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Sample records for harbors genetic polymorphisms

  1. Genetics Home Reference: Floating-Harbor syndrome

    MedlinePlus

    ... Understand Genetics Home Health Conditions Floating-Harbor syndrome Floating-Harbor syndrome Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description Floating-Harbor syndrome is a disorder involving short stature, ...

  2. 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.

  3. Genetic polymorphisms linked to susceptibility to malaria.

    PubMed

    Driss, Adel; Hibbert, Jacqueline M; Wilson, Nana O; Iqbal, Shareen A; Adamkiewicz, Thomas V; Stiles, Jonathan K

    2011-09-19

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

  4. Genetic salivary protein polymorphism in Mexican population.

    PubMed

    Banderas Tarabay, J A; González Begné, M

    1996-01-01

    Genetic polymorphism is the major contributor that affects human salivary composition. In order to determine the molecular phenotypes in saliva, it is important to know the distribution of proteins with specific functions which allows the clinical diagnosis of specific diseases. Unstimulated human whole saliva samples from 120 subjects were subjected to sodium dodecyl sulfate polyacrylamide slab gel electrophoresis (SDS-PAGE). The phenotype distribution of several molecules including MG1, MG2, alpha-Amylase, PRP-I and cystatins were similar. Qualitative and quantitative characteristics were specific in each subject.

  5. Special considerations in prognostic research in cancer involving genetic polymorphisms

    PubMed Central

    2013-01-01

    Analysis of genetic polymorphisms may help identify putative prognostic markers and determine the biological basis of variable prognosis in patients. However, in contrast to other variables commonly used in the prognostic studies, there are special considerations when studying genetic polymorphisms. For example, variable inheritance patterns (recessive, dominant, codominant, and additive genetic models) need to be explored to identify the specific genotypes associated with the outcome. In addition, several characteristics of genetic polymorphisms, such as their minor allele frequency and linkage disequilibrium among multiple polymorphisms, and the population substructure of the cohort investigated need to be accounted for in the analyses. In addition, in cancer research due to the genomic differences between the tumor and non-tumor DNA, differences in the genetic information obtained using these tissues need to be carefully assessed in prognostic studies. In this article, we review these and other considerations specific to genetic polymorphism by focusing on genetic prognostic studies in cancer. PMID:23773794

  6. A stable genetic polymorphism underpinning microbial syntrophy

    PubMed Central

    Großkopf, Tobias; Zenobi, Simone; Alston, Mark; Folkes, Leighton; Swarbreck, David; Soyer, Orkun S

    2016-01-01

    Syntrophies are metabolic cooperations, whereby two organisms co-metabolize a substrate in an interdependent manner. Many of the observed natural syntrophic interactions are mandatory in the absence of strong electron acceptors, such that one species in the syntrophy has to assume the role of electron sink for the other. While this presents an ecological setting for syntrophy to be beneficial, the potential genetic drivers of syntrophy remain unknown to date. Here, we show that the syntrophic sulfate-reducing species Desulfovibrio vulgaris displays a stable genetic polymorphism, where only a specific genotype is able to engage in syntrophy with the hydrogenotrophic methanogen Methanococcus maripaludis. This 'syntrophic' genotype is characterized by two genetic alterations, one of which is an in-frame deletion in the gene encoding for the ion-translocating subunit cooK of the membrane-bound COO hydrogenase. We show that this genotype presents a specific physiology, in which reshaping of energy conservation in the lactate oxidation pathway enables it to produce sufficient intermediate hydrogen for sustained M. maripaludis growth and thus, syntrophy. To our knowledge, these findings provide for the first time a genetic basis for syntrophy in nature and bring us closer to the rational engineering of syntrophy in synthetic microbial communities. PMID:27258948

  7. Impact of host genetic polymorphisms on vaccine induced antibody response

    PubMed Central

    Linnik, Janina E.; Egli, Adrian

    2016-01-01

    ABSTRACT Many host- and vaccine-specific factors modulate an antibody response. Host genetic polymorphisms, in particular, modulate the immune response in multiple ways on different scales. This review article describes how information on host genetic polymorphisms and corresponding immune cascades may be used to generate personalized vaccine strategies to optimize the antibody response. PMID:26809773

  8. 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

  9. 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

  10. Alu polymorphic insertions reveal genetic structure of north Indian populations.

    PubMed

    Tripathi, Manorama; Tripathi, Piyush; Chauhan, Ugam Kumari; Herrera, Rene J; Agrawal, Suraksha

    2008-10-01

    The Indian subcontinent is characterized by the ancestral and cultural diversity of its people. Genetic input from several unique source populations and from the unique social architecture provided by the caste system has shaped the current genetic landscape of India. In the present study 200 individuals each from three upper-caste and four middle-caste Hindu groups and from two Muslim populations in North India were examined for 10 polymorphic Alu insertions (PAIs). The investigated PAIs exhibit high levels of polymorphism and average heterozygosity. Limited interpopulation variance and genetic flow in the present study suggest admixture. The results of this study demonstrate that, contrary to common belief, the caste system has not provided an impermeable barrier to genetic exchange among Indian groups.

  11. Salivary proteome and its genetic polymorphisms.

    PubMed

    Oppenheim, Frank G; Salih, Erdjan; Siqueira, Walter L; Zhang, Weimin; Helmerhorst, Eva J

    2007-03-01

    Salivary diagnostics for oral as well as systemic diseases is dependent on the identification of biomolecules reflecting a characteristic change in presence, absence, composition, or structure of saliva components found under healthy conditions. Most of the biomarkers suitable for diagnostics comprise proteins and peptides. The usefulness of salivary proteins for diagnostics requires the recognition of typical features, which make saliva as a body fluid unique. Salivary secretions reflect a degree of redundancy displayed by extensive polymorphisms forming families for each of the major salivary proteins. The structural differences among these polymorphic isoforms range from distinct to subtle, which may in some cases not even affect the mass of different family members. To facilitate the use of modern state-of-the-art proteomics and the development of nanotechnology-based analytical approaches in the field of diagnostics, the salient features of the major salivary protein families are reviewed at the molecular level. Knowledge of the structure and function of salivary gland-derived proteins/peptides has a critical impact on the rapid and correct identification of biomarkers, whether they originate from exocrine or non-exocrine sources.

  12. 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.

  13. Aspirin-induced peptic ulcer and genetic polymorphisms.

    PubMed

    Shiotani, Akiko; Sakakibara, Takashi; Nomura, Maki; Yamanaka, Yoshiyuki; Nishi, Ryuji; Imamura, Hiroshi; Tarumi, Ken-ichi; Kamada, Tomoari; Hata, Jiro; Haruma, Ken

    2010-05-01

    There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)-induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX-1-1676T alleles was a significant risk factor for peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non-aspirin NSAID-related GI bleeding. The polymorphisms of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL-1beta-511 T allele was significantly associated with peptic ulcer among low-dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro-inflammatory cytokines seems to reduce NSAIDs or aspirin-related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large-scale clinical studies are required.

  14. 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

  15. Rabbit MSTN gene polymorphisms and genetic effect analysis.

    PubMed

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

    2014-04-08

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

  16. 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.

  17. Disrupted cell cycle control in cultured endometrial cells from patients with endometriosis harboring the progesterone receptor polymorphism PROGINS.

    PubMed

    D'Amora, Paulo; Maciel, Thiago Trovati; Tambellini, Rodrigo; Mori, Marcelo A; Pesquero, João Bosco; Sato, Helio; Girão, Manoel João Batista Castello; Guerreiro da Silva, Ismael Dale Cotrim; Schor, Eduardo

    2009-07-01

    Presently, little is understood about how endometriosis is established or maintained, or how genetic factors can predispose women to the disease. Because of the crucial role that the progesterone receptor polymorphism PROGINS plays in predisposing women to the development of endometriosis, we hypothesized that this variant may influence critical steps during endometrial cell metabolism that are involved in the pathogenesis of endometriosis. Eutopic endometria were collected from three sources: women with endometriosis who had a single PROGINS allele (from the progesterone receptor gene); women with endometriosis who had the wild-type progesterone receptor allele; and women without endometriosis who had the wild-type allele. Cells prepared from the eutopic endometria of these women were stimulated with both estradiol and progesterone, and then examined for cell proliferation, viability, and apoptosis. The cells from women with endometriosis that carried the PROGINS allele demonstrated increased proliferation, greater viability, and decreased apoptosis following progesterone treatment. In general, these parameters were very different as compared with those of women with endometriosis but without the PROGINS allele and women in the control group. This result indicates there is a reduced level of progesterone responsiveness in women who carry the PROGINS polymorphism. Because progesterone responsiveness is known to be an important characteristic of women with endometriosis, these data support the contention that the PROGINS polymorphism enhances the endometriosis phenotype.

  18. Genetic polymorphisms for vascular endothelial growth factor in perinatal complications.

    PubMed

    Bányász, Ilona; Bokodi, Géza; Vásárhelyi, Barna; Treszl, András; Derzbach, László; Szabó, András; Tulassay, Tivadar; Vannay, Adám

    2006-12-01

    Low birth weight (LBW) infants have increased susceptibility to perinatal complications. An immature and impaired vascular system may possibly participate in these complications. There is evidence that supports the notion that vascular endothelial growth factor (VEGF), which is an essential regulator of embryonic angiogenesis, plays a central role in the pathogenesis of perinatal complications. We aimed to test whether functional genetic polymorphisms of VEGF are associated with the risk of preterm birth or perinatal morbidity. We enrolled 128 LBW infants (< or = 1500 grams). VEGF T-460C, VEGF C-2578A and VEGF G+405C polymorphisms were determined by real-time PCR or PCR-RFLP, respectively. Their genotypes were compared with VEGF genotypes of 200 healthy, term neonates. The prevalence of the VEGF+405 C allele was higher in LBW infants than in healthy, term neonates (OR [95% CI]: 1.29 [1.01-1.65]). Carrier state for the VEGF -2578A allele was an independent risk factor for enterocolitis necrotisans (NEC) (adjusted OR [95% CI]: 2.77 [1.00-7.65]). The carrier state for the VEGF -2578AA genotype was associated with a decreased risk of acute renal failure (ARF) (adjusted OR [95% CI]: 0.2 [0.05-0.78]). These results suggest that VEGF G+405C polymorphism might be associated with a higher risk of preterm birth and that VEGF C-2578A polymorphism may participate in the development of perinatal complications such as NEC and ARF.

  19. Genetic polymorphism in the NRF2 gene as a prognosis marker for cancer chemotherapy.

    PubMed

    Ishikawa, Toshihisa

    2014-01-01

    NF-E2-related factor 2 (NRF2) is a transcription factor that controls the expression of a variety of antioxidant and detoxification genes. Accumulating evidence strongly suggests that NRF2 mediates cancer cell proliferation and drug resistance, as well. Single nucleotide polymorphism (SNP) -617C > A in the anti-oxidant response element-like loci of the human NRF2 gene play a pivotal role in the positive feedback loop of transcriptional activation of the NRF2 gene. Since the SNP (-617A) reportedly decreases the binding affinity to the transcription factors of NRF2/small multiple alignment format (MafK), the homozygous -617A/A allele may attenuate the positive feedback loop of transcriptional activation of the NRF2 gene and reduce the NRF2 protein level. As the consequence, cancer cells are considered to become more sensitive to therapy and less aggressive than cancer cells harboring the -617C (WT) allele. Indeed, Japanese lung cancer patients carrying SNP homozygous alleles (c. -617A/A) exhibited remarkable survival over 1,700 days after surgical operation (log-rank p = 0.021). The genetic polymorphism in the human NRF2 gene is considered as one of prognosis markers for cancer therapy.

  20. 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

  1. Genetic Association Between PER3 Genetic Polymorphisms and Cancer Susceptibility

    PubMed Central

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

    2015-01-01

    Abstract The genes along the circadian pathways control and modulate circadian rhythms essential for the maintenance of physiological homeostasis through self-sustained transcription-translation feedback loops. PER3 (period 3) is a circadian pathway gene and its variants (rs1012477, 4/5-repeat) have frequently been associated with human cancer. The mixed findings, however, make the role of the 2 variants in cancer susceptibility elusive. We aimed in this article to clarify the association of PER3 variants with cancer. We collected genetic data from 8 studies, providing 6149 individuals for rs1012477 and 5241 individuals for 4/5-repeat. Based on the genotype and allele frequency, we chose the fixed-effects model to estimate risk of cancer. Overall analysis did not suggest a global role of rs1012477 in cancer susceptibility. For PER3 4/5-repeat variant, we found a moderate increase in risk of cancer among individuals with the 5-allele compared to individuals with the 4-allele, although this association was not statistically significant (homozygous model: odds ratio [OR] 1.17, 95% confidence interval [CI] 0.81–1.67; recessive model: OR 1.17, 95% CI 0.82–1.67). No substantial heterogeneity was revealed in this analysis. Our meta-analysis provides no evidence supporting a global association of PER3 genetic variants with the incidence of cancer. PMID:25837749

  2. 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.

  3. 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.

  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. Genetic colour polymorphism is associated with avian malarial infections.

    PubMed

    Gangoso, Laura; Gutiérrez-López, Rafael; Martínez-de la Puente, Josué; Figuerola, Jordi

    2016-12-01

    Individual genetic diversity is predicted to influence host-parasite interactions. Together with the genes directly associated with immune responses, variation in genes regulating vertebrate melanin-based pigmentation may play an important role in these interactions, mainly through the pleiotropic effects that affect colour-specific physiology, behaviour and immunity. Here, we test the hypothesis that the prevalence of avian malarial parasites differs between phenotypes in a raptor species in which the genetic basis of colour polymorphism and its pleiotropic effects over immune functions are known. We found that dark morphs had a higher prevalence of Plasmodium parasites than pale ones but detected no such association for Haemoproteus This pattern may be associated with unequal exposure to vectors or, as suggested by our circumstantial evidence, to a differential ability to mount an immune response against blood parasites.

  6. 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.

  7. 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

  8. 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.

  9. [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.

  10. 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

  11. 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.

  12. 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

  13. Genetic diversity of Eurycoma longifolia inferred from single nucleotide polymorphisms.

    PubMed

    Osman, Asiah; Jordan, Barbara; Lessard, Philip A; Muhammad, Norwati; Haron, M Rosli; Riffin, Norifiza Mat; Sinskey, Anthony J; Rha, ChoKyun; Housman, David E

    2003-03-01

    Eurycoma longifolia Jack. is a treelet that grows in the forests of Southeast Asia and is widely used throughout the region because of its reported medicinal properties. Widespread harvesting of wild-grown trees has led to rapid thinning of natural populations, causing a potential decrease in genetic diversity among E. longifolia. Suitable genetic markers would be very useful for propagation and breeding programs to support conservation of this species, although no such markers currently exist. To meet this need, we have applied a genome complexity reduction strategy to identify a series of single nucleotide polymorphisms (SNPs) within the genomes of several E. longifolia accessions. We have found that the occurrence of these SNPs reflects the geographic origins of individual plants and can distinguish different natural populations. This work demonstrates the rapid development of molecular genetic markers in species for which little or no genomic sequence information is available. The SNP markers that we have developed in this study will also be useful for identifying genetic fingerprints that correlate with other properties of E. longifolia, such as high regenerability or the appearance of bioactive metabolites.

  14. 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

  15. 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.

  16. 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.

  17. Genetic diversity among Clostridium botulinum strains harboring bont/A2 and bont/A3 genes.

    PubMed

    Lúquez, Carolina; Raphael, Brian H; Joseph, Lavin A; Meno, Sarah R; Fernández, Rafael A; Maslanka, Susan E

    2012-12-01

    Clostridium botulinum type A strains are known to be genetically diverse and widespread throughout the world. Genetic diversity studies have focused mainly on strains harboring one type A botulinum toxin gene, bont/A1, although all reported bont/A gene variants have been associated with botulism cases. Our study provides insight into the genetic diversity of C. botulinum type A strains, which contain bont/A2 (n = 42) and bont/A3 (n = 4) genes, isolated from diverse samples and geographic origins. Genetic diversity was assessed by using bont nucleotide sequencing, content analysis of the bont gene clusters, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Sequences of bont genes obtained in this study showed 99.9 to 100% identity with other bont/A2 or bont/A3 gene sequences available in public databases. The neurotoxin gene clusters of the subtype A2 and A3 strains analyzed in this study were similar in gene content. C. botulinum strains harboring bont/A2 and bont/A3 genes were divided into six and two MLST profiles, respectively. Four groups of strains shared a similarity of at least 95% by PFGE; the largest group included 21 out of 46 strains. The strains analyzed in this study showed relatively limited genetic diversity using either MLST or PFGE.

  18. [Genetic polymorphisms commonly influencing efficacy of diverse addictive substances].

    PubMed

    Nishizawa, Daisuke; Ikeda, Kazutaka

    2014-04-01

    Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. The authors have focused on G-protein-activated inwardly rectifying potassium (GIRK) channel subunits, GIRK2 and GIRK3, that are important molecules in opioid transmission, and found that the single-nucleotide polymorphisms (SNPs) within the GIRK2 and GIRK3 gene regions were significantly associated with postoperative requirements of analgesics including opioids in patients who underwent abdominal surgery and mRNA expression of these genes in postmortem specimens, one of which was also associated with vulnerability to methamphetamine (METH) dependence. Further, by conducting a multistage genome-wide association study (GWAS) in healthy subjects, the authors found that genetic polymorphisms within a linkage disequilibrium block that spans 2q33.3-2q34 were strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery. The C allele of the best candidate SNP, rs2952768, was associated with more analgesic requirements, and consistent results were obtained in patients who underwent abdominal surgery. In addition, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence in patients with methamphetamine dependence, alcohol dependence, and eating disorders and a lower 'Reward Dependence score on a personality questionnaire in healthy subjects. Furthermore, the C/C genotype of this SNP was significantly associated with the elevated expression of a neighboring gene, CREB1. The results show that SNPs in this locus are the most potent genetic factors associated with human opioid sensitivity known to date, affecting both the efficacy of opioid analgesics and liability to severe substance dependence. These outcomes provide valuable information for the

  19. Genetic diversity among elite Sorghum lines revealed by restriction fragment length polymorphisms and random amplified polymorphic DNAs.

    PubMed

    Vierling, R A; Xiang, Z; Joshi, C P; Gilbert, M L; Nguyen, H T

    1994-02-01

    The genetic diversity of sorghum, as compared to corn, is less well characterized at the genetic and molecular levels despite its worldwide economic importance. The objectives of this study were to: (1) investigate genetic diversity for restriction fragment length polymorphism (RFLPs) and random amplified polymorphic DNAs (RAPDs) in elite sorghum lines, (2) compare similarities based on molecular markers with pedigree relationships, and (3) examine the potential of RFLPs and RAPDs for assigning sorghum lines to the A/B (sterile) and R (restorer) groups. Using four restriction enzymes, polymorphism was detected with 61% of the RFLP probes used, compared to 77% of the random primers. One hundred and sixteen (64%) probe-enzyme combinations yielded multiple-band profiles compared to 98% of the random primers. RFLP profiles generated 290 polymorphic bands compared to 177 polymorphic RAPDs. Pair-wise comparisons of polymorphic RFLPs and RAPDs were used to calculate Nei and Jaccard coefficients. These were employed to generate phenograms using UPGMA and neighborjoining clustering methods. Analysis of RFLP data with Jaccard's coefficient and neighbor-joining clustering produced the phenogram with the closest topology to the known pedigree.

  20. Detected microsatellite polymorphisms in genetically altered inbred mouse strains.

    PubMed

    Du, Xiaoyan; Cui, Jing; Wang, Chao; Huo, Xueyun; Lu, Jing; Li, Yichen; Chen, Zhenwen

    2013-08-01

    Microsatellites are 50-200 repetitive DNA sequences composed of 1- to 6-base-pair-long reiterative motifs within the genome. They are vulnerable to DNA modifications, such as recombination and/or integration, and are recognized as "sentinel" DNA. Our previous report indicated that the genotypes of the microsatellite loci could change from mono- to poly-morphisms (CMP) in gene knockout (KO) mice, implying that genetic modification induces microsatellite mutation. However, it is still unclear whether the random insertion of DNA fragments into mice genomes produced via transgene (Tg) or N-ethyl-N-nitrosourea (ENU) would also result in microsatellite mutations or microsatellite loci genotypes changes. This study was designed to find possible clues to answer this question. In brief, 198 microsatellite loci that were distributed among almost all of the chromosomes (except for the Y) were examined through polymerase chain reaction to screen possible CMPs in six Tg strains. First, for each strain, the microsatellite sequences of all loci were compared between Tg and the corresponding background strain to exclude genetic interference. Simultaneously, to exclude spontaneous mutation-related CMPs that might exist in the examined six strains, mice from five spontaneously mutated inbred strains were used as the negative controls. Additionally, the sequences of all loci in these spontaneous mutated mice were compared to corresponding genetic background controls. The results showed that 40 of the 198 (20.2%) loci were identified as having CMPs in the examined Tg mice strains. The CMP genotypes were either homozygous or heterozygous compared to the background controls. Next, we applied the 40 CMP positive loci in ENU-mutated mice and their corresponding background controls. After that, a general comparison of CMPs that exist among Tg, ENU-treated and KO mouse strains was performed. The results indicated that four (D11mit258, D13mit3, D14mit102 and DXmit172) of the 40 (10%) CMP

  1. 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.

  2. Genetic structure of Hepatica nobilis var. japonica, focusing on within population flower color polymorphism.

    PubMed

    Kameoka, Shinichiro; Sakio, Hitoshi; Abe, Harue; Ikeda, Hajime; Setoguchi, Hiroaki

    2017-03-01

    How phenotypic or genetic diversity is maintained in a natural habitat is a fundamental question in evolutionary biology. Flower color polymorphism in plants is a common polymorphism. Hepatica nobilis var. japonica on the Sea of Japan (SJ) side of the Japanese mainland exhibits within population flower color polymorphism (e.g., white, pink, and purple), while only white flowers are observed on the Pacific Ocean (PO) side. To determine the relationships between flower color polymorphism, within and among populations, and the genetic structure of H. nobilis var. japonica, we estimated the genetic variation using simple sequence repeat (SSR) markers. First, we examined whether cryptic lineages corresponding to distinct flower colors contribute to the flower color polymorphisms in H. nobilis var. japonica. In our field observations, no bias in color frequency was observed among populations on Sado Island, a region with high variation in flower color. Simple sequence repeat (SSR) analyses revealed that 18% of the genetic variance was explained by differences among populations, whereas no genetic variation was explained by flower color hue or intensity (0% for both components). These results indicate that the flower color polymorphism is likely not explained by cryptic lineages that have different flower colors. In contrast, populations in the SJ and PO regions were genetically distinguishable. As with the other plant species in these regions, refugial isolation and subsequent migration history may have caused the genetic structure as well as the spatially heterogeneous patterns of flower color polymorphisms in H. nobilis var. japonica.

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

    PubMed

    Cox, Christian L; Chippindale, Paul T

    2014-08-01

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

  4. Genetic polymorphisms in human drug-metabolizing enzymes: potential uses of reverse genetics to identify genes of toxicological relevance.

    PubMed

    Puga, A; Nebert, D W; McKinnon, R A; Menon, A G

    1997-03-01

    The human mind was engaged with fundamental questions on the nature of heredity long before the study of genetics became a scientific discipline. Many traits, such as height, eye color, blood pressure, or cancer susceptibility, have been known to run in families, although the genes or combination of genes that underlie these observable characteristics remain unknown in most cases. Differences in susceptibility to environmental agents in humans are likewise determined by variations in genetic background--genetic polymorphisms. In this article, we review the current status of studies on human polymorphisms in drug-metabolizing enzymes and discuss various approaches to the analysis of genetic polymorphisms. We expect that in the near future, novel methods in genetic analysis of human populations will be likely to play a key role in the identification of genes of toxicological relevance.

  5. 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

  6. Genetic polymorphisms of the Caucasus ethnic groups: distribution of some blood group genetic markers (Part II).

    PubMed

    Nasidze, I S

    1995-08-01

    The compiled data on the distribution of polymorphic blood groups (ABO, Diego, Duffy, Kell-Cellano, Kidd, MN, MNSs, P, Penney, Rh(D), Rh-Hr), secretion ABH antigens in saliva, HLA system (HLA-A, HLA-B, HLA-C, HLA-DR), immunoglobulin (GM1) and other miscellaneous data (phenylthiocarbamide taste, tongue rolling) in the Caucasus are presented. Results of the interpopulation heterogeneity test show that, in spite of the limited territory of the Caucasus, a high level of genetic variability was observed. In terms of gene frequencies, these ethnic groups are approximately equidistant from European and West Asian Populations.

  7. 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) ...

  8. Prenatal mercury exposure, neurodevelopment and apolipoprotein E genetic polymorphism.

    PubMed

    Snoj Tratnik, Janja; Falnoga, Ingrid; Trdin, Ajda; Mazej, Darja; Fajon, Vesna; Miklavčič, Ana; Kobal, Alfred B; Osredkar, Joško; Sešek Briški, Alenka; Krsnik, Mladen; Neubauer, David; Kodrič, Jana; Stropnik, Staša; Gosar, David; Lešnik Musek, Petra; Marc, Janja; Jurkovič Mlakar, Simona; Petrović, Oleg; Vlašić-Cicvarić, Inge; Prpić, Igor; Milardović, Ana; Radić Nišević, Jelena; Vuković, Danijela; Fišić, Elizabeta; Špirić, Zdravko; Horvat, Milena

    2017-01-01

    The aim of the present study was to evaluate the association between prenatal exposure to mercury (Hg) and neurodevelopment of the child, taking into account genetic polymorphism of apolipoprotein E (Apoe) and other relevant confounders. Six hundred and one mother-child pairs were recruited from the central Slovenia region and 243 from Rijeka, on the Croatian coast of the northern Adriatic. The total Hg in cord blood, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessment at 18 months of age and Apoe genotyping was performed on 361 children; 237 of them were from Slovenia and 124 from Croatia. The results showed negative association between low-to-moderate Hg exposure in children with normal neurodevelopmental outcome and cognitive and fine motor scores at 18 months of age as assessed by Bayley III. The Hg-related decrease in cognitive score was observed only in children carrying at least one Apoe ε4 allele, while the decrease in fine motor scores was independent of the Apoe genotype. Adjusting for selenium (Se) and lead (Pb) levels, a positive association between Se and the language score and a negative association between Pb and the motor score was observed, but not in the subgroup of children carrying the ε4 allele.

  9. 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

  10. Genetic polymorphisms and non-small-cell lung cancer: future paradigms

    PubMed Central

    de Mello, Ramon Andrade Bezerra

    2014-01-01

    This article addresses some current issues about genetic polymorphisms studied in the non-small-cell lung cancer translational field. Furthermore, it discusses about new potential biomarkers regarding lung cancer risk and prognosis. PMID:25628210

  11. Influence of GSTT1 Genetic Polymorphisms on Arsenic Metabolism

    PubMed Central

    Kile, Molly L.; Houseman, E. Andres; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Hsueh, Yu-Mei; Christiani, David C.

    2014-01-01

    SUMMARY A repeated measures study was conducted in Pabna, Bangladesh to investigate factors that influence biomarkers of arsenic exposure. Drinking water arsenic concentrations were measured by inductively-coupled plasma mass spectrometry (ICP-MS) and urinary arsenic species [arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)] were detected using High Performance Liquid Chromatography (HPLC) and Hydride Generated Atomic Absorption Spectrometry (HGAAS). Linear mixed effects models with random intercepts were used to evaluate the effects of arsenic contaminated drinking water, genetic polymorphisms in glutathione-S-transferase (GSTT1 and GSTM1) on total urinary arsenic, primary methylation index [MMA/(As3+As5)], secondary methylation index (DMA/MMA), and total methylation index [(MMA+DMA)/(As3+As5)]. Drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and total methylation index. A significant gene-environment interaction was observed between urinary arsenic exposure in drinking water GSTT1 but not GSTM1 where GSTT1 null individuals had a slightly higher excretion rate of arsenic compared to GSTT1 wildtypes after adjusting for other factors. Additionally, individuals with GSTT1 null genotypes had a higher primary methylation index and lower secondary methylation index compared to GSTT1 wildtype after adjusting for other factors. This data suggests that GSTT1 contributes to the observed variability in arsenic metabolism. Since individuals with a higher primary methylation index and lower secondary methylation index are more susceptible to arsenic related disease, these results suggest that GSTT1 null individuals may be more susceptible to arsenic-related toxicity. No significant associations were observed between GSTM1 and any of the arsenic methylation indices. PMID:24511153

  12. Influence of GSTT1 Genetic Polymorphisms on Arsenic Metabolism.

    PubMed

    Kile, Molly L; Houseman, E Andres; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Hsueh, Yu-Mei; Christiani, David C

    2013-08-01

    A repeated measures study was conducted in Pabna, Bangladesh to investigate factors that influence biomarkers of arsenic exposure. Drinking water arsenic concentrations were measured by inductively-coupled plasma mass spectrometry (ICP-MS) and urinary arsenic species [arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)] were detected using High Performance Liquid Chromatography (HPLC) and Hydride Generated Atomic Absorption Spectrometry (HGAAS). Linear mixed effects models with random intercepts were used to evaluate the effects of arsenic contaminated drinking water, genetic polymorphisms in glutathione-S-transferase (GSTT1 and GSTM1) on total urinary arsenic, primary methylation index [MMA/(As3+As5)], secondary methylation index (DMA/MMA), and total methylation index [(MMA+DMA)/(As3+As5)]. Drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and total methylation index. A significant gene-environment interaction was observed between urinary arsenic exposure in drinking water GSTT1 but not GSTM1 where GSTT1 null individuals had a slightly higher excretion rate of arsenic compared to GSTT1 wildtypes after adjusting for other factors. Additionally, individuals with GSTT1 null genotypes had a higher primary methylation index and lower secondary methylation index compared to GSTT1 wildtype after adjusting for other factors. This data suggests that GSTT1 contributes to the observed variability in arsenic metabolism. Since individuals with a higher primary methylation index and lower secondary methylation index are more susceptible to arsenic related disease, these results suggest that GSTT1 null individuals may be more susceptible to arsenic-related toxicity. No significant associations were observed between GSTM1 and any of the arsenic methylation indices.

  13. Genetic and epigenetic diversity and structure of Phragmites australis from local habitats of the Songnen Prairie using amplified fragment length polymorphism markers.

    PubMed

    Qiu, T; Jiang, L L; Yang, Y F

    2016-08-19

    The genetic and epigenetic diversity and structure of naturally occurring Phragmites australis populations occupying two different habitats on a small spatial scale in the Songnen Prairie in northeastern China were investigated by assessing amplified fragment length polymorphisms (AFLPs) and methylation-sensitive amplified polymorphisms (MSAPs) through fluorescent capillary detection. The two groups of P. australis were located in a seasonal waterlogged low-lying and alkalized meadow with a pH of 8-8.5 and in an alkaline patch without accumulated rainwater and with a pH greater than 10. These groups showed high levels of genetic diversity at the habitat level based on the percentage of polymorphic bands (90.32, 82.56%), Nei's gene diversity index (0.262, 0.248), and the Shannon diversity index (0.407, 0.383). Although little is known about the between-habitat genetic differentiation of P. australis on a small spatial scale, our results implied significant genetic differentiation between habitats. Extensive epigenetic diversity within habitats, along with clear differentiation, was found. Specifically, the former habitat (Habitat 1, designated H1) harbored higher levels of genetic and epigenetic diversity than the latter (Habitat 2, designated H2), and population-level diversity was also high. This study represents one of few attempts to predict habitat-based genetic differentiation of reeds on a small scale. These assessments of genetic and epigenetic variation are integral aspects of molecular ecological studies on P. australis. Possible causes for within- and between-habitat genetic and epigenetic variations are discussed.

  14. Combined effect of genetic polymorphisms of AURKA and environmental factors on oral cancer development in Taiwan

    PubMed Central

    Chou, Chia-Hsuan; Chou, Ying-Erh; Chuang, Chun-Yi; Yang, Shun-Fa; Lin, Chiao-Wen

    2017-01-01

    Background Oral squamous cell carcinoma (OSCC) is the sixth and fourth most common cause of cancer death in men worldwide and in Taiwan, respectively. AURKA, which encodes a centrosome-related serine/threonine kinase, is frequently amplified and overexpressed in many human cancers, particularly advanced OSCC. We conducted a hospital-based case-control study to estimate AURKA single-nucleotide polymorphisms (SNPs) and environmental risk factors to determine OSCC susceptibility and clinicopathological characteristics. Methodology/Principal findings We enrolled a total of 876 OSCC patients and 1200 controls. Four SNPs of AURKA, namely rs1047972, rs2273535, rs2064863, and rs6024836, were analyzed using real-time polymerase chain reaction (PCR). Among the 1420 smokers, the AURKA polymorphism carriers with the betel nut chewing habit had a higher risk of oral cancer than AURKA wild-type (WT) carriers without the betel nut chewing habit. Patients with the AURKA rs2064863 gene had a 1.365-fold higher risk of stage III or IV OSCC (95% confidence interval [CI] 1.029–1.811) than those with the rs2064863 WT gene. Furthermore, carriers of the AURKA rs1047972/rs2273535/rs2064863 C-A-T haplotype had a 1.736-fold (95% CI 1.110–2.715) higher risk of OSCC than controls (C-T-T, the most common haplotype). Among patients with the betel quid chewing habit, carriers of other haplotypes (C-T-T, C-A-G, T-A-T, T-A-G, T-T-T, and C-T-G) had a 12.857-fold (95% CI 10.731–15.404) increased risk, and carriers of the C-A-T haplotype had the highest risk (AOR: 31.120; 95% CI 13.864–69.850) of OSCC, compared with those without the betel quid chewing who harbored other haplotypes. Conclusions In conclusion, betel nut chewing combined with the AURKA C-A-T haplotypes lead to a high risk of OSCC. These findings reveal a novel genetic-environmental predisposition for oral tumorigenesis. PMID:28152093

  15. 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…

  16. Genetic Susceptibility to Multiple Sclerosis: The Role of FOXP3 Gene Polymorphism

    PubMed Central

    IŞIK, Nihal; YILDIZ MANUKYAN, Nüket; AYDIN CANTÜRK, İlknur; CANDAN, Fatma; ÜNSAL ÇAKMAK, Ayşen; SARU HAN DİRESKENELİ, Güher

    2014-01-01

    Introduction It is well recognized that both genetic and environmental factors play an important role in the pathogenesis of multiple sclerosis (MS). Immune pathogenesis of MS focuses on pathogenic CD4+ T lymphocytes. CD4+CD25+ regulatory T cells have suppressive function in this cell group. FOXP3 (forkhead boxP3) transcription factor is a key structure in the development and function of regulatory cells. Functional alterations in FOXP3 gene expression have been observed in various autoimmune diseases. Methods We screened a non-synonymous coding single nucleotide polymorphism (exon +2710 C/T) (rs2232369) of human FOXP3 gene in 148 MS patients (118 with Relapsing Remitting MS, 30 with Secondary Progressive MS) and 102 age- and sex-matched healthy controls. The association of polymorphisms with susceptibility, and course of the disease was evaluated. Results We could not detect any single nucleotide polymorphism in MS patients, however, polymorphic allele was detected in 3% of the control group. Consequently, a genetic association between the FOXP3 gene polymorphism and MS was not revealed. Conclusion The distribution of this polymorphism has not been screened in any other MS populations before. Although we could not succeed to find any association between susceptibility to MS and screened FOXP3 gene polymorphisms, we suggest that this particular polymorphism is not appropriate for these kind of studies in the future.

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

    PubMed Central

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

    2012-01-01

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

  18. 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

  19. 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

  20. A genetic map of Lophopyrum ponticum chromosome 7E, harboring resistance genes to Fusarium head blight and leaf rust.

    PubMed

    Zhang, Xiuli; Shen, Xiaorong; Hao, Yuanfeng; Cai, Jinjin; Ohm, Herbert W; Kong, Lingrang

    2011-02-01

    The leaf rust resistance gene Lr19 and Fusarium head blight (FHB) resistance quantitative trait loci (QTL) derived from the wild wheatgrass Lophopyrum ponticum have been located on chromosome 7E. The main objectives of the present study were to develop a genetic map of chromosome 7E and map the two resistance loci using a population of 237 F(7:8) recombinant inbred lines (RILs) derived from a cross between two Thatcher-L. ponticum substitution lines, K11463 (7el(1)(7D)) and K2620 (7el(2)(7D)). 532 G-SSR, E-SSR and STS markers from wheat chromosome group 7 were screened in the parent lines. Of these, 118 markers were polymorphic, with a polymorphism frequency of 22.2%. A genetic map of L. ponticum chromosome 7E was constructed with 64 markers, covering 95.76 cM, with an average genetic distance of 1.47 cM between markers. The major FHB resistance locus, temporarily assigned as FhbLoP, was mapped to the very distal region of the long arm of chromosome 7E within a 3.71 cM interval flanked by Xcfa2240 and Xswes19, which accounts for 30.46% of the phenotypic variance. Lr19 was bracketed by Xwmc273 and XBE404744, with a map distance of 1.54 and 1.43 cM from either side, respectively. The closely linked markers identified in this study will be helpful for marker-assisted introgression of the L. ponticum-derived FhbLoP and Lr19 genes into elite cultivars of wheat, and the development of a genetic map will accelerate the map-based cloning of these two genes.

  1. Genetic analysis of Apuleia leiocarpa as revealed by random amplified polymorphic DNA markers: prospects for population genetic studies.

    PubMed

    Lencina, K H; Konzen, E R; Tsai, S M; Bisognin, D A

    2016-12-19

    Apuleia leiocarpa (Vogel) J.F. MacBride is a hardwood species native to South America, which is at serious risk of extinction. Therefore, it is of prime importance to examine the genetic diversity of this species, information required for developing conservation, sustainable management, and breeding strategies. Although scarcely used in recent years, random amplified polymorphic DNA markers are useful resources for the analysis of genetic diversity and structure of tree species. This study represents the first genetic analysis based on DNA markers in A. leiocarpa that aimed to investigate the levels of polymorphism and to select markers for the precise characterization of its genetic structure. We adapted the original DNA extraction protocol based on cetyltrimethyl ammonium bromide, and describe a simple procedure that can be used to obtain high-quality samples from leaf tissues of this tree. Eighteen primers were selected, revealing 92 bands, from which 75 were polymorphic and 61 were sufficient to represent the overall genetic structure of the population without compromising the precision of the analysis. Some fragments were conserved among individuals, which can be sequenced and used to analyze nucleotide diversity parameters through a wider set of A. leiocarpa individuals and populations. The individuals were separated into 11 distinct groups with variable levels of genetic diversity, which is important for selecting desirable genotypes and for the development of a conservation and sustainable management program. Our results are of prime importance for further investigations concerning the genetic characterization of this important, but vulnerable species.

  2. Genetic modifiers of chromatin acetylation antagonize the reprogramming of epi-polymorphisms.

    PubMed

    Abraham, Anne-Laure; Nagarajan, Muniyandi; Veyrieras, Jean-Baptiste; Bottin, Hélène; Steinmetz, Lars M; Yvert, Gaël

    2012-09-01

    Natural populations are known to differ not only in DNA but also in their chromatin-associated epigenetic marks. When such inter-individual epigenomic differences (or "epi-polymorphisms") are observed, their stability is usually not known: they may or may not be reprogrammed over time or upon environmental changes. In addition, their origin may be purely epigenetic, or they may result from regulatory variation encoded in the DNA. Studying epi-polymorphisms requires, therefore, an assessment of their nature and stability. Here we estimate the stability of yeast epi-polymorphisms of chromatin acetylation, and we provide a genome-by-epigenome map of their genetic control. A transient epi-drug treatment was able to reprogram acetylation variation at more than one thousand nucleosomes, whereas a similar amount of variation persisted, distinguishing "labile" from "persistent" epi-polymorphisms. Hundreds of genetic loci underlied acetylation variation at 2,418 nucleosomes either locally (in cis) or distantly (in trans), and this genetic control overlapped only partially with the genetic control of gene expression. Trans-acting regulators were not necessarily associated with genes coding for chromatin modifying enzymes. Strikingly, "labile" and "persistent" epi-polymorphisms were associated with poor and strong genetic control, respectively, showing that genetic modifiers contribute to persistence. These results estimate the amount of natural epigenomic variation that can be lost after transient environmental exposures, and they reveal the complex genetic architecture of the DNA-encoded determinism of chromatin epi-polymorphisms. Our observations provide a basis for the development of population epigenetics.

  3. Mouse genetics meets molecular biology at Cold Spring Harbor. Mouse Molecular Genetics sponsored by the Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA, August 29-September 2, 1990.

    PubMed

    Wagner, E F

    1990-12-01

    As stated earlier, the digestion of roughly 100 short talks delivered within a few days and containing very condensed information is, even for experts, quite demanding. Sometimes one felt in danger of becoming "psyched out" by all the experiments described; perhaps smaller group discussions dealing with experiments that have not worked, as well as the elimination of redundancies in the presentations, would have added to the flavor of the meeting. But what is the "take home message" from the 1990 CSH Mouse Meeting? With all the described breakthroughs, has mouse molecular genetics and development arrived at a turning point? I am inclined to answer this question with a "yes" on the basis of the following considerations: The elegant studies of development in Drosophila and Caenorhabditis elegans were made possible by the power of genetics with the use of developmental mutations. These studies taught us that the sequential activation of a hierarchy of regulatory genes dictates the temporal and spatial patterns of expression of proteins that define cell phenotypes and the body plan, and thereby control development. With the identification of important regulatory genes responsible for many classical as well as experimentally induced mouse mutations, in conjunction with traditional transgenic studies and the power of deleting and altering genes via ES cell chimeras, the study of mouse development has now gained an important new dimension. It is feasible that the consequences of subtle but precise genetic changes, such as the modification of regulatory elements or DNA-binding domains, can be studied in the whole organism by use of ES cells.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Genetic and Molecular Basis of Quantitative Trait Loci of Arthritis in Rat: Genes and Polymorphisms1

    PubMed Central

    Xiong, Qing; Jiao, Yan; Hasty, Karen A.; Stuart, John M.; Postlethwaite, Arnold; Kang, Andrew H.; Gu, Weikuan

    2012-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease, the pathogenesis of which is affected by multiple genetic and environmental factors. To understand the genetic and molecular basis of RA, a large number of quantitative trait loci (QTL) that regulate experimental autoimmune arthritis have been identified using various rat models for RA. However, identifying the particular responsible genes within these QTL remains a major challenge. Using currently available genome data and gene annotation information, we systematically examined RA-associated genes and polymorphisms within and outside QTL over the whole rat genome. By the whole genome analysis of genes and polymorphisms, we found that there are significantly more RA-associated genes in QTL regions as contrasted with non-QTL regions. Further experimental studies are necessary to determine whether these known RA-associated genes or polymorphisms are genetic components causing the QTL effect. PMID:18606636

  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 inflammatory…

  6. Genetic Diversity Revealed by Single Nucleotide Polymorphism Markers in a Worldwide Germplasm Collection of Durum Wheat

    PubMed Central

    Ren, Jing; Sun, Daokun; Chen, Liang; You, Frank M.; Wang, Jirui; Peng, Yunliang; Nevo, Eviatar; Sun, Dongfa; Luo, Ming-Cheng; Peng, Junhua

    2013-01-01

    Evaluation of genetic diversity and genetic structure in crops has important implications for plant breeding programs and the conservation of genetic resources. Newly developed single nucleotide polymorphism (SNP) markers are effective in detecting genetic diversity. In the present study, a worldwide durum wheat collection consisting of 150 accessions was used. Genetic diversity and genetic structure were investigated using 946 polymorphic SNP markers covering the whole genome of tetraploid wheat. Genetic structure was greatly impacted by multiple factors, such as environmental conditions, breeding methods reflected by release periods of varieties, and gene flows via human activities. A loss of genetic diversity was observed from landraces and old cultivars to the modern cultivars released during periods of the Early Green Revolution, but an increase in cultivars released during the Post Green Revolution. Furthermore, a comparative analysis of genetic diversity among the 10 mega ecogeographical regions indicated that South America, North America, and Europe possessed the richest genetic variability, while the Middle East showed moderate levels of genetic diversity. PMID:23538839

  7. 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.

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

    PubMed Central

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

    2016-01-01

    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/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. PMID:27068490

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

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

    PubMed

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

    2015-12-01

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

  16. 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.

  17. 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

  18. Start codon targeted polymorphism for evaluation of functional genetic variation and relationships in cultivated peanut (Arachis hypogaea L.) genotypes.

    PubMed

    Xiong, Faqian; Zhong, Ruichun; Han, Zhuqiang; Jiang, Jing; He, Liangqiong; Zhuang, Weijian; Tang, Ronghua

    2011-06-01

    Cultivated peanut possesses an extremely narrow genetic basis. Polymorphism is considerably difficult to identify with the use of conventional biochemical and molecular tools. For the purpose of obtaining considerable DNA polymorphisms and fingerprinting cultivated peanut genotypes in a convenient manner, start codon targeted polymorphism technique was used to study genetic diversity and relatedness among 20 accessions of four major botanical varieties of peanut. Of 36 primers screened, 18 primers could produce unambiguous and reproducible bands. All 18 primers generated a total of 157 fragments, with a mean of 8.72 ranging from 4 to 17 per primer. Of 157 bands, 60 (38.22%) were polymorphic. One to seven polymorphic bands were amplified per primer, with 3.33 polymorphic bands on average. Polymorphism per primer ranged from 14.29 to 66.67%, with an average of 36.76%. The results revealed that not all accessions of the same variety were grouped together and high genetic similarity was detected among the tested genotypes based on cluster analysis and genetic distance analysis, respectively. Further, accession-specific markers were observed in several accessions. All these results demonstrated the following: (1) start codon targeted polymorphism technique can be utilized to identify DNA polymorphisms and fingerprint cultivars in domesticated peanut, and (2) it possesses considerable potential for studying genetic diversity and relationships among peanut accessions.

  19. IMPDH2 genetic polymorphism: a promoter single-nucleotide polymorphism disrupts a cyclic adenosine monophosphate responsive element.

    PubMed

    Garat, Anne; Cauffiez, Christelle; Hamdan-Khalil, Rima; Glowacki, François; Devos, Aurore; Leclerc, Julie; Lionet, Arnaud; Allorge, Delphine; Lo-Guidice, Jean-Marc; Broly, Franck

    2009-12-01

    Inosine 5'-monophosphate dehydrogenase (IMPDH), which catalyzes a key step in the de novo biosynthesis of guanine nucleotide, is mediated by two highly conserved isoforms, IMPDH1 and IMPDH2. In this study, IMPDH2 genetic polymorphism was investigated in 96 individuals of Caucasian origin. Four single-nucleotide polymorphisms were identified, comprising one previously described single base-pair substitution in the close vicinity of the consensus donor splice site of intron 7 (IVS7+10T>C), and three novel polymorphisms, one silent substitution in exon 9 (c.915C>G), one single base-pair insertion (g.6971_6972insT) within the 3'-untranslated region of the gene, and one substitution located in the promoter region (c.-95T>G) in a transcription factor binding site CRE(A) (cyclic adenosine monophosphate [cAMP] response element). Considering the nature and location of this latter polymorphism, its functional relevance was examined by transfecting HEK293 and Jurkat cell lines with constructs of the related region of IMPDH2/luciferase reporter gene. The c.-95T>G mutation leads to a significant decrease of luciferase activity (HEK293: 55% decrease, p < 0.05; Jurkat: 65% decrease, p < 0.05) compared with the wild-type promoter sequence and, therefore, is likely to determine interindividual differences in IMPDH2 transcriptional regulation. These results might contribute to a better understanding of the variability in clinical outcome and dose adjustments of certain immunosuppressors that are metabolized through the IMPDH pathway or that are IMPDH inhibitors.

  20. 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.

  1. The Role of Dopamine in Anticipatory Pursuit Eye Movements: Insights from Genetic Polymorphisms in Healthy Adults

    PubMed Central

    Hennig, Jürgen

    2016-01-01

    Abstract There is a long history of eye movement research in patients with psychiatric diseases for which dysfunctions of neurotransmission are considered to be the major pathologic mechanism. However, neuromodulation of oculomotor control is still hardly understood. We aimed to investigate in particular the impact of dopamine on smooth pursuit eye movements. Systematic variability in dopaminergic transmission due to genetic polymorphisms in healthy subjects offers a noninvasive opportunity to determine functional associations. We measured smooth pursuit in 110 healthy subjects genotyped for two well-documented polymorphisms, the COMT Val158Met polymorphism and the SLC6A3 3′-UTR-VNTR polymorphism. Pursuit paradigms were chosen to particularly assess the ability of the pursuit system to initiate tracking when target motion onset is blanked, reflecting the impact of extraretinal signals. In contrast, when following a fully visible target sensory, retinal signals are available. Our results highlight the crucial functional role of dopamine for anticipatory, but not for sensory-driven, pursuit processes. We found the COMT Val158Met polymorphism specifically associated with anticipatory pursuit parameters, emphasizing the dominant impact of prefrontal dopamine activity on complex oculomotor control. In contrast, modulation of striatal dopamine activity by the SLC6A3 3′-UTR-VNTR polymorphism had no significant functional effect. Though often neglected so far, individual differences in healthy subjects provide a promising approach to uncovering functional mechanisms and can be used as a bridge to understanding deficits in patients. PMID:28101524

  2. Genetic polymorphisms of XPD and CDA and lung cancer risk.

    PubMed

    Zhou, Min; Wan, Huan-Ying; Gao, Bei-Li; Ding, Yong-Jie; Jun, Rong-Xia

    2012-08-01

    To determine the susceptibility genes of lung cancer, we investigated the frequency distributions of the xeroderma pigmentosum complementary group D (XPD) and cytidine deaminase (CDA) genes in patients. A case-control study was conducted involving lung cancer patients and healthy controls. The genotypic distributions of XPD exon 10 G→A (Asp312Asn) and 23 T→G (Lys751Gln), and CDA 79 A→C (Lys27Gln) and 208 G→A (Ala70Thr), were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results demonstrated that the XPD Asp312Asn genotype distribution was G/G (82.52%) and A/G (17.48%) in the lung cancer patients, and G/G (82.52%), A/G (16.50%) and A/A (10.98%) in the controls. The genotypes of Lys751Gln were T/T (83.49%) and T/G (16.50%) in the lung cancer patients, and T/T (84.47%) and T/G (15.53%) in the controls. Mutations in the XPD single nucleotide polymorphism loci did not demonstrate a significant difference between the two groups (P>0.05). The risk of lung cancer in individuals with mutations at positions 312 and 751 increased 6.13-fold (P=0.047). The CDA Lys27Gln genotype distribution was A/A (78.65%), A/C (20.39%) and C/C (0.98%) in the lung cancer patients, and A/A (79.61%), A/C (19.42%) and C/C (0.98%) in the controls (P=0.985). The CDA Ala70Thr genotype distribution was G/G (98.06%) and A/G (1.94%) in the controls, while all the genotypes were wild-type in the lung cancer patients. The difference between the lung cancer patients and the controls was not statistically significant (P=0.155). There was also no significant difference in the frequency distribution of XPD or CDA between the different pathological types (P>0.05). Our findings demonstrate that the mutation of XPD codons 312 and 751 increases the risk of lung cancer. By contrast, polymorphisms of CDA appear to have little association with lung cancer.

  3. [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.

  4. 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

  5. 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

    2008-07-22

    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.

  6. Genetic polymorphisms between altruism and selfishness close to the Hamilton threshold rb = c

    PubMed Central

    Curnow, Robert N.

    2017-01-01

    Genes that in certain conditions make their carriers altruistic are being identified, and altruism and selfishness have shown to be heritable in man. This raises the possibility that genetic polymorphisms for altruism/selfishness exist in man and other animals. Here we characterize some of the conditions in which genetic polymorphisms may occur. We show for dominant or recessive alleles how the positions of stable equilibria depend on the benefit to the recipient, b, and the cost to the altruist, c, for diploid altruists helping half or full sibs, and haplodiploid altruists helping sisters. Stable polymorphisms always occur close to the Hamilton threshold rb = c. The position of the stable equilibrium moves away 0 or 1 with both increases in c, the cost paid by the altruist, and increasing divergence from the Hamilton threshold, and alleles for selfishness can reach frequencies around 50%. We evaluate quantitative estimates of b, c and r from field studies in the light of these predictions, but the values do not fall in the regions where genetic polymorphisms are expected. Nevertheless, it will be interesting to see as genes for altruism are discovered whether they are accompanied by alternate alleles for selfishness. PMID:28386424

  7. Rank-Order Selection Is Capable of Maintaining All Genetic Polymorphisms

    PubMed Central

    Wills, Christopher

    1978-01-01

    The fitness of organisms may be due chiefly to a fitness curve imposed on their ranking in the population with respect to heterozygosity. If this is so, then the number of polymorphisms that can be retained at a particular selective equilibrium increases as the square of the population size. All of the genetic variation that we currently observe and infer to exist can probably be maintained by selection in a population of about 10 5 individuals. Selection acting in this way is so strong that these polymorphisms can be expected to behave very differently from neutral ones. PMID:17248841

  8. 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.

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

    PubMed

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

    2015-01-01

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

  10. 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.

  11. [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.

  12. 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

  13. High temperatures reveal cryptic genetic variation in a polymorphic female sperm storage organ.

    PubMed

    Berger, David; Bauerfeind, Stephanie Sandra; Blanckenhorn, Wolf Ulrich; Schäfer, Martin Andreas

    2011-10-01

    Variation in female reproductive morphology may play a decisive role in reproductive isolation by affecting the relative fertilization success of alternative male phenotypes. Yet, knowledge of how environmental variation may influence the development of the female reproductive tract and thus alter the arena of postcopulatory sexual selection is limited. Yellow dung fly females possess either three or four sperm storage compartments, a polymorphism with documented influence on sperm precedence. We performed a quantitative genetics study including 12 populations reared at three developmental temperatures complemented by extensive field data to show that warm developmental temperatures increase the frequency of females with four compartments, revealing striking hidden genetic variation for the polymorphism. Systematic genetic differentiation in growth rate and spermathecal number along latitude, and phenotypic covariance between the traits across temperature treatments suggest that the genetic architecture underlying the polymorphism is shaped by selection on metabolic rate. Our findings illustrate how temperature can modulate the preconditions for sexual selection by differentially exposing novel variation in reproductive morphology. This implies that environmental change may substantially alter the dynamics of sexual selection. We further discuss how temperature-dependent developmental plasticity may have contributed to observed rapid evolutionary transitions in spermathecal morphology.

  14. Genetic linkage between protein and DNA polymorphisms and antioxidant capacity of Cuminum cyminum L. accessions.

    PubMed

    Abdelhaliem, E; Al-Huqail, A A

    2016-10-06

    This study aimed to link the genetic variation observed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and random amplified polymorphic DNA (RAPD) analysis among 11 Cuminum cyminum L. accessions, collected from diverse ecogeographical areas in Saudi Arabia, with their antioxidant capacity to better identify potential genotypes for breeding programs for this medicinal spice. SDS-PAGE analysis revealed genetic variation among cumin germplasms and distinct polymorphisms (100%). Protein polymorphisms were identified based on the number of polypeptide bands (288) with molecular weights ranging from 13.85 to 350 kDa, band intensity, the appearance of new bands, and the absence of other bands. RAPD analysis revealed 363 amplified DNA products with a high polymorphism value (98.88%) based on DNA band type (unique, non-unique, and monomorphic), DNA 90 to 1085-bp long, and band intensity. The unweighted pair group method with arithmetic mean clustering based on SDS-PAGE or RAPD and Jaccard's similarity coefficient divided cumin accessions into similar but distinct clusters with respect to their location of collection. The antioxidant potential of cumin accessions based on 1, 1-diphenyl-2-picrylhydrazyl radical scavenging activity, the β-carotene-linoleate model system, and total phenolic and flavonoid contents revealed distinct variability. These data indicate that cumin is a valuable genetic resource with high antioxidant activity. Additionally, clustering based on antioxidant activity was not identical to that based on SDS-PAGE and RAPD. Data and clustering of SDS-PAGE and RAPD, combined with the high antioxidant capacity of cumin accessions, are important for the efficient use of genetic resources of cumin in breeding strategies and genetic improvement programs.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Genetic polymorphisms: impact on the risk of fetal alcohol spectrum disorders.

    PubMed

    Warren, Kenneth R; Li, Ting-Kai

    2005-04-01

    Clinical reports on monozygotic and dizygotic twins provided the initial evidence for the involvement of genetic factors in risk vulnerability for fetal alcohol spectrum disorders (FASD) including fetal alcohol syndrome (FAS). Research with selectively bred and inbred rodents, genetic crosses of these lines and strains, and embryo culture studies have further clarified the role of both maternal and fetal genetics in the development of FASD. Research to identify specific polymorphisms contributing to FASD is still at an early stage. To date, polymorphisms of only one of the genes for the alcohol dehydrogenase enzyme family, the ADH1B, have been demonstrated to contribute to FASD vulnerability. In comparison with ADH1B*1, both maternal and fetal ADH1B*2 have been shown to reduce risk for FAS in a mixed ancestry South African population. ADH1B*3 appears to afford protection for FASD outcomes in African-American populations. Other candidate genes should be examined with respect to FASD risk, including those for the enzymes of serotonin metabolism, in particular the serotonin transporter. By its very nature, alcohol teratogenesis is the expression of the interaction of genes with environment. The study of genetic factors in FASD falls within the new field of ecogenetics. Understanding of the array of genetic factors in FASD will be enhanced by future genetic investigations, including case-control, family association, and linkage studies.

  1. [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.

  2. 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.

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

    PubMed Central

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

    2010-01-01

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

  4. TCF21 genetic polymorphisms and breast cancer risk in Chinese women

    PubMed Central

    Gao, Xueren; Yang, Jiaojiao; Wang, Mingxi; Zhang, Jianqiong

    2016-01-01

    Transcription factor 21 (TCF21) functions as a tumor suppressor and is inactivated in several types of cancer. The purpose of this study is to investigate whether TCF21 genetic polymorphisms(rs2327429 T>C, rs2327430 T>C, rs2327433 A>G, rs12190287 C>G, rs7766238 G>A, rs4896011 T>A) are associated with the risk of breast cancer in Chinese women. Logistic regression analyses showed that TCF21 rs12190287 polymorphism was significantly associated with the reduced risk of breast cancer. Stratified analyses based on pathological type indicated that TCF21 rs12190287 polymorphism was only associated with the reduced risk of infiltrative ductal carcinoma. Real-time quantitative PCR analyses revealed that compared with those carrying rs12190287 CC genotype, subjects with GG genotype had higher expression levels of TCF21 mRNA in normal breast tissues. Furthermore, luciferase activity assay showed that the rs12190287 G allele weakened the binding affinity of hsa-miR-224 to TCF21 3′ UTR. These findings suggest that TCF21 rs12190287 polymorphism can regulate TCF21 expression and may serve as a potential marker for genetic susceptibility to breast cancer. PMID:27270650

  5. [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.

  6. 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.

  7. Genetic polymorphism of 15 STR loci in central western Colombia.

    PubMed

    Porras, L; Beltrán, L; Ortiz, T; Sanchez-Diz, P; Carracedo, A; Henao, J

    2008-01-01

    Fifteen autosomal short tandem repeat (STR) loci were analyzed using the AmpFISTR Identifiler PCR Amplification Kit in 1944 samples of healthy unrelated individuals, born in the regions of Caldas, Quindio and Risaralda, Colombia. Allele frequencies and statistical parameters of forensic interest are presented for all markers (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, THO1, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA). All loci of the pooled data were in agreement with Hardy-Weinberg equilibrium, after Bonferroni correction. Comparisons with neighboring Latin American populations and Andalucia (Spain) revealed significant differences in allele distributions. Genetic data presented in this study can be used for routine forensic applications in the region.

  8. 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

  9. 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.

  10. [Genetic polymorphism of beta-adrenergic receptors and mortality in ischemic heart disease].

    PubMed

    Jaillon, Patrice; Simon, Tabassome

    2007-01-01

    The genetic polymorphism of beta-2 adrenergic receptors (B2AR) could play a major role in the prognostic of patients with a coronary heart disease. Two recent epidemiological studies could support this hypothesis. In 597 patients treated by a beta-blocker and followed for 3 years after a myocardial infarction or an acute coronary syndrome, the death rate was 5.4 times higher in homozygous Arg 16 and Gln 27 B2AR genotypes than in heterozygous or homozygous Gly 16 and Glu 27 B2AR genotypes. The beta-1 adrenergic receptor (B1AR) genetic polymorphism did not modify mortality. In a second study, in a prospective cohort of 5249 patients aged > or =65 years, the incidence of sudden cardiac death was 1.56 times higher in patients with homozygous Gln 27 B2AR than in heterozygous or homozygous Glu 27 B2AR genotype. This result was confirmed by a case-control study (155 cases of sudden cardiac death versus 144 control subjects). These data suggest that B2AR genetic polymorphism should be systematically studied in clinical trials in myocardial ischemia, with or without congestive heart failure.

  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. 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.

  13. 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.

  14. 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

  15. 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.

  16. Study of the association between ITPKC genetic polymorphisms and calcium nephrolithiasis.

    PubMed

    Kan, Wei-Chih; Chou, Yii-Her; Chiu, Siou-Jin; Hsu, Yu-Wen; Lu, Hsing-Fang; Hsu, Wenli; Chang, Wei-Chiao

    2014-01-01

    Nephrolithiasis is a multifactorial disease caused by environmental, hormonal, and genetic factors. Genetic polymorphisms of ORAI1, which codes for the main subunit of the store-operated calcium (SOC) channel, were reported to be associated with the risk and recurrence of calcium nephrolithiasis. Inositol 1,4,5-trisphosphate (IP3) 3-kinase C (ITPKC) is a negative regulator of the SOC channel-mediated signaling pathway. We investigated the association between calcium containing nephrolithiasis and genetic variants of ITPKC gene in Taiwanese patients. 365 patients were recruited in this study. Eight tagging single nucleotide polymorphisms of ITPKC were selected for genotyping. ITPKC genotypes were determined by TaqMan assay. ITPKC plasmids were transfected into cells to evaluate the intracellular calcium mobilization. Our results indicated that rs2607420 CC genotype in the intron region of the ITPKC gene is associated with a lower eGFR by both Modification of Diet in Renal Diseases (P = 0.0405) and Cockcroft-Gault (P = 0.0215) equations in patients with calcium nephrolithiasis. Our results identify a novel polymorphism for renal function and highlight the importance of ITPKC as a key molecule to regulate calcium signaling.

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

    PubMed

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

    2016-01-01

    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 alterations in genome structure (inversions) through nonallelic homologous recombination. The near identity of the inverted repeats is an example of concerted evolution through gene conversion. While the laboratory in its entirety is designed for college level genetics courses, portions of the laboratory are appropriate for courses at other levels. Because the polymorphism is on the X-chromosome, the laboratory can be used in introductory biology courses to enhance understanding of sex-linkage and to test for Hardy-Weinberg equilibrium in females. More advanced topics, such as chromosome interference, the molecular model for recombination, and inversion heterozygosity suppression of recombination can be explored in upper-level genetics and evolution courses. DNA isolation, restriction digests, ligation, long PCR, and iPCR provide experience with techniques in molecular biology. This investigative laboratory weaves together topics stretching from molecular genetics to cytogenetics and sex-linkage, population genetics and evolutionary genetics.

  18. 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.

  19. 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

    2016-05-09

    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.

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

    PubMed Central

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

    1995-01-01

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

  1. COMT val158met and 5-HTTLPR Genetic Polymorphisms Moderate Executive Control in Cannabis Users

    PubMed Central

    Verdejo-García, Antonio; Beatriz Fagundo, Ana; Cuenca, Aida; Rodriguez, Joan; Cuyás, Elisabet; Langohr, Klaus; de Sola Llopis, Susana; Civit, Ester; Farré, Magí; Peña-Casanova, Jordi; de la Torre, Rafael

    2013-01-01

    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. PMID:23449176

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

    PubMed

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

    2007-06-01

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

  3. 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

  4. Mitochondrial polymorphisms in rat genetic models of hypertension.

    PubMed

    Kumarasamy, Sivarajan; Gopalakrishnan, Kathirvel; Shafton, Asher; Nixon, Jeremy; Thangavel, Jayakumar; Farms, Phyllis; Joe, Bina

    2010-06-01

    Hypertension is a complex trait that has been studied extensively for genetic contributions of the nuclear genome. We examined mitochondrial genomes of the hypertensive strains: the Dahl Salt-Sensitive (S) rat, the Spontaneously Hypertensive Rat (SHR), and the Albino Surgery (AS) rat, and the relatively normotensive strains: the Dahl Salt-Resistant (R) rat, the Milan Normotensive Strain (MNS), and the Lewis rat (LEW). These strains were used previously for linkage analysis for blood pressure (BP) in our laboratory. The results provide evidence to suggest that variations in the mitochondrial genome do not account for observed differences in blood pressure between the S and R rats. However, variants were detected among the mitochondrial genomes of the various hypertensive strains, S, SHR, and AS, and also among the normotensive strains R, MNS, and LEW. A total of 115, 114, 106, 106, and 16 variations in mtDNA were observed between the comparisons S versus LEW, S versus MNS, S versus SHR, S versus AS, and SHR versus AS, respectively. Among the 13 genes coding for proteins of the electron transport chain, 8 genes had nonsynonymous variations between S, LEW, MNS, SHR, and AS. The lack of any sequence variants between the mitochondrial genomes of S and R rats provides conclusive evidence that divergence in blood pressure between these two inbred strains is exclusively programmed through their nuclear genomes. The variations detected among the various hypertensive strains provides the basis to construct conplastic strains and further evaluate the effects of these variants on hypertension and associated phenotypes.

  5. Genetic polymorphisms modulate the folate metabolism of Brazilian individuals with Down syndrome.

    PubMed

    Biselli, J M; Zampieri, B L; Goloni-Bertollo, E M; Haddad, R; Fonseca, M F R; Eberlin, M N; Vannucchi, H; Carvalho, V M; Pavarino, E C

    2012-10-01

    Individuals with Down syndrome (DS) carry three copies of the Cystathionine β-synthase (CβS) gene. The increase in the dosage of this gene results in an altered profile of metabolites involved in the folate pathway, including reduced homocysteine (Hcy), methionine, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM). Furthermore, previous studies in individuals with DS have shown that genetic variants in genes involved in the folate pathway influence the concentrations of this metabolism's products. The purpose of this study is to investigate whether polymorphisms in genes involved in folate metabolism affect the plasma concentrations of Hcy and methylmalonic acid (MMA) along with the concentration of serum folate in individuals with DS. Twelve genetic polymorphisms were investigated in 90 individuals with DS (median age 1.29 years, range 0.07-30.35 years; 49 male and 41 female). Genotyping for the polymorphisms was performed either by polymerase chain reaction (PCR) based techniques or by direct sequencing. Plasma concentrations of Hcy and MMA were measured by liquid chromatography-tandem mass spectrometry as previously described, and serum folate was quantified using a competitive immunoassay. Our results indicate that the MTHFR C677T, MTR A2756G, TC2 C776G and BHMT G742A polymorphisms along with MMA concentration are predictors of Hcy concentration. They also show that age and Hcy concentration are predictors of MMA concentration. These findings could help to understand how genetic variation impacts folate metabolism and what metabolic consequences these variants have in individuals with trisomy 21.

  6. Association between genetic polymorphisms of interleukins and cerebral infarction risk: a meta-analysis

    PubMed Central

    Wang, Jiantao; Fan, Niannian; Deng, Yili; Zhu, Jie; Mei, Jing; Chen, Yao; Yang, Heng

    2016-01-01

    Interleukins (ILs) are the most typical inflammatory and immunoregulatory cytokines. Evidences have shown that polymorphisms in ILs are associated with cerebral infarction risk. However, the results remain inconclusive. The present study was to evaluate the role of ILs polymorphisms in cerebral infarction susceptibility. Relevant case-control studies published between January 2000 and December 2015 were searched and retrieved from the electronic databases of Web of Science, PubMed, Embase and the Chinese Biomedical Database. The odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the strength of association. A total of 55 articles including 12619 cerebral infarction patients and 14436 controls were screened out. Four ILs (IL-1, IL-6, IL-10 and IL-18) contained nine single nucleotide polymorphisms (SNPs; IL-1α −899C/T, IL-1β −511C/T and IL-1β +3953C/T; IL-6 −174G/C and −572C/G; IL-10 −819C/T and −1082A/G; IL-18 −607C/A and −137G/C). Our result showed that IL-1α −899C/T and IL-18 −607C/A (under all the genetic models), and IL-6 −572C/G (under the allelic model, heterogeneity model and dominant model) were associated with increased the risk of cerebral infarction (P<0.05). Subgroup analysis by ethnicity showed that IL-6 −174G/C polymorphism (under all the five models) and IL-10 −1082A/G polymorphism (under the allelic model and heterologous model) were significantly associated with increased the cerebral infarction risk in Asians. Other genetic polymorphisms were not related with cerebral infarction susceptibility under any genetic models. In conclusion, IL-1α −899C/T, IL-6 −572C/G and IL-18 −607C/A might be risk factors for cerebral infarction development. Further studies with well-designed and large sample size are still required. PMID:27679860

  7. 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.

  8. Genetic ACE I/D and ACTN3 R577X polymorphisms and adolescent idiopathic scoliosis.

    PubMed

    Luciano, R P; Wajchenberg, M; Almeida, S S; Amorim, C E N; Rodrigues, L M R; Araujo, R C; Puertas, E B; Faloppa, F

    2016-11-03

    The etiology of adolescent idiopathic scoliosis remains unknown. Angiotensin-converting enzyme and α-actinin-3 polymorphisms influence the characteristics of muscle fibers. The aim of this study was to examine the association between idiopathic scoliosis and genetic polymorphism of angiotensin-converting enzyme and α-actinin-3. Ninety-seven females with scoliosis, and 137 healthy, age-matched control females were studied. The presence of polymorphisms was determined by PCR. A χ(2) test was used to analyze differences, and odds ratios were estimated. The frequencies of ACE genotypes in the scoliotic group were 46.4% DD, 45.4% ID, and 8.2% II, while in the control group they were 40.1% DD, 43.8% ID, and 16.1% II (P = 0.197). The D allele had a frequency of 69.1% in patients with idiopathic scoliosis and 62% in the control group (P = 0.116). The frequencies of ACTN3 genotypes in females with scoliosis were 31.8% RR, 49.4% RX, and 18.8% XX, while in the control group they were 35% RR, 49% RX, and 16% XX (P = 0.810). The frequency of the R allele was 56.4% in the scoliotic group and 59.6% in the control group (P = 0.518). There was no statistically significant association between angiotensin-converting enzyme or α-actinin-3 polymorphisms and the presence of adolescent idiopathic scoliosis in females.

  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. 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.

  12. 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.

  13. Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis

    PubMed Central

    Chen, Cheng; Wang, Lingyan; Liao, Qi; Xu, Leiting; Huang, Yi; Zhang, Cheng; Ye, Huadan; Xu, Xuting

    2014-01-01

    Objective: The aim of this study was to determine whether six genetic polymorphisms confer susceptibility to colorectal cancer (CRC). Methods: A systematic search for candidate genes of CRC was performed among several online databases, including PubMed, Embase, Web of Science, the Cochrane Library, CNKI, and Wanfang online libraries. After a comprehensive filtering procedure, we harvested five genes, including MGMT (rs12917 and rs2308321), ADH1B (rs1229984), SOD2 (rs4880), XPC (rs2228001), and PPARG (rs1801282). Using the REVMAN and Stata software, six meta-analyses were conducted for associations between CRC and the just-mentioned genetic variants. Results: A total of 34 comparative studies among 17,289 cases and 54,927 controls were involved in our meta-analyses. Significant association was found between ADH1B rs1229984 polymorphism and CRC (p=0.03, odds ratio [OR]=1.18, 95% confidence interval [CI]=1.01–1.36). We also found significant association between PPARG rs1801282 polymorphism and CRC (p=0.004, OR=1.498, 95% CI=1.139–1.970), and this significant association is specific in Caucasians (p=0.004, OR=1.603, 95% CI=1.165–2.205). Conclusions: The current meta-analysis has established that ADH1B (rs1229984) and PPARG (rs1801282) are two risk variants of CRC. PMID:24552298

  14. Genetic polymorphisms of vein wall remodeling in chronic venous disease: a narrative and systematic review.

    PubMed

    Bharath, Vighnesh; Kahn, Susan R; Lazo-Langner, Alejandro

    2014-08-21

    Chronic venous disease encompasses a spectrum of disorders caused by an abnormal venous system. They include chronic venous insufficiency, varicose veins, lipodermatosclerosis, postthrombotic syndrome, and venous ulceration. Some evidence suggests a genetic predisposition to chronic venous disease from gene polymorphisms associated mainly with vein wall remodeling. The literature exploring these polymorphisms has not been reviewed and compiled thus far. In this narrative and systematic review, we present the current evidence available on the role of polymorphisms in genes involved in vein wall remodeling and other pathways as contributors to chronic venous disease. We searched the EMBASE, Medline, and PubMed databases from inception to 2013 for basic science or clinical studies relating to genetic associations in chronic venous disease and obtained 38 relevant studies for this review. Important candidate genes/proteins include the matrix metalloproteinases (extracellular matrix degradation), vascular endothelial growth factors (angiogenesis and vessel wall integrity), FOXC2 (vascular development), hemochromatosis (involved in venous ulceration and iron absorption), and various types of collagen (contributors to vein wall strength). The data on associations between these genes/proteins and the postthrombotic syndrome are limited and additional studies are required. These associations might have future prognostic and therapeutic implications.

  15. Genetic association between COPD and polymorphisms in TNF, ADRB2 and EPHX1.

    PubMed

    Brøgger, J; Steen, V M; Eiken, H G; Gulsvik, A; Bakke, P

    2006-04-01

    There is evidence of a hereditary component in chronic obstructive pulmonary disease (COPD). A number of genetic association studies have been performed to find susceptibility genes of COPD. The current authors performed a case-control, genetic-association study and a meta-analysis of 16 studies, involving seven polymorphisms in three well-studied genes: microsomal epoxide hydroxylase (EPHX1); tumour necrosis factor; and beta2-adrenoreceptor. A total of 492 Caucasian smokers and former smokers were recruited from hospital databases and population cohort studies. In the present study, a protective effect of the EPHX1 Tyr113His polymorphism was found (homozygous odds ratio (OR) 0.5). In the meta-analysis, homozygotes for this single nucleotide polymorphism (SNP) also had a pooled OR of 0.5. The same effect has been found in several lung cancer studies. Effects for other candidate SNPs were weak or statistically insignificant, and probable genotyping error was common. In conclusion, the present data and meta-analysis support a role for microsomal epoxide hydroxylase in the aetiology of chronic obstructive pulmonary disease.

  16. 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.

  17. Allergic rhinitis and genetic components: focus on Toll-like receptors (TLRs) gene polymorphism

    PubMed Central

    Gao, Zhiwei; Rennie, Donna C; Senthilselvan, Ambikaipakan

    2010-01-01

    Allergic rhinitis represents a global health issue affecting 10% to 25% of the population worldwide. Over the years, studies have found that allergic diseases, including allergic rhinitis, are associated with immunological responses to antigens driven by a Th2-mediated immune response. Because Toll-like receptors (TLRs) are involved in both innate and adaptive immune responses to a broad variety of antigens, the association between polymorphisms of TLRs and allergic diseases has been the focus in many animal and human studies. Although the etiology of allergic rhinitis is still unknown, extensive research over the years has confirmed that the underlying causes of allergic diseases are due to many genetic and environmental factors, along with the interactions among them, which include gene–environment, gene–gene, and environment–environment interactions. Currently, there is great inconsistency among studies mainly due to differences in genetic background and unique gene–environment interactions. This paper reviews studies focusing on the association between TLR polymorphisms and allergic diseases, including allergic rhinitis, which would help researchers better understand the role of TLR polymorphisms in the development of allergic rhinitis, and ultimately lead to more efficient therapeutic interventions being developed. PMID:23776356

  18. Effect of genetic polymorphisms in the folate pathway on methotrexate therapy in rheumatic diseases.

    PubMed

    Stamp, Lisa K; Roberts, Rebecca L

    2011-10-01

    Methotrexate (MTX) is the first-line treatment for rheumatoid arthritis and is frequently used in the management of other forms of inflammatory arthritis. It is currently challenging to predict which patients will achieve adequate disease control and which patients will develop adverse effects while taking MTX. As an analog of dihydrofolic acid, MTX enters cells through the reduced folate carrier-1 protein, and is polyglutamated. MTX polyglutamates inhibit key enzymes in the folate pathway to produce an anti-inflammatory effect. It has been suggested that genetic polymorphisms in the folate pathway may influence intracellular folate and MTX polyglutamates pools, and thus MTX response. However, studies to identify genetic predictors have yielded inconclusive results. Nonreplication across studies has been attributed to insufficient statistical power as well as pharmacological and clinical confounders. Prospective studies, standardizing the definitions of response and toxicity, and application of genome-wide approaches may advance the search for genetic predictors of MTX response.

  19. 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.

  20. 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.

  1. Folate-related nutrients, genetic polymorphisms, and colorectal cancer risk: the fukuoka colorectal cancer study.

    PubMed

    Morita, Makiko; Yin, Guang; Yoshimitsu, Shin-ichiro; Ohnaka, Keizo; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji

    2013-01-01

    One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin B6 intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin B2, vitamin B6, and vitamin B12 with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin B12 intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin B6. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.

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

    PubMed Central

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

    1998-01-01

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

  3. Genetic Polymorphisms in Non-alcoholic Fatty Liver Disease in Obese Egyptian Children

    PubMed Central

    El-Koofy, Nehal M.; El-Karaksy, Hanaa M.; Mandour, Iman M.; Anwar, Ghada M.; El-Raziky, Mona S.; El-Hennawy, Ahmad M.

    2011-01-01

    Background/Aim: Polymorphisms in the promoter of microsomal triglyceride transfer protein (MTP) lead to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. Therefore, functional polymorphisms in MTP may be involved in determining susceptibility to nonalcoholic steatohepatitis (NASH). The aim of this study is to examine the effect of some genetic influences among a group of obese Egyptian children. Patients and Methods: A cross-sectional study was conducted on 76 overweight and obese children presenting to the Pediatric Endocrinology Unit, Cairo University Children's Hospital, Egypt, as well as on 20 healthy controls. Anthropometric measurements were taken for all the patients and they underwent clinical examination, ultrasonographic examination of the liver, and liver biopsy when appropriate. Liver functions, blood glucose, serum insulin, C-peptide, and lipid profile were assessed and HOMA-IR calculated. Blood samples from biopsy-proven NASH patients and controls were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism for the –493 G/T polymorphism in the promoter of MTP and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD). Results: Eight had biopsy-proven simple steatosis and 7 had NASH. NASH patients had a much higher incidence of the MTP G/G genotype (P = 0.002, CI: 2.9–392) compared with the controls. NASH patients also had a 100% prevalence of the MnSOD T/T genotype. Conclusion: Certain genotypes in MTP and MnSOD are significantly more prevalent among obese children with NASH and may be responsible for such a phenotype. PMID:21727734

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

    PubMed Central

    2012-01-01

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

  5. Role of Genetic Polymorphisms in the Development and Prognosis of Sporadic and Familial Prostate Cancer

    PubMed Central

    Reis, Sabrina T.; Viana, Nayara I.; Leite, Katia R. M.; Diogenes, Erico; Antunes, Alberto A.; Iscaife, Alexandre; Nesrallah, Adriano J.; Passerotti, Carlo C.; Srougi, Victor; Pontes-Junior, José; Salles, Mary Ellen; Nahas, William C.; Srougi, Miguel

    2016-01-01

    Backgrounds Our aim was to evaluate the role of 20 genetic polymorphisms in the development and prognosis of sporadic and familial PC. A case-control study of 185 patients who underwent radical prostatectomy from 1997 to 2011. These patients were divided into two groups based on their family history. Gleason grade, PSA value and pathological TNM 2002 stage were used as prognostic factors. Blood samples from 70 men without PC were used as controls. The SNPs were genotyped using a TaqMan® SNP Genotyping Assay Kit. Results Considering susceptibility, the polymorphic allele in the SNP rs2660753 on chromosome 3 was significantly more prevalent in controls (p = 0.01). For familial clustering, the polymorphic homozygote genotype of the SNP rs7931342 was five times more frequent in patients with familial PC compared to sporadic PC (p = 0.01). Regarding the SNP 1447295, the polymorphic homozygote genotype was more prevalent in patients with organ-confined PC (p = 0.05), and most importantly, the polymorphic allele occurred more frequently in patients without biochemical recurrence (p = 0.01). Kaplan-Meier analysis showed a median biochemical recurrence free survival of 124.2 compared to 85.6 months for patients with the wild-type allele (p = 0.007). Conclusion Our findings provide the evidence for the association of 20 recently highlighted SNPs and their susceptibility, familial clustering, staging, Gleason score and biochemical recurrence of PC. We believe that the association between these SNPs and PC may contribute to the development of alternative tools that can facilitate the early detection and prognosis of this disease. PMID:27906997

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

    PubMed Central

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

    2015-01-01

    Abstract Much attention has been directed to the association between cancer risk and rs2066827 polymorphism of the CDKN1B gene. However, the results are indefinitive and inconclusive. This study was devised to evaluate the hypothesis that rs2066827 polymorphism is associated with the risk of cancer. Computer-based databases (EMBASE, PubMed, and CNKI) were used to seek all case–control studies evaluating rs2066827 polymorphism and susceptibility to cancer. The genetic risk was assessed by calculating pooled odds ratio (OR) with its corresponding 95% confidence interval (CI). Fixed-effects pooled ORs were calculated by the Mantel–Haenszel method (Ph > 0.05), and random-effects pooled ORs were estimated by the DerSimonian–Laird method (Ph < 0.05). Data on rs2066827 polymorphism and cancer risk were available for 9038 cancer cases and 11,596 controls participating in 17 studies. Carriage of a TG genotype was associated with a minor but significant decrease in the risk of cancer (pooled OR 0.92, 95% CI: 0.86–0.99; model, TG vs. TT). We observed a moderately decreased risk of ovarian cancer based on 1829 cases and 2868 controls (pooled OR 0.85, 95% CI: 0.74–0.97; model, TG vs. TT). A slightly deceased risk of cancer was also indicated in Caucasians consisting of 6707 cases and 8279 controls (pooled OR 0.91, 95% CI: 0.85–0.98; model, TG vs. TT). These data suggest that carriage of a TG genotype at rs2066827 polymorphism may be associated with decreased susceptibility to cancer, ovarian cancer in particular. PMID:26579796

  7. [Role of genetic polymorphisms of the hemostatic system in the development of multiple organ dysfunctions in acute disseminated intravascular coagulation].

    PubMed

    Vorob'eva, N A; Kapustin, S I

    2007-01-01

    The paper deals with the hereditary predisposition of the hemostatic system to the severe course of acute disseminated intravascular coagulation (DIC). The results of evaluation of some types of genetic polymorphisms of the factors of coagulation and of the fibrinolytic system are recent and important for clinical application. Analysis of mortality in the fulminant course of acute DIC showed significant differences in the detection rates of the variants of genetic polymorphism in the type I plasminogen activator inhibitor gene, which is indicative of the possible genetic determination of acute DIC.

  8. Genetic polymorphisms of 54 mitochondrial DNA SNP loci in Chinese Xibe ethnic minority group

    PubMed Central

    Shen, Chun-Mei; Hu, Li; Yang, Chun-Hua; Yin, Cai-Yong; Li, Zhi-Dan; Meng, Hao-Tian; Guo, Yu-Xin; Mei, Ting; Chen, Feng; Zhu, Bo-Feng

    2017-01-01

    We analyzed the genetic polymorphisms of 54 mitochondrial DNA (mtDNA) variants in Chinese Xibe ethnic minority group. A total of 137 unrelated healthy volunteers from Chinese Xibe group were the objects of our study. Among the selected loci, there were 51 variable positions including transitions and transversions, and single nucleotide transitions were common (83.93%) versus transversions. These variations defined 64 different mtDNA haplotypes exclusive of (CA)n and 9 bp deletion variation. The haplotype diversity and discrimination power in Xibe population were 0.9800 ± 0.004 and 0.9699, respectively. Besides, we compared Xibe group with 18 other populations and reconstructed a phylogenetic tree using Neighbor-Joining method. The result revealed that Xibe group was a close to Xinjiang Han and Yanbian Korean groups. Our data also indicated that Xibe group has a close relationship with Daur and Ewenki groups, which is reflected by the history that Xibe was influenced by Daur and Ewenki groups during the development of these groups. In conclusion, the variants we studied are polymorphic and could be used as informative genetic markers for forensic and population genetic application. PMID:28327596

  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

    2014-06-02

    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. Twenty-one polymorphic markers from human chromosome 12 for integration of genetic and physical maps

    SciTech Connect

    LeBlanc-Straceski, J.M.; Kissel, H.; Murtaugh, L.; Kucherlapati, R.; Montogmery, K.T.; Krauter, K.S. ); Tsai, P.; Ward, D.C. )

    1994-01-15

    Twenty-one physically mapped, polymorphic markers have been developed from a chromosome 12-specific cosmid library. The markers consist of CA repeat-containing sequence-tagged sites (STSs) derived from cosmid clones mapped by fluorescence in situ hybridization (FISH). Three methods for determining the sequence flanking CA microsatellites were used, including one using degenerate primer sets for direct sequence analysis. Oligonucleotide primer pairs suitable for use in polymerase chain reaction (PCR) were selected from the sequences flanking the CA microsatellite and were tested for their ability to generate unique PCR products. The informativeness of these STSs as genetic markers was determined by typing 10 unrelated individuals who are part of the Centre d'Etude du Polymorphisme Humaine (EPH) pedigrees. Eleven of the 21 FISH-mapped, polymorphic STSs are heterozygous in 7 or more of the individuals tested. Since these markers are derived from physically mapped cosmids, genetic linkage analysis with them will facilitate the integration of the developing physical and genetic maps of chromosome 12. 29 refs., 4 figs., 2 tabs.

  11. Emotion appraisal is modulated by the genetic polymorphism of the serotonin transporter.

    PubMed

    Szily, Erika; Bowen, John; Unoka, Zsolt; Simon, Lajos; Kéri, Szabolcs

    2008-06-01

    We investigated the relationship between the genetic polymorphism of the promoter of the serotonin transporter gene (SLC64A) and emotion appraisal profiles for fear, sadness, and joy in 114 healthy volunteers. Results revealed that carriers of the s-allele achieved higher scores than non-carriers for unpleasantness and goal-hindrance but scored lower for coping ability in the case of fear and sadness. There were no such differences in the case of joy. These results indicate that the s-allele of the serotonin transporter gene is associated with a vulnerable cognitive style related to the appraisal of negative emotions.

  12. Genetic analysis of Trichinella populations by 'cold' single-strand conformation polymorphism analysis.

    PubMed

    Gasser, Robin B; Hu, Min; El-Osta, Youssef Abs; Zarlenga, Dante S; Pozio, Edoardo

    2005-09-05

    A non-isotopic single-strand conformation polymorphism ('cold' SSCP) technique has been assessed for the analysis of sequence variability in the expansion segment 5 (ES5) of domain IV and the D3 domain of nuclear ribosomal DNA within and/or among isolates and individual muscle (first-stage) larvae representing all currently recognized species/genotypes of Trichinella. Data are consistent with the ability of cold SSCP to identify intra-specific as well as inter-specific variability among Trichinella genotypes. The cold SSCP approach should be applicable to a range of other genetic markers for comparative studies of Trichinella populations globally.

  13. 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.

  14. 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.

  15. Polymorphisms of the lipoprotein lipase gene as genetic markers for stroke in colombian population: a case control study

    PubMed Central

    Vargas Castellanos, Clara Inés; Silva Sieger, Federico Arturo

    2016-01-01

    Abstract Objective: To analyze if there is an association between the presence of polymorphisms in the LPL gene (rs320, rs285 and rs328) with development of acute ischemic stroke in Colombian population. Methods: In a case control design, 133 acute ischemic stroke patients (clinical diagnosis and x-ray CT) and 269 subjects without stroke as controls were studied. PCR -RFLP technique was used to detect rs320, rs285 and rs328 polymorphisms in the LPL gene. Results: In the present research was not found any association between any of the LPL gene polymorphism and acute ischemic stroke in the population studied; the allele and genotypic frequencies of the studied polymorphisms were similar in cases and controls and followed the Hardy-Weinberg equilibrium. The study was approved by the IRB and each subject signed the informed consent. Conclusion: LPL gene polymorphisms are not genetic markers for the development of stroke in the Colombian sample used. PMID:28293042

  16. Single nucleotide polymorphisms for assessing genetic diversity in castor bean (Ricinus communis)

    PubMed Central

    2010-01-01

    Background Castor bean (Ricinus communis) is an agricultural crop and garden ornamental that is widely cultivated and has been introduced worldwide. Understanding population structure and the distribution of castor bean cultivars has been challenging because of limited genetic variability. We analyzed the population genetics of R. communis in a worldwide collection of plants from germplasm and from naturalized populations in Florida, U.S. To assess genetic diversity we conducted survey sequencing of the genomes of seven diverse cultivars and compared the data to a reference genome assembly of a widespread cultivar (Hale). We determined the population genetic structure of 676 samples using single nucleotide polymorphisms (SNPs) at 48 loci. Results Bayesian clustering indicated five main groups worldwide and a repeated pattern of mixed genotypes in most countries. High levels of population differentiation occurred between most populations but this structure was not geographically based. Most molecular variance occurred within populations (74%) followed by 22% among populations, and 4% among continents. Samples from naturalized populations in Florida indicated significant population structuring consistent with local demes. There was significant population differentiation for 56 of 78 comparisons in Florida (pairwise population ϕPT values, p < 0.01). Conclusion Low levels of genetic diversity and mixing of genotypes have led to minimal geographic structuring of castor bean populations worldwide. Relatively few lineages occur and these are widely distributed. Our approach of determining population genetic structure using SNPs from genome-wide comparisons constitutes a framework for high-throughput analyses of genetic diversity in plants, particularly in species with limited genetic diversity. PMID:20082707

  17. Genetic polymorphisms in β-defensin II gene in Amazon sheep from Brazil.

    PubMed

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

    2015-10-19

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

  18. Genetics of bipolar disorder: focus on BDNF Val66Met polymorphism.

    PubMed

    Fan, Jinbo; Sklar, Pamela

    2008-01-01

    Bipolar disorder is a chronic severe mood disorder that has been consistently demonstrated to have a strong inherited component. Traditional approaches to gene discovery have produced conflicting results regarding the association between genes and bipolar disorder. Numerous genes have been proposed as associated with bipolar disorder. This paper will focus on one of these, brain-derived neurotrophic factor (BDNF). BDNF is an interesting candidate gene for bipolar disorder because of its important role in the neurodevelopment of the CNS. Previous genetic work has identified a potential association between a Val66Met polymorphism in the BDNF gene and bipolar disorder. Meta-analysis based on all original published association studies between the Val66Met polymorphism and bipolar disorder up to May 2007 shows modest but statistically significant evidence for the association between the Val66Met polymorphism and bipolar disorder (random-effects pooled odds ratio [OR] = 1.13, 95% Confidence Interval [CI] = 1.04-1.23, Z = 2.85, P = 0.004) from 14 studies consisting of 4248 cases, 7080 control subjects and 858 nuclear families. Further large-scale studies are warranted to elucidate the relevant BDNF gene variation(s) that act as risk factors for bipolar disorder susceptibility.

  19. Genetic polymorphism of chemokine receptors CCR2 and CCR5 in Swedish cervical cancer patients.

    PubMed

    Zheng, Biying; Wiklund, Fredrik; Gharizadeh, Baback; Sadat, Mehdi; Gambelunghe, Giovanni; Hallmans, Göran; Dillner, Joakim; Wallin, Keng-Ling; Ghaderi, Mehran

    2006-01-01

    Chemokines are chemotactic cytokines that orchestrate leukocyte trafficking in tissues, thus, playing an important role in regulation of immunological processes. The aim of this study was to investigate the association of human papillomavirus (HPV) infection and cervical cancer with two DNA polymorphisms of the chemokine receptors CCR5-delta32 and CCR2-64I. The study material consisted of 50 cervical intraepithelial neoplasia (CIN) cases and 50 of age and sampling-date matched controls, 100 invasive cervix cancer cases and 100 of their corresponding matched disease-free controls. Pyrosequencing was employed to genotype the CCR2-64I polymorphism. CCR5-delta32 was genotyped using standard PCR fragment length analysis. The frequencies of CCR2 and CCR5 genotypes from 150 patients and 150 healthy controls were representative of the general population according to the Hardy-Weinberg equilibrium analysis. Risk association was computed with conditional logistic regression analysis. HPV-positive individuals with the rare CCR5deelta32/delta32 genotype have a risk of 4.58 (CI = 0.40-52.64, p-value = 0.045) compare to HPV negative group. The delta-32 mutation on the CCR locus is imperceptibly associated with increased risk of HPV infection. In total, cervical neoplasia was not associated with genetic polymorphism of CCR2 and CCR5.

  20. Update on the Genetic Polymorphisms of Drug-Metabolizing Enzymes in Antiepileptic Drug Therapy

    PubMed Central

    Saruwatari, Junji; Ishitsu, Takateru; Nakagawa, Kazuko

    2010-01-01

    Genetic polymorphisms in the genes that encode drug-metabolizing enzymes are implicated in the inter-individual variability in the pharmacokinetics and pharmaco-dynamics of antiepileptic drugs (AEDs). However, the clinical impact of these polymorphisms on AED therapy still remains controversial. The defective alleles of cytochrome P450 (CYP) 2C9 and/or CYP2C19 could affect not only the pharmacokinetics, but also the pharmacodynamics of phenytoin therapy. CYP2C19 deficient genotypes were associated with the higher serum concentration of an active metabolite of clobazam, N-desmethylclobazam, and with the higher clinical efficacy of clobazam therapy than the other CYP2C19 genotypes. The defective alleles of CYP2C9 and/or CYP2C19 were also found to have clinically significant effects on the inter-individual variabilities in the population pharmacokinetics of phenobarbital, valproic acid and zonisamide. EPHX1 polymorphisms may be associated with the pharmacokinetics of carbamazepine and the risk of phenytoin-induced congenital malformations. Similarly, the UDP-glucuronosyltransferase 2B7 genotype may affect the pharmacokinetics of lamotrigine. Gluthatione S-transferase null genotypes are implicated in an increased risk of hepatotoxicity caused by carbamazepine and valproic acid. This article summarizes the state of research on the effects of mutations of drug-metabolizing enzymes on the pharmacokinetics and pharmacodynamics of AED therapies. Future directions for the dose-adjustment of AED are discussed. PMID:27713373

  1. Genetic polymorphisms in the serotonergic system are associated with circadian manifestations of bruxism.

    PubMed

    Oporto, G H; Bornhardt, T; Iturriaga, V; Salazar, L A

    2016-11-01

    Bruxism (BRX) is a condition of great interest for researchers and clinicians in dental and medical areas. BRX has two circadian manifestations; it can occur during sleep (sleep bruxism, SB) or during wakefulness (awake bruxism, WB). However, it can be suffered together. Recent investigations suggest that central nervous system neurotransmitters and their genes could be involved in the genesis of BRX. Serotonin is responsible for the circadian rhythm, maintaining arousal, regulating stress response, muscle tone and breathing. Thus, serotonin could be associated with BRX pathogenesis. The aim of this work was to evaluate the frequency of genetic polymorphisms in the genes HTR1A (rs6295), HTR2A (rs1923884, rs4941573, rs6313, rs2770304), HTR2C (rs17260565) and SLC6A4 (rs63749047) in subjects undergoing BRX treatment. Patients included were classified according to their diagnosis in awake bruxism (61 patients), sleep bruxism (26 patients) and both (43 patients). The control group included 59 healthy patients with no signs of BRX. Data showed significant differences in allelic frequencies for the HTR2A rs2770304 polymorphism, where the C allele was associated with increased risk of SB (odds ratio = 2·13, 95% confidence interval: 1·08-4·21, P = 0·03). Our results suggest that polymorphisms in serotonergic pathways are involved in sleep bruxism. Further research is needed to clarify and increase the current understanding of BRX physiopathology.

  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. New views on the selection acting on genetic polymorphism in central metabolic genes.

    PubMed

    Eanes, Walter F

    2017-02-01

    Studies of the polymorphism of central metabolic genes as a source of fitness variation in natural populations date back to the discovery of allozymes in the 1960s. The unique features of these genes and their enzymes and our knowledge base greatly facilitates the systems-level study of this group. The expectation that pathway flux control is central to understanding the molecular evolution of genes is discussed, as well as studies that attempt to place gene-specific molecular evolution and polymorphism into a context of pathway and network architecture. There is an increasingly complex picture of the metabolic genes assuming additional roles beyond their textbook anabolic and catabolic reactions. In particular, this review emphasizes the potential role of these genes as part of the energy-sensing machinery. It is underscored that the concentrations of key cellular metabolites are the reflections of cellular energy status and nutritional input. These metabolites are the top-down signaling messengers that set signaling through signaling pathways that are involved in energy economy. I propose that the polymorphisms in central metabolic genes shift metabolite concentrations and in that fashion act as genetic modifiers of the energy-state coupling to the transcriptional networks that affect physiological trade-offs with significant fitness consequences.

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

    PubMed Central

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

    1999-01-01

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

  5. Analysis of population genetic structure from Bucaramanga (Colombia) based on gene polymorphisms associated with the regulation of blood pressure

    PubMed Central

    Rondón, Fernando; Vargas, Clara Inés; Oróstegui, Myriam; Bautista, Leonelo; Serrano, Norma Cecilia; Páez, María c; Castillo, Adriana

    2012-01-01

    Introduction: In spite of nearly 40% of variability in blood pressure being explained by genetic factors, the identification of genes associated with essential high blood pressure is difficult to determine in populations where individuals have different genetic backgrounds. In these circumstances it is necessary to determinate whether the population is sub-structured because this can bias studies associated with this disease. Objective: To determine the genetic structure of the population in Bucaramanga from genetic polymorphisms associated with the regulation of blood pressure: 448G>T, 679C>T y 1711C>T from the gene kinase 4 of the dopaminergic receptor linked to the protein G and Glu298Asp, -786T>C and the VNTR of the intron 4 of the gene of endothelial nitric oxide. Methods: A sample of 552 unrelated individuals was studied through analysis of restriction fragment length polymorphism. The allelic, haplotypic and genotypic frequencies were calculated, the Hardy-Weinberg equilibrium was determined and a molecular analysis of variance was performed to determine the genetic structure. Results: Thirty-eight (38) Haplotypes were identified with GCCTG4b being the most frequent (21.2%). The most diverse polymorphism was 448G>T with a frequency of 49.9% for heterozygous. The six polymorphisms were found in genetic equilibrium and a genetic structure of populations was not evidenced (FST= 0.0038). Conclusion: The population studied does not present a genetic sub-structure and the polymorphisms analyzed were found in genetic equilibrium. This indicates that the population mixes randomly and there are no sub-groups capable of affecting the results of the association studies. PMID:24893057

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

    PubMed

    Galbiatti, Ana Lívia Silva; da Silva, Lidia Maria Rebolho Batista; Ruiz-Cintra, Mariangela Torreglosa; Raposo, Luis Sérgio; Maníglia, José Victor; Pavarino, Erika Cristina; Goloni-Bertollo, Eny Maria

    2012-07-01

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

  7. Identification and genetic homogeneity of Trichophyton tonsurans isolated from several regions by random amplified polymorphic DNA.

    PubMed

    Kim, J A; Takizawa, K; Fukushima, K; Nishimura, K; Miyaji, M

    1999-01-01

    Trichophyton tonsurans is an anthropophilic dermatophyte mostly causing tinea capitis and tinea corporis. This study was carried out to identify T. tonsurans and to clarify whether it has any genetic differences depending on the phenotype or region of isolation by random amplified polymorphic DNA (RAPD) analysis with three random primers. The assay was performed in 11 Korean, 2 Japanese, 2 Taiwanese, 5 Brazilian and 1 American isolates of T. tonsurans together with the other 10 anamorphic species of dermatophytes and 3 Arthroderma spp. All tested species of dermatophytes showed distinct bands and T. tonsurans was differentiated from other dermatophytes. It was most clearly differentiated from T. mentagrophytes by using primer 5'-GAAGGCTCCC-3' (OPAO-15). No difference was found in RAPD band patterns in all strains of T. tonsurans with these random primers. It was considered that T. tonsurans is a genetically homogeneous species regardless of its isolation regions, morphologic or physiologic characteristics.

  8. [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,…

  9. Association of Oseltamivir Activation with Gender and Carboxylesterase 1 Genetic Polymorphisms.

    PubMed

    Shi, Jian; Wang, Xinwen; Eyler, Rachel F; Liang, Yan; Liu, Li; Mueller, Bruce A; Zhu, Hao-Jie

    2016-12-01

    Oseltamivir, an inactive anti-influenza virus prodrug, is activated (hydrolysed) in vivo by carboxylesterase 1 (CES1) to its active metabolite oseltamivir carboxylate. CES1 functions are significantly associated with certain CES1 genetic variants and some non-genetic factors. The purpose of this study was to investigate the effect of gender and several CES1 genetic polymorphisms on oseltamivir activation using a large set of individual human liver samples. CES1-mediated oseltamivir hydrolysis and CES1 genotypes, including the G143E (rs71647871), rs2244613, rs8192935, the -816A>C (rs3785161) and the CES1P1/CES1P1VAR, were determined in 104 individual human livers. The results showed that hepatic CES1 protein expression in females was 17.3% higher than that in males (p = 0.039), while oseltamivir activation rate in the livers from female donors was 27.8% higher than that from males (p = 0.076). As for CES1 genetic polymorphisms, neither CES1 protein expression nor CES1 activity on oseltamivir activation was significantly associated with the rs2244613, rs8192935, -816A>C or CES1P1/CES1P1VAR genotypes. However, oseltamivir hydrolysis in the livers with the genotype 143G/E was approximately 40% of that with the 143G/G genotype (0.7 ± 0.2 versus 1.8 ± 1.1 nmole/mg protein/min, p = 0.005). In summary, the results suggest that hepatic oseltamivir activation appears to be more efficient in females than that in males, and the activation can be impaired by functional CES1 variants, such as the G143E. However, clinical implication of CES1 gender differences and pharmacogenetics in oseltamivir pharmacotherapy warrants further investigations.

  10. 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

  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. Genetic association analyses of PDYN polymorphisms with heroin and cocaine addiction.

    PubMed

    Clarke, T-K; Ambrose-Lanci, L; Ferraro, T N; Berrettini, W H; Kampman, K M; Dackis, C A; Pettinati, H M; O'Brien, C P; Oslin, D W; Lohoff, F W

    2012-06-01

    Genetic factors are believed to account for 30-50% of the risk for cocaine and heroin addiction. Dynorphin peptides, derived from the prodynorphin (PDYN) precursor, bind to opioid receptors, preferentially the kappa-opioid receptor, and may mediate the aversive effects of drugs of abuse. Dynorphin peptides produce place aversion in animals and produce dysphoria in humans. Cocaine and heroin have both been shown to increase expression of PDYN in brain regions relevant for drug reward and use. Polymorphisms in PDYN are therefore hypothesized to increase risk for addiction to drugs of abuse. In this study, 3 polymorphisms in PDYN (rs1022563, rs910080 and rs1997794) were genotyped in opioid-addicted [248 African Americans (AAs) and 1040 European Americans (EAs)], cocaine-addicted (1248 AAs and 336 EAs) and control individuals (674 AAs and 656 EAs). Sex-specific analyses were also performed as a previous study identified PDYN polymorphisms to be more significantly associated with female opioid addicts. We found rs1022563 to be significantly associated with opioid addiction in EAs [P = 0.03, odds ratio (OR) = 1.31; false discovery rate (FDR) corrected q-value]; however, when we performed female-specific association analyses, the OR increased from 1.31 to 1.51. Increased ORs were observed for rs910080 and rs199774 in female opioid addicts also in EAs. No statistically significant associations were observed with cocaine or opioid addiction in AAs. These data show that polymorphisms in PDYN are associated with opioid addiction in EAs and provide further evidence that these risk variants may be more relevant in females.

  13. DNA promoter methylation in breast tumors: no association with genetic polymorphisms in MTHFR and MTR.

    PubMed

    Tao, Meng Hua; Shields, Peter G; Nie, Jing; Marian, Catalin; Ambrosone, Christine B; McCann, Susan E; Platek, Mary; Krishnan, Shiva S; Xie, Bin; Edge, Stephen B; Winston, Janet; Vito, Dominica; Trevisan, Maurizio; Freudenheim, Jo L

    2009-03-01

    Aberrant promoter methylation is recognized as an important feature of breast carcinogenesis. We hypothesized that genetic variation of genes for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR), two critical enzymes in the one-carbon metabolism, may alter DNA methylation levels and thus influence DNA methylation in breast cancer. We evaluated case-control association of MTHFR C677T, A1298C, and MTR A2756G polymorphisms for cases strata-defined by promoter methylation status for each of three genes, E-cadherin, p16, and RAR-beta2 in breast cancer; in addition, we evaluated case-case comparisons of the likelihood of promoter methylation in relation to genotypes using a population-based case-control study conducted in Western New York State. Methylation was evaluated with real-time methylation-specific PCRs for 803 paraffin-embedded breast tumor tissues from women with primary, incident breast cancer. We applied unordered polytomous regression and unconditional logistic regression to derive adjusted odds ratios and 95% confidence intervals. We did not find any association of MTHFR and MTR polymorphisms with breast cancer risk stratified by methylation status nor between polymorphisms and likelihood of promoter methylation of any of the genes. There was no evidence of difference within strata defined by menopausal status, estrogen receptor status, folate intake, and lifetime alcohol consumption. Overall, we found no evidence that these common polymorphisms of the MTHFR and MTR genes are associated with promoter methylation of E-cadherin, p16, and RAR-beta2 genes in breast cancer.

  14. Evaluation of insulin like growth facror-1 genetic polymorphism with gastric cancer susceptibility and clinicopathological features.

    PubMed

    Farahani, Roya Kishani; Azimzadeh, Pedram; Rostami, Elham; Malekpour, Habib; Aghdae, Hamid Asadzadeh; Pourhoseingholi, Mohamad Amin; Nazemalhosseini Mojarad, Ehsan; Zali, Mohammad Reza

    2015-01-01

    Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancer deaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have been associated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth, proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatory elements may lead to alter in IGF-1 expression level and GC susceptibility. The aim of this study was to investigate the influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for the first time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controls were recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). The frequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%, 2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. The frequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively. Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerful genetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population.

  15. DNA promoter methylation in breast tumors: No association with genetic polymorphisms in MTHFR and MTR

    PubMed Central

    Tao, Meng Hua; Shields, Peter G.; Nie, Jing; Marian, Catalin; Ambrosone, Christine B.; McCann, Susan E.; Platek, Mary; Krishnan, Shiva S.; Xie, Bin; Edge, Stephen B.; Winston, Janet; Vito, Dominica; Trevisan, Maurizio; Freudenheim, Jo L.

    2013-01-01

    Aberrant promoter methylation is recognized as an important feature of breast carcinogenesis. We hypothesized that genetic variation of genes for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR), two critical enzymes in one-carbon metabolism, may alter DNA methylation levels, and thus influence DNA methylation in breast cancer. We evaluated case-control association of MTHFR C677T, A1298C, and MTR A2756G polymorphisms for cases strata defined by promoter methylation status for each of three genes, E- cadherin, p16, and RAR-β2 in breast cancer; in addition, we evaluated case-case comparisons of likelihood of promoter methylation in relation to genotypes using a population-based case-control study conducted in Western New York State. Methylation was evaluated with real time methylation-specific PCRs for 803 paraffin embedded breast tumor tissues from women with primary, incident breast cancer. We applied unordered polytomous regression and unconditional logistic regression to derive adjusted odds ratios (OR) and 95% confidence intervals (CI). We did not find any association of MTHFR and MTR polymorphisms with breast cancer risk stratified by methylation status nor between polymorphisms and likelihood of promoter methylation of any of the genes. There was no evidence of difference within strata defined by menopausal status, ER status, folate intake and lifetime alcohol consumption. Overall, we found no evidence that these common polymorphisms of the MTHFR and MTR genes are associated with promoter methylation of E- cadherin, p16, and RAR-β2 genes in breast cancer. PMID:19240236

  16. 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.

  17. Genetic polymorphism at 15 STR loci among three important subpopulation of Bihar, India.

    PubMed

    Ashma, R; Kashyap, V K

    2002-11-05

    Genotype polymorphism studies at 15 highly polymorphic short tandem repeat (STR) loci were carried out in three genetically important minor caste groups (Yadav, Kurmi and Baniya) of Bihar, a eastern state of India to evaluate their significance in human identification and population genetics study. The selected communities practice endogamy. Despite of same geographical area, the physical features of Yadavs and Baniyas resemble North Indian Indo-Caucasoids whereas Kurmis resemble more to Indo-Austroloids. Among the chosen 15 loci, two are penta-nucleotide repeat: Penta-D and Penta-E, and 13 are tetra-nucleotide repeat: vWA D8S1179, TPOX, FGA, D5S818, D13S317, D7S820, D16S539, D3S1358, THO1, CSF1PO, D21S11, D18S51 and are validated for other population of India and world for forensic testing and human population study. Thirteen of these STR loci are present in the combined DNA index system (CODIS) [J. Forensic Sci. 44 (1999) 1277] and world-wide data is available.

  18. 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.

  19. 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.

  20. Fatal methadone toxicity: potential role of CYP3A4 genetic polymorphism.

    PubMed

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

    2014-10-01

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

  1. 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

  2. Drug resistance associated genetic polymorphisms in Plasmodium falciparum and Plasmodium vivax collected in Honduras, Central America

    PubMed Central

    2011-01-01

    Background In Honduras, chloroquine and primaquine are recommended and still appear to be effective for treatment of Plasmodium falciparum and Plasmodium vivax malaria. The aim of this study was to determine the proportion of resistance associated genetic polymorphisms in P. falciparum and P. vivax collected in Honduras. Methods Blood samples were collected from patients seeking medical attention at the Hospital Escuela in Tegucigalpa from 2004 to 2006 as well as three regional hospitals, two health centres and one regional laboratory during 2009. Single nucleotide polymorphisms in P. falciparum chloroquine resistance transporter (pfcrt), multidrug resistance 1 (pfmdr1), dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes and in P. vivax multidrug resistance 1 (pvmdr1) and dihydrofolate reductase (pvdhfr) genes were detected using PCR based methods. Results Thirty seven P. falciparum and 64 P. vivax samples were collected. All P. falciparum infections acquired in Honduras carried pfcrt, pfmdr1, pfdhps and pfdhfr alleles associated with chloroquine, amodiaquine and sulphadoxine-pyrimethamine sensitivity only. One patient with parasites acquired on a Pacific Island had pfcrt 76 T and pfmdr1 86Y alleles. That patient and a patient infected in West Africa had pfdhfr 51I, 59 R and 108 N alleles. Pvmdr1 976 F was found in 7/37 and two copies of pvmdr1 were found in 1/37 samples. Pvdhfr 57 L + 58 R was observed in 2/57 samples. Conclusion The results indicate that P. falciparum from Honduras remain sensitive to chloroquine and sulphadoxine-pyrimethamine. This suggests that chloroquine and sulphadoxine-pyrimethamine should be efficacious for treatment of uncomplicated P. falciparum malaria, supporting current national treatment guidelines. However, genetic polymorphisms associated with chloroquine and sulphadoxine-pyrimethamine tolerance were detected in local P. vivax and imported P. falciparum infections. Continuous monitoring of the prevalence

  3. 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.

  4. The prognostic significance of genetic polymorphisms (Methylenetetrahydrofolate Reductase C677T, Methionine Synthase A2756G, Thymidilate Synthase tandem repeat polymorphism) in multimodally treated oesophageal squamous cell carcinoma

    PubMed Central

    Sarbia, M; Stahl, M; von Weyhern, C; Weirich, G; Pühringer-Oppermann, F

    2006-01-01

    The present study retrospectively examined the correlation between the outcome of patients with locally advanced oesophageal squamous cell carcinoma (cT3-4 cN0-1 cM0) after multimodal treatment (radiochemotherapy±surgical resection), and the presence of genetic polymorphisms in genes involved in folate metabolism. In total, 68 patients who took part in a prospective multicentric trial received 5-fluorouracil (FU)-based radiochemotherapy, optionally followed by surgery. DNA was extracted from pretherapeutic tumour biopsies and was subsequently genotyped for common genetic polymorphisms of three genes (MTHFR C677T, MTR A2756G, TS tandem repeat polymorphism) involved in folate metabolism and potentially in sensitivity to 5-FU-based chemotherapy. The genotypes were correlated with tumour response to polychemotherapy, radiochemotherapy and with overall survival. Tumours with the MTR wild-type genotype (2756AA) showed a median survival time of 16 months, whereas tumours with an MTR variant genotype (2756AG/2756GG) showed a median survival time of 42 months (P=0.0463). No prognostic impact could be verified for the genotypes of the MTHFR genes and the TS gene. Among tumours treated with radiochemotherapy and subsequent resection, MTR variant genotype showed higher histopathological response rate than tumours with MTR wild-type genotype (P=0.0442). In contrast, no significant relationship between clinically determined tumour regression after polychemotherapy and polymorphisms of the three genes under analysis was observed. In conclusion, pretherapeutic determination of the MTR A2756G polymorphism may predict survival of multimodally treated oesophageal squamous cell carcinomas. Determination of MTHFR C677T and TS tandem repeat polymorphism has no predictive value. PMID:16333305

  5. The prognostic significance of genetic polymorphisms (Methylenetetrahydrofolate Reductase C677T, Methionine Synthase A2756G, Thymidilate Synthase tandem repeat polymorphism) in multimodally treated oesophageal squamous cell carcinoma.

    PubMed

    Sarbia, M; Stahl, M; von Weyhern, C; Weirich, G; Pühringer-Oppermann, F

    2006-01-30

    The present study retrospectively examined the correlation between the outcome of patients with locally advanced oesophageal squamous cell carcinoma (cT3-4 cN0-1 cM0) after multimodal treatment (radiochemotherapy+/-surgical resection), and the presence of genetic polymorphisms in genes involved in folate metabolism. In total, 68 patients who took part in a prospective multicentric trial received 5-fluorouracil (FU)-based radiochemotherapy, optionally followed by surgery. DNA was extracted from pretherapeutic tumour biopsies and was subsequently genotyped for common genetic polymorphisms of three genes (MTHFR C677T, MTR A2756G, TS tandem repeat polymorphism) involved in folate metabolism and potentially in sensitivity to 5-FU-based chemotherapy. The genotypes were correlated with tumour response to polychemotherapy, radiochemotherapy and with overall survival. Tumours with the MTR wild-type genotype (2756AA) showed a median survival time of 16 months, whereas tumours with an MTR variant genotype (2756AG/2756GG) showed a median survival time of 42 months (P=0.0463). No prognostic impact could be verified for the genotypes of the MTHFR genes and the TS gene. Among tumours treated with radiochemotherapy and subsequent resection, MTR variant genotype showed higher histopathological response rate than tumours with MTR wild-type genotype (P=0.0442). In contrast, no significant relationship between clinically determined tumour regression after polychemotherapy and polymorphisms of the three genes under analysis was observed. In conclusion, pretherapeutic determination of the MTR A2756G polymorphism may predict survival of multimodally treated oesophageal squamous cell carcinomas. Determination of MTHFR C677T and TS tandem repeat polymorphism has no predictive value.

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

    PubMed Central

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

    2012-01-01

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

  7. Single strand conformation polymorphism of genomic and EST-SSRs marker and its utility in genetic evaluation of sugarcane.

    PubMed

    Kalwade, Sachin B; Devarumath, Rachayya M

    2014-07-01

    Sugarcane is an important crop producing around 75 % of sugar in world and used as first generation biofuel. In present study, the genomic and gene based microsatellite markers were analyzed by low cost Single Strand Confirmation Polymorphism technique for genetic evaluation of 22 selected sugarcane genotypes. Total 16 genomic and 12 Expression Sequence Tag derived markers were able to amplify the selected sugarcane genotypes. Total 138 alleles were amplified of which 99 alleles (72 %) found polymorphic with an average of 4.9 alleles per locus. Microsatellite marker, VCSSR7 and VCSSR 12 showed monomorphic alleles with frequency 7.1 % over the average of 3.5 obtained for polymorphic locus. The level of Polymorphic Information Content (PIC) varied from 0.09 in VCSSR 6 to 0.88 in VCSSR 11 marker respectively with a mean of 0.49. Genomic SSRs showed more polymorphism than EST-SSRs markers on selected sugarcane genotypes whereas, the genetic similarity indices calculated by Jaccard's similarity coefficient varied from 0.55 to 0.81 indicate a high level of genetic similarity among the genotypes that was mainly attributed to intra specific diversity. Hence, the SSR-SSCP technique helped to identify the genetically diverse clones which could be used in crossing program for introgression of sugar and stress related traits in hybrid sugarcane.

  8. 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.

  9. 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.

  10. Genetic polymorphisms in host antiviral genes: associations with humoral and cellular immunity to measles vaccine.

    PubMed

    Haralambieva, Iana H; Ovsyannikova, Inna G; Umlauf, Benjamin J; Vierkant, Robert A; Shane Pankratz, V; Jacobson, Robert M; Poland, Gregory A

    2011-11-08

    Host antiviral genes are important regulators of antiviral immunity and plausible genetic determinants of immune response heterogeneity after vaccination. We genotyped and analyzed 307 common candidate tagSNPs from 12 antiviral genes in a cohort of 745 schoolchildren immunized with two doses of measles-mumps-rubella (MMR) vaccine. Associations between SNPs/haplotypes and measles virus-specific immune outcomes were assessed using linear regression methodologies in Caucasians and African-Americans. Genetic variants within the DDX58/RIG-I gene, including a coding polymorphism (rs3205166/Val800Val), were associated as single-SNPs (p≤0.017; although these SNPs did not remain significant after correction for false discovery rate/FDR) and in haplotype-level analysis, with measles-specific antibody variations in Caucasians (haplotype allele p-value=0.021; haplotype global p-value=0.076). Four DDX58 polymorphisms, in high LD, demonstrated also associations (after correction for FDR) with variations in both measles-specific IFN-γ and IL-2 secretion in Caucasians (p≤0.001, q=0.193). Two intronic OAS1 polymorphisms, including the functional OAS1 SNP rs10774671 (p=0.003), demonstrated evidence of association with a significant allele-dose-related increase in neutralizing antibody levels in African-Americans. Genotype and haplotype-level associations demonstrated the role of ADAR genetic variants, including a non-synonymous SNP (rs2229857/Arg384Lys; p=0.01), in regulating measles virus-specific IFN-γ Elispot responses in Caucasians (haplotype global p-value=0.017). After correction for FDR, 15 single-SNP associations (11 SNPs in Caucasians and 4 SNPs in African-Americans) still remained significant at the q-value<0.20. In conclusion, our findings strongly point to genetic variants/genes, involved in antiviral sensing and antiviral control, as critical determinants, differentially modulating the adaptive immune responses to live attenuated measles vaccine in Caucasians and

  11. Typing of bacteriophages by randomly amplified polymorphic DNA (RAPD)-PCR to assess genetic diversity.

    PubMed

    Gutiérrez, Diana; Martín-Platero, Antonio M; Rodríguez, Ana; Martínez-Bueno, Manuel; García, Pilar; Martínez, Beatriz

    2011-09-01

    The recent boom in phage therapy and phage biocontrol requires the design of suitable cocktails of genetically different bacteriophages. The current methods for typing phages need significant quantities of purified DNA, may require a priori genetic information and are cost and time consuming. We have evaluated the randomly amplified polymorphic DNA (RAPD)-PCR technique to produce unique and reproducible band patterns from 26 different bacteriophages infecting Staphylococcus epidermidis, Staphylococcus aureus, Lactococcus lactis, Escherichia coli, Streptococcus thermophilus, Bacillus subtilis and Lactobacillus casei bacterial strains. Initially, purified DNA and phage suspensions of seven selected phages were used as a template. The conditions that were found to be optimal 8 μM of 10-mer primers, 3 μM magnesium oxalacetate and 5% dimethyl sulfoxide. The RAPD genomic fingerprints using a phage titer suspension higher than 10(9) PFU mL(-1) were highly reproducible. Clustering by the Pearson correlation coefficient and the unweighted pair group method with arithmetic averages clustering algorithm correlated largely with genetically different phages infecting the same bacterial species, although closely related phages with a similar DNA restriction pattern were indistinguishable. The results support the use of RAPD-PCR for quick typing of phage isolates and preliminary assessment of their genetic diversity bypassing tedious DNA purification protocols and previous knowledge of their sequence.

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

    PubMed Central

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

    2010-01-01

    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 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

  13. High genetic polymorphism of relapsing P. vivax isolates in northwest Colombia.

    PubMed

    Restrepo, Eliana; Imwong, Mallika; Rojas, Winston; Carmona-Fonseca, Jaime; Maestre, Amanda

    2011-07-01

    Genetic diversity of Plasmodium populations has been more extensively documented in Colombia for Plasmodium falciparum than for Plasmodium vivax. Recently, highly variable microsatellite markers have been described and used in population-level studies of genetic variation of P. vivax throughout the world. We applied this approach to understand the genetic structure of P. vivax populations and to identify recurrence-associated haplotypes. In this, three microsatellite markers of P. vivax were amplified and the combined size of the fragments was used to establish genotypes. Patients from an ongoing treatment efficacy trial who were kept either in endemic or non-endemic regions in the northwest of Colombia were included in the study. In total 58 paired clinical isolates, were amplified. A total of 54 haplotypes were observed among the two regions. Some haplotypes were exclusive to the endemic region where the highest degree of polymorphism was detected. In addition, we confirmed the different genotypes of recurrent-relapsing and primary infection isolates suggesting the activation of heterologous hypnozoite populations. We conclude that analysis of the three microsatellites is a valuable tool to establish the genetic characteristics of P. vivax populations in Colombia.

  14. Characterization of genetic polymorphism of novel MHC B-LB II alleles in Chinese indigenous chickens.

    PubMed

    Xu, Rifu; Li, Kui; Chen, Guohong; Xu, Hui; Qiang, Bayangzong; Li, Changchun; Liu, Bang

    2007-02-01

    Genetic polymorphism of the major histocompatibility complex (MHC) B-LB II gene was studied by amplification of exon 2 using PCR, followed by cloning and DNA sequencing in eight indigenous Chinese chicken populations. To reveal the genetic variation of the B-LB II gene, 37 types of patterns detected by PCR-SSCP were investigated first, which would be used to screen novel B-LB II sequences within the breeds. The types of PCR-SSCP patterns and final sequencing allowed for the identification of 31 novel MHC B-LB II alleles from 30 unrelated individuals of Chinese chickens that were sampled. These are the first designators for the alleles of chicken MHC B-LB II gene based on the rule of assignment for novel mammalian alleles. Sequence alignment of the 31 B-LB II alleles revealed a total of 68 variable sites in the fragment of exon 2, of which 51 parsimony informative and 17 singleton variable sites were observed. Among the polymorphic sites, the nucleotide substitutions in the first and second positions of the codons accounted for 36.76% and 35.29%, respectively. The sequence similarities between the alleles were estimated to be 90.6%-99.5%. The relative frequencies of synonymous and nonsynonymous nucleotide substitutions within the region were 2.92%+/-0.94% and 14.64%+/-2.67%, respectively. These results indicated that the genetic variation within exon 2 appeared to have largely arisen by gene recombination and balancing selection. Alignment of the deduced amino acid sequences of the beta1 domain coded by exon 2 revealed 6 synonymous mutations and 27 nonsynonymous substitutions at the 33 disparate sites. In particular, the nonsynonymous substitutions at the putative peptide-binding sites are considered to be associated with immunological specificity of MHC B-LB II molecule in Chinese native chickens. These results can provide a molecular biological basis for the study of disease resistance in chicken breeding.

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

    PubMed

    Kumar, Pradeep; Yadav, Upendra; Rai, Vandana

    2015-12-01

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

  17. Genetic polymorphisms in catalase and CYP1B1 determine DNA adduct formation by benzo(a)pyrene ex vivo.

    PubMed

    Schults, Marten A; Chiu, Roland K; Nagle, Peter W; Wilms, Lonneke C; Kleinjans, Jos C; van Schooten, Frederik J; Godschalk, Roger W

    2013-03-01

    Genetic polymorphisms can partially explain the large inter-individual variation in DNA adduct levels following exposure to polycyclic aromatic hydrocarbons. Effects of genetic polymorphisms on DNA adduct formation are difficult to assess in human studies because exposure misclassification attenuates underlying relationships. Conversely, ex vivo studies offer the advantage of controlled exposure settings, allowing the possibility to better elucidate genotype-phenotype relationships and gene-gene interactions. Therefore, we exposed lymphocytes of 168 non-smoking volunteers ex vivo to the environmental pollutant benzo(a)pyrene (BaP) and BaP-related DNA adducts were quantified. Thirty-four genetic polymorphisms were assessed in genes involved in carcinogen metabolism, oxidative stress and DNA repair. Polymorphisms in catalase (CAT, rs1001179) and cytochrome P450 1B1 (CYP1B1, rs1800440) were significantly associated with DNA adduct levels, especially when combined. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) analysis in a subset of 30 subjects revealed that expression of catalase correlated strongly with expression of CYP1B1 (R = 0.92, P < 0.001). To further investigate the mechanism by which catalase influences CYP1B1 and how they simultaneously affect BaP-related DNA adduct levels, catalase expression was transiently knocked down in the human lung epithelial cell line A549. Although catalase knockdown did not immediately change CYP1B1 gene expression, recovery of catalase expression 8 h after the knockdown coincided with a 2.2-fold increased expression of CYP1B1 (P < 0.05). We conclude that the genetic polymorphism in the promoter region of CAT may determine the amount and activity of catalase, which may subsequently regulate the expression of CYP1B1. As a result, both genetic polymorphisms modulate DNA adduct levels in lymphocytes by BaP ex vivo.

  18. 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.

  19. Genetic diversity in somatic mutants of grape (Vitis vinifera) cultivar Italia based on random amplified polymorphic DNA.

    PubMed

    Maia, S H Z; Mangolin, C A; Collet, S A O; Machado, M F P S

    2009-01-13

    Random amplified polymorphic DNA (RAPD) markers were used to detect polymorphism and to examine relationships among four table grape clones from northwestern Paraná, in southern Brazil. The 10 primers used for RAPD fingerprints generated 126 reproducible fragments, of which 63, 68, 76, and 72 were polymorphic in cultivars Italia, Rubi, Benitaka, and Brasil, respectively. Among the primers, OPP-08 generated the highest number of fragments, whereas OPE-15 was the most efficient for discriminating polymorphic fragments. The distribution of the clones by cluster analysis indicated that there were no differences in RAPD markers between the colored mutant and the original clone (cultivar Italia), supporting the hypothesis that the non-colored and the colored mutant are the same cultivar. However, we found high levels of polymorphism within and between the cultivars Italia, Rubi, Benitaka, and Brasil (65.1%), contrary to a previous hypothesis that the four clones are genetically uniform. This confirmed our expectation of genetic variation among the clones and within each clone. We conclude that the primers are useful for analyzing the development of the genetic diversity within each of these clones.

  20. 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

  1. 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

  2. Dopamine D1 receptor (DRD1) genetic polymorphism: pleiotropic effects on heritable renal traits

    PubMed Central

    Fung, Maple M.; Rana, Brinda K.; Tang, Chih-Min; Shiina, Tetsuo; Nievergelt, Caroline M.; Rao, Fangwen; Salem, Rany M.; Waalen, Jill; Ziegler, Michael G.; Insel, Paul A.; O'Connor, Daniel T.

    2009-01-01

    Because dopamine D1 receptors (DRD1) influence renal sodium transport and vascular hemodynamics, we examined whether genetic polymorphisms play a role in renal function. We conducted polymorphism discovery across the DRD1 open reading frame and its 5′-UTR and then performed association studies with estimated glomerular filtration rate (eGFR), plasma creatinine (pCr), and fractional excretion of uric acid (FeUA). We used a twin/family group of 428 subjects from 195 families and a replication cohort of 677 patients from the Kaiser health-care organization sampled from the lower percentiles of diastolic blood pressures. Although the coding region lacked common non-synonymous variants, we identified two polymorphisms in the DRD1 5′-UTR (G-94A, A-48G) that occurred with frequencies of 15 and 30%, respectively. In the twin/family study, renal traits were highly heritable, such that DRD1 G-94A significantly associated with eGFR, pCr, and FeUA. Homozygotes for the G-94A minor allele (A/A) exhibited lower eGFR, higher pCr, and lower FeUA. No effects were noted for DRD1 A-48G. Patients in the Kaiser group had similar effects of G-94A on eGFR and pCr. Kidney cells transfected with the -94A variant but not the wild type vectors had increased receptor density. Because the -94A allele is common and may reduce glomerular capillary hydrostatic pressure, G-94A profiling may aid in predicting survival of renal function in patients with progressive renal disease. PMID:19675531

  3. 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

  4. An Overview of Genetic Polymorphisms and Pancreatic Cancer Risk in Molecular Epidemiologic Studies

    PubMed Central

    Lin, Yingsong; Yagyu, Kiyoko; Egawa, Naoto; Ueno, Makoto; Mori, Mitsuru; Nakao, Haruhisa; Ishii, Hiroshi; Nakamura, Kozue; Wakai, Kenji; Hosono, Satoyo; Tamakoshi, Akiko; Kikuchi, Shogo

    2011-01-01

    Background Although pancreatic cancer has been extensively studied, few risk factors have been identified, and no validated biomarkers or screening tools exist for early detection in asymptomatic individuals. We present a broad overview of molecular epidemiologic studies that have addressed the relationship between pancreatic cancer risk and genetic polymorphisms in several candidate genes and suggest avenues for future research. Methods A comprehensive literature search was performed using the PubMed database. Results Overall, individual polymorphisms did not seem to confer great susceptibility to pancreatic cancer; however, interactions of polymorphisms in carcinogen-metabolizing genes, DNA repair genes, and folate-metabolizing genes with smoking, diet, and obesity were shown in some studies. The major problem with these studies is that, due to small sample sizes, they lack sufficient statistical power to explore gene–gene or gene–environment interactions. Another important challenge is that the measurement of environmental influence needs to be improved to better define gene–environment interaction. It is noteworthy that 2 recent genome-wide association studies of pancreatic cancer have reported that variants in ABO blood type and in 3 other chromosomal regions are associated with risk for this cancer, thus providing new insight into pancreatic cancer etiology. Conclusions As is the case in other complex diseases, common, low-risk variants in different genes may act collectively to confer susceptibility to pancreatic cancer in individuals with repeated environmental exposures, such as smoking and red meat intake. Clarification of gene–gene and gene–environmental interaction is therefore indispensable for future studies. To address these issues, a rigorously designed molecular epidemiologic study with a large sample is desirable. PMID:21071884

  5. [Genetic polymorphism of steroidogenic enzymes and steroid receptor level in tumors of the reproductive system].

    PubMed

    Berstein, L M; Zimarina, T S; Tsyrlina, E V; Kovalevskiĭ, A Iu; Imianitov, E N

    2004-01-01

    The strategy of therapy and prognosis of reproductive system neoplasia generally depend on the steroid receptor status of tumor. The causes of formation of steroid receptor-free tumors are to be investigated. The genetic polymorphism of CYP19 (aromatase), CYP17 (17-hydroxylase; 17,20-lyase), CYP1B1 (4-estrogen hydroxylase) and COMT (catechol-O-methyl transferase) was studied in a total of 254 patients with breast and endometrial cancer, with particular reference to the association of certain polymorphisms and receptor status of tumor. It was found that the lack of estrogen receptor (ER) in breast tumor was due to a deficit in the A3A6 allele (p(0.01), while the absence of progesterone receptors was associated with a lower incidence of the A1A1 and A1A2 variants (p = 0.022) of tetranucleotide repeats in the CYP19 gene. In the same patients, receptor-negative tumors occurred more often (p = 0.032) than in combinations of higher level of 4-hydroxylase estradiol of S-allele in position 48 (Gly/Arg) of the CYP1B1 gene. Moreover, endometrial carcinoma patients tended to reveal (p = 0.058) an increased ratio of A6A7-CYP19 to allele A1-containing variant. No other distinctions between R(+) and R(-) tumors were identified. It is suggested that peculiar polymorphisms of steroidogenic enzymes may moderately influence the genesis of R(-) neoplasms which may be associated with either the rate of estrogen biosynthesis or, as in the case of CYP1B1, with formation of genotoxic derivatives of estrogens. The latter point is to be investigated further.

  6. Genetic correlates of behavioral endophenotypes in Alzheimer disease: role of COMT, 5-HTTLPR and APOE polymorphisms.

    PubMed

    Borroni, B; Grassi, M; Agosti, C; Costanzi, C; Archetti, S; Franzoni, S; Caltagirone, C; Di Luca, M; Caimi, L; Padovani, A

    2006-11-01

    Several studies have been conducted to understand the genetic correlates of Alzheimer disease (AD)-related behavioral and psychological symptoms in dementia (BPSD). However, given that BPSD rarely occur in isolation, it has been suggested that targeting BPSD individually is too narrow of an approach if one wants to accurately define all the associated risk factors. To date, we know of no work on genetic polymorphisms related to behavioral endophenotypes in AD. The present study sought to evaluate the relationship between such behavioral endophenotypes in AD and genetic variations in dopamine- or serotonin-related genes, such as catechol-O-methyltransferase (COMT) or 5-HTT gene-linked promoter region (5-HTTLPR), and apolipoprotein E (APOE). Among 232 AD patients who underwent clinical and neuropsychological examination, a behavioral and psychiatric evaluation, and genotyping at COMT, 5-HTTPLR, and APOE; 66.4% showed more than one behavioral symptom. By Principal Component Analysis of Neuropsychiatric Inventory (NPI) symptoms four endophenotypes were identified, these were termed "psychosis", "moods", "apathy", and "frontal". Modeling NPI symptom-endophenotype-genotype relationships, and taking into account possible confounds (i.e. demographic characteristics, comorbidities, concomitant pharmacological treatments, and disease severity) by latent variable models, COMT and 5-HTTLPR genetic variations correlated with "frontal" and "psychosis" endophenotypes. APOE genotype did not correlate with any endophenotype. These findings suggest that the possibility of identifying distinct phenotypes on a genetic basis among AD patients exists, and suggest that clustering of BPSD into endophenotypes might provide a new strategy for guiding future research on this issue.

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

    PubMed

    Moravčíková, Nina; Trakovická, Anna; Navrátilová, Alica

    2013-01-01

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

  8. Genetic change in the polynesian population of Easter Island: evidence from Alu insertion polymorphisms.

    PubMed

    González-Pérez, E; Esteban, E; Via, M; García-Moro, C; Hernández, M; Moral, P

    2006-11-01

    The origin of Pacific islanders is still an open issue in human population genetics. To address this topic we analyzed a set of 18 Alu insertion polymorphisms in a total of 176 chromosomes from native Easter Island inhabitants (Rapanui). Available genealogical records allowed us to subdivide the total island sample into two groups, representative of the native population living in the island around 1900, and another formed by individuals with some ancestors of non-Rapanui origin. Significant genetic differentiation was found between these groups, allowing us to make some biodemographic and historical inferences about the origin and evolution of this geographically isolated island population. Our data are consistent with equivalent and recent contributions from Amerindian and European migrants to the 1900s Rapanui population, with an accelerated increase in the European gene flow during the 20(th) century, especially since the 1960s. Comparative analysis of our results with other available Alu variation data on neighbouring populations supports the "Voyaging Corridor" model of Polynesian human settlement, which indicates that pre-Polynesians are mainly derived from Southeast Asian and Wallacean populations rather than from Taiwan or the Philippines. This study underlines the importance of sampling and taking into account historical information in genetic studies to unravel the recent evolution of human populations.

  9. Genetic polymorphisms and their association with brain and behavioural measures in heterogeneous stock mice

    PubMed Central

    Janecka, Magdalena; Marzi, Sarah J.; Parsons, Michael J.; Liu, Lin; Paya-Cano, Jose L.; Smith, Rebecca G.; Fernandes, Cathy; Schalkwyk, Leonard C.

    2017-01-01

    Although the search for quantitative trait loci for behaviour remains a considerable challenge, the complicated genetic architecture of quantitative traits is beginning to be understood. The current project utilised heterogeneous stock (HS) male mice (n = 580) to investigate the genetic basis for brain weights, activity, anxiety and cognitive phenotypes. We identified 126 single nucleotide polymorphisms (SNPs) in genes involved in regulation of neurotransmitter systems, nerve growth/death and gene expression, and subsequently investigated their associations with changes in behaviour and/or brain weights in our sample. We found significant associations between four SNP-phenotype pairs, after controlling for multiple testing. Specificity protein 2 (Sp2, rs3708840), tryptophan hydroxylase 1 (Tph1, rs262731280) and serotonin receptor 3A (Htr3a, rs50670893) were associated with activity/anxiety behaviours, and microtubule-associated protein 2 (Map2, rs13475902) was associated with cognitive performance. All these genes except for Tph1 were expressed in the brain above the array median, and remained significantly associated with relevant behaviours after controlling for the family structure. Additionally, we found evidence for a correlation between Htr3a expression and activity. We discuss our findings in the light of the advantages and limitations of currently available mouse genetic tools, suggesting further directions for association studies in rodents. PMID:28145470

  10. Applications of single-strand conformation polymorphism (SSCP) to taxonomy, diagnosis, population genetics and molecular evolution of parasitic nematodes.

    PubMed

    Gasser, R B; Chilton, N B

    2001-11-22

    The analysis of genetic variation in parasitic nematodes has important implications for studying aspects of taxonomy, diagnosis, population genetics, drug resistance and molecular evolution. This article highlights some applications of PCR-based single-strand conformation polymorphism (SSCP) for the analysis of sequence variation in individual parasites (and their populations) to address some of these areas. It also describes the principles and advantages of SSCP, and provides some examples for future applications in parasitology.

  11. 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...

  12. 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...

  13. Evaluation of DNMT3A genetic polymorphisms as outcome predictors in AML patients

    PubMed Central

    Yuan, Xiao-Qing; Zhang, Dao-Yu; Yan, Han; Yang, Yong-Long; Zhu, Ke-Wei; Chen, Yan-Hong; Li, Xi; Yin, Ji-Ye; Li, Xiao-Lin; Zeng, Hui; Chen, Xiao-Ping

    2016-01-01

    DNMT3A mutation is known as a recurrent event in acute myelogenous leukemia (AML) patients. However, association between DNMT3A genetic polymorphisms and AML patients' outcomes is unknown. DNMT3A 11 SNPs (rs11695471, rs2289195, rs734693, rs2276598, rs1465825, rs7590760, rs13401241, rs7581217, rs749131, rs41284843 and rs7560488) were genotyped in 344 diagnostic non-FAB-M3 AML patients from southern China. Patients underwent combined chemotherapy with cytarabine and anthracyclines. DNMT3A mRNA expression was analyzed in PBMCs from randomly selected AML patients. Multivariate analysis and combined genotype analysis showed that rs2276598 was associated with increased while rs11695471 and rs734693 were associated with decreased chemosensitivity (P<0.05), while rs11695471 (worse for OS), rs2289195 (favorable for OS and DFS) and rs2276598 (favorable for DFS) were significantly associated with disease prognosis (P<0.05). In conclusion, DNMT3A polymorphisms may be potential predictive markers for AML patients' outcomes, which might improve prognostic stratification of AML. PMID:27528035

  14. Evaluation of DNMT3A genetic polymorphisms as outcome predictors in AML patients.

    PubMed

    Yuan, Xiao-Qing; Zhang, Dao-Yu; Yan, Han; Yang, Yong-Long; Zhu, Ke-Wei; Chen, Yan-Hong; Li, Xi; Yin, Ji-Ye; Li, Xiao-Lin; Zeng, Hui; Chen, Xiao-Ping

    2016-09-13

    DNMT3A mutation is known as a recurrent event in acute myelogenous leukemia (AML) patients. However, association between DNMT3A genetic polymorphisms and AML patients' outcomes is unknown. DNMT3A 11 SNPs (rs11695471, rs2289195, rs734693, rs2276598, rs1465825, rs7590760, rs13401241, rs7581217, rs749131, rs41284843 and rs7560488) were genotyped in 344 diagnostic non-FAB-M3 AML patients from southern China. Patients underwent combined chemotherapy with cytarabine and anthracyclines. DNMT3A mRNA expression was analyzed in PBMCs from randomly selected AML patients. Multivariate analysis and combined genotype analysis showed that rs2276598 was associated with increased while rs11695471 and rs734693 were associated with decreased chemosensitivity (P<0.05), while rs11695471 (worse for OS), rs2289195 (favorable for OS and DFS) and rs2276598 (favorable for DFS) were significantly associated with disease prognosis (P<0.05). In conclusion, DNMT3A polymorphisms may be potential predictive markers for AML patients' outcomes, which might improve prognostic stratification of AML.

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

    PubMed

    Manwell, C; Baker, C M

    1975-12-01

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

  16. 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).

  17. Single-strand conformation polymorphism (SSCP) for the analysis of genetic variation.

    PubMed

    Gasser, Robin B; Hu, Min; Chilton, Neil B; Campbell, Bronwyn E; Jex, Aaron J; Otranto, Domenico; Cafarchia, Claudia; Beveridge, Ian; Zhu, Xingquan

    2006-01-01

    The accurate analysis of genetic variation has major implications in many areas of biomedical research, including the identification of infectious agents (such as parasites), the diagnosis of infections, and the detection of unknown or known disease-causing mutations. Mutation scanning methods, including PCR-coupled single-strand conformation polymorphism (SSCP), have significant advantages over many other nucleic acid techniques for the accurate analysis of allelic and mutational sequence variation. The present protocol describes the SSCP method of analysis, including all steps from the small-scale isolation of genomic DNA and PCR amplification of target sequences, through to the gel-based separation of amplicons and scanning for mutations by SSCP (either by the analysis of radiolabeled amplicons in mutation detection enhancement (MDE) gels or by non-isotopic SSCP using precast GMA gels). The subsequent sequence analysis of polymorphic bands isolated from gels is also detailed. The SSCP protocol can readily detect point mutations for amplicon sizes of up to 450-500 bp, and usually takes 1-2 days to carry out. This user-friendly, low-cost, potentially high-throughput platform has demonstrated the utility to study a wide range of pathogens and diseases, and has the potential to be applied to any gene of any organism.

  18. 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.

  19. Genetic polymorphisms in ALDH2 are associated with drug addiction in a Chinese Han population.

    PubMed

    Zhang, Chan; Ding, Heng; Cheng, Yujing; Chen, Wanlu; Li, Qi; Li, Qing; Dai, Run; Luo, Manlin

    2017-01-31

    We investigated the association between single nucleotide polymorphisms (SNPs) in ALDH2, which has been associated with alcohol dependence and several types of diseases, and the risk of drug addiction in a Chinese Han population. In a case-control study that included 692 cases and 700 healthy controls, eight SNPs in ALDH2 were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and gender. We determined that rs671 is significantly associated with a 1.551-fold increased drug addiction risk (95% CI = 1.263-1.903; p < 0.001). In the genetic model analysis, we found that rs671 is associated with an increased risk of drug addiction under additive, dominant and recessive models (p < 0.001), while rs886205, rs441 and rs4646778 displayed a decreased drug addiction risk under additive and recessive model, respectively (p < 0.05). SNP rs671 remained significant after Bonferroni correction (p<0.00125). Additionally, we observed that haplotype "GTCAC" was associated with increased drug addiction risk (OR = 1.668; 95% CI, 1.328-2.094, p < 0.001); in contrast, "ATCGC" was a protective haplotype for drug addiction risk (OR = 0.444; 95% CI, 0.281-0.704, p < 0.001). Our findings showed that ALDH2 polymorphisms are significantly associated with the risk of drug addiction in the Chinese Han population.

  20. Genetic polymorphisms of vascular endothelial growth factor in severe pre-eclampsia.

    PubMed

    Bányász, Ilona; Szabó, Szilvia; Bokodi, Géza; Vannay, Adám; Vásárhelyi, Barna; Szabó, András; Tulassay, Tivadar; Rigó, János

    2006-04-01

    Several lines of evidence support the hypothesis that vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of pre-eclampsia (PE). VEGF is a key component in the regulation of vascular remodelling and the survival of cytotrophoblasts in the placenta. In this case-control study, we aimed to test whether VEGF genetic polymorphisms are associated with the risk of severe PE. We enrolled 84 nulliparous pregnant women with severe PE (PE group). Their VEGF G(+405)C and VEGF C(-2578)A genotypes were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) from venous blood samples and were compared with the corresponding VEGF genotypes of 96 nulliparous patients with uncomplicated pregnancies (control group). Carriers of the VEGF(+405)G allele occurred less frequently in PE than in the control group [P = 0.039; adjusted odds ratio (aOR) = 0.28, range: 0.08-0.93]. Hypertension and proteinuria were diagnosed earlier (by 1.6 weeks and 1.9 weeks, respectively) in PE patients with VEGF(-2578)A only after adjustment of this association for risk factors of PE. Our results suggest that carriers of VEGF(+405)G allele have a decreased susceptibility to PE and that the progression of PE may be modified by the presence of VEGF(-2578)A allele. Nevertheless, the clinical significance of these findings remains to be determined.

  1. 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.

  2. [Genetic polymorphisms of STR loci THO1, TPOX, CSF1PO in Guizhou Han population].

    PubMed

    Zhou, Qiang; Wu, Si-Kun; Yu, Fang; He, Rong-Yue

    2004-01-01

    To understand the genetic polymorphism at THO1, TPOX, CSF1PO STR loci for Han population in Guizhou Province, and construct a preliminary database, EDTA-blood specimens were collected from the 110 unrelated individuals in Han population from Guizhou. The DNA samples were extracted with Chelex method and amplified by multiplex polymerase chain reaction. The PAGE was used to type the PCR products. The allele frequencies were compared with other Han populations. The genotype distributions of THO1, TPOX and CSF1PO were in accordance with Hardy-Weinberg equilibrium. The combined PD and PE were 0.9986 and 0.832 respectively. All of the three loci in this study provide useful marker for forensic paternity test and individual identification.

  3. 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.

  4. Antipsychotic drugs and QTc prolongation: the potential role of CYP2D6 genetic polymorphism.

    PubMed

    Dorado, Pedro; Berecz, Roland; Peñas-Lledó, Eva M; Llerena, Adrián

    2007-02-01

    Although the most common, and usually serious, side effects of first-generation (or typical) antipsychotic drugs, such as Parkinsonism, dystonias and tardive dyskinesia, were known from early times, their cardiovascular safety was not properly in the focus of treatment management. The growing evidence of these drug-related cardiac changes and the appearance of potentially fatal dysrhythmias have increased the interest on their safety profile. Thus, the introduction of the new second-generation (atypical) antipsychotic drugs put emphasis on the preregistration evaluation of the potential cardiac side effects and electrocardiogram predictors (QT interval lengthening). In spite of this, these drugs do not appear to be exempt from these potential risks. The present review summarizes up-to-date knowledge about the cardiac safety of antipsychotic drugs, and analyses the role of drug metabolic processes (CYP2D6 genetic polymorphism) in the complex pathophysiology of the phenomenon. In addition, some recommendations are formulated.

  5. Possible genetic basis of pederin polymorphism in rove beetles (Paederus riparius).

    PubMed

    Kellner, R L

    2000-01-01

    In Paederus riparius, (+) females able to biosynthesize the unique hemolymph toxin pederin and (-) females lacking this ability co-occur in natural populations. Larvae descended from both types of females were reared in the laboratory and the imagoes were crossed in order to get information about a possible genetic basis of this polymorphism. The daughters of (+) mothers become (+) females or (-) females, while the progeny of (-) mothers comprises only (-) females. This suggests a matrilineal trait because pederin biosynthesis cannot be inherited from the father. The rather stable proportion of nearly 90% (+) females in collected females is not maintained, however, when the beetles are reared in the laboratory. This observation is discussed with regard to artificial rearing conditions, where individuals are kept separate and cannot prey on conspecifics.

  6. [Genetic polymorphism of clones and their seed progeny in the scotch pine clone plantation].

    PubMed

    Korshikov, I I; Demkovich, A E

    2010-01-01

    Genetic variation at 12 allozyme loci (10 of them being polymorphic ones) has been studied in the archive-clone plantation of 23 Pinus sylvestris plus-trees and their seed progeny in the south-east of Ukraine. More than a half of clones had 4-8 heterozygous loci, whereas their seed progeny was marked by a lower variation than maternal trees. Seed progeny was obtained at a high outcrossing rate (t(m) = 95%). The clone progeny was characterized by a high percentage of abnormal allele segregation in megagametophytes. There was also a high frequency of significant deviation in distribution of seed embryo genotypes from the theoretically expected one according to the Hardy-Weinberg law.

  7. Genetic polymorphisms of the CST2 locus coding for cystatin SA.

    PubMed

    Shintani, M; Minaguchi, K; Isemura, S; Saitoh, E; Sanada, K; Semba, T

    1994-07-01

    A new genetic polymorphism of cystatin SA has been identified in human submandibular-sublingual saliva by means of basic gel electrophoresis and immunoblotting with anti-cystatin S. Two proteins, SA1 and SA2, are given by two alleles of CST2, viz., CST2*1 and CST*2. Inheritance is controlled by two codominant alleles at an autosomal locus. This hypothesis is supported by studies of 16 families 32 children. Gene frequencies for CST2*1 and CST2*2 are 0.935 and 0.065, respectively (n = 341). Eighteen amino acids determined among 20 N-terminal residues of cystatin SA2 are identical with the sequence encoded by CST2. Three forms of cystatin S (mono-phosphorylated cystatin S, di-phosphorylated cystatin S, and non-phosphorylated cystatin S) are present in the 341 saliva samples tested.

  8. 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.

  9. Type 2 diabetes mellitus-related genetic polymorphisms in microRNAs and microRNA target sites.

    PubMed

    Gong, Weijing; Xiao, Di; Ming, Guangfeng; Yin, Jiye; Zhou, Honghao; Liu, Zhaoqian

    2014-07-01

    MicroRNAs (miRNAs) are important endogenous regulators in eukaryotic gene expression and a broad range of biological processes. MiRNA-related genetic variations have been proved to be associated with human diseases, such as type 2 diabetes mellitus (T2DM). Polymorphisms in miRNA genes (primary miRNAs, precursor miRNAs, mature miRNAs, and miRNA regulatory regions) may be involved in the development of T2DM by changing the expression and structure of miRNAs and target gene expression. Genetic polymorphisms of the 3'-untranslated region (UTR) in miRNA target genes may destroy putative miRNA binding sites or create new miRNA binding sites, which affects the binding of UTRs with miRNAs, finally resulting in susceptibility to and development of T2DM. Therefore, focusing on studies into genetic polymorphisms in miRNAs or miRNA binding sites will help our understanding of the pathophysiology of T2DM development and lead to better health management. Herein, we review the association of genetic polymorphisms in miRNA and miRNA targets genes with T2DM development.

  10. 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 ...

  11. 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

  12. 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 ...

  13. 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

  14. Monitoring low benzene exposure: comparative evaluation of urinary biomarkers, influence of cigarette smoking, and genetic polymorphisms.

    PubMed

    Fustinoni, Silvia; Consonni, Dario; Campo, Laura; Buratti, Marina; Colombi, Antonio; Pesatori, Angela C; Bonzini, Matteo; Bertazzi, Pier A; Foà, Vito; Garte, Seymour; Farmer, Peter B; Levy, Leonard S; Pala, Mauro; Valerio, Federico; Fontana, Vincenzo; Desideri, Arianna; Merlo, Domenico F

    2005-09-01

    Benzene is a human carcinogen and an ubiquitous environmental pollutant. Identification of specific and sensitive biological markers is critical for the definition of exposure to low benzene level and the evaluation of the health risk posed by this exposure. This investigation compared urinary trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid, and benzene (U-benzene) as biomarkers to assess benzene exposure and evaluated the influence of smoking and the genetic polymorphisms CYP2E1 (RsaI and DraI) and NADPH quinone oxidoreductase-1 on these indices. Gas station attendants, urban policemen, bus drivers, and two groups of controls were studied (415 subjects). Median benzene exposure was 61, 22, 21, 9 and 6 microg/m(3), respectively, with higher levels in workers than in controls. U-benzene, but not t,t-MA and S-phenylmercapturic acid, showed an exposure-related increase. All the biomarkers were strongly influenced by cigarette smoking, with values up to 8-fold higher in smokers compared with nonsmokers. Significant correlations of the biomarkers with each other and with urinary cotinine were found. A possible influence of genetic polymorphism of CYP2E1 (RsaI and/or DraI) on t,t-MA and U-benzene in subjects with a variant allele was found. Multiple linear regression analysis correlated the urinary markers with exposure, smoking status, and CYP2E1 (RsaI; R(2) up to 0.55 for U-benzene). In conclusion, in the range of investigated benzene levels (<478 micro/m(3) or <0.15 ppm), smoking may be regarded as the major source of benzene intake; among the study indices, U-benzene is the marker of choice for biomonitoring low-level occupational and environmental benzene exposure.

  15. Gender-specific association of ADA genetic polymorphism with human longevity.

    PubMed

    Napolioni, Valerio; Lucarini, Nazzareno

    2010-08-01

    Aim of this study was to investigate whether the polymorphic ADA (Adenosine Deaminase, EC 3.5.4.4) gene, which determines the cellular level of adenosine and plays a crucial role in the regulation of the immune system and in the control of metabolic rates, is involved in longevity. 884 unrelated healthy individuals (age range 10-106 years, 400 males and 484 females) from central Italy were studied. ADA genotyping was performed by RFLP-PCR. Frequency distributions were compared using the chi-square test and a three-way contingency table analysis by a log linear model was applied to test independence between the variables. We found that ADA influences human life-span in a sex and age specific way. An increased frequency of ADA*2 carriers was found in males aged 80-85, and a decreased frequency in males over 85 (chi(2) = 13.93; df = 3; P = 0.003); significant differences among the age groups was not found in females. A strong interaction among age groups, ADA genotype and sex (G = 15.086; df = 3; P = 0.0017) was found. Males aged 80-85 could be protected from ischemic stroke by higher levels of adenosine (determined by the ADA*2 allele). The decrease of ADA*2 carriers in males over 85 may depend essentially on immunological factors; reduced levels of adenosine protect from asthma and other pulmonary diseases and lead to a reduced activation of inflammatory cells and pro-inflammatory cytokines production. Moreover, the low level of adenosine may potentiate the activity of NK and other cellular effectors against tumor cells. The negligible effect of ADA genetic polymorphism in females suggest a marginal influence of genetic factors in determining longevity in this sex, confirming previous reports.

  16. The role of genetic polymorphisms in metabolism of carcinogenic heterocyclic aromatic amines.

    PubMed

    Turesky, R J

    2004-04-01

    More than twenty heterocyclic aromatic amines (HAAs) have been identified in grilled meats, fish, poultry, and tobacco smoke condensate. HAAs are carcinogens and induce tumors at multiple sites in experimental laboratory animals. Because of the widespread occurrence of HAAs in foods, these chemicals may contribute to the etiology of several common human cancers that are associated with frequent consumption of grilled meats including colon, rectum, prostate, and breast. HAAs require metabolism in order to exert their genotoxic effects. Metabolic activation occurs by N-hydroxylation, a reaction catalyzed by cytochromes p450 (CYP). Some N-hydroxy-HAA metabolites may directly react with DNA, but further metabolism by N-acetyltransferases (NATs) or sulfotransferases (SULTs) may occur to form highly reactive N-acetoxy or N-sulfonyloxy esters that readily react with DNA bases. The N-acetoxy ester of the HAA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is detoxified by glutathione S-transferases (GSTs), which catalyze the reduction of the reactive intermediate back to the parent amine. Some HAAs also undergo detoxification through conjugation reactions with the phase II enzymes such as UDP-glucuronosyltransferases (UGTs) or SULTs to form stable, polar products that are readily eliminated. All of these xenobiotic metabolism enzyme systems (XMEs) display common genetic polymorphisms, which may affect protein expression, protein stability, catalytic activity, and thus, the biological potency of these procarcinogens. In this review, the roles of common genetic polymorphisms of XMEs involved in HAA metabolism and cancer risk are discussed.

  17. Genetic polymorphisms and response to 5-fluorouracil, doxorubicin and cyclophosphamide chemotherapy in breast cancer patients

    PubMed Central

    Tecza, Karolina; Pamula-Pilat, Jolanta; Lanuszewska, Joanna; Grzybowska, Ewa

    2016-01-01

    Clinical resistance to chemotherapy is one of the major problems in breast cancer treatment. In this study we analyzed possible impact of 22 polymorphic variants on the treatment response in 324 breast cancer patients. Selected genes were involved in FAC chemotherapy drugs transport (ABCB1, ABCC2, ABCG2, SLC22A16), metabolism (CYP1B1, CYP2C19, GSTT1, GSTM1, GSTP1, TYMS, MTHFR, DPYD), drug-induced damage repair (ERCC1, ERCC2, XRCC1) and involved in regulation of DNA damage response and cell cycle control (ATM, TP53). Apart from preexisting metastases three polymorphic variants were independent prognostic high risk factors of lack of response to FAC chemotherapy. Our results showed that the response to treatment depended of the variability in genes engaged in drugs’ transport (ABCC2 c.-24C>T, ABCB1 p.Ser893Ala/Thr) and in DNA repair machinery (ERCC2 p.Lys751Gln). Furthermore, the growing number of high-risk genotypes was reflected in gradual increase in risk of the non-responsiveness to treatment- from OR 2.68 for presence of two genotypes to OR 9.93 for carriers of all three negative genotypes in the group of all patients. Similar gene-dosage effect was observed in the subgroup of TNBCs. Also, TFFS significantly shortened with the increasing number of high-risk genotypes, with median of 54.4 months for carriers of one variant, to 51.5 and 34.9 months for the carriers of two and three genotypes, respectively. Our results demonstrate that results of cancer treatment are the effect of many clinical and genetic factors. It seems that multifactorial polymorphic models could be a potentially useful tool in personalization of cancer therapies. The novelty in our model is the over representation of triple negative breast cancer (TNBC) patients among the carriers of all unfavorable polymorphic variants. This finding contributes to the elucidation of the mechanisms of drug resistance in this subgroup of breast cancer patients. PMID:27527855

  18. 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

  19. 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.

  20. 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

  1. Analysis of the genetic polymorphism of Paracoccidioides brasiliensis and Paracoccidioides cerebriformis "Moore" by random amplified polymorphic DNA (RAPD) and 28S ribosomal DNA sequencing--Paracoccidioides cerebriformis revisited.

    PubMed

    Cavalcanti, Sarah Desirée Barbosa; Levi, José Eduardo; Dantas, Kátia Cristina; Martins, José Eduardo Costa

    2005-01-01

    Our purpose was to compare the genetic polymorphism of six samples of P. brasiliensis (113, 339, BAT, T1F1, T3B6, T5LN1), with four samples of P. cerebriformis (735, 741, 750, 361) from the Mycological Laboratory of the Instituto de Medicina Tropical de São Paulo, using Random Amplified Polymorphic DNA Analysis (RAPD). RAPD profiles clearly segregated P. brasiliensis and P. cerebriformis isolates. However, the variation on band patterns among P. cerebriformis isolates was high. Sequencing of the 28S rDNA gene showed nucleotide conservancy among P. cerebriformis isolates, providing basis for taxonomical grouping, and disclosing high divergence to P. brasiliensis supporting that they are in fact two distinct species. Moreover, DNA sequence suggests that P. cerebriformis belongs in fact to the Aspergillus genus.

  2. [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.

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

    PubMed Central

    Kikuchi, Naoki; Nakazato, Koichi

    2015-01-01

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

  4. Interaction between MLL3 genetic polymorphisms, smoking, and alcohol drinking in laryngeal cancer: a case-control study.

    PubMed

    Chen, Dong; Gong, Liang; Jiang, Qichuan; Wang, Xuefeng; Zhang, Bin

    2016-03-01

    A previous study indicated that MLL3 genetic polymorphisms were associated with human cancer. However, whether MLL3 genetic variants are associated with the risk of laryngeal cancer is not clear. This study investigated the association between MLL3 gene polymorphisms and laryngeal cancer in a Chinese population. Four polymorphisms of the MLL3 gene (rs6943984, rs4725443, rs3800836, rs6464211) were genotyped using the TaqMan method in 592 patients with larynx cancer and 602 age- and sex-matched noncancer controls. We found that rs6943984 and rs4725443 of the MLL3 gene were significantly associated with the risk of larynx cancer after Bonferroni correction. The minor allele A for rs6943984 was associated with increased larynx cancer risk (P < 0.001, OR = 1.960, 95% CI = 1.587-2.420). C allele frequency (0.151) for rs4725443 was significantly higher in the case group than the control group (0.072, P < 0.001). Haplotype analyses showed that haplotypes A-T-A-C and G-T-G-C increased the risk of laryngeal cancer (OR = 2.406, 95% CI: 1.820-3.180, P < 0.001; OR = 1.399, 95% CI: 1.180-1.659, respectively), and haplotypes G-T-A-C and G-T-G-T significantly reduced the risk of laryngeal cancer (OR = 0.332, 95% CI: 0.271-0.408, P < 0.001; OR = 0.742, 95% CI: 0.607-0.908, respectively). We also found that MLL3 rs6943984 and rs4725443 polymorphisms had synergistic effects with smoking or alcohol drinking for the risk of laryngeal cancer. This study indicated that MLL3 genetic polymorphisms and haplotypes were associated with larynx cancer in a Chinese population. There was a mutually synergistic effect between smoking, alcohol drinking, and MLL3 gene polymorphisms for laryngeal cancer.

  5. 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.

  6. 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

  7. 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.

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

    PubMed Central

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

    2013-01-01

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

  9. 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

    2016-03-26

    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.

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

    PubMed

    Fornal, Agnieszka; Radko, Anna; Piestrzyńska-Kajtoch, Agata

    2013-01-01

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

  11. Structuring the genetic heterogeneity of the Basque population: a view from classical polymorphisms.

    PubMed

    Manzano, C; de, la Rúa C; Iriondo, M; Mazón, L I; Vicario, A; Aguirre, A

    2002-02-01

    In this study we analyze 18 classical polymorphisms (ABO, Rh, MNSs, Lewis, P, Duffy, Kell, ADA, ESD, PGM1, PGD, AK1, ACP1, GLO1, HP, GC, TF, and PI) in over 2000 autochthonous individuals from 14 natural districts in three provinces of the Basque Country (Alava, Guipuzcoa, and Biscay). Heterogeneity analysis via the chi2 test and a calculation of F(ST) indicate that there is significant genetic heterogeneity between the Basque districts. The R matrix informs us that this heterogeneity is not significantly concentrated in a single district or in the districts of a single province, but is rather distributed among several districts belonging to the three provinces analyzed. We undertake to assess the influence of various historical, geographical, and cultural factors on the genetic structure of the Basque population. Analysis suggests that allele distribution is geographically patterned in the Basque Country. The gradient distributions observed in the case of some alleles (ABO*O, RH*cDE, RH*cde, MNS*MS, and ACP1*C) on the basis of Moran's autocorrelation coefficient I, along with the influence of the two main travel routes through the Basque Country (western route through Bilbao and eastern route through Vitoria), suggest that the gene flow tends toward the coast. As regards other factors considered (administrative division, repopulation processes, linguistic heterogeneity, and north vs. south cultural heterogeneity), we detected only a certain influence exerted by an old tribal differentiation (2000 B.P.), which would diminish with the passage of time.

  12. 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.

  13. Prostate pathology of genetically engineered mice: definitions and classification. The consensus report from the Bar Harbor meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee.

    PubMed

    Shappell, Scott B; Thomas, George V; Roberts, Richard L; Herbert, Ron; Ittmann, Michael M; Rubin, Mark A; Humphrey, Peter A; Sundberg, John P; Rozengurt, Nora; Barrios, Roberto; Ward, Jerrold M; Cardiff, Robert D

    2004-03-15

    The Pathological Classification of Prostate Lesions in Genetically Engineered Mice (GEM) is the result of a directive from the National Cancer Institute Mouse Models of Human Cancer Consortium Prostate Steering Committee to provide a hierarchical taxonomy of disorders of the mouse prostate to facilitate classification of existing and newly created mouse models and the translation to human prostate pathology. The proposed Bar Harbor Classification system is the culmination of three meetings and workshops attended by various members of the Prostate Pathology Committee of the Mouse Models of Human Cancer Consortium. A 2-day Pathology Workshop was held at The Jackson Laboratory in Bar Harbor, Maine, in October 2001, in which study sets of 93 slides from 22 GEM models were provided to individual panel members. The comparison of mouse and human prostate anatomy and disease demonstrates significant differences and considerable similarities that bear on the interpretation of the origin and natural history of their diseases. The recommended classification of mouse prostate pathology is hierarchical, and includes developmental, inflammatory, benign proliferative, and neoplastic disorders. Among the neoplastic disorders, preinvasive, microinvasive, and poorly differentiated neoplasms received the most attention. Specific criteria were recommended and will be discussed. Transitions between neoplastic states were of particular concern. Preinvasive neoplasias of the mouse prostate were recognized as focal, atypical, and progressive lesions. These lesions were designated as mouse prostatic intraepithelial neoplasia (mPIN). Some atypical lesions were identified in mouse models without evidence of progression to malignancy. The panel recommended that mPIN lesions not be given histological grades, but that mPIN be further classified as to the absence or presence of documented associated progression to invasive carcinoma. Criteria for recognizing microinvasion, for classification of

  14. Molecular Genetics of Cystinuria: Identification of Four New Mutations and Seven Polymorphisms, and Evidence for Genetic Heterogeneity

    PubMed Central

    Gasparini, Paolo; Calonge, Maria Julia; Bisceglia, Luigi; Purroy, Jesus; Dianzani, Irma; Notarangelo, Angelo; Rousaud, Ferran; Gallucci, Michele; Testar, Xavier; Ponzone, Alberto; Estivill, Xavier; Zorzano, Antonio; Palacin, Manuel; Nunes, Virginia; Zelante, Leopoldo

    1995-01-01

    A cystinuria disease gene (rBAT) has been recently identified, and some mutations causing the disease have been described. The frequency of these mutations has been investigated in a large sample of 51 Italian and Spanish cystinuric patients. In addition, to identify new mutated alleles, genomic DNA has been analyzed by an accurate and sensitive method able to detect nucleotide changes. Because of the lack of information available on the genomic structure of rBAT gene, the study was carried out using the sequence data so far obtained by us. More than 70% of the entire coding sequence and 8 intron-exon boundaries have been analyzed. Four new mutations and seven intragenic polymorphisms have been detected. All mutations so far identified in rBAT belong only to cystinuria type I alleles, accounting for ∼44% of all type I cystinuric chromosomes. Mutation M467T is the most common mutated allele in the Italian and Spanish populations. After analysis of 70% of the rBAT coding region, we have detected normal sequences in cystinuria type II and type III chromosomes. The presence of rBAT mutated alleles only in type I chromosomes of homozygous (type I/I) and heterozygous (type I/III) patients provides evidence for genetic heterogeneity where rBAT would be responsible only for type I cystinuria and suggests a complementation mechanism to explain the intermediate type I/type III phenotype. PMID:7573036

  15. 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.

  16. Short report: Genetic diversity of Thottapalayam virus, a Hantavirus harbored by the Asian house shrew (Suncus murinus) in Nepal.

    PubMed

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

    2011-09-01

    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.

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

    PubMed Central

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

    2016-01-01

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

  18. Genetic Polymorphisms of Catechol-O-Methyltransferase Modify the Neurobehavioral Effects of Mercury in Children

    PubMed Central

    Woods, James S.; Heyer, Nicholas J.; Russo, Joan E.; Martin, Michael D.; Pillai, Pradeep B.; Bammler, Theodor K.; Farin, Federico M.

    2014-01-01

    Mercury (Hg) is neurotoxic and children may be particularly susceptible to this effect. A current major challenge is identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. This study examined the hypothesis that genetic variants of catechol-O-methyltransferase (COMT) that are reported to alter neurobehavioral functions that are also affected by Hg in adults might modify the adverse neurobehavioral effects of Hg exposure in children. Five hundred and seven children, 8–12 yr of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings. Subjects were evaluated at baseline and at seven subsequent annual intervals for neurobehavioral performance and urinary Hg levels. Following the clinical trial, genotyping assays were performed for single-nucleotide polymorphisms (SNPs) of COMT rs4680, rs4633, rs4818, and rs6269 on biological samples provided by 330 of the trial participants. Regression-modeling strategies were employed to evaluate associations between allelic status, Hg exposure, and neurobehavioral test outcomes. Similar analysis was performed using haplotypes of COMT SNPs. Among girls, few interactions for Hg exposure and COMT variants were found. In contrast, among boys, numerous gene–Hg interactions were observed between individual COMT SNPs, as well as with a common COMT haplotype affecting multiple domains of neurobehavioral function. These findings suggest increased susceptibility to the adverse neurobehavioral effects of Hg among children with common genetic variants of COMT, and may have important implications for strategies aimed at protecting children from the potential health risks associated with Hg exposure. PMID:24593143

  19. Genetic variation and RNA binding proteins: tools and techniques to detect functional polymorphisms.

    PubMed

    Soemedi, Rachel; Vega, Hugo; Belmont, Judson M; Ramachandran, Sohini; Fairbrother, William G

    2014-01-01

    At its most fundamental level the goal of genetics is to connect genotype to phenotype. This question is asked at a basic level evaluating the role of genes and pathways in genetic model organism. Increasingly, this question is being asked in the clinic. Genomes of individuals and populations are being sequenced and compared. The challenge often comes at the stage of analysis. The variant positions are analyzed with the hope of understanding human disease. However after a genome or exome has been sequenced, the researcher is often deluged with hundreds of potentially relevant variations. Traditionally, amino-acid changing mutations were considered the tractable class of disease-causing mutations; however, mutations that disrupt noncoding elements are the subject of growing interest. These noncoding changes are a major avenue of disease (e.g., one in three hereditary disease alleles are predicted to affect splicing). Here, we review some current practices of medical genetics, the basic theory behind biochemical binding and functional assays, and then explore technical advances in how variations that alter RNA protein recognition events are detected and studied. These advances are advances in scale-high-throughput implementations of traditional biochemical assays that are feasible to perform in any molecular biology laboratory. This chapter utilizes a case study approach to illustrate some methods for analyzing polymorphisms. The first characterizes a functional intronic SNP that deletes a high affinity PTB site using traditional low-throughput biochemical and functional assays. From here we demonstrate the utility of high-throughput splicing and spliceosome assembly assays for screening large sets of SNPs and disease alleles for allelic differences in gene expression. Finally we perform three pilot drug screens with small molecules (G418, tetracycline, and valproic acid) that illustrate how compounds that rescue specific instances of differential pre-mRNA processing

  20. 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.

  1. Genetic Effects of FTO and MC4R Polymorphisms on Body Mass in Constitutional Types.

    PubMed

    Cha, Seongwon; Koo, Imhoi; Park, Byung L; Jeong, Sangkyun; Choi, Sun M; Kim, Kil S; Shin, Hyoung D; Kim, Jong Y

    2011-01-01

    Sasang constitutional medicine (SCM), a Korean tailored medicine, categorizes human beings into four types through states of physiological imbalances and responsiveness to herbal medicine. One SCM type susceptible to obesity seems sensitive to energy intake due to an imbalance toward preserving energy. Common variants of fat mass and obesity associated (FTO) and melanocortin 4 receptor (MC4R) genes have been associated with increased body mass index (BMI) by affecting energy intake. Here, we statistically examined the association of FTO and MC4R polymorphisms with BMI in two populations with 1370 Koreans before and after SCM typing, and with the lowering of BMI in 538 individuals who underwent a 1-month lifestyle intervention. The increased BMI replicated the association with FTO haplotypes (effect size ≃ 1.1 kg/m(2)) and MC4R variants (effect size ≃ 0.64 kg/m(2)). After the lifestyle intervention, the carriers of the haplotype represented by the minor allele of rs1075440 had a tendency to lose more waist-to-hip ratio (0.76%) than non-carriers. The constitutional discrepancy for the accumulation of body mass by the effects of FTO and/or MC4R variants seemed to reflect the physique differences shown in each group of SCM constitutional types. In conclusion, FTO and MC4R polymorphisms appear to play an important role in weight gain, while only FTO variants play a role in weight loss after lifestyle intervention. Different trends were observed among individuals of SCM types, especially for weight gain. Therefore, classification of individuals based on physiological imbalance would offer a good genetic stratification system in assessing the effects of obesity genes.

  2. 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

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

    PubMed

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

    2014-12-01

    We examined regional changes in brain volume in healthy adults (N=167, age 19-79years at baseline; N=90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the Hc, CbH, In, OF, and PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants modified shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1β C-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFR C677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) 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.

  4. CHRNA3 genetic polymorphism and the risk of lung cancer in the Chinese Han smoking population.

    PubMed

    Zhou, Wenjing; Geng, Tingting; Wang, Huijuan; Xun, Xiaojie; Feng, Tian; Zou, Hui; Kang, Longli; Jin, Tianbo; Chen, Chao

    2015-07-01

    Lung cancer is the leading cause of cancer-related deaths worldwide that result from the combined effected of smoking exposure and genetic susceptibility. CHRNA3, a nicotinic acetylcholine receptor gene, was associated with lung cancer risk. The aim of this study was to identify whether CHRNA3 polymorphisms increase lung cancer risk directly or indirectly through smoking behavior in the Chinese Han individuals. We conducted a case-control study including 228 individuals with lung cancer and 301 healthy individuals. Seventeen known SNPs within CHRNA3 were selected for genotyping. Odds ratios (OR) and 95 % confidence interval (CI) were calculated by unconditional logistic regression with adjustment for gender and age. Two SNPs (rs8042059 and rs7177514) showed a 1.54-fold (p = 0.036; 95 % CI = 1.03-2.32) and 1.52-fold (p = 0.043; 95 % CI = 1.01-2.27) increased risk for lung cancer in smokers, respectively. Rs8042059 also showed a significant association for variant genotypes (CA/AA) compared with the wild-type genotype (CC), with an OR = 1.84 (p = 0.042; 95 % CI, 1.02-3.33) in the dominant model. In addition, the haplotype analysis found that the haplotypes "TCAC" and "CTGT," composed of rs938682, rs12914385, rs11637630, and rs2869546, were associated with a 1.79-fold and 501-fold increased lung cancer risk, respectively. However, the polymorphisms of all SNPs were not significantly different between controls and cases among general or nonsmokers population. Rs8042059 and rs7177514 may increase lung cancer risk indirectly through smoking behavior in the Chinese Han population.

  5. 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

  6. 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.

  7. Effects of ADAMTS14 genetic polymorphism and cigarette smoking on the clinicopathologic development of hepatocellular carcinoma

    PubMed Central

    Chou, Ying-Erh; Wang, Po-Hui; Yeh, Chao-Bin; Yang, Shun-Fa; Lee, Hsiang-Lin; Liu, Yu-Fan

    2017-01-01

    Background ADAMTS14 is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs), which are proteolytic enzymes with a variety of further ancillary domain in the C-terminal region for substrate specificity and enzyme localization via extracellular matrix association. However, whether ADAMTS14 genetic variants play a role in hepatocellular carcinoma (HCC) susceptibility remains unknown. Methodology/Principal findings Four non-synonymous single-nucleotide polymorphisms (nsSNPs) of the ADAMTS14 gene were examined from 680 controls and 340 patients with HCC. Among 141 HCC patients with smoking behaviour, we found significant associations of the rs12774070 (CC+AA vs CC) and rs61573157 (CT+TT vs CC) variants with a clinical stage of HCC (OR: 2.500 and 2.767; 95% CI: 1.148–5.446 and 1.096–6.483; P = 0.019 and 0.026, respectively) and tumour size (OR: 2.387 and 2.659; 95% CI: 1.098–5.188 and 1.055–6.704; P = 0.026 and 0.034, respectively), but not with lymph node metastasis or other clinical statuses. Moreover, an additional integrated in silico analysis proposed that rs12774070 and rs61573157 affected essential post-translation O-glycosylation site within the 3rd thrombospondin type 1 repeat and a novel proline-rich region embedded within the C-terminal extension, respectively. Conclusions Taken together, our results suggest an involvement of ADAMTS14 SNP rs12774070 and rs61573157 in the liver tumorigenesis and implicate the ADAMTS14 gene polymorphism as a predict factor during the progression of HCC. PMID:28231306

  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. 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

  10. [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.

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

    PubMed Central

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

    2015-01-01

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

  12. Genetic Predisposition of Polymorphisms in HMGB1-Related Genes to Breast Cancer Prognosis in Korean Women

    PubMed Central

    Lee, Junsu; Choi, Jaesung; Chung, Seokang; Park, JooYong; Kim, Ji-Eun; Sung, Hyuna; Han, Wonshik; Lee, Jong Won; Park, Sue K.; Kim, Mi Kyung; Ahn, Sei-Hyun; Noh, Dong-Young; Yoo, Keun-Young; Kang, Daehee

    2017-01-01

    Purpose The high mobility group box 1 (HMGB1) protein has roles in apoptosis and immune responses by acting as a ligand for receptor for advanced glycation end products (RAGE), Toll-like receptors (TLRs), and triggering receptor expressed on myeloid cells 1. In particular, HMGB1/RAGE is involved in tumor metastasis by inducing matrix metalloproteinase 2 (MMP2) and MMP9 expression. We investigated the associations between genetic variations in HMGB1-related genes and disease-free survival (DFS) and overall survival (OS) in Korean female breast cancer patients. Methods A total of 2,027 patients in the Seoul Breast Cancer Study were included in the analysis. One hundred sixteen single nucleotide polymorphisms (SNPs) were extracted from eight genes. A multivariate Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) of each SNP. The effects of the SNPs on breast cancer prognosis were assessed at cumulative levels with polygenic risk scores. Results The SNPs significantly associated with DFS were rs243867 (hazard ratio, 1.26; 95% CI, 1.05–1.50) and rs243842 (hazard ratio, 1.24; 95% CI, 1.03–1.50); both SNPs were in MMP2. The SNPs significantly associated with OS were rs243842 in MMP2 (hazard ratio, 1.33; 95% CI 1.03–1.71), rs4145277 in HMGB1 (hazard ratio, 1.29; 95% CI, 1.00–1.66), rs7656411 in TLR2 (hazard ratio, 0.76; 95% CI, 0.60–0.98), and rs7045953 in TLR4 (hazard ratio, 0.50; 95% CI, 0.29–0.84). The polygenic risk score results for the DFS and OS patients showed third tertile hazard ratios of 1.72 (95% CI, 1.27–2.34) and 2.75 (95% CI, 1.79–4.23), respectively, over their first tertile references. Conclusion The results of the present study indicate that genetic polymorphisms in HMGB1-related genes are related to breast cancer prognosis in Korean women. PMID:28382092

  13. Lung Adenocarcinoma of Never Smokers and Smokers Harbor Differential Regions of Genetic Alteration and Exhibit Different Levels of Genomic Instability

    PubMed Central

    Thu, Kelsie L.; Vucic, Emily A.; Chari, Raj; Zhang, Wei; Lockwood, William W.; English, John C.; Fu, Rong; Wang, Pei; Feng, Ziding; MacAulay, Calum E.; Gazdar, Adi F.; Lam, Stephen; Lam, Wan L.

    2012-01-01

    Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS) extend beyond specific gene mutations, such as EGFR, EML4-ALK, and KRAS, some of which have been translated into targeted therapies. However, the molecular alterations identified thus far cannot explain all of the clinical and biological disparities observed in lung tumors of NS and smokers. To this end, we performed an unbiased genome-wide, comparative study to identify novel genomic aberrations that differ between smokers and NS. High resolution whole genome DNA copy number profiling of 69 lung adenocarcinomas from smokers (n = 39) and NS (n = 30) revealed both global and regional disparities in the tumor genomes of these two groups. We found that NS lung tumors had a greater proportion of their genomes altered than those of smokers. Moreover, copy number gains on chromosomes 5q, 7p, and 16p occurred more frequently in NS. We validated our findings in two independently generated public datasets. Our findings provide a novel line of evidence distinguishing genetic differences between smoker and NS lung tumors, namely, that the extent of segmental genomic alterations is greater in NS tumors. Collectively, our findings provide evidence that these lung tumors are globally and genetically different, which implies they are likely driven by distinct molecular mechanisms. PMID:22412972

  14. 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.

  15. 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.

  16. Use of genetic polymorphisms detected by the random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) for differentiation and identification of Aedes aegypti subspecies and populations.

    PubMed

    Ballinger-Crabtree, M E; Black, W C; Miller, B R

    1992-12-01

    Amplification of random regions of genomic DNA using 10-base primers in the random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) was used to differentiate and identify mosquito populations based on genetic variation. Genomic DNA was extracted from individual mosquitoes from 11 geographic populations of Aedes aegypti and amplified in PCR reactions using single primers of arbitrary nucleotide sequence. Discriminant analysis of the population frequencies of RAPD fragments produced using three different primers allowed accurate discrimination between the geographic populations in 89% of individuals and between subspecies (Ae. aegypti aegypti versus Ae. aegypti formosus) in 100% of mosquitoes tested. The genetic relatedness of the populations was estimated using three different statistical methods, and unknown populations were correctly classified in a blind test. These results indicate that the RAPD-PCR technique will be useful in studies of arthropod molecular taxonomy and in epidemiologic studies of the relatedness of geographic populations and vector movement.

  17. Relationship between genetic polymorphisms of DNA ligase 1 and non-small cell lung cancer susceptibility and radiosensitivity.

    PubMed

    Tian, H; He, X; Yin, L; Guo, W J; Xia, Y Y; Jiang, Z X

    2015-06-26

    The aim of this study was to examine the relationship between genetic polymorphisms in DNA ligase 1 (LIG1) and non-small cell lung cancer (NSCLC) susceptibility and radiosensitivity in a Chinese population. This was a case-control study that included 352 NSCLC patients and 448 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was conducted to detect HaeIII polymorphisms in exon 6 of the LIG1 gene in this popula-tion. This information was used to observe the effects of radiation in pa-tients with different genotypes in order to determine the genotypes as-sociated with radiosensitivity. The CC genotype and C allele frequency were significantly higher in the NSCLC group than in the control group (P = 0.012 and P = 0.023, respectively). The relative risk of experienc-ing NSCLC was 2.55 [95% confidence interval (CI), 1.12-3.98] for CC homozygous patients and 0.87 (95%CI, 0.46-1.88) for AA homozygous patients. Analysis of LIG1 genetic polymorphisms and radiosensitiv-ity of NSCLC patients showed that AA homozygous patients were sig-nificantly more radiosensitive than the control group (AA vs AC, P = 0.014; AA vs CC, P < 0.001; AC vs CC, P = 0.023). Therefore, the LIG1 CC genotype was associated with susceptibility to NSCLC, and the AA genotype demonstrated increased radiosensitivity compared to the AC and CC genotypes.

  18. 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

  19. 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

  20. Genetic polymorphisms in patients with endometriosis: an analytical study in Goiânia (Central West of Brazil).

    PubMed

    Silva, K S F; Moura, K K V O

    2016-05-25

    In healthy women, intra- and extracellular controls prevent the attachment and proliferation of ectopic endometrial cells. During endometriosis, abnormalities in these control mechanisms permit the survival of endometrial cells, their subsequent attachment to the peritoneal cavity, and disease progression. These abnormal cells cause invasion of tissues and induce an inflammatory response. Several genetic, immunological, and environmental factors contribute to this complex process. In this study we examined 6 polymorphisms for 6 different genes (p53; estrogen receptor β; progesterone receptor; GSTM1; GSTT1; CYP1A1). We obtained polymorphic genotype frequencies of all genes for 50 patients and analyzed them using the Fisher exact test or G test. Initially, we analyzed the genes in groups of 2, followed by 3. We found a significant association between polymorphisms in 6 pairs of genes (p53-ERβshowed 5.9-times higher frequency in the experimental group, p53-GSTM1 showed 2.39 times higher, 65.5% patients showed p53-CYP1A1 polymorphism, ERβ-PROGINS showed 3.0-times higher frequency, while 31.25% patients showed GSTM1- PROGINS and GSTT1-CYP1A1 polymorphism). Positive results were found in 15 situations when genes were analyzed in groups of 3; the most significant result corresponded to polymorphisms of p53, ERβand GSTM1 seen in 20%; PROGINS, ERβand GSTM1 in 18%; and p53, ERβand PROGINS in 12% patients. The results indicate that the presence of polymorphisms in more than one endometriosis-related gene is associated with onset of disease and progression. Future studies should focus on these genes to understand their inter-relationships and explore the possibility of developing new diagnostic techniques based on molecular markers.

  1. 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.

  2. 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

  3. 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

  4. Genetic polymorphisms (rs10636 and rs28366003) in metallothionein 2A increase breast cancer risk in Chinese Han population

    PubMed Central

    Wang, Xi-Jing; Kang, Hua-Feng; Jin, Tian-Bo; Zhang, Shu-Qun; Guan, Hai-Tao; Yang, Peng-Tao; Liu, Kang; Liu, Xing-Han; Xu, Peng; Zheng, Yi; Dai, Zhi-Jun

    2017-01-01

    Genetic polymorphisms of MT2A are frequently observed in many different cancers. We performed this case-control study, including 459 breast cancer (BC) patients and 549 healthy controls from Northwest China, to evaluate the associations between two common MT2A polymorphisms (rs10636 and rs28366003) and BC risk. The MT2A polymorphisms were genotyped via Sequenom MassARRAY. The individuals with the rs28366003 A/G, A/G-G/G genotypes underwent a higher risk of BC (P<0.0001). And, the minor allele G of rs28366003 was related to an increased BC risk (P<0.0001). We also found a significantly increased BC risk with rs10636 polymorphism among homozygote and recessive models (P<0.05). Further subgroup analysis by clinical characteristics of BC patients showed that Scarff, Bloom and Richardson tumor grade (SBR) 1-2 have a higher expression of the minor allele of these two MT2A loci than SBR 3. Our results indicated that the rs10636 and rs28366003 polymorphisms in MT2A increased BC risk in Northwest Chinese Han population.   PMID:28228606

  5. CYP1A1 and CYP1B1 genetic polymorphisms and uterine leiomyoma risk in Chinese women

    PubMed Central

    Ye, Yi; Cheng, Xiao; Luo, Hai-Bo; Liu, Li; Li, Ying-Bi

    2008-01-01

    Purpose The aim of the study was to evaluate the association of CYP1A1 and CYP1B1 polymorphisms with uterine leiomyoma in Chinese women. Methods We investigated 100 women with clinically diagnosed uterine leiomyoma and 110 healthy normal subjects from Chinese women. The genetic distribution of two CYP1A1 polymorphisms at MspI, Ile462Val and four CYP1B1 polymorphisms at Arg48Gly, Ala119Ser, Leu432Val, Asp449Asp were analyzed by polymerase chain reaction–restriction fragment length polymorphism and DNA sequencing method. Results All the SNPs showed polymorphisms in Chinese women. The genotype A/G and the allele G on Ile462Val was significantly different between uterine leiomyoma patients and controls (P < 0.05). Conclusion These results suggest that the genotype of CYP1A1 Ile462Val was associated with the increased risk of uterine leiomyomas in Chinese women. PMID:18763031

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

    PubMed Central

    Jiang, Bei-ge; Yang, Yuan; Liu, Hui; Gu, Fang-ming; Yang, Yun; Zhao, Lin-Hao; Yuan, Sheng-xian; Wang, Ruo-yu; Zhang, Jin; Zhou, Wei-ping

    2015-01-01

    Abstract Previous studies showed that suppressor of cytokine signaling 3 (SOCS3) protein is associated with incidence and progression of hepatocellular carcinoma (HCC); however, the association between the genetic polymorphism of SOCS3 gene and HCC remains unknown. A total of 254 HCC patients and 354 healthy controls were enrolled. All HCC patients underwent partial hepatectomy as initial treatment and were followed. Three SOCS3 gene polymorphisms, namely, rs4969170 A>G, rs8064821 C>T, and rs12953258 C>A were determined. Our data show that the rs4969170 A>G polymorphism dramatically affects the susceptibility to HCC in our cohorts. Logistic regression analyses revealed that the rs4969170 GG is a risk factor for HCC after the adjustment with confounding factors. The rs4969170A>G polymorphism is also associated with the clinical features of HCC patients and predicts the postoperative relapse-free survival and overall survival. The rs4969170GG genotype carrier had a worse prognosis than the rs4969170AG and rs4969170AA carrier. Our findings suggest that the rs4969170A>G polymorphism of SOCS3 gene may be used as a prognostic predictor for HCC patients who underwent surgical treatment. PMID:26447993

  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. Genetic polymorphisms in cytochrome P450s, GSTs, NATs, alcohol consumption and risk of Non-Hodgkin lymphoma

    PubMed Central

    Li, Yonghong; Zheng, Tongzhang; Kilfoy, Briseis A.; Lan, Qing; Zahm, Shelia; Holford, Theodore; Zhao, Ping; Dai, Min; Leaderer, Brian; Rothman, Nat; Zhang, Yawei

    2010-01-01

    The aim of this study was to investigate whether genetic polymorphisms in cytochrome P450s (CYPs), glutathione S-transferases (GSTs) and N-acetyltransferases (NATs) genes modify the relationship between alcohol consumption and risk of non-Hodgkin's Lymphoma (NHL) in a population-based case-control study including 1,115 Connecticut women. Although we did not find strong evidence that the genetic polymorphisms modify the relationship between alcohol consumption and risk of NHL, we identified significant interactions for multiple GSTs and NATs and alcohol intake among persons with DLBCL. Our results confer support investigation of the gene-environment interaction in a larger study population of DLBCL. PMID:20131310

  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

    2012-09-06

    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. 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

  11. Functional characterization of genetic polymorphisms in the H2AFX distal promoter.

    PubMed

    Bretherick, Karla L; Leach, Stephen; Brooks-Wilson, Angela R

    2014-01-01

    Due to the critical role of the H2AX histone variant in double-strand break repair, genetic variants in the H2AX gene, H2AFX, may influence cancer susceptibility. Genetic association studies have correlated H2AFX upstream variants with cancer risk; however it is unclear if any are causal. H2AFX has at least two alternate transcripts that encode the same reading frame; a short 0.6kb transcript that lacks an intron or poly-A tail and is predicted to be highly expressed during the replication stage of the cell cycle, and a long 1.6kb poly-A tailed transcript that is expressed in a replication-independent manner. To examine the functional impact of the rs643788, rs8551, rs7759, and rs2509049 upstream variants, we characterized their influence on gene expression, cell survival after DNA assault, and transcription factor binding. Analysis of allelic imbalance using quantitative sequencing of cDNA from lymphoblast cell lines did not reveal any difference in expression of the 1.6kb polyadenylated transcript between the common H2AFX upstream haplotypes. We did, however, identify a previously unreported 197 base pair intron in the H2AFX 3'untranslated region that appears to be present regardless of haplotype. Assessment of cell survival after irradiation treatment did not show any difference in survival between cell lines of different haplotypes. Gel shift assays revealed that the rs643788 C allele disrupts YY1 transcription factor binding and the rs2509049 C allele binds more strongly to a protein complex than does the rs2509049 T allele. Though we did not identify any differences in expression or survival between haplotypes, differential protein binding at two of the polymorphisms suggests further functional analyses may reveal a role for these variants in influencing gene expression at specific points of the cell cycle or in specific tissues.

  12. Exposure assessment of benzene in Thai workers, DNA-repair capacity and influence of genetic polymorphisms.

    PubMed

    Chanvaivit, Sirirat; Navasumrit, Panida; Hunsonti, Potchanee; Autrup, Herman; Ruchirawat, Mathuros

    2007-01-10

    of deletions in laboratory workers (0.22 per metaphase cell) and gasoline service attendants (0.39 per metaphase cell) were significantly higher than in control workers (0.16 per metaphase cell, p<0.01 and p<0.001, respectively). An increase in radiation-induced dicentrics and deletions indicate a lower DNA-repair capacity in benzene-exposed workers. The influence of genetic polymorphisms on the biomarkers was assessed. Benzene-exposed workers who carried CYP2E1*1/*5 or *5/*5 genotypes excreted slightly higher levels of trans,trans-muconic acid than workers who carried the CYP2E1*1/*1 genotype. In this study, NQO1 and GSTT1 genotypes did not have any effect on the levels of trans,trans-muconic acid. In the case of XRCC1, laboratory workers with 399Arg/Gln or Gln/Gln had a lower DNA-repair capacity--measured as radiation-induced frequency of dicentrics and deletions--than those with the 399Arg/Arg genotype (p<0.01). Our results show that biomarkers of internal dose and early biological effect in people occupationally exposed to benzene are influenced by genetic polymorphisms in susceptibility genes.

  13. 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.

  14. Genetic polymorphisms in very important pharmacogenomic (VIP) variants in the Tibetan population.

    PubMed

    Jin, T B; Xun, X J; Shi, X G; Yuan, D Y; Feng, T; Geng, T T; Kang, L L

    2015-10-16

    Genetic polymorphisms of very important pharmacogenomic (VIP) variants are important for personalized medicine. However, these have not been extensively studied in the Tibetan population. In this study, 82 VIP variants were detected in the Tibetan and Han (HAN) populations from northwestern China. Subsequently, we compared the differences between the Tibetan population and ten populations, including the HAN, Japanese in Tokyo (JPT), Mexican ancestry in Los Angeles (MEX), Toscans in Italy (TSI), African ancestry in Southwest USA (ASW), Luhya in California Webuye, Kenya (LWK), Gujarati Indians in Houston, Texas (GIH), Maasai in Kinyawa, Kenya (MKK), Yoruba in Ibadan, Nigeria (YRI), and Utah residents with Northern and Western European ancestry from the CEPH collection (CEU). Using the χ(2) test, we identified differences in the frequency distribution of 4, 4, 7, 10, 11, 11, 13, 15, 19, and 20 loci in the Tibetan population, compared to the HAN, JPT, MEX, TSI, ASW, LWK, GIH, MKK, YRI, and CEU populations, respectively [P < 0.05/(82*10)]. rs2115819, rs9934438, and rs689466, located in the ALOX5 (arachidonate 5-lipoxygenase), VKORC1 (vitamin K epoxide reductase complex, subunit 1) and PTGS2 (prostaglandin-endoperoxide synthase 2) genes, respectively, in the Tibetan population were different from those in most of the populations. Our results complement the information provided by the database of pharmacogenomics on Tibetan people, and provide an avenue for personalized treatment in the Tibetan population.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. [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.

  1. 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.

  2. Genetic polymorphisms in the catechol estrogen metabolism pathway and breast cancer risk

    PubMed Central

    Reding, Kerryn W.; Weiss, Noel S.; Chen, Chu; Li, Christopher I.; Carlson, Christopher S.; Wilkerson, Hui-Wen; Farin, Federico M.; Thummel, Kenneth E.; Daling, Janet R.; Malone, Kathleen E.

    2009-01-01

    Background This study investigated whether single nucleotide polymorphisms (SNPs) in genes within the catechol estrogen metabolism pathway altered the risk of breast cancer alone or in combination, as well as whether menopausal hormone therapy (HT) modified the effect of these SNPs on breast cancer risk. Methods In a population-based case-control study of breast cancer, 891 cases and 878 controls were genotyped for six functional SNPs in the COMT, CYP1B1, GSTM1, GSTP1, and GSTT1 genes. Results Women homozygous with the T allele in CYP1B1*2 (Ser119; rs1056827) were at 1.69 (95% confidence interval [CI]: 1.17–2.46) times the risk of women homozygous with the G allele; women homozygous with the G allele in GSTP1 (Val105; rs1695) were at 0.73 (95% CI: 0.54–0.99) times the risk of breast cancer compared to women homozygous with the A allele. No other SNPs tested were associated with breast cancer to any appreciable degree. Potential gene-gene and gene-HT interactions were investigated. Conclusion With the exception of GSTP1 and possibly CYP1B1*2, our findings do not provide support for the role of genetic variation in the catechol estrogen metabolism pathway and breast cancer risk in post-menopausal women. PMID:19383894

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

    PubMed Central

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

    1989-01-01

    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. Images Figure 1 PMID:2757028

  4. 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.

  5. TFCP2 Genetic Polymorphism Is Associated with Predisposition to and Transplant Prognosis of Hepatocellular Carcinoma

    PubMed Central

    Liu, Zhikun; Gao, Feng; Shao, Zhou; Xie, Haiyang; Zhou, Lin

    2017-01-01

    TFCP2 is an oncogene and plays crucial roles in the incidence and progression of hepatocellular carcinoma (HCC). However, no reports are available on the impact of TFCP2 genetic polymorphism on the susceptibility to and the transplant prognosis of HCC. Here, we genotyped 7 SNPs of TFCP2 in a case-control study of 119 patients with HCC and 200 patients with chronic liver disease. Of the 7 SNPs in TFCP2, rs7959378 distributed differentially between patients with versus patients without HCC. The patients with the CA (OR = 0.58, 95% CI = 0.35–0.96), the CC (OR = 0.39, 95% CI = 0.20–0.76), and the CA/CC (OR = 0.52, 95% CI = 0.32–0.83) genotypes had significantly decreased risk for HCC compared with those carrying the rs7959378 AA genotype. After adjusting for confounding factors, rs7959378 still conferred significant risk for HCC. Furthermore, the patients who carried rs7959378 AC/CC had a higher overall survival and lower relapse-free survival than those with the rs7959378 AA genotype. Similar results were found in the multivariate analysis adjusted by AFP, tumor size and tumor number, and differentiation. These findings indicate that rs7959378 is associated with the risk of HCC in patient with chronic liver disease and prognosis of HCC patients after liver transplantation. PMID:28348581

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. Aurora kinase-A overexpression in mouse mammary epithelium induces mammary adenocarcinomas harboring genetic alterations shared with human breast cancer.

    PubMed

    Treekitkarnmongkol, Warapen; Katayama, Hiroshi; Kai, Kazuharu; Sasai, Kaori; Jones, Jennifer Carter; Wang, Jing; Shen, Li; Sahin, Aysegul A; Gagea, Mihai; Ueno, Naoto T; Creighton, Chad J; Sen, Subrata

    2016-12-01

    Recent data from The Cancer Genome Atlas analysis have revealed that Aurora kinase A (AURKA) amplification and overexpression characterize a distinct subset of human tumors across multiple cancer types. Although elevated expression of AURKA has been shown to induce oncogenic phenotypes in cells in vitro, findings from transgenic mouse models of Aurora-A overexpression in mammary glands have been distinct depending on the models generated. In the present study, we report that prolonged overexpression of AURKA transgene in mammary epithelium driven by ovine β-lactoglobulin promoter, activated through multiple pregnancy and lactation cycles, results in the development of mammary adenocarcinomas with alterations in cancer-relevant genes and epithelial-to-mesenchymal transition. The tumor incidence was 38.9% (7/18) in Aurora-A transgenic mice at 16 months of age following 4-5 pregnancy cycles. Aurora-A overexpression in the tumor tissues accompanied activation of Akt, elevation of Cyclin D1, Tpx2 and Plk1 along with downregulation of ERα and p53 proteins, albeit at varying levels. Microarray comparative genomic hybridization (CGH) analyses of transgenic mouse mammary adenocarcinomas revealed copy gain of Glp1r and losses of Ercc5, Pten and Tcf7l2 loci. Review of human breast tumor transcriptomic data sets showed association of these genes at varying levels with Aurora-A gain of function alterations. Whole exome sequencing of the mouse tumors also identified gene mutations detected in Aurora-A overexpressing human breast cancers. Our findings demonstrate that prolonged overexpression of Aurora-A can be a driver somatic genetic event in mammary adenocarcinomas associated with deregulated tumor-relevant pathways in the Aurora-A subset of human breast cancer.

  11. Genetic polymorphism in CD14 gene, a co-receptor of TLR4 associated with non-alcoholic fatty liver disease

    PubMed Central

    Kapil, Shweta; Duseja, Ajay; Sharma, Bal Krishan; Singla, Bhupesh; Chakraborti, Anuradha; Das, Ashim; Ray, Pallab; Dhiman, Radha K; Chawla, Yogesh

    2016-01-01

    AIM To evaluate the pathogenic role of toll-like receptor (TLR) gene polymorphisms in patients with non-alcoholic fatty liver disease (NAFLD). METHODS Two hundred and fifty subjects (NAFLD = 200, healthy volunteers = 50) underwent polymerase chain reaction and restriction fragment length polymorphism to assess one polymorphism in the toll-like receptor 2 (TLR2) gene (A753G), two polymorphisms in the TLR4 gene (TLR4 Asp299Gly and Thr399Ile allele), and two polymorphisms in the cluster of differentiation 14 (CD14) (C-159T and C-550T) gene, a co-receptor of TLR4. Association of TLR gene polymorphisms with NAFLD and its severity was evaluated by genetic models of association. RESULTS On both multiplicative and recessive models of gene polymorphism association, there was significant association of CD14 C (-159) T polymorphism with NAFLD; patients with TT genotype had a 2.6 fold increased risk of developing NAFLD in comparison to CC genotype. There was no association of TLR2 Arg753Gln, TLR4 Asp299Gly, Thr399Ile, and CD14 C (-550) T polymorphisms with NAFLD. None of the TLR gene polymorphisms had an association with histological severity of NAFLD. CONCLUSION Patients with CD14 C (-159) T gene polymorphism, a co-receptor of TLR4, have an increased risk of NAFLD development. PMID:27895422

  12. No association of genetic polymorphisms in CYP1B1 with primary open-angle glaucoma: a meta- and gene-based analysis

    PubMed Central

    Dong, Shuqian; Yang, Jingyun; Yu, Weihong; Kota, Pravina; Xia, Xiaobo

    2012-01-01

    Purpose To examine the effects of genetic polymorphisms in cytochrome P450, subfamily 1, polypeptide 1 (C1P1B1) on primary open-angle glaucoma (POAG). Methods A systematic literature search was performed, and random-effects meta-analyses were used to evaluate genetic polymorphisms in CYP1B1 with POAG. A gene-based analysis was conducted to investigate the cumulative effects of genetic polymorphisms in CYP1B1. Results A total of six studies from published papers were included in our analysis. Random-effects meta-analyses failed to detect any significant association of POAG with genetic polymorphisms in CYP1B1, including rs180040, rs1056836, rs10012, rs1056827, rs1056837, and rs2567206. The gene-based analysis indicated that the cumulative effect of genetic polymorphisms in CYP1B1 is not associated with POAG (p>0.50). Conclusions We did not find any evidence of strong association of POAG with CYP1B1 genetic polymorphisms and their cumulative effect. PMID:22509109

  13. 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.

  14. Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene and susceptibility to depression in Asian population: a systematic meta-analysis.

    PubMed

    Rai, V

    2014-01-01

    Genetic association studies on MTHFR C677 T polymorphism and depression have been repeatedly performed over the last two decades and results are generally inconsistent. The aim of the present study was to assess the risk of MTHFR C677T polymorphism for depression in Asian population. The author performed a meta-analysis and pooled data from individual case-control studies that examined the association between C677T polymorphism and depression (meta-analysis: 13 studies, 1,120 cases and 1,688 controls).The pooled Odd Ratios (OR) were estimated by both fixed effects and random effects models. Overall, there was an association between MTHFR C677T polymorphism and increased risk of depression under five genetic models (OR T vs. C=1.44, 95% CI= 1.56-1.78, P=0.001; OR TT vs. CC= 1.78, 95% CI 1.17– 2.69, P=0.006; OR CT vs CC=1.102, 95% CI=0.91-1.32,P=0.31; OR TT vs. CT+CC=1.73, 95% CI= 0.87-3.41, P=0.11; OR TT+CT vs. CC=1.26, 95% CI=0.96-1.64, P=0.08). Sensitivity analysis suggested exclusion of any single study did not alter the overall pooled Ors. In conclusion results of present meta-analysis supports that there is a significant association between MTHFR C677T polymorphism and depression risk, and MTHFR 677T allele contributes to increased risk of depression in Asian individuals.

  15. 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.

  16. Correlation between XRCC1 Arg399Gln genetic polymorphisms and susceptibility to bladder cancer: a meta-analysis

    PubMed Central

    Liu, Nannan; Fei, Xiawei; Shen, Yi; Shi, Weifeng; Ma, Jinhong

    2016-01-01

    The relationship between XRCC1 polymorphisms and bladder cancer has been widely studied. Here, our meta-analysis was conducted to evaluate the correlations between common genetic polymorphisms in XRCC1 and susceptibility to bladder cancer. In order to derive a more precise estimation of the association, 27 clinical case-control studies (which met all the inclusion criteria) were included in this meta-analysis. A total of 8,539 cancer cases and 10,750 controls were involved in this meta-analysis. Overall, no significant association was detected in allelic model (A allele vs T allele odds ratio [OR] =0.87, 95% confidence interval [CI], 0.71–1.06), homozygote comparison (AA vs GG OR =1.12, 95% CI, 0.68–1.85), heterozygote comparison (AT vs TT OR =1.01, 95% CI, 0.81–1.26), dominant model (AA + AG vs GG OR =0.93, 95% CI, 0.85–1.02), and recessive model (AA vs AG + GG OR =1.01, 95% CI, 0.88–1.15), but a moderately significant association was found for AG vs GG (OR =0.241, 95% CI =0.17–0.35). Subgroup analysis based on ethnicity. Ethnicity analysis suggested that genetic polymorphisms in XRCC1 were not correlated with increased bladder cancer risk among Asians (all P>0.05). Therefore, we concluded that XRCC1 genetic polymorphism may not contribute to bladder cancer susceptibility in the present meta-analysis, and further well-designed studies with a large sample size are warranted to validate our conclusion. PMID:26869802

  17. 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.

  18. IL-10 Genetic Polymorphisms Were Associated with Valvular Calcification in Han, Uygur and Kazak Populations in Xinjiang, China

    PubMed Central

    Ma, Yi-Tong; Wulasihan, Muhuyati; Huang, Ying; Adi, Dilare; Yang, Yi-Ning; Ma, Xiang; Li, Xiao-Mei; Xie, Xiang; Huang, Ding; Liu, Fen; Chen, Bang-Dang

    2015-01-01

    Objective Valvular calcification occurs via ongoing endothelial injury associated with inflammation. IL-10 is an anti-inflammatory cytokine and 75% of the variation in IL-10 production is genetically determined. However, the relationship between genetic polymorphisms of IL-10 and valvular calcification has not been studied. The objective of this study was to investigate the association between valvular calcification and IL-10 genetic polymorphisms in the Han, Uygur and Kazak populations in China. Patients and Methods All of the participants were selected from subjects participating in the Cardiovascular Risk Survey (CRS) study. The single nucleotide polymorphisms (SNPs) rs1800871 and rs1800872 of the IL-10 gene were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Three independent case-control studies involving the Han population, the Uygur population and the Kazak population were used in the analysis. Results For the Han and Kazak populations, rs1800871 was found to be associated with valvular calcification in the recessive model, and the difference remained statistically significant following multivariate adjustment (p<0.001, p=0.031, respectively). For the Han, Uygur and Kazak populations, rs1800872 was found to be associated with valvular calcification in the dominant model, and the difference remained statistically significant following multivariate adjustment (p<0.001, p=0.009, and p=0.023,respectively) Conclusion Both rs1800871 and rs1800872 of the IL-10 gene are associated with valvular calcification in the Han and Kazak populations in China. Rs1800872 is also associated with valvular calcification in the Uygur population. PMID:26039365

  19. 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

  20. Genetic Polymorphism of the Serotonin Transporter Gene, SLC6A4 rs16965628, Is Associated with Obsessive Compulsive Disorder.

    PubMed

    Cengiz, Mujgan; Okutan, Saide Nur; Bayoglu, Burcu; Sakalli Kani, Ayse; Bayar, Reha; Kocabasoglu, Nese

    2015-05-01

    Obsessive compulsive disorder (OCD) is a psychiatric disorder characterized by obsessive ideas and compulsive behaviors. Genetic studies have centered on candidate genes involved in OCD etiology related to serotonergic and dopaminergic systems. In this study, the relationship between cathechol-O-methyltransferase (COMT) -287A/G (rs2097063), serotonin transporters 5-HTTLPR I/D, and SLC6A4 rs16965628 polymorphisms in 80 OCD patients and 100 healthy controls was determined. Patients and controls were genotyped for COMT rs2097063 and SLC6A4 rs16965628 polymorphisms by real-time polymerase chain reaction (PCR). The 5-HTTLPR I/D polymorphism was genotyped using PCR and agarose gel electrophoresis. Severity of symptoms was checked with a Yale-Brown Obsession Compulsion Scale (Y-BOCS). When the OCD group and controls were compared, no significant difference was found between COMT -287A/G (rs2097063), 5-HTTLPR I/D polymorphisms, and OCD. However, a significant difference was found between 5-HTT rs16965628 polymorphism and OCD (p=0.025, OR=3.43, 95% CI 1.41-10.35). In addition, the G allele frequency was found to be higher for rs16965628 in the OCD group. No significant difference was observed between COMT -287A/G (rs2097063), SLC6A4 rs16965628, and 5-HTTLPR I/D polymorphisms and Y-BOCS scores (p>0.05). There was also lack of correlation between Yale-Brown scores and gender of OCD patients. On the other hand, combined genotypes of SLC6A4 rs16965628 GG+GC were found to be risk factors for OCD development (p=0.02, OR=3.464; 95% CI 1.214-9.883) in logistic regression analysis adjusted for age and gender. Our findings suggest that subjects carrying the G allele of rs16965628 have genetic susceptibility to OCD. These data are the first to suggest that polymorphism in serotonin transporter (rs16965628) is associated with the development of OCD in the Turkish population.

  1. 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...

  2. 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.

  3. 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

    2016-06-17

    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.

  4. Analysis of genetic diversity of Tunisian pistachio (Pistacia vera L.) using sequence-related amplified polymorphism (SRAP) markers.

    PubMed

    Guenni, K; Aouadi, M; Chatti, K; Salhi-Hannachi, A

    2016-10-17

    Sequence-related amplified polymorphism (SRAP) markers preferentially amplify open reading frames and were used to study the genetic diversity of Tunisian pistachio. In the present study, 43 Pistacia vera accessions were screened using seven SRAP primer pairs. A total of 78 markers was revealed (95.12%) with an average polymorphic information content of 0.850. The results suggest that there is strong genetic differentiation, which characterizes the local resources (GST = 0.307). High gene flow (Nm = 1.127) among groups was explained by the exchange of plant material among regions. Analysis of molecular variance revealed significant differences within groups and showed that 73.88% of the total genetic diversity occurred within groups, whereas the remaining 26.12% occurred among groups. Bayesian clustering and principal component analysis identified three pools, El Guettar, Pollenizers, and the rest of the pistachios belonging to the Gabès, Kasserine, and Sfax localities. Bayesian analysis revealed that El Guettar and male genotypes were assigned with more than 80% probability. The BayeScan method proposed that locus 59 (F13-R9) could be used in the development of sex-linked SCAR markers from SRAP since it is a commonly detected locus in comparisons involving the Pollenizers group. This is the first application of SRAP markers for the assessment of genetic diversity in Tunisian germplasm of P. vera. Such information will be useful to define conservation strategies and improvement programs for this species.

  5. 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.

  6. EST-derived single nucleotide polymorphism markers for assembling genetic and physical maps of the barley genome.

    PubMed

    Kota, R; Varshney, R K; Prasad, M; Zhang, H; Stein, N; Graner, A

    2008-08-01

    In a panel of seven genotypes, 437 expressed sequence tag (EST)-derived DNA fragments were sequenced. Single nucleotide polymorphisms (SNPs) that were polymorphic between the parents of three mapping populations were mapped by heteroduplex analysis and a genome-wide consensus map comprising 216 EST-derived SNPs and 4 InDel (insertion/deletion) markers was constructed. The average frequency of SNPs amounted to 1/130 bp and 1/107.8 bp for a set of randomly selected and a set of mapped ESTs, respectively. The calculated nucleotide diversities (pi) ranged from 0 to 40.0 x 10(-3) (average 3.1 x 10(-3)) and 0.52 x 10(-3) to 39.51 x 10(-3) (average 4.37 x 10(-3)) for random and mapped ESTs, respectively. The polymorphism information content value for mapped SNPs ranged from 0.24 to 0.50 with an average of 0.34. As expected, combination of SNPs present in an amplicon (haplotype) exhibited a higher information content ranging from 0.24 to 0.85 with an average of 0.50. Cleaved amplified polymorphic sequence assays (including InDels) were designed for a total of 87 (39.5%) SNP markers. The high abundance of SNPs in the barley genome provides avenues for the systematic development of saturated genetic maps and their integration with physical maps.

  7. Genetic polymorphisms of the drug-metabolizing enzyme CYP2C19 in the Uyghur population in northwest China.

    PubMed

    Jin, Tianbo; Zhang, Mingxia; Yang, Hua; Geng, Tingting; Zhang, Ning; Feng, Tian; Ma, Yajuan; Yuan, Dongya; Kang, Longli

    2015-11-02

    1. CYP2C19 is a clinically important enzyme and is involved in the metabolism of approximately 10% of drugs used in daily clinical practice. Previous studies mainly focused on Chinese Han populations or other ethnic groups, little is known about Uyghur populations. 2. The present study was designed to determine the genetic basis of CYP2C19 polymorphisms. 3. We used direct sequencing to investigate the promoter, exons and surrounding introns, and 3'-untranslated region of the CYP2C19 gene in 96 unrelated healthy Uyghur individuals. 4. A total of 31 different CYP2C19 polymorphisms were identified in the Uyghur population, three of which were novel, including two nonsynonymous variants (57807A > M, Gln279Pro and 19257G > R, Asp262Asn) and one synonymous variants in exon 5 (19184T > Y, Leu237Leu). In addition, CYP2C19*1, *2 and *3 alleles showed frequencies of 83.34%, 14.06% and 2.08%, respectively. 5. This is the first study that systematically screened the polymorphisms of the whole CYP2C19 gene in Uyghur population. Hence, our results provided important information on CYP2C19 polymorphisms in Uyghur population and could be helpful for future personalized medicine studies in Uyghur population generally.

  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.

  9. Genetic contribution of catechol-O-methyltransferase polymorphism (Val158Met) in children with chronic tension-type headache.

    PubMed

    Fernández-de-las-Peñas, César; Ambite-Quesada, Silvia; Rivas-Martínez, Inés; Ortega-Santiago, Ricardo; de-la-Llave-Rincón, Ana Isabel; Fernández-Mayoralas, Daniel M; Pareja, Juan A

    2011-10-01

    Our aim was to investigate the relationship between Val158Met polymorphisms, headache, and pressure hypersensitivity in children with chronic tension-type headache (CTTH). A case-control study with blinded assessor was conducted. Seventy children with CTTH associated with pericranial tenderness and 70 healthy children participated. After amplifying Val158Met polymorphism by polymerase chain reactions, we assessed genotype frequencies and allele distributions. We classified children according to their Val158Met polymorphism: Val/Val, Val/Met, Met/Met. Pressure pain thresholds (PPT) were bilaterally assessed over the temporalis, upper trapezius, second metacarpal, and tibialis anterior muscles. The distribution of Val158Met genotypes was not significantly different (p = 0.335), between children with CTTH and healthy children, and between boys and girls (p = 0.872). Children with CTTH with the Met/Met genotype showed a longer headache history compared with those with Met/Val (p = 0.001) or Val/Val (p = 0.002) genotype. Children with CTTH with Met/Met genotype showed lower PPT over upper trapezius and temporalis muscles than children with CTTH with Met/Val or Val/Val genotype (p < 0.01). The Val158Met catechol-O-methyltransferase (COMT) polymorphism does not appear to be involved in predisposition to suffer from CTTH in children; nevertheless, this genetic factor may be involved in the phenotypic expression, as pressure hypersensitivity was greater in those CTTH children with the Met/Met genotype.

  10. 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.

  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. Amplified fragment length polymorphism-based genetic relationships among weedy Amaranthus species.

    PubMed

    Wassom, J J; Tranel, P J

    2005-01-01

    Weedy Amaranthus species frequently cause economically significant reductions in crop yields. Accurate identification of Amaranthus species is important for efficient weed control, but Amaranthus species can interbreed, which might cause difficulty when identifying hybrid-derived specimens. To determine which of several economically important weedy Amaranthus species are most genetically similar, and thus most likely to produce viable hybrids, we performed amplified fragment length polymorphism (AFLP)-based unweighted pair group method with arithmetic mean (UPGMA) analysis on 8 of these species, with 141 specimens representing 98 accessions. The analysis grouped the specimens into four principal clusters composed of Palmer amaranth (Amaranthus palmeri S. Wats.) and spiny amaranth (Amaranthus spinosus L.); Powell amaranth (Amaranthus powellii S. Wats.), redroot pigweed (Amaranthus retroflexus L.), and smooth pigweed (Amaranthus hybridus L.); waterhemp (Amaranthus tuberculatus (Moq.) Sauer) and sandhills amaranth (Amaranthus arenicola I.M. Johnst.); and tumble pigweed (Amaranthus albus L.). The cluster analysis provided evidence suggesting hybridization among Powell amaranth, redroot pigweed, and smooth pigweed. Further investigations using molecular analysis of the ribosomal internal transcribed spacer region from atypical plants supported this notion. Three species, Palmer amaranth, sandhills amaranth, and waterhemp, are dioecious; nevertheless, the Palmer amaranth and waterhemp-sandhills amaranth clusters were distinct from each other. The Palmer amaranth-spiny amaranth cluster included a cluster of Palmer amaranth and two clusters of spiny amaranth, a monoecious species. Thus the dioecious species Palmer amaranth and waterhemp may not necessarily hybridize with each other more readily than they would to one or more of the monoecious Amaranthus species.

  13. Cell type specificity and host genetic polymorphisms influence antibody-dependent enhancement of dengue virus infection.

    PubMed

    Boonnak, Kobporn; Dambach, Kaitlyn M; Donofrio, Gina C; Tassaneetrithep, Boonrat; Marovich, Mary A

    2011-02-01

    Antibody-dependent enhancement (ADE) is implicated in severe, usually secondary, dengue virus (DV) infections. Preexisting heterotypic antibodies, via their Fc-gamma receptor (FcγR) interactions, may increase disease severity through enhanced target cell infection. Greater numbers of infected target cells may contribute to higher viremia and excess cytokine levels often observed in severe disease. Monocytes, macrophages, and immature and mature dendritic cells (DC) are considered major cellular targets of DV. Apheresis of multiple donors allowed isolation of autologous primary myeloid target cell types for head-to-head comparison of infection rates, viral output, and cytokine production under direct infection (without antibody) or ADE conditions (with antibody). All studied cell types except immature DC supported ADE. All cells undergoing ADE secreted proinflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNF-α]) at enhancement titers, but distinct cell-type-specific patterns were observed for other relevant proteins (alpha/beta interferon [IFN-α/β] and IL-10). Macrophages produced type I interferons (IFN-α/β) that were modulated by ADE. Mature DC mainly secreted IFN-β. Interestingly, only monocytes secreted IL-10, and only upon antibody-enhanced infection. While ADE infection rates were remarkably consistent in monocytes (10 to 15%) across donors, IL-10 protein levels varied according to previously described regulatory single nucleotide polymorphisms (SNPs) in the IL-10 promoter region. The homozygous GCC haplotype was associated with high-level IL-10 secretion, while the ACC and ATA haplotypes produced intermediate and low levels of IL-10, respectively. Our data suggest that ADE effects are cell type specific, are influenced by host genetics, and, depending on relative infection rates, may further contribute to the complexity of DV pathogenesis.

  14. 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.

  15. Genetic Diversity of Actinobacillus pleuropneumoniae Assessed by Amplified Fragment Length Polymorphism Analysis▿

    PubMed Central

    Kokotovic, Branko; Angen, Øystein

    2007-01-01

    Amplified fragment length polymorphism (AFLP) was evaluated as a method for genotypic characterization and subtyping within the bacterial species Actinobacillus pleuropneumoniae. A total of 155 isolates of A. pleuropneumoniae, representing the serotypic variation described to occur within this species, were analyzed. In order to elucidate the species boundaries, six strains of the phylogenetically closely related species Actinobacillus lignieresii were also included. Furthermore, the ability of AFLP to subtype was studied using 42 isolates of serovar 2 and the performance compared to that obtained by pulsed-field gel electrophoresis (PFGE). AFLP analysis provided a clear separation of A. lignieresii and A. pleuropneumoniae and divided the isolates of A. pleuropneumoniae into 20 clusters. Most of the serovars of A. pleuropneumoniae were represented by single and quite homogeneous clusters. The exceptions were serovars 10, K2:O7, and K1:O7, which were represented by two clusters each. In the cases where the serovars were represented by more than one cluster, the existence of these clusters was supported by additional phenotypic or genotypic properties. Furthermore, AFLP typing was able to allocate serologically nontypeable isolates to appropriate genetic groups within the species. Further investigations are needed to determine whether some of the clusters revealed through AFLP analysis represent additional serovars. When evaluated as a method for subtyping within serovar 2 of A. pleuropneumoniae, AFLP was found to achieve a degree of separation among isolates superior to that obtained by PFGE. However, a higher degree of separation between serovar 2 isolates was obtained by a combination of the two methods. PMID:17959758

  16. Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.

    PubMed Central

    Carlson, G A; Goodman, P A; Lovett, M; Taylor, B A; Marshall, S T; Peterson-Torchia, M; Westaway, D; Prusiner, S B

    1988-01-01

    The mouse prion protein (PrP) gene (Prn-p), which encodes the only macromolecule that has been identified in scrapie prions, is tightly linked or identical to a gene (Prn-i) that controls the duration of the scrapie incubation period in mice. Constellations of restriction fragment length polymorphisms distinguish haplotypes a to f of Prn-p. The Prn-pb allele encodes a PrP that differs in sequence from those encoded by the other haplotypes and, in inbred mouse strains, correlates with long scrapie incubation time (Westaway et al., Cell 51: 651-662, 1987). In segregating crosses of mice, we identified rare individuals with a divergent scrapie incubation time phenotype and Prn-p genotype, but progeny testing to demonstrate meiotic recombination was not possible because scrapie is a lethal disease. Crosses involving the a, d, and e haplotypes demonstrated that genes unlinked to Prn-p could modulate scrapie incubation time and that there were only two alleles of Prn-i among the mouse strains tested. All inbred strains of mice that had the Prnb haplotype were probably direct descendants of the I/LnJ progenitors. We established the linkage relationship between the prion gene complex (Prn) and other chromosome 2 genes; the gene order, proximal to distal, is B2m-II-1a-Prn-Itp-A. Recombination suppression in the B2m-Prn-p interval occurred during the crosses involved in transferring the I/LnJ Prnb complex into a C57BL/6J background. Transmission ratio distortion by Prna/Prnb heterozygous males was also observed in the same crosses. These phenomena, together with the founder effect, would favor apparent linkage disequilibrium between Prn-p and Prn-i. Therefore, transmission genetics may underestimate the number of genes in Prn. Images PMID:3149717

  17. Effects of omeprazole and genetic polymorphism of CYP2C19 on the clopidogrel active metabolite.

    PubMed

    Boulenc, Xavier; Djebli, Nassim; Shi, Juan; Perrin, Laurent; Brian, William; Van Horn, Robert; Hurbin, Fabrice

    2012-01-01

    Clopidogrel is an antiplatelet agent widely used in cardiovascular diseases and an inactive prodrug that needs to be converted to an active metabolite in two sequential metabolic steps. Several CYP450 isoforms involved in these two steps have been described, although the relative contribution in vivo of each enzyme is still under debate. CYP2C19 is considered to be the major contributor to active metabolite formation. In the current study, net CYP2C19 contribution to the active metabolite formation was determined from exposure of the active metabolite in two clinical studies (one phase I study with well balanced genetic polymorphic populations and a meta-analysis with a total of 396 healthy volunteers) at different clopidogrel doses. CYP2C19 involvements were estimated to be from 58 to 67% in intermediate metabolizers (IMs), from 58 to 72% in extensive metabolizers (EMs), and from 56 to 74% in ultrarapid metabolizers (UMs), depending on the study and the dose. For this purpose, a static model was proposed to estimate the net contribution of a given enzyme to the secondary metabolite formation. This static model was compared with a dynamic approach (Simcyp model) and showed good consistency. In parallel, in vitro investigations showed that omeprazole is a mechanism-based inhibitor of CYP2C19 with K(I) of 8.56 μM and K(inact) of 0.156 min(-1). These values were combined with the net CYP2C19 contribution to the active metabolite formation, through a static approach, to predict the inhibitory effect at 80-mg omeprazole doses in EM, IM, and UM CYP2C19 populations, with good consistency, compared with observed clinical values.

  18. Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia

    PubMed Central

    Bruzzoni-Giovanelli, Heriberto; González, Juan R.; Sigaux, François; Villoutreix, Bruno O.; Cayuela, Jean Michel; Guilhot, Joëlle; Preudhomme, Claude; Guilhot, François; Poyet, Jean-Luc; Rousselot, Philippe

    2015-01-01

    Little is known about inherited factors associated with the risk of developing chronic myelogenous leukemia (CML). We used a dedicated DNA chip containing 16 561 single nucleotide polymorphisms (SNPs) covering 1 916 candidate genes to analyze 437 CML patients and 1 144 healthy control individuals. Single SNP association analysis identified 139 SNPs that passed multiple comparisons (1% false discovery rate). The HDAC9, AVEN, SEMA3C, IKBKB, GSTA3, RIPK1 and FGF2 genes were each represented by three SNPs, the PSM family by four SNPs and the SLC15A1 gene by six. Haplotype analysis showed that certain combinations of rare alleles of these genes increased the risk of developing CML by more than two or three-fold. A classification tree model identified five SNPs belonging to the genes PSMB10, TNFRSF10D, PSMB2, PPARD and CYP26B1, which were associated with CML predisposition. A CML-risk-allele score was created using these five SNPs. This score was accurate for discriminating CML status (AUC: 0.61, 95%CI: 0.58–0.64). Interestingly, the score was associated with age at diagnosis and the average number of risk alleles was significantly higher in younger patients. The risk-allele score showed the same distribution in the general population (HapMap CEU samples) as in our control individuals and was associated with differential gene expression patterns of two genes (VAPA and TDRKH). In conclusion, we describe haplotypes and a genetic score that are significantly associated with a predisposition to develop CML. The SNPs identified will also serve to drive fundamental research on the putative role of these genes in CML development. PMID:26474455

  19. Association of genetic polymorphisms of vascular endothelial growth factor and risk for proliferative retinopathy of prematurity.

    PubMed

    Vannay, Adám; Dunai, György; Bányász, Ilona; Szabó, Miklós; Vámos, Rita; Treszl, András; Hajdú, Júlia; Tulassay, Tivadar; Vásárhelyi, Barna

    2005-03-01

    The intention of our retrospective study was to determine whether vascular endothelial growth factor (VEGF) genetic polymorphisms are associated with risk for proliferative retinopathy of prematurity (ROP), a condition that is characterized by abnormal retinal neovascularization and can lead to retinal detachment and result in blindness. We enrolled 86 very low birth weight infants (birth weight < or =1500 g) who had been treated with cryo/laser therapy because of the risk for proliferative ROP (treated group). Their VEGF T-460C and G+405C genotypes were determined from dried blood samples and were compared with VEGF genotypes of 115 VLBW infants who were not treated with cryo/laser therapy (untreated group). We found that the allele frequency of VEGF +405C was higher in the treated group than in the untreated group (0.30 versus 0.41; p <0.05). The likelihood of being treated for ROP was higher in heterozygous and homozygous carriers of VEGF +405C alleles [odds ratios adjusted for risk factors of ROP (95% CI): 2.00 (1.02-3.92; p=0.04) and 3.37 (1.17-9.65; p=0.007), respectively]. VEGF -460TT/+405CC haplotype was more prevalent in the treated patients than in the untreated patients (13 of 86 versus 1 of 115; p <0.001), and the association remained significant (p <0.01) even after the adjustment for risk factors of ROP (gestational age, supplemental oxygen therapy, and gender). These findings suggest that the VEGF genotype may be associated with risk for proliferative ROP in VLBW infants.

  20. 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

  1. Effect of GSTM1 and GSTT1 Polymorphisms on Genetic Damage in Humans Populations Exposed to Radiation From Mobile Towers.

    PubMed

    Gulati, Sachin; Yadav, Anita; Kumar, Neeraj; Kanupriya; Aggarwal, Neeraj K; Kumar, Rajesh; Gupta, Ranjan

    2016-04-01

    All over the world, people have been debating about associated health risks due to radiation from mobile phones and mobile towers. The carcinogenicity of this nonionizing radiation has been the greatest health concern associated with mobile towers exposure until recently. The objective of our study was to evaluate the genetic damage caused by radiation from mobile towers and to find an association between genetic polymorphism of GSTM1 and GSTT1 genes and DNA damage. In our study, 116 persons exposed to radiation from mobile towers and 106 control subjects were genotyped for polymorphisms in the GSTM1 and GSTT1 genes by multiplex polymerase chain reaction method. DNA damage in peripheral blood lymphocytes was determined using alkaline comet assay in terms of tail moment (TM) value and micronucleus assay in buccal cells (BMN). There was a significant increase in BMN frequency and TM value in exposed subjects (3.65 ± 2.44 and 6.63 ± 2.32) compared with control subjects (1.23 ± 0.97 and 0.26 ± 0.27). However, there was no association of GSTM1 and GSTT1 polymorphisms with the level of DNA damage in both exposed and control groups.

  2. Association between Genetic Polymorphisms of CYP2D6 and Outcomes in Breast Cancer Patients with Tamoxifen Treatment

    PubMed Central

    Park, Hyung Seok; Choi, Ji-Yeob; Lee, Mi-Jeong; Park, Seho; Yeo, Chang-Woo; Lee, Sang Seop; Shin, Jae-Gook

    2011-01-01

    The aim of the study was to evaluate the association between genetic polymorphisms of CYP2D6 and outcomes in breast cancer patients with tamoxifen treatment. We evaluated the CYP2D6 genetic polymorphisms in 766 breast cancer patients. Among them, 110 patients whose samples were prospectively collected before surgery and treated with tamoxifen were included to evaluate the association between CYP2D6 and outcomes. The genotypes of CYP2D6 were categorized as extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) according to the activity score. The clinicopathologic features of 110 patients were not significantly different among the three groups except for the T-stage and nodal status. The high T-stage and axillary metastasis were more frequent in the PM group. While recurrence-free and overall survival in the PM group was poorer than the other groups, there was no significant difference between the EM and the IM group. The difference between the PM and the other groups on univariate analysis disappeared on multivariate analysis. These conflicting results suggest that the clinical value of CYP2D6 polymorphisms is still unclear and more large-sized and comprehensively designed trials are necessary. PMID:21860550

  3. Genetic polymorphisms of CXCR5 and CXCL13 are associated with non-responsiveness to the hepatitis B vaccine.

    PubMed

    Duan, Zhaojun; Chen, Xiangmei; Liang, Zhenglun; Zeng, Ying; Zhu, Fengcai; Long, Lu; McCrae, Malcolm A; Zhuang, Hui; Shen, Tao; Lu, Fengmin

    2014-09-15

    A cohort based study has been undertaken to investigate the possible association of genetic polymorphisms in genes functionally related to follicular T helper (TfH) cells with non-responsiveness to hepatitis B virus (HBV) vaccination. A total of 24 single nucleotide polymorphisms (SNPs) in 6 TfH related genes (CXCR5, ICOS, CXCL13, IL-21, BCL6 and CD40L) were investigated in 20 non-responders and 45 responders to HBV vaccination. Genetic association analysis revealed that three SNPs (rs497916, rs3922, rs676925) in CXCR5 and one SNP (rs355687) in CXCL13 were associated with hepatitis B vaccine efficacy. In addition, significantly unbalanced distributions of two haplotypes, defined by three SNPs (rs497916, rs3922, rs676925) within CXCR5, were also seen between non-responders and responders. Furthermore, we demonstrated that the rs3922 "GG" genotype was associated with higher levels of CXCR5 than the "AG" and "AA" genotype in a group of healthy volunteers. A dual luciferase report assay was used to confirm that the "G" allele in rs3922 may lead to higher gene expression than the "A" allele, implicating that rs3922 might be a functional SNP affecting CXCR5 expression. These results indicated that polymorphism associated changes in CXCR5 expression in TfH cells may be associated with non-responsiveness to hepatitis B vaccination.

  4. 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.

  5. 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

  6. Genetic Susceptibility to Cancer: the Role of Polymorphisms in Candidate Genes

    PubMed Central

    Dong, Linda M; Potter, John D; White, Emily; Ulrich, Cornelia M; Cardon, Lon R; Peters, Ulrike

    2009-01-01

    Context Continuing advances in genotyping technologies and the inclusion of DNA collection in observational studies have resulted in an increasing number of genetic association studies. Objective To evaluate the overall progress and contribution of candidate gene association studies to current understanding of the genetic susceptibility to cancer. Data Sources We systematically examined the results of meta- and pooled analyses for genetic polymorphisms and cancer risk published through March 2008. Study Selection We identified 161 meta- and pooled analyses, encompassing 18 cancer sites and 99 genes. Analyses had to meet the following criteria: 1) at least 500 cases, 2) cancer risk as outcome, 3) not focused on HLA genetic markers, and 4) published in English. Data Extraction Information on cancer site, gene name, variant, point estimate and 95% confidence interval, allelic frequency, number of studies and cases, tests of study heterogeneity and publication bias were extracted by one investigator and reviewed by other investigators. Results These 161 analyses evaluated 344 gene-variant/cancer associations and included on average 7.3 studies and 3,551 cases (range: 508–19,729 cases) per investigated association. The summary OR for 98 (28%) statistically significant associations (p-value <0.05) were further evaluated by estimating the false-positive report probability (FPRP) at a given prior probability and statistical power. At a prior probability level of 0.001 and statistical power to detect an OR of 1.5, thirteen gene-variant/cancer associations remained noteworthy (FPRP<0.2). Assuming a very low prior probability of 0.000001, similar to a probability assumed for a randomly selected SNP in a genome-wide association study, and statistical power to detect an OR of 1.5, four associations were considered noteworthy as denoted by a FPRP value < 0.2: 1) GSTM1 null and bladder cancer (OR:1.5, 95% CI: 1.3–1.6, p-value=1.9×10−14), 2) NAT2 slow acetylator and bladder

  7. 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.

  8. Morph-specific genetic and environmental variation in innate and acquired immune response in a color polymorphic raptor.

    PubMed

    Gangoso, Laura; Roulin, Alexandre; Ducrest, Anne-Lyse; Grande, Juan Manuel; Figuerola, Jordi

    2015-08-01

    Genetic color polymorphism is widespread in nature. There is an increasing interest in understanding the adaptive value of heritable color variation and trade-off resolution by differently colored individuals. Melanin-based pigmentation is often associated with variation in many different life history traits. These associations have recently been suggested to be the outcome of pleiotropic effects of the melanocortin system. Although pharmacological research supports that MC1R, a gene with a major role in vertebrate pigmentation, has important immunomodulatory effects, evidence regarding pleiotropy at MC1R in natural populations is still under debate. We experimentally assessed whether MC1R-based pigmentation covaries with both inflammatory and humoral immune responses in the color polymorphic Eleonora's falcon. By means of a cross-fostering experiment, we disentangled potential genetic effects from environmental effects on the covariation between coloration and immunity. Variation in both immune responses was primarily due to genetic factors via the nestlings' MC1R-related color genotype/phenotype, although environmental effects via the color morph of the foster father also had an influence. Overall, dark nestlings had lower immune responses than pale ones. The effect of the color morph of the foster father was also high, but in the opposite direction, and nestlings raised by dark eumelanic foster fathers had higher immune responses than those raised by pale foster fathers. Although we cannot completely discard alternative explanations, our results suggest that MC1R might influence immunity in this species. Morph-specific variation in immunity as well as pathogen pressure may therefore contribute to the long-term maintenance of genetic color polymorphism in natural populations.

  9. 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.

  10. Red cell enzyme polymorphisms in Moroccans and southern Spaniards: new data for the genetic history of the western Mediterranean.

    PubMed

    Kandil, M; Moral, P; Esteban, E; Autori, L; Mameli, G E; Zaoui, D; Calo, C; Luna, F; Vacca, L; Vona, G

    1999-10-01

    Population samples from Morocco (El Jadida, south Atlantic coast) and La Alpujarra (Granada mountains, Spain), located on both shores of the western Mediterranean, were typed for 8 erythrocyte genetic markers: ACP1, ESD, PGD, AK1, GLO1, PGM1, SODA, and DIA. Genetic heterogeneity within western Mediterranean groups was investigated on the basis of allele frequencies of these 8 polymorphisms plus ABO and Rh (CDE). Only slight peculiarities for the ACP1, GLO1, and AK1 systems were observed in the 2 samples compared with other Mediterranean data. The new data are consistent with a main north to south genetic differentiation in the Mediterranean region. However, with regard to other European groups, the La Alpujarra population shows a particular affinity with North Africans that may be compatible with both an ancient common substratum and/or a special historical influence during the Muslim domination of the Iberian Peninsula.

  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)

    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...

  12. 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

  13. GSTO and AS3MT genetic polymorphisms and differences in urinary arsenic concentrations among residents in Bangladesh

    PubMed Central

    Rodrigues, Ema G.; Kile, Molly; Hoffman, Elaine; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Hsueh, Yumei; Christiani, David C.

    2012-01-01

    We determined whether single nucleotide polymorphisms (SNPs) in the glutathione S-transferase omega (GSTO) and arsenic(III)methyltransferase (AS3MT) genes were associated with concentrations of urinary arsenic metabolites among 900 individualswithout skin lesions in Bangladesh. Four SNPs were assessed in these genes. A pathway analysis evaluated the association between urinary arsenic metabolites and SNPs. GSTO1 rs4925 homozygous wild type was significantly associated with higher monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) urinary concentrations, whereas wild type AS3MT rs11191439 had significantly lower levels of AsIII and MMA. Genetic polymorphisms GSTO and As3MT modify arsenic metabolism as evidenced by altered urinary arsenic excretion. PMID:22339537

  14. Genetic diversity among Bacillus anthracis, Bacillus cereus and Bacillus thuringiensis strains using repetitive element polymorphism-PCR.

    PubMed

    Brumlik, Michael J; Bielawska-Drózd, Agata; Zakowska, Dorota; Liang, Xudong; Spalletta, Ronald A; Patra, Guy; Delvecchio, Vito G

    2004-01-01

    Repetitive element polymorphism-PCR (REP-PCR) is one of the tools that has been used to elucidate genetic diversity of related microorganisms. Using the MB1 primer, REP-PCR fingerprints from 110 Bacillus strains within the "B. cereus group" have identified eighteen distinct categories, while other more distantly related bacterial species fell within six additional categories. All Bacillus anthracis strains tested were found to be monomorphic by fluorophore-enhanced REP-PCR (FERP) fingerprinting using the MB1 primer. In contrast, other non- B. anthracis isolates displayed a high degree of polymorphism. Dendrogramic analysis revealed that the non- B. anthracis strains possessing the Ba813 chromosomal marker were divided into two clusters. One of the clusters shared identity with the B. cereus strains examined.

  15. Genetic linkage between Becker muscular dystrophy and a polymorphic DNA sequence on the short arm of the X chromosome.

    PubMed Central

    Kingston, H M; Thomas, N S; Pearson, P L; Sarfarazi, M; Harper, P S

    1983-01-01

    A study of DNA restriction fragment polymorphisms and Becker muscular dystrophy has shown eight families informative for the cloned sequence L1.28, which is located on the short arm of the X chromosome between Xp110 and Xp113. Analysis of these families reveals linkage between the two loci, with the maximum likelihood estimate of the genetic distance being 16 centiMorgans (95% confidence limits between 7 and 32 centiMorgans). Since a study of DNA polymorphisms in Duchenne muscular dystrophy has shown a comparable linkage distance with L1.28, our results suggest that the locus for Becker muscular dystrophy, like that for Duchenne dystrophy, is on the short arm of the X chromosome, and further that these two loci may be closely linked or possibly allelic. Images PMID:6620324

  16. Single-Nucleotide Polymorphism Markers from De-Novo Assembly of the Pomegranate Transcriptome Reveal Germplasm Genetic Diversity

    PubMed Central

    Ophir, Ron; Sherman, Amir; Rubinstein, Mor; Eshed, Ravit; Sharabi Schwager, Michal; Harel-Beja, Rotem; Bar-Ya'akov, Irit; Holland, Doron

    2014-01-01

    Pomegranate is a valuable crop that is grown commercially in many parts of the world. Wild species have been reported from India, Turkmenistan and Socotra. Pomegranate fruit has a variety of health-beneficial qualities. However, despite this crop's importance, only moderate effort has been invested in studying its biochemical or physiological properties or in establishing genomic and genetic infrastructures. In this study, we reconstructed a transcriptome from two phenotypically different accessions using 454-GS-FLX Titanium technology. These data were used to explore the functional annotation of 45,187 fully annotated contigs. We further compiled a genetic-variation resource of 7,155 simple-sequence repeats (SSRs) and 6,500 single-nucleotide polymorphisms (SNPs). A subset of 480 SNPs was sampled to investigate the genetic structure of the broad pomegranate germplasm collection at the Agricultural Research Organization (ARO), which includes accessions from different geographical areas worldwide. This subset of SNPs was found to be polymorphic, with 10.7% loci with minor allele frequencies of (MAF<0.05). These SNPs were successfully used to classify the ARO pomegranate collection into two major groups of accessions: one from India, China and Iran, composed of mainly unknown country origin and which was more of an admixture than the other major group, composed of accessions mainly from the Mediterranean basin, Central Asia and California. This study establishes a high-throughput transcriptome and genetic-marker infrastructure. Moreover, it sheds new light on the genetic interrelations between pomegranate species worldwide and more accurately defines their genetic nature. PMID:24558460

  17. Genetic Diversity of Pinus Roxburghii Sarg. Collected from Different Himalayan Regions of India Assessed by Random Amplified Polymorphic DNA Analysis

    PubMed Central

    Sinha, Dwaipayan; Singh, Jyotsna; Tandon, P. K.; Kakkar, Poonam

    2013-01-01

    Present study was aimed at molecular genetic fingerprint profile of 15 genotypes of three populations of Pinus roxburghii Sarg. from Himalayan regions of India using random amplified polymorphic DNA (RAPD) based markers. Needles of Pinus roxburghii Sarg. were collected from Dharamshala, Himachal Pradesh (HP), Nainital, Uttarakhand (UK) and Darjeeling, West Bengal (WB) regions of India. The samples were subjected to DNA extraction and RAPD analysis using oligonucleotide purification cartridge (OPC) primers. Out of 15 primers tested, nine primers gave scorable bands. Altogether 48 bands were obtained, out of which 43 were found to be polymorphic. Number of amplified fragments with RAPD primers ranged from four to eight with the size of amplicon ranging from 500 to 7,000bp. Investigation of natural diversity at intraspecies level was performed with 15 genotypes. Forty-eight amplification products were scored by RAPD and showed 89.58% polymorphism with a mean intrapopulation genetic diversity (Hpop) of 0.2754. A significant inter- and intrapopulation diversity was observed, with the percentage of polymorphic loci (Pp) ranging from 50.09 to 70.83%, Shannon's information index (I) from 0.3262 to 0.4689 and Nei's gene diversity (h) from 0.2032 to 0.3335 with mean Nei's gene diversity 0.377 and the overall estimate of gene flow being (Nm) 1.3555. Unweighted pair-group method with arithmetic average (UPGMA) analysis based Dendrogram showed single cluster. The variation amongst the samples of the three ecological regions can be attributed to varied climatic conditions and may help in conservation/future cultivation of these species. PMID:24403729

  18. Genetic polymorphisms of inflammatory response gene TNF-α and its influence on sporadic pancreatic neuroendocrine tumors predisposition risk.

    PubMed

    Karakaxas, Dimitrios; Gazouli, Maria; Coker, Ahmet; Agalianos, Christos; Papanikolaou, Ioannis S; Patapis, Pavlos; Liakakos, Theodoros; Dervenis, Christos

    2014-10-01

    The diagnosed incidence of pancreatic neuroendocrine tumors (pNETs) is increasing; however, their etiology remains poorly understood. PNETs are a rare, heterogeneous group of tumors arising from the endocrine cells of the pancreas, and genetic risk factors for sporadic pNETs are inadequately understood. It is known that pNETs secrete biogenic amines, hormones and growth factors, tumor necrosis factor-a (TNF-α) being one of them. Furthermore, cytokines and other proinflammatory mediators have been implicated in inflammatory pancreatic diseases including pancreatitis and cancer. The aim of our study was to analyze TNF-α promoter gene polymorphisms as risk factors for pNETs using germline DNA collected in a population-based case-control study of pancreatic cancer [42 pNET cases, 78 pancreatic ductal adenocarcinoma (PDAC) cases, 17 intraductal papillary mucinous neoplasm (IPMN) and 98 healthy controls] conducted in the Athens, Greece and Izmir, Turkey areas. For subsequent analysis, we excluded cases and controls with known genetic syndromes. The CC genotype at the -1031 position was more frequent in pNET and IPMN patients (p=0.0002 and p=0.009, respectively), suggesting its possible role in pNET development. Furthermore, the AA genotype at the -308 position was overrepresented in IPMN cases (p=0.03), and AA genotype at the -238 position was more frequent in PDAC cases (p=0.03) compared to healthy individuals. With regard to tumor characteristics, no statistically significant association was detected. Our findings suggest the putative role of TNF-α -1031 polymorphism in the development of pNET and IPMN, whereas the -308 polymorphism seems to be overrepresented among IPMN cases and -238 polymorphism among PDAC cases.

  19. Association of the IFN-γ (+874A/T) Genetic Polymorphism with Paranoid Schizophrenia in Tunisian Population.

    PubMed

    Jemli, Achraf; Eshili, Awatef; Trifa, Fatma; Mechri, Anouar; Zaafrane, Ferid; Gaha, Lotfi; Juckel, George; Tensaout, Besma Bel Hadj Jrad

    2017-02-01

    Since growing evidence suggests a significant role of chronic low-grade inflammation in the physiopathology of schizophrenia, we have hypothesized that functional genetic variant of the IFN gamma (IFN-γ; +874A/T; rs2430561) gene may be involved in the predisposition to schizophrenia. This research is based on a case-control study which aims to identify whether polymorphism of the IFN-γ gene is a risk factor for the development of schizophrenia. The RFLP-PCR genotyping of the IFN-γ gene was conducted on a Tunisian population composed of 218 patients and 162 controls. The IFN-γ (+874A/T) polymorphism analysis showed higher frequencies of minor homozygous genotype (TT) and allele (T) in all patients compared with controls (11.5 vs. 4.9%; p = 0.03, OR = 2.64 and 30.7 vs. 24.1%, p = 0.04, OR = 1.4, respectively). This correlation was confirmed for male but not for female patients. Also, the T allele was significantly more common among patients with paranoid schizophrenia when compared with controls (25.8 vs. 4.9%, p = 0.0001; OR = 6.7). Using the binary regression analysis to eliminate confounding factors as age and sex, only this last association remained significant (p = 0.03; OR = 1.76, CI = 1.05-2.93). In conclusion, our results showed a significant association between +874A/T polymorphism of IFN-γ and paranoid schizophrenia, suggesting that this single nucleotide polymorphism (SNP) or another at proximity could predispose to paranoid schizophrenia. Since the minor allele of this polymorphism was correlated with an increased expression of their product, our study validates the hypothesis of excessive pro-inflammatory cytokine in the physiopathology of paranoid schizophrenia.

  20. Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer

    PubMed Central

    Sáenz-López, Pablo; Carretero, Rafael; Cózar, José Manuel; Romero, José Maria; Canton, Julia; Vilchez, José Ramón; Tallada, Miguel; Garrido, Federico; Ruiz-Cabello, Francisco

    2008-01-01

    Background Inflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk. Methods A case-control study design was used to test the association between prostate cancer risk and the polymorphisms TNF-A-308 A/G (rs 1800629), RANTES-403 G/A (rs 2107538), IL1-A-889 C/T (rs 1800587) and MCP-1 2518 G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311 healthy controls from the same area. Results Diagnosis of prostate cancer was significantly associated with TNF-A GA + AA genotype (OR, 1.61; 95% CI, 1.09–2.64) and RANTES GA + AA genotype (OR, 1.44; 95% CI, 1.09–2.38). A alleles in TNF-A and RANTES influenced prostate cancer susceptibility and acted independently of each other in these subjects. No epistatic effect was found for the combination of different polymorphisms studied. Finally, no overall association was found between prostate cancer risk and IL1-A or MCP-1 polymorphisms. Conclusion Our results and previously published findings on genes associated with innate immunity support the hypothesis that polymorphisms in proinflammatory genes may be important in prostate cancer development. PMID:19099590

  1. 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

  2. Genetic Diversity among Rhizobium leguminosarum bv. Trifolii Strains Revealed by Allozyme and Restriction Fragment Length Polymorphism Analyses

    PubMed Central

    Demezas, David H.; Reardon, Terry B.; Watson, John M.; Gibson, Alan H.

    1991-01-01

    Allozyme electrophoresis and restriction fragment length polymorphism (RFLP) analyses were used to examine the genetic diversity of a collection of 18 Rhizobium leguminosarum bv. trifolii, 1 R. leguminosarum bv. viciae, and 2 R. meliloti strains. Allozyme analysis at 28 loci revealed 16 electrophoretic types. The mean genetic distance between electrophoretic types of R. leguminosarum and R. meliloti was 0.83. Within R. leguminosarum, the single strain of bv. viciae differed at an average of 0.65 from strains of bv. trifolii, while electrophoretic types of bv. trifolii differed at a range of 0.23 to 0.62. Analysis of RFLPs around two chromosomal DNA probes also delineated 16 unique RFLP patterns and yielded genetic diversity similar to that revealed by the allozyme data. Analysis of RFLPs around three Sym (symbiotic) plasmid-derived probes demonstrated that the Sym plasmids reflect genetic divergence similar to that of their bacterial hosts. The large genetic distances between many strains precluded reliable estimates of their genetic relationships. PMID:16348600

  3. 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.

  4. 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

  5. Biotype status and genetic polymorphism of the whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) in Greece: mitochondrial DNA and microsatellites.

    PubMed

    Tsagkarakou, A; Tsigenopoulos, C S; Gorman, K; Lagnel, J; Bedford, I D

    2007-02-01

    The genetic polymorphism and the biotype identity of the tobacco whitefly Bemisia tabaci (Gennadius) have been studied in population samples taken from different localities within Greece from cultivated plants growing in greenhouses or in open environments and from non-cultivated plants. Two different approaches were used: sequencing of the mitochondrial cytochrome oxidase I (mtCOI) gene and genotyping using microsatellite markers. Analyses of the mtCOI sequences revealed a high homogeneity between the Greek samples which clustered together with Q biotype samples that had been collected from other countries. When genetic polymorphism was examined using six microsatellite markers, the Greek samples, which were all characterized as Q biotype were significantly differentiated from each other and clustered into at least two distinct genetic populations. Moreover, based on the fixed differences revealed by the mtCOI comparison of known B. tabaci biotype sequences, two diagnostic tests for discriminating between Q and B and non-Q/non-B biotypes were developed. Implementation of these diagnostic tools allowed an absence of the B biotype and presence of the Q biotype in the Greek samples to be determined.

  6. Developmentally Restricted Genetic Determinants of Human Arsenic Metabolism: Association between Urinary Methylated Arsenic and CYT19 Polymorphisms in Children

    PubMed Central

    Meza, Maria Mercedes; Yu, Lizhi; Rodriguez, Yelitza Y.; Guild, Mischa; Thompson, David; Gandolfi, A. Jay; Klimecki, Walter T.

    2005-01-01

    We report the results of a screen for genetic association with urinary arsenic metabolite levels in three arsenic metabolism candidate genes, PNP, GSTO, and CYT19, in 135 arsenic-exposed subjects from the Yaqui Valley in Sonora, Mexico, who were exposed to drinking water concentrations ranging from 5.5 to 43.3 ppb. We chose 23 polymorphic sites to test in the arsenic-exposed population. Initial phenotypes evaluated included the ratio of urinary inorganic arsenic(III) to inorganic arsenic(V) and the ratio of urinary dimethylarsenic(V) to monomethylarsenic(V) (D:M). In the initial association screening, three polymorphic sites in the CYT19 gene were significantly associated with D:M ratios in the total population. Subsequent analysis of this association revealed that the association signal for the entire population was actually caused by an extremely strong association in only the children (7–11 years of age) between CYT19 genotype and D:M levels. With children removed from the analysis, no significant genetic association was observed in adults (18–79 years). The existence of a strong, developmentally regulated genetic association between CYT19 and arsenic metabolism carries import for both arsenic pharmacogenetics and arsenic toxicology, as well as for public health and governmental regulatory officials. PMID:15929903

  7. Different genetic components in the Norwegian population revealed by the analysis of mtDNA and Y chromosome polymorphisms.

    PubMed

    Passarino, Giuseppe; Cavalleri, Gianpiero L; Lin, Alice A; Cavalli-Sforza, Luigi Luca; Børresen-Dale, Anne-Lise; Underhill, Peter A

    2002-09-01

    The genetic composition of the Norwegian population was investigated by analysing polymorphisms associated with both the mitochondrial DNA (mtDNA) and Y chromosome loci in a sample of 74 Norwegian males. The combination of their uniparental mode of inheritance and the absence of recombination make these haplotypic stretches of DNA the tools of choice in evaluating the different components of a population's gene pool. The sequencing of the Dloop and two diagnostic RFLPs (AluI 7025 and HinfI at 12 308) allowed us to classify the mtDNA molecules in 10 previously described groups. As for the Y chromosome the combination of binary markers and microsatellites allowed us to compare our results to those obtained elsewhere in Europe. Both mtDNA and Y chromosome polymorphisms showed a noticeable genetic affinity between Norwegians and central Europeans, especially Germans. When the phylogeographic analysis of the Y chromosome haplotypes was attempted some interesting clues on the peopling of Norway emerged. Although Y chromosome binary and microsatellite data indicate that 80% of the haplotypes are closely related to Central and western Europeans, the remainder share a unique binary marker (M17) common in eastern Europeans with informative microsatellite haplotypes suggesting a different demographic history. Other minor genetic influences on the Norwegian population from Uralic speakers and Mediterranean populations were also highlighted.

  8. Population genetics of coagulant factor IX: frequencies of two DNA polymorphisms in five ethnic groups.

    PubMed Central

    Lubahn, D B; Lord, S T; Bosco, J; Kirshtein, J; Jeffries, O J; Parker, N; Levtzow, C; Silverman, L M; Graham, J B

    1987-01-01

    Two frequently used restriction-enzyme polymorphisms (RFLPs) of coagulant F.IX, TaqI and XmnI, have been examined in five ethnic groups: white Americans, black Americans, East Indians, Chinese, and Malays. There is a distinct "cline" in the frequencies of both polymorphisms, from white Americans to Malays. The rarer type 2 alleles of both polymorphisms, in which middle recognition sites are present--and which in our sample reach their highest frequencies in white Americans--are marginally higher in four groups of Europeans previously reported by others. The frequencies of the rarer alleles are significantly higher in Europeans than in black Americans and East Indians, and these alleles are essentially absent in Chinese and Malays. The frequency of heterozygosity diminishes in the same order, being zero in Malays for both polymorphisms. The polymorphisms are in strong linkage disequilibrium, and in all groups the type 1 allele for TaqI is disproportionately accompanied by the type 1 allele for XmnI. The paucity of type 2 alleles and the low rate of heterozygosity in four non-European groups suggest that the polymorphisms will be of little diagnostic value south of Gibraltar and east of Suez. This prediction is confirmed by the observed haplotype frequencies in the black American and the Oriental groups. PMID:2884869

  9. 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

  10. [Genetic polymorphism of the IL8 gene and its associations with milk traits and SCS in Chinese Holstein].

    PubMed

    Chen, Ren-Jin; Yang, Zhang-Ping; Mao, Yong-Jiang; Chen, Ying; Chang, Ling-Ling; Ji, De-Jun; Wu, Hai-Tao; Li, Yun-Long; Li, Rui

    2010-12-01

    The polymorphism of Interleukin-8 (IL8) gene were investigated for 610 Chinese Holstein cows of 30 bull families from a dairy farm in Shanghai using Polymerase Chain Reaction-Single Strand Conformation Polymorphism (PCR-SSCP) technique with a mixed animal model to verify the effects of the polymorphisms on some milk productive performance, tested day milk yield, tested day fat percentage, tested day milk protein percentage, 305 d corrected milk yield, 305 d milk fat yield, 305 d milk protein yield, and somatic cell score (SCS). The aim was to explore the significant molecular marker in practical dairy production. Three genotypes were identified and the genotypic frequencies of KK, KA, and AA were 0.187, 0.451, and 0.362, respectively. The gene frequencies of K and A were 0.412 and 0.588. The results showed highly significant (P < 0.01) association of IL8 mutations with tested day milk yield, 305 d milk protein yield, 305 d corrected milk yield and 305 d milk fat yield, SCS and tested day milk protein percentage (P < 0.05). However, no association (P > 0.05) with tested day milk fat percentage was recorded. The cows with KK genotype had higher tested day milk yield, 305 d milk protein yield, 305 d corrected milk yield and 305 d milk fat yield than those with AA and KA genotypes (P < 0.01). The least square mean of SCS for KK was significantly lower than that with AA and KA genotypes (P < 0.01). AA genotype was significant lower in tested day milk protein percentage than KK and KA genotypes (P < 0.05). The IL8 gene genetic diversity has a great genetic effect on milk traits and mastitis resistance and could be a useful genetic marker for Chinese Holstein breeding.

  11. Genetic Polymorphisms Contribute to the Individual Variations of Imatinib Mesylate Plasma Levels and Adverse Reactions in Chinese GIST Patients

    PubMed Central

    Liu, Jing; Chen, Zhiyu; Chen, Hanmei; Hou, Yingyong; Lu, Weiqi; He, Junyi; Tong, Hanxing; Zhou, Yuhong; Cai, Weimin

    2017-01-01

    Imatinib mesylate (IM) has dramatically improved the outcomes of gastrointestinal stromal tumor (GIST) patients. However, the clinical responses of IM may considerably vary among single individuals. This study aimed to investigate the influences of genetic polymorphisms of drug-metabolizing enzyme (CYP3A4), transporters (ABCB1, ABCG2), and nuclear receptor (Pregnane X Receptor (PXR, encoded by NR1I2)) on IM plasma levels and related adverse reactions in Chinese GIST patients. A total of 68 Chinese GIST patients who have received IM 300–600 mg/day were genotyped for six single nucleotide polymorphisms (SNPs) (CYP3A4 rs2242480; ABCB1 rs1045642; ABCG2 rs2231137; NRI12 rs3814055, rs6785049, rs2276706), and the steady-state IM trough plasma concentrations were measured by a validated HPLC method. There were statistically significant variances in the steady-state IM trough plasma concentrations (from 272.22 to 4365.96 ng/mL). Subjects of GG in rs2242480, T allele carriers in rs1045642 and CC in rs3814055 had significantly higher steady-state IM dose-adjusted trough plasma concentrations. Subjects of CC in rs3814055 had significantly higher incidence rate of edema. The genetic polymorphisms of rs2242480, rs1045642, rs3814055 were significantly associated with IM plasma levels, and the genetic variations of rs3814055 were significantly associated with the incidence rate of edema in Chinese GIST patients. The current results may serve as valuable fundamental knowledge for IM therapy in Chinese GIST patients. PMID:28335376

  12. Genetic polymorphisms in CYP1A1, CYP1B1 and COMT genes in Greenlandic Inuit and Europeans

    PubMed Central

    Ghisari, Mandana; Long, Manhai; Bonefeld-Jørgensen, Eva C.

    2013-01-01

    Background The Indigenous Arctic population is of Asian descent, and their genetic background is different from the Caucasian populations. Relatively little is known about the specific genetic polymorphisms in genes involved in the activation and detoxification mechanisms of environmental contaminants in Inuit and its relation to health risk. The Greenlandic Inuit are highly exposed to legacy persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), and an elucidation of gene–environment interactions in relation to health risks is needed. Objectives The aim of this study was to determine and compare the genotype and allele frequencies of the cytochrome P450 CYP1A1 Ile462Val (rs1048943), CYP1B1 Leu432Val (rs1056836) and catechol-O-methyltransferase COMT Val158Met (rs4680) in Greenlandic Inuit (n=254) and Europeans (n=262) and explore the possible relation between the genotypes and serum levels of POPs. Results The genotype and allele frequency distributions of the three genetic polymorphisms differed significantly between the Inuit and Europeans. For Inuit, the genotype distribution was more similar to those reported for Asian populations. We observed a significant difference in serum polychlorinated biphenyl (CB-153) and the pesticide 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p′-DDE) levels between Inuit and Europeans, and for Inuit also associations between the POP levels and genotypes for CYP1A1, CYP1B1 and COMT. Conclusion Our data provide new information on gene polymorphisms in Greenlandic Inuit that might support evaluation of susceptibility to environmental contaminants and warrant further studies. PMID:23785672

  13. FOXP3 -3279 and IVS9+459 polymorphisms are associated with genetic susceptibility to myasthenia gravis.

    PubMed

    Zhang, Junmei; Chen, Yuqian; Jia, Ge; Chen, Xiaoli; Lu, Jiayin; Yang, Huan; Zhou, Wenbin; Xiao, Bo; Zhang, Ning; Li, Jing

    2013-02-08

    Myasthenia gravis (MG) is an autoimmune disorder in which CD4(+)CD25(+) FOXP3(+)regulatory T cells (Tregs) are thought to play important roles in driving the ongoing autoimmune response. Although it is known that single-nucleotide polymorphisms (SNPs) in the fork head/winged-helix transcription factor 3 (FOXP3) gene contribute to some autoimmune diseases, information about the role of this gene in MG is limited. We therefore evaluated the association between FOXP3 gene SNPs and susceptibility to MG in a Han Chinese population. In a hospital-based, case-control study, two SNPs in the FOXP3 gene (-3279 and IVS9+459) were investigated in 118 MG and 124 healthy controls, and their relationship with the four parameters of gender, onset age, thymus pathology, and clinical classification of MG were performed with a stratified analysis. We found that the frequency of the FOXP3 IVS9+459 G allele was significantly lower in MG patients than in healthy controls (P=0.041), while the frequency of the FOXP3 -3279 polymorphisms was not significantly different between the two groups. Our results suggest that FOXP3 IVS9+459 polymorphisms appear to have an effect on the risk of MG in a Han Chinese population, and the G allele may be a genetic protective factor to MG.

  14. Methylenetetrahydrofolate reductase genetic polymorphisms and esophageal squamous cell carcinoma susceptibility: A meta-analysis of case-control studies

    PubMed Central

    Shujuan, Yang; Jianxing, Zhang; Xin-yue, Chen

    2013-01-01

    Objectives: Genetic factors and environmental factors play a role in pathogenesis of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the association of folate intake and Methylenetetrahydrofolate reductase C677T polymorphism with ESCC was conflicting. We conducted a meta-analysis to investigate the association of MTHFR C677T and folate intake with esophageal cancer risk. Methodology: MEDLINE, EMBASE and the Chinese Biomedical Database were searched in our study. The quality of studies were evaluated by predefined scale, and The association of polymorphisms of MTHFR C677T and folate intake and ESCC risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs). Results: Nineteen studies (4239 cases and 5575 controls) were included for meta-analysis. A significant association was seen between individuals with MTHFR 677 CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC risk (p<0.05). Low intake of folate had significantly higher risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high intake of folate did not find significant high risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]. Conclusions: Our meta-analysis indicated the folate intake and MTHFR 677CT/TT are associated with the risk of ESCC, and folate showed a significant interaction with polymorphism of MTHFR C677T. PMID:24353609

  15. A genetic polymorphism (rs17251221) in the calcium-sensing receptor is associated with ovarian cancer susceptibility.

    PubMed

    Yan, Shi; Yuan, Cunzhong; Yang, Qifeng; Li, Xiaoyan; Yang, Ning; Liu, Xiaoyan; Dong, Ruihua; Zhang, Xi; Yuan, Zeng; Zhang, Ning; Kong, Beihua

    2015-10-01

    Calcium-sensing receptor (CaSR) is a G-protein‑ coupled receptor that senses blood calcium. In vivo, CaSR is required for normal epidermal differentiation by mediating calcium signaling. CaSR was confirmed to be a tumor suppressor in colon and breast cancer. The single-nucleotide polymorphism (SNP) rs17251221, located on the intron, is a genetic variation of the CaSR gene. We analyzed rs17251221 in ovarian cancer using an allelic discrimination assay. Cycling probes were used for genotyping 290 ovarian cancer patients and 312 age-matched cancer-free females. rs17251221 and clinicopathological characteristics of ovarian cancer were analyzed statistically. The AG and GG genotypes were confirmed to appear in fewer cancer cases than in controls and the genotype distribution between cases and controls was statistically significant. The AG+GG genotype was correlated with low ovarian cancer risk, while rs17251221 was not associated with clinicopathological variables including age at diagnosis, tumor size, histologic type, pathological subtype, lymph node metastasis, CA-125 expression, clinical stage, or degree of differentiation. The rs17251221 polymorphism genotype was not correlated with survival in ovarian cancer. These results suggest that the G allele of the CaSR rs17251221 polymorphism is protective against ovarian cancer and the homozygous GG genotype may be a protective genotype as well. The rs17251221 may play an important role in the development of ovarian cancer and could be used as a biomarker for predicting ovarian cancer.

  16. Paradoxical psoriasiform reactions to anti-TNFα drugs are associated with genetic polymorphisms in patients with psoriasis.

    PubMed

    Cabaleiro, T; Prieto-Pérez, R; Navarro, R; Solano, G; Román, M; Ochoa, D; Abad-Santos, F; Daudén, E

    2016-08-01

    Paradoxical psoriasiform reactions to anti-tumor necrosis factor α (TNFα) agents have been described. We aimed to study the association between these reactions and polymorphisms in genes previously associated with psoriasis or other autoimmune diseases. A total of 161 patients with plaque-type psoriasis treated with anti-TNFα drugs were genotyped for 173 single-nucleotide polymorphisms (SNPs) using the Illumina Veracode genotyping platform. Among the 161 patients, 25 patients developed a paradoxical psoriasiform reaction consisting of a change in morphology, mostly to guttate psoriasis (88%). These lesions developed 9.20±13.52 months after initiating treatment, mainly with etanercept (72%). Psoriasis type and a Psoriasis Area and Severity Index (PASI) 75 response to treatment were not associated with lesions. Multivariate logistic regression revealed that five SNPs (rs11209026 in IL23R, rs10782001 in FBXL19, rs3087243 in CTLA4, rs651630 in SLC12A8 and rs1800453 in TAP1) were associated with paradoxical reactions. This is the first study to show an association between genetic polymorphisms and paradoxical reactions in patients with psoriasis treated with anti-TNFα drugs.The Pharmacogenomics Journal advance online publication, 21 July 2015; doi:10.1038/tpj.2015.53.

  17. Complex interaction between serum folate levels and genetic polymorphisms in folate pathway genes: biomarkers of prostate cancer aggressiveness.

    PubMed

    Jackson, Maria D; Tulloch-Reid, Marshall K; McFarlane-Anderson, Norma; Watson, Alexis; Seers, Vestra; Bennett, Franklyn I; Egleston, Brian; Ragin, Camille

    2013-03-01

    Little is known about the role of folate and polymorphisms associated with folate metabolism on prostate cancer risk in populations of African origin. We examined the relationship between serum folate and prostate cancer and whether any association was modified by genetic polymorphisms for folate metabolism. The study was case-control in design and consisted of 218 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 236 cancer-free men attending the same urology clinics in Jamaica, March 2005-July 2007. Serum folate was measured by an immunoassay method and genomic DNA evaluated for MTHR (C677T and A1298C), MTRR A66G, and MTR A2756G polymorphisms. Mean serum folate concentration was higher among cases (12.3 ± 4.1 nmol/L) than controls (9.7 ± 4.2 nmol/L). Serum folate concentration showed a positive association with prostate cancer (OR, 4.41; CI, 2.52-7.72 per 10 nmol/L) regardless of grade. No interactions were observed between genotype and folate concentration, but a weak gene effect was observed for MTHFR A1298C and low-grade prostate cancer. Larger studies to investigate the role of gene-gene/gene-diet interactions in Black men are needed.

  18. Pinning down a polymorphic parasite: new genetic and morphological descriptions of Eimeria macropodis from the Tammar wallaby (Macropus eugenii).

    PubMed

    Hill, Nichola J; Richter, Carolin; Power, Michelle L

    2012-09-01

    Identification of the protozoan parasite, Eimeria has traditionally relied on oocyst morphology, host range and life-cycle attributes. However, it is increasingly recognized that Eimeria species can vary in size and shape across their host range, an attribute known as 'polymorphism' that presents a unique challenge for identification. Advances in molecular tools hold promise for characterising Eimeria that may otherwise be misclassified based on morphology. Our study used morphologic and molecular traits of the oocyst life stage to identify a polymorphic parasite, Eimeria macropodis in a captive Tammar wallaby (Macropus eugenii) population in Australia. Molecular characterization highlighted the need to use multiple genetic markers (18S SSU and cytochrome c oxidase subunit I) to accurately identify E. macropodis owing to heterozygous alleles at the 18S SSU locus. This study provided an opportunity to assess the utility and shortcomings of morphologic and molecular techniques for 'pinning down' a polymorphic species. Moreover, our study was able to place E. macropodis in an evolutionary context and enhance resolution of the under-studied marsupial clade.

  19. 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

  20. 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

  1. Incremental effect for antisocial personality disorder genetic risk combining 5-HTTLPR and 5-HTTVNTR polymorphisms.

    PubMed

    Garcia, Luis F; Aluja, Anton; Fibla, Joan; Cuevas, Lara; García, Oscar

    2010-05-15

    As the serotonin transporter gene (SLC6A4 or 5-HTT) is a key regulator of central serotonergic activity, several association studies between Antisocial Personality Disorder (APD) and the SLC6A4 polymorphisms have been conducted in the last decade. In the present study, the role of both 5-HTTLPR and 5-HTTVNTR polymorphisms of the SLC6A4 gene in APD is investigated. A sample of 147 male inmates was analyzed. APD was assessed by Aluja's Antisocial Personality Disorder Scale, a measure that correlates 0.73 with the dimensional score of DSM-IV APD and 0.62 with factor II of the Psychopathy Checklist-Revised. Inmates presenting both 5-HTTLPR S/S+S/L and 5-HTTVNTR 12/12 had a higher risk of being classified in the APD group (Odds ratio=3.48). The results also showed that the genotype and haplotype distribution was more dissimilar when extreme groups were compared with odds ratios up to 6.50. Our results supported that, in addition to the widely investigated 5-HTTLPR polymorphism, the 5-HTTVNTR polymorphism might be an interesting candidate for association studies with APD. Results also suggested that previous failures to replicate the association between serotonin transporter gene polymorphisms and APD, or similar phenotypes, could have been due to an under-representation of extremely high APD subjects in the samples analyzed.

  2. 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.

  3. Genetic Polymorphisms in CYP2E1: Association with Schizophrenia Susceptibility and Risperidone Response in the Chinese Han Population

    PubMed Central

    Wei, Zhiyun; Shen, Lu; Xiong, Yuyu; Wu, Xi; Niu, Jiamin; Han, Xia; Tian, Zhengan; Yang, Lun; Feng, Guoyin; He, Lin; Qin, Shengying

    2012-01-01

    Background CYP2E1 is a member of the cytochrome P450 superfamily, which is involved in the metabolism and activation of both endobiotics and xenobiotics. The genetic polymorphisms of CYP2E1 gene (Chromosome 10q26.3, Accession Number NC_000010.10) are reported to be related to the development of several mental diseases and to be involved in the clinical efficacy of some psychiatric medications. We investigated the possible association of CYP2E1 polymorphisms with susceptibility to schizophrenia in the Chinese Han Population as well as the relationship with response to risperidone in schizophrenia patients. Methods In a case-control study, we identified 11 polymorphisms in the 5' flanking region of CYP2E1 in 228 schizophrenia patients and 384 healthy controls of Chinese Han origin. From among the cases, we chose 130 patients who had undergone 8 weeks of risperidone monotherapy to examine the relationship between their response to risperidone and CYP2E1 polymorphisms. Clinical efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS). Results Statistically significant differences in allele or genotype frequencies were found between cases and controls at rs8192766 (genotype p = 0.0048, permutation p = 0.0483) and rs2070673 (allele: p = 0.0018, permutation p = 0.0199, OR = 1.4528 95%CI = 1.1487–1.8374; genotype: p = 0.0020, permutation p = 0.0225). In addition, a GTCAC haplotype containing 5 SNPs (rs3813867, rs2031920, rs2031921, rs3813870 and rs2031922) was observed to be significantly associated with schizophrenia (p = 7.47E-12, permutation p<0.0001). However, no association was found between CYP2E1 polymorphisms/haplotypes and risperidone response. Conclusions Our results suggest that CYP2E1 may be a potential risk gene for schizophrenia in the Chinese Han population. However, polymorphisms of the CYP2E1 gene may not contribute significantly to individual differences in the therapeutic efficacy of risperidone. Further

  4. Genetic polymorphisms, the metabolism of estrogens and breast cancer: a review.

    PubMed

    Bugano, D D G; Conforti-Froes, N; Yamaguchi, N H; Baracat, E C

    2008-01-01

    Breast cancer is the most common female cancer and the second cause of cancer death in women. Despite recent breakthroughs, much of the etiology of this disease is unknown and the most important risk factor, i.e., exposure to endogenous and exogenous estrogen throughout life cannot explain the heterogeneity of prognosis nor clinical features of patients. Recently, many gene polymorphisms in the metabolism of breast cancer have been described as possible neoplasm etiologic factors. This review is an attempt to summarize the current knowledge about these polymorphisms and to determine new target genes for diagnosis and treatment of the disease. Polymorphisms in the genes CYP17, CYP19, CYP1A1, CYP1A2, CYP1B1, UGT1A1, SULT1A1, 17-hydroxysteroid-dehydrogenase, COMT, GST, ESR1, and ESR2 are described.

  5. The use of genetic markers for detecting DNA polymorphism, genotype identification and phylogenetic relationships among banana cultivars.

    PubMed

    Venkatachalam, L; Sreedhar, R V; Bhagyalakshmi, N

    2008-06-01

    Genetic variations and relationships among 21 commercially important banana cultivars of South India were evaluated using 50 decamer RAPD primers and 12 ISSR primers. The primers were selected after a preliminary screening of several such primers for their ability to produce clear and reproducible patterns of multiple bands. The analyses resulted in the amplification of totally 641 bands of 200-3100bp, of which 382 bands were polymorphic, corresponding to nearly 60% genetic diversity. The RAPD and ISSR surveys between pairs of 21 cultivars revealed 60.15% and 56.73% of polymorphic bands, respectively. A strong linear relationship was observed between the Resolving power (Rp) of the primer and its ability to distinguish genotypes. Based on these data, a genetic similarity matrix was established and a dendrogram for each set of primers was developed by UPGMA. The genetic similarity coefficients in RAPD analysis ranged from 0.3177 to 0.7818 and in ISSR analysis from 0.1800 to 0.8462. A fingerprinting key was generated where the presence/absence of specific RAPD/ISSR bands were recorded for each cultivar. The presence of a specific RAPD (OPC-5(800)) band was observed for an endemic cultivar--Nanjanagudu Rasabale (NR). The study resulted in the identification and molecular classification of South Indian banana cultivars of which Robusta and Williams are global and others have either limited geographical distribution or purely endemic to South India. A group of eight cultivars was identified that are highly distinct from one another. The members of this group may be useful for generating 2X and 4X breeding populations for further use in breeding secondary triploid hybrids.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. PRELIMINARY REPORT ON THE PUTATIVE ASSOCIATION OF IL10 -3575 T/A GENETIC POLYMORPHISM WITH MALARIA SYMPTOMS.

    PubMed

    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.

  11. Association between genetic polymorphism in NFKB1 and NFKBIA and coronary artery disease in a Chinese Han population

    PubMed Central

    Lai, Hongmei; Chen, Qingjie; Li, Xiaomei; Ma, Yitong; Xu, Rui; Zhai, Hui; Liu, Fen; Chen, Bangdang; Yang, Yining

    2015-01-01

    Objectives: Prior studies have demonstrated NF-κB plays an important role in the development and progression of inflammatory diseases. The aim of this study was to investigate whether promoter polymorphisms in NFKB1 and NFKBIA gene are associated with coronary artery disease (CAD) in a Chinese Han population. Methods: A total of 1140 Han CAD patients and 1156 Han control subjects were genotyped for 4 single-nucleotide polymorphisms (SNPs) in the promoter region of NFKBIA gene (rs3138053, rs2233406, rs2233409) and NFKB1 gene (-94 ins/del ATTG, rs28362491) by using the TaqMan SNP genotyping assays, and then NFKBIA haplotype blocks were reconstructed according to our genotyping data. Results: For total, men, and women, the distribution of genotypes, alleles of rs3138053, rs2233406, rs2233409 and haplotype polymorphisms showed no significant difference between CAD cases and controls. None of the studied NFKBIA SNPs were associated with CAD. For total, men, and women, there was significant difference in the distribution of the genotypes (P=0.001, P=0.024, P= 0.022) and alleles (P=0.001, P=0.012, P=0.031) of rs28362491 in CAD cases and controls. For total, men, and women, the rs28362491 was associated with increased risk of CAD in a recessive model after adjustment for covariates (OR=1.505, 95% CI 1.190 to 1.903, P=0.001; OR=1.469, 95% CI 1.082-1.993, P=0.014; OR=1.622, 95% CI 1.118 to 2.352, P=0.011, respectively). Conclusions: In our study, the -94 ins/del ATTG polymorphism in NFKB1 promoter is associated with CAD susceptibility in Chinese Han population, providing a new insight into the genetics of CAD in Chinese Han population. PMID:26885097

  12. Susceptibility to Ulcerative Colitis and Genetic Polymorphisms of A251G SOD1 and C-262T CAT

    PubMed Central

    El-Kheshen, Gadier; Moeini, Maryam

    2016-01-01

    Summary Background Reactive oxygen species can attack and damage almost every molecule found in living cells, including proteins, carbohydrates, lipids, and DNA. For this reason, their production is normally tightly controlled. Among the most important defenses against these radicals are the superoxide dismutase (SOD) enzymes and catalase (CAT). Increasing attention has been given to the role of reactive oxygen metabolites in the pathogenesis of ulcerative colitis (UC), which is defined as an idiopathic and chronic intestinal inflammation. Accordingly, we hypothesized a relation between genetic polymorphisms in the two antioxidant enzymes SOD1 A251G (rs2070424) and CAT C-262T (rs1001179) and the risk of UC. Methods The present case-control study included 109 UC patients (46 males and 50 females) and 186 (67 males and 119 females) gender-matched healthy controls. Genotyping was done by the PCR-RFLP method. Results After adjusting for age and gender, a significant association was observed between the AG+GG genotypes of SOD1 A251G polymorphism (vs. AA genotype) and risk of UC (OR=0.29, 95% CI: 0.10–0.86, P= 0.025) after adjusting for age and gender. Our statistical analysis revealed that the CAT C-262T polymorphism did not associate with the risk of UC before and/or after adjusting for age and gender. Conclusions Based on the present statistical analysis, the G allele of the SOD1 A251G polymorphism decreases the risk of UC, thus it might be assumed that the G allele has a protective role.

  13. 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.

  14. 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.

  15. BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related stem cell transplantation

    PubMed Central

    Piras, Ignazio Stefano; Angius, Andrea; Andreani, Marco; Testi, Manuela; Lucarelli, Guido; Floris, Matteo; Marktel, Sarah; Ciceri, Fabio; La Nasa, Giorgio; Fleischhauer, Katharina; Roncarolo, Maria Grazia; Bulfone, Alessandro

    2014-01-01

    The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We applied a whole genome analysis to investigate genetic variants - other than HLA class I and II - associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 β-Thalassemic patients. We identified two single nucleotide polymorphisms in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong Linkage Disequilibrium between each other (R2=0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P < 0.00001 for BAT2 SNP rs11538264, and P < 0.0001 for BAT3 SNP rs10484558). Whereas, the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs. 2.6%, nominal P = 1.15×10−8; and adjusted P = 0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT. PMID:25111513

  16. Aging males' symptoms in relation to the genetically determined androgen receptor CAG polymorphism, sex hormone levels and sample membership.

    PubMed

    Schneider, Gudrun; Nienhaus, Kathrin; Gromoll, Jörg; Heuft, Gereon; Nieschlag, Eberhard; Zitzmann, Michael

    2010-05-01

    Late-onset hypogonadism describes the co-occurrence of a range of physical, psychological and sexual symptoms in aging men, with the implication that these symptoms are caused by androgen deficiency. Previous investigations examined mostly population samples and did not take into account the testosterone modulating effects of the genetically determined CAG repeat polymorphism (CAGn) of the androgen receptor (AR) gene. This is the first study which investigates aging male symptoms (AMS) in relation to the genetically determined androgen receptor CAG polymorphism, estradiol and testosterone levels in men > or =50 years of age in a healthy population sample (n=100), outpatients of an andrological department (n=76) who presented with sexual and "aging male" symptoms and a psychosomatic/psychiatric sample (n=120) who presented with various psychological and medically unexplained somatic complaints. Although the population sample was significantly older than the two patient groups, they reported significantly fewer AMS and had higher testosterone levels and shorter CAG repeats of the AR. Regression analysis revealed influences of CAGn on the AMS global score and the psychological and somatic subscale only in the two patient samples, while testosterone had some impact on the sexual subscale. Our results suggest that the so-called aging male symptoms show a certain association to androgenicity, but that they are rather unspecific and of multifactorial origin. Other factors contributing to AMS need further clarification.

  17. Novel approach of molecular genetic understanding of iridology: relationship between iris constitution and angiotensin converting enzyme gene polymorphism.

    PubMed

    Um, Jae-Young; An, Nyeon-Hyoung; Yang, Gui-Bi; Lee, Geon-Mok; Cho, Ju-Jang; Cho, Jae-Woon; Hwang, Woo-Jun; Chae, Han-Jung; Kim, Hyung-Ryong; Hong, Seung-Heon; Kim, Hyung-Min

    2005-01-01

    Iridology is the study of the iris of the eye to detect the conditions of the body and its organs, genetic strengths and weaknesses, etc. Although iridology is not widely used as a scientific tool for healthcare professionals to get to the source of people's health conditions, it has been used as a supplementary source to help the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris among some Korean Oriental medical doctors. Angiotensin converting enzyme (ACE) gene polymorphism is one of the most well studied genetic markers of vascular disease. We investigated the relationship between iridological constitution and ACE polymorphism in hypertensives. We classified 87 hypertensives and 79 controls according to iris constitution and determined the ACE genotype of each individual. DD genotype was more prevalent in patients with a neurogenic constitution than in controls. This finding supports the hypothesis that D allele is a candidate gene for hypertension and demonstrates the association among ACE genotype, Korean hypertensives and iris constitution.

  18. Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population.

    PubMed

    Trinks, J; Hulaniuk, M L; Caputo, M; Pratx, L Burgos; Ré, V; Fortuny, L; Pontoriero, A; Frías, A; Torres, O; Nuñez, F; Gadano, A; Corach, D; Flichman, D

    2014-12-01

    The prevalence of genetic polymorphisms identified as predictors of therapeutic-induced hepatitis C virus (HCV) clearance differs among ethnic groups. However, there is a paucity of information about their prevalence in South American populations, whose genetic background is highly admixed. Hence, single-nucleotide polymorphisms rs12979860, rs1127354 and rs7270101 were characterized in 1350 healthy individuals, and ethnicity was assessed in 259 randomly selected samples. The frequency of rs12979860CC, associated to HCV treatment response, and rs1127354nonCC, related to protection against hemolytic anemia, were significantly higher among individuals with maternal and paternal Non-native American haplogroups (64.5% and 24.2%), intermediate among admixed samples (44.1% and 20.4%) and the lowest for individuals with Native American ancestry (30.4% and 6.5%). This is the first systematic study focused on analyzing HCV predictors of antiviral response and ethnicity in South American populations. The characterization of these variants is critical to evaluate the risk-benefit of antiviral treatment according to the patient ancestry in admixed populations.

  19. Hyperhomocysteinemia and related genetic polymorphisms correlate with ulcerative colitis in Chinese Han population in Central China [corrected].

    PubMed

    Jiang, Yi; Xia, Xuanping; Wang, Wenxing; Lin, Limiao; Xu, Changlong; Cai, Zhenzai; Zheng, Bo; Pei, Jihua; Shen, Sujian; Xia, Bing

    2012-01-01

    Increased levels of homocysteine are found systemically and in intestinal mucosa of patients with inflammatory bowel disease, and, specifically, in ulcerative colitis (UC). However, there are controversial reports regarding the factors contributing to increased levels of homocysteine in UC. Furthermore, little information is available regarding the relationship between hyperhomocysteinemia (HHcy), vitamin status, and genetic polymorphisms of homocysteine-related enzymes in these patients. This study examined four functional polymorphisms linked to homocysteine metabolism (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G), and evaluated plasma levels of homocysteine, folate, and vitamin B(12) in 310 consecutive patients with UC and 936 age- and sex-matched healthy controls from southeast China. The variant allele and genotypic frequencies in MTHFR A1298C, MTR A2756G and MTRR A66G genes were significantly higher in patients with UC compared to healthy controls. Further, HHcy and low levels of folate and vitamin B(12) were more frequent in patients with UC. The MTR 2756G allele, extent of the disease, and gender were the independent determinants of HHcy in these patients. These findings suggest that genetic and nutritional factors have a synergetic effect on HHcy in patients with UC. In conclusion, our data highlight a prevention strategy for moderation of HHcy and supplementation with folate and vitamine B(12) in patients with UC from Southeast China.

  20. Association between survivin genetic polymorphisms and epidermal growth factor receptor mutation in non-small-cell lung cancer

    PubMed Central

    Liu, Tu-Chen; Hsieh, Ming-Ju; Wu, Wen-Jun; Chou, Ying-Erh; Chiang, Whei-Ling; Yang, Shun-Fa; Su, Shih-Chi; Tsao, Thomas Chang-Yao

    2016-01-01

    Survivin is an anti-apoptotic protein that is implicated in the regulation of apoptosis and cell cycle in various types of cancers. The current study explored the effect of survivin gene polymorphisms and EGFR mutations in non-small-cell lung carcinoma (NSCLC) patients. A total of 360 participants, including 291 adenocarcinoma lung cancer and 69 squamous cell carcinoma lung cancer patients, were selected for the analysis of three survivin genetic variants (survivin -31, +9194, and +9809) by using real-time PCR genotyping. The results indicated that GC+CC genotypes of survivin -31 were significant association with EGFR mutation in lung adenocarcinoma patients (adjusted odds ratio=3.498, 95% CI = 1.171-10.448; p<0.01). Moreover, The GC+CC genotypes of survivin -31 were associated with EGFR L858R mutation but not in exon 19 in-frame deletions. Furthermore, among patients in exon 19 in-frame deletions, those who have at least one polymorphic G allele of survivin -31 have an increased incidence to develop late-stage when compared with those patients homozygous for C/C (OR, 4.800; 95% CI, 1.305-17.658). In conclusion, our results showed that survivin genetic variants were related to EGFR mutation in lung adenocarcinoma patients and might contribute to pathological development to NSCLC. PMID:27994498

  1. Biochemical and genetic polymorphisms for carboxylesterase and acetylesterase in grape clones of Vitis vinifera L. (Vitaceae) cultivars.

    PubMed

    Orasmo, Gleice Ribeiro; Oliveira-Collet, Sandra A; Lapenta, Ana Sílvia; de Fátima P S Machado, Maria

    2007-10-01

    Native polyacrylamide gel electrophoresis (PAGE) was employed to show the highest number of esterase loci and to detect alpha- and beta-esterase polymorphisms in leaf buds of Vitis vinifera cultivars. A total of 16 esterase isozymes were detected in leaf buds from 235 plants including Italia, Rubi, Benitaka, and Brasil cultivars. Biochemical characterization of the grape esterases using ester substrates revealed alpha-, beta-, and alpha/beta-esterases with inhibitor tests distinguishing both carboxylesterases (EST-2, EST-3, EST-5, EST-6, EST-7, EST-8, EST-9, EST-10, and EST-16 isozymes) and acetylesterases (EST-4, EST-11, EST-12, EST-13, EST-14, EST-15 isozymes). No allele variation for alpha-, beta-, and alpha/beta-esterases was detected; however, EST-3 alpha-carboxylesterase was absent in 61.7% of vines, and EST-4 alpha/beta-acetylesterase was absent in one vine of Rubi cv. Null EST-3 carboxylesterase phenotype (61.7%) cannot be explained in this article, but the high genetic polymorphism in four V. vinifera clones is a positive aspect for genetic selection and development of new clones with different characteristics.

  2. Association Study of Vitamin D Receptor (VDR) - Related Genetic Polymorphisms and their Haplotypes with Chronic Periodontitis in Colombian Population

    PubMed Central

    Isaza-Guzmán, Diana María; Pineda-Trujillo, Nicolás

    2017-01-01

    Introduction There is strong evidence that both genetic and environmental factors may affect the periodontal clinical status. However, epidemiological evidence on the association between Vitamin D Receptor (VDR) polymorphisms and Chronic Periodontitis (CP) has been inconsistent. Aim The focus of this study was to identify if a possible association between VDR Single-Nucleotide Polymorphisms (SNPs) may be implicated in the aetiopathogenesis of CP in Colombian population. Materials and Methods One hundred and ten CP patients and 50 Healthy Controls (HC) were recruited. Periodontal status was assessed based on probing depth, clinical attachment level, extent, and severity of periodontal breakdown. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify the VDR rs7975232, rs1544410, rs2228570, and rs731236 SNPs from saliva samples. Odds Ratios (ORs) along with their 95% Confidence Intervals (CIs) were computed to compare the distribution of genotypes/alleles between HC and CP patients, alongside with analysis of Linkage Disequilibrium (LD) and haplotype associations between SNPs. Also, an analysis of the interaction between genetic findings and those significant demographic factors was performed for all SNPs. Results There was no association neither between the different genotypes/allele frequencies nor haplotypes and CP. Similarly, no significant differences in extent or severity amongst genotype/allele groups were observed. Even so, interaction analysis revealed significant synergistic interactions between each SNP and age associated with the disease status. Conclusion Although these results do not support that VDR SNPs could be identified as independent risk predictor variables for CP in the Colombian population, synergistic biological interactive effects of all these SNPs related to age might play a significant role in the pathogenic pathways of CP. PMID:28384983

  3. Genetic Analysis of Aedes aegypti Using Random Amplified Polymorphic DNA (RAPD) Markers from Dengue Outbreaks in Pakistan

    PubMed Central

    Ashraf, Hafiz Muhammad; Zahoor, Muhammad Kashif; Nasir, Shabab; Majeed, Humara Naz; Zahoor, Sarwat

    2016-01-01

    Background: Keeping in view the havoc situation of dengue fever in Pakistan, the current study was designed to demonstrate the genetic variations, gene flow and rate of migration from Lahore and Faisalabad. Methods: The larvae were collected from both natural and artificial breeding places from each collection site. The adult mosquitoes were collected by means of sweep net and battery-operated aspirator. DNA extraction was performed using TNE buffer method. Ten GeneLink-A series RAPD primers were used for PCR amplification and the data was analyzed through POPGENE. Results: The number of amplification products produced per primer varied from 8–12, ranging from 200 to 2000 bp with an average of 10.0 bands per primer. The percentage of polymorphic loci amplified by each primer varied from 22.5 to 51%. The UPGMA dendrogram demonstrates two distinct groups from Faisalabad and Lahore populations. The genetic diversity ranged from 0.260 in Faisalabad to 0.294 in Lahore with a total heterozygosity of 0.379. The GST value for nine populations within Lahore was 0.131 (Nm= 3.317), whereas for nine populations in Faisalabad GST value was 0.117 (Nm= 3.773). The overall genetic variation among eighteen populations showed GST= 0.341 and Nm= 1.966. Conclusion: The genetic relatedness and Nm value show that Ae. aegypti populations exhibit intra-population gene flow both in Faisalabad and Lahore. Although, both cities show a distinct pattern of genetic structure; however, few areas from both the cities show genetic similarity. The gene flow and the genetic relatedness in few populations of Lahore and Faisalabad cities need further investigation. PMID:28032107

  4. Genetic Polymorphism of 1019C/G (rs6295) Promoter of Serotonin 1A Receptor and Catechol-O-Methyltransferase in Panic Disorder

    PubMed Central

    Ishiguro, Shin; Aoki, Akiko; Ueda, Mikito; Hayashi, Yuki; Akiyama, Kazufumi; Kato, Kazuko; Shimoda, Kazutaka

    2017-01-01

    Objective Family and twin studies have suggested genetic liability for panic disorder (PD) and therefore we sought to determine the role of noradrenergic and serotonergic candidate genes for susceptibility for PD in a Japanese population. Methods In this age- and gender-matched case-control study involving 119 PD patients and 119 healthy controls, we examined the genotype distributions and allele frequencies of the serotonin transporter gene linked polymorphic region (5-HTTLPR), −1019C/G (rs6295) promoter polymorphism of the serotonin receptor 1A (5-HT1A), and catechol-O-methyltransferase (COMT) gene polymorphism (rs4680) and their association with PD. Results No significant differences were evident in the allele frequencies or genotype distributions of the COMT (rs4680), 5-HTTLPR polymorphisms or the −1019C/G (rs6295) promoter polymorphism of 5-HT1A between PD patients and controls. Although there were no significant associations of these polymorphisms with in subgroups of PD patients differentiated by gender or in subgroup comorbid with agoraphobia (AP), significant difference was observed in genotype distributions of the −1019C/G (rs6295) promoter polymorphism of 5-HT1A between PD patients without AP and controls (p=0.047). Conclusion In this association study, the 1019C/G (rs6295) promoter polymorphism of the 5-HT1A receptor G/G genotype was associated with PD without AP in a Japanese population. PMID:28096880

  5. Association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population.

    PubMed

    Park, Chul-Soo; Park, So-Young; Lee, Chul-Soon; Sohn, Jin-Wook; Hahn, Gyu-Hee; Kim, Bong-Jo

    2006-06-01

    Family, twin, and adoption studies have demonstrated that genes play an important role in the development of alcoholism. We investigated the association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population. The genotype of the GABAA receptor gene polymorphisms were determined by performing polymerase chain reaction genotyping for 172 normal controls and 162 male alcoholics who are hospitalized in alcoholism treatment institute. We found a significant association between the genetic polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene and alcoholism. The GG genotype of the GABAA alpha1 receptor gene was associated with the onset age of alcoholism and alcohol withdrawal symptoms, and a high score on the Korean version of the ADS. However, there was no association between the genetic polymorphisms of the GABAA beta2 and gamma2 receptor gene and alcoholisms. Our finding suggest that genetic polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene may be associated with the development of alcoholism and that the GG genotype of the GABAA alpha1 receptor gene play an important role in the development of the early onset and the severe type of alcoholism.

  6. Genetic diversity of the Phaseolus acutifolius A. Gray collection of the USDA National Plant Germplasm system using targeted region amplified polymorphism markers designed from genes associated with heat and drought stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Molecular genetic relationships among 222 accessions of the Phaseolus acutifolius A. Gray collection were assessed using Targeted Region Amplified Polymorphic (TRAP) markers designed from sequences of genes associated with heat and drought tolerance. Genetic relationships were compared to reactions ...

  7. General and Specific Genetic Polymorphism of Cytokines-Related Gene in AITD

    PubMed Central

    Yizhou, Mei; Bei, He; Huilong, Li; Xin, Wang; Rui, Hu; Lu, Li

    2017-01-01

    Autoimmune thyroid disease (AITD) shows the highest incidence among organ-specific autoimmune diseases and is the most common thyroid disease in humans, including Graves' disease (GD) and Hashimoto's thyroiditis (HT). The susceptibility to autoimmune diseases is affected by increased autoantibody levels, susceptibility gene polymorphisms, environmental factors, and psychological factors, but the pathogenesis remains unclear. Various cytokines and related genes encoding them play important roles in the development and progression of AITD. CD152, an expression product of the CTLA-4 gene, downregulates T cell activation. The A/A genotype polymorphism in the CT60 locus may reduce the production of thyroid autoantibodies. The C1858T polymorphism of the PTNP22 gene reduces the expression of its encoded LYP, which increases the risk of GD and HT. GD is an organ-specific autoimmune disease involving increased secretion of thyroid hormone, whereas HT may be associated with the destruction of thyroid gland tissue and hypothyroidism. These two diseases exhibit similar pathogenesis but opposite trends in the clinical manifestations. In this review, we focus on the structure and function of these cytokines and related genes in AITD, as well as the association of polymorphisms with susceptibility to GD and HT, and attempt to describe their differences in pathogenesis and clinical manifestations. PMID:28133421

  8. 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...

  9. Stable genetic polymorphism in heterogeneous environments: balance between asymmetrical dispersal and selection in the acorn barnacle.

    PubMed

    Véliz, D; Duchesne, P; Bourget, E; Bernatchez, L

    2006-03-01

    Elucidating the processes responsible for maintaining polymorphism at ecologically relevant genes is intimately related to understanding the interplay between selection imposed by habitat heterogeneity and a species' capacity for dispersal in the face of environmental constraints. In this paper, we used a model-based approach to solve equilibria of balanced polymorphism, given values of fitness and larval dispersal among different habitats in the acorn barnacle Semibalanus balanoides from the Gulf of St Lawrence. Our results showed that allele frequencies observed at both MPI* and GPI* loci represented stable equilibria, given empirical estimates of fitness values, and that considerably more larvae dispersed from one region (north) to the other (south) than vice versa. Dispersal conditions were predicted to be similar for the maintenance of polymorphism at both loci. Moreover, the values of asymmetrical dispersal required by the model to reach stable equilibria were compatible with empirical estimates of larval dispersal and oceanic circulation documented in this system. Overall, this study illustrated the usefulness of a modified and computable version of Bulmer's model (1972) in order to test hypotheses of balanced polymorphism resulting from interactions between spatial selection and asymmetrical dispersal.

  10. [Identification of genetic polymorphisms associated with overweight in athletes of winter sports].

    PubMed

    Sorokina, E Iu; Solntseva, T N; Radzhabkadiev, R M; Samoĭlov, A S

    2013-01-01

    The identification of polymorphisms rs9939609 gene FTO, Trp64Arg ADRB3 and gene -866G> A UCP2 gene using multiplex allele-specific PCR hybridization-fluorescence detection in real time has been carried out in highly skilled athletes under the age of 30 years engaged in biathlon (n = 25) and bobsleigh (n = 28). The data on the frequency of allele risk of obesity has been obtained. The study of polymorphism rs9939609 of the FTO gene in biathletes found that 30% of them are carriers of the risk allele of obesity (A). Among the bobsledder the frequency of allele A is slightly higher than in European populations and is 55.4%. The study of gene polymorphism Trp64Arg ADRB3 shored that the frequency of risk allele of obesity 64Arg in biathletes (14%) was slightly higher than in the European population and biathletes (5.4%). The results of the identification of polymorphism -866G> A gene UCP2 in biathletes and bobsledders, found the incidence of obesity risk allele, respectively, 52 and 58.7%.

  11. 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

  12. Calving traits of crossbred Brahman Cows are Associated with Heat Shock Protein 70 Genetic Polymorphisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives were to: 1) identify single nucleotide polymorphisms (SNP) located in the promoter region of the bovine heat shock protein 70 gene, and 2) evaluate associations between Hsp70 SNP and calving rates of Brahman-influenced cows. Specific primers were designed for PCR amplification of a 539 b...

  13. 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…

  14. [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.

  15. 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

  16. Polymorphic heterologous microsatellite loci for population genetics studies of the white-faced ibis Plegadis chihi (Vieillot, 1817) (Pelecaniformes, Threskiornithidae)

    PubMed Central

    de Castro e Souza, Andiara Silos Moraes; Miño, Carolina Isabel; Del Lama, Silvia Nassif

    2012-01-01

    We screened 44 heterologous microsatellites isolated in species of the families Threskiornithidae, Ciconiidae and Ardeidae for their use in a migratory waterbird, the white-faced ibis Plegadis chihi (Vieillot, 1817) (Threskiornithidae). Of the screened loci, 57% amplified successfully and 24% were polymorphic. In two breeding colonies from southern Brazil (N = 131) we detected 32 alleles (2–10 alleles/locus). Average He over all loci and colonies was 0.55, and the combined probability of excluding false parents, 98%. There was no departure from HWE in any loci or population. Eru6 and Eru4 loci were in non-random association in the Alvorada colony, and NnNF5 and Eru5 in both populations. AMOVA analysis indicated that most of the genetic diversity was contained within populations. Structure analysis suggested a single population, and FST value showed weak genetic structuring (FST = 0.009, p = 0.05). The two populations are apparently connected through gene-flow. The panel of six microsatellites optimized here was sufficiently informative for characterizing the genetic diversity and structure in these natural populations of the white-faced ibis. The information generated could be useful in future studies of genetic diversity, relatedness and the mating system in Plegadis chihi and related species. PMID:22481877

  17. Genetic differentiation among 6 populations of red deer (Cervus elaphus L.) in Poland based on microsatellite DNA polymorphism.

    PubMed

    Radko, Anna; Zalewski, D; Rubiś, Dominika; Szumiec, Agnieszka

    2014-12-01

    Recently, there has been considerable interest in genetic differentiation in the Cervidae family. A common tool used to determine genetic variation in different species, breeds and populations is DNA analysis, which allows for direct determination of the differences and changes within a group of animals. Because the analysis of microsatellite polymorphism in different Cervidae populations revealed considerable genetic variability in individual populations, it was important to test a set of markers in animals from these populations.The study was performed with muscle tissue and blood samples collected from a total of 793 red deer. Six groups (subpopulations) of red deer were defined according to region: Masurian (330 animals), Bieszczady (194 animals), Małopolska (80 animals), Sudety (76 animals), Lower Silesian (62 animals) and Lubusz (51 animals). The analysis involved 12 STR markers (BM1818, OarAE129, OarFCB5, OarFCB304, RM188, RT 1, RT 13, T26, T156, T193, T501, TGLA53), for which conditions for simultaneous amplification were established.Based on this study, it is concluded that the chosen set of 12 microsatellite markers could be used to evaluate the genetic structure and to monitor changes in Poland's red deer population.

  18. The association between hepatitis C virus infection, genetic polymorphisms of oxidative stress genes and B-cell non-Hodgkin's lymphoma risk in Egypt.

    PubMed

    Farawela, Hala; Khorshied, Mervat; Shaheen, Iman; Gouda, Heba; Nasef, Aya; Abulata, Nelly; Mahmoud, Hebat-Allah; Zawam, Hamdy M; Mousa, Somaia M

    2012-08-01

    Hepatitis C virus (HCV) has been postulated to be an etiological agent for lymphoid malignancies. Polymorphisms in oxidative stress genes as; superoxide dismutase (SOD2), glutathione peroxidase (GPX1), catalase (CAT), myeloperoxidase (MPO) and nitric oxide synthase (NOS2) may influence non-Hodgkin's lymphoma (NHL) risk. HCV screening and polymorphisms in these five genes coding for antioxidant enzymes were studied in 100 Egyptian patients with B cell-NHL and 100 controls to clarify the association between HCV infection, oxidative stress genes polymorphisms and B cell-NHL risk. A significantly higher prevalence of HCV infection was detected among NHL patients relative to controls and this carried a 14-fold increased NHL risk (odds ratio (OR)=14.3, 95% confidence interval (CI)=5.4-38.3, p<0.0001). GPX1 and MPO genetic polymorphisms conveyed increase in B-NHL risk (OR=3.3, 95% CI=1.4-7.4, p=0.004 and OR=4.4, 95% CI=1.3-14.2, p=0.009 respectively). Further analyses stratified by HCV infection revealed that concomitant HCV infection and GPX1 gene polymorphism had a synergetic effect on NHL risk with an OR of 15 (95%CI=2.2-69.6, p<0.0001). In addition, combined HCV infection and MPO gene polymorphisms had a pronounced NHL risk (OR=9.2, 95%CI=2.5-33.9, p<0.0001). SOD2, CAT and NOS2 genetic polymorphisms were not found to confer increased NHL risk. This study revealed that HCV infection is a risk factor for NHL in Egypt. Polymorphisms in GPX1 and MPO genes may influence NHL risk in HCV infected Egyptian patients. Larger scale studies are warranted to establish this genetic susceptibility for NHL.

  19. Genetic association between hOGG1 C8069G polymorphism and colorectal cancer risk

    PubMed Central

    Sun, Xiaoge; Yang, Hao; Lin, Yu; Zhao, Jianguo; Bao, Yinna; Liu, Xiulan; Qi, Zhen; Wang, Shaojun; Huang, Congxiu; Yu, Zhilong

    2015-01-01

    Background: hOGG1 C8069G polymorphism has been extensively investigated in single studies as well as meta-analyses in terms of the association with colorectal cancer (CRC). But the results remain contradictory. This study was undertaken to comprehensively evaluate the association of the commonly studied hOGG1 C8069G polymorphism and the susceptibility to CRC. Methods: By searching the electronic databases of PubMed, Embase, and Web of science, 16 available publications consisting of 4,866 cases and 7,363 controls were finally included in our meta-analysis. Stratified analyses by ethnicity and source of control were also carried out to further assess the association between hOGG1 C8069G polymorphism and CRC risk. Results: hOGG1 C8069G polymorphism was not observed to have statistical significance with the susceptibility to CRC (ORCC vs. GG = 0.97, 95% CI = 0.91-1.05; P = 0.995; ORCC + CG vs. GG = 0.98, 95% CI = 0.93-1.04; P = 0.993; ORCC vs. CG + GG = 0.96, 95% CI = 0.90-1.02; P = 0.339; ORallele C vs. allele G = 0.98, 95% CI = 0.94-1.02; P = 0.912; ORCG vs. GG = 0.95, 95% CI = 0.88-1.03; P = 0.526). Similarly, no association was found in the subgroup analysis by ethnicity or the source of control. Conclusions: The results of our meta-analysis did not demonstrate any evidence for significant association between hOGG1 C8069G polymorphism and CRC risk. Future large-scale studies are expected to be conducted to further confirm our findings. PMID:26885047

  20. CYP1A1 genetic polymorphisms and uterine leiomyoma risk: a meta-analysis

    PubMed Central

    Wang, Fen; Chen, Jiying; Wang, Lin; Ma, Yulan; Mayinuer, Niyazi

    2015-01-01

    Background: Some studies assessed the association between CYP1A1 MspI and Ile462Val polymorphisms and uterine leiomyoma (UL) risk. However, the results were controversial. We did this meta-analysis to determine the association between CYP1A1 MspI and Ile462Val polymorphisms and UL risk. Materials and methods: We searched databases containing PubMed, Springer Link, EMBASE, Chinese National Knowledge Infrastructure (CNKI) up to 11 October 2014. Pooled ORs and 95% CIs were used to assess the strength of the associations. Results: In total, 9 case-control studies with 2157 UL cases and 2197 healthy controls were included in this meta-analysis. CYP1A1 Ile462Val polymorphism was significantly associated with UL risk (OR = 2.29, 95% CI 1.75-2.99, P < 0.00001). In the subgroup analysis by race, significantly increased risks were found in the Asians (OR = 2.76, 95% CI 1.86-4.09, P < 0.00001) and Caucasians (OR = 1.87, 95% CI 1.30-2.68, P = 0.0007). However, MspI polymorphism was not significantly associated with UL risk (OR = 1.15, 95% CI 0.90-1.47, P = 0.27). In the subgroup analysis by race, no significant association was found in the Asians (OR = 1.15, 95% CI 0.86-1.54, P = 0.35). Conclusion: In summary, the results of the meta-analysis suggested that CYP1A1 Ile462Val polymorphism was significantly associated with UL risk. PMID:26064254

  1. CYP1A1 genetic polymorphism and polycyclic aromatic hydrocarbons on pulmonary function in the elderly: haplotype-based approach for gene-environment interaction.

    PubMed

    Choi, Yoon-Hyeong; Kim, Jin Hee; Hong, Yun-Chul

    2013-08-29

    Lung function may be impaired by environmental pollutants not only acting alone, but working with genetic factors as well. Few epidemiologic studies have been conducted to explore the interplay of polycyclic aromatic hydrocarbons (PAHs) exposure and genetic polymorphism on lung function in the elderly. For genetic polymorphism, haplotype is considered a more informative unit than single nucleotide polymorphism markers. Therefore, we examined the role of haplotype based-CYP1A1 polymorphism in the effect of PAHs exposure on lung function in 422 participants from a community-based panel of elderly adults in Seoul, Korea. Linear mixed effect models were fit to evaluate the association of PAH exposure markers (urinary 1-hydroxypyrene and 2-naphthol) with FVC, FEV₁, FEV₁/FVC, and FEF₂₅₋₇₅, and then the interaction with CYP1A1 haplotype constructed from three single nucleotide polymorphisms of the gene (rs4646421/rs4646422/rs1048943). Urinary 1-hydroxypyrene levels were inversely associated with FEV₁/FVC (p<0.05), whereas urinary 2-naphthol levels failed to show associations with lung function. Urinary 1-hydroxypyrene was significantly associated with decrease in FEV₁/FVC among participants with rs4646421 variants (CT+TT), rs4646422 wild-type (GG), and rs1048943 wild-type (AA). At least one TGA haplotype predicted a 0.88% (95% confidence interval, 0.31-1.45%) reduction in FEV₁/FVC with an interquartile range increase in 1-hydroxypyrene, whereas no relationship was observed in participants without TGA haplotype (p for interaction=0.045). Similar patterns were also observed in FEF₂₅₋₇₅. We did not find any main effects of CYP1A1 genetic polymorphisms on lung functions. Our findings suggest that PAH exposure producing 1-hydroxypyrene as a metabolite compromises lung function in the elderly, and that haplotype-based CYP1A1 polymorphism modifies the risk.

  2. Population genetic structure of clinical and environmental isolates of Blastomyces dermatitidis, Based on 27 Polymorphic Microsatellite Markers

    USGS Publications Warehouse

    Meece, J.K.; Anderson, J.L.; Fisher, M.C.; Henk, D.A.; Sloss, Brian L.; Reed, K.D.

    2011-01-01

    Blastomyces dermatitidis, a thermally dimorphic fungus, is the etiologic agent of North American blastomycosis. Clinical presentation is varied, ranging from silent infections to fulminant respiratory disease and dissemination to skin and other sites. Exploration of the population genetic structure of B. dermatitidis would improve our knowledge regarding variation in virulence phenotypes, geographic distribution, and difference in host specificity. The objective of this study was to develop and test a panel of microsatellite markers to delineate the population genetic structure within a group of clinical and environmental isolates of B. dermatitidis. We developed 27 microsatellite markers and genotyped B. dermatitidis isolates from various hosts and environmental sources (n = 112). Assembly of a neighbor-joining tree of allele-sharing distance revealed two genetically distinct groups, separated by a deep node. Bayesian admixture analysis showed that two populations were statistically supported. Principal coordinate analysis also reinforced support for two genetic groups, with the primary axis explaining 61.41% of the genetic variability. Group 1 isolates average 1.8 alleles/locus, whereas group 2 isolates are highly polymorphic, averaging 8.2 alleles/locus. In this data set, alleles at three loci are unshared between the two groups and appear diagnostic. The mating type of individual isolates was determined by PCR. Both mating type-specific genes, the HMG and ??-box domains, were represented in each of the genetic groups, with slightly more isolates having the HMG allele. One interpretation of this study is that the species currently designated B. dermatitidis includes a cryptic subspecies or perhaps a separate species. ?? 2011, American Society for Microbiology.

  3. Population genetic structure of clinical and environmental isolates of Blastomyces dermatitidis based on 27 polymorphic microsatellite markers

    USGS Publications Warehouse

    Meece, Jennifer K.; Anderson, Jennifer L.; Fisher, Matthew C.; Henk, Daniel A.; Sloss, Brian L.; Reed, Kurt D.

    2011-01-01

    Blastomyces dermatitidis, a thermally dimorphic fungus, is the etiologic agent of North American blastomycosis. Clinical presentation is varied, ranging from silent infections to fulminant respiratory disease and dissemination to skin and other sites. Exploration of the population genetic structure of B. dermatitidis would improve our knowledge regarding variation in virulence phenotypes, geographic distribution, and difference in host specificity. The objective of this study was to develop and test a panel of microsatellite markers to delineate the population genetic structure within a group of clinical and environmental isolates of B. dermatitidis. We developed 27 microsatellite markers and genotyped B. dermatitidis isolates from various hosts and environmental sources (n=112). Assembly of a neighbor-joining tree of allele-sharing distance revealed two genetically distinct groups, separated by a deep node. Bayesian admixture analysis showed that two populations were statistically supported. Principal coordinate analysis also reinforced support for two genetic groups, with the primary axis explaining 61.41% of the genetic variability. Group 1 isolates average 1.8 alleles/locus, whereas group 2 isolates are highly polymorphic, averaging 8.2 alleles/locus. In this data set, alleles at three loci are unshared between the two groups and appear diagnostic. The mating type of individual isolates was determined by PCR. Both mating type-specific genes, the HMG and α-box domains, were represented in each of the genetic groups, with slightly more isolates having the HMG allele. One interpretation of this study is that the species currently designated B. dermatitidis includes a cryptic subspecies or perhaps a separate species.

  4. Adaptive Color Polymorphism and Unusually High Local Genetic Diversity in the Side-Blotched Lizard, Uta stansburiana

    PubMed Central

    Micheletti, Steven; Parra, Eliseo; Routman, Eric J.

    2012-01-01

    Recently, studies of adaptive color variation have become popular as models for examining the genetics of natural selection. We examined color pattern polymorphism and genetic variation in a population of side-blotched lizards (Uta stansburiana) that is found in habitats with both dark (lava) and light colored (granite) substrates. We conducted a limited experiment for adult phenotypic plasticity in laboratory conditions. We recorded both substrate and lizard color patterns in the field to determine whether lizards tended to match their substrate. Finally we examined genetic variation in a gene (melanocortin 1 receptor) that has been shown to affect lizard color in other species and in a presumably neutral gene (mitochondrial cytochrome b). Populations were sampled in the immediate area of the lava flows as well as from a more distant site to examine the role of population structure. Our captive Uta did not change color to match their background. We show that side-blotched lizards tend to match the substrate on which it was caught in the field and that variation in the melanocortin 1 receptor gene does not correlate well with color pattern in this population. Perhaps the most remarkable result is that this population of side-blotched lizards shows extremely high levels of variation at both genetic markers, in the sense of allele numbers, with relatively low levels of between-allele sequence variation. Genetic variation across this small region was as great or greater than that seen in samples of pelagic fish species collected worldwide. Statistical analysis of genetic variation suggests rapid population expansion may be responsible for the high levels of variation. PMID:23133520

  5. Potential relationship between single nucleotide polymorphisms used in forensic genetics and diseases or other traits in European population.

    PubMed

    Pombar-Gomez, Maria; Lopez-Lopez, Elixabet; Martin-Guerrero, Idoia; Garcia-Orad Carles, Africa; de Pancorbo, Marian M

    2015-05-01

    Single nucleotide polymorphisms (SNPs) are an interesting option to facilitate the analysis of highly degraded DNA by allowing the reduction of the size of the DNA amplicons. The SNPforID 52-plex panel is a clear example of the use of non-coding SNPs in forensic genetics. However, nonstop advances in studies of genetic polymorphisms are leading to the discovery of new associations between SNPs and diseases. The aim of this study was to perform a comprehensive review of the state of association between the 52 SNPs in the 52-plex panel and diseases or other traits related to their treatment, such as drug response characters. In order to achieve this goal, we have conducted a bioinformatic search for each SNP included in the panel and the SNPs in linkage disequilibrium (LD) with them in the European population (r (2)  > 0.8). A total of 424 SNPs (52 in the panel and 372 in LD) were investigated in PubMed, Scopus, and dbSNP databases. Our results show that three SNPs in the SNPforID 52-plex panel (rs2107612, rs1979255, rs1463729) have been associated with diseases such as hypertension or macular degeneration, as well as drug response. Similarly, three out of the 372 SNPs in LD (rs2107614, r (2)  = 0.859; rs765250, r (2)  = 0.858; rs11064560, r (2)  = 0,887) are also associated with various pathologies. In view of these results, we propose the need for a periodic review of the SNPs used in forensic genetics in order to keep their associations with diseases or related phenotypes updated and to evaluate their continuity in forensic panels for avoiding legal and ethical conflicts.

  6. The influence of genetic polymorphisms on the efficacy and side effects of anastrozole in postmenopausal breast cancer patients.

    PubMed

    Abubakar, Murtala B; Wei, Keat; Gan, Siew Hua

    2014-12-01

    Breast cancer is a common cause of cancer mortality among women. Several genetic factors have been implicated in its development. Current treatment guidelines for estrogen receptor-positive breast cancer recommend that anastrozole [or any of the other two aromatase inhibitors (letrozole and exemestane)] is used as an alternative to tamoxifen or following several years of tamoxifen treatment. Nevertheless, this approach is still associated with many challenges, ranging from the recurrence of breast cancer to considerable interindividual variability in the tolerability of anastrozole, which may cause adverse effects, such as musculoskeletal symptoms, and lead to the withdrawal of many patients from treatment. Variabilities in the genes encoding the drug target (aromatase) or its metabolizing enzymes (CYP3A and UGT1A) contribute toward the interindividual variability in anastrozole's pharmacokinetics and/or pharmacodynamics. This paper reviews the role of genetic polymorphisms of CYP19A1, CYP3A4, and UGT1A4 in the responses of female hormone receptor-positive postmenopausal breast cancer patients to anastrozole. Many reviews in the literature have suggested that the study of functional polymorphisms and investigation of relevant genetic markers may provide valuable information in predicting responses to anastrozole in terms of its therapeutic and adverse effects. Nevertheless, more studies are required before the knowledge of its pharmacogenomics can be applied to the individualization of treatment to ensure that patients receive the maximum benefits. Therefore, future analyses, including but not limited to genome-wide association studies, are encouraged to address some of the gray areas in the pharmacogenomics of anastrozole therapy in postmenopausal breast cancer cases; this will help in providing guidance for future pharmacogenomics protocols when anastrozole is utilized in patients' management.

  7. Population-level diversity in the association of genetic polymorphisms of one-carbon metabolism with breast cancer risk.

    PubMed

    Naushad, Shaik Mohammad; Divya, Chandrasekhar; Janaki Ramaiah, M; Hussain, Tajamul; Alrokayan, Salman A; Kutala, Vijay Kumar

    2016-10-01

    Aberrations in one-carbon metabolism were reported to increase breast cancer risk by influencing the DNA synthesis and methylation of DNA and catecholamines. However, the results of these association studies remain inconclusive. We have explored the contribution of eight genetic polymorphisms in modulating the susceptibility to breast cancer by performing a meta-analysis of worldwide studies. In total, 62 case-control studies representing 17 different populations involving 18,117 breast cancer cases and 23,573 healthy controls were included in this meta-analysis. Out of the eight polymorphisms analyzed, methylenetetrahydrofolate reductase (MTHFR) C677T exhibited positive association with the breast cancer risk in both fixed effects (OR 1.14, 95 % CI 1.10-1.17) and random effects (OR 1.10, 95 % CI 1.02-1.18) models. Solute carrier family 19 (folate transporter), member 1 (SLC19A1) G80A exhibited positive association (OR 1.16, 95 % CI 1.03-1.31) while MTR A2756G exhibited an inverse association (OR 0.78, 95 % CI 0.75-0.82) with the breast in fixed effect model alone. Significant heterogeneity was observed in the association of MTHFR C677T with breast cancer even between studies from the same geographical area, specifically among Chinese, Indians, and Turks. Subgroup analysis revealed MTHFR C677T-mediated breast cancer risk in post-menopausal women and women with low dietary intake of folate. Geographical area wise segregation of data revealed MTHFR-mediated increased breast cancer risk in populations who consume methionine-rich diet. Altitude-level variations were observed in the association of SHMT1 C1420T with breast cancer. India and Brazil of same altitude showed an inverse association with this polymorphism, while USA and China that share similar altitude showed a null association. MTHFR C677T and SLC19A1 G80A are the two polymorphisms of one-carbon metabolic pathway that increase breast cancer in the worldwide population. Dietary patterns and altitudinal

  8. Role of Genetic Polymorphisms in NFKB-Mediated Inflammatory Pathways in Response to Primary Chemoradiation Therapy for Rectal Cancer

    SciTech Connect

    Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

    2014-11-01

    Purpose: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Methods and Materials: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. Results: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Conclusions: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment.

  9. FAS and FASL genetic polymorphisms impact on clinical outcome of malignant pleural mesothelioma

    PubMed Central

    El-Hamamsy, Manal; Ghali, Ramy R; Saad, Amr S; Shaheen, Sara M; Salem, Ahmed M

    2016-01-01

    Background FAS-670 A>G (rs1800682) and FASL-844 C>T (rs763110) polymorphisms have been previously correlated with clinical outcome of non-small cell lung cancer (NSCLC) and breast and bladder cancers. We investigated the influence of these polymorphisms on clinical outcome of malignant pleural mesothelioma (MPM) patients. Patients and methods In this cohort study (NCT02269878), 68 epithelioid MPM Egyptian patients treated with first-line platinum-based chemotherapy were recruited in the period between April 2014 and May 2015. The genotype analysis was performed using TaqMan® single-nucleotide polymorphism genotyping assay. The association between the selected polymorphisms and response rate, progression-free survival (PFS) and overall survival (OS) at 18 months was evaluated. Results The median age of patients was 55 years and 45.6% of them received platinum in combination with pemetrexed, while 54.4% received platinum in combination with gemcitabine. FASL-844 CC genotype was more common than expected in early-stage tumor (P=0.042). It was found that there was no association between the investigated polymorphisms and response rate or 18-month OS. However, the PFS rate at 18 months for FASL-844 CC genotype carriers was 45% versus 10.6% for FASL-844 CT/TT genotypes carriers (log-rank: 6.2; P=0.013). Also, the number of platinum-based cycles and tumor stage were found to be significant variables for PFS by univariate analysis (P≤0.001 and P=0.006, respectively). Stratified Cox regression showed that the carriers of FASL-844 CT/TT genotypes were still more susceptible to disease progression than carriers of FASL-844 CC genotype (adjusted HR =3.77, 95% CI: 1.34–10.62, P=0.012). Conclusion The results of this study suggest that FASL-844 C/T polymorphism could predict PFS in MPM patients receiving platinum-based chemotherapy; therefore, this should be further evaluated as a potential marker for the prediction of clinical outcome in patients with MPM. PMID:27853379

  10. Biomarkers of susceptibility following benzene exposure: influence of genetic polymorphisms on benzene metabolism and health effects.

    PubMed

    Carbonari, Damiano; Chiarella, Pieranna; Mansi, Antonella; Pigini, Daniela; Iavicoli, Sergio; Tranfo, Giovanna

    2016-01-01

    Benzene is a ubiquitous occupational and environmental pollutant. Improved industrial hygiene allowed airborne concentrations close to the environmental context (1-1000 µg/m(3)). Conversely, new limits for benzene levels in urban air were set (5 µg/m(3)). The biomonitoring of exposure to such low benzene concentrations are performed measuring specific and sensitive biomarkers such as S-phenylmercapturic acid, trans, trans-muconic acid and urinary benzene: many studies referred high variability in the levels of these biomarkers, suggesting the involvement of polymorphic metabolic genes in the individual susceptibility to benzene toxicity. We reviewed the influence of metabolic polymorphisms on the biomarkers levels of benzene exposure and effect, in order to understand the real impact of benzene exposure on subjects with increased susceptibility.

  11. Genetic polymorphisms of vascular endothelial growth factor and angiopoietin 2 in retinopathy of prematurity.

    PubMed

    Bányász, Ilona; Bokodi, Géza; Vannay, Adám; Szebeni, Beáta; Treszl, András; Vásárhelyi, Barna; Tulassay, Tivadar; Szabó, András

    2006-01-01

    Angiogenic factors such as vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) contribute to development of retinopathy of prematurity (ROP). We aimed to test whether polymorphisms of these factors are associated with ROP. VEGF(-2578) and Ang2(-35) polymorphisms were analyzed with PCR-RFLP method in 200 preterm infants without ROP or with ROP stages 1-5. Our results suggest that there is no association between carrier state of VEGF(-2578) and Ang2(-35) and risk of ROP in preterm infants. The prevalence of VEGF(-2578) "A" allele was lower in preterm boys with severe ROP (stages 4-5) than in those without or with mild ROP (stages 1-3).

  12. Oxidative stress is associated with genetic polymorphisms in one-carbon metabolism in coronary artery disease.

    PubMed

    Vijaya Lakshmi, S V; Naushad, Shaik Mohammad; Seshagiri Rao, D; Kutala, Vijay Kumar

    2013-11-01

    In view of growing body of evidence favouring the association of aberrations in one-carbon metabolism and oxidative stress in the aetiology of coronary artery disease (CAD), we investigated the risk associated with polymorphisms regulating the folate uptake and transport such as the glutamate carboxypeptidase II (GCPII) C1561T, reduced folate carrier 1 (RFC1) G80A and cytosolic serine hydroxymethyltransferase (cSHMT) C1420T. We further evaluated the impact of seven putatively functional polymorphisms of this pathway on oxidative stress markers. Genotyping was performed on 288 CAD cases and 266 healthy controls along with the dietary folate assessment. GCPII C1561T polymorphism was found to be an independent risk factor (OR 2.71, 95% CI 1.47-4.98) for CAD, whereas cSHMT C1420T conferred protection (OR 0.51, 95% CI 0.37-0.70). Oxidative stress markers like the plasma levels of malondialdehyde, protein carbonyls and 8-oxo-deoxyguanosine were significantly increased and total glutathione was significantly decreased in CAD cases. Elevated oxidative stress was observed in subjects carrying GCPII 1561T and MTRR 66A-variant alleles and low oxidative stress was observed in the subjects carrying cSHMT 1420T and TYMS 5'-UTR 2R allele. GCPII C1561T, MTHFR C677T and MTRR A66G polymorphisms were observed to influence the homocysteine levels (P < 0.05). SHMT and TYMS variants were found to decrease oxidative stress by increasing the folate pool (r = 0.38, P = 0.003) and also by increasing the antioxidant status (r = 0.28, P = 0.03). Influence of dietary folate status was not observed. Overall, this study revealed elevated oxidative stress that was associated with the aberrations in one-carbon metabolism which could possibly influence the CAD risk.

  13. Human genetic selection on the MTHFR 677C>T polymorphism

    PubMed Central

    Mayor-Olea, Álvaro; Callejón, Gonzalo; Palomares, Arturo R; Jiménez, Ana J; Gaitán, María Jesús; Rodríguez, Alfonso; Ruiz, Maximiliano; Reyes-Engel, Armando

    2008-01-01

    Background The prevalence of genotypes of the 677C>T polymorphism for the MTHFR gene varies among humans. In previous studies, we found changes in the genotypic frequencies of this polymorphism in populations of different ages, suggesting that this could be caused by an increase in the intake of folate and multivitamins by women during the periconceptional period. The aim was to analyze changes in the allelic frequencies of this polymorphism in a Spanish population, including samples from spontaneous abortions (SA). Methods A total of 1305 subjects born in the 20th century were genotyped for the 677C>T polymorphism using allele specific real-time PCR with Taqman® probes. A section of our population (n = 276) born in 1980–1989 was compared with fetal samples (n = 344) from SA of unknown etiology from the same period. Results An increase in the frequency of the T allele (0.38 vs 0.47; p < 0.001) and of the TT genotype (0.14 vs 0.24; p < 0.001) in subjects born in the last quarter of the century was observed. In the 1980–1989 period, the results show that the frequency of the wild type genotype (CC) is about tenfold lower in the SA samples than in the controls (0.03 vs 0.33; p < 0.001) and that the frequency of the TT genotype increases in the controls (0.19 to 0.27) and in the SA samples (0.20 to 0.33 (p < 0.01)); r = 0.98. Conclusion Selection in favor of the T allele has been detected. This selection could be due to the increased fetal viability in early stages of embryonic development, as is deduced by the increase of mutants in both living and SA populations. PMID:19040733

  14. The Associations between Two Vital GSTs Genetic Polymorphisms and Lung Cancer Risk in the Chinese Population: Evidence from 71 Studies

    PubMed Central

    Ma, Ting; Han, Liyuan; Mao, Guochuan; Chen, Jian; Yue, Xia; Wang, Huiqin; Zhang, Lu; Jin, Guixiu; Jiang, Jianmin; Zhao, Jinshun; Zou, Baobo

    2014-01-01

    Background The genetic polymorphisms of glutathione S-transferase (GSTs) have been suspected to be related to the development of lung cancer while the current results are conflicting, especially in the Chinese population. Methods Data on genetic polymorphisms of glutathione S-transferase Mu 1 (GSTM1) from 68 studies, glutathione S-transferase theta 1 (GSTT1) from 17 studies and GSTM1-GSTT1 from 8 studies in the Chinese population were reanalyzed on their association with lung cancer risk. Odds ratios (OR) were pooled using forest plots. 9 subgroups were all or partly performed in the subgroup analyses. The Galbraith plot was used to identify the heterogeneous records. Potential publication biases were detected by Begg's and Egger's tests. Results 71 eligible studies were identified after screening of 1608 articles. The increased association between two vital GSTs genetic polymorphisms and lung cancer risk was detected by random-effects model based on a comparable heterogeneity. Subgroup analysis showed a significant relationship between squamous carcinoma (SC), adenocarcinoma (AC) or small cell lung carcinoma (SCLC) and GSTM1 null genotype, as well as SC or AC and GSTT1 null genotype. Additionally, smokers with GSTM1 null genotype had a higher lung cancer risk than non-smokers. Our cumulative meta-analysis demonstrated a stable and reliable result of the relationship between GSTM1 null genotype and lung cancer risk. After the possible heterogeneous articles were omitted, the adjusted risk of GSTs and lung cancer susceptibility increased (fixed-effects model: ORGSTM1 = 1.23, 95% CI: 1.19 to 1.27, P<0.001; ORGSTT1 = 1.18, 95% CI: 1.10 to 1.26, P<0.001; ORGSTM1-GSTT1 = 1.33, 95% CI: 1.10 to 1.61, P = 0.004). Conclusions An increased risk of lung cancer with GSTM1 and GSTT1 null genotype, especially with dual null genotype, was found in the Chinese population. In addition, special histopathological classification of lung cancers and a wide range of gene

  15. Prevalence of CYP2B6 polymorphisms in Argentinians: the role of genetic testing.

    PubMed

    Scibona, P; Vazquez, C; Cajal, A R; Argibay, P F; Belloso, W H

    2015-12-11

    CYP2B6 is a highly polymorphic isoenzyme involved in the metabolism of many drugs including cyclophosphamide, bupropion, and efavirenz. A single nucleotide polymorphism (SNP) in CYP2B6 (516G>T) resulted in decreased expression and function associated with the CYP2B6*6 haplotype. Among the clinical implications of this phenotype, decreased activation of cyclophosphamide and increased plasma levels of efavirenz associated with increased central nervous system toxicity have been reported. The frequency of the CYP2B6 (516G>T) SNP has been studied in several different populations, but there is no data regarding distribution among Argentinians. In this study, 102 DNA samples from healthy volunteers were analyzed using a polymerase chain reaction-restriction fragment length polymorphism reaction specific for the CYP2B6 (516G>T) SNP. Our results showed a prevalence of 71.08% for the G allele and 28.92% for the T allele. This was distributed as 52.9% for the GG genotype (reduced dosage required), 36.6% for the GT genotype (normal dosage range), and 10.8% for the TT genotype (high drug toxicity). There was no preferential gender distribution observed. The relatively high prevalence of the TT genotype in our population supports the clinical use of genotyping as an additional tool in personalized medicine.

  16. APBB2 genetic polymorphisms are associated with severe cognitive impairment in centenarians.

    PubMed

    Golanska, Ewa; Sieruta, Monika; Gresner, Sylwia M; Pfeffer, Anna; Chodakowska-Zebrowska, Malgorzata; Sobow, Tomasz M; Klich, Izabela; Mossakowska, Malgorzata; Szybinska, Aleksandra; Barcikowska, Maria; Liberski, Pawel P

    2013-04-01

    APBB2 gene encodes for β-amyloid precursor protein-binding family B member 2, (APBB2, FE65-like, FE65L1), an adaptor protein binding to the cytoplasmatic domain of β-amyloid precursor protein (βAPP). Over-expression of APBB2 promotes formation of β-amyloid (Aβ), the main constituent of senile plaques. Polymorphisms within APBB2 gene have been proposed as candidate risk factors for Alzheimer's disease. However, their association with longevity has never been investigated. Here we present the first attempt to analyze APBB2 polymorphisms in centenarians. We used a PCR-RFLP method to analyze two intronic nucleotide substitutions: hCV1558625 (rs17443013) and rs13133980. We found no differences in genotype or allele distribution between centenarians and young controls. After stratification of centenarians upon their cognitive performance, the APBB2 rs13133980 G allele was over-represented in centenarians with severe cognitive impairment compared to individuals without this disability. Also the hCV1558625-rs13133980 AG haplotype increased relative risk for severe cognitive impairment in centenarians. Our results support the concept of APBB2 polymorphism association with cognitive performance in the oldest age.

  17. Polymorphism and genetic mapping of the human oxytocin receptor gene on chromosome 3

    SciTech Connect

    Michelini, S.; Urbanek, M.; Goldman, D.

    1995-06-19

    Centrally administered oxytocin has been reported to facilitate affiliative and social behaviors, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection. The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene. A portion of the 3{prime} untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two alleles occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected was used to map the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma. 53 refs., 2 figs., 1 tab.

  18. Association of GSTO2 (N142D) Genetic Polymorphism and Acute Rejection of Liver

    PubMed Central

    Khosravi, M.; Saadat, I.; Karimi, M. H.; Malek Hosseini, S. A.

    2016-01-01

    Background: Acute rejection is the main problem in liver transplantation that occurs in the first days or months of transplantation. It includes histological and cellular rejection. Acute histological rejection is confirmed by biopsy. Glutathione S-transferase family is the most important genes in phase II detoxification working in xenobiotic and drug metabolism. GSTO2 is one of the members of this family. GSTO2 (N142D) polymorphism may influence metabolism of immunosuppressive drugs. Objective: To determine if GSTO2 polymorphism has association with acute liver rejection. Methods: The present study included 120 patients with histological-proven acute liver rejection and 182 patients without acute rejection. Both groups were matched for sex and age. To determine variants of GSTO2, we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: There was a significant association between the GSTO2 genotype and acute liver rejection (NN: OR: 3.642, 95% CI: 1.179–5.444) and (ND: OR: 2.533, 95% CI: 1.672–8.149) compared to those with DD geneotype. Conclusion: Recipients with either NN or ND genotype for GSTO2 are more likely to develop acute liver rejection compared to those with DD genotype. PMID:27721965

  19. Genetic polymorphism of the CAPN1 gene is associated with meat quality traits in Japanese quail.

    PubMed

    Rasouli, Z; Zerehdaran, S; Azari, M A; Shargh, M S

    2013-01-01

    1. The objective of the study was to investigate the polymorphisms in two regions of the calpain 1 (CAPN1) gene and their association with breast and thigh meat quality in Japanese quail (ultimate pH (pHu), lightness, redness, yellowness, drip loss, thawing-cooking loss, water holding capacity and shear force, SF). 2. Blood samples were collected randomly from 100 birds and DNA was extracted using a commercial kit. Genotypes were determined by PCR amplification followed by single-strand conformation polymorphism (SSCP) analysis. The effect of CAPN1 genotypes on meat quality traits were analysed using a general linear model (GLM) procedure. 3. Genotypes of the CAPN1 gene in the first region (217-bp) analysed were significantly associated with yellowness and SF. The TT genotype showed significantly higher yellowness and lower shear force (more tenderness) than CT and CC genotypes. Genotypes of the second region of the gene (intron 4, 800-bp) were significantly associated with pHu, redness and SF of the breast meat. The BB genotype showed significantly lower pHu and redness and higher SF (lower tenderness) than other genotypes. 4. Information on polymorphisms of the CAPN1 gene will eventually provide useful information for improving meat quality of Japanese quail through marker-assisted selection.

  20. Genetic polymorphisms of estrogen receptor alpha and catechol-O-methyltransferase genes in Turkish patients with familial prostate carcinoma

    PubMed Central

    Pazarbasi, Ayfer; Yilmaz, M. Bertan; Alptekin, Davut; Luleyap, Umit; Tansug, Zuhtu; Ozpak, Lutfiye; Izmirli, Muz