential protective GST genotypes. This case–control study indicates that particular defective GST genotypes may enhance the defense against oxidative stress. The potential relationship between the investigated antioxidative enzymes and microelements, and common functional genetic polymorphism of GST was observed mostly in control subjects. PMID:18850183

  10. Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case-control study.

    PubMed

    Reszka, Edyta; Wasowicz, Wojciech; Gromadzinska, Jolanta

    2007-12-01

    Oxidative stress and xenobiotic metabolizing enzymes are suspected to be related to carcinogenesis by different cellular mechanisms. Hence, our study aimed at identifying potential relationships between antioxidant defense parameters measured in blood and glutathione S-transferase (GST) genetic polymorphisms of four GST izoenzymes in lung cancer patients and reference individuals. The case-control study included 404 lung cancer patients and 410 non-cancer subjects as controls, matched by age, gender and place of living (central Poland). In control subjects with GSTM3*A/*A, GSTT1 null, GSTM1 null + GSTT1 null, GSTM3*A/*A + GSTT1 null genotype, glutathione peroxidase activity was significantly higher (P < 0.05) than in controls possessing respective potential protective GST genotypes. Controls with GSTM3*A/*A + GSTP1*B genotype presented significantly higher ceruloplasmin activity (P < 0.05) than GSTM3*B + GSTP1*A/*A carriers. Zinc level was significantly higher (P < 0.05) in controls and cases with GSTP1*B + GSTT1 null genotype and in cases with GSTM1 null + GSTP1*B genotype, when compared with respective potential protective GST genotypes. This case-control study indicates that particular defective GST genotypes may enhance the defense against oxidative stress. The potential relationship between the investigated antioxidative enzymes and microelements, and common functional genetic polymorphism of GST was observed mostly in control subjects. PMID:18850183

  11. 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 (χ2 = 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

  12. Polymorphic Regions in the Interleukin-1 Gene and Susceptibility to Chronic Periodontitis: A Genetic Association Study

    PubMed Central

    Lavu, Vamsi; Venkatesan, Vettriselvi; Lakkakula, Bhaskar Venkata Kameswara Subrahmanya; Venugopal, Priyanka; Paul, Solomon Franklin Durairaj

    2015-01-01

    Objective: The objectives of this study were to determine the association between single nucleotide polymorphisms (SNPs) in IL1B (−511, +3954), IL1A (−889, +4845), and the variable number of tandem repeats (VNTRs) polymorphism in the IL-1RN gene with chronic periodontitis susceptibility and to analyze gene–gene interactions in a hospital-based sample population from South India. Subjects and Methods: A total of 400 individuals were recruited for this study; 200 individuals with healthy gingiva and 200 chronic periodontitis patients. Genomic DNA was isolated from peripheral blood samples and genotyping was performed for the above-mentioned single nucleotide and VNTR polymorphisms by polymerase chain reaction, DNA sequencing, and agarose gel electrophoresis. Results: A higher proportion of the variant alleles were observed in the chronic periodontitis group for all the SNPs examined. The SNP at +3954 (C>T) in the IL1B gene was found to be significantly associated with chronic periodontitis (p=0.007). VNTR genotypes (χ2 value: 5.163, df=1, p=0.023) and alleles (χ2 value: 6.818, df=1, p=0.009) were found to have a significant association with chronic periodontitis susceptibility. Conclusion: In the study population examined, the SNP in the IL1B gene (+3954) and VNTR polymorphisms in the IL1RN gene were found to have a significant association with chronic periodontitis susceptibility. PMID:25710474

  13. [Genetic polymorphism of cytochrome P450 2E1 and the risk of nasopharyngeal carcinoma].

    PubMed

    Ben Chaaben, Arij; Abaza, Hajer; Douik, Hayet; Chaouch, Leila; Ayari, Fayza; Ouni, Nesrine; Mamoghli, Tasnim; Ben Guezella, Dorra; Mejri, Rachida; Harzallah, Latifa; Guemira, Fethi

    2015-12-01

    Cytochrome P450 2E1 (CYP2E1) is a detoxifying enzyme that belongs to the phase I metabolism of xenobiotics. This enzyme is encoded by a highly polymorphic gene whose common polymorphism corresponds to the substitution of cytosine (C) and thymine (T) at position -1019 (rs2031920). This polymorphism has been identified in several cancers including nasopharyngeal cancer (NPC). The study involved 124 patients with nasopharyngeal carcinoma, compared with 166 healthy controls. The presence or absence of the polymorphism is determined by PCR-RFLP. The frequency comparison between the two groups is determined by the χ(2) test. The analysis of our results showed a significant difference between the two groups regarding the mutant genotype (C2/C2) (5% vs. 0.5%, P=0.04) and has a risk factor for NPC in Tunisia (OR=8.39; CI 95% [0.99-388.1]). Also, the C2 allele was significantly associated with the group of patients than the control group (6% vs. 2%, P=0.016) and increased three times the risk of NPC in Tunisia (OR=2.99, CI 95% [1.12-8.79]). Our results confirm the results reported in other populations and emphasize the importance of the involvement of this gene in the development of detoxification of the NPC, which seems more and more strongly associated with environmental factors.

  14. Human Xq28 Inversion Polymorphism: From Sex Linkage to Genomics--A Genetic Mother Lode

    ERIC Educational Resources Information Center

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

    2016-01-01

    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…

  15. Verification of genetic identity of introduced cacao germplasm in Ghana using single nucleotide polymorphism (SNP) markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accurate identification of individual genotypes is important for cacao (Theobroma cacao L.) breeding, germplasm conservation and seed propagation. The development of single nucleotide polymorphism (SNP) markers in cacao offers an effective way to use a high-throughput genotyping system for cacao gen...

  16. Genetic Polymorphisms of TLR4 and MICA are Associated with Severity of Trachoma Disease in Tanzania

    PubMed Central

    Abbas, Muneer; Berka, Noureddine; Khraiwesh, Mozna; Ramadan, Ali; Apprey, Victor; Furbert-Harris, Paulette; Quinn, Thomas; Brim, Hassan; Dunston, Georgia

    2016-01-01

    Aim To examine the association of TLR4 Asp299Gly and MICA exon 5 microsatellites polymorphisms with severity of trachoma in a sub-Saharan East Africa population of Tanzanian villagers. Methods The samples were genotyped for MICA exon 5 microsatellites and the TLR4 299 A/G polymorphism by Restriction Fragment Length Polymorphism (RFLP), and GeneScan®, respectively. The association of TLR4 Asp299Gly and MICA exon 5 microsatellites with inflammatory trachoma (TI) and trichiasis (TI) were examined. Results The results showed an association between TLR4 and MICA polymorphisms and trachoma disease severity, as well as with protection. TLR4 an allele was significantly associated with inflammatory trachoma (p=0.0410), while the G allele (p=0.0410) was associated with protection. Conclusion TLR4 and MICA may modulate the risk of severity to trachoma disease by modulating the immune response to Ct. In addition; the increased frequency of MICA-A9 heterozygote in controls may suggest a positive selection of these alleles in adaptation to environments where Ct is endemic.

  17. Genetic Polymorphisms of TLR4 and MICA are Associated with Severity of Trachoma Disease in Tanzania

    PubMed Central

    Abbas, Muneer; Berka, Noureddine; Khraiwesh, Mozna; Ramadan, Ali; Apprey, Victor; Furbert-Harris, Paulette; Quinn, Thomas; Brim, Hassan; Dunston, Georgia

    2016-01-01

    Aim To examine the association of TLR4 Asp299Gly and MICA exon 5 microsatellites polymorphisms with severity of trachoma in a sub-Saharan East Africa population of Tanzanian villagers. Methods The samples were genotyped for MICA exon 5 microsatellites and the TLR4 299 A/G polymorphism by Restriction Fragment Length Polymorphism (RFLP), and GeneScan®, respectively. The association of TLR4 Asp299Gly and MICA exon 5 microsatellites with inflammatory trachoma (TI) and trichiasis (TI) were examined. Results The results showed an association between TLR4 and MICA polymorphisms and trachoma disease severity, as well as with protection. TLR4 an allele was significantly associated with inflammatory trachoma (p=0.0410), while the G allele (p=0.0410) was associated with protection. Conclusion TLR4 and MICA may modulate the risk of severity to trachoma disease by modulating the immune response to Ct. In addition; the increased frequency of MICA-A9 heterozygote in controls may suggest a positive selection of these alleles in adaptation to environments where Ct is endemic. PMID:27559544

  18. Amplified fragment length polymorphism used to investigate genetic variability of the stable fly (Diptera: Muscidae) across North America.

    PubMed

    Kneeland, K M; Skoda, S R; Foster, J E

    2013-09-01

    The stable fly, Stomoxys calcitrans (L.), is a cosmopolitan pest of livestock and humans. The pestiferous nature and painful bite cause stress to cattle and other animals. The stress and resulting avoidance behaviors manifest as reductions in weight gain or milk production in cattle; estimated annual economic loss in the United States exceeds US$2 billion. Understanding the population genetics of stable flies could provide information on their population dynamics, origins of outbreaks, and geographical patterns of insecticide resistance, resulting in a tactical advantage for developing management strategies. Previous studies, mostly on a local scale, reported a high level of gene flow between locations. Here, we report results wherein amplified fragment length polymorphism was used to determine genetic diversity of stable fly samples consisting of 11-40 individuals from 12 locations representing the United States, Canada, and Panama. The Analysis of Molecular Variance showed that the majority of genetic diversity was within groups; very little was among groups. The F(ST) and G(ST) values were low (< 0.4), Nm values high (> 1.0). The tests of neutrality suggested population expansion, and no genetic differentiation was found between locations. These results show that stable flies have a high level of gene flow on a continental scale, with limited isolation owing to distance or geographical barriers.

  19. Genetic polymorphisms of interleukin 20 (IL-20) in patients with ulcerative colitis.

    PubMed

    Yamamoto-Furusho, Jesús K; De-León-Rendón, Jorge L; de la Torre, Monica García; Alvarez-León, Edith; Vargas-Alarcón, Gilberto

    2013-01-01

    Interleukin (IL)-20 belongs to the IL-10 family and is a potent immunomodulatory cytokine with implications for pathogenesis in the inflammatory bowel disease (IBD). The interleukin 20 gene is located within a 200kb region of q31-32 locus of chromosome 1. No previous studies have reported this novel association between ulcerative colitis (UC) and IL-20 polymorphisms. In the present work, we evaluated the role of IL-20 gene polymorphisms as susceptibility markers for UC. Three polymorphisms of IL-20 gene (rs2981573, rs2232360, rs1518108) were genotyped by 5' exonuclease TaqMan genotyping assays on an ABI Prism 7900 HT Fast Real-Time PCR system in a group of 198 Mexican Mestizo patients with UC and 698 ethnically matched healthy unrelated individuals with no family history