WorldWideScience

Sample records for haplotype relative risk

  1. [The genotype-based haplotype relative risk and transmission disequilibrium test analyses of familial febrile convulsions].

    Science.gov (United States)

    Qi, Y; Wu, X; Guo, Z; Zhang, J; Pan, H; Li, M; Bao, X; Peng, J; Zou, L; Lin, Q

    1999-10-01

    To confirm the linkage of familial febrile convulsions to the short arm of chromosome 6(6p) or the long arm of chromosome 8(8q). The authors finished genotyping of Pst I locus on the coding region of heat shock protein (HSP) 70, 5'untranslated region of HSP70-1, 3' untranslated region of HSP70-2, D8S84 and D8S85. The data were processed by the genotype-based haplotype relative risk(GHRR) and transmission disequilibrium test(TDT) methods in PPAP. Some signs of association and disequilibrium between D8S85 and FC were shown by GHRR and TDT. A suspect linkage of familial febrile convulsions to the long arm of chromosome 8 has been proposed.

  2. Modeling and E-M estimation of haplotype-specific relative risks from genotype data for a case-control study of unrelated individuals.

    Science.gov (United States)

    Stram, Daniel O; Leigh Pearce, Celeste; Bretsky, Phillip; Freedman, Matthew; Hirschhorn, Joel N; Altshuler, David; Kolonel, Laurence N; Henderson, Brian E; Thomas, Duncan C

    2003-01-01

    The US National Cancer Institute has recently sponsored the formation of a Cohort Consortium (http://2002.cancer.gov/scpgenes.htm) to facilitate the pooling of data on very large numbers of people, concerning the effects of genes and environment on cancer incidence. One likely goal of these efforts will be generate a large population-based case-control series for which a number of candidate genes will be investigated using SNP haplotype as well as genotype analysis. The goal of this paper is to outline the issues involved in choosing a method of estimating haplotype-specific risk estimates for such data that is technically appropriate and yet attractive to epidemiologists who are already comfortable with odds ratios and logistic regression. Our interest is to develop and evaluate extensions of methods, based on haplotype imputation, that have been recently described (Schaid et al., Am J Hum Genet, 2002, and Zaykin et al., Hum Hered, 2002) as providing score tests of the null hypothesis of no effect of SNP haplotypes upon risk, which may be used for more complex tasks, such as providing confidence intervals, and tests of equivalence of haplotype-specific risks in two or more separate populations. In order to do so we (1) develop a cohort approach towards odds ratio analysis by expanding the E-M algorithm to provide maximum likelihood estimates of haplotype-specific odds ratios as well as genotype frequencies; (2) show how to correct the cohort approach, to give essentially unbiased estimates for population-based or nested case-control studies by incorporating the probability of selection as a case or control into the likelihood, based on a simplified model of case and control selection, and (3) finally, in an example data set (CYP17 and breast cancer, from the Multiethnic Cohort Study) we compare likelihood-based confidence interval estimates from the two methods with each other, and with the use of the single-imputation approach of Zaykin et al. applied under both

  3. Analysis of SNPs and haplotypes in vitamin D pathway genes and renal cancer risk.

    Directory of Open Access Journals (Sweden)

    Sara Karami

    2009-09-01

    Full Text Available In the kidney vitamin D is converted to its active form. Since vitamin D exerts its activity through binding to the nuclear vitamin D receptor (VDR, most genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR and other vitamin D pathway genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC etiology. RCC cases (N = 777 and controls (N = 1,035 were genotyped to investigate the relationship between RCC risk and variation in eight target genes. Minimum-p-value permutation (Min-P tests were used to identify genes associated with risk. A three single nucleotide polymorphism (SNP sliding window was used to identify chromosomal regions with a False Discovery Rate of <10%, where subsequently, haplotype relative risks were computed in Haplostats. Min-P values showed that VDR (p-value = 0.02 and retinoid-X-receptor-alpha (RXRA (p-value = 0.10 were associated with RCC risk. Within VDR, three haplotypes across two chromosomal regions of interest were identified. The first region, located within intron 2, contained two haplotypes that increased RCC risk by approximately 25%. The second region included a haplotype (rs2239179, rs12717991 across intron 4 that increased risk among participants with the TC (OR = 1.31, 95% CI = 1.09-1.57 haplotype compared to participants with the common haplotype, TT. Across RXRA, one haplotype located 3' of the coding sequence (rs748964, rs3118523, increased RCC risk 35% among individuals with the variant haplotype compared to those with the most common haplotype. This study comprehensively evaluated genetic variation across eight vitamin D pathway genes in relation to RCC risk. We found increased risk associated with VDR and RXRA. Replication studies are warranted to confirm these findings.

  4. Association analysis of the dopamine D{sub 2} receptor gene in Tourette`s syndrome using the haplotype relative risk method

    Energy Technology Data Exchange (ETDEWEB)

    Noethen, M.M.; Cichon, S.; Propping, P. [Univ. of Bonn (Germany)] [and others

    1994-09-15

    Comings et al. have recently reported a highly significant association between Tourette`s syndrome (TS) and a restriction fragment length polymorphism (RFLP) of the dopamine D{sub 2} receptor gene (DRD2) locus. The A1 allele of the DRD2 Taq I RFLP was present in 45% of the Tourette patients compared with 25% of controls. We tried to replicate this finding by using the haplotype relative risk (HRR) method for association analysis. This method overcomes a major problem of conventional case-control studies, where undetected ethnic differences between patients and controls may result in a false-positive finding, by using parental alleles not inherited by the proband as control alleles. Sixty-one nuclear families encompassing an affected child and parents were typed for the DRD2 Taq I polymorphism. No significant differences in DRD2 A1 allele frequency were observed between TS probands, sub-populations of probands classified according to tic severity, or parental control alleles. Our data do not support the hypothesis that the DRD2 locus may act as a modifying gene in the expression of the disorder in TS probands. 40 refs., 1 tab.

  5. F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort

    Science.gov (United States)

    Schwarz, John; Astermark, Jan; Menius, Erika D.; Carrington, Mary; Donfield, Sharyne M.; Gomperts, Edward D.; Nelson, George W.; Oldenburg, Johannes; Pavlova, Anna; Shapiro, Amy D.; Winkler, Cheryl A.; Berntorp, Erik

    2012-01-01

    Background Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in hemophilia A. It has been suggested that differences in the distribution of factor VIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Design and Methods Data from the HIGS Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1+H2) and inhibitor risk among individuals of genetically-determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and HLA were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Results H3 was associated with higher inhibitor risk among those genetically-identified (N=49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N=223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Conclusion H3 was not an independent predictor of inhibitor risk. Further, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual. PMID:22958194

  6. The interaction between coagulation factor 2 receptor and interleukin 6 haplotypes increases the risk of myocardial infarction in men.

    Directory of Open Access Journals (Sweden)

    Bruna Gigante

    Full Text Available The aim of the study was to investigate if the interaction between the coagulation factor 2 receptor (F2R and the interleukin 6 (IL6 haplotypes modulates the risk of myocardial infarction (MI in the Stockholm Heart Epidemiology Program (SHEEP. Seven SNPs at the F2R locus and three SNPs at the IL6 locus were genotyped. Haplotypes and haplotype pairs (IL6*F2R were generated. A logistic regression analysis was performed to analyze the association of the haplotypes and haplotype pairs with the MI risk. Presence of an interaction between the two haplotypes in each haplotype pair was calculated using two different methods: the statistical, on a multiplicative scale, which includes the cross product of the two factors into the logistic regression model; the biological, on an additive scale, which evaluates the relative risk associated with the joint presence of both factors. The ratio between the observed and the predicted effect of the joint exposure, the synergy index (S, indicates the presence of a synergy (S>1 or of an antagonism (S<1. None of the haplotypes within the two loci was associated with the risk of MI. Out of 22 different haplotype pairs, the haplotype pair 17 GGG*ADGTCCT was associated with an increased risk of MI with an OR (95%CI of 1.58 (1.05-2.41 (p = 0.02 in the crude and an OR of 1.72 (1.11-2.67 (p = 0.01 in the adjusted analysis. We observed the presence of an interaction on a multiplicative scale with an OR (95%CI of 2.24 (1.27-3.95 (p = 0.005 and a slight interactive effect between the two haplotypes on an additive scale with an OR (95%CI of 1.56 (1.02-2.37 (p = 0.03 and S of 1.66 (0.89-31. In conclusion, our results support the hypothesis that the interaction between these two functionally related genes may influence the risk of MI and suggest new mechanisms involved in the genetic susceptibility to MI.

  7. Common ataxia telangiectasia mutated haplotypes and risk of breast cancer: a nested case–control study

    International Nuclear Information System (INIS)

    Tamimi, Rulla M; Hankinson, Susan E; Spiegelman, Donna; Kraft, Peter; Colditz, Graham A; Hunter, David J

    2004-01-01

    The ataxia telangiectasia mutated (ATM) gene is a tumor suppressor gene with functions in cell cycle arrest, apoptosis, and repair of DNA double-strand breaks. Based on family studies, women heterozygous for mutations in the ATM gene are reported to have a fourfold to fivefold increased risk of breast cancer compared with noncarriers of the mutations, although not all studies have confirmed this association. Haplotype analysis has been suggested as an efficient method for investigating the role of common variation in the ATM gene and breast cancer. Five biallelic haplotype tagging single nucleotide polymorphisms are estimated to capture 99% of the haplotype diversity in Caucasian populations. We conducted a nested case–control study of breast cancer within the Nurses' Health Study cohort to address the role of common ATM haplotypes and breast cancer. Cases and controls were genotyped for five haplotype tagging single nucleotide polymorphisms. Haplotypes were predicted for 1309 cases and 1761 controls for which genotype information was available. Six unique haplotypes were predicted in this study, five of which occur at a frequency of 5% or greater. The overall distribution of haplotypes was not significantly different between cases and controls (χ 2 = 3.43, five degrees of freedom, P = 0.63). There was no evidence that common haplotypes of ATM are associated with breast cancer risk. Extensive single nucleotide polymorphism detection using the entire genomic sequence of ATM will be necessary to rule out less common variation in ATM and sporadic breast cancer risk

  8. Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

    DEFF Research Database (Denmark)

    Schierup, M.H.; Mailund, T.; Li, H.

    2009-01-01

    Background: A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI) are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular...

  9. Breast cancer risk in ataxia telangiectasia (AT) heterozygotes: haplotype study in French AT families

    Science.gov (United States)

    Janin, N; Andrieu, N; Ossian, K; Laugé, A; Croquette, M-F; Griscelli, C; Debré, M; Bressac-de-Paillerets, B; Aurias, A; Stoppa-Lyonnet, D

    1999-01-01

    Epidemiological studies in ataxia telangiectasia (AT) families have suggested that AT heterozygotes could have an increased cancer risk, especially breast cancer (BC) in women. It has also been suggested that an increased sensibility of AT heterozygotes to the effect of ionizing radiation could be responsible for the increased BC risk. BC relative risk (RR) estimation in AT heterozygotes within families ascertained through AT children is presented here. Family data collected included demographic characteristics, occurrence of cancers, past radiation exposures and blood samples. DNA samples were studied using seven ATM linked microsatellites markers allowing AT haplotypes reconstitution. The relative risk of BC was assessed using French estimated incidence rates. A significant increase risk of BC is found among obligate ATM heterozygotes with a point estimate of 3.32 (P = 0.002). BC relative risk calculated according to age is significantly increased among the obligate ATM heterozygotes female relatives with an age ≤ 44 years (RR = 4.55, P = 0.005). The BC relative risk is statistically borderline among the obligate ATM heterozygote female relatives with an age ≥ 45 years (RR = 2.48, P = 0.08). The estimated BC relative risk among ATM heterozygotes is consistent with previously published data. However, the increased risk is only a little higher than classical reproductive risk factors and similar to the risk associated with a first-degree relative affected by BC. © 1999 Cancer Research Campaign PMID:10362113

  10. Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

    DEFF Research Database (Denmark)

    Schierup, M.H.; Mailund, T.; Li, H.

    2009-01-01

    Background: A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI) are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular r...

  11. Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer

    International Nuclear Information System (INIS)

    Cox, David G; Kraft, Peter; Hankinson, Susan E; Hunter, David J

    2005-01-01

    Truncation mutations in the BRCA1 gene cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population and account for little of the overall incidence of sporadic breast cancer. We used whole-gene resequencing data to select haplotype tagging single nucleotide polymorphisms, and examined the association between common haplotypes of BRCA1 and breast cancer in a nested case-control study in the Nurses' Health Study (1323 cases and 1910 controls). One haplotype was associated with a slight increase in risk (odds ratio 1.18, 95% confidence interval 1.02–1.37). A significant interaction (P = 0.05) was seen between this haplotype, positive family history of breast cancer, and breast cancer risk. Although not statistically significant, similar interactions were observed with age at diagnosis and with menopausal status at diagnosis; risk tended to be higher among younger, pre-menopausal women. We have described a haplotype in the BRCA1 gene that was associated with an approximately 20% increase in risk of sporadic breast cancer in the general population. However, the functional variant(s) responsible for the association are unclear

  12. VNTR alleles associated with the {alpha}-globin locus are haplotype and population related

    Energy Technology Data Exchange (ETDEWEB)

    Martinson, J.J.; Clegg, J.B.; Boyce, A.J. [Univ. of Oxford (United Kingdom)

    1994-09-01

    The human {alpha}-globin complex contains several polymorphic restriction-enzyme sites (i.e., RFLPs) linked to form haplotypes and is flanked by two hypervariable VNTR loci, the 5{prime} hypervariable region (HVR) and the more highly polymorphic 3{prime}HVR. Using a combination of RFLP analysis and PCR, the authors have characterized the 5{prime}HVR and 3{prime}HVR alleles associated with the {alpha}-globin haplotypes of 133 chromosomes, and they here show that specific {alpha}-globin haplotypes are each associated with discrete subsets of the alleles observed at these two VNTR loci. This statistically highly significant association is observed over a region spanning {approximately} 100 kb. With the exception of closely related haplotypes, different haplotypes do not share identically sized 3{prime}HVR alleles. Earlier studies have shown that {alpha}-globin haplotype distributions differ between populations; the current findings also reveal extensive population substructure in the repertoire of {alpha}-globin VNTRs. If similar features are characteristic of other VNTR loci, this will have important implications for forensic and anthropological studies. 42 refs., 5 figs., 5 tabs.

  13. A DRD1 haplotype is associated with risk for autism spectrum disorders in male-only affected sib-pair families.

    Science.gov (United States)

    Hettinger, Joe A; Liu, Xudong; Schwartz, Charles E; Michaelis, Ron C; Holden, Jeanette J A

    2008-07-05

    Individuals with autism spectrum disorders (ASDs) have impairments in executive function and social cognition, with males generally being more severely affected in these areas than females. Because the dopamine D1 receptor (encoded by DRD1) is integral to the neural circuitry mediating these processes, we examined the DRD1 gene for its role in susceptibility to ASDs by performing single marker and haplotype case-control comparisons, family-based association tests, and genotype-phenotype assessments (quantitative transmission disequilibrium tests: QTDT) using three DRD1 polymorphisms, rs265981C/T, rs4532A/G, and rs686T/C. Our previous findings suggested that the dopaminergic system may be more integrally involved in families with affected males only than in other families. We therefore restricted our study to families with two or more affected males (N = 112). There was over-transmission of rs265981-C and rs4532-A in these families (P = 0.040, P = 0.038), with haplotype TDT analysis showing over-transmission of the C-A-T haplotype (P = 0.022) from mothers to affected sons (P = 0.013). In addition, haplotype case-control comparisons revealed an increase of this putative risk haplotype in affected individuals relative to a comparison group (P = 0.004). QTDT analyses showed associations of the rs265981-C, rs4532-A, rs686-T alleles, and the C-A-T haplotype with more severe problems in social interaction, greater difficulties with nonverbal communication and increased stereotypies compared to individuals with other haplotypes. Preferential haplotype transmission of markers at the DRD1 locus and an increased frequency of a specific haplotype support the DRD1 gene as a risk gene for core symptoms of ASD in families having only affected males. Copyright 2008 Wiley-Liss, Inc.

  14. Novel Tenascin-C Haplotype Modifies the Risk for a Failure to Heal After Rotator Cuff Repair.

    Science.gov (United States)

    Kluger, Rainer; Huber, Klaus R; Seely, Philipp G; Berger, Christian E; Frommlet, Florian

    2017-11-01

    Several single-nucleotide polymorphisms (SNPs) in the TNC gene have recently been found to be associated with degenerative rotator cuff tears. Exonic SNPs in the TNC gene are related to the risk for a failure to heal after rotator cuff repair. Case-control study; Level of evidence, 3. A total of 302 patients from the Vienna area and European Caucasian ancestry underwent mini-open rotator cuff repair for a full-thickness superior or posterosuperior tear and were assessed for the integrity of the repair 1 year postoperatively with a real-time 7.5- to 10-MHz ultrasound linear array transducer. Outcomes were classified as intact (complete footprint coverage), small (T] was protective for a large recurrent defect (odds ratio = 0.16; 95% CI, 0.09-0.31). The role of rs1138545 was further backed by haplotype analysis, which showed that the combination of the C allele at rs1138545 [C>T], the A allele at rs2104772 [A>T], and the G allele at rs10759752 [A>G] formed the risk-related haplotype [CAG]. The CAG haplotype was associated with large recurrent defects ( P rotator cuff repairs are clinically relevant, and a heritable component of the disorder is plausible on the basis of a genetic association with 8 TNC variants. Characterization of TNC sequences that favor tendon healing will help engineer new products in regenerative medicine.

  15. Oestrogen receptor α gene haplotype and postmenopausal breast cancer risk: a case control study

    International Nuclear Information System (INIS)

    Wedrén, Sara; Stiger, Fredrik; Persson, Ingemar; Baron, John; Weiderpass, Elisabete; Lovmar, Lovisa; Humphreys, Keith; Magnusson, Cecilia; Melhus, Håkan; Syvänen, Ann-Christine; Kindmark, Andreas; Landegren, Ulf; Fermér, Maria Lagerström

    2004-01-01

    Oestrogen receptor α, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor α gene (ESR1) are associated with breast cancer risk. We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TA n , 1514 cases and 1514 controls; c.454-397C → T, 1557 cases and 1512 controls; c.454-351A → G, 1556 cases and 1512 controls; c.729C → T, 1562 cases and 1513 controls; c.975C → G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data. There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A → G or c.454-397C → T and c.975C → G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A → G and c.975C → G haplotype entailed an OR of 1.19 (95% CI 1.06–1.33) and two copies with an OR of 1.42 (95% CI 1.15–1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C → T and c.975C → G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant. We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women

  16. BMP4 and FGF3 haplotypes increase the risk of tendinopathy in volleyball athletes.

    Science.gov (United States)

    Salles, José Inácio; Amaral, Marcus Vinícius; Aguiar, Diego Pinheiro; Lira, Daisy Anne; Quinelato, Valquiria; Bonato, Letícia Ladeira; Duarte, Maria Eugenia Leite; Vieira, Alexandre Rezende; Casado, Priscila Ladeira

    2015-03-01

    To investigate whether genetic variants can be correlated with tendinopathy in elite male volleyball athletes. Case-control study. Fifteen single nucleotide polymorphisms within BMP4, FGF3, FGF10, FGFR1 genes were investigated in 138 elite volleyball athletes, aged between 18 and 35 years, who undergo 4-5h of training per day: 52 with tendinopathy and 86 with no history of pain suggestive of tendinopathy in patellar, Achilles, shoulder, and hip abductors tendons. The clinical diagnostic criterion was progressive pain during training, confirmed by magnetic resonance image. Genomic DNA was obtained from saliva samples. Genetic markers were genotyped using TaqMan real-time PCR. Chi-square test compared genotypes and haplotype differences between groups. Multivariate logistic regression analyzed the significance of covariates and incidence of tendinopathy. Statistical analysis revealed participant age (p=0.005) and years of practice (p=0.004) were risk factors for tendinopathy. A significant association between BMP4 rs2761884 (p=0.03) and tendinopathy was observed. Athletes with a polymorphic genotype have 2.4 times more susceptibility to tendinopathy (OR=2.39; 95%CI=1.10-5.19). Also, association between disease and haplotype TTGGA in BMP4 (p=0.01) was observed. The FGF3 TGGTA haplotype showed a tendency of association with tendinopathy (p=0.05), and so did FGF10 rs900379. FGFR1 showed no association with disease. These findings indicate that haplotypes in BMP4 and FGF3 genes may contribute to the tendon disease process in elite volleyball athletes. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  17. Risk of Pediatric Celiac Disease According to HLA Haplotype and Country

    Science.gov (United States)

    Liu, Edwin; Lee, Hye-Seung; Aronsson, Carin A.; Hagopian, William A.; Koletzko, Sibylle; Rewers, Marian J.; Eisenbarth, George S.; Bingley, Polly J.; Bonifacio, Ezio; Simell, Ville; Agardh, Daniel

    2014-01-01

    BACKGROUND The presence of HLA haplotype DR3–DQ2 or DR4–DQ8 is associated with an increased risk of celiac disease. In addition, nearly all children with celiac disease have serum antibodies against tissue transglutaminase (tTG). METHODS We studied 6403 children with HLA haplotype DR3–DQ2 or DR4–DQ8 prospectively from birth in the United States, Finland, Germany, and Sweden. The primary end point was the development of celiac disease autoimmunity, which was defined as the presence of tTG antibodies on two consecutive tests at least 3 months apart. The secondary end point was the development of celiac disease, which was defined for the purpose of this study as either a diagnosis on biopsy or persistently high levels of tTG antibodies. RESULTS The median follow-up was 60 months (interquartile range, 46 to 77). Celiac disease autoimmunity developed in 786 children (12%). Of the 350 children who underwent biopsy, 291 had confirmed celiac disease; an additional 21 children who did not undergo biopsy had persistently high levels of tTG antibodies. The risks of celiac disease autoimmunity and celiac disease by the age of 5 years were 11% and 3%, respectively, among children with a single DR3–DQ2 haplotype, and 26% and 11%, respectively, among those with two copies (DR3–DQ2 homozygosity). In the adjusted model, the hazard ratios for celiac disease autoimmunity were 2.09 (95% confidence interval [CI], 1.70 to 2.56) among heterozygotes and 5.70 (95% CI, 4.66 to 6.97) among homozygotes, as compared with children who had the lowest-risk genotypes (DR4–DQ8 heterozygotes or homozygotes). Residence in Sweden was also independently associated with an increased risk of celiac disease autoimmunity (hazard ratio, 1.90; 95% CI, 1.61 to 2.25). CONCLUSIONS Children with the HLA haplotype DR3–DQ2, especially homozygotes, were found to be at high risk for celiac disease autoimmunity and celiac disease early in childhood. The higher risk in Sweden than in other countries

  18. Assessment of M2/ANXA5 haplotype as a risk factor in couples with placenta-mediated pregnancy complications.

    Science.gov (United States)

    Rogenhofer, Nina; Nienaber, Lara R M; Amshoff, Lea C; Bogdanova, Nadia; Petroff, David; Wieacker, Peter; Thaler, Christian J; Markoff, Arseni

    2018-01-01

    The aim of this study was to confirm the associated M2/ANXA5 carrier risk in women with placenta-mediated pregnancy complications (PMPC) and to test their male partners for such association. Further analysis evaluated the influence of maternal vs. paternal M2 alleles on miscarriage. Two hundred eighty-eight couples with preeclampsia (PE), intrauterine growth restriction (IUGR), or premature birth (PB) were recruited (n = 96 of each phenotype). The prevalence of the M2 haplotype was compared to two control cohorts. They included a group of women with a history of normal pregnancy without gestational pathology (Munich controls, n = 94) and a random population sample (PopGen controls, n = 533). Significant association of M2 haplotype and pregnancy complications was confirmed for women and for couples, where prevalence was elevated from 15.4 to 23.8% (p pregnancy complication. M2/ANXA5 appears to be a risk factor for adverse pregnancy outcomes related, but not limited to miscarriages, with similar prevalence in women and their male partners. These findings support the proposed physiological function of ANXA5 as an embryonic anticoagulant that appears deficient in contiguous specter of thrombophilia-related pregnancy complications culminating more frequently in miscarriage in a maternal M2 carrier background.

  19. The Systemic Lupus Erythematosus IRF5 Risk Haplotype Is Associated with Systemic Sclerosis

    Science.gov (United States)

    Beretta, Lorenzo; Simeón, Carmen P.; Carreira, Patricia E.; Callejas, José Luis; Fernández-Castro, Mónica; Sáez-Comet, Luis; Beltrán, Emma; Camps, María Teresa; Egurbide, María Victoria; Airó, Paolo; Scorza, Raffaella; Lunardi, Claudio; Hunzelmann, Nicolas; Riemekasten, Gabriela; Witte, Torsten; Kreuter, Alexander; Distler, Jörg H. W.; Madhok, Rajan; Shiels, Paul; van Laar, Jacob M.; Fonseca, Carmen; Denton, Christopher; Herrick, Ariane; Worthington, Jane; Schuerwegh, Annemie J.; Vonk, Madelon C.; Voskuyl, Alexandre E.; Radstake, Timothy R. D. J.; Martín, Javier

    2013-01-01

    Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P  = 1.34×10−8, OR  = 1.22, CI 95%  = 1.14–1.30; rs2004640: P  = 4.60×10−7, OR  = 0.84, CI 95%  = 0.78–0.90; rs10488631: P  = 7.53×10−20, OR  = 1.63, CI 95%  = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P  = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P  = 9.04×10−22, OR  = 1.75, CI 95%  = 1.56–1.97) better explained the observed association (likelihood P-value  = 1.48×10−4), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that

  20. High Frequency of Haplotype HLA-DQ7 in Celiac Disease Patients from South Italy: Retrospective Evaluation of 5,535 Subjects at Risk of Celiac Disease.

    Directory of Open Access Journals (Sweden)

    Nadia Tinto

    Full Text Available Celiac disease (CD has a strong genetic component mainly due to HLA DQ2/DQ8 encoding genes. However, a minority of CD patients are DQ2/DQ8-negative. To address this issue, we retrospectively characterized HLA haplotypes in 5,535 subjects at risk of CD (either relatives of CD patients or subjects with CD-like symptoms referred to our center during a 10-year period.We identified loci DQA1/DQB1/DRB1 by sequence-specific oligonucleotide-PCR and sequence-specific primer-PCR; anti-transglutaminase IgA/IgG and anti-endomysium IgA by ELISA and indirect immunofluorescence, respectively.We diagnosed CD in 666/5,535 individuals, 4.2% of whom were DQ2/DQ8-negative. Interestingly, DQ7 was one of the most abundant haplotypes in all CD patients and significantly more frequent in DQ2/DQ8-negative (38% than in DQ2/DQ8-positive CD patients (24% (p<0.05.Our data lend support to the concept that DQ7 represents an additive or independent CD risk haplotype with respect to DQ2/DQ8 haplotypes but this finding should be verified in other large CD populations.

  1. Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density

    Directory of Open Access Journals (Sweden)

    Chanock Stephen J

    2010-03-01

    Full Text Available Abstract Background Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a woman's life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here. Methods Samples from 964 postmenopausal Norwegian women aged 55-71 years were collected as a part of the Tromsø Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI. The main statistical analyses were conducted with the PROC HAPLOTYPE procedure within SAS/GENETICS™ (SAS 9.1.3. Results The haplotype analysis revealed six haploblocks within the studied genes. Of those, four had significant associations with circulating levels of IGF1 or IGFBP3 and/or mammographic density. One haplotype variant in the IGF1 gene was found to be associated with mammographic density. Within the IGF2 gene one haplotype variant was associated with levels of both IGF1 and IGFBP3. Two haplotype variants in the IGF2R were associated with the level of IGF1. Both variants of the IGFBP3 haplotype were associated with the IGFBP3 level and indicate regulation in cis. Conclusion Polymorphisms within the IGF1 gene and related genes were associated with plasma levels of IGF1, IGFBP3 and mammographic density in this study of postmenopausal women.

  2. Different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease.

    Science.gov (United States)

    Alshiekh, S; Zhao, L P; Lernmark, Å; Geraghty, D E; Naluai, Å T; Agardh, D

    2017-08-01

    Celiac disease is associated with the HLA-DR3-DQA1*05:01-DQB1*02:01 and DR4-DQA1*03:01-DQB1*03:02 haplotypes. In addition, there are currently over 40 non-HLA loci associated with celiac disease. This study extends previous analyses on different HLA haplotypes in celiac disease using next generation targeted sequencing. Included were 143 patients with celiac disease and 135 non-celiac disease controls investigated at median 9.8 years (1.4-18.3 years). PCR-based amplification of HLA and sequencing with Illumina MiSeq technology were used for extended sequencing of the HLA class II haplotypes HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1, respectively. Odds ratios were computed marginally for every allele and haplotype as the ratio of allelic frequency in patients and controls as ratio of exposure rates (RR), when comparing a null reference with equal exposure rates in cases and controls. Among the extended HLA haplotypes, the strongest risk haplotype for celiac disease was shown for DRB3*01:01:02 in linkage with DQA1*05:01-DQB1*02:01 (RR = 6.34; P-value celiac disease among non-Scandinavians (RR = 7.94; P = .011). The data also revealed 2 distinct celiac disease risk DR3-DQA1*05:01-DQB*02:01 haplotypes distinguished by either the DRB3*01:01:02 or DRB3*02:02:01 alleles, indicating that different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease. The associated risk of celiac disease for DR3-DRB3*01:01:02-DQA1*05:01-DQB1*02:01 is predominant among patients of Scandinavian ethnicity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Novel Nucleotide Variations, Haplotypes Structure and Associations with Growth Related Traits of Goat AT Motif-Binding Factor ( Gene

    Directory of Open Access Journals (Sweden)

    Xiaoyan Zhang

    2015-10-01

    Full Text Available The AT motif-binding factor (ATBF1 not only interacts with protein inhibitor of activated signal transducer and activator of transcription 3 (STAT3 (PIAS3 to suppress STAT3 signaling regulating embryo early development and cell differentiation, but is required for early activation of the pituitary specific transcription factor 1 (Pit1 gene (also known as POU1F1 critically affecting mammalian growth and development. The goal of this study was to detect novel nucleotide variations and haplotypes structure of the ATBF1 gene, as well as to test their associations with growth-related traits in goats. Herein, a total of seven novel single nucleotide polymorphisms (SNPs (SNP 1-7 within this gene were found in two well-known Chinese native goat breeds. Haplotypes structure analysis demonstrated that there were four haplotypes in Hainan black goat while seventeen haplotypes in Xinong Saanen dairy goat, and both breeds only shared one haplotype (hap1. Association testing revealed that the SNP2, SNP5, SNP6, and SNP7 loci were also found to significantly associate with growth-related traits in goats, respectively. Moreover, one diplotype in Xinong Saanen dairy goats significantly linked to growth related traits. These preliminary findings not only would extend the spectrum of genetic variations of the goat ATBF1 gene, but also would contribute to implementing marker-assisted selection in genetics and breeding in goats.

  4. Compound Heterozygosity for Null Mutations and a Common Hypomorphic Risk Haplotype in TBX6 Causes Congenital Scoliosis.

    Science.gov (United States)

    Takeda, Kazuki; Kou, Ikuyo; Kawakami, Noriaki; Iida, Aritoshi; Nakajima, Masahiro; Ogura, Yoji; Imagawa, Eri; Miyake, Noriko; Matsumoto, Naomichi; Yasuhiko, Yukuto; Sudo, Hideki; Kotani, Toshiaki; Nakamura, Masaya; Matsumoto, Morio; Watanabe, Kota; Ikegawa, Shiro

    2017-03-01

    Congenital scoliosis (CS) occurs as a result of vertebral malformations and has an incidence of 0.5-1/1,000 births. Recently, TBX6 on chromosome 16p11.2 was reported as a disease gene for CS; about 10% of Chinese CS patients were compound heterozygotes for rare null mutations and a common haplotype defined by three SNPs in TBX6. All patients had hemivertebrae. We recruited 94 Japanese CS patients, investigated the TBX6 locus for both mutations and the risk haplotype, examined transcriptional activities of mutant TBX6 in vitro, and evaluated clinical and radiographic features. We identified TBX6 null mutations in nine patients, including a missense mutation that had a loss of function in vitro. All had the risk haplotype in the opposite allele. One of the mutations showed dominant negative effect. Although all Chinese patients had one or more hemivertebrae, two Japanese patients did not have hemivertebra. The compound heterozygosity of null mutations and the common risk haplotype in TBX6 also causes CS in Japanese patients with similar incidence. Hemivertebra was not a specific type of spinal malformation in TBX6-associated CS (TACS). A heterozygous TBX6 loss-of-function mutation has been reported in a family with autosomal-dominant spondylocostal dysostosis, but it may represent a spectrum of the same disease with TACS. © 2017 WILEY PERIODICALS, INC.

  5. Haplotype specific alteration of diabetes MHC risk by olfactory receptor gene polymorphism.

    Science.gov (United States)

    Jahromi, Mohamed M

    2012-12-01

    Evidence for genes associated with risk for Type 1 diabetes (T1D) in the extended region of the major histocompatibility complex (MHC) genes is accumulating. The aim of this study was to investigate the association pattern of the extended MHC region with T1D susceptibility to identify effects independent of well established DR/DQ genes. A total of 394 Europid families with T1D were genotyped for the single nucleotide polymorphism (SNP) in the olfactory receptor family 14, subfamily J, member 1 (OR14J1) gene, rs9257691, in the MHC telomeric region. The OR provides "an internal depiction of our external world" through the capture of odorant molecules in the main OR system by several large families of G-protein coupled receptors (GPCR). These receptors transduce and chemosignals into the central nervous system (CNS). This SNP was chosen to identify its association with T1D. Interestingly, OR14J1C allele was significantly associated with T1D that seems to go with DRB1*0401, Χ(2)=10.9, p=0.0003. However, by fixing both genes of DR*0401-DQB1*0302, high risk, the association of T1D with OR14J1C still existed, Χ(2)=7.4, p=0.005. The occurrence of association of the OR14J1C allele with T1D patients with DRB1*401/DQB1*0302 is an independent risk for T1D. As an accumulative report suggests the role of OR in the pathogenesis of diabetic microvascular and other diabetic complications, undoubtedly, this haplotype specific alteration of T1D risk is an independent risk for the disease and can address the promising MHC-linked gene other than DR/DQ. Moreover, there is nothing to hinder for that this might be a signal that identifies the role of OR gene in the pathogenesis of T1D in patients who are prone to diabetic complications. Copyright © 2012. Published by Elsevier B.V.

  6. A haplotype of polymorphisms in ASE-1, RAI and ERCC1 and the effects of tobacco smoking and alcohol consumption on risk of colorectal cancer: a danish prospective case-cohort study

    International Nuclear Information System (INIS)

    Hansen, Rikke D; Sørensen, Mette; Tjønneland, Anne; Overvad, Kim; Wallin, Håkan; Raaschou-Nielsen, Ole; Vogel, Ulla

    2008-01-01

    Single nucleotide polymorphisms (SNPs) are the most frequent type of genetic variation in the human genome, and are of interest for the study of susceptibility to and protection from diseases. The haplotype at chromosome 19q13.2-3 encompassing the three SNPs ASE-1 G-21A, RAI IVS1 A4364G and ERCC1 Asn118Asn have been associated with risk of breast cancer and lung cancer. Haplotype carriers are defined as the homozygous carriers of RAI IVS1 A4364G A , ERCC1 Asn118Asn T and ASE-1 G-21A G . We aimed to evaluate whether the three polymorphisms and the haplotype are associated to risk of colorectal cancer, and investigated gene-environment associations between the polymorphisms and the haplotype and smoking status at enrolment, smoking duration, average smoking intensity and alcohol consumption, respectively, in relation to risk of colorectal cancer. Associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were examined, as well as gene-environment interaction, in a Danish case-cohort study including 405 cases and a comparison group of 810 persons. Incidence rate ratio (IRR) were estimated by the Cox proportional hazards model stratified according to gender, and two-sided 95% confidence intervals (CI) and p-values were calculated based on robust estimates of the variance-covariance matrix and Wald's test of the Cox regression parameter. No consistent associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were found. No statistically significant interactions between the genotypes and the lifestyle exposures smoking or alcohol consumption were observed. Our results suggest that the ASE-1 G-21A, RAI IVS1 A4364G and ERCC1 Asn118Asn polymorphisms and the previously identified haplotype are not associated with risk of colorectal cancer. We found no evidence of gene-environment interaction between the three polymorphisms and the haplotype and smoking intensity and alcohol consumption

  7. Paraoxonase 1 polymorphisms and haplotypes and the risk for having offspring affected with spina bifida in Southeast Mexico.

    Science.gov (United States)

    Gonzalez-Herrera, Lizbeth; Martín Cerda-Flores, Ricardo; Luna-Rivero, Marianne; Canto-Herrera, Jorge; Pinto-Escalante, Doris; Perez-Herrera, Norma; Quintanilla-Vega, Betzabet

    2010-11-01

    Spina bifida (SB) is a common congenital malformation in Southeast Mexico. Parents of children with SB reside in areas with frequent pesticide spraying or have agriculture activities, suggesting potential exposure to pesticides. Paraoxonase 1 (PON1) is the responsible enzyme for deactivation of organophosphates (OP) in the central nervous system. Polymorphisms of PON1 genes influence the catalytic activity and plasma protein level of the enzyme, therefore, genotypic characterization of PON1 gene represents a potential predictor for susceptibility to OP-related effects. The frequency of PON1 haplotypes and polymorphisms (-108CT, L55M, and Q192R) were determined in this study. A case-control study was performed to evaluate the risk for having offspring affected by SB in 152 cases and 160 control parents. Polymorphisms were determined by PCR amplification and restriction fragment length polymorphism and Real Time-PCR. Odds ratios and confidence interval 95% were estimated. Genotype frequencies for the three PON1 polymorphisms were distributed according to Hardy-Weinberg expectations (p > 0.05) and were significantly different between cases and controls (p Mexico. © 2010 Wiley-Liss, Inc.

  8. Do polymorphisms and haplotypes of mismatch repair genes modulate risk of sporadic colorectal cancer?

    Czech Academy of Sciences Publication Activity Database

    Tulupová, Elena; Kumar, R.; Hánová, Monika; Slyšková, Jana; Pardini, Barbara; Poláková, Veronika; Naccarati, Alessio; Vodičková, Ludmila; Novotný, J.; Halamková, J.; Hemminki, K.; Vodička, Pavel

    2008-01-01

    Roč. 648, 1-2 (2008), s. 40-45 ISSN 0027-5107 R&D Projects: GA ČR GA310/07/1430 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : DNA mismatch repair * Genetic polymorphism * Haplotype analysis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.198, year: 2008

  9. Haplotype CGC from XPD, hOGG1 and ITGA2 polymorphisms increases the risk of nasopharyngeal carcinoma in Malaysia.

    Directory of Open Access Journals (Sweden)

    Eng-Zhuan Ban

    Full Text Available 8-oxoG, a common DNA lesion resulting from reactive oxygen species (ROS, has been shown to be associated with cancer initiation. hOGG1 DNA glycosylase is the primary enzyme responsible for excision of 8-oxoG through base excision repair (BER. Integrins are members of a family of cell surface receptors that mediate the cell-cell and extracellular matrix (ECM interactions. Integrins are involved in almost every aspect of carcinogenesis, from cell differentiation, cell proliferation, metastasis to angiogenesis. Loss of ITGA2 expression was associated with enhanced tumor intravasation and metastasis of breast and colon cancer. XPD gene encodes DNA helicase enzyme that is involved in nucleotide excision repair (NER. It is shown in previous research that XPD homozygous wildtype Lys/Lys genotype was associated with higher odds of NPC.We conducted a 1 to N case-control study involving 300 nasopharyngeal carcinoma (NPC cases and 533 controls matched by age, gender and ethnicity to investigate the effect of hOGG1 Ser326Cys, ITGA2 C807T and XPD Lys751Gln polymorphisms on NPC risk. Linkage disequilibrium and haplotype analysis were conducted to explore the association of allele combinations with NPC risk. Restriction fragment length polymorphism (RFLP-PCR was used for DNA genotyping.No significant association was observed between hOGG1 Ser326Cys and ITGA2 C807T polymorphisms with NPC risk after adjustment for age, gender, ethnicity, cigarette smoking, alcohol and salted fish consumption. Lys/Lys genotype of XPD Lys751Gln polymorphism was associated with increased NPC risk (OR = 1.60, 95% CI = 1.06-2.43. Subjects with history of smoking (OR = 1.81, 95% CI = 1.26-2.60, and salted fish consumption before age of 10 (OR = 1.77, 95% CI = 1.30-2.42 were observed to have increased odds of NPC. The odds of developing NPC of CGC haplotype was significantly higher compared to reference AGC haplotype (OR = 2.20, 95% CI = 1.06-4.58.The allele combination of CGC from h

  10. Haplotype CGC from XPD, hOGG1 and ITGA2 polymorphisms increases the risk of nasopharyngeal carcinoma in Malaysia.

    Science.gov (United States)

    Ban, Eng-Zhuan; Lye, Munn-Sann; Chong, Pei Pei; Yap, Yoke-Yeow; Lim, Siew Ying Crystale; Abdul Rahman, Hejar

    2017-01-01

    8-oxoG, a common DNA lesion resulting from reactive oxygen species (ROS), has been shown to be associated with cancer initiation. hOGG1 DNA glycosylase is the primary enzyme responsible for excision of 8-oxoG through base excision repair (BER). Integrins are members of a family of cell surface receptors that mediate the cell-cell and extracellular matrix (ECM) interactions. Integrins are involved in almost every aspect of carcinogenesis, from cell differentiation, cell proliferation, metastasis to angiogenesis. Loss of ITGA2 expression was associated with enhanced tumor intravasation and metastasis of breast and colon cancer. XPD gene encodes DNA helicase enzyme that is involved in nucleotide excision repair (NER). It is shown in previous research that XPD homozygous wildtype Lys/Lys genotype was associated with higher odds of NPC. We conducted a 1 to N case-control study involving 300 nasopharyngeal carcinoma (NPC) cases and 533 controls matched by age, gender and ethnicity to investigate the effect of hOGG1 Ser326Cys, ITGA2 C807T and XPD Lys751Gln polymorphisms on NPC risk. Linkage disequilibrium and haplotype analysis were conducted to explore the association of allele combinations with NPC risk. Restriction fragment length polymorphism (RFLP-PCR) was used for DNA genotyping. No significant association was observed between hOGG1 Ser326Cys and ITGA2 C807T polymorphisms with NPC risk after adjustment for age, gender, ethnicity, cigarette smoking, alcohol and salted fish consumption. Lys/Lys genotype of XPD Lys751Gln polymorphism was associated with increased NPC risk (OR = 1.60, 95% CI = 1.06-2.43). Subjects with history of smoking (OR = 1.81, 95% CI = 1.26-2.60), and salted fish consumption before age of 10 (OR = 1.77, 95% CI = 1.30-2.42) were observed to have increased odds of NPC. The odds of developing NPC of CGC haplotype was significantly higher compared to reference AGC haplotype (OR = 2.20, 95% CI = 1.06-4.58). The allele combination of CGC from hOGG1

  11. Association of Air Pollution Exposure and Interleukin-13 Haplotype with the Risk of Aggregate Bronchitic Symptoms in Children

    Directory of Open Access Journals (Sweden)

    Yungling Leo Lee

    2018-03-01

    Full Text Available Interleukin-13(IL-13 might play an important role in driving aggregate bronchitic symptoms pathogenesis. However, none of the studies assessed the interaction between air pollutants exposure and IL-13 gene on the risk of aggregate bronchitic symptoms in non-asthma children. To assess the independent and joint effects of the exposure to air pollution and IL-13 haplotypes on the risk of aggregate bronchitic symptoms, we conducted a cross-sectional study and focused on non-asthma children. The study population consisted of 2944 children. The effect of each air pollutant on the risk of aggregate bronchitic symptoms was estimated as odds ratios per interquartile range (IQR change. In the multiple logistic regressions, adjusted for confounding factors, the risk of chronic phlegm was associated with PM2.5 exposure (aOR, 1.59; 95% CI, 1.07–2.37 per 12.51 μg/m3 change, O3 exposure (aOR, 1.54 95% CI, 1.05–2.27 per 8.28 ppb change and SO2 exposure (aOR, 1.19; 95% CI, 1.02–1.39 per 0.98 ppb change. Our study further provides the evidence that gene-environment interactions between IL-13 haplotype and O3 exposure on chronic phlegm (95% CI for interaction, 1.01–1.38. Identifying children who are more sensitive to air pollution helps us to provide them an efficient prevention to avoid aggregate bronchitic symptoms. Keywords: Air pollutants, Interleukin-13, Bronchitic symptoms

  12. Haplotype Analysis Discriminates Genetic Risk for DR3-Associated Endocrine Autoimmunity and Helps Define Extreme Risk for Addison’s Disease

    Science.gov (United States)

    Baker, Peter R.; Baschal, Erin E.; Fain, Pam R.; Triolo, Taylor M.; Nanduri, Priyaanka; Siebert, Janet C.; Armstrong, Taylor K.; Babu, Sunanda R.; Rewers, Marian J.; Gottlieb, Peter A.; Barker, Jennifer M.; Eisenbarth, George S.

    2010-01-01

    Context: Multiple autoimmune disorders (e.g. Addison’s disease, type 1 diabetes, celiac disease) are associated with HLA-DR3, but it is likely that alleles of additional genes in linkage disequilibrium with HLA-DRB1 contribute to disease. Objective: The objective of the study was to characterize major histocompatability complex (MHC) haplotypes conferring extreme risk for autoimmune Addison’s disease (AD). Design, Setting, and Participants: Eighty-six 21-hydroxylase autoantibody-positive, nonautoimmune polyendocrine syndrome type 1, Caucasian individuals collected from 1992 to 2009 with clinical AD from 68 families (12 multiplex and 56 simplex) were genotyped for HLA-DRB1, HLA-DQB1, MICA, HLA-B, and HLA-A as well as high density MHC single-nucleotide polymorphism (SNP) analysis for 34. Main Outcome Measures: AD and genotype were measured. Result: Ninety-seven percent of the multiplex individuals had both HLA-DR3 and HLA-B8 vs. 60% of simplex AD patients (P = 9.72 × 10−4) and 13% of general population controls (P = 3.00 × 10−19). The genotype DR3/DR4 with B8 was present in 85% of AD multiplex patients, 24% of simplex patients, and 1.5% of control individuals (P = 4.92 × 10−191). The DR3-B8 haplotype of AD patients had HLA-A1 less often (47%) than controls (81%, P = 7.00 × 10−5) and type 1 diabetes patients (73%, P = 1.93 × 10−3). Analysis of 1228 SNPs across the MHC for individuals with AD revealed a shorter conserved haplotype (3.8) with the loss of the extended conserved 3.8.1 haplotype approximately halfway between HLA-B and HLA-A. Conclusion: Extreme risk for AD, especially in multiplex families, is associated with haplotypic DR3 variants, in particular a portion (3.8) but not all of the conserved 3.8.1 haplotype. PMID:20631027

  13. Haplotype frequency distribution for 7 microsatellites in chromosome 8 and 11 in relation to the metabolic syndrome in four ethnic groups: Tehran Lipid and Glucose Study.

    Science.gov (United States)

    Daneshpour, Maryam Sadat; Hosseinzadeh, Nima; Zarkesh, Maryam; Azizi, Fereidoun

    2012-03-01

    Different variants of haplotype frequencies may lead to various frequencies of the same variants in individuals with drug resistance and disease susceptibility at the population level. In this study, the haplotype frequencies of 4 STR loci including the D8S1132, D8S1779, D8S514 and D8S1743, and 3 STR loci including D11S1304, D11S1998 and D11S934 were investigated in 563 individuals of four Iranian ethnic groups in the capital city of Iran, Tehran. One hundred thirty subjects had the metabolic syndrome. Haplotype frequencies of all markers were calculated. There were significant differences in the haplotype frequencies in short and long alleles between the metabolic affected subjects and controls. In addition, haplotype frequencies were significant in the four ethnic groups in both chromosomes 8 and 11. Our findings show a relation between the short allele of D8S1743 in all related haplotype frequencies of subjects with metabolic syndrome. These findings may require more studies of some candidate genes, including the lipoprotein lipase gene, in this chromosomal region. Copyright © 2011. Published by Elsevier B.V.

  14. Decreasing Relative Risk Premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    relative risk premium in the small implies decreasing relative risk premium in the large, and decreasing relative risk premium everywhere implies risk aversion. We finally show that preferences with decreasing relative risk premium may be equivalently expressed in terms of certain preferences on risky......We consider the risk premium demanded by a decision maker with wealth x in order to be indifferent between obtaining a new level of wealth y1 with certainty, or to participate in a lottery which either results in unchanged present wealth or a level of wealth y2 > y1. We define the relative risk...... premium as the quotient between the risk premium and the increase in wealth y1–x which the decision maker puts on the line by choosing the lottery in place of receiving y1 with certainty. We study preferences such that the relative risk premium is a decreasing function of present wealth, and we determine...

  15. Structural insertion/deletion variation in IRF5 is associated with a risk haplotype and defines the precise IRF5 isoforms expressed in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Kozyrev, Sergey V; Lewén, Susanna; Reddy, Prasad M V Linga

    2007-01-01

    -alpha. The SNP most strongly associated with SLE was SNP no. rs2070197 (P=5.2x10(-11)), which is a proxy of the risk haplotype, but does not appear to be functional. CONCLUSION: None of the functional variants investigated in this study is strongly associated with SLE, with the exception of the exon 1B donor......OBJECTIVE: To determine whether specific isoforms of IRF5 are transcribed in patients with systemic lupus erythematosus (SLE) who have risk genotypes in the exon 1B donor splice site at single-nucleotide polymorphism (SNP) no. rs2004640. METHODS: Peripheral blood mononuclear cells were obtained...... interaction domain. The insertion segregates in the risk haplotype with the high expression allele of a poly(A) site SNP no. rs10954213 and the exon 1B donor splice allele of the 5'-UTR SNP no. rs2004640. The poly(A) polymorphism correlated with levels of IRF5 in cells stimulated with interferon...

  16. ADHD and DAT1: Further evidence of paternal over-transmission of risk alleles and haplotype

    NARCIS (Netherlands)

    Hawi, Z.; Kent, L.; Hill, M.; Anney, R.J.; Brookes, K. J.; Barry, E.; Franke, B.; Banaschewski, T.; Buitelaar, J.; Ebstein, R.; Miranda, A.; Oades, R.D.; Roeyers, H.; Rothenberger, A.; Sergeant, J.A.; Sonuga-Barke, E.; Steinhausen, H.C.; Faraone, S.V.; Asherson, P.; Gill, M.

    2009-01-01

    We [Hawi et al. (2005); Am J Hum Genet 77:958-965] reported paternal over-transmission of risk alleles in some ADHD-associated genes. This was particularly clear in the case of the DAT1 30-UTR VNTR. In the current investigation, we analyzed three new sample comprising of 1,248 ADHD nuclear families

  17. ADHD and DAT1: further evidence of paternal over-transmission of risk alleles and haplotype.

    NARCIS (Netherlands)

    Hawi, Z.; Kent, L.; Hill, M.; Anney, R.J.; Brookes, K.J.; Barry, E.; Franke, B.; Banaschewski, T.; Buitelaar, J.K.; Ebstein, R.; Miranda, A.; Oades, R.D.; Roeyers, H.; Rothenberger, A.; Sergeant, J.A.; Sonuga-Barke, E.J.S.; Steinhausen, H.C.; Faraone, S.V.; Asherson, P.; Gill, M.

    2010-01-01

    We [Hawi et al. (2005); Am J Hum Genet 77:958-965] reported paternal over-transmission of risk alleles in some ADHD-associated genes. This was particularly clear in the case of the DAT1 3'-UTR VNTR. In the current investigation, we analyzed three new sample comprising of 1,248 ADHD nuclear families

  18. The Additive Risk Model for Estimation of Effect of Haplotype Match in BMT Studies

    DEFF Research Database (Denmark)

    Scheike, Thomas; Martinussen, T; Zhang, MJ

    2011-01-01

    leads to a missing data problem. We show how Aalen's additive risk model can be applied in this setting with the benefit that the time-varying haplomatch effect can be easily studied. This problem has not been considered before, and the standard approach where one would use the expected-maximization (EM......) algorithm cannot be applied for this model because the likelihood is hard to evaluate without additional assumptions. We suggest an approach based on multivariate estimating equations that are solved using a recursive structure. This approach leads to an estimator where the large sample properties can...... be developed using product-integration theory. Small sample properties are investigated using simulations in a setting that mimics the motivating haplomatch problem....

  19. Decreasing relative risk premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    2007-01-01

    such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...

  20. HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 Haplotype Protects Autoantibody-Positive Relatives From Type 1 Diabetes Throughout the Stages of Disease Progression.

    Science.gov (United States)

    Pugliese, Alberto; Boulware, David; Yu, Liping; Babu, Sunanda; Steck, Andrea K; Becker, Dorothy; Rodriguez, Henry; DiMeglio, Linda; Evans-Molina, Carmella; Harrison, Leonard C; Schatz, Desmond; Palmer, Jerry P; Greenbaum, Carla; Eisenbarth, George S; Sosenko, Jay M

    2016-04-01

    The HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is linked to protection from the development of type 1 diabetes (T1D). However, it is not known at which stages in the natural history of T1D development this haplotype affords protection. We examined a cohort of 3,358 autoantibody-positive relatives of T1D patients in the Pathway to Prevention (PTP) Study of the Type 1 Diabetes TrialNet. The PTP study examines risk factors for T1D and disease progression in relatives. HLA typing revealed that 155 relatives carried this protective haplotype. A comparison with 60 autoantibody-negative relatives suggested protection from autoantibody development. Moreover, the relatives with DRB1*15:01-DQA1*01:02-DQB1*06:02 less frequently expressed autoantibodies associated with higher T1D risk, were less likely to have multiple autoantibodies at baseline, and rarely converted from single to multiple autoantibody positivity on follow-up. These relatives also had lower frequencies of metabolic abnormalities at baseline and exhibited no overall metabolic worsening on follow-up. Ultimately, they had a very low 5-year cumulative incidence of T1D. In conclusion, the protective influence of DRB1*15:01-DQA1*01:02-DQB1*06:02 spans from autoantibody development through all stages of progression, and relatives with this allele only rarely develop T1D. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  1. Fuel related risks; Braenslerisker

    Energy Technology Data Exchange (ETDEWEB)

    Englund, Jessica; Sernhed, Kerstin; Nystroem, Olle; Graveus, Frank (Grontmij AB, (Sweden))

    2012-02-15

    The project, within which this work report was prepared, aimed to complement the Vaermeforsk publication 'Handbook of fuels' on fuel related risks and measures to reduce the risks. The fuels examined in this project where the fuels included in the first version of the handbook from 2005 plus four additional fuels that will be included in the second and next edition of the handbook. Following fuels were included: woodfuels (sawdust, wood chips, powder, briquettes), slash, recycled wood, salix, bark, hardwood, stumps, straw, reed canary grass, hemp, cereal, cereal waste, olive waste, cocoa beans, citrus waste, shea, sludge, forest industrial sludge, manure, Paper Wood Plastic, tyre, leather waste, cardboard rejects, meat and bone meal, liquid animal and vegetable wastes, tall oil pitch, peat, residues from food industry, biomal (including slaughterhouse waste) and lignin. The report includes two main chapters; a general risk chapter and a chapter of fuel specific risks. The first one deals with the general concept of risk, it highlights laws and rules relevant for risk management and it discuss general risks that are related to the different steps of fuel handling, i.e. unloading, storing, processing the fuel, transportation within the facility, combustion and handling of ashes. The information that was used to produce this chapter was gathered through a literature review, site visits, and the project group's experience from risk management. The other main chapter deals with fuel-specific risks and the measures to reduce the risks for the steps of unloading, storing, processing the fuel, internal transportation, combustion and handling of the ashes. Risks and measures were considered for all the biofuels included in the second version in the handbook of fuels. Information about the risks and risk management was gathered through interviews with people working with different kinds of fuels in electricity and heat plants in Sweden. The information from

  2. Annexin A5 Promoter Haplotype M2 Is Not a Risk Factor for Recurrent Pregnancy Loss in Northern Europe

    DEFF Research Database (Denmark)

    Nagirnaja, Liina; Nõmmemees, Diana; Rull, Kristiina

    2015-01-01

    and recurrent pregnancy loss (RPL), however with inconclusive results. STUDY SUBJECTS AND METHODS: A retrospective case-control study combining resequencing and restriction fragment length polymorphism (RFLP) analysis was undertaken in 313 women with unexplained RPL and 214 fertile women from Estonia...... compared to controls both in Estonia (8.1% vs 15.2%, respectively) and Denmark (9.7% vs 12.6%). The high M2 prevalence in fertile controls was consistent with estimations for European and East Asian populations (9.6%-16.0%). CONCLUSIONS: This study cautions to consider the M2 haplotype as a deterministic...

  3. The HLA-B*39 allele increases type 1 diabetes risk conferred by HLA-DRB1*04:04-DQB1*03:02 and HLA-DRB1*08-DQB1*04 class II haplotypes.

    Science.gov (United States)

    Mikk, M-L; Kiviniemi, M; Laine, A-P; Härkönen, T; Veijola, R; Simell, O; Knip, M; Ilonen, J

    2014-01-01

    To further characterise the effect of the HLA-B*39 allele on type 1 diabetes risk we assessed its role in different HLA-DR/DQ haplotypes and genotypes using 1764 nuclear families with a diabetic child collected in the framework of the Finnish Paediatric Diabetes Register. HLA assays were based on sequence specific hybridization using lanthanide labelled oligonucleotide probes. Transmissions of major HLA-DR/DQ haplotypes with and without the HLA-B*39 allele to diabetic index cases were analysed by direct haplotype and allele counting. The HLA-B*39 allele significantly increased the disease risk conferred by DRB1*04:04-DQA1*03-DQB1*03:02 and (DR8)-DQB1*04 haplotypes. The same effect was observed on genotype level as disease association for the HLA-B*39 allele was observed in multiple genotypes containing DRB1*04:04-DQA1*03-DQB1*03:02 or (DR8)-DQB1*04 haplotypes. Finally we considered the two common subtypes of the HLA-B*39 allele, B*39:01 and B*39:06 and observed their unequal distribution when stratified for specific DR-DQ haplotypes. The risk for type 1 diabetes conferred by certain DR/DQ haplotypes is modified by the presence of the HLA-B*39 and this confirms the independent disease predisposing effect of the HLA-B*39 allele. The results can be applied in enhancing the sensitivity and specificity of DR/DQ based screening programs for subjects at disease risk. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  4. Pathways to injury in chronic pancreatitis: decoding the role of the high-risk SPINK1 N34S haplotype using meta-analysis.

    Directory of Open Access Journals (Sweden)

    Elie Aoun

    2008-04-01

    Full Text Available The complex interactions between recurrent trypsin-mediated pancreatic injury, alcohol-associated pancreatic injury and SPINK1 polymorphisms in chronic pancreatitis (CP are undefined. We hypothesize that CP occurs as a result of multiple pathological mechanisms (pathways that are initiated by different metabolic or environmental factors (etiologies and may be influenced differentially by downstream genetic risk factors. We tested this hypothesis by evaluating the differences in effect size of the high risk SPINK1 N34S haplotype on CP from multiple etiologies after combining clinical reports of SPINK1 N34S frequency using meta-analysis.The Pubmed and the Embase databases were reviewed. We studied 24 reports of SPINK1 N34S in CP (2,421 cases, 4,857 controls using reported etiological factors as surrogates for pathways and multiple meta-analyses to determine the differential effects of SPINK1 N34S between alcoholic and non-alcoholic etiologies. Using estimates of between-study heterogeneity, we sub-classified our 24 studies into four specific clusters. We found that SPINK1 N34S is strongly associated with CP overall (OR 11.00; 95% CI: 7.59-15.93, but the effect of SPINK1 N34S in alcoholic CP (OR 4.98, 95% CI: 3.16-7.85 was significantly smaller than in idiopathic CP (OR 14.97, 95% C.I. = 9.09-24.67 or tropical CP (OR 19.15, 95% C.I. = 8.83-41.56. Studies analyzing familial CP showed very high heterogeneity suggestive of a complex etiology with an I(2 = 80.95%.The small effect of SPINK1 N34S in alcoholic subjects suggests that CP is driven through a different pathway that is largely trypsin-independent. The results also suggest that large effect sizes of SPINK1 N34S in small candidate gene studies in CP may be related to a mixture of multiple etiologic pathways leading to the same clinical endpoint.

  5. Haplotype Variation of Flowering Time Genes of Sugar Beet and Its Wild Relatives and the Impact on Life Cycle Regimes

    Directory of Open Access Journals (Sweden)

    Nadine Höft

    2018-01-01

    Full Text Available The species Beta vulgaris encompasses wild and cultivated members with a broad range of phenological development. The annual life cycle is commonly found in sea beets (ssp. maritima from Mediterranean environments which germinate, bolt, and flower within one season under long day conditions. Biennials such as the cultivated sugar beet (B. vulgaris ssp. vulgaris as well as sea beets from northern latitudes require prolonged exposure to cold temperature over winter to acquire floral competence. Sugar beet is mainly cultivated for sugar production in Europe and is likely to have originated from sea beet. Flowering time strongly affects seed yield and yield potential and is thus a trait of high agronomic relevance. Besides environmental cues, there are complex genetic networks known to impact life cycle switch in flowering plants. In sugar beet, BTC1, BvBBX19, BvFT1, and BvFT2 are major flowering time regulators. In this study, we phenotyped plants from a diversity Beta panel encompassing cultivated and wild species from different geographical origin. Plants were grown under different day length regimes with and without vernalization. Haplotype analysis of BTC1, BvBBX19, BvFT1, and BvFT2 was performed to identify natural diversity of these genes and their impact on flowering. We found that accessions from northern latitudes flowered significantly later than those from southern latitudes. Some plants did not flower at all, indicating a strong impact of latitude of origin on life cycle. Haplotype analysis revealed a high conservation of the CCT-, REC-, BBX-, and PEBP-domains with regard to SNP occurrence. We identified sequence variation which may impact life cycle adaptation in beet. Our data endorse the importance of BTC1 in the domestication process of cultivated beets and contribute to the understanding of distribution and adaption of Beta species to different life cycle regimes in response to different environments. Moreover, our data provide a

  6. Mineralocorticoid receptor haplotype moderates the effects of oral contraceptives and menstrual cycle on emotional information processing.

    Science.gov (United States)

    Hamstra, Danielle A; de Kloet, E Ronald; Tollenaar, Marieke; Verkuil, Bart; Manai, Meriem; Putman, Peter; Van der Does, Willem

    2016-10-01

    The processing of emotional information is affected by menstrual cycle phase and by the use of oral contraceptives (OCs). The stress hormone cortisol is known to affect emotional information processing via the limbic mineralocorticoid receptor (MR). We investigated in an exploratory study whether the MR-genotype moderates the effect of both OC-use and menstrual cycle phase on emotional cognition. Healthy premenopausal volunteers (n=93) of West-European descent completed a battery of emotional cognition tests. Forty-nine participants were OC users and 44 naturally cycling, 21 of whom were tested in the early follicular (EF) and 23 in the mid-luteal (ML) phase of the menstrual cycle. In MR-haplotype 1/3 carriers, ML women gambled more than EF women when their risk to lose was relatively small. In MR-haplotype 2, ML women gambled more than EF women, regardless of their odds of winning. OC-users with MR-haplotype 1/3 recognised fewer facial expressions than ML women with MR-haplotype 1/3. MR-haplotype 1/3 carriers may be more sensitive to the influence of their female hormonal status. MR-haplotype 2 carriers showed more risky decision-making. As this may reflect optimistic expectations, this finding may support previous observations in female carriers of MR-haplotype 2 in a naturalistic cohort study. © The Author(s) 2016.

  7. [Genetic Variability and Structure of SNP Haplotypes in the DMPK Gene in Yakuts and Other Ethnic Groups of Northern Eurasia in Relation to Myotonic Dystrophy].

    Science.gov (United States)

    Swarovskaya, M G; Stepanova, S K; Marussin, A V; Sukhomyasova, A L; Maximova, N R; Stepanov, V A

    2015-06-01

    The genetic variability of the DMPK locus has been studied in relation to six SNP markers (rs2070736, rs572634, rs1799894, rs527221, rs915915, and rs10415988) in Yakuts with myotonic dystrophy (MD) in the Yakut population and in populations of northern Eurasia. Significant differences were observed in the allele frequencies between patients and a population sample of Yakuts for three SNP loci (rs915915, rs1799894, and rs10415988) associated with a high chance of disease manifestation. The odds ratios (OR) of MD development in representatives of the Yakut population for these three loci were 2.59 (95% CI, p = 0,004), 4.99 (95% CI, p = 0.000), and 3.15 (95% CI, p = 0.01), respectively. Haplotype TTTCTC, which is associated with MD, and haplotype GTCCTT, which was observed only in Yakut MD patients (never in MD patients of non-Yakut origin), were revealed. A low level of variability in the locus of DMRK gene in Yakuts (H(e) = 0.283) compared with other examined populations was noted. An analysis of pairwise genetic relationships between populations revealed their significant differentiation for all the examined loci. In addition, a low level of differentiation in territorial groups of Yakut populations (F(ST) = 0.79%), which was related to the high subdivision of the northern Eurasian population (F(ST) = 11.83%), was observed.

  8. The polymorphism and haplotypes of PIN1 gene are associated with the risk of lung cancer in Southern and Eastern Chinese populations.

    Science.gov (United States)

    Lu, Jiachun; Yang, Lei; Zhao, Hongjun; Liu, Bin; Li, Yinyan; Wu, Hongxia; Li, Qingchu; Zeng, Bohang; Wang, Yunnan; Ji, Weidong; Zhou, Yifeng

    2011-11-01

    Peptidyl-prolyl cis/trans isomerase (PPIase), PIN1, has been found to be a critical catalyst that involves in multiple oncogenic signaling pathways. Recently, several putative functional polymorphisms of the PIN1 gene have been identified to be associated with cancer risk. In this study, we tested the hypothesis that two common polymorphisms, c.-842G>C (rs2233678) and c.-667C>T (rs2233679), in the PIN1 promoter are associated with risk of lung cancer. In two independent case-control studies of 1,559 lung cancer cases and 1,679 controls conducted in Southern and Eastern Chinese population, we found that compared with the most common c.-842GG genotype, the carriers of c.-842C variant genotypes (GC + CC) had a decreased risk of lung cancer (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.51-0.78, p = 1.13 × 10(-5) ). Although no association was observed between the c.-667C>T polymorphism and cancer risk, we found that the haplotype "C-C" had a greater protective effect (OR = 0.39, 95% CI = 0.23-0.67, p = 5.03 × 10(-4) ). The stratification analysis showed that the protective role of c.-842C variants was more pronounced in current smokers (p = 4.45 × 10(-5) ), especially in male smokers (p = 6.71 × 10(-6) ) and in those who smoked more than 20 pack-years (p = 2.30 × 10(-5) ) and the c.-842C variant genotypes interacted with smoking status (P(interaction) = 0.019) or pack-years smoked (P(interaction) = 0.008) on reducing cancer risk. Further functional assay revealed that the c.-842C variant allele had a lower transcription activity in luciferase assay and a lower DNA-binding ability with nuclear proteins, and low transcription activity in western blot assay. In conclusions, our data suggest that functional c.-842C variants and haplotype "C-C" in the PIN1 promoter contribute to decreased risk of lung cancer by diminishing the promoter activity, which may be susceptibility biomarkers for lung cancer. © 2011 Wiley Periodicals, Inc.

  9. Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes.

    Science.gov (United States)

    Miller, F W; Chen, W; O'Hanlon, T P; Cooper, R G; Vencovsky, J; Rider, L G; Danko, K; Wedderburn, L R; Lundberg, I E; Pachman, L M; Reed, A M; Ytterberg, S R; Padyukov, L; Selva-O'Callaghan, A; Radstake, T R; Isenberg, D A; Chinoy, H; Ollier, W E R; Scheet, P; Peng, B; Lee, A; Byun, J; Lamb, J A; Gregersen, P K; Amos, C I

    2015-10-01

    Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes influenced by genetic and environmental factors. To identify genetic risk factors in patients of European ancestry, we conducted a genome-wide association study (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202 adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 4724 controls. Single-nucleotide polymorphisms showing strong associations (Pmyositis phenotypes together, as well as for the four clinical and autoantibody phenotypes studied separately. Imputation and regression analyses found that alleles comprising the human leukocyte antigen (HLA) 8.1 ancestral haplotype (AH8.1) defined essentially all the genetic risk in the phenotypes studied. Although the HLA DRB1*03:01 allele showed slightly stronger associations with adult and juvenile dermatomyositis, and HLA B*08:01 with polymyositis and anti-Jo-1 autoantibody-positive myositis, multiple alleles of AH8.1 were required for the full risk effects. Our findings establish that alleles of the AH8.1 comprise the primary genetic risk factors associated with the major myositis phenotypes in geographically diverse Caucasian populations.

  10. Fine definition of the pedigree haplotypes of closely related rice cultivars by means of genome-wide discovery of single-nucleotide polymorphisms.

    Science.gov (United States)

    Yamamoto, Toshio; Nagasaki, Hideki; Yonemaru, Jun-ichi; Ebana, Kaworu; Nakajima, Maiko; Shibaya, Taeko; Yano, Masahiro

    2010-04-27

    To create useful gene combinations in crop breeding, it is necessary to clarify the dynamics of the genome composition created by breeding practices. A large quantity of single-nucleotide polymorphism (SNP) data is required to permit discrimination of chromosome segments among modern cultivars, which are genetically related. Here, we used a high-throughput sequencer to conduct whole-genome sequencing of an elite Japanese rice cultivar, Koshihikari, which is closely related to Nipponbare, whose genome sequencing has been completed. Then we designed a high-throughput typing array based on the SNP information by comparison of the two sequences. Finally, we applied this array to analyze historical representative rice cultivars to understand the dynamics of their genome composition. The total 5.89-Gb sequence for Koshihikari, equivalent to 15.7 x the entire rice genome, was mapped using the Pseudomolecules 4.0 database for Nipponbare. The resultant Koshihikari genome sequence corresponded to 80.1% of the Nipponbare sequence and led to the identification of 67,051 SNPs. A high-throughput typing array consisting of 1917 SNP sites distributed throughout the genome was designed to genotype 151 representative Japanese cultivars that have been grown during the past 150 years. We could identify the ancestral origin of the pedigree haplotypes in 60.9% of the Koshihikari genome and 18 consensus haplotype blocks which are inherited from traditional landraces to current improved varieties. Moreover, it was predicted that modern breeding practices have generally decreased genetic diversity Detection of genome-wide SNPs by both high-throughput sequencer and typing array made it possible to evaluate genomic composition of genetically related rice varieties. With the aid of their pedigree information, we clarified the dynamics of chromosome recombination during the historical rice breeding process. We also found several genomic regions decreasing genetic diversity which might be

  11. GSTM1 copy number and promoter haplotype as predictors for risk of recurrence and/or second primary tumor in patients with head and neck cancer

    Directory of Open Access Journals (Sweden)

    Zhang X

    2013-03-01

    Full Text Available Xuemei Zhang,1 Maosheng Huang,2 Xifeng Wu,2 Susan Kadlubar,1 Jie Lin,2 Xinfeng Yu,1 Chunyang Fan,3 Baitang Ning,4 Fred F Kadlubar1†1University of Arkansas for Medical Sciences, Little Rock, Arkansas, 2The University of Texas MD Anderson Cancer Center, Houston, Texas, 3VA hospital, Little Rock, Arkansas, 4National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA†Fred F Kadlubar passed away on December 4, 2010.Abstract: The objective of this study was to determine copy number variant (CNV and promoter genetic variants in glutathione S-transferase Mu class 1 (GSTM1 and the risk of recurrence (REC/second primary tumor (SPT in patients with previously diagnosed early stage head and neck cancer. Among 441 subjects, 133 experienced REC and/or an SPT, while 308 had single primary disease. TaqMan real-time polymerase chain reaction was used to measure the exact copy number of GSTM1 and direct sequencing was used to determine genetic variants in the GSTM1 promoter region. Multivariate Cox regression analysis was performed to estimate hazard ratios (HRs and 95% confidence intervals (95% CIs associated with copy number and genetic variants. REC/SPT-free survival times were compared by constructing Kaplan–Meier curves and differences between curves were tested by logrank test. Results showed a significantly decreased REC/SPT (HR = 0.57; 95% CI = 0.35–0.95 and longer REC/SPT-free survival in subjects with at least two copies of GSTM1 compared with the GSTM1 homozygous deletion, but not in those with one copy of GSTM1. The −498G, −426G, and −339T alleles were significantly associated with REC/SPT, with HRs of 0.11 (0.02–0.85, 0.28 (0.11–0.74 and 2.02 (1.07–3.82, respectively. Kaplan–Meier survival analysis showed that the −498G, −426G, and −339C alleles were also significantly associated with increased REC/SPT-free survival. Further haplotype analysis showed the haplotype P-498G--426G--339

  12. Association between β2-adrenoceptor (ADRB2) haplotypes and insulin resistance in PCOS.

    Science.gov (United States)

    Tellechea, Mariana L; Muzzio, Damián O; Iglesias Molli, Andrea E; Belli, Susana H; Graffigna, Mabel N; Levalle, Oscar A; Frechtel, Gustavo D; Cerrone, Gloria E

    2013-04-01

    The aim of this study was to explore β2-adrenoceptor (ADRB2) haplotype associations with phenotypes and quantitative traits related to insulin resistance (IR) and the metabolic syndrome (MS) in a polycystic ovary syndrome (PCOS) population. A secondary purpose was to assess the association between ADRB2 haplotype and PCOS. Genetic polymorphism analysis. Cross-sectional case-control association study. Medical University Hospital and research laboratory. One hundred and sixty-five unrelated women with PCOS and 116 unrelated women without PCOS (control sample). Clinical and biochemical measurements, and ADRB2 genotyping in PCOS patients and control subjects. ADRB2 haplotypes (comprising rs1042711, rs1801704, rs1042713 and rs1042714 in that order), genotyping and statistical analysis to evaluate associations with continuous variables and traits related to IR and MS in a PCOS population. Associations between ADRB2 haplotypes and PCOS were also assessed. We observed an age-adjusted association between ADRB2 haplotype CCGG and lower insulin (P = 0·018) and HOMA (P = 0·008) in the PCOS sample. Interestingly, the expected differences in surrogate measures of IR between cases and controls were not significant in CCGG/CCGG carriers. In the case-control study, genotype CCGG/CCGG was associated with a 14% decrease in PCOS risk (P = 0·043), taking into account confounding variables. Haplotype I (CCGG) has a protective role for IR and MS in PCOS. © 2012 Blackwell Publishing Ltd.

  13. The relativity of risk

    International Nuclear Information System (INIS)

    Fisk, R.H.

    1987-01-01

    The transport of radioactive material has long been a subject of emotive controversy. For a realistic assessment of the risks involved, however, they must be seen in the context of the transport of any hazardous cargoes, especially those which are energy-producing products

  14. [Construction of haplotype and haplotype block based on tag single nucleotide polymorphisms and their applications in association studies].

    Science.gov (United States)

    Gu, Ming-liang; Chu, Jia-you

    2007-12-01

    Human genome has structures of haplotype and haplotype block which provide valuable information on human evolutionary history and may lead to the development of more efficient strategies to identify genetic variants that increase susceptibility to complex diseases. Haplotype block can be divided into discrete blocks of limited haplotype diversity. In each block, a small fraction of ptag SNPsq can be used to distinguish a large fraction of the haplotypes. These tag SNPs can be potentially useful for construction of haplotype and haplotype block, and association studies in complex diseases. There are two general classes of methods to construct haplotype and haplotype blocks based on genotypes on large pedigrees and statistical algorithms respectively. The author evaluate several construction methods to assess the power of different association tests with a variety of disease models and block-partitioning criteria. The advantages, limitations and applications of each method and the application in the association studies are discussed equitably. With the completion of the HapMap and development of statistical algorithms for addressing haplotype reconstruction, ideas of construction of haplotype based on combination of mathematics, physics, and computer science etc will have profound impacts on population genetics, location and cloning for susceptible genes in complex diseases, and related domain with life science etc.

  15. The DQB1 *03:02 HLA haplotype is associated with increased risk of chronic pain after inguinal hernia surgery and lumbar disc herniation.

    Science.gov (United States)

    Dominguez, Cecilia A; Kalliomäki, Maija; Gunnarsson, Ulf; Moen, Aurora; Sandblom, Gabriel; Kockum, Ingrid; Lavant, Ewa; Olsson, Tomas; Nyberg, Fred; Rygh, Lars Jørgen; Røe, Cecilie; Gjerstad, Johannes; Gordh, Torsten; Piehl, Fredrik

    2013-03-01

    Neuropathic pain conditions are common after nerve injuries and are suggested to be regulated in part by genetic factors. We have previously demonstrated a strong genetic influence of the rat major histocompatibility complex on development of neuropathic pain behavior after peripheral nerve injury. In order to study if the corresponding human leukocyte antigen complex (HLA) also influences susceptibility to pain, we performed an association study in patients that had undergone surgery for inguinal hernia (n=189). One group had developed a chronic pain state following the surgical procedure, while the control group had undergone the same type of operation, without any persistent pain. HLA DRB1genotyping revealed a significantly increased proportion of patients in the pain group carrying DRB1*04 compared to patients in the pain-free group. Additional typing of the DQB1 gene further strengthened the association; carriers of the DQB1*03:02 allele together with DRB1*04 displayed an increased risk of postsurgery pain with an odds risk of 3.16 (1.61-6.22) compared to noncarriers. This finding was subsequently replicated in the clinical material of patients with lumbar disc herniation (n=258), where carriers of the DQB1*03:02 allele displayed a slower recovery and increased pain. In conclusion, we here for the first time demonstrate that there is an HLA-dependent risk of developing pain after surgery or lumbar disc herniation; mediated by the DRB1*04 - DQB1*03:02 haplotype. Further experimental and clinical studies are needed to fine-map the HLA effect and to address underlying mechanisms. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  16. Role of MMP-3 and MMP-9 and their haplotypes in risk of bladder cancer in North Indian cohort.

    Science.gov (United States)

    Srivastava, Priyanka; Mandhani, Anil; Kapoor, Rakesh; Mittal, Rama D

    2010-11-01

    Matrix metalloproteinases (MMPs) play critical roles in cancer development and progression. Nonsynonymous single nucleotide polymorphisms (SNPs) in functional domain of MMP-3 and MMP-9 contribute appreciably to cancer predisposition and aggression. To test this proposition we examined whether six SNPs of the MMP-3 and MMP-9 genes are associated with risk of bladder cancer (BC) in a North Indian population. Six SNPs of MMP-3 and MMP-9 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a case-control study including 200 BC patients and 200 age/gender/ethnicity-matched controls. Increased risk for BC susceptibility was observed in MMP-3 (1171) 5A/5A [P = 0.022; odds ratio (OR), 3.46; 95% confidence interval (CI), 1.20-9.98], MMP-9 (Q279R) QQ (P = 0.048; OR, 1.92; 95%CI, 1.01-3.66), MMP-9 (P574R) PR (P BCG)-treated non-muscle-invasive BC (NMIBC) patients (log-rank P = 0.025). Our data suggested that MMP-3-1171 5A/5A and MMP-9 (Q279R) QQ, MMP-9 (P574R) PR, PR + RR, and R allele are associated with high risk of BC.

  17. Haplotype analysis of the genes encoding glutamine synthetase plastic isoforms and their association with nitrogen-use- and yield-related traits in bread wheat.

    Science.gov (United States)

    Li, Xin-Peng; Zhao, Xue-Qiang; He, Xue; Zhao, Guang-Yao; Li, Bin; Liu, Dong-Cheng; Zhang, Ai-Min; Zhang, Xue-Yong; Tong, Yi-Ping; Li, Zhen-Sheng

    2011-01-01

    Glutamine synthetase (GS) plays a key role in the growth, nitrogen (N) use and yield potential of cereal crops. Investigating the haplotype variation of GS genes and its association with agronomic traits may provide useful information for improving wheat N-use efficiency and yield. We isolated the promoter and coding region sequences of the plastic glutamine synthetase isoform (GS2) genes located on chromosomes 2A, 2B and 2D in bread wheat. By analyzing nucleotide sequence variations of the coding region, two, six and two haplotypes were distinguished for TaGS2-A1 (a and b), TaGS2-B1 (a-f) and TaGS2-D1 (a and b), respectively. By analyzing the frequency data of different haplotypes and their association with N use and agronomic traits, four major and favorable TaGS2 haplotypes (A1b, B1a, B1b, D1a) were revealed. These favorable haplotypes may confer better seedling growth, better agronomic performance, and improved N uptake during vegetative growth or grain N concentration. Our data suggest that certain TaGS2 haplotypes may be valuable in breeding wheat varieties with improved agronomic performance and N-use efficiency. © The Authors (2010). Journal compilation © New Phytologist Trust (2010).

  18. Polymorphisms and haplotypes of the interleukin 2 gene are associated with an increased risk of gastric cancer. The possible involvement of Helicobacter pylori.

    Science.gov (United States)

    Melchiades, Jessica L; Zabaglia, Luanna M; Sallas, Mayara L; Orcini, Wilson A; Chen, Elizabeth; Smith, Marilia A C; Payão, Spencer L M; Rasmussen, Lucas T

    2017-08-01

    , a high risk was found in subjects carrying the +114 TT genotype (OR=6.36, 95% CI: 2.66-15.21, pgastric cancer. Therefore, our results show that, among patients with H. pylori infection, the -330 GG and +114 TT genotypes are significantly associated with a high risk of developing gastric cancer, as is the -330G/+114T haplotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Absolute risk, absolute risk reduction and relative risk

    Directory of Open Access Journals (Sweden)

    Jose Andres Calvache

    2012-12-01

    Full Text Available This article illustrates the epidemiological concepts of absolute risk, absolute risk reduction and relative risk through a clinical example. In addition, it emphasizes the usefulness of these concepts in clinical practice, clinical research and health decision-making process.

  20. Genomic sequence of 'Candidatus Liberibacter solanacearum' haplotype C and its comparison with haplotype A and B genomes.

    Directory of Open Access Journals (Sweden)

    Jinhui Wang

    Full Text Available Haplotypes A and B of 'Candidatus Liberibacter solanacearum' (CLso are associated with diseases of solanaceous plants, especially Zebra chip disease of potato, and haplotypes C, D and E are associated with symptoms on apiaceous plants. To date, one complete genome of haplotype B and two high quality draft genomes of haplotype A have been obtained for these unculturable bacteria using metagenomics from the psyllid vector Bactericera cockerelli. Here, we present the first genomic sequences obtained for the carrot-associated CLso. These two genomic sequences of haplotype C, FIN114 (1.24 Mbp and FIN111 (1.20 Mbp, were obtained from carrot psyllids (Trioza apicalis harboring CLso. Genomic comparisons between the haplotypes A, B and C revealed that the genome organization differs between these haplotypes, due to large inversions and other recombinations. Comparison of protein-coding genes indicated that the core genome of CLso consists of 885 ortholog groups, with the pan-genome consisting of 1327 ortholog groups. Twenty-seven ortholog groups are unique to CLso haplotype C, whilst 11 ortholog groups shared by the haplotypes A and B, are not found in the haplotype C. Some of these ortholog groups that are not part of the core genome may encode functions related to interactions with the different host plant and psyllid species.

  1. A haplotype of polymorphisms in ASE-1, RAI and ERCC1 and the effects of tobacco smoking and alcohol consumption on risk of colorectal cancer: a Danish prospective case-cohort study

    DEFF Research Database (Denmark)

    Hansen, Rikke D; Sørensen, Mette; Tjønneland, Anne

    2008-01-01

    BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most frequent type of genetic variation in the human genome, and are of interest for the study of susceptibility to and protection from diseases. The haplotype at chromosome 19q13.2-3 encompassing the three SNPs ASE-1 G-21A, RAI IVS1 A4364G...... and ERCC1 Asn118Asn have been associated with risk of breast cancer and lung cancer. Haplotype carriers are defined as the homozygous carriers of RAI IVS1 A4364GA, ERCC1 Asn118AsnT and ASE-1 G-21AG. We aimed to evaluate whether the three polymorphisms and the haplotype are associated to risk of colorectal...... of colorectal cancer were found. No statistically significant interactions between the genotypes and the lifestyle exposures smoking or alcohol consumption were observed. CONCLUSION: Our results suggest that the ASE-1 G-21A, RAI IVS1 A4364G and ERCC1 Asn118Asn polymorphisms and the previously identified...

  2. Employment relations, flexibility and risk

    DEFF Research Database (Denmark)

    Jensen, Carsten Strøby

    Employment relations literature often distinguishes between social democratic/corporatist models of employment relations and liberal models of employment relations as they are seen as opposite or at least different ways of organizing labor markets. They are often characterized as having very...... different risk profiles in terms of relationships between employees, employers, and the state. Low levels of labor market regulation very often characterize the liberal models of employment relations as we know them from, for instance, the USA and the UK. This means that employment conditions are very often...... insecure and that the burden of unemployment risk mostly lies with the employees rather than the employer. Corporatist – or social democratic – employment relations models are, in contrast to the liberal models, often characterized by stricter regulation of the labor market and by high standards...

  3. Haplotype association analysis of human disease traits using genotype data of unrelated individuals

    DEFF Research Database (Denmark)

    Tan, Qihua; Christiansen, Lene; Christensen, Kaare

    2005-01-01

    unphased multi-locus genotype data, ranging from the early approach by the simple gene-counting method to the recent work using the generalized linear model. However, these methods are either confined to case – control design or unable to yield unbiased point and interval estimates of haplotype effects....... Based on the popular logistic regression model, we present a new approach for haplotype association analysis of human disease traits. Using haplotype-based parameterization, our model infers the effects of specific haplotypes (point estimation) and constructs confidence interval for the risks...... on the well-known logistic regression model is a useful tool for haplotype association analysis of human disease traits....

  4. Beta-globin gene cluster haplotypes of Amerindian populations from the Brazilian Amazon region.

    Science.gov (United States)

    Guerreiro, J F; Figueiredo, M S; Zago, M A

    1994-01-01

    We have determined the beta-globin cluster haplotypes for 80 Indians from four Brazilian Amazon tribes: Kayapó, Wayampí, Wayana-Apalaí, and Arára. The results are analyzed together with 20 Yanomámi previously studied. From 2 to 4 different haplotypes were identified for each tribe, and 7 of the possible 32 haplotypes were found in a sample of 172 chromosomes for which the beta haplotypes were directly determined or derived from family studies. The haplotype distribution does not differ significantly among the five populations. The two most common haplotypes in all tribes were haplotypes 2 and 6, with average frequencies of 0.843 and 0.122, respectively. The genetic affinities between Brazilian Indians and other human populations were evaluated by estimates of genetic distance based on haplotype data. The lowest values were observed in relation to Asians, especially Chinese, Polynesians, and Micronesians.

  5. Are molecular haplotypes worth the time and expense? A cost-effective method for applying molecular haplotypes.

    Directory of Open Access Journals (Sweden)

    Mark A Levenstien

    2006-08-01

    Full Text Available Because current molecular haplotyping methods are expensive and not amenable to automation, many researchers rely on statistical methods to infer haplotype pairs from multilocus genotypes, and subsequently treat these inferred haplotype pairs as observations. These procedures are prone to haplotype misclassification. We examine the effect of these misclassification errors on the false-positive rate and power for two association tests. These tests include the standard likelihood ratio test (LRTstd and a likelihood ratio test that employs a double-sampling approach to allow for the misclassification inherent in the haplotype inference procedure (LRTae. We aim to determine the cost-benefit relationship of increasing the proportion of individuals with molecular haplotype measurements in addition to genotypes to raise the power gain of the LRTae over the LRTstd. This analysis should provide a guideline for determining the minimum number of molecular haplotypes required for desired power. Our simulations under the null hypothesis of equal haplotype frequencies in cases and controls indicate that (1 for each statistic, permutation methods maintain the correct type I error; (2 specific multilocus genotypes that are misclassified as the incorrect haplotype pair are consistently misclassified throughout each entire dataset; and (3 our simulations under the alternative hypothesis showed a significant power gain for the LRTae over the LRTstd for a subset of the parameter settings. Permutation methods should be used exclusively to determine significance for each statistic. For fixed cost, the power gain of the LRTae over the LRTstd varied depending on the relative costs of genotyping, molecular haplotyping, and phenotyping. The LRTae showed the greatest benefit over the LRTstd when the cost of phenotyping was very high relative to the cost of genotyping. This situation is likely to occur in a replication study as opposed to a whole-genome association study.

  6. Haplotyping Problem, A Clustering Approach

    International Nuclear Information System (INIS)

    Eslahchi, Changiz; Sadeghi, Mehdi; Pezeshk, Hamid; Kargar, Mehdi; Poormohammadi, Hadi

    2007-01-01

    Construction of two haplotypes from a set of Single Nucleotide Polymorphism (SNP) fragments is called haplotype reconstruction problem. One of the most popular computational model for this problem is Minimum Error Correction (MEC). Since MEC is an NP-hard problem, here we propose a novel heuristic algorithm based on clustering analysis in data mining for haplotype reconstruction problem. Based on hamming distance and similarity between two fragments, our iterative algorithm produces two clusters of fragments; then, in each iteration, the algorithm assigns a fragment to one of the clusters. Our results suggest that the algorithm has less reconstruction error rate in comparison with other algorithms

  7. Mapping Haplotype-haplotype Interactions with Adaptive LASSO

    Directory of Open Access Journals (Sweden)

    Li Ming

    2010-08-01

    Full Text Available Abstract Background The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs have been extensively studied. Recently, haplotype-based analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it presents daunting challenges in statistical modeling and testing of the interaction effects, largely due to the complicated higher order epistatic complexity. Results In this article, we propose a new strategy in modeling haplotype-haplotype interactions under the penalized logistic regression framework with adaptive L1-penalty. We consider interactions of sequence variants between haplotype blocks. The adaptive L1-penalty allows simultaneous effect estimation and variable selection in a single model. We propose a new parameter estimation method which estimates and selects parameters by the modified Gauss-Seidel method nested within the EM algorithm. Simulation studies show that it has low false positive rate and reasonable power in detecting haplotype interactions. The method is applied to test haplotype interactions involved in mother and offspring genome in a small for gestational age (SGA neonates data set, and significant interactions between different genomes are detected. Conclusions As demonstrated by the simulation studies and real data analysis, the approach developed provides an efficient tool for the modeling and testing of haplotype interactions. The implementation of the method in R codes can be

  8. Opposing effects of the HLA-DRB1*0301-DQB1*0201 haplotype on the risk for multiple sclerosis in diverse Arab populations in Israel.

    Science.gov (United States)

    Benedek, G; Paperna, T; Avidan, N; Lejbkowicz, I; Oksenberg, J R; Wang, J; Brautbar, C; Israel, S; Miller, A

    2010-07-01

    Different multiple sclerosis (MS) prevalence rates were reported for Muslim and Christian Arabs in Israel. In this study, we evaluated whether associations of human leukocyte antigen (HLA) genes with MS may contribute to this prevalence difference. DNA samples from Israeli Arab MS patients (n=109) and controls (n=132) were typed for HLA class I (HLA-A, -B and -C) and II (HLA-DRB1 and -DQB1) genes. Global comparisons of HLA allele frequencies revealed significant differences between Christians and Muslims; therefore, case-control analyses were stratified by religious affiliation. Disease characteristics of Muslim and Christian Arab MS patients were similar to those reported for European populations. Opposing association signals with MS were observed for alleles composing the DRB1*0301-DQB1*0201 haplotype: positive association of the HLA-DRB1*0301 allele in Muslims (P(Bonferroni)=0.004, odds ratio (OR)=3.07), and negative association in Christian Arabs (P(Bonferroni)=0.01, OR=0.12), with similar results obtained for HLA-DQB1*0201. HLA-B*52 was negatively associated with MS only in Muslims (P(Bonferroni)=0.01, OR=0.03). The study presents for the first time a high-resolution HLA gene analysis in clinically well-characterized Arab populations with MS, and shows the population-specific contribution of the DRB1*0301-DQB1*0201 haplotype to disease susceptibility.

  9. Haplotype reconstruction error as a classical misclassification problem: introducing sensitivity and specificity as error measures.

    Directory of Open Access Journals (Sweden)

    Claudia Lamina

    Full Text Available BACKGROUND: Statistically reconstructing haplotypes from single nucleotide polymorphism (SNP genotypes, can lead to falsely classified haplotypes. This can be an issue when interpreting haplotype association results or when selecting subjects with certain haplotypes for subsequent functional studies. It was our aim to quantify haplotype reconstruction error and to provide tools for it. METHODS AND RESULTS: By numerous simulation scenarios, we systematically investigated several error measures, including discrepancy, error rate, and R(2, and introduced the sensitivity and specificity to this context. We exemplified several measures in the KORA study, a large population-based study from Southern Germany. We find that the specificity is slightly reduced only for common haplotypes, while the sensitivity was decreased for some, but not all rare haplotypes. The overall error rate was generally increasing with increasing number of loci, increasing minor allele frequency of SNPs, decreasing correlation between the alleles and increasing ambiguity. CONCLUSIONS: We conclude that, with the analytical approach presented here, haplotype-specific error measures can be computed to gain insight into the haplotype uncertainty. This method provides the information, if a specific risk haplotype can be expected to be reconstructed with rather no or high misclassification and thus on the magnitude of expected bias in association estimates. We also illustrate that sensitivity and specificity separate two dimensions of the haplotype reconstruction error, which completely describe the misclassification matrix and thus provide the prerequisite for methods accounting for misclassification.

  10. Allelic variation of the COMT gene in a despotic primate society: A haplotype is related to cortisol excretion in Macaca fuscata.

    Science.gov (United States)

    Pflüger, Lena S; Gutleb, Daria R; Hofer, Martin; Fieder, Martin; Wallner, Bernard; Steinborn, Ralf

    2016-02-01

    Sequence variations in genes of the monoamine neurotransmitter system and their common function in human and non-human primate species are an ongoing issue of investigation. However, the COMT gene, coding for the catechol-O-methyltransferase, has not yet attracted much scientific attention regarding its functional role in non-human primates. Considering that a polymorphism of the human COMT gene affects the enzyme activity and cortisol level in response to a social stressor, this study investigated the impact of COMT on endocrine stress and behavioural parameters in Japanese macaques (Macaca fuscata). The species exemplifies a despotic hierarchy in which males' social rank positions require an adaptation of behaviour strategies. During the mating period steroid secretion and the frequency of aggressive encounters between males increase. We addressed i) whether this species exhibits potential functional COMT variants, ii) whether these variants are associated with faecal cortisol excretion of males, iii) how they are distributed among different social rank positions and iv) whether they are associated with behavioural strategies during times of mate competition. By genotyping 26 males we identified three COMT haplotypes (HT), including a putative splice mutant (HT3). This variant was associated with increased cortisol excretion. Given the observed inverse correlation between cortisol and physical aggression, we assume that different COMT haplotypes may predispose individuals to pursue more or less aggressive strategies. How these gene-stress effects might favour a specific social role is discussed. Our study of non-invasive genotyping in combination with behavioural and endocrine parameters represents an important step towards the understanding of gene-stress effects in a hierarchically organised primate society. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Dimensional Anxiety Mediates Linkage of GABRA2 Haplotypes With Alcoholism

    Science.gov (United States)

    Enoch, Mary-Anne; Schwartz, Lori; Albaugh, Bernard; Virkkunen, Matti; Goldman, David

    2015-01-01

    The GABAAα2 receptor gene (GABRA2) modulates anxiety and stress response. Three recent association studies implicate GABRA2 in alcoholism, however in these papers both common, opposite-configuration haplotypes in the region distal to intron3 predict risk. We have now replicated the GABRA2 association with alcoholism in 331 Plains Indian men and women and 461 Finnish Caucasian men. Using a dimensional measure of anxiety, harm avoidance (HA), we also found that the association with alcoholism is mediated, or moderated, by anxiety. Nine SNPs were genotyped revealing two haplotype blocks. Within the previously implicated block 2 region, we identified the two common, opposite-configuration risk haplotypes, A and B. Their frequencies differed markedly in Finns and Plains Indians. In both populations, most block 2 SNPs were significantly associated with alcoholism. The associations were due to increased frequencies of both homozygotes in alcoholics, indicating the possibility of alcoholic subtypes with opposite genotypes. Congruently, there was no significant haplotype association. Using HA as an indicator variable for anxiety, we found haplotype linkage to alcoholism with high and low dimensional anxiety, and to HA itself, in both populations. High HA alcoholics had the highest frequency of the more abundant haplotype (A in Finns, B in Plains Indians); low HA alcoholics had the highest frequency of the less abundant haplotype (B in Finns, A in Plains Indians) (Finns: P α0.007, OR α2.1, Plains Indians: P α0.040, OR α1.9). Non-alcoholics had intermediate frequencies. Our results suggest that within the distal GABRA2 region is a functional locus or loci that may differ between populations but that alters risk for alcoholism via the mediating action of anxiety. PMID:16874763

  12. HERC1 polymorphisms: population-specific variations in haplotype composition.

    Science.gov (United States)

    Yuasa, Isao; Umetsu, Kazuo; Nishimukai, Hiroaki; Fukumori, Yasuo; Harihara, Shinji; Saitou, Naruya; Jin, Feng; Chattopadhyay, Prasanta K; Henke, Lotte; Henke, Jürgen

    2009-08-01

    Human HERC1 is one of six HERC proteins and may play an important role in intracellular membrane trafficking. The human HERC1 gene is suggested to have been affected by local positive selection. To assess the global frequency distributions of coding and non-coding single nucleotide polymorphisms (SNPs) in the HERC1 gene, we developed a new simultaneous genotyping method for four SNPs, and applied this method to investigate 1213 individuals from 12 global populations. The results confirmed remarked differences in the allele and haplotype frequencies between East Asian and non-East Asian populations. One of the three common haplotypes observed was found to be characteristic of East Asians, who showed a relatively uniform distribution of haplotypes. Information on haplotypes would be useful for testing the function of polymorphisms in the HERC1 gene. This is the first study to investigate the distribution of HERC1 polymorphisms in various populations. (c) 2009 John Wiley & Sons, Ltd.

  13. Haplotype inference in general pedigrees with two sites

    Directory of Open Access Journals (Sweden)

    Doan Duong D

    2011-04-01

    Full Text Available Abstract Background Genetic disease studies investigate relationships between changes in chromosomes and genetic diseases. Single haplotypes provide useful information for these studies but extracting single haplotypes directly by biochemical methods is expensive. A computational method to infer haplotypes from genotype data is therefore important. We investigate the problem of computing the minimum number of recombination events for general pedigrees with two sites for all members. Results We show that this NP-hard problem can be parametrically reduced to the Bipartization by Edge Removal problem and therefore can be solved by an O(2k · n2 exact algorithm, where n is the number of members and k is the number of recombination events. Conclusions Our work can therefore be useful for genetic disease studies to track down how changes in haplotypes such as recombinations relate to genetic disease.

  14. Approximation properties of haplotype tagging

    Directory of Open Access Journals (Sweden)

    Dreiseitl Stephan

    2006-01-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are locations at which the genomic sequences of population members differ. Since these differences are known to follow patterns, disease association studies are facilitated by identifying SNPs that allow the unique identification of such patterns. This process, known as haplotype tagging, is formulated as a combinatorial optimization problem and analyzed in terms of complexity and approximation properties. Results It is shown that the tagging problem is NP-hard but approximable within 1 + ln((n2 - n/2 for n haplotypes but not approximable within (1 - ε ln(n/2 for any ε > 0 unless NP ⊂ DTIME(nlog log n. A simple, very easily implementable algorithm that exhibits the above upper bound on solution quality is presented. This algorithm has running time O((2m - p + 1 ≤ O(m(n2 - n/2 where p ≤ min(n, m for n haplotypes of size m. As we show that the approximation bound is asymptotically tight, the algorithm presented is optimal with respect to this asymptotic bound. Conclusion The haplotype tagging problem is hard, but approachable with a fast, practical, and surprisingly simple algorithm that cannot be significantly improved upon on a single processor machine. Hence, significant improvement in computatational efforts expended can only be expected if the computational effort is distributed and done in parallel.

  15. Risk Aversion Relates to Cognitive Ability

    DEFF Research Database (Denmark)

    Andersson, Ola; Holm, Håkan J.; Tyran, Jean-Robert Karl

    2016-01-01

    Recent experimental studies suggest that risk aversion is negatively related to cognitive ability. In this paper we report evidence that this relation might be spurious. We recruit a large subject pool drawn from the general Danish population for our experiment. By presenting subjects with choice...... tasks that vary the bias induced by random choices, we are able to generate both negative and positive correlations between risk aversion and cognitive ability. Structural estimation allowing for heterogeneity of noise yields no significant relation between risk aversion and cognitive ability. Our...... results suggest that cognitive ability is related to random decision making, rather than to risk preferences....

  16. Risk aversion relates to cognitive ability

    DEFF Research Database (Denmark)

    Andersson, Ola; Holm, Håkan J.; Tyran, Jean-Robert Karl

    Recent experimental studies suggest that risk aversion is negatively related to cognitive ability. In this paper we report evidence that this relation might be spurious. We recruit a large subject pool drawn from the general Danish population for our experiment. By presenting subjects with choice...... tasks that vary the bias induced by random choices, we are able to generate both negative and positive correlations between risk aversion and cognitive ability. Structural estimation allowing for heterogeneity of noise yields no significant relation between risk aversion and cognitive ability. Our...... results suggest that cognitive ability is related to random decision making rather than to risk preferences....

  17. Detecting structure of haplotypes and local ancestry

    Science.gov (United States)

    We present a two-layer hidden Markov model to detect the structure of haplotypes for unrelated individuals. This allows us to model two scales of linkage disequilibrium (one within a group of haplotypes and one between groups), thereby taking advantage of rich haplotype information to infer local an...

  18. Modeling coverage gaps in haplotype frequencies via Bayesian inference to improve stem cell donor selection.

    Science.gov (United States)

    Louzoun, Yoram; Alter, Idan; Gragert, Loren; Albrecht, Mark; Maiers, Martin

    2018-05-01

    Regardless of sampling depth, accurate genotype imputation is limited in regions of high polymorphism which often have a heavy-tailed haplotype frequency distribution. Many rare haplotypes are thus unobserved. Statistical methods to improve imputation by extending reference haplotype distributions using linkage disequilibrium patterns that relate allele and haplotype frequencies have not yet been explored. In the field of unrelated stem cell transplantation, imputation of highly polymorphic human leukocyte antigen (HLA) genes has an important application in identifying the best-matched stem cell donor when searching large registries totaling over 28,000,000 donors worldwide. Despite these large registry sizes, a significant proportion of searched patients present novel HLA haplotypes. Supporting this observation, HLA population genetic models have indicated that many extant HLA haplotypes remain unobserved. The absent haplotypes are a significant cause of error in haplotype matching. We have applied a Bayesian inference methodology for extending haplotype frequency distributions, using a model where new haplotypes are created by recombination of observed alleles. Applications of this joint probability model offer significant improvement in frequency distribution estimates over the best existing alternative methods, as we illustrate using five-locus HLA frequency data from the National Marrow Donor Program registry. Transplant matching algorithms and disease association studies involving phasing and imputation of rare variants may benefit from this statistical inference framework.

  19. In Vivo Characterization of Human APOA5 Haplotypes

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Akiyama, Jennifer; Chapman-Helleboid, Audrey; Fruchart, Jamila; Pennacchio, Len A.

    2006-10-01

    Increased plasma triglycerides concentrations are an independent risk factor for cardiovascular disease. Numerous studies support a reproducible genetic association between two minor haplotypes in the human apolipoprotein A5 gene (APOA5) and increased plasma triglyceride concentrations. We thus sought to investigate the effect of these minor haplotypes (APOA5*2 and APOA5*3) on ApoAV plasma levels through the precise insertion of single-copy intact APOA5 haplotypes at a targeted location in the mouse genome. While we found no difference in the amount of human plasma ApoAV in mice containing the common APOA5*1 and minor APOA5*2 haplotype, the introduction of the single APOA5*3 defining allele (19W) resulted in 3-fold lower ApoAV plasma levels consistent with existing genetic association studies. These results indicate that S19W polymorphism is likely to be functional and explain the strong association of this variant with plasma triglycerides supporting the value of sensitive in vivo assays to define the functional nature of human haplotypes.

  20. Risk Estimates and Risk Factors Related to Psychiatric Inpatient Suicide

    DEFF Research Database (Denmark)

    Madsen, Trine; Erlangsen, Annette; Nordentoft, Merete

    2017-01-01

    trends, and socio-demographic and clinical risk factors of suicide in psychiatric inpatients. Psychiatric inpatients have a very high risk of suicide relative to the background population, but it remains challenging for clinicians to identify those patients that are most likely to die from suicide during......People with mental illness have an increased risk of suicide. The aim of this paper is to provide an overview of suicide risk estimates among psychiatric inpatients based on the body of evidence found in scientific peer-reviewed literature; primarily focusing on the relative risks, rates, time...... admission. Most studies are based on low power, thus compromising quality and generalisability. The few studies with sufficient statistical power mainly identified non-modifiable risk predictors such as male gender, diagnosis, or recent deliberate self-harm. Also, the predictive value of these predictors...

  1. Risk Estimates and Risk Factors Related to Psychiatric Inpatient Suicide

    DEFF Research Database (Denmark)

    Madsen, Trine; Erlangsen, Annette; Nordentoft, Merete

    2017-01-01

    People with mental illness have an increased risk of suicide. The aim of this paper is to provide an overview of suicide risk estimates among psychiatric inpatients based on the body of evidence found in scientific peer-reviewed literature; primarily focusing on the relative risks, rates, time...... trends, and socio-demographic and clinical risk factors of suicide in psychiatric inpatients. Psychiatric inpatients have a very high risk of suicide relative to the background population, but it remains challenging for clinicians to identify those patients that are most likely to die from suicide during...... is low. It would be of great benefit if future studies would be based on large samples while focusing on modifiable predictors over the course of an admission, such as hopelessness, depressive symptoms, and family/social situations. This would improve our chances of developing better risk assessment...

  2. Calculating excess lifetime risk in relative risk models

    International Nuclear Information System (INIS)

    Vaeth, M.; Pierce, D.A.

    1990-01-01

    When assessing the impact of radiation exposure it is common practice to present the final conclusions in terms of excess lifetime cancer risk in a population exposed to a given dose. The present investigation is mainly a methodological study focusing on some of the major issues and uncertainties involved in calculating such excess lifetime risks and related risk projection methods. The age-constant relative risk model used in the recent analyses of the cancer mortality that was observed in the follow-up of the cohort of A-bomb survivors in Hiroshima and Nagasaki is used to describe the effect of the exposure on the cancer mortality. In this type of model the excess relative risk is constant in age-at-risk, but depends on the age-at-exposure. Calculation of excess lifetime risks usually requires rather complicated life-table computations. In this paper we propose a simple approximation to the excess lifetime risk; the validity of the approximation for low levels of exposure is justified empirically as well as theoretically. This approximation provides important guidance in understanding the influence of the various factors involved in risk projections. Among the further topics considered are the influence of a latent period, the additional problems involved in calculations of site-specific excess lifetime cancer risks, the consequences of a leveling off or a plateau in the excess relative risk, and the uncertainties involved in transferring results from one population to another. The main part of this study relates to the situation with a single, instantaneous exposure, but a brief discussion is also given of the problem with a continuous exposure at a low-dose rate

  3. Mapping of HLA- DQ haplotypes in a group of Danish patients with celiac disease

    DEFF Research Database (Denmark)

    Lund, Flemming; Hermansen, Mette N; Pedersen, Merete F

    2015-01-01

    BACKGROUND: A cost-effective identification of HLA- DQ risk haplotypes using the single nucleotide polymorphism (SNP) technique has recently been applied in the diagnosis of celiac disease (CD) in four European populations. The objective of the study was to map risk HLA- DQ haplotypes in a group...... of Danish CD patients using the SNP technique. METHODS: Cohort A: Among 65 patients with gastrointestinal symptoms we compared the HLA- DQ2 and HLA- DQ8 risk haplotypes obtained by the SNP technique (method 1) with results based on a sequence specific primer amplification technique (method 2...

  4. Managing risk in statistics - "Relative risk" | Durrheim | South African ...

    African Journals Online (AJOL)

    South African Family Practice. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 45, No 8 (2003) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Managing risk in statistics - "Relative risk". DN Durrheim ...

  5. The analysis of APOL1 genetic variation and haplotype diversity provided by 1000 Genomes project.

    Science.gov (United States)

    Peng, Ting; Wang, Li; Li, Guisen

    2017-08-11

    The APOL1 gene variants has been shown to be associated with an increased risk of multiple kinds of diseases, particularly in African Americans, but not in Caucasians and Asians. In this study, we explored the single nucleotide polymorphism (SNP) and haplotype diversity of APOL1 gene in different races provided by 1000 Genomes project. Variants of APOL1 gene in 1000 Genome Project were obtained and SNPs located in the regulatory region or coding region were selected for genetic variation analysis. Total 2504 individuals from 26 populations were classified as four groups that included Africa, Europe, Asia and Admixed populations. Tag SNPs were selected to evaluate the haplotype diversities in the four populations by HaploStats software. APOL1 gene was surrounded by some of the most polymorphic genes in the human genome, variation of APOL1 gene was common, with up to 613 SNP (1000 Genome Project reported) and 99 of them (16.2%) with MAF ≥ 1%. There were 79 SNPs in the URR and 92 SNPs in 3'UTR. Total 12 SNPs in URR and 24 SNPs in 3'UTR were considered as common variants with MAF ≥ 1%. It is worth noting that URR-1 was presents lower frequencies in European populations, while other three haplotypes taken an opposite pattern; 3'UTR presents several high-frequency variation sites in a short segment, and the differences of its haplotypes among different population were significant (P < 0.01), UTR-1 and UTR-5 presented much higher frequency in African population, while UTR-2, UTR-3 and UTR-4 were much lower. APOL1 coding region showed that two SNP of G1 with higher frequency are actually pull down the haplotype H-1 frequency when considering all populations pooled together, and the diversity among the four populations be widen by the G1 two mutation (P 1  = 3.33E-4 vs P 2  = 3.61E-30). The distributions of APOL1 gene variants and haplotypes were significantly different among the different populations, in either regulatory or coding regions. It could provide

  6. Risk sharing relations and enforcement mechanisms

    NARCIS (Netherlands)

    Barr, A.; Dekker, M.; Fafchamps, M.

    2008-01-01

    We investigate whether the set of available enforcement mechanisms affects the formation of risk sharing relations by applying dyadic regression analysis to data from a specifically designed behavioural experiment, two surveys and a genealogical mapping exercise. During the experiment participants

  7. Human Immunodeficiency Virus Related Knowledge, Risk ...

    African Journals Online (AJOL)

    There was poor HIV preventive practices; indicating ... Gyawali, et al.: HIV related knowledge, risk perception and practices among married women. Annals of Medical .... of this study correspond to the Indian, Nigerian and Iranian studies cited ...

  8. Roadway related tort liability and risk management.

    Science.gov (United States)

    2010-06-01

    This workbook provide government employees background information related to tort liability and risk management. Past experience with lawsuits against government entities are summarized. The reasons for the lawsuits and results are analyzed. The obje...

  9. Testing for changes in spatial relative risk.

    Science.gov (United States)

    Hazelton, Martin L

    2017-07-30

    The spatial relative risk function is a useful tool for describing geographical variation in disease incidence. We consider the problem of comparing relative risk functions between two time periods, with the idea of detecting alterations in the spatial pattern of disease risk irrespective of whether there has been a change in the overall incidence rate. Using case-control datasets for each period, we use kernel smoothing methods to derive a test statistic based on the difference between the log-relative risk functions, which we term the log-relative risk ratio. For testing a null hypothesis of an unchanging spatial pattern of risk, we show how p-values can be computed using both randomization methods and an asymptotic normal approximation. The methodology is applied to data on campylobacteriosis from 2006 to 2013 in a region of New Zealand. We find clear evidence of a change in the spatial pattern of risk between those years, which can be explained in differences by response to a public health initiative between urban and rural communities. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Clustering, haplotype diversity and locations of MIC-3: a unique root-specific defense-related gene family in upland cotton (Gossypium hirsutum L.)

    Science.gov (United States)

    MIC-3-related genes of cotton (Gossypium spp.) were identified and shown to have root-specific expression, associated with pathogen defense-related function and specifically increased expression in root-knot nematode (RKN) resistant plants after nematode infection. Here we cloned and sequenced MIC-...

  11. RTEL1 tagging SNPs and haplotypes were associated with glioma development.

    Science.gov (United States)

    Li, Gang; Jin, Tianbo; Liang, Hongjuan; Zhang, Zhiguo; He, Shiming; Tu, Yanyang; Yang, Haixia; Geng, Tingting; Cui, Guangbin; Chen, Chao; Gao, Guodong

    2013-05-17

    As glioma ranks as the first most prevalent solid tumors in primary central nervous system, certain single-nucleotide polymorphisms (SNPs) may be related to increased glioma risk, and have implications in carcinogenesis. The present case-control study was carried out to elucidate how common variants contribute to glioma susceptibility. Ten candidate tagging SNPs (tSNPs) were selected from seven genes whose polymorphisms have been proven by classical literatures and reliable databases to be tended to relate with gliomas, and with the minor allele frequency (MAF)>5% in the HapMap Asian population. The selected tSNPs were genotyped in 629 glioma patients and 645 controls from a Han Chinese population using the multiplexed SNP MassEXTEND assay calibrated. Two significant tSNPs in RTEL1 gene were observed to be associated with glioma risk (rs6010620, P=0.0016, OR: 1.32, 95% CI: 1.11-1.56; rs2297440, P=0.001, OR: 1.33, 95% CI: 1.12-1.58) by χ2 test. It was identified the genotype "GG" of rs6010620 acted as the protective genotype for glioma (OR, 0.46; 95% CI, 0.31-0.7; P=0.0002), while the genotype "CC" of rs2297440 as the protective genotype in glioma (OR, 0.47; 95% CI, 0.31-0.71; P=0.0003). Furthermore, haplotype "GCT" in RTEL1 gene was found to be associated with risk of glioma (OR, 0.7; 95% CI, 0.57-0.86; Fisher's P=0.0005; Pearson's P=0.0005), and haplotype "ATT" was detected to be associated with risk of glioma (OR, 1.32; 95% CI, 1.12-1.57; Fisher's P=0.0013; Pearson's P=0.0013). Two single variants, the genotypes of "GG" of rs6010620 and "CC" of rs2297440 (rs6010620 and rs2297440) in the RTEL1 gene, together with two haplotypes of GCT and ATT, were identified to be associated with glioma development. And it might be used to evaluate the glioma development risks to screen the above RTEL1 tagging SNPs and haplotypes. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1993021136961998.

  12. Genetic relationships among native americans based on beta-globin gene cluster haplotype frequencies

    Directory of Open Access Journals (Sweden)

    Rita de Cassia Mousinho-Ribeiro

    2003-01-01

    Full Text Available The distribution of b-globin gene haplotypes was studied in 209 Amerindians from eight tribes of the Brazilian Amazon: Asurini from Xingú, Awá-Guajá, Parakanã, Urubú-Kaapór, Zoé, Kayapó (Xikrin from the Bacajá village, Katuena, and Tiriyó. Nine different haplotypes were found, two of which (n. 11 and 13 had not been previously identified in Brazilian indigenous populations. Haplotype 2 (+ - - - - was the most common in all groups studied, with frequencies varying from 70% to 100%, followed by haplotype 6 (- + + - +, with frequencies between 7% and 18%. The frequency distribution of the b-globin gene haplotypes in the eighteen Brazilian Amerindian populations studied to date is characterized by a reduced number of haplotypes (average of 3.5 and low levels of heterozygosity and intrapopulational differentiation, with a single clearly predominant haplotype in most tribes (haplotype 2. The Parakanã, Urubú-Kaapór, Tiriyó and Xavante tribes constitute exceptions, presenting at least four haplotypes with relatively high frequencies. The closest genetic relationships were observed between the Brazilian and the Colombian Amerindians (Wayuu, Kamsa and Inga, and, to a lesser extent, with the Huichol of Mexico. North-American Amerindians are more differentiated and clearly separated from all other tribes, except the Xavante, from Brazil, and the Mapuche, from Argentina. A restricted pool of ancestral haplotypes may explain the low diversity observed among most present-day Brazilian and Colombian Amerindian groups, while interethnic admixture could be the most important factor to explain the high number of haplotypes and high levels of diversity observed in some South-American and most North-American tribes.

  13. Estimating haplotype effects for survival data

    DEFF Research Database (Denmark)

    Scheike, Thomas; Martinussen, Torben; Silver, J

    2010-01-01

    Genetic association studies often investigate the effect of haplotypes on an outcome of interest. Haplotypes are not observed directly, and this complicates the inclusion of such effects in survival models. We describe a new estimating equations approach for Cox's regression model to assess haplo...

  14. Haplotype-Based Genotyping in Polyploids

    Directory of Open Access Journals (Sweden)

    Josh P. Clevenger

    2018-04-01

    Full Text Available Accurate identification of polymorphisms from sequence data is crucial to unlocking the potential of high throughput sequencing for genomics. Single nucleotide polymorphisms (SNPs are difficult to accurately identify in polyploid crops due to the duplicative nature of polyploid genomes leading to low confidence in the true alignment of short reads. Implementing a haplotype-based method in contrasting subgenome-specific sequences leads to higher accuracy of SNP identification in polyploids. To test this method, a large-scale 48K SNP array (Axiom Arachis2 was developed for Arachis hypogaea (peanut, an allotetraploid, in which 1,674 haplotype-based SNPs were included. Results of the array show that 74% of the haplotype-based SNP markers could be validated, which is considerably higher than previous methods used for peanut. The haplotype method has been implemented in a standalone program, HAPLOSWEEP, which takes as input bam files and a vcf file and identifies haplotype-based markers. Haplotype discovery can be made within single reads or span paired reads, and can leverage long read technology by targeting any length of haplotype. Haplotype-based genotyping is applicable in all allopolyploid genomes and provides confidence in marker identification and in silico-based genotyping for polyploid genomics.

  15. Polymorphisms in genes related to inflammation, NSAID use, and the risk of prostate cancer among Danish men

    DEFF Research Database (Denmark)

    Kopp, Tine Iskov; Friis, Søren; Christensen, Jane

    2013-01-01

    The etiology of prostate cancer (PC) remains mostly unknown, but increasing evidence suggests that chronic inflammation in the prostate is associated with an increased risk of PC. Epidemiological studies have suggested that use of nonsteroidal anti-inflammatory drugs (NSAIDs) may protect against PC....... Inborn variations in genes involved in the inflammatory response may modulate the risk of PC and interact with NSAIDs. The aims of this study were 1) to evaluate whether polymorphisms and haplotypes of the inflammation-related genes COX-2, Il1B, NFKB1, and PPARG are associated with risk of PC; 2......) to investigate gene–environment interactions between polymorphisms and NSAID use; and 3) to examine whether the studied polymorphisms were associated with the aggressiveness of PC. The study population consisted of 370 cases of PC and 370 risk-set matched (age) controls nested within the prospective Danish “Diet...

  16. Serpin peptidase inhibitor (SERPINB5) haplotypes are associated with susceptibility to hepatocellular carcinoma

    Science.gov (United States)

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

    2016-05-01

    Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related death worldwide. The serpin peptidase inhibitor SERPINB5 is a tumour-suppressor gene that promotes the development of various cancers in humans. However, whether SERPINB5 gene variants play a role in HCC susceptibility remains unknown. In this study, we genotyped 6 SNPs of the SERPINB5 gene in an independent cohort from a replicate population comprising 302 cases and 590 controls. Additionally, patients who had at least one rs2289520 C allele in SERPINB5 tended to exhibit better liver function than patients with genotype GG (Child-Pugh grade A vs. B or C; P = 0.047). Next, haplotype blocks were reconstructed according to the linkage disequilibrium structure of the SERPINB5 gene. A haplotype “C-C-C” (rs17071138 + rs3744941 + rs8089204) in SERPINB5-correlated promoter showed a significant association with an increased HCC risk (AOR = 1.450 P = 0.031). Haplotypes “T-C-A” and “C-C-C” (rs2289519 + rs2289520 + rs1455555) located in the SERPINB5 coding region had a decreased (AOR = 0.744 P = 0.031) and increased (AOR = 1.981 P = 0.001) HCC risk, respectively. Finally, an additional integrated in silico analysis confirmed that these SNPs affected SERPINB5 expression and protein stability, which significantly correlated with tumour expression and subsequently with tumour development and aggressiveness. Taken together, our findings regarding these biomarkers provide a prediction model for risk assessment.

  17. Haplotype phasing and inheritance of copy number variants in nuclear families.

    Science.gov (United States)

    Palta, Priit; Kaplinski, Lauris; Nagirnaja, Liina; Veidenberg, Andres; Möls, Märt; Nelis, Mari; Esko, Tõnu; Metspalu, Andres; Laan, Maris; Remm, Maido

    2015-01-01

    DNA copy number variants (CNVs) that alter the copy number of a particular DNA segment in the genome play an important role in human phenotypic variability and disease susceptibility. A number of CNVs overlapping with genes have been shown to confer risk to a variety of human diseases thus highlighting the relevance of addressing the variability of CNVs at a higher resolution. So far, it has not been possible to deterministically infer the allelic composition of different haplotypes present within the CNV regions. We have developed a novel computational method, called PiCNV, which enables to resolve the haplotype sequence composition within CNV regions in nuclear families based on SNP genotyping microarray data. The algorithm allows to i) phase normal and CNV-carrying haplotypes in the copy number variable regions, ii) resolve the allelic copies of rearranged DNA sequence within the haplotypes and iii) infer the heritability of identified haplotypes in trios or larger nuclear families. To our knowledge this is the first program available that can deterministically phase null, mono-, di-, tri- and tetraploid genotypes in CNV loci. We applied our method to study the composition and inheritance of haplotypes in CNV regions of 30 HapMap Yoruban trios and 34 Estonian families. For 93.6% of the CNV loci, PiCNV enabled to unambiguously phase normal and CNV-carrying haplotypes and follow their transmission in the corresponding families. Furthermore, allelic composition analysis identified the co-occurrence of alternative allelic copies within 66.7% of haplotypes carrying copy number gains. We also observed less frequent transmission of CNV-carrying haplotypes from parents to children compared to normal haplotypes and identified an emergence of several de novo deletions and duplications in the offspring.

  18. Haplotype phasing and inheritance of copy number variants in nuclear families.

    Directory of Open Access Journals (Sweden)

    Priit Palta

    Full Text Available DNA copy number variants (CNVs that alter the copy number of a particular DNA segment in the genome play an important role in human phenotypic variability and disease susceptibility. A number of CNVs overlapping with genes have been shown to confer risk to a variety of human diseases thus highlighting the relevance of addressing the variability of CNVs at a higher resolution. So far, it has not been possible to deterministically infer the allelic composition of different haplotypes present within the CNV regions. We have developed a novel computational method, called PiCNV, which enables to resolve the haplotype sequence composition within CNV regions in nuclear families based on SNP genotyping microarray data. The algorithm allows to i phase normal and CNV-carrying haplotypes in the copy number variable regions, ii resolve the allelic copies of rearranged DNA sequence within the haplotypes and iii infer the heritability of identified haplotypes in trios or larger nuclear families. To our knowledge this is the first program available that can deterministically phase null, mono-, di-, tri- and tetraploid genotypes in CNV loci. We applied our method to study the composition and inheritance of haplotypes in CNV regions of 30 HapMap Yoruban trios and 34 Estonian families. For 93.6% of the CNV loci, PiCNV enabled to unambiguously phase normal and CNV-carrying haplotypes and follow their transmission in the corresponding families. Furthermore, allelic composition analysis identified the co-occurrence of alternative allelic copies within 66.7% of haplotypes carrying copy number gains. We also observed less frequent transmission of CNV-carrying haplotypes from parents to children compared to normal haplotypes and identified an emergence of several de novo deletions and duplications in the offspring.

  19. Genetics of chloroquine-resistant malaria: a haplotypic view

    Directory of Open Access Journals (Sweden)

    Gauri Awasthi

    2013-12-01

    Full Text Available The development and rapid spread of chloroquine resistance (CQR in Plasmodium falciparum have triggered the identification of several genetic target(s in the P. falciparum genome. In particular, mutations in the Pfcrt gene, specifically, K76T and mutations in three other amino acids in the region adjoining K76 (residues 72, 74, 75 and 76, are considered to be highly related to CQR. These various mutations form several different haplotypes and Pfcrt gene polymorphisms and the global distribution of the different CQR- Pfcrt haplotypes in endemic and non-endemic regions of P. falciparum malaria have been the subject of extensive study. Despite the fact that the Pfcrt gene is considered to be the primary CQR gene in P. falciparum , several studies have suggested that this may not be the case. Furthermore, there is a poor correlation between the evolutionary implications of the Pfcrt haplotypes and the inferred migration of CQR P. falciparum based on CQR epidemiological surveillance data. The present paper aims to clarify the existing knowledge on the genetic basis of the different CQR- Pfcrt haplotypes that are prevalent in worldwide populations based on the published literature and to analyse the data to generate hypotheses on the genetics and evolution of CQR malaria.

  20. Factor IX gene haplotypes in Amerindians.

    Science.gov (United States)

    Franco, R F; Araújo, A G; Zago, M A; Guerreiro, J F; Figueiredo, M S

    1997-02-01

    We have determined the haplotypes of the factor IX gene for 95 Indians from 5 Brazilian Amazon tribes: Wayampí, Wayana-Apalaí, Kayapó, Arára, and Yanomámi. Eight polymorphisms linked to the factor IX gene were investigated: MseI (at 5', nt -698), BamHI (at 5', nt -561), DdeI (intron 1), BamHI (intron 2), XmnI (intron 3), TaqI (intron 4), MspI (intron 4), and HhaI (at 3', approximately 8 kb). The results of the haplotype distribution and the allele frequencies for each of the factor IX gene polymorphisms in Amerindians were similar to the results reported for Asian populations but differed from results for other ethnic groups. Only five haplotypes were identified within the entire Amerindian study population, and the haplotype distribution was significantly different among the five tribes, with one (Arára) to four (Wayampí) haplotypes being found per tribe. These findings indicate a significant heterogeneity among the Indian tribes and contrast with the homogeneous distribution of the beta-globin gene cluster haplotypes but agree with our recent findings on the distribution of alpha-globin gene cluster haplotypes and the allele frequencies for six VNTRs in the same Amerindian tribes. Our data represent the first study of factor IX-associated polymorphisms in Amerindian populations and emphasizes the applicability of these genetic markers for population and human evolution studies.

  1. Risk considerations related to lung modeling

    International Nuclear Information System (INIS)

    Masse, R.; Cross, F.T.

    1989-01-01

    Improved lung models provide a more accurate assessment of dose from inhalation exposures and, therefore, more accurate dose-response relationships for risk evaluation and exposure limitation. Epidemiological data for externally irradiated persons indicate that the numbers of excess respiratory tract carcinomas differ in the upper airways, bronchi, and distal lung. Neither their histogenesis and anatomical location nor their progenitor cells are known with sufficient accuracy for accurate assessment of the microdosimetry. The nuclei of sensitive cells generally can be assumed to be distributed at random in the epithelium, beneath the mucus and tips of the beating cilia and cells. In stratified epithelia, basal cells may be considered the only cells at risk. Upper-airway tumors have been observed in both therapeutically irradiated patients and in Hiroshima-Nagasaki survivors. The current International Commission on Radiological Protection Lung-Model Task Group proposes that the upper airways and lung have a similar relative risk coefficient for cancer induction. The partition of the risk weighting factor, therefore, will be proportional to the spontaneous death rate from tumors, and 80% of the weighting factor for the respiratory tract should be attributed to the lung. For Weibel lung-model branching generations 0 to 16 and 17 to 23, the Task Group proposes an 80/20 partition of the risk, i.e., 64% and 16%, respectively, of the total risk. Regarding risk in animals, recent data in rats indicate a significantly lower effectiveness for lung-cancer induction at low doses from insoluble long-lived alpha-emitters than from Rn daughters. These findings are due, in part, to the fact that different regions of the lung are irradiated. Tumors in the lymph nodes are rare in people and animals exposed to radiation.44 references

  2. Risk factors for age-related maculopathy.

    Science.gov (United States)

    Connell, Paul P; Keane, Pearse A; O'Neill, Evelyn C; Altaie, Rasha W; Loane, Edward; Neelam, Kumari; Nolan, John M; Beatty, Stephen

    2009-01-01

    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

  3. Risk Factors for Age-Related Maculopathy

    Directory of Open Access Journals (Sweden)

    Paul P. Connell

    2009-01-01

    Full Text Available Age-related maculopathy (ARM is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

  4. Risk factors for age-related maculopathy.

    LENUS (Irish Health Repository)

    Connell, Paul P

    2012-02-01

    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715\\/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

  5. Complement factor H polymorphisms in Japanese population with age-related macular degeneration.

    Science.gov (United States)

    Okamoto, Haru; Umeda, Shinsuke; Obazawa, Minoru; Minami, Masayoshi; Noda, Toru; Mizota, Atsushi; Honda, Miki; Tanaka, Minoru; Koyama, Risa; Takagi, Ikue; Sakamoto, Yoshihiro; Saito, Yoshihiro; Miyake, Yozo; Iwata, Takeshi

    2006-03-06

    To study the frequency of five haplotypes previously reported in the complement factor H (CFH) gene for Japanese patients with age-related macular degeneration (AMD). Genomic DNA was isolated from peripheral blood samples taken from 96 Japanese AMD patients and 89 age-matched controls. All patients were diagnosed as having exudative (wet-type) AMD. The amplified polymerase chain reaction (PCR) products of CFH exons 2, 9, and 13, and intron 6 were analyzed by temperature gradient capillary electrophoresis (TGCE) and by direct sequencing. The haplotypes were identified, and their frequencies were calculated and compared with reported results. Five haplotypes were identified in the Japanese population including four already reported in the American population. The frequencies of these haplotypes were significantly different between Japanese and American in both control and case groups. The haplotype containing Y402H, which was previously reported to be associated with AMD, was only 4% in the control and case population, with a p value of 0.802. However, two other haplotypes were found as risk factors, which gave an increased likelihood of AMD of 1.9 and 2.5 fold (95% CI 1.12-3.69 and 1.42-6.38). One protective haplotype that decreased the likelihood of AMD by 1.6 fold (95% CI 0.26-0.67) was identified. The frequencies for five haplotypes previously identified were analyzed in a Japanese population with AMD. Four previously found haplotypes were identified and one additional haplotype was found. The frequencies of each haplotype were significantly different from that in found Americans affected with AMD. Two of the haplotypes were identified as risk factors and one was considered protective.

  6. HLA-G regulatory haplotypes and implantation outcome in couples who underwent assisted reproduction treatment.

    Science.gov (United States)

    Costa, Cynthia Hernandes; Gelmini, Georgia Fernanda; Wowk, Pryscilla Fanini; Mattar, Sibelle Botogosque; Vargas, Rafael Gustavo; Roxo, Valéria Maria Munhoz Sperandio; Schuffner, Alessandro; Bicalho, Maria da Graça

    2012-09-01

    The role of HLA-G in several clinical conditions related to reproduction has been investigated. Important polymorphisms have been found within the 5'URR and 3'UTR regions of the HLA-G promoter. The aim of the present study was to investigate 16 SNPs in the 5'URR and 14-bp insertion/deletion (ins/del) polymorphism located in the 3'UTR region of the HLA-G gene and its possible association with the implantation outcome in couples who underwent assisted reproduction treatments (ART). The case group was composed of 25 ART couples. Ninety-four couples with two or more term pregnancies composed the control group. Polymorphism haplotype frequencies of the HLA-G were determined for both groups. The Haplotype 5, Haplotype 8 and Haplotype 11 were absolute absence in ART couples. The HLA-G*01:01:02a, HLA-G*01:01:02b alleles and the 14-bp ins polymorphism, Haplotype 2, showed an increased frequency in case women and similar distribution between case and control men. However, this susceptibility haplotype is significantly presented in case women and in couple with failure implantation after treatment, which led us to suggest a maternal effect, associated with this haplotype, once their presence in women is related to a higher number of couples who underwent ART. Copyright © 2012. Published by Elsevier Inc.

  7. Y-chromosome STR haplotypes in Somalis

    DEFF Research Database (Denmark)

    Hallenberg, Charlotte; Simonsen, Bo; Sanchez Sanchez, Juan Jose

    2005-01-01

    A total of 201 males from Somalia were typed for the Y-chromosome STRs DYS19, DYS385a/b, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439 with the PowerPlex Y kit (Promega). A total of 96 different haplotypes were observed and the haplotype diversity was 0.9715. The ......A total of 201 males from Somalia were typed for the Y-chromosome STRs DYS19, DYS385a/b, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439 with the PowerPlex Y kit (Promega). A total of 96 different haplotypes were observed and the haplotype diversity was 0...

  8. Effects of the number of markers per haplotype and clustering of haplotypes on the accuracy of QTL mapping and prediction of genomic breeding values

    Directory of Open Access Journals (Sweden)

    Schrooten Chris

    2009-01-01

    Full Text Available Abstract The aim of this paper was to compare the effect of haplotype definition on the precision of QTL-mapping and on the accuracy of predicted genomic breeding values. In a multiple QTL model using identity-by-descent (IBD probabilities between haplotypes, various haplotype definitions were tested i.e. including 2, 6, 12 or 20 marker alleles and clustering base haplotypes related with an IBD probability of > 0.55, 0.75 or 0.95. Simulated data contained 1100 animals with known genotypes and phenotypes and 1000 animals with known genotypes and unknown phenotypes. Genomes comprising 3 Morgan were simulated and contained 74 polymorphic QTL and 383 polymorphic SNP markers with an average r2 value of 0.14 between adjacent markers. The total number of haplotypes decreased up to 50% when the window size was increased from two to 20 markers and decreased by at least 50% when haplotypes related with an IBD probability of > 0.55 instead of > 0.95 were clustered. An intermediate window size led to more precise QTL mapping. Window size and clustering had a limited effect on the accuracy of predicted total breeding values, ranging from 0.79 to 0.81. Our conclusion is that different optimal window sizes should be used in QTL-mapping versus genome-wide breeding value prediction.

  9. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Spindler, Karen-Lise Garm; Andersen, Rikke Fredslund

    2010-01-01

    Abstract: New prognostic markers in patients with colorectal cancer (CRC) are a prerequisite for individualized treatment. Prognostic importance of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene has been proposed. The objective of the present study...... using the PHASE program. The prognostic influence was evaluated using Kaplan-Meir plots and log rank tests. Cox regression method was used to analyze the independent prognostic importance of different markers. All three SNPs were significantly related to survival. A haplotype combination, responsible...... findings in a second and independent cohort. Haplotype combinations call for further investigation. Keywords: colorectal neoplasm; single nucleotide polymorphisms; haplotypes; vascular endothelial growth factor A; survival...

  10. Mutation Analysis in Classical Phenylketonuria Patients Followed by Detecting Haplotypes Linked to Some PAH Mutations.

    Science.gov (United States)

    Dehghanian, Fatemeh; Silawi, Mohammad; Tabei, Seyed M B

    2017-02-01

    Deficiency of phenylalanine hydroxylase (PAH) enzyme and elevation of phenylalanine in body fluids cause phenylketonuria (PKU). The gold standard for confirming PKU and PAH deficiency is detecting causal mutations by direct sequencing of the coding exons and splicing involved sequences of the PAH gene. Furthermore, haplotype analysis could be considered as an auxiliary approach for detecting PKU causative mutations before direct sequencing of the PAH gene by making comparisons between prior detected mutation linked-haplotypes and new PKU case haplotypes with undetermined mutations. In this study, 13 unrelated classical PKU patients took part in the study detecting causative mutations. Mutations were identified by polymerase chain reaction (PCR) and direct sequencing in all patients. After that, haplotype analysis was performed by studying VNTR and PAHSTR markers (linked genetic markers of the PAH gene) through application of PCR and capillary electrophoresis (CE). Mutation analysis was performed successfully and the detected mutations were as follows: c.782G>A, c.754C>T, c.842C>G, c.113-115delTCT, c.688G>A, and c.696A>G. Additionally, PAHSTR/VNTR haplotypes were detected to discover haplotypes linked to each mutation. Mutation detection is the best approach for confirming PAH enzyme deficiency in PKU patients. Due to the relatively large size of the PAH gene and high cost of the direct sequencing in developing countries, haplotype analysis could be used before DNA sequencing and mutation detection for a faster and cheaper way via identifying probable mutated exons.

  11. Epistatic interaction between haplotypes of the ghrelin ligand and receptor genes influence susceptibility to myocardial infarction and coronary artery disease.

    Science.gov (United States)

    Baessler, Andrea; Fischer, Marcus; Mayer, Bjoern; Koehler, Martina; Wiedmann, Silke; Stark, Klaus; Doering, Angela; Erdmann, Jeanette; Riegger, Guenter; Schunkert, Heribert; Kwitek, Anne E; Hengstenberg, Christian

    2007-04-15

    Data from both experimental models and humans provide evidence that ghrelin and its receptor, the growth hormone secretagogue receptor (ghrelin receptor, GHSR), possess a variety of cardiovascular effects. Thus, we hypothesized that genetic variants within the ghrelin system (ligand ghrelin and its receptor GHSR) are associated with susceptibility to myocardial infarction (MI) and coronary artery disease (CAD). Seven single nucleotide polymorphisms (SNPs) covering the GHSR region as well as eight SNPs across the ghrelin gene (GHRL) region were genotyped in index MI patients (864 Caucasians, 'index MI cases') from the German MI family study and in matched controls without evidence of CAD (864 Caucasians, 'controls', MONICA Augsburg). In addition, siblings of these MI patients with documented severe CAD (826 'affected sibs') were matched likewise with controls (n = 826 Caucasian 'controls') and used for verification. The effect of interactions between genetic variants of both genes of the ghrelin system was explored by conditional classification tree models. We found association of several GHSR SNPs with MI [best SNP odds ratio (OR) 1.7 (1.2-2.5); P = 0.002] using a recessive model. Moreover, we identified a common GHSR haplotype which significantly increases the risk for MI [multivariate adjusted OR for homozygous carriers 1.6 (1.1-2.5) and CAD OR 1.6 (1.1-2.5)]. In contrast, no relationship between genetic variants and the disease could be revealed for GHRL. However, the increase in MI/CAD frequency related to the susceptible GHSR haplotype was abolished when it coincided with a common GHRL haplotype. Multivariate adjustments as well as permutation-based methods conveyed the same results. These data are the first to demonstrate an association of SNPs and haplotypes within important genes of the ghrelin system and the susceptibility to MI, whereas association with MI/CAD could be identified for genetic variants across GHSR, no relationship could be revealed for GHRL

  12. The MLH1 c.-27C>A and c.85G>T variants are linked to dominantly inherited MLH1 epimutation and are borne on a European ancestral haplotype.

    Science.gov (United States)

    Kwok, Chau-To; Vogelaar, Ingrid P; van Zelst-Stams, Wendy A; Mensenkamp, Arjen R; Ligtenberg, Marjolijn J; Rapkins, Robert W; Ward, Robyn L; Chun, Nicolette; Ford, James M; Ladabaum, Uri; McKinnon, Wendy C; Greenblatt, Marc S; Hitchins, Megan P

    2014-05-01

    Germline mutations of the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2, and deletions affecting the EPCAM gene adjacent to MSH2, underlie Lynch syndrome by predisposing to early-onset colorectal, endometrial and other cancers. An alternative but rare cause of Lynch syndrome is constitutional epimutation of MLH1, whereby promoter methylation and transcriptional silencing of one allele occurs throughout normal tissues. A dominantly transmitted constitutional MLH1 epimutation has been linked to an MLH1 haplotype bearing two single-nucleotide variants, NM_000249.2: c.-27C>A and c.85G>T, in a Caucasian family with Lynch syndrome from Western Australia. Subsequently, a second seemingly unrelated Caucasian Australian case with the same MLH1 haplotype and concomitant epimutation was reported. We now describe three additional, ostensibly unrelated, cancer-affected families of European heritage with this MLH1 haplotype in association with constitutional epimutation, bringing the number of index cases reported to five. Array-based genotyping in four of these families revealed shared haplotypes between individual families that extended across ≤2.6-≤6.4 megabase regions of chromosome 3p, indicating common ancestry. A minimal ≤2.6 megabase founder haplotype common to all four families was identified, which encompassed MLH1 and additional flanking genes and segregated with the MLH1 epimutation in each family. Our findings indicate that the MLH1 c.-27C>A and c.85G>T variants are borne on a European ancestral haplotype and provide conclusive evidence for its pathogenicity via a mechanism of epigenetic silencing of MLH1 within normal tissues. Additional descendants bearing this founder haplotype may exist who are also at high risk of developing Lynch syndrome-related cancers.

  13. Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

    KAUST Repository

    Tawe, Leabaneng

    2018-03-14

    Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed different haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic profile. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a different haplotype structure due to the different genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence.

  14. Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

    KAUST Repository

    Tawe, Leabaneng; Motshoge, Thato; Ramatlho, Pleasure; Mutukwa, Naledi; Muthoga, Charles Waithaka; Dongho, Ghyslaine Bruna Djeunang; Martinelli, Axel; Peloewetse, Elias; Russo, Gianluca; Quaye, Isaac Kweku; Paganotti, Giacomo Maria

    2018-01-01

    Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed different haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic profile. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a different haplotype structure due to the different genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence.

  15. Effects of Single Nucleotide Polymorphism Marker Density on Haplotype Block Partition

    Directory of Open Access Journals (Sweden)

    Sun Ah Kim

    2016-12-01

    Full Text Available Many researchers have found that one of the most important characteristics of the structure of linkage disequilibrium is that the human genome can be divided into non-overlapping block partitions in which only a small number of haplotypes are observed. The location and distribution of haplotype blocks can be seen as a population property influenced by population genetic events such as selection, mutation, recombination and population structure. In this study, we investigate the effects of the density of markers relative to the full set of all polymorphisms in the region on the results of haplotype partitioning for five popular haplotype block partition methods: three methods in Haploview (confidence interval, four gamete test, and solid spine, MIG++ implemented in PLINK 1.9 and S-MIG++. We used several experimental datasets obtained by sampling subsets of single nucleotide polymorphism (SNP markers of chromosome 22 region in the 1000 Genomes Project data and also the HapMap phase 3 data to compare the results of haplotype block partitions by five methods. With decreasing sampling ratio down to 20% of the original SNP markers, the total number of haplotype blocks decreases and the length of haplotype blocks increases for all algorithms. When we examined the marker-independence of the haplotype block locations constructed from the datasets of different density, the results using below 50% of the entire SNP markers were very different from the results using the entire SNP markers. We conclude that the haplotype block construction results should be used and interpreted carefully depending on the selection of markers and the purpose of the study.

  16. People at High Risk of Developing Flu-Related Complications

    Science.gov (United States)

    ... Influenza Types Seasonal Avian Swine Variant Pandemic Other People at High Risk of Developing Flu–Related Complications ... related complications if they get sick with influenza. People at High Risk for Developing Flu-Related Complications ...

  17. Peripheral intravenous catheter-related phlebitis and related risk factors.

    Science.gov (United States)

    Nassaji-Zavareh, M; Ghorbani, R

    2007-08-01

    Peripheral intravenous catheter-related phlebitis is a common and significant problem in clinical practice. This study aims to investigate the incidence of phlebitis and to evaluate some important related factors. 300 patients admitted to medical and surgical wards of hospitals in Semnan, Iran from April 2003 to February 2004 were prospectively studied. Variables evaluated were age, gender, site and size of catheter, type of insertion and underlying conditions (diabetes mellitus, trauma, infectious disease and burns). Phlebitis was defined when at least four criteria were fulfilled (erythema, pain, tenderness, warmth, induration, palpable cord and swelling). Any patient who was discharged or their catheter removed before three days were excluded. Phlebitis occurred in 26 percent (95 percent confidence interval [CI] 21- 31 percent) of patients. There was no significant relationship between age, catheter bore size, trauma and phlebitis. Related risk factors were gender (odds-ratio [OR] 1.50, 95 percent CI 1.01-2.22), site (OR 3.25, 95 percent CI 2.26-4.67) and type of insertion (OR 2.04, 95 percent CI 1.36-3.05) of catheter, diabetes mellitus (OR 7.78, 95 percent CI 4.59-13.21), infectious disease (OR 6.21, 95 percent CI 4.27-9.03) and burns (OR 3.96, 95 percent CI 3.26-4.82). Phlebitis is still an important and ongoing problem in medical practice. In patients with diabetes mellitus and infectious diseases, more attention is needed.

  18. Haplotype-based stratification of Huntington's disease.

    Science.gov (United States)

    Chao, Michael J; Gillis, Tammy; Atwal, Ranjit S; Mysore, Jayalakshmi Srinidhi; Arjomand, Jamshid; Harold, Denise; Holmans, Peter; Jones, Lesley; Orth, Michael; Myers, Richard H; Kwak, Seung; Wheeler, Vanessa C; MacDonald, Marcy E; Gusella, James F; Lee, Jong-Min

    2017-11-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat in HTT, resulting in an extended polyglutamine tract in huntingtin. We and others have previously determined that the HD-causing expansion occurs on multiple different haplotype backbones, reflecting more than one ancestral origin of the same type of mutation. In view of the therapeutic potential of mutant allele-specific gene silencing, we have compared and integrated two major systems of HTT haplotype definition, combining data from 74 sequence variants to identify the most frequent disease-associated and control chromosome backbones and revealing that there is potential for additional resolution of HD haplotypes. We have used the large collection of 4078 heterozygous HD subjects analyzed in our recent genome-wide association study of HD age at onset to estimate the frequency of these haplotypes in European subjects, finding that common genetic variation at HTT can distinguish the normal and CAG-expanded chromosomes for more than 95% of European HD individuals. As a resource for the HD research community, we have also determined the haplotypes present in a series of publicly available HD subject-derived fibroblasts, induced pluripotent cells, and embryonic stem cells in order to facilitate efforts to develop inclusive methods of allele-specific HTT silencing applicable to most HD patients. Our data providing genetic guidance for therapeutic gene-based targeting will significantly contribute to the developments of rational treatments and implementation of precision medicine in HD.

  19. Estimating haplotype effects for survival data.

    Science.gov (United States)

    Scheike, Thomas H; Martinussen, Torben; Silver, Jeremy D

    2010-09-01

    Genetic association studies often investigate the effect of haplotypes on an outcome of interest. Haplotypes are not observed directly, and this complicates the inclusion of such effects in survival models. We describe a new estimating equations approach for Cox's regression model to assess haplotype effects for survival data. These estimating equations are simple to implement and avoid the use of the EM algorithm, which may be slow in the context of the semiparametric Cox model with incomplete covariate information. These estimating equations also lead to easily computable, direct estimators of standard errors, and thus overcome some of the difficulty in obtaining variance estimators based on the EM algorithm in this setting. We also develop an easily implemented goodness-of-fit procedure for Cox's regression model including haplotype effects. Finally, we apply the procedures presented in this article to investigate possible haplotype effects of the PAF-receptor on cardiovascular events in patients with coronary artery disease, and compare our results to those based on the EM algorithm. © 2009, The International Biometric Society.

  20. Strong association between a splice mutation (IVS12+5G{r_arrow}A) and haplotype 6 in hereditary tyrosinemia type I

    Energy Technology Data Exchange (ETDEWEB)

    Tanguay, R.M.; St-Louis, M.; Gibson, K. [Universite Laval, Ste-Foy (Canada)] [and others

    1994-09-01

    Hereditary tyrosinemia type I (HT I; McKusick 276700) is a severe inborn error of tyrosine catabolism pathway caused by a deficiency of fumarylacetoacetate hydrolase (FAH). The highest frequency reported is the one in Saguenay-Lac St-Jean (Quebec, Canada) where 1:1,846 births are affected. The FAH gene has been cloned and several mutations have been described. Allele specific oligonucleotide (ASO) hybridization was used to examine the frequency of a splice (IVS12-5G{r_arrow}A) mutation recently reported and RFLP analysis was done to identify haplotypes related to HT I. The splice mutation was found on 45/50 alleles (90%) in patients from SLSJ and 12/66 (18%) alleles from patients world-wide. All 25 patients from the SLSJ region were positive with 20 being homozygous, indicating that this mutation is the major cause of HT I in French Canada. Of these 25 patients, 96% were positive for one haplotype called no 6 which is these 25 patients, 96% were positive for one haplotype called no 6 which is identified by TaqI, RsaI, BglII, MspI and KpnI digestions. These data show a really strong association between the mutation (IVS12+5G{r_arrow}A) and haplotype 6. Among our patients from around the world, {approximately}52% were positive for haplotype 6 indicating its strong relation with HT I. These results provide the rationale for DNA-based carrier testing for HT I in the F-C population at risk as well as in HT I patients in general.

  1. Climate Change and Food-Related Risks

    Directory of Open Access Journals (Sweden)

    Isidro Juan Mirón Pérez

    2017-06-01

    Full Text Available There are two principal concepts to take into account relating food and climate change: food security and food safety. Most papers linking climate change to food risks deal with the first one: the security of the food supply.The increase of the concentration of carbon dioxide in the atmosphere, together with the rise of the temperatures on a global level would theorically lead to greater yields of crops grown for human and animal consumption. Howevwe, most of these studies have shown that, in general, crop yields are decreasing as this global change also brings about an increase in the frequency of extreme weather events. In adition, these weather anomalies would be unevenly spread and affect developing countries, which are less capable of tackling this change, more severely. All these factors would result in greater uncertainty in the supply of food, which consequently would be less predictable and leave it more exposed to market speculation.A rise in average temperatures would be expected to increase the risk of proliferation of foodborne disease-causing microorganisms such as Salmonella or Campylobacter. Nevertheless, a trend of this sort has not been detected yet in developed countries, where information systems allow the temporal evolution of the occurrence of those diseases to be tracked, since means for food preservation and food controls are wide spread.

  2. Regional scale ecological risk assessment: using the relative risk model

    National Research Council Canada - National Science Library

    Landis, Wayne G

    2005-01-01

    ...) in the performance of regional-scale ecological risk assessments. The initial chapters present the methodology and the critical nature of the interaction between risk assessors and decision makers...

  3. Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted).

    Science.gov (United States)

    Ark, B; Gummere, G; Bennett, D; Artzt, K

    1991-06-01

    Pim-1 is an oncogene activated in mouse T-cell lymphomas induced by Moloney and AKR mink cell focus (MCF) viruses. Pim-1 was previously mapped to chromosome 17 by somatic cell hybrids, and subsequently to the region between the hemoglobin alpha-chain pseudogene 4 (Hba-4ps) and the alpha-crystalline gene (Crya-1) by Southern blot analysis of DNA obtained from panels of recombinant inbred strains. We have now mapped Pim-1 more accurately in t-haplotypes by analysis of recombinant t-chromosomes. The recombinants were derived from Tts6tf/t12 parents backcrossed to + tf/ + tf, and scored for recombination between the loci of T and tf. For simplicity all t-complex lethal genes properly named tcl-tx are shortened to tx. The Pim-1 gene was localized 0.6 cM proximal to the tw12 lethal gene, thus placing the Pim-1 gene 5.2 cM distal to the H-2 region in t-haplotypes. Once mapped, the Pim-1 gene was used as a marker for further genetic analysis of t-haplotypes. tw12 is so close to tf that even with a large number of recombinants it was not possible to determine whether it is proximal or distal to tf. Southern blot analysis of DNA from T-tf recombinants with a separation of tw12 and tf indicated that tw12 is proximal to tf. The mapping of two allelic t-lethals, t0 and t6 with respect to tw12 and tf has also been a problem.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. MCP1 haplotypes associated with protection from pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Owusu-Dabo Ellis

    2011-04-01

    Full Text Available Abstract Background The monocyte chemoattractant protein 1 (MCP-1 is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB case-control study group, associations of the MCP1 -362C and the MCP1 -2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the MCP1 gene in order to determine causal variants or haplotypes genetically and functionally. Results A 14 base-pair deletion in the first MCP1 intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, Pcorrected = 0.00098. Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, Pnominal = 0.00002; adjusted Pglobal = 0.0028. In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the MCP1 mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006. The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB. Conclusions In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the MCP1 -362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91. Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the

  5. Relative Hazard and Risk Measure Calculation Methodology

    International Nuclear Information System (INIS)

    Stenner, Robert D.; Strenge, Dennis L.; Elder, Matthew S.; Andrews, William B.; Walton, Terry L.

    2003-01-01

    The RHRM equations, as represented in methodology and code presented in this report, are primarily a collection of key factors normally used in risk assessment that are relevant to understanding the hazards and risks associated with projected mitigation, cleanup, and risk management activities. The RHRM code has broad application potential. For example, it can be used to compare one mitigation, cleanup, or risk management activity with another, instead of just comparing it to just the fixed baseline. If the appropriate source term data are available, it can be used in its non-ratio form to estimate absolute values of the associated controlling hazards and risks. These estimated values of controlling hazards and risks can then be examined to help understand which mitigation, cleanup, or risk management activities are addressing the higher hazard conditions and risk reduction potential at a site. Graphics can be generated from these absolute controlling hazard and risk values to graphically compare these high hazard and risk reduction potential conditions. If the RHRM code is used in this manner, care must be taken to specifically define and qualify (e.g., identify which factors were considered and which ones tended to drive the hazard and risk estimates) the resultant absolute controlling hazard and risk values

  6. Affect and Acceptability: Exploring Teachers' Technology-Related Risk Perceptions

    Science.gov (United States)

    Howard, Sarah K.

    2011-01-01

    Educational change, such as technology integration, involves risk. Teachers are encouraged to "take risks", but what risks they are asked to take and how do they perceive these risks? Developing an understanding of teachers' technology-related risk perceptions can help explain their choices and behaviours. This paper presents a way to…

  7. Pregnancy-related venous thromboembolism and risk of occult cancer

    DEFF Research Database (Denmark)

    Hansen, Anette Tarp; Veres, Katalin; Horváth-Puhó, Erzsébet

    2017-01-01

    The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected. An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk.......The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected. An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk....

  8. Cis-acting mutation and duplication: History of molecular evolution in a P450 haplotype responsible for insecticide resistance in Culex quinquefasciatus.

    Science.gov (United States)

    Itokawa, Kentaro; Komagata, Osamu; Kasai, Shinji; Masada, Masahiro; Tomita, Takashi

    2011-07-01

    A cytochrome P450 gene, Cyp9m10, is more than 200-fold overexpressed in a pyrethroid resistant strain of Culex quinquefasciatus, JPal-per. The haplotype of this strain contains two copies of Cyp9m10 resulted from recent tandem duplication. In this study, we discovered and isolated a Cyp9m10 haplotype closely related to this duplicated Cyp9m10 haplotype from JHB, a strain used for the recent genome project for this mosquito species. The isolated haplotype (JHB-NIID-B haplotype) shared the same insertion of a transposable element upstream of the coding region with JPal-per strain but not duplicated. The JHB-NIID-B haplotype was considered to have diverged from the JPal-per lineage just before the duplication event. Cyp9m10 was moderately overexpressed in larvae with the JHB-NIID-B haplotype. The overexpressions in JHB-NIID-B and JPal-per haplotypes were developmentally regulated in similar pattern indicating both haplotypes share a common cis-acting mutation responsible for the overexpressions. The isolated moderately overexpressed haplotype conferred resistance, however, its efficacy was relatively small. We hypothesized that the first cis-acting mutation modified the consequence of the subsequent duplication in JPal-per lineage to confer stronger phenotypic effect than that if it occurred before the first cis-acting mutation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Managing IT-related operational risks

    Directory of Open Access Journals (Sweden)

    Savić Ana

    2008-01-01

    Full Text Available Not so long ago, information technology (IT risk occupied a small corner of operational risk - the opportunity loss from a missed IT development deadline. Today, the success of an entire financial institution may lay on managing a broad landscape of IT risks. IT risk is a potential damage to an organization's value, resulting from inadequate managing of processes and technologies. IT risk includes the failure to respond to security and privacy requirements, as well as many other issues such as: human error, internal fraud through software manipulation, external fraud by intruders, obsolesce in applications and machines, reliability issues or mismanagement. The World Economic Forum provides best information about this problem. They rank a breakdown of critical information infrastructure among the most likely core global risks, with 10-20 % likelihood over the next 10 years and potential worldwide impact of $250 billion. Sustained investment in IT - almost $1.2 trillion or 29% of 2006 private-sector capital investment in the U.S. alone fuels growing exposure to IT risk. Greg Hughes, chief strategy officer in Symantec Corp. recently claimed "IT risk management is more than using technology to solve security problems. With proper planning and broad support, it can give an organization the confidence to innovate, using IT to outdistance competitors".

  10. The effect of genealogy-based haplotypes on genomic prediction

    DEFF Research Database (Denmark)

    Edriss, Vahid; Fernando, Rohan L.; Su, Guosheng

    2013-01-01

    on haplotypes instead of regression on individual markers. The aim of this study was to investigate the accuracy of genomic prediction using haplotypes based on local genealogy information. Methods A total of 4429 Danish Holstein bulls were genotyped with the 50K SNP chip. Haplotypes were constructed using...... local genealogical trees. Effects of haplotype covariates were estimated with two types of prediction models: (1) assuming that effects had the same distribution for all haplotype covariates, i.e. the GBLUP method and (2) assuming that a large proportion (pi) of the haplotype covariates had zero effect......, i.e. a Bayesian mixture method. Results About 7.5 times more covariate effects were estimated when fitting haplotypes based on local genealogical trees compared to fitting individuals markers. Genealogy-based haplotype clustering slightly increased the accuracy of genomic prediction and, in some...

  11. Determination of haplotypes at structurally complex regions using emulsion haplotype fusion PCR.

    Science.gov (United States)

    Tyson, Jess; Armour, John A L

    2012-12-11

    Genotyping and massively-parallel sequencing projects result in a vast amount of diploid data that is only rarely resolved into its constituent haplotypes. It is nevertheless this phased information that is transmitted from one generation to the next and is most directly associated with biological function and the genetic causes of biological effects. Despite progress made in genome-wide sequencing and phasing algorithms and methods, problems assembling (and reconstructing linear haplotypes in) regions of repetitive DNA and structural variation remain. These dynamic and structurally complex regions are often poorly understood from a sequence point of view. Regions such as these that are highly similar in their sequence tend to be collapsed onto the genome assembly. This is turn means downstream determination of the true sequence haplotype in these regions poses a particular challenge. For structurally complex regions, a more focussed approach to assembling haplotypes may be required. In order to investigate reconstruction of spatial information at structurally complex regions, we have used an emulsion haplotype fusion PCR approach to reproducibly link sequences of up to 1kb in length to allow phasing of multiple variants from neighbouring loci, using allele-specific PCR and sequencing to detect the phase. By using emulsion systems linking flanking regions to amplicons within the CNV, this led to the reconstruction of a 59kb haplotype across the DEFA1A3 CNV in HapMap individuals. This study has demonstrated a novel use for emulsion haplotype fusion PCR in addressing the issue of reconstructing structural haplotypes at multiallelic copy variable regions, using the DEFA1A3 locus as an example.

  12. Determination of haplotypes at structurally complex regions using emulsion haplotype fusion PCR

    Directory of Open Access Journals (Sweden)

    Tyson Jess

    2012-12-01

    Full Text Available Abstract Background Genotyping and massively-parallel sequencing projects result in a vast amount of diploid data that is only rarely resolved into its constituent haplotypes. It is nevertheless this phased information that is transmitted from one generation to the next and is most directly associated with biological function and the genetic causes of biological effects. Despite progress made in genome-wide sequencing and phasing algorithms and methods, problems assembling (and reconstructing linear haplotypes in regions of repetitive DNA and structural variation remain. These dynamic and structurally complex regions are often poorly understood from a sequence point of view. Regions such as these that are highly similar in their sequence tend to be collapsed onto the genome assembly. This is turn means downstream determination of the true sequence haplotype in these regions poses a particular challenge. For structurally complex regions, a more focussed approach to assembling haplotypes may be required. Results In order to investigate reconstruction of spatial information at structurally complex regions, we have used an emulsion haplotype fusion PCR approach to reproducibly link sequences of up to 1kb in length to allow phasing of multiple variants from neighbouring loci, using allele-specific PCR and sequencing to detect the phase. By using emulsion systems linking flanking regions to amplicons within the CNV, this led to the reconstruction of a 59kb haplotype across the DEFA1A3 CNV in HapMap individuals. Conclusion This study has demonstrated a novel use for emulsion haplotype fusion PCR in addressing the issue of reconstructing structural haplotypes at multiallelic copy variable regions, using the DEFA1A3 locus as an example.

  13. Association between firearm ownership, firearm-related risk and risk reduction behaviours and alcohol-related risk behaviours.

    Science.gov (United States)

    Wintemute, Garen J

    2011-12-01

    Alcohol use and firearm ownership are risk factors for violent injury and death. To determine whether firearm ownership and specific firearm-related behaviours are associated with alcohol-related risk behaviours, the author conducted a cross-sectional study using Behavioral Risk Factor Surveillance System data for eight states in the USA from 1996 to 1997 (the most recent data available). Altogether, 15 474 respondents provided information on firearm exposure. After adjustment for demographics and state of residence, firearm owners were more likely than those with no firearms at home to have ≥5 drinks on one occasion (OR 1.32; 95% CI 1.16 to 1.50), to drink and drive (OR 1.79; 95% CI 1.34 to 2.39) and to have ≥60 drinks per month (OR 1.45; 95% CI 1.14 to 1.83). Heavy alcohol use was most common among firearm owners who also engaged in behaviours such as carrying a firearm for protection against other people and keeping a firearm at home that was both loaded and not locked away. The author concludes that firearm ownership and specific firearm-related behaviours are associated with alcohol-related risk behaviours.

  14. Haplotype-based approach for noninvasive prenatal tests of Duchenne muscular dystrophy using cell-free fetal DNA in maternal plasma

    DEFF Research Database (Denmark)

    Xu, Yan; Li, Xuchao; Ge, Hui-Juan

    2015-01-01

    Purpose:This study demonstrates noninvasive prenatal testing (NIPT) for Duchenne muscular dystrophy (DMD) using a newly developed haplotype-based approach.Methods:Eight families at risk for DMD were recruited for this study. Parental haplotypes were constructed using target-region sequencing data...

  15. An ancestral haplotype of the human PERIOD2 gene associates with reduced sensitivity to light-induced melatonin suppression.

    Directory of Open Access Journals (Sweden)

    Tokiho Akiyama

    Full Text Available Humans show various responses to the environmental stimulus in individual levels as "physiological variations." However, it has been unclear if these are caused by genetic variations. In this study, we examined the association between the physiological variation of response to light-stimulus and genetic polymorphisms. We collected physiological data from 43 subjects, including light-induced melatonin suppression, and performed haplotype analyses on the clock genes, PER2 and PER3, exhibiting geographical differentiation of allele frequencies. Among the haplotypes of PER3, no significant difference in light sensitivity was found. However, three common haplotypes of PER2 accounted for more than 96% of the chromosomes in subjects, and 1 of those 3 had a significantly low-sensitive response to light-stimulus (P < 0.05. The homozygote of the low-sensitive PER2 haplotype showed significantly lower percentages of melatonin suppression (P < 0.05, and the heterozygotes of the haplotypes varied their ratios, indicating that the physiological variation for light-sensitivity is evidently related to the PER2 polymorphism. Compared with global haplotype frequencies, the haplotype with a low-sensitive response was more frequent in Africans than in non-Africans, and came to the root in the phylogenetic tree, suggesting that the low light-sensitive haplotype is the ancestral type, whereas the other haplotypes with high sensitivity to light are the derived types. Hence, we speculate that the high light-sensitive haplotypes have spread throughout the world after the Out-of-Africa migration of modern humans.

  16. A risk-based microbiological criterion that uses the relative risk as the critical limit

    DEFF Research Database (Denmark)

    Andersen, Jens Kirk; Nørrung, Birgit; da Costa Alves Machado, Simone

    2015-01-01

    A risk-based microbiological criterion is described, that is based on the relative risk associated to the analytical result of a number of samples taken from a food lot. The acceptable limit is a specific level of risk and not a specific number of microorganisms, as in other microbiological...... criteria. The approach requires the availability of a quantitative microbiological risk assessment model to get risk estimates for food products from sampled food lots. By relating these food lot risk estimates to the mean risk estimate associated to a representative baseline data set, a relative risk...... estimate can be obtained. This relative risk estimate then can be compared with a critical value, defined by the criterion. This microbiological criterion based on a relative risk limit is particularly useful when quantitative enumeration data are available and when the prevalence of the microorganism...

  17. Relative and absolute risk in epidemiology and health physics

    International Nuclear Information System (INIS)

    Goldsmith, R.; Peterson, H.T. Jr.

    1983-01-01

    The health risk from ionizing radiation commonly is expressed in two forms: (1) the relative risk, which is the percentage increase in natural disease rate and (2) the absolute or attributable risk which represents the difference between the natural rate and the rate associated with the agent in question. Relative risk estimates for ionizing radiation generally are higher than those expressed as the absolute risk. This raises the question of which risk estimator is the most appropriate under different conditions. The absolute risk has generally been used for radiation risk assessment, although mathematical combinations such as the arithmetic or geometric mean of both the absolute and relative risks, have also been used. Combinations of the two risk estimators are not valid because the absolute and relative risk are not independent variables. Both human epidemiologic studies and animal experimental data can be found to illustrate the functional relationship between the natural cancer risk and the risk associated with radiation. This implies that the radiation risk estimate derived from one population may not be appropriate for predictions in another population, unless it is adjusted for the difference in the natural disease incidence between the two populations

  18. Relationship between polymorphisms in vitamin D metabolism-related genes and the risk of rickets in Han Chinese children.

    Science.gov (United States)

    Zhang, Yuling; Yang, Shufen; Liu, Ye; Ren, Lihong

    2013-09-30

    Vitamin D deficiency rickets is common in China. Genetic factors may play an important role in the susceptibility to rickets. Our study aimed to identify the relationship between three vitamin D-related genes (group specific component [GC], cytochrome P450, family 2, subfamily R, polypeptide 1 (CYP2R1), and 7-dehydrocholesterol reductase/nicotinamide-adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) and rickets in Han Chinese children from northeastern China. A total of 506 Han children from northeastern China were enrolled in the current study. Twelve SNPs in three candidate genes were genotyped using the SNaPshot assay. Linear regression was used to examine the effect of 12 single-nucleotide polymorphisms (SNPs) on the risk of rickets. In our case-control cohort, six alleles of the 12 SNPs conferred a significantly increased risk of rickets in GC (rs4588 C, P = 0.003, OR: 0.583, 95% CI: 0.412-0.836; rs222020 C, P = 0.009, OR: 1.526, 95% CI: 1.117-2.0985; rs2282679 A, P = 0.010, OR: 0.636, 95% CI: 0.449-0.900; and rs2298849 C, P = 0.001, OR: 1.709, 95% CI: 1.250-2.338) and in CYP2R1 (rs10741657 G, P = 0.019, OR: 1.467, 95% CI: 1.070-2.011; and rs2060793 G, P = 0.023, OR: 0.689, 95% CI: 0.502-0.944). The results remained significant after adjustment for sex and body mass index. We further analyzed the effect of genotypes under three different genetic models. After using Bonferroni's method for multiple corrections, rs4588, rs2282679, and rs2298849 of the GC gene were significantly associated with rickets under the dominant (P =0.003 for rs4588, P =0.024 for rs2282679, and P =0.005 for rs2298849) and additive models (P = 0.006 for rs4588, P = 0.024 for rs2282679, and P = 0.005 for rs2298849). Haplotype analysis showed that the CAT haplotype of the GC gene (P = 0.005) and the GAA haplotype of the CYP2R1 gene (P = 0.026) were associated with susceptibility to rickets. This case-control study confirmed the strong effect of GC

  19. Identification of the Mislabeled Breast Cancer Samples by Mitochondrial DNA Haplotyping

    Directory of Open Access Journals (Sweden)

    Xiaogang Chen

    2015-01-01

    Full Text Available The task to identify whether an archival malignant tumor specimen had been mislabeled or interchanged is a challenging one for forensic genetics. The nuclear DNA (nDNA markers were affected by the aberration of tumor cells, so they were not suitable for personal identification when the tumor tissues were tested. In this study, we focused on a new solution - mitochondrial single nucleotide polymorphism (mtSNP haplotyping by a multiplex SNaPshot assay. To validate our strategy of haplotyping with 25 mtSNPs, we analyzed 15 pairs of cancerous/healthy tissues taken from patients with ductal breast carcinoma. The haplotypes of all the fifteen breast cancer tissues were matched with their paired breast tissues. The heteroplasmy at 2 sites, 14783A/G and 16519C/T was observed in one breast tissue, which indicated a mixture of related mitochondrial haplotypes. However, only one haplotype was retained in the paired breast cancer tissue, which could be considered the result of proliferation of tumor subclone. The allele drop-out and allele drop-in were observed when 39 STRs and 20 tri-allelic SNPs of nDNA were applied. Compared to nDNA markers applied, 25 mtSNPs were more stable without interference from aberrance of breast cancer. Also, two cases were presented where the investigation of haplotype with 25 mtSNPs was used to prove the origin of biopsy specimen with breast cancer. The mislabeling of biopsy specimen with breast cancer could be certified in one case but could not be supported in the other case. We highlight the importance of stability of mtSNP haplotype in breast cancer. It was implied that our multiplex SNaPshot assay with 25 mtSNPs was a useful strategy to identify mislabeled breast cancer specimen.

  20. Relative Hazard and Risk Measure Calculation Methodology Rev 1

    International Nuclear Information System (INIS)

    Stenner, Robert D.; White, Michael K.; Strenge, Dennis L.; Aaberg, Rosanne L.; Andrews, William B.

    2000-01-01

    Documentation of the methodology used to calculate relative hazard and risk measure results for the DOE complex wide risk profiles. This methodology is used on major site risk profiles. In February 1997, the Center for Risk Excellence (CRE) was created and charged as a technical, field-based partner to the Office of Science and Risk Policy (EM-52). One of the initial charges to the CRE is to assist the sites in the development of ''site risk profiles.'' These profiles are to be relatively short summaries (periodically updated) that present a broad perspective on the major risk related challenges that face the respective site. The risk profiles are intended to serve as a high-level communication tool for interested internal and external parties to enhance the understanding of these risk-related challenges. The risk profiles for each site have been designed to qualitatively present the following information: (1) a brief overview of the site, (2) a brief discussion on the historical mission of the site, (3) a quote from the site manager indicating the site's commitment to risk management, (4) a listing of the site's top risk-related challenges, (5) a brief discussion and detailed table presenting the site's current risk picture, (6) a brief discussion and detailed table presenting the site's future risk reduction picture, and (7) graphic illustrations of the projected management of the relative hazards at the site. The graphic illustrations were included to provide the reader of the risk profiles with a high-level mental picture to associate with all the qualitative information presented in the risk profile. Inclusion of these graphic illustrations presented the CRE with the challenge of how to fold this high-level qualitative risk information into a system to produce a numeric result that would depict the relative change in hazard, associated with each major risk management action, so it could be presented graphically. This report presents the methodology developed

  1. Mitochondrial control region haplotypes of the South American sea lion Otaria flavescens (Shaw, 1800).

    Science.gov (United States)

    Artico, L O; Bianchini, A; Grubel, K S; Monteiro, D S; Estima, S C; Oliveira, L R de; Bonatto, S L; Marins, L F

    2010-09-01

    The South American sea lion, Otaria flavescens, is widely distributed along the Pacific and Atlantic coasts of South America. However, along the Brazilian coast, there are only two nonbreeding sites for the species (Refúgio de Vida Silvestre da Ilha dos Lobos and Refúgio de Vida Silvestre do Molhe Leste da Barra do Rio Grande), both in Southern Brazil. In this region, the species is continuously under the effect of anthropic activities, mainly those related to environmental contamination with organic and inorganic chemicals and fishery interactions. This paper reports, for the first time, the genetic diversity of O. flavescens found along the Southern Brazilian coast. A 287-bp fragment of the mitochondrial DNA control region (D-loop) was analyzed. Seven novel haplotypes were found in 56 individuals (OFA1-OFA7), with OFA1 being the most frequent (47.54%). Nucleotide diversity was moderate (π = 0.62%) and haplotype diversity was relatively low (67%). Furthermore, the median joining network analysis indicated that Brazilian haplotypes formed a reciprocal monophyletic clade when compared to the haplotypes from the Peruvian population on the Pacific coast. These two populations do not share haplotypes and may have become isolated some time back. Further genetic studies covering the entire species distribution are necessary to better understand the biological implications of the results reported here for the management and conservation of South American sea lions.

  2. Mitochondrial control region haplotypes of the South American sea lion Otaria flavescens (Shaw, 1800

    Directory of Open Access Journals (Sweden)

    L.O. Artico

    2010-09-01

    Full Text Available The South American sea lion, Otaria flavescens, is widely distributed along the Pacific and Atlantic coasts of South America. However, along the Brazilian coast, there are only two nonbreeding sites for the species (Refúgio de Vida Silvestre da Ilha dos Lobos and Refúgio de Vida Silvestre do Molhe Leste da Barra do Rio Grande, both in Southern Brazil. In this region, the species is continuously under the effect of anthropic activities, mainly those related to environmental contamination with organic and inorganic chemicals and fishery interactions. This paper reports, for the first time, the genetic diversity of O. flavescens found along the Southern Brazilian coast. A 287-bp fragment of the mitochondrial DNA control region (D-loop was analyzed. Seven novel haplotypes were found in 56 individuals (OFA1-OFA7, with OFA1 being the most frequent (47.54%. Nucleotide diversity was moderate (π = 0.62% and haplotype diversity was relatively low (67%. Furthermore, the median joining network analysis indicated that Brazilian haplotypes formed a reciprocal monophyletic clade when compared to the haplotypes from the Peruvian population on the Pacific coast. These two populations do not share haplotypes and may have become isolated some time back. Further genetic studies covering the entire species distribution are necessary to better understand the biological implications of the results reported here for the management and conservation of South American sea lions.

  3. The performance of phylogenetic algorithms in estimating haplotype genealogies with migration.

    Science.gov (United States)

    Salzburger, Walter; Ewing, Greg B; Von Haeseler, Arndt

    2011-05-01

    Genealogies estimated from haplotypic genetic data play a prominent role in various biological disciplines in general and in phylogenetics, population genetics and phylogeography in particular. Several software packages have specifically been developed for the purpose of reconstructing genealogies from closely related, and hence, highly similar haplotype sequence data. Here, we use simulated data sets to test the performance of traditional phylogenetic algorithms, neighbour-joining, maximum parsimony and maximum likelihood in estimating genealogies from nonrecombining haplotypic genetic data. We demonstrate that these methods are suitable for constructing genealogies from sets of closely related DNA sequences with or without migration. As genealogies based on phylogenetic reconstructions are fully resolved, but not necessarily bifurcating, and without reticulations, these approaches outperform widespread 'network' constructing methods. In our simulations of coalescent scenarios involving panmictic, symmetric and asymmetric migration, we found that phylogenetic reconstruction methods performed well, while the statistical parsimony approach as implemented in TCS performed poorly. Overall, parsimony as implemented in the PHYLIP package performed slightly better than other methods. We further point out that we are not making the case that widespread 'network' constructing methods are bad, but that traditional phylogenetic tree finding methods are applicable to haplotypic data and exhibit reasonable performance with respect to accuracy and robustness. We also discuss some of the problems of converting a tree to a haplotype genealogy, in particular that it is nonunique. © 2011 Blackwell Publishing Ltd.

  4. Pregnancy-related venous thromboembolism and risk of occult cancer

    DEFF Research Database (Denmark)

    Tarp Hansen, Anette; Veres, Katalin; Horváth-Puhó, Erzsébet

    2017-01-01

    The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected.An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk.......The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected.An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk....

  5. Safety in relation to risk and benefit

    International Nuclear Information System (INIS)

    Siddall, E.

    1985-01-01

    The proper definition and quantification of human safety is discussed and from this basis the historical development of our present very high standard of safety is traced. It is shown that increased safety is closely associated with increased wealth, and the quantitative relationship between then is derived from different sources of evidence. When this factor is applied to the production of wealth by industry, a safety benefit is indicated which exceeds the asserted risks by orders of magnitude. It is concluded that present policies and attitudes in respect to the safety of industry may be diametrically wrong. (orig.) [de

  6. The relation of risk assessment and health impact assessment

    DEFF Research Database (Denmark)

    Ádám, Balázs; Gulis, Gabriel

    2013-01-01

    than assessing a present situation. As part of this process, however, methods applied in risk assessment are used. Risk assessment typically characterises relation of a well-defined risk factor to a well-defined health outcome. Within HIA usually several individual risk assessments are needed...... of the causal chain from the proposal through related health determinants and risk factors to health outcomes. The stepwise analysis, systematic prioritization and consideration of horizontal interactions between the causal pathways make it feasible to use widely recognized risk assessment methods in the HIA......The level and distribution of health risks in a society is substantially influenced by measures of various policies, programmes or projects. Risk assessment can evaluate the nature, likelihood and severity of an adverse effect. Health impact assessment (HIA) provides similar function when used...

  7. Reliable reconstruction of HIV-1 whole genome haplotypes reveals clonal interference and genetic hitchhiking among immune escape variants

    Science.gov (United States)

    2014-01-01

    Background Following transmission, HIV-1 evolves into a diverse population, and next generation sequencing enables us to detect variants occurring at low frequencies. Studying viral evolution at the level of whole genomes was hitherto not possible because next generation sequencing delivers relatively short reads. Results We here provide a proof of principle that whole HIV-1 genomes can be reliably reconstructed from short reads, and use this to study the selection of immune escape mutations at the level of whole genome haplotypes. Using realistically simulated HIV-1 populations, we demonstrate that reconstruction of complete genome haplotypes is feasible with high fidelity. We do not reconstruct all genetically distinct genomes, but each reconstructed haplotype represents one or more of the quasispecies in the HIV-1 population. We then reconstruct 30 whole genome haplotypes from published short sequence reads sampled longitudinally from a single HIV-1 infected patient. We confirm the reliability of the reconstruction by validating our predicted haplotype genes with single genome amplification sequences, and by comparing haplotype frequencies with observed epitope escape frequencies. Conclusions Phylogenetic analysis shows that the HIV-1 population undergoes selection driven evolution, with successive replacement of the viral population by novel dominant strains. We demonstrate that immune escape mutants evolve in a dependent manner with various mutations hitchhiking along with others. As a consequence of this clonal interference, selection coefficients have to be estimated for complete haplotypes and not for individual immune escapes. PMID:24996694

  8. 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects

    Directory of Open Access Journals (Sweden)

    Shaw Gary M

    2009-06-01

    Full Text Available Abstract Background Folic acid taken in early pregnancy reduces risks for delivering offspring with several congenital anomalies. The mechanism by which folic acid reduces risk is unknown. Investigations into genetic variation that influences transport and metabolism of folate will help fill this data gap. We focused on 118 SNPs involved in folate transport and metabolism. Methods Using data from a California population-based registry, we investigated whether risks of spina bifida or conotruncal heart defects were influenced by 118 single nucleotide polymorphisms (SNPs associated with the complex folate pathway. This case-control study included 259 infants with spina bifida and a random sample of 359 nonmalformed control infants born during 1983–86 or 1994–95. It also included 214 infants with conotruncal heart defects born during 1983–86. Infant genotyping was performed blinded to case or control status using a designed SNPlex assay. We examined single SNP effects for each of the 118 SNPs, as well as haplotypes, for each of the two outcomes. Results Few odds ratios (ORs revealed sizable departures from 1.0. With respect to spina bifida, we observed ORs with 95% confidence intervals that did not include 1.0 for the following SNPs (heterozygous or homozygous relative to the reference genotype: BHMT (rs3733890 OR = 1.8 (1.1–3.1, CBS (rs2851391 OR = 2.0 (1.2–3.1; CBS (rs234713 OR = 2.9 (1.3–6.7; MTHFD1 (rs2236224 OR = 1.7 (1.1–2.7; MTHFD1 (hcv11462908 OR = 0.2 (0–0.9; MTHFD2 (rs702465 OR = 0.6 (0.4–0.9; MTHFD2 (rs7571842 OR = 0.6 (0.4–0.9; MTHFR (rs1801133 OR = 2.0 (1.2–3.1; MTRR (rs162036 OR = 3.0 (1.5–5.9; MTRR (rs10380 OR = 3.4 (1.6–7.1; MTRR (rs1801394 OR = 0.7 (0.5–0.9; MTRR (rs9332 OR = 2.7 (1.3–5.3; TYMS (rs2847149 OR = 2.2 (1.4–3.5; TYMS (rs1001761 OR = 2.4 (1.5–3.8; and TYMS (rs502396 OR = 2.1 (1.3–3.3. However, multiple SNPs observed for a given gene showed evidence of linkage disequilibrium indicating

  9. The impact of sample size and marker selection on the study of haplotype structures

    Directory of Open Access Journals (Sweden)

    Sun Xiao

    2004-03-01

    Full Text Available Abstract Several studies of haplotype structures in the human genome in various populations have found that the human chromosomes are structured such that each chromosome can be divided into many blocks, within which there is limited haplotype diversity. In addition, only a few genetic markers in a putative block are needed to capture most of the diversity within a block. There has been no systematic empirical study of the effects of sample size and marker set on the identified block structures and representative marker sets, however. The purpose of this study was to conduct a detailed empirical study to examine such impacts. Towards this goal, we have analysed three representative autosomal regions from a large genome-wide study of haplotypes with samples consisting of African-Americans and samples consisting of Japanese and Chinese individuals. For both populations, we have found that the sample size and marker set have significant impact on the number of blocks and the total number of representative markers identified. The marker set in particular has very strong impacts, and our results indicate that the marker density in the original datasets may not be adequate to allow a meaningful characterisation of haplotype structures. In general, we conclude that we need a relatively large sample size and a very dense marker panel in the study of haplotype structures in human populations.

  10. Humorous Relations: Attentiveness, Pleasure and Risk

    Science.gov (United States)

    Mayo, Cris

    2014-01-01

    This article focuses on the structures of humor and joke telling that require particular kinds of attentiveness and particular relationships between speaker and audience, or more specifically, between classmates. First, I will analyze the pedagogical and relational preconditions that are necessary for humor to work. If humor is to work well, the…

  11. Elderly Taiwanese's Intrinsic Risk Factors for Fall-related Injuries

    OpenAIRE

    In-Fun Li; Yvonne Hsiung; Hui-Fen Hsing; Mei-Yu Lee; Te-Hsin Chang; Ming-Yuan Huang

    2016-01-01

    Background: As a vital issue in geriatric research, risk factors for falls were concluded to be multifactorial, and prevention has been mostly aimed at decreasing situational and environmental risks that cause and aggravate fall-related injuries, particularly within the institutions. While knowledge is limited about older patients' intrinsic determinants, the purpose of this study was to explore elderly Taiwanese's intrinsic risk factors associated with severe fall-related injuries. Method...

  12. Public attitudes towards industrial, work-related and other risks

    International Nuclear Information System (INIS)

    Prescott-Clarke, P.

    1982-01-01

    Two reports describing work sponsored by the Health and Safety Executive are presented. The first describes a study of public attitudes towards industrial, work related, nuclear industry related and other risks. The second report describes public attitudes towards the acceptability of risks. (U.K.)

  13. Brain tumour risk in relation to mobile telephone use

    DEFF Research Database (Denmark)

    Johansen, Christoffer

    2010-01-01

    The rapid increase in mobile telephone use has generated concern about possible health risks related to radiofrequency electromagnetic fields from this technology.......The rapid increase in mobile telephone use has generated concern about possible health risks related to radiofrequency electromagnetic fields from this technology....

  14. Association between SLC19A1 Gene Polymorphism and High Dose Methotrexate Toxicity in Childhood Acute Lymphoblastic Leukaemia and Non Hodgkin Malignant Lymphoma: Introducing a Haplotype based Approach

    Science.gov (United States)

    Kotnik, Barbara Faganel; Jazbec, Janez; Grabar, Petra Bohanec; Rodriguez-Antona, Cristina

    2017-01-01

    Abstract Background We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML). Patients and methods Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities. Results Patients with rs2838958 TT genotype had higher probability for mucositis development as compared to carriers of at least one rs2838958 C allele (OR 0.226 (0.071–0.725), p < 0.009). Haplotype TGTTCCG (H4) statistically significantly reduced the risk for the occurrence of adverse events during treatment with HD-MTX (OR 0.143 (0.023–0.852), p = 0.030). Conclusions SLC 19A1 SNP and haplotype analysis could provide additional information in a personalized HD-MTX therapy for children with ALL/NHML in order to achieve better treatment outcome. However further studies are needed to validate the results. PMID:29333125

  15. A comprehensive literature review of haplotyping software and methods for use with unrelated individuals

    Directory of Open Access Journals (Sweden)

    Salem Rany M

    2005-03-01

    Full Text Available Abstract Interest in the assignment and frequency analysis of haplotypes in samples of unrelated individuals has increased immeasurably as a result of the emphasis placed on haplotype analyses by, for example, the International HapMap Project and related initiatives. Although there are many available computer programs for haplotype analysis applicable to samples of unrelated individuals, many of these programs have limitations and/or very specific uses. In this paper, the key features of available haplotype analysis software for use with unrelated individuals, as well as pooled DNA samples from unrelated individuals, are summarised. Programs for haplotype analysis were identified through keyword searches on PUBMED and various internet search engines, a review of citations from retrieved papers and personal communications, up to June 2004. Priority was given to functioning computer programs, rather than theoretical models and methods. The available software was considered in light of a number of factors: the algorithm(s used, algorithm accuracy, assumptions, the accommodation of genotyping error, implementation of hypothesis testing, handling of missing data, software characteristics and web-based implementations. Review papers comparing specific methods and programs are also summarised. Forty-six haplotyping programs were identified and reviewed. The programs were divided into two groups: those designed for individual genotype data (a total of 43 programs and those designed for use with pooled DNA samples (a total of three programs. The accuracy of programs using various criteria are assessed and the programs are categorised and discussed in light of: algorithm and method, accuracy, assumptions, genotyping error, hypothesis testing, missing data, software characteristics and web implementation. Many available programs have limitations (eg some cannot accommodate missing data and/or are designed with specific tasks in mind (eg estimating

  16. Casein haplotypes and their association with milk production traits in Norwegian Red cattle

    Directory of Open Access Journals (Sweden)

    Nome Torfinn

    2009-02-01

    Full Text Available Abstract A high resolution SNP map was constructed for the bovine casein region to identify haplotype structures and study associations with milk traits in Norwegian Red cattle. Our analyses suggest separation of the casein cluster into two haplotype blocks, one consisting of the CSN1S1, CSN2 and CSN1S2 genes and another one consisting of the CSN3 gene. Highly significant associations with both protein and milk yield were found for both single SNPs and haplotypes within the CSN1S1-CSN2-CSN1S2 haplotype block. In contrast, no significant association was found for single SNPs or haplotypes within the CSN3 block. Our results point towards CSN2 and CSN1S2 as the most likely loci harbouring the underlying causative DNA variation. In our study, the most significant results were found for the SNP CSN2_67 with the C allele consistently associated with both higher protein and milk yields. CSN2_67 calls a C to an A substitution at codon 67 in β-casein gene resulting in histidine replacing proline in the amino acid sequence. This polymorphism determines the protein variants A1/B (CSN2_67 A allele versus A2/A3 (CSN2_67 C allele. Other studies have suggested that a high consumption of A1/B milk may affect human health by increasing the risk of diabetes and heart diseases. Altogether these results argue for an increase in the frequency of the CSN2_67 C allele or haplotypes containing this allele in the Norwegian Red cattle population by selective breeding.

  17. Assessing the risk of work-related international travel.

    Science.gov (United States)

    Druckman, Myles; Harber, Philip; Liu, Yihang; Quigley, Robert L

    2014-11-01

    To identify factors affecting the likelihood of requiring medical services during international business trips. Data from more than 800,000 international trips and medical assistance cases provided to 48 multinational corporations in 2009. Travel destination countries were grouped into four a priori risk-related categories. Travel to "low" medical risk countries in aggregate accounted for more hospitalizations and medical evacuations than travel to "high" medical risk countries. Nevertheless, the risk per trip was much higher for travel to higher medical risk countries. Corporations with employees on international travel should allocate sufficient resources to manage and ideally prevent medical issues during business travel. Travel medicine must focus on more than infectious diseases, and programs are necessary for both high- and low-risk regions. Improved understanding of travel-related needs determines resource allocation and risk mitigation efforts.

  18. Risk related behaviour under different ambient scent conditions

    Directory of Open Access Journals (Sweden)

    Alina Gagarina

    2016-09-01

    Full Text Available The article analyses the effect of two ambient scents (peppermint and vanilla and their intensiveness on risk related behaviour that is expressed through selected decision making heuristics. Purpose of the article: The purpose of this article is to identify the relationship of ambient scent type and intensiveness with risk related behaviour that is expressed through selected decision making heuristics. Methodology/methods: 2×2 factorial experiment with control group was run. Ambient scent type (vanilla vs. peppermint and intensiveness (8 (1mg vs. 16 sprays (2mg of scent concentrate in the same room were manipulated as between subject variables. Risk aversion, effect of anchoring heuristic on bidding, and affect (risk and benefit heuristics were tracked as dependent variables. Scientific aim: To identify whether ambient scent type and intensiveness have effect on risk related behaviour. Findings: Evidence suggests that there are effects of ambient scent on risk related behaviour, thus fulfilling the missing gap to relate ambient environment to decision making heuristics when risks are involved. However, not all heuristics were affected by experimental conditions. Subjects were bidding significantly higher amounts under low anchor conditions, when peppermint scent was around (if compared to vanilla group. Affect risk was perceived as lower in peppermint ambient scent conditions, if compared to the control group. Intensity of ambient scent also had influence on affect risk: subjects perceived less risk under high scent intensity conditions. Conclusions: By manipulating ambient scent, marketers may reduce or increase consumers risk perception and behaviour and as a consequence influence their purchase decisions. Marketers could use peppermint scent in high intensiveness in the situations where they want consumers to undertake higher risks (expensive purchases, gambling, insurance, since stakes were higher under peppermint ambient scent condition

  19. A novel HURRAH protocol reveals high numbers of monomorphic MHC class II loci and two asymmetric multi-locus haplotypes in the Père David's deer.

    Directory of Open Access Journals (Sweden)

    Qiu-Hong Wan

    Full Text Available The Père David's deer is a highly inbred, but recovered, species, making it interesting to consider their adaptive molecular evolution from an immunological perspective. Prior to this study, genomic sequencing was the only method for isolating all functional MHC genes within a certain species. Here, we report a novel protocol for isolating MHC class II loci from a species, and its use to investigate the adaptive evolution of this endangered deer at the level of multi-locus haplotypes. This protocol was designated "HURRAH" based on its various steps and used to estimate the total number of MHC class II loci. We confirmed the validity of this novel protocol in the giant panda and then used it to examine the Père David's deer. Our results revealed that the Père David's deer possesses nine MHC class II loci and therefore has more functional MHC class II loci than the eight genome-sequenced mammals for which full MHC data are currently available. This could potentially account at least in part for the strong survival ability of this species in the face of severe bottlenecking. The results from the HURRAH protocol also revealed that: (1 All of the identified MHC class II loci were monomorphic at their antigen-binding regions, although DRA was dimorphic at its cytoplasmic tail; and (2 these genes constituted two asymmetric functional MHC class II multi-locus haplotypes: DRA1*01 ∼ DRB1 ∼ DRB3 ∼ DQA1 ∼ DQB2 (H1 and DRA1*02 ∼ DRB2 ∼ DRB4 ∼ DQA2 ∼ DQB1 (H2. The latter finding indicates that the current members of the deer species have lost the powerful ancestral MHC class II haplotypes of nine or more loci, and have instead fixed two relatively weak haplotypes containing five genes. As a result, the Père David's deer are currently at risk for increased susceptibility to infectious pathogens.

  20. iHAP – integrated haplotype analysis pipeline for characterizing the haplotype structure of genes

    Directory of Open Access Journals (Sweden)

    Lim Yun Ping

    2006-12-01

    Full Text Available Abstract Background The advent of genotype data from large-scale efforts that catalog the genetic variants of different populations have given rise to new avenues for multifactorial disease association studies. Recent work shows that genotype data from the International HapMap Project have a high degree of transferability to the wider population. This implies that the design of genotyping studies on local populations may be facilitated through inferences drawn from information contained in HapMap populations. Results To facilitate analysis of HapMap data for characterizing the haplotype structure of genes or any chromosomal regions, we have developed an integrated web-based resource, iHAP. In addition to incorporating genotype and haplotype data from the International HapMap Project and gene information from the UCSC Genome Browser Database, iHAP also provides capabilities for inferring haplotype blocks and selecting tag SNPs that are representative of haplotype patterns. These include block partitioning algorithms, block definitions, tag SNP definitions, as well as SNPs to be "force included" as tags. Based on the parameters defined at the input stage, iHAP performs on-the-fly analysis and displays the result graphically as a webpage. To facilitate analysis, intermediate and final result files can be downloaded. Conclusion The iHAP resource, available at http://ihap.bii.a-star.edu.sg, provides a convenient yet flexible approach for the user community to analyze HapMap data and identify candidate targets for genotyping studies.

  1. The clinical application of single-sperm-based SNP haplotyping for PGD of osteogenesis imperfecta.

    Science.gov (United States)

    Chen, Linjun; Diao, Zhenyu; Xu, Zhipeng; Zhou, Jianjun; Yan, Guijun; Sun, Haixiang

    2018-05-15

    Osteogenesis imperfecta (OI) is a genetically heterogeneous disorder, presenting either autosomal dominant, autosomal recessive or X-linked inheritance patterns. The majority of OI cases are autosomal dominant and are caused by heterozygous mutations in either the COL1A1 or COL1A2 gene. In these dominant disorders, allele dropout (ADO) can lead to misdiagnosis in preimplantation genetic diagnosis (PGD). Polymorphic markers linked to the mutated genes have been used to establish haplotypes for identifying ADO and ensuring the accuracy of PGD. However, the haplotype of male patients cannot be determined without data from affected relatives. Here, we developed a method for single-sperm-based single-nucleotide polymorphism (SNP) haplotyping via next-generation sequencing (NGS) for the PGD of OI. After NGS, 10 informative polymorphic SNP markers located upstream and downstream of the COL1A1 gene and its pathogenic mutation site were linked to individual alleles in a single sperm from an affected male. After haplotyping, a normal blastocyst was transferred to the uterus for a subsequent frozen embryo transfer cycle. The accuracy of PGD was confirmed by amniocentesis at 19 weeks of gestation. A healthy infant weighing 4,250 g was born via vaginal delivery at the 40th week of gestation. Single-sperm-based SNP haplotyping can be applied for PGD of any monogenic disorders or de novo mutations in males in whom the haplotype of paternal mutations cannot be determined due to a lack of affected relatives. ADO: allele dropout; DI: dentinogenesis imperfect; ESHRE: European Society of Human Reproduction and Embryology; FET: frozen embryo transfer; gDNA: genomic DNA; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; MDA: multiple displacement amplification; NGS: next-generation sequencing; OI: osteogenesis imperfect; PBS: phosphate buffer saline; PCR: polymerase chain reaction; PGD: preimplantation genetic diagnosis; SNP: single-nucleotide polymorphism; STR

  2. Evaluation of energy related risk acceptance (APHA energy task force)

    International Nuclear Information System (INIS)

    Hull, A.P.

    1977-01-01

    Living in a technological society with large energy requirements involves a number of related actities with attendant health risks, both to the working and to the general public. Therefore, the formulation of some general principles for risk acceptance is necessary. In addition to maximizing benefits and minimizing risk, relevant considerations must be made about the perception of risk as voluntary or involuntary, the number of persons collectively at risk at any one occasion, and the extent to which a risk is a familiar one. With regard to a given benefit, such as a given amount of energy, comparisons of the risks of alternate modes of production may be utilized. However, cost-benefit consideration is essential to the amelioration of current or prospective risks. This is unusual, since it is based on some estimate of the monetary value per premature death averted. It is proposed that increased longevity would be a more satisfactory measure. On a societal basis, large expenditures for additional energy-related pollution control do not appear justifiable since much larger, nonenergy-related health risks are relatively underaddressed. Knowledgeable health professionals could benefit the public by imparting authoritative information in this area

  3. Worldwide distribution of the MYH9 kidney disease susceptibility alleles and haplotypes: evidence of historical selection in Africa.

    Directory of Open Access Journals (Sweden)

    Taras K Oleksyk

    2010-07-01

    Full Text Available MYH9 was recently identified as renal susceptibility gene (OR 3-8, p or = 60% than in European Americans (< 4%, revealing a genetic basis for a major health disparity. The population distributions of MYH9 risk alleles and the E-1 risk haplotype and the demographic and selective forces acting on the MYH9 region are not well explored. We reconstructed MYH9 haplotypes from 4 tagging single nucleotide polymorphisms (SNPs spanning introns 12-23 using available data from HapMap Phase II, and by genotyping 938 DNAs from the Human Genome Diversity Panel (HGDP. The E-1 risk haplotype followed a cline, being most frequent within sub-Saharan African populations (range 50-80%, less frequent in populations from the Middle East (9-27% and Europe (0-9%, and rare or absent in Asia, the Americas, and Oceania. The fixation indexes (F(ST for pairwise comparisons between the risk haplotypes for continental populations were calculated for MYH9 haplotypes; F(ST ranged from 0.27-0.40 for Africa compared to other continental populations, possibly due to selection. Uniquely in Africa, the Yoruba population showed high frequency extended haplotype length around the core risk allele (C compared to the alternative allele (T at the same locus (rs4821481, iHs = 2.67, as well as high population differentiation (F(ST(CEU vs. YRI = 0.51 in HapMap Phase II data, also observable only in the Yoruba population from HGDP (F(ST = 0.49, pointing to an instance of recent selection in the genomic region. The population-specific divergence in MYH9 risk allele frequencies among the world's populations may prove important in risk assessment and public health policies to mitigate the burden of kidney disease in vulnerable populations.

  4. Varied definitions of risk related to sensation seeking trait

    International Nuclear Information System (INIS)

    Daastoel, P.Oe.U.; Drottz-Sjoeberg, B.M.

    1999-01-01

    This pilot study is based on the assumption and the knowledge that previous results show that the normal use of the word risk varies across subjects. The risk definitions the subjects use have also been shown to be related to various educational interests. A related field of research has developed measures for Sensation Seeking personality trait, with four facets. Three independent groups of first year psychology students reported their normal definition of the word risk using one of three measurement formats. The results showed, e.g. that the typical open-ended response to the personal definition of risk was danger. Subjects who defined risk as the combination of probability and consequences tended to score higher on the total Sensation Seeking Scale, as compared to those defining risk as the probability of an event

  5. Varied definitions of risk related to sensation seeking trait

    Energy Technology Data Exchange (ETDEWEB)

    Daastoel, P.Oe.U.; Drottz-Sjoeberg, B.M. [Norwegian Univ. of Science and Technology, Trondheim (Norway). Dept. of Psychology

    1999-12-01

    This pilot study is based on the assumption and the knowledge that previous results show that the normal use of the word risk varies across subjects. The risk definitions the subjects use have also been shown to be related to various educational interests. A related field of research has developed measures for Sensation Seeking personality trait, with four facets. Three independent groups of first year psychology students reported their normal definition of the word risk using one of three measurement formats. The results showed, e.g. that the typical open-ended response to the personal definition of risk was danger. Subjects who defined risk as the combination of probability and consequences tended to score higher on the total Sensation Seeking Scale, as compared to those defining risk as the probability of an event.

  6. Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Zhenglin Yang

    2010-02-01

    Full Text Available A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.

  7. An unusual haplotype structure on human chromosome 8p23 derived from the inversion polymorphism.

    Science.gov (United States)

    Deng, Libin; Zhang, Yuezheng; Kang, Jian; Liu, Tao; Zhao, Hongbin; Gao, Yang; Li, Chaohua; Pan, Hao; Tang, Xiaoli; Wang, Dunmei; Niu, Tianhua; Yang, Huanming; Zeng, Changqing

    2008-10-01

    Chromosomal inversion is an important type of genomic variations involved in both evolution and disease pathogenesis. Here, we describe the refined genetic structure of a 3.8-Mb inversion polymorphism at chromosome 8p23. Using HapMap data of 1,073 SNPs generated from 209 unrelated samples from CEPH-Utah residents with ancestry from northern and western Europe (CEU); Yoruba in Ibadan, Nigeria (YRI); and Asian (ASN) samples, which were comprised of Han Chinese from Beijing, China (CHB) and Japanese from Tokyo, Japan (JPT)-we successfully deduced the inversion orientations of all their 418 haplotypes. In particular, distinct haplotype subgroups were identified based on principal component analysis (PCA). Such genetic substructures were consistent with clustering patterns based on neighbor-joining tree reconstruction, which revealed a total of four haplotype clades across all samples. Metaphase fluorescence in situ hybridization (FISH) in a subset of 10 HapMap samples verified their inversion orientations predicted by PCA or phylogenetic tree reconstruction. Positioning of the outgroup haplotype within one of YRI clades suggested that Human NCBI Build 36-inverted order is most likely the ancestral orientation. Furthermore, the population differentiation test and the relative extended haplotype homozygosity (REHH) analysis in this region discovered multiple selection signals, also in a population-specific manner. A positive selection signal was detected at XKR6 in the ASN population. These results revealed the correlation of inversion polymorphisms to population-specific genetic structures, and various selection patterns as possible mechanisms for the maintenance of a large chromosomal rearrangement at 8p23 region during evolution. In addition, our study also showed that haplotype-based clustering methods, such as PCA, can be applied in scanning for cryptic inversion polymorphisms at a genome-wide scale.

  8. Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes.

    Science.gov (United States)

    Long, Ji-Rong; Zhao, Lan-Juan; Liu, Peng-Yuan; Lu, Yan; Dvornyk, Volodymyr; Shen, Hui; Liu, Yong-Jun; Zhang, Yuan-Yuan; Xiong, Dong-Hai; Xiao, Peng; Deng, Hong-Wen

    2004-05-24

    The adequacy of association studies for complex diseases depends critically on the existence of linkage disequilibrium (LD) between functional alleles and surrounding SNP markers. We examined the patterns of LD and haplotype distribution in eight candidate genes for osteoporosis and/or obesity using 31 SNPs in 1,873 subjects. These eight genes are apolipoprotein E (APOE), type I collagen alpha1 (COL1A1), estrogen receptor-alpha (ER-alpha), leptin receptor (LEPR), parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1), transforming growth factor-beta1 (TGF-beta1), uncoupling protein 3 (UCP3), and vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR). Yin yang haplotypes, two high-frequency haplotypes composed of completely mismatching SNP alleles, were examined. To quantify LD patterns, two common measures of LD, D' and r2, were calculated for the SNPs within the genes. The haplotype distribution varied in the different genes. Yin yang haplotypes were observed only in PTHR1 and UCP3. D' ranged from 0.020 to 1.000 with the average of 0.475, whereas the average r2 was 0.158 (ranging from 0.000 to 0.883). A decay of LD was observed as the intermarker distance increased, however, there was a great difference in LD characteristics of different genes or even in different regions within gene. The differences in haplotype distributions and LD patterns among the genes underscore the importance of characterizing genomic regions of interest prior to association studies.

  9. Effects of trust and governance on relational risk

    NARCIS (Netherlands)

    Nooteboom, B.; Berger, J.; Noorderhaven, N.G.

    In transaction cost economics, foist has been treated as redundant or even misleading. This study tested the effects of governance and trust the risk perceived by agents of firms in alliances. Two dimensions of relational risk were assessed: the probability that something will go wrong and the size

  10. Beyond the contract: managing risk in supply chain relations

    NARCIS (Netherlands)

    Dekker, H.C.; Sakaguchi, J.; Kawai, T.

    2013-01-01

    As a consequence of the development of intensified relations with suppliers, for many firms the supply chain has become a significant source of risk exposure. In this paper we examine firms' use of control practices to manage risks associated with intensified collaboration with supply chain

  11. Evidence and Consequence of a Highly Adapted Clonal Haplotype within the Australian Ascochyta rabiei Population

    Directory of Open Access Journals (Sweden)

    Yasir Mehmood

    2017-06-01

    Full Text Available The Australian Ascochyta rabiei (Pass. Labr. (syn. Phoma rabiei population has low genotypic diversity with only one mating type detected to date, potentially precluding substantial evolution through recombination. However, a large diversity in aggressiveness exists. In an effort to better understand the risk from selective adaptation to currently used resistance sources and chemical control strategies, the population was examined in detail. For this, a total of 598 isolates were quasi-hierarchically sampled between 2013 and 2015 across all major Australian chickpea growing regions and commonly grown host genotypes. Although a large number of haplotypes were identified (66 through short sequence repeat (SSR genotyping, overall low gene diversity (Hexp = 0.066 and genotypic diversity (D = 0.57 was detected. Almost 70% of the isolates assessed were of a single dominant haplotype (ARH01. Disease screening on a differential host set, including three commonly deployed resistance sources, revealed distinct aggressiveness among the isolates, with 17% of all isolates identified as highly aggressive. Almost 75% of these were of the ARH01 haplotype. A similar pattern was observed at the host level, with 46% of all isolates collected from the commonly grown host genotype Genesis090 (classified as “resistant” during the term of collection identified as highly aggressive. Of these, 63% belonged to the ARH01 haplotype. In conclusion, the ARH01 haplotype represents a significant risk to the Australian chickpea industry, being not only widely adapted to the diverse agro-geographical environments of the Australian chickpea growing regions, but also containing a disproportionately large number of aggressive isolates, indicating fitness to survive and replicate on the best resistance sources in the Australian germplasm.

  12. Risk related behaviour under different ambient scent conditions

    OpenAIRE

    Alina Gagarina; Indre Pikturniene

    2016-01-01

    The article analyses the effect of two ambient scents (peppermint and vanilla) and their intensiveness on risk related behaviour that is expressed through selected decision making heuristics. Purpose of the article: The purpose of this article is to identify the relationship of ambient scent type and intensiveness with risk related behaviour that is expressed through selected decision making heuristics. Methodology/methods: 2×2 factorial experiment with control group was run. Ambi...

  13. Estimating internal exposure risks by the relative risk and the National Institute of Health risk models

    International Nuclear Information System (INIS)

    Mehta, S.K.; Sarangapani, R.

    1995-01-01

    This paper presents tabulations of risk (R) and person-years of life lost (PYLL) for acute exposures of individual organs at ages 20 and 40 yrs for the Indian and Japanese populations to illustrate the effect of age at exposure in the two models. Results are also presented for the organ wise nominal probability coefficients (NPC) and PYLL for individual organs for the age distributed Indian population by the two models. The results presented show that for all organs the estimates of PYLL and NPC for the Indian population are lower than those for the Japanese population by both models except for oesophagus, breast and ovary by the relative risk (RR) model, where the opposite trend is observed. The results also show that the Indian all-cancer values of NPC averaged over the two models is 2.9 x 10 -2 Sv -1 , significantly lower than the world average value of 5x10 -2 Sv -1 estimated by the ICRP. (author). 9 refs., 2 figs., 2 tabs

  14. Climate risk assessment in museums : degradation risks determined from temperature and relative humidity data

    NARCIS (Netherlands)

    Martens, M.H.J.

    2012-01-01

    The main subject of this thesis is the determination of climate risks to objects in museums on the basis of measured and/or simulated temperature and relative humidity data. The focus is on the quantification of climate related risks for the preservation quality of indoor climate in Dutch museums.

  15. The association between individual SNPs or haplotypes of matrix metalloproteinase 1 and gastric cancer susceptibility, progression and prognosis.

    Directory of Open Access Journals (Sweden)

    Yong-Xi Song

    Full Text Available BACKGROUND: The single nucleotide polymorphisms (SNPs in matrix metalloproteinase 1(MMP-1 play important roles in some cancers. This study examined the associations between individual SNPs or haplotypes in MMP-1 and susceptibility, clinicopathological parameters and prognosis of gastric cancer in a large sample of the Han population in northern China. METHODS: In this case-controlled study, there were 404 patients with gastric cancer and 404 healthy controls. Seven SNPs were genotyped using the MALDI-TOF MS system. Then, SPSS software, Haploview 4.2 software, Haplo.states software and THEsias software were used to estimate the association between individual SNPs or haplotypes of MMP-1 and gastric cancer susceptibility, progression and prognosis. RESULTS: Among seven SNPs, there were no individual SNPs correlated to gastric cancer risk. Moreover, only the rs470206 genotype had a correlation with histologic grades, and the patients with GA/AA had well cell differentiation compared to the patients with genotype GG (OR=0.573; 95%CI: 0.353-0.929; P=0.023. Then, we constructed a four-marker haplotype block that contained 4 common haplotypes: TCCG, GCCG, TTCG and TTTA. However, all four common haplotypes had no correlation with gastric cancer risk and we did not find any relationship between these haplotypes and clinicopathological parameters in gastric cancer. Furthermore, neither individual SNPs nor haplotypes had an association with the survival of patients with gastric cancer. CONCLUSIONS: This study evaluated polymorphisms of the MMP-1 gene in gastric cancer with a MALDI-TOF MS method in a large northern Chinese case-controlled cohort. Our results indicated that these seven SNPs of MMP-1 might not be useful as significant markers to predict gastric cancer susceptibility, progression or prognosis, at least in the Han population in northern China.

  16. Risk communication related to animal products derived from biotechnology.

    Science.gov (United States)

    McCrea, D

    2005-04-01

    Previous chapters of this review have dealt with the key considerations related to the application of biotechnology in veterinary science and animal production. This article explores the theory and practice of risk communication and sets out the basic principles for good risk communication when dealing with new technologies, uncertainty, and cautious and sceptical consumers. After failure to communicate with consumers and stakeholders about the risk to human health from bovine spongiform encephalopathy (BSE) in the 1990s, Government Agencies in the United Kingdom have made significant improvements in risk communication. The official inquiry that followed the BSE crisis concluded that a policy of openness was the correct approach, and this article emphasises the importance of consultation, consistency and transparency. There are, however, many different factors that affect public perception of risk (religious, political, social, cultural, etc.) and developing effective risk communication strategies must take all of these complex issues into consideration.

  17. Adequacy of relative and absolute risk models for lifetime risk estimate of radiation-induced cancer

    International Nuclear Information System (INIS)

    McBride, M.; Coldman, A.J.

    1988-03-01

    This report examines the applicability of the relative (multiplicative) and absolute (additive) models in predicting lifetime risk of radiation-induced cancer. A review of the epidemiologic literature, and a discussion of the mathematical models of carcinogenesis and their relationship to these models of lifetime risk, are included. Based on the available data, the relative risk model for the estimation of lifetime risk is preferred for non-sex-specific epithelial tumours. However, because of lack of knowledge concerning other determinants of radiation risk and of background incidence rates, considerable uncertainty in modelling lifetime risk still exists. Therefore, it is essential that follow-up of exposed cohorts be continued so that population-based estimates of lifetime risk are available

  18. Association of Xmn I Polymorphism and Hemoglobin E Haplotypes on Postnatal Gamma Globin Gene Expression in Homozygous Hemoglobin E

    Directory of Open Access Journals (Sweden)

    Supachai Ekwattanakit

    2012-01-01

    Full Text Available Background and Objectives. To explore the role of cis-regulatory sequences within the β globin gene cluster at chromosome 11 on human γ globin gene expression related to Hb E allele, we analyze baseline hematological data and Hb F values together with β globin haplotypes in homozygous Hb E. Patients and Methods. 80 individuals with molecularly confirmed homozygous Hb E were analyzed for the β globin haplotypes and Xmn I polymorphism using PCR-RFLPs. 74 individuals with complete laboratory data were further studied for association analyses. Results. Eight different β globin haplotypes were found linked to Hb E alleles; three major haplotypes were (a (III, (b (V, and (c (IV accounting for 94% of Hb E chromosomes. A new haplotype (Th-1 was identified and most likely converted from the major ones. The majority of individuals had Hb F < 5%; only 10.8% of homozygous Hb E had high Hb F (average 10.5%, range 5.8–14.3%. No association was found on a specific haplotype or Xmn I in these individuals with high Hb F, measured by alkaline denaturation. Conclusion. The cis-regulation of γ globin gene expression might not be apparent under a milder condition with lesser globin imbalance such as homozygous Hb E.

  19. Musical aptitude is associated with AVPR1A-haplotypes.

    Directory of Open Access Journals (Sweden)

    Liisa T Ukkola

    Full Text Available Artistic creativity forms the basis of music culture and music industry. Composing, improvising and arranging music are complex creative functions of the human brain, which biological value remains unknown. We hypothesized that practicing music is social communication that needs musical aptitude and even creativity in music. In order to understand the neurobiological basis of music in human evolution and communication we analyzed polymorphisms of the arginine vasopressin receptor 1A (AVPR1A, serotonin transporter (SLC6A4, catecol-O-methyltranferase (COMT, dopamin receptor D2 (DRD2 and tyrosine hydroxylase 1 (TPH1, genes associated with social bonding and cognitive functions in 19 Finnish families (n = 343 members with professional musicians and/or active amateurs. All family members were tested for musical aptitude using the auditory structuring ability test (Karma Music test; KMT and Carl Seashores tests for pitch (SP and for time (ST. Data on creativity in music (composing, improvising and/or arranging music was surveyed using a web-based questionnaire. Here we show for the first time that creative functions in music have a strong genetic component (h(2 = .84; composing h(2 = .40; arranging h(2 = .46; improvising h(2 = .62 in Finnish multigenerational families. We also show that high music test scores are significantly associated with creative functions in music (p<.0001. We discovered an overall haplotype association with AVPR1A gene (markers RS1 and RS3 and KMT (p = 0.0008; corrected p = 0.00002, SP (p = 0.0261; corrected p = 0.0072 and combined music test scores (COMB (p = 0.0056; corrected p = 0.0006. AVPR1A haplotype AVR+RS1 further suggested a positive association with ST (p = 0.0038; corrected p = 0.00184 and COMB (p = 0.0083; corrected p = 0.0040 using haplotype-based association test HBAT. The results suggest that the neurobiology of music perception and production is likely to be related to the pathways affecting intrinsic attachment

  20. HLA class II linkage disequilibrium and haplotype evolution in the Cayapa Indians of Ecuador

    Energy Technology Data Exchange (ETDEWEB)

    Trachtenberg, E.A.; Erlich, H.A. [Roche Molecular Systems, Alameda, CA (United States); Klitz, W. [Univ. of California, Berkeley, CA (United States)] [and others

    1995-08-01

    DNA-based typing of the HLA class II loci in a sample of the Cayapa Indians of Ecuador reveals several lines of evidence that selection has operated to maintain and to diversify the existing level of polymorphism in the class II region. As has been noticed for other Native American groups, the overall level of polymorphism at the DRB1, DQA1, DQB1, and DPB1 loci is reduced relative to that found in other human populations. Nonetheless, the relative eveness in the distribution of allele frequencies at each of the four loci points to the role of balancing selection in the maintenance of the polymorphism. The DQA1 and DQB1 loci, in particular, have near-maximum departures from the neutrality model, which suggests that balancing selection has been especially strong in these cases. Several novel DQA1-DQB1 haplotypes and the discovery of a new DRB1 allele demonstrate an evolutionary tendency favoring the diversification of class II alleles and haplotypes. The recombination interval between the centromeric DPB1 locus and the other class II loci will, in the absence of other forces such as selection, reduce disequilibrium across this region. However, nearly all common alleles were found to be part of DR-DP haplotypes in strong disequilibrium, consistent with the recent action of selection acting on these haplotypes in the Cayapa. 50 refs., 3 figs., 3 tabs.

  1. Effects of Bos taurus autosome 9-located quantitative trait loci haplotypes on the disease phenotypes of dairy cows with experimentally induced Escherichia coli mastitis

    DEFF Research Database (Denmark)

    Khatun, Momena; Sørensen, Peter; Jørgensen, Hanne Birgitte Hede

    2013-01-01

    Several quantitative trait loci (QTL) affecting mastitis incidence and mastitis-related traits such as somatic cell score exist in dairy cows. Previously, QTL haplotypes associated with susceptibility to Escherichia coli mastitis in Nordic Holstein-Friesian (HF) cows were identified on Bos taurus...... autosome 9. In the present study, we induced experimental E. coli mastitis in Danish HF cows to investigate the effect of 2 E. coli mastitis-associated QTL haplotypes on the cows' disease phenotypes and recovery in early lactation. Thirty-two cows were divided in 2 groups bearing haplotypes with either low...... the HH group did. However, we also found interactions between the effects of haplotype and biopsy for body temperature, heart rate, and PMNL. In conclusion, when challenged with E. coli mastitis, HF cows with the specific Bos taurus autosome 9-located QTL haplotypes were associated with differences...

  2. Alcohol-Related Problems And High Risk Sexual Behaviour In ...

    African Journals Online (AJOL)

    There was a significant association between alcohol-related problems and risky sexual behavior. Alcohol-related problems are fairly common in people already infected with HIV/AIDS and are associated with high-risk sexual behavior. Thus, screening and treatment should be part of an effective HIV intervention program.

  3. Risk of cancer in relatives of patients with myotonic dystrophy

    DEFF Research Database (Denmark)

    Lund, M; Diaz, L J; Gørtz, S

    2014-01-01

    BACKGROUND AND PURPOSE: Myotonic dystrophies (DM) are autosomal dominantly inherited neuromuscular disorders caused by unstable nucleotide repeat expansions. DM and cancer have been associated, but the pathogenesis behind the association remains unclear. It could relate to derived effects of the DM...... genotype in which case non-DM relatives of DM patients would not be expected to be at increased risk of cancer. To elucidate this, a population-based cohort study investigating risk of cancer in relatives of DM patients was conducted. METHODS: DM was identified using the National Danish Patient Registry...

  4. HapCol : Accurate and memory-efficient haplotype assembly from long reads

    NARCIS (Netherlands)

    Pirola, Yuri; Zaccaria, Simone; Dondi, Riccardo; Klau, Gunnar W.; Pisanti, Nadia; Bonizzoni, Paola

    2016-01-01

    Motivation: Haplotype assembly is the computational problem of reconstructing haplotypes in diploid organisms and is of fundamental importance for characterizing the effects of single-nucleotide polymorphisms on the expression of phenotypic traits. Haplotype assembly highly benefits from the advent

  5. HapCol: Accurate and Memory-efficient Haplotype Assembly from Long Reads

    NARCIS (Netherlands)

    Y. Pirola (Yuri); S. Zaccaria (Simone); R. Dondi (Riccardo); G.W. Klau (Gunnar); N. Pisanti (Nadia); P. Bonizzoni (Paola)

    2015-01-01

    htmlabstractMotivation: Haplotype assembly is the computational problem of reconstructing haplotypes in diploid organisms and is of fundamental importance for characterizing the effects of single-nucleotide polymorphisms on the expression of phenotypic traits. Haplotype assembly highly benefits from

  6. Urbanization and traffic related exposures as risk factors for Schizophrenia

    DEFF Research Database (Denmark)

    Pedersen, Carsten Bøcker; Mortensen, Preben Bo

    2006-01-01

    to nearest major road had no significant effect. CONCLUSIONS: The cause(s) or exposure(s) responsible for the urban-rural differences in schizophrenia risk were closer related to the degree of urbanization than to the geographical distance to nearest major road. Traffic related exposures might thus be less......BACKGROUND: Urban birth or upbringing increase schizophrenia risk. Though unknown, the causes of these urban-rural differences have been hypothesized to include, e.g., infections, diet, toxic exposures, social class, or an artefact due to selective migration. METHODS: We investigated the hypothesis...... that traffic related exposures affect schizophrenia risk and that this potential effect is responsible for the urban-rural differences. The geographical distance from place of residence to nearest major road was used as a proxy variable for traffic related exposures. We used a large population-based sample...

  7. CD28/CTLA-4/ICOS haplotypes confers susceptibility to Graves' disease and modulates clinical phenotype of disease.

    Science.gov (United States)

    Pawlak-Adamska, Edyta; Frydecka, Irena; Bolanowski, Marek; Tomkiewicz, Anna; Jonkisz, Anna; Karabon, Lidia; Partyka, Anna; Nowak, Oskar; Szalinski, Marek; Daroszewski, Jacek

    2017-01-01

    Graves' disease, an autoimmune disease with heterogeneous symptoms including Graves' orbitopathy, has a combined genetic/environmental background, where variations within CD28/CTLA-4/ICOS genes are considered as disease markers.Association of CD28c.17+3T>C(rs3116496), CTLA-4g.319C>T(rs5742909), CTLA-4c.49A>G(rs231775), CTLA-4g.*642AT(8_33), CT60(rs3087243), Jo31(rs11571302), ICOSc.1554+4GT(8_15) polymorphisms with susceptibility to Graves' disease and clinical outcome was investigated. The study group comprised of 561 Polish Caucasians, including 172 unrelated Graves' disease patients. CTLA-4c.49A>G, CTLA-4g.319C>T, and CT60 were genotyped by PCR-RFLP; Jo31 and CD28c.17+3C>T by minisequencing; CTLA-4g.*642AT(8_33) and ICOSc.1554+4GT(8_15)-PCR and fluorescence-based technique. CD28c.17+3T>C(rs3116496)T/CTLA-4g.319C>T(rs5742909)C/CTLA-4c.49A>G(rs231775)G/CTLA-4g.*642AT(8_33)(AT 16-21 )/CT60(rs3087243)G/Jo31(rs11571302)G/ICOSc.1554+4GT(8_15)(m) and TCA(AT Graves' disease, especially in males, as well as overall Graves' orbitopathy development with severe outcome. TCG(AT 16-21 )GG(l) haplotype increased risk of Graves' disease and reduced the chance of successful medical treatment. Although this haplotype was mainly observed in patients without signs of Graves' orbitopathy, if Graves' orbitopathy developed it favored a Graves' orbitopathy outcome. Haplotype TCA(AT >21 )GT(m) increased Graves' disease risk in women and, in all patients, was linked to Graves' disease without Graves' orbitopathy. TCG(AT Graves' disease risk factor, whereas CT60 was an independent factor for disease progression. Sporadic Graves' disease was related to presence of CTLA-4c.49A>G[A] and the rare CTLA-4g.319C>T[T] allele variant. Familial background of the disease was exclusively associated with CTLA-4g.*642AT(8_33)[AT >21 ]/[AT >21 ] genotype. CD28/CTLA-4/ICOS loci may confer inherited susceptibility to Graves' disease or may be involved in susceptibility to Graves' disease and play a

  8. Relations between radiation risks and radiation protection measuring techniques

    International Nuclear Information System (INIS)

    Herrmann, K.; Kraus, W.

    Relations between radiation risks and radiation protection measuring techniques are considered as components of the radiation risk. The influence of the exposure risk on type and extent of radiation protection measurements is discussed with regard to different measuring tasks. Based upon measuring results concerning the frequency of certain external and internal occupational exposures in the GDR, it has been shown that only a small fraction of the monitored persons are subjected to a high exposure risk. As a consequence the following recommendations are presented: occupationally exposed persons with small exposure risk should be monitored using only a long-term desimeter (for instance a thermoluminescence desimeter). In the case of internal exposure, the surface and air contamination levels should be controlled so strictly that routine measurements of internal contamination need not be performed

  9. Musical Aptitude Is Associated with AVPR1A-Haplotypes

    Science.gov (United States)

    Ukkola, Liisa T.; Onkamo, Päivi; Raijas, Pirre; Karma, Kai; Järvelä, Irma

    2009-01-01

    Artistic creativity forms the basis of music culture and music industry. Composing, improvising and arranging music are complex creative functions of the human brain, which biological value remains unknown. We hypothesized that practicing music is social communication that needs musical aptitude and even creativity in music. In order to understand the neurobiological basis of music in human evolution and communication we analyzed polymorphisms of the arginine vasopressin receptor 1A (AVPR1A), serotonin transporter (SLC6A4), catecol-O-methyltranferase (COMT), dopamin receptor D2 (DRD2) and tyrosine hydroxylase 1 (TPH1), genes associated with social bonding and cognitive functions in 19 Finnish families (n = 343 members) with professional musicians and/or active amateurs. All family members were tested for musical aptitude using the auditory structuring ability test (Karma Music test; KMT) and Carl Seashores tests for pitch (SP) and for time (ST). Data on creativity in music (composing, improvising and/or arranging music) was surveyed using a web-based questionnaire. Here we show for the first time that creative functions in music have a strong genetic component (h2 = .84; composing h2 = .40; arranging h2 = .46; improvising h2 = .62) in Finnish multigenerational families. We also show that high music test scores are significantly associated with creative functions in music (pmusic test scores (COMB) (p = 0.0056; corrected p = 0.0006). AVPR1A haplotype AVR+RS1 further suggested a positive association with ST (p = 0.0038; corrected p = 0.00184) and COMB (p = 0.0083; corrected p = 0.0040) using haplotype-based association test HBAT. The results suggest that the neurobiology of music perception and production is likely to be related to the pathways affecting intrinsic attachment behavior. PMID:19461995

  10. Musical aptitude is associated with AVPR1A-haplotypes.

    Science.gov (United States)

    Ukkola, Liisa T; Onkamo, Päivi; Raijas, Pirre; Karma, Kai; Järvelä, Irma

    2009-05-20

    Artistic creativity forms the basis of music culture and music industry. Composing, improvising and arranging music are complex creative functions of the human brain, which biological value remains unknown. We hypothesized that practicing music is social communication that needs musical aptitude and even creativity in music. In order to understand the neurobiological basis of music in human evolution and communication we analyzed polymorphisms of the arginine vasopressin receptor 1A (AVPR1A), serotonin transporter (SLC6A4), catecol-O-methyltranferase (COMT), dopamin receptor D2 (DRD2) and tyrosine hydroxylase 1 (TPH1), genes associated with social bonding and cognitive functions in 19 Finnish families (n = 343 members) with professional musicians and/or active amateurs. All family members were tested for musical aptitude using the auditory structuring ability test (Karma Music test; KMT) and Carl Seashores tests for pitch (SP) and for time (ST). Data on creativity in music (composing, improvising and/or arranging music) was surveyed using a web-based questionnaire. Here we show for the first time that creative functions in music have a strong genetic component (h(2) = .84; composing h(2) = .40; arranging h(2) = .46; improvising h(2) = .62) in Finnish multigenerational families. We also show that high music test scores are significantly associated with creative functions in music (pmusic test scores (COMB) (p = 0.0056; corrected p = 0.0006). AVPR1A haplotype AVR+RS1 further suggested a positive association with ST (p = 0.0038; corrected p = 0.00184) and COMB (p = 0.0083; corrected p = 0.0040) using haplotype-based association test HBAT. The results suggest that the neurobiology of music perception and production is likely to be related to the pathways affecting intrinsic attachment behavior.

  11. Global spread and genetic variants of the two CYP9M10 haplotype forms associated with insecticide resistance in Culex quinquefasciatus Say.

    Science.gov (United States)

    Itokawa, K; Komagata, O; Kasai, S; Kawada, H; Mwatele, C; Dida, G O; Njenga, S M; Mwandawiro, C; Tomita, T

    2013-09-01

    Insecticide resistance develops as a genetic factor (allele) conferring lower susceptibility to insecticides proliferates within a target insect population under strong positive selection. Intriguingly, a resistance allele pre-existing in a population often bears a series of further adaptive allelic variants through new mutations. This phenomenon occasionally results in replacement of the predominating resistance allele by fitter new derivatives, and consequently, development of greater resistance at the population level. The overexpression of the cytochrome P450 gene CYP9M10 is associated with pyrethroid resistance in the southern house mosquito Culex quinquefasciatus. Previously, we have found two genealogically related overexpressing CYP9M10 haplotypes, which differ in gene copy number (duplicated and non-duplicated). The duplicated haplotype was derived from the non-duplicated overproducer probably recently. In the present study, we investigated allelic series of CYP9M10 involved in three C. quinquefasciatus laboratory colonies recently collected from three different localities. Duplicated and non-duplicated overproducing haplotypes coexisted in African and Asian colonies indicating a global distribution of both haplotype lineages. The duplicated haplotypes both in the Asian and African colonies were associated with higher expression levels and stronger resistance than non-duplicated overproducing haplotypes. There were slight variation in expression level among the non-duplicated overproducing haplotypes. The nucleotide sequences in coding and upstream regions among members of this group also showed a little diversity. Non-duplicated overproducing haplotypes with relatively higher expression were genealogically closer to the duplicated haplotypes than the other non-duplicated overproducing haplotypes, suggesting multiple cis-acting mutations before duplication.

  12. Nighttime parenting strategies and sleep-related risks to infants.

    Science.gov (United States)

    Volpe, Lane E; Ball, Helen L; McKenna, James J

    2013-02-01

    A large social science and public health literature addresses infant sleep safety, with implications for infant mortality in the context of accidental deaths and Sudden Infant Death Syndrome (SIDS). As part of risk reduction campaigns in the USA, parents are encouraged to place infants supine and to alter infant bedding and elements of the sleep environment, and are discouraged from allowing infants to sleep unsupervised, from bed-sharing either at all or under specific circumstances, or from sofa-sharing. These recommendations are based on findings from large-scale epidemiological studies that generate odds ratios or relative risk statistics for various practices; however, detailed behavioural data on nighttime parenting and infant sleep environments are limited. To address this issue, this paper presents and discusses the implications of four case studies based on overnight observations conducted with first-time mothers and their four-month old infants. These case studies were collected at the Mother-Baby Behavioral Sleep Lab at the University of Notre Dame USA between September 2002 and June 2004. Each case study provides a detailed description based on video analysis of sleep-related risks observed while mother-infant dyads spent the night in a sleep lab. The case studies provide examples of mothers engaged in the strategic management of nighttime parenting for whom sleep-related risks to infants arose as a result of these strategies. Although risk reduction guidelines focus on eliminating potentially risky infant sleep practices as if the probability of death from each were equal, the majority of instances in which these occur are unlikely to result in infant mortality. Therefore, we hypothesise that mothers assess potential costs and benefits within margins of risk which are not acknowledged by risk-reduction campaigns. Exploring why mothers might choose to manage sleep and nighttime parenting in ways that appear to increase potential risks to infants may

  13. Risk of bleeding related to antithrombotic treatment in cardiovascular disease

    DEFF Research Database (Denmark)

    Sørensen, Rikke; Olesen, Jonas B; Charlot, Mette

    2012-01-01

    Antithrombotic therapy is a cornerstone of treatment in patients with cardiovascular disease with bleeding being the most feared complication. This review describes the risk of bleeding related to different combinations of antithrombotic drugs used for cardiovascular disease: acute coronary...... syndrome (ACS), atrial fibrillation (AF), cerebrovascular (CVD) and peripheral arterial disease (PAD). Different risk assessment schemes and bleeding definitions are compared. The HAS-BLED risk score is recommended in patients with AF and in ACS patients with AF. In patients with ACS with or without...

  14. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer

    International Nuclear Information System (INIS)

    Hansen, Torben F.; Spindler, Karen-Lise G.; Andersen, Rikke F.; Lindebjerg, Jan; Kølvraa, Steen; Brandslund, Ivan; Jakobsen, Anders

    2010-01-01

    New prognostic markers in patients with colorectal cancer (CRC) are a prerequisite for individualized treatment. Prognostic importance of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene has been proposed. The objective of the present study was to investigate the prognostic importance of haplotypes in the VEGF-A gene in patients with CRC. The study included 486 patients surgically resected for stage II and III CRC, divided into two independent cohorts. Three SNPs in the VEGF-A gene were analyzed by polymerase chain reaction. Haplotypes were estimated using the PHASE program. The prognostic influence was evaluated using Kaplan-Meir plots and log rank tests. Cox regression method was used to analyze the independent prognostic importance of different markers. All three SNPs were significantly related to survival. A haplotype combination, responsible for this effect, was present in approximately 30% of the patients and demonstrated a significant relationship with poor survival, and it remained an independent prognostic marker after multivariate analysis, hazard ratio 2.46 (95% confidence interval 1.49–4.06), p < 0.001. Validation was provided by consistent findings in a second and independent cohort. Haplotype combinations call for further investigation

  15. Haplotype frequencies at the DRD2 locus in populations of the East European Plain

    Directory of Open Access Journals (Sweden)

    Mikulich Alexey I

    2009-09-01

    Full Text Available Abstract Background It was demonstrated previously that the three-locus RFLP haplotype, TaqI B-TaqI D-TaqI A (B-D-A, at the DRD2 locus constitutes a powerful genetic marker and probably reflects the most ancient dispersal of anatomically modern humans. Results We investigated TaqI B, BclI, MboI, TaqI D, and TaqI A RFLPs in 17 contemporary populations of the East European Plain and Siberia. Most of these populations belong to the Indo-European or Uralic language families. We identified three common haplotypes, which occurred in more than 90% of chromosomes investigated. The frequencies of the haplotypes differed according to linguistic and geographical affiliation. Conclusion Populations in the northwestern (Byelorussians from Mjadel', northern (Russians from Mezen' and Oshevensk, and eastern (Russians from Puchezh parts of the East European Plain had relatively high frequencies of haplotype B2-D2-A2, which may reflect admixture with Uralic-speaking populations that inhabited all of these regions in the Early Middle Ages.

  16. Introgression of a Rare Haplotype from Southeastern Africa to Breed California Blackeyes with Larger Seeds

    Directory of Open Access Journals (Sweden)

    Mitchell R Lucas

    2015-03-01

    Full Text Available Seed size distinguishes most crops from their wild relatives and is an important quality trait for the grain legume cowpea. In order to breed cowpea varieties with larger seeds we introgressed a rare haplotype associated with large seeds at the Css-1 locus from an African buff seed type cultivar, IT82E-18 (18.5g/100 seeds, into a blackeye seed type cultivar, CB27 (22g/100 seed. Four RILs derived from these two parents were chosen for marker-assisted breeding based on SNP genotyping with a goal of stacking large seed haplotypes into a CB27 background. Foreground and background selection were performed during two cycles of backcrossing based on genome-wide SNP markers. The average seed size of introgression lines homozygous for haplotypes associated with large seeds was 28.7g/100 seed and 24.8g/100 seed for cycles 1 and 2, respectively. One cycle 1 introgression line with desirable seed quality was selfed for two generations to make families with very large seeds (28-35g/100 seeds. Field-based performance trials helped identify breeding lines that not only have large seeds but are also desirable in terms of yield, maturity, and plant architecture when compared to industry standards. A principal component analysis was used to explore the relationships between the parents relative to a core set of landraces and improved varieties based on high-density SNP data. The geographic distribution of haplotypes at the Css-1 locus suggest the haplotype associated with large seeds is unique to accessions collected from Southeastern Africa. Therefore this QTL has a strong potential to develop larger seeded varieties for other growing regions which is demonstrated in this work using a California pedigree.

  17. Anesthesiologist- and System-Related Risk Factors for Risk-Adjusted Pediatric Anesthesia-Related Cardiac Arrest.

    Science.gov (United States)

    Zgleszewski, Steven E; Graham, Dionne A; Hickey, Paul R; Brustowicz, Robert M; Odegard, Kirsten C; Koka, Rahul; Seefelder, Christian; Navedo, Andres T; Randolph, Adrienne G

    2016-02-01

    Pediatric anesthesia-related cardiac arrest (ARCA) is an uncommon but potentially preventable adverse event. Infants and children with more severe underlying disease are at highest risk. We aimed to identify system- and anesthesiologist-related risk factors for ARCA. We analyzed a prospectively collected patient cohort data set of anesthetics administered from 2000 to 2011 to children at a large tertiary pediatric hospital. Pre-procedure systemic disease level was characterized by ASA physical status (ASA-PS). Two reviewers independently reviewed cardiac arrests and categorized their anesthesia relatedness. Factors associated with ARCA in the univariate analyses were identified for reevaluation after adjustment for patient age and ASA-PS. Cardiac arrest occurred in 142 of 276,209 anesthetics (incidence 5.1/10,000 anesthetics); 72 (2.6/10,000 anesthetics) were classified as anesthesia-related. In the univariate analyses, risk of ARCA was much higher in cardiac patients and for anesthesiologists with lower annual caseload and/or fewer annual days delivering anesthetics (all P risk adjustment for ASA-PS ≥ III and age ≤ 6 months, however, the association with lower annual days delivering anesthetics remained (P = 0.03), but the other factors were no longer significant. Case-mix explained most associations between higher risk of pediatric ARCA and anesthesiologist-related variables at our institution, but the association with fewer annual days delivering anesthetics remained. Our findings highlight the need for rigorous adjustment for patient risk factors in anesthesia patient safety studies.

  18. A spatial haplotype copying model with applications to genotype imputation.

    Science.gov (United States)

    Yang, Wen-Yun; Hormozdiari, Farhad; Eskin, Eleazar; Pasaniuc, Bogdan

    2015-05-01

    Ever since its introduction, the haplotype copy model has proven to be one of the most successful approaches for modeling genetic variation in human populations, with applications ranging from ancestry inference to genotype phasing and imputation. Motivated by coalescent theory, this approach assumes that any chromosome (haplotype) can be modeled as a mosaic of segments copied from a set of chromosomes sampled from the same population. At the core of the model is the assumption that any chromosome from the sample is equally likely to contribute a priori to the copying process. Motivated by recent works that model genetic variation in a geographic continuum, we propose a new spatial-aware haplotype copy model that jointly models geography and the haplotype copying process. We extend hidden Markov models of haplotype diversity such that at any given location, haplotypes that are closest in the genetic-geographic continuum map are a priori more likely to contribute to the copying process than distant ones. Through simulations starting from the 1000 Genomes data, we show that our model achieves superior accuracy in genotype imputation over the standard spatial-unaware haplotype copy model. In addition, we show the utility of our model in selecting a small personalized reference panel for imputation that leads to both improved accuracy as well as to a lower computational runtime than the standard approach. Finally, we show our proposed model can be used to localize individuals on the genetic-geographical map on the basis of their genotype data.

  19. Common pitfalls in statistical analysis: Absolute risk reduction, relative risk reduction, and number needed to treat

    Science.gov (United States)

    Ranganathan, Priya; Pramesh, C. S.; Aggarwal, Rakesh

    2016-01-01

    In the previous article in this series on common pitfalls in statistical analysis, we looked at the difference between risk and odds. Risk, which refers to the probability of occurrence of an event or outcome, can be defined in absolute or relative terms. Understanding what these measures represent is essential for the accurate interpretation of study results. PMID:26952180

  20. Heterogenous Intertemporal Elasticity of Substitution and Relative Risk Aversion

    DEFF Research Database (Denmark)

    Khorunzhina, Natalia; Gayle, Wayne-Roy

    This paper investigates the existence and degree of variation across house holds and over time in the intertemporal elasticity of substitution (IES) and the coefficient of relative risk aversion (RRA) that is generated by habit forming preferences. To do so, we develop a new nonlinear GMM estimator...... in food consumption. Using these estimates, we develop bounds for the expectation of the implied heterogenous intertemporal elasticity of substitution and relative risk aversion that account for measurement errors and compute asymptotically valid confidence intervals on these bounds. We find...

  1. Fitchi: haplotype genealogy graphs based on the Fitch algorithm.

    Science.gov (United States)

    Matschiner, Michael

    2016-04-15

    : In population genetics and phylogeography, haplotype genealogy graphs are important tools for the visualization of population structure based on sequence data. In this type of graph, node sizes are often drawn in proportion to haplotype frequencies and edge lengths represent the minimum number of mutations separating adjacent nodes. I here present Fitchi, a new program that produces publication-ready haplotype genealogy graphs based on the Fitch algorithm. http://www.evoinformatics.eu/fitchi.htm : michaelmatschiner@mac.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Cancer-related fatigue: Mechanisms, risk factors, and treatments

    Science.gov (United States)

    Bower, Julienne E.

    2015-01-01

    Fatigue is one of the most common and distressing side effects of cancer and its treatment, and may persist for years after treatment completion in otherwise healthy survivors. Cancer-related fatigue causes disruption in all aspects of quality of life and may be a risk factor for reduced survival. The prevalence and course of fatigue in cancer patients has been well characterized, and there is growing understanding of underlying biological mechanisms. Inflammation has emerged as a key biological pathway for cancer-related fatigue, with studies documenting links between markers of inflammation and fatigue before, during, and particularly after treatment. There is considerable variability in the experience of cancer-related fatigue that is not explained by disease- or treatment-related characteristics, suggesting that host factors may play an important role in the development and persistence of this symptom. Indeed, longitudinal studies have begun to identify genetic, biological, psychosocial, and behavioral risk factors for cancer-related fatigue. Given the multi-factorial nature of cancer-related fatigue, a variety of intervention approaches have been examined in randomized controlled trials, including physical activity, psychosocial, mind-body, and pharmacological treatments. Although there is currently no gold standard for treating fatigue, several of these approaches have shown beneficial effects and can be recommended to patients. This report provides a state of the science review of mechanisms, risk factors, and interventions for cancer-related fatigue, with a focus on recent longitudinal studies and randomized trials that have targeted fatigued patients. PMID:25113839

  3. Are we overestimating the stroke risk related to contraceptive pills?

    Science.gov (United States)

    Gompel, Anne; Plu-Bureau, Genevieve

    2014-02-01

    Hormonal contraceptives are used by million of women worldwide. Ischemic stroke is one of the major harmful effects of hormonal contraceptives, but remains a very uncommon disease before menopause. The increased risk of stroke under third and fourth-generation contraceptive pills and nonoral contraceptives has been recently highlighted. Given the benefits associated with combined hormonal contraceptives (COCs), it is important to properly evaluate their risks in order to provide a better benefit/risk balance to young women. Scarce studies addressing the rates of stroke in young women suggest that the fraction attributable to the contraceptive pill remains low. In contrast, there is abundant literature on the relative risks of stroke under COCs. The risk of arterial disease seems to be similar among users of second and third-generation pills, drospirenone-containing pills and nonoral hormonal contraceptives. Progestin-only contraceptives do not appear to be associated with an increased risk of stroke. New formulations of hormonal contraceptives are not safer than second-generation COCs. Even if the absolute numbers of strokes attributable to hormonal contraceptives is very low, stringent selection of patients should help to reduce the events still more, and progestin-only contraceptives/nonhormonal methods should be preferred in cases of associated risk factors.

  4. Risk of bleeding related to antithrombotic treatment in cardiovascular disease

    DEFF Research Database (Denmark)

    Sørensen, Rikke; Olesen, Jonas B; Charlot, Mette

    2012-01-01

    Antithrombotic therapy is a cornerstone of treatment in patients with cardiovascular disease with bleeding being the most feared complication. This review describes the risk of bleeding related to different combinations of antithrombotic drugs used for cardiovascular disease: acute coronary...... syndrome (ACS), atrial fibrillation (AF), cerebrovascular (CVD) and peripheral arterial disease (PAD). Different risk assessment schemes and bleeding definitions are compared. The HAS-BLED risk score is recommended in patients with AF and in ACS patients with AF. In patients with ACS with or without...... a stent dual antiplatelet therapy with a P2Y12 receptor antagonist and acetylsalicylic acid (ASA) is recommended for 12 months, preferable with prasugrel or ticagrelor unless there is an additional indication of warfarin or increased risk of bleeding. In patients with AF, warfarin is recommended...

  5. Human capital and risk aversion in relational incentive contracts

    International Nuclear Information System (INIS)

    Kvaloey, Ola

    2003-01-01

    This paper examines a self-enforced relational incentive contract between a risk neutral principal and a risk averse agent where the agent's human capital is essential in ex post realization of values. I analyse the effect of outside options on the optimal bonus level, showing how the presence of ex post outside options may impede desirable degrees of performance pay. The effect of risk aversion and incentive responsiveness is analysed by allowing for linear contracts. I show that the first order effect of these parameters are the same as in verifiable contracts, but second order effects show that the optimal bonus level's sensitivity to risk aversion and incentive responsiveness increases with the discount factor. The analysis has interesting implications on firm boundaries and specificity choices. (author)

  6. Elite athletes experiences with risk related to cardiac screening

    DEFF Research Database (Denmark)

    Christensen, Jonas Schmidt; Thing, Lone Friis

    Society of Cardiology as well as major sports federations such as the International Olympic Committee, however, these recommendations seem to be based on an inadequate empirical foundation, just as the costs of performing cardiac screening on a larger scale seem out of proportion. Additionally, the field...... perspective on risk (Foucault 1988). For most elite athletes participation in cardiac screening is done out of a wish to obtain an acquittal from risks. Symptomatic of the risk society cardiac screening can from an athlete perspective at the same time be seen as an attempt to gain control over......Elite Athletes experiences with risks related to Cardiac Screening Jonas Schmidt Christensen1, Lone Friis Thing1 1University of Copenhagen - Department of Nutrition, Exercise and Sports (NEXS), Cardiac screening of elite athletes are recommended by both the American Heart Association & the European...

  7. Contrasted patterns of molecular evolution in dominant and recessive self-incompatibility haplotypes in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Pauline M Goubet

    Full Text Available Self-incompatibility has been considered by geneticists a model system for reproductive biology and balancing selection, but our understanding of the genetic basis and evolution of this molecular lock-and-key system has remained limited by the extreme level of sequence divergence among haplotypes, resulting in a lack of appropriate genomic sequences. In this study, we report and analyze the full sequence of eleven distinct haplotypes of the self-incompatibility locus (S-locus in two closely related Arabidopsis species, obtained from individual BAC libraries. We use this extensive dataset to highlight sharply contrasted patterns of molecular evolution of each of the two genes controlling self-incompatibility themselves, as well as of the genomic region surrounding them. We find strong collinearity of the flanking regions among haplotypes on each side of the S-locus together with high levels of sequence similarity. In contrast, the S-locus region itself shows spectacularly deep gene genealogies, high variability in size and gene organization, as well as complete absence of sequence similarity in intergenic sequences and striking accumulation of transposable elements. Of particular interest, we demonstrate that dominant and recessive S-haplotypes experience sharply contrasted patterns of molecular evolution. Indeed, dominant haplotypes exhibit larger size and a much higher density of transposable elements, being matched only by that in the centromere. Overall, these properties highlight that the S-locus presents many striking similarities with other regions involved in the determination of mating-types, such as sex chromosomes in animals or in plants, or the mating-type locus in fungi and green algae.

  8. Enhancing the mathematical properties of new haplotype homozygosity statistics for the detection of selective sweeps.

    Science.gov (United States)

    Garud, Nandita R; Rosenberg, Noah A

    2015-06-01

    Soft selective sweeps represent an important form of adaptation in which multiple haplotypes bearing adaptive alleles rise to high frequency. Most statistical methods for detecting selective sweeps from genetic polymorphism data, however, have focused on identifying hard selective sweeps in which a favored allele appears on a single haplotypic background; these methods might be underpowered to detect soft sweeps. Among exceptions is the set of haplotype homozygosity statistics introduced for the detection of soft sweeps by Garud et al. (2015). These statistics, examining frequencies of multiple haplotypes in relation to each other, include H12, a statistic designed to identify both hard and soft selective sweeps, and H2/H1, a statistic that conditional on high H12 values seeks to distinguish between hard and soft sweeps. A challenge in the use of H2/H1 is that its range depends on the associated value of H12, so that equal H2/H1 values might provide different levels of support for a soft sweep model at different values of H12. Here, we enhance the H12 and H2/H1 haplotype homozygosity statistics for selective sweep detection by deriving the upper bound on H2/H1 as a function of H12, thereby generating a statistic that normalizes H2/H1 to lie between 0 and 1. Through a reanalysis of resequencing data from inbred lines of Drosophila, we show that the enhanced statistic both strengthens interpretations obtained with the unnormalized statistic and leads to empirical insights that are less readily apparent without the normalization. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Distribution of QPY and RAH haplotypes of granzyme B gene in distinct Brazilian populations

    Directory of Open Access Journals (Sweden)

    Fernanda Bernadelli Garcia

    2012-08-01

    Full Text Available INTRODUCTION: The cytolysis mediated by granules is one of the most important effector functions of cytotoxic T lymphocytes and natural killer cells. Recently, three single nucleotide polymorphisms (SNPs were identified at exons 2, 3, and 5 of the granzyme B gene, resulting in a haplotype in which three amino acids of mature protein Q48P88Y245 are changed to R48A88H245, which leads to loss of cytotoxic activity of the protein. In this study, we evaluated the frequency of these polymorphisms in Brazilian populations. METHODS: We evaluated the frequency of these polymorphisms in Brazilian ethnic groups (white, Afro-Brazilian, and Asian by sequencing these regions. RESULTS: The allelic and genotypic frequencies of SNP 2364A/G at exon 2 in Afro-Brazilian individuals (42.3% and 17.3% were significantly higher when compared with those in whites and Asians (p < 0.0001 and p = 0.0007, respectively. The polymorphisms 2933C/G and 4243C/T also were more frequent in Afro-Brazilians but without any significant difference regarding the other groups. The Afro-Brazilian group presented greater diversity of haplotypes, and the RAH haplotype seemed to be more frequent in this group (25%, followed by the whites (20.7% and by the Asians (11.9%, similar to the frequency presented in the literature. CONCLUSIONS: There is a higher frequency of polymorphisms in Afro-Brazilians, and the RAH haplotype was more frequent in these individuals. We believe that further studies should aim to investigate the correlation of this haplotype with diseases related to immunity mediated by cytotoxic lymphocytes, and if this correlation is confirmed, novel treatment strategies might be elaborated.

  10. The IGF1 small dog haplotype is derived from Middle Eastern grey wolves

    Directory of Open Access Journals (Sweden)

    Ostrander Elaine A

    2010-02-01

    Full Text Available Abstract Background A selective sweep containing the insulin-like growth factor 1 (IGF1 gene is associated with size variation in domestic dogs. Intron 2 of IGF1 contains a SINE element and single nucleotide polymorphism (SNP found in all small dog breeds that is almost entirely absent from large breeds. In this study, we surveyed a large sample of grey wolf populations to better understand the ancestral pattern of variation at IGF1 with a particular focus on the distribution of the small dog haplotype and its relationship to the origin of the dog. Results We present DNA sequence data that confirms the absence of the derived small SNP allele in the intron 2 region of IGF1 in a large sample of grey wolves and further establishes the absence of a small dog associated SINE element in all wild canids and most large dog breeds. Grey wolf haplotypes from the Middle East have higher nucleotide diversity suggesting an origin there. Additionally, PCA and phylogenetic analyses suggests a closer kinship of the small domestic dog IGF1 haplotype with those from Middle Eastern grey wolves. Conclusions The absence of both the SINE element and SNP allele in grey wolves suggests that the mutation for small body size post-dates the domestication of dogs. However, because all small dogs possess these diagnostic mutations, the mutations likely arose early in the history of domestic dogs. Our results show that the small dog haplotype is closely related to those in Middle Eastern wolves and is consistent with an ancient origin of the small dog haplotype there. Thus, in concordance with past archeological studies, our molecular analysis is consistent with the early evolution of small size in dogs from the Middle East. See associated opinion by Driscoll and Macdonald: http://jbiol.com/content/9/2/10

  11. [Occupational risk related to optical radiation exposure in construction workers].

    Science.gov (United States)

    Gobba, F; Modenese, A

    2012-01-01

    Optical Radiation is a relevant occupational risk in construction workers, mainly as a consequence of the exposure to the ultraviolet (UV) component of solar radiation (SR). Available data show that UV occupational limits are frequently exceeded in these workers, resulting in an increased occupational risk of various acute and chronic effects, mainly to skin and to the eye. One of the foremost is the carcinogenic effect: SR is indeed included in Group 1 IARC (carcinogenic to humans). UV exposure is related to an increase of the incidence of basal cell carcinoma, squamous cell carcinoma of the skin and cutaneous malignant melanoma (CMM). The incidence of these tumors, especially CMM, is constantly increasing in Caucasians in the last 50 years. As a conclusion, an adequate evaluation of the occupational risk related to SR, and adequate preventive measures are essential in construction workers. The role of occupational physicians in prevention is fundamental.

  12. Urbanization and traffic related exposures as risk factors for Schizophrenia

    DEFF Research Database (Denmark)

    Pedersen, Carsten Bøcker; Mortensen, Preben Bo

    2006-01-01

    : The geographical distance from place of residence to nearest major road had a significant effect. The highest risk was found in children living 500-1000 metres from nearest major road (RR=1.30 (95% Confidence Interval: 1.17-1.44). However, when we accounted for the degree of urbanization, the geographical distance...... that traffic related exposures affect schizophrenia risk and that this potential effect is responsible for the urban-rural differences. The geographical distance from place of residence to nearest major road was used as a proxy variable for traffic related exposures. We used a large population-based sample......BACKGROUND: Urban birth or upbringing increase schizophrenia risk. Though unknown, the causes of these urban-rural differences have been hypothesized to include, e.g., infections, diet, toxic exposures, social class, or an artefact due to selective migration. METHODS: We investigated the hypothesis...

  13. Birth of a healthy infant following preimplantation PKHD1 haplotyping for autosomal recessive polycystic kidney disease using multiple displacement amplification

    Science.gov (United States)

    Janson, Marleen M.; Roesler, Mark R.; Avner, Ellis D.; Strawn, Estil Y.; Bick, David P.

    2010-01-01

    Purpose To develop a reliable preimplantation genetic diagnosis protocol for couples who both carry a mutant PKHD1 gene wishing to conceive children unaffected with autosomal recessive polycystic kidney disease (ARPKD). Methods Development of a unique protocol for preimplantation genetic testing using whole genome amplification of single blastomeres by multiple displacement amplification (MDA), and haplotype analysis with novel short tandem repeat (STR) markers from the PKHD1 gene and flanking sequences, and a case report of successful utilization of the protocol followed by successful IVF resulting in the birth of an infant unaffected with ARPKD. Results We have developed 20 polymorphic STR markers suitable for linkage analysis of ARPKD. These linked STR markers have enabled unambiguous identification of the PKHD1 haplotypes of embryos produced by at-risk couples. Conclusions We have developed a reliable protocol for preimplantation genetic diagnosis of ARPKD using single-cell MDA products for PKHD1 haplotyping. PMID:20490649

  14. Aerobic fitness related to cardiovascular risk factors in young children

    DEFF Research Database (Denmark)

    Dencker, Magnus; Thorsson, Ola; Karlsson, Magnus K

    2012-01-01

    Low aerobic fitness (maximum oxygen uptake (VO(2PEAK))) is predictive for poor health in adults. In a cross-sectional study, we assessed if VO(2PEAK) is related to a composite risk factor score for cardiovascular disease (CVD) in 243 children (136 boys and 107 girls) aged 8 to 11 years. VO(2PEAK...

  15. HIV/AIDS Related Knowledge and Perceived Risk Associated with ...

    African Journals Online (AJOL)

    Using data from the 2004 National Survey of Adolescents in Uganda, logistic regression models were fitted to examine the odds that HIV/AIDS related knowledge and perceived risk of HIV infection are associated with condom use among adolescents. After including demographic measures, findings indicated that correct ...

  16. Cancer-related fatigue--mechanisms, risk factors, and treatments.

    Science.gov (United States)

    Bower, Julienne E

    2014-10-01

    Fatigue is one of the most common adverse effects of cancer that might persist for years after treatment completion in otherwise healthy survivors. Cancer-related fatigue causes disruption in all aspects of quality of life and might be a risk factor of reduced survival. The prevalence and course of fatigue in patients with cancer have been well characterized and there is growing understanding of the underlying biological mechanisms. Inflammation seems to have a key role in fatigue before, during, and after cancer-treatment. However, there is a considerable variability in the presentation of cancer-related fatigue, much of which is not explained by disease-related or treatment-related characteristics, suggesting that host factors might be important in the development and persistence of this symptom. Indeed, longitudinal studies have identified genetic, biological, psychosocial, and behavioural risk factors associated with cancer-related fatigue. Although no current gold-standard treatment for fatigue is available, a variety of intervention approaches have shown beneficial effects in randomized controlled trials, including physical activity, psychosocial, mind-body, and pharmacological treatments. This Review describes the mechanisms, risk factors, and possible interventions for cancer-related fatigue, focusing on recent longitudinal studies and randomized trials that have targeted fatigued patients.

  17. Honey bee-inspired algorithms for SNP haplotype reconstruction problem

    Science.gov (United States)

    PourkamaliAnaraki, Maryam; Sadeghi, Mehdi

    2016-03-01

    Reconstructing haplotypes from SNP fragments is an important problem in computational biology. There have been a lot of interests in this field because haplotypes have been shown to contain promising data for disease association research. It is proved that haplotype reconstruction in Minimum Error Correction model is an NP-hard problem. Therefore, several methods such as clustering techniques, evolutionary algorithms, neural networks and swarm intelligence approaches have been proposed in order to solve this problem in appropriate time. In this paper, we have focused on various evolutionary clustering techniques and try to find an efficient technique for solving haplotype reconstruction problem. It can be referred from our experiments that the clustering methods relying on the behaviour of honey bee colony in nature, specifically bees algorithm and artificial bee colony methods, are expected to result in more efficient solutions. An application program of the methods is available at the following link. http://www.bioinf.cs.ipm.ir/software/haprs/

  18. De novo assembly of a haplotype-resolved human genome.

    Science.gov (United States)

    Cao, Hongzhi; Wu, Honglong; Luo, Ruibang; Huang, Shujia; Sun, Yuhui; Tong, Xin; Xie, Yinlong; Liu, Binghang; Yang, Hailong; Zheng, Hancheng; Li, Jian; Li, Bo; Wang, Yu; Yang, Fang; Sun, Peng; Liu, Siyang; Gao, Peng; Huang, Haodong; Sun, Jing; Chen, Dan; He, Guangzhu; Huang, Weihua; Huang, Zheng; Li, Yue; Tellier, Laurent C A M; Liu, Xiao; Feng, Qiang; Xu, Xun; Zhang, Xiuqing; Bolund, Lars; Krogh, Anders; Kristiansen, Karsten; Drmanac, Radoje; Drmanac, Snezana; Nielsen, Rasmus; Li, Songgang; Wang, Jian; Yang, Huanming; Li, Yingrui; Wong, Gane Ka-Shu; Wang, Jun

    2015-06-01

    The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should aid in translating genotypes to phenotypes for the development of personalized medicine.

  19. Identification of Tribolium castaneum (Herbst) haplotypes, the pest of ...

    African Journals Online (AJOL)

    SARAH

    2016-07-31

    Jul 31, 2016 ... haplotypes of T. castaneum and their distribution in Senegal. Methodology ... very strong marketing of cereals and vegetables in that area. The mutations ..... for each channel by sampling the various parameters every 1000 ...

  20. [Risk factors related to surgical site infection in elective surgery].

    Science.gov (United States)

    Angeles-Garay, Ulises; Morales-Márquez, Lucy Isabel; Sandoval-Balanzarios, Miguel Antonio; Velázquez-García, José Arturo; Maldonado-Torres, Lulia; Méndez-Cano, Andrea Fernanda

    2014-01-01

    The risk factors for surgical site infections in surgery should be measured and monitored from admission to 30 days after the surgical procedure, because 30% of Surgical Site Infection is detected when the patient was discharged. Calculate the Relative Risk of associated factors to surgical site infections in adult with elective surgery. Patients were classified according to the surgery contamination degree; patient with surgery clean was defined as no exposed and patient with clean-contaminated or contaminated surgery was defined exposed. Risk factors for infection were classified as: inherent to the patient, pre-operative, intra-operative and post-operative. Statistical analysis; we realized Student t or Mann-Whitney U, chi square for Relative Risk (RR) and multivariate analysis by Cox proportional hazards. Were monitored up to 30 days after surgery 403 patients (59.8% women), 35 (8.7%) developed surgical site infections. The factors associated in multivariate analysis were: smoking, RR of 3.21, underweight 3.4 hand washing unsuitable techniques 4.61, transfusion during the procedure 3.22, contaminated surgery 60, and intensive care stay 8 to 14 days 11.64, permanence of 1 to 3 days 2.4 and use of catheter 1 to 3 days 2.27. To avoid all risk factors is almost impossible; therefore close monitoring of elective surgery patients can prevent infectious complications.

  1. Improving preimplantation genetic diagnosis (PGD) reliability by selection of sperm donor with the most informative haplotype.

    Science.gov (United States)

    Malcov, Mira; Gold, Veronica; Peleg, Sagit; Frumkin, Tsvia; Azem, Foad; Amit, Ami; Ben-Yosef, Dalit; Yaron, Yuval; Reches, Adi; Barda, Shimi; Kleiman, Sandra E; Yogev, Leah; Hauser, Ron

    2017-04-26

    The study is aimed to describe a novel strategy that increases the accuracy and reliability of PGD in patients using sperm donation by pre-selecting the donor whose haplotype does not overlap the carrier's one. A panel of 4-9 informative polymorphic markers, flanking the mutation in carriers of autosomal dominant/X-linked disorders, was tested in DNA of sperm donors before PGD. Whenever the lengths of donors' repeats overlapped those of the women, additional donors' DNA samples were analyzed. The donor that demonstrated the minimal overlapping with the patient was selected for IVF. In 8 out of 17 carriers the markers of the initially chosen donors overlapped the patients' alleles and 2-8 additional sperm donors for each patient were haplotyped. The selection of additional sperm donors increased the number of informative markers and reduced misdiagnosis risk from 6.00% ± 7.48 to 0.48% ±0.68. The PGD results were confirmed and no misdiagnosis was detected. Our study demonstrates that pre-selecting a sperm donor whose haplotype has minimal overlapping with the female's haplotype, is critical for reducing the misdiagnosis risk and ensuring a reliable PGD. This strategy may contribute to prevent the transmission of affected IVF-PGD embryos using a simple and economical procedure. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. DNA testing of donors was approved by the institutional Helsinki committee (registration number 319-08TLV, 2008). The present study was approved by the institutional Helsinki committee (registration number 0385-13TLV, 2013).

  2. Are all risks equal? Early experiences of poverty-related risk and children's functioning.

    Science.gov (United States)

    Roy, Amanda L; Raver, C Cybele

    2014-06-01

    Using cumulative risk and latent class analysis (LCA) models, we examined how exposure to deep poverty (income-to-needs ratio risks (i.e., single-parent household, residential crowding, caregiver depression, and multiple life stressors) in preschool is related to children's future difficulty in school in a longitudinal sample of 602 Head Start-enrolled, low-income families. Results from the LCA revealed 4 risk profiles: low risk, deep poverty and single, single and stressed, and deep poverty and crowded household. Tests of measurement invariance across racial/ethnic groups established that, although patterns of risk are similar across groups (i.e., risks covary in the same way), the prevalence of risk profiles differs. African American families were overrepresented in the "deep poverty and single" profile while Latino and White families were overrepresented in the "deep poverty and crowded" profile. Finally, children's third grade functioning in 3 domains (i.e., academic performance, behavior problems, and self-regulatory skills) was predicted using a cumulative risk index and LCA-identified risk profiles. Both approaches demonstrated that children who experienced higher levels of risk in preschool had worse school performance than children with low levels of risk. However, LCA also revealed that children who experienced "single and stressed" family settings had more behavior problems than low-risk children while children who experienced "deep poverty and crowded" family settings had worse academic performance. The results indicate that all risks are not equal for children's development and highlight the utility of LCA for tailoring intervention efforts to best meet the needs of target populations. PsycINFO Database Record (c) 2014 APA, all rights reserved

  3. Food for thought - Communicating food-related risks

    Directory of Open Access Journals (Sweden)

    Sturloni Giancarlo

    2003-03-01

    Full Text Available In the last few years, a continuous series of food alerts have caught the attention of the media and the public in Europe. First, eggs and pork contaminated with dioxins; then, “mad cow” disease, while, all along in the background, a battle against genetically modified plants has been in progress. These food alerts have had complex repercussions on the perception of risks associated with food production. Experts have often been divided over these issues, and the uncertainty of scientific data has been indicated on more than one occasion as one of the factors that influence risk perception. However, the most important factor seems to be undoubtedly the way in which the risk has been communicated (or not communicated to the public. Therefore, risk communication analysis offers an excellent opportunity to understand the profound changes that are taking place in relations among the scientific community, mass media and other members of civil society now that they are fully aware that scientific and technological innovation, the real driving force of modern industrial society, is a source of development but also a source of risks which are not always acceptable. Within this different context, a debate open to all interested parties appears to have become a dire necessity for the “risk society”, especially as far as food is concerned because food has extremely important psychological, ethical and cultural values.

  4. Explanatory risk factors in the relations between schizotypy and indicators of suicide risk.

    Science.gov (United States)

    Jahn, Danielle R; DeVylder, Jordan E; Hilimire, Matthew R

    2016-04-30

    Schizotypy has been linked to suicide risk, but it is not known whether established suicide-related risk factors mediate this relation. The aim of this study was to assess the mediating effects of depressive symptoms, social anxiety, self-esteem, and intimate disclosure in peer relationships in the relation between interpersonal schizotypy and suicide ideation or lifetime suicide attempts. This aim was tested in 590 young adults using a nonparametric bootstrapping procedure. After inclusion of the mediators, interpersonal schizotypy was no longer directly associated with either suicide ideation or lifetime suicide attempts. Depression and self-esteem mediated the relation between interpersonal schizotypy and suicide ideation. No variables mediated the relation between interpersonal schizotypy and lifetime suicide attempts, and there were no significant direct relations when mediators were included. Schizotypy appears to be a distal risk factor for suicidal behavior; assessing depressive symptoms and self-esteem may provide more proximal information about suicide risk, and may be targets for mitigating suicide risk in individuals with schizotypy. Published by Elsevier Ireland Ltd.

  5. Analysis of DR4 haplotypes in insulin dependent diabetes (IDD)

    International Nuclear Information System (INIS)

    Monos, D.S.; Radka, S.F.; Zmijewski, C.M.; Kamoun, M.

    1986-01-01

    Population studies indicate that HLA-DR4 is implicated in the susceptibility of IDD. However, biochemical characterization of the serologically defined DR4 haplotype from normal individuals revealed five DR4 and three DQW3 molecular forms. Hence, in this study, they investigated the heterogeneity of the DR4 haplotype, using B-lymphoblastoid cell lines (B-LCL) generated from patients with IDD and seropositive for DR4. Class II molecules, metabolically labeled with 35 S-methionine, were immunoprecipitated with monoclonal antibodies specific for DR(L243), DQ(N297), DQW3(IVD12) or DR and DQ(SG465) and analyzed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The isoelectrofocusing (IEF) conditions employed in this study allow representation only of the DR4 haplotype from either DR3/4 or DR4/4 cell lines. The analysis of six different DR4 haplotypes from seven IDD patients, revealed the presence of two DR4 β and two DQW3 β chains. Three of the six DR4 β haplotypes analyzed shared the same DR4 β chain and three others shared a different one. Additionally five of the six haplotypes shared a different one. Additionally five of the six haplotypes shared the same DQW3 β chain and only one was carrying a different one. Different combinations of the two DR4 and two DQW3 β chains constitute three distinct patterns of DR4 haplotypes. These results suggest the prevalence of a DQW3 β chain in the small sample of IDD patients studied. Studies of a large number of patients should clarify whether IDD is associated with unique variants of DR4 or DQW3 β chains

  6. Aerobic exercise reduces biomarkers related to cardiovascular risk among cleaners

    DEFF Research Database (Denmark)

    Korshøj, Mette; Ravn, Marie Højbjerg; Holtermann, Andreas

    2016-01-01

    PURPOSE: Blue-collar workers have an increased risk of cardiovascular disease. Accordingly, elevated levels of biomarkers related to risk of cardiovascular disease, such as high-sensitive C-reactive protein, have been observed among blue-collar workers. The objective was to examine whether...... an aerobic exercise worksite intervention changes the level of inflammation biomarkers among cleaners. METHODS: The design was a cluster-randomized controlled trial with 4-month worksite intervention. Before the 116 cleaners aged 18-65 years were randomized, they signed an informed consent form...

  7. MHC Class II haplotypes of Colombian Amerindian tribes

    Science.gov (United States)

    Yunis, Juan J.; Yunis, Edmond J.; Yunis, Emilio

    2013-01-01

    We analyzed 1041 individuals belonging to 17 Amerindian tribes of Colombia, Chimila, Bari and Tunebo (Chibcha linguistic family), Embera, Waunana (Choco linguistic family), Puinave and Nukak (Maku-Puinave linguistic families), Cubeo, Guanano, Tucano, Desano and Piratapuyo (Tukano linguistic family), Guahibo and Guayabero (Guayabero Linguistic Family), Curripaco and Piapoco (Arawak linguistic family) and Yucpa (Karib linguistic family). for MHC class II haplotypes (HLA-DRB1, DQA1, DQB1). Approximately 90% of the MHC class II haplotypes found among these tribes are haplotypes frequently encountered in other Amerindian tribes. Nonetheless, striking differences were observed among Chibcha and non-Chibcha speaking tribes. The DRB1*04:04, DRB1*04:11, DRB1*09:01 carrying haplotypes were frequently found among non-Chibcha speaking tribes, while the DRB1*04:07 haplotype showed significant frequencies among Chibcha speaking tribes, and only marginal frequencies among non-Chibcha speaking tribes. Our results suggest that the differences in MHC class II haplotype frequency found among Chibcha and non-Chibcha speaking tribes could be due to genetic differentiation in Mesoamerica of the ancestral Amerindian population into Chibcha and non-Chibcha speaking populations before they entered into South America. PMID:23885196

  8. Relative Risk Appraisal, the September 11 Attacks, and Terrorism-Related Fears

    Science.gov (United States)

    Marshall, Randall D.; Bryant, Richard A.; Amsel, Lawrence; Suh, Eun Jung; Cook, Joan M.; Neria, Yuval

    2013-01-01

    There are now replicated findings that posttraumatic stress disorder (PTSD) symptoms related to the September 11, 2001, attacks occurred in large numbers of persons who did not fit the traditional definition of exposure to a traumatic event. These data are not explained by traditional epidemiologic “bull’s eye” disaster models, which assume the psychological effects are narrowly, geographically circumscribed, or by existing models of PTSD onset. In this article, the authors develop a researchable model to explain these and other terrorism-related phenomena by synthesizing research and concepts from the cognitive science, risk appraisal, traumatic stress, and anxiety disorders literatures. They propose the new term relative risk appraisal to capture the psychological function that is the missing link between the event and subjective response in these and other terrorism-related studies to date. Relative risk appraisal highlights the core notion from cognitive science that human perception is an active, multidimensional process, such that for unpredictable societal threats, proximity to the event is only one of several factors that influence behavioral responses. Addressing distortions in relative risk appraisal effectively could reduce individual and societal vulnerability to a wide range of adverse economic and ethnopolitical consequences to terrorist attacks. The authors present ways in which these concepts and related techniques can be helpful in treating persons with September 11– or terrorism-related distress or psychopathology. PMID:17516775

  9. Strategies for haplotype-based association mapping in complex pedigreed populations

    DEFF Research Database (Denmark)

    Boleckova, J; Christensen, Ole Fredslund; Sørensen, Peter

    2012-01-01

    In association mapping, haplotype-based methods are generally regarded to provide higher power and increased precision than methods based on single markers. For haplotype-based association mapping most studies use a fixed haplotype effect in the model. However, an increase in haplotype length inc...

  10. MicroRNA Related Polymorphisms and Breast Cancer Risk

    DEFF Research Database (Denmark)

    Khan, Sofia; Greco, Dario; Michailidou, Kyriaki

    2014-01-01

    Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer....... We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41......,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated...

  11. Risk Factors and Biomarkers of Age-Related Macular Degeneration

    Science.gov (United States)

    Lambert, Nathan G.; Singh, Malkit K.; ElShelmani, Hanan; Mansergh, Fiona C.; Wride, Michael A.; Padilla, Maximilian; Keegan, David; Hogg, Ruth E.; Ambati, Balamurali K.

    2016-01-01

    A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings. PMID:27156982

  12. Building-related risk factors and work-related lower respiratory symptoms in 80 office buildings

    Energy Technology Data Exchange (ETDEWEB)

    Mendell, M.J.; Naco, G.M.; Wilcox, T.G.; Sieber, W.K.

    2002-01-01

    We assessed building-related risk factors for lower respiratory symptoms in office workers. The National Institute for Occupational Safety and Health in 1993 collected data during indoor environmental health investigations of workplaces. We used multivariate logistic regression analyses to assess relationships between lower respiratory symptoms in office workers and risk factors plausibly related to microbiologic contamination. Among 2,435 occupants in 80 office buildings, frequent, work-related multiple lower respiratory symptoms were strongly associated, in multivariate models, with two risk factors for microbiologic contamination: poor pan drainage under cooling coils and debris in outside air intake. Associations tended to be stronger among those with a history of physician-diagnosed asthma. These findings suggest that adverse lower respiratory health effects from indoor work environments, although unusual, may occur in relation to poorly designed or maintained ventilation systems, particularly among previously diagnosed asthmatics. These findings require confirmation in more representative buildings.

  13. Building-related risk factors and work-related lower respiratory symptoms in 80 office buildings

    International Nuclear Information System (INIS)

    Mendell, M.J.; Naco, G.M.; Wilcox, T.G.; Sieber, W.K.

    2002-01-01

    We assessed building-related risk factors for lower respiratory symptoms in office workers. The National Institute for Occupational Safety and Health in 1993 collected data during indoor environmental health investigations of workplaces. We used multivariate logistic regression analyses to assess relationships between lower respiratory symptoms in office workers and risk factors plausibly related to microbiologic contamination. Among 2,435 occupants in 80 office buildings, frequent, work-related multiple lower respiratory symptoms were strongly associated, in multivariate models, with two risk factors for microbiologic contamination: poor pan drainage under cooling coils and debris in outside air intake. Associations tended to be stronger among those with a history of physician-diagnosed asthma. These findings suggest that adverse lower respiratory health effects from indoor work environments, although unusual, may occur in relation to poorly designed or maintained ventilation systems, particularly among previously diagnosed asthmatics. These findings require confirmation in more representative buildings

  14. [Identification of risk factors in relatives of type-2 diabetics].

    Science.gov (United States)

    Cuevas-Alvarez, Norma Angélica; Vela-Otero, Yolanda; Carrada-Brav, Teodoro

    2006-01-01

    To identify risk factors and warning signs in a sample of first-degree relatives of type-2 diabetics at the Family Medicine Unit 2 of the General Hospital in Irapuato, Guanajuato, Mexico. In a non-probabilistic sample of 360 relatives, a 14-item questionnaire was applied to measure abdominal perimeter and body mass index (obesity and overweight), eating habits, addictions and sedentarism. The questionnaire was made by general consent of experts, by applying Cronbach's alpha reliability coefficient. Specific rates of prevalence by sex and age groups were estimated. 233 (65%) relatives were females. As part of their family history background, arterial hypertension was recorded in 263 (73%) and acute myocardial infarction in 97 (27%). Among the dangerous food for health consumed by the relatives of diabetics are cola drinks in 94.7%, red meat in 83%, candies in 74.7% and chips in 65.8%; only half of them consumed fresh fruits and vegetables; a quarter of them ate prickly pears or whole wheat bread. There were 163 (45.3%) persons with high-risk abdominal perimeter, and sedentarism was present in 267 (74.2%). However, obesity was 3 times more frequent in females, but excessive drinking or smoking habits were 7 times more prevailing in males. A high-risk behavior was demonstrated among relativies of diabetic patients. Therefore, a public-health educational program is required to modify risky habits. A change towards prevention rather than cure is much needed in health staff.

  15. AIDS Risk Perception and its related factors in Women with High-Risk Behaviors in Iran

    Directory of Open Access Journals (Sweden)

    Mahin Tafazoli

    2016-02-01

    Full Text Available Background & aim: AIDS is one of the major public health challenges all over the world. Perceived risk is a significant predictor of high-risk behaviors related to AIDS. Women constitute more than half of the HIV patients, and the rate of female sex workers with AIDS is more than the rest of female population. Therefore, the present study aimed to evaluate AIDS risk perception and its related factors in females with high-risk behaviors in Mashhad, Iran. Methods:This descriptive study was performed on 58 women who were arrested on prostitution charges and imprisoned in Mashhad Vakil Abad Prison in 2013. The data were collected using self-designed questionnaires assessing knowledge regarding AIDS as well as sexual activities and also perceived risk of HIV questionnaire. One-way ANOVA, independent samples t-test, linear regression, and Chi-square tests were run, using SPSS version 16. Results: The mean score of HIV risk perception was 18.43±5.92, which was average. There was a significant relationship between the mean score of perceived risk of HIV and knowledge regarding AIDS (P=0.005, alcohol consumption (P=0.04, history of addiction (P=0.008, using contraceptive methods (P=0.01, condom use during intercourse (P=0.02, voluntary HIV testing (P=0.001, and follow-up of HIV test (P=0.009. Conclusion:The findings of the present study revealed that knowledge, alcohol consumption, history of addiction, contraceptive methods, the rate of condom use during intercourse, as well as voluntary HIV testing and follow-up were associated with perceived risk of HIV infection. Therefore, taking the necessary steps towards health promotion through appropriate training and interventional approaches seems to be mandatory for reducing high-risk behaviors in populations with low risk perception.

  16. Risk factors of age-related macular degeneration in Argentina

    Directory of Open Access Journals (Sweden)

    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  17. Risk Estimates and Risk Factors Related to Psychiatric Inpatient Suicide—An Overview

    Directory of Open Access Journals (Sweden)

    Trine Madsen

    2017-03-01

    Full Text Available People with mental illness have an increased risk of suicide. The aim of this paper is to provide an overview of suicide risk estimates among psychiatric inpatients based on the body of evidence found in scientific peer-reviewed literature; primarily focusing on the relative risks, rates, time trends, and socio-demographic and clinical risk factors of suicide in psychiatric inpatients. Psychiatric inpatients have a very high risk of suicide relative to the background population, but it remains challenging for clinicians to identify those patients that are most likely to die from suicide during admission. Most studies are based on low power, thus compromising quality and generalisability. The few studies with sufficient statistical power mainly identified non-modifiable risk predictors such as male gender, diagnosis, or recent deliberate self-harm. Also, the predictive value of these predictors is low. It would be of great benefit if future studies would be based on large samples while focusing on modifiable predictors over the course of an admission, such as hopelessness, depressive symptoms, and family/social situations. This would improve our chances of developing better risk assessment tools.

  18. Differentiation analysis for estimating individual ancestry from the Tibetan Plateau by an archaic altitude adaptation EPAS1 haplotype among East Asian populations.

    Science.gov (United States)

    Jiang, Li; Peng, Jianxiong; Huang, Meisha; Liu, Jing; Wang, Ling; Ma, Quan; Zhao, Hui; Yang, Xin; Ji, Anquan; Li, Caixia

    2018-02-10

    Tibetans have adapted to the extreme environment of high altitude for hundreds of generations. A highly differentiated 5-SNP (Single Nucleotide Polymorphism) haplotype motif (AGGAA) on a hypoxic pathway gene, EPAS1, is observed in Tibetans and lowlanders. To evaluate the potential usage of the 5-SNP haplotype in ancestry inference for Tibetan or Tibetan-related populations, we analyzed this haplotype in 1053 individuals of 12 Chinese populations residing on the Tibetan Plateau, peripheral regions of Tibet, and plain regions. These data were integrated with the genotypes from the 1000 Genome populations and populations in a previously reported paper for population structure analyses. We found that populations representing highland and lowland groups have different dominant ancestry components. The core Denisovan haplotype (AGGAA) was observed at a frequency of 72.32% in the Tibetan Plateau, with a frequency range from 9.48 to 21.05% in the peripheral regions and Tibetan Plateau carried the archaic haplotype, while < 5% of the Chinese Han people carried the haplotype. Our findings indicate that the 5-SNP haplotype has a special distribution pattern in populations of Tibet and peripheral regions and could be integrated into AISNP (Ancestry Informative Single Nucleotide Polymorphism) panels to enhance ancestry resolution.

  19. Relation of Cardiometabolic Risk Factors between Parents and Children.

    Science.gov (United States)

    Halvorsen, Tanya; Moran, Antoinette; Jacobs, David R; Steffen, Lyn M; Sinaiko, Alan R; Zhou, Xia; Steinberger, Julia

    2015-11-01

    To explore the relations of parent-child cardiometabolic risk factors and assess the influence of adiposity on these associations. Associations of adiposity, blood pressure (BP), lipids, fasting insulin and glucose, and a risk factor cluster score (CS) were evaluated in a cross-sectional study of 179 parents and their children (6-18 years, N = 255). Insulin resistance was assessed by euglycemic clamp in parents and children aged 10 years or older. Metabolic syndrome in parents was defined by National Cholesterol Education Program's Adult Treatment Panel III criteria. CSs of the risk factors were created based on age-specific z-scores. Analyses included Pearson correlation and linear regression, adjusted for parent and child age, sex, race, and body mass index (BMI), accounting for within-family correlation. We found positive parent-child correlations for measures of adiposity (BMI, BMI percentile, waist, subcutaneous fat, and visceral fat; r = 0.22-0.34, all P ≤ .003), systolic BP (r = 0.20, P = .002), total cholesterol (r = 0.39, P parent-child correlations, except systolic BP, remained significant. Although adiposity is strongly correlated between parents and children, many cardiometabolic risk factors correlate independent of parent and child BMI. Adverse parental cardiometabolic profiles may identify at-risk children independent of the child's adiposity status. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Analysis of related risk factors for pancreatic fistula after pancreaticoduodenectomy

    Directory of Open Access Journals (Sweden)

    Qi-Song Yu

    2016-08-01

    Full Text Available Objective: To explore the related risk factors for pancreatic fistula after pancreaticoduodenectomy to provide a theoretical evidence for effectively preventing the occurrence of pancreatic fistula. Methods: A total of 100 patients who were admitted in our hospital from January, 2012 to January, 2015 and had performed pancreaticoduodenectomy were included in the study. The related risk factors for developing pancreatic fistula were collected for single factor and Logistic multi-factor analysis. Results: Among the included patients, 16 had pancreatic fistula, and the total occurrence rate was 16% (16/100. The single-factor analysis showed that the upper abdominal operation history, preoperative bilirubin, pancreatic texture, pancreatic duct diameter, intraoperative amount of bleeding, postoperative hemoglobin, and application of somatostatin after operation were the risk factors for developing pancreatic fistula (P<0.05. The multi-factor analysis showed that the upper abdominal operation history, the soft pancreatic texture, small pancreatic duct diameter, and low postoperative hemoglobin were the dependent risk factors for developing pancreatic fistula (OR=4.162, 6.104, 5.613, 4.034, P<0.05. Conclusions: The occurrence of pancreatic fistula after pancreaticoduodenectomy is closely associated with the upper abdominal operation history, the soft pancreatic texture, small pancreatic duct diameter, and low postoperative hemoglobin; therefore, effective measures should be taken to reduce the occurrence of pancreatic fistula according to the patients’ own conditions.

  1. Young people's perspectives on health-related risks

    Directory of Open Access Journals (Sweden)

    Grace Elisabeth Spencer

    2008-07-01

    Full Text Available Drawing upon current socio-cultural understandings of risk, this study highlights the disjunction between the expert risk discourses that permeate official public health policy and practice, and young people’s own perspectives on health and risk. Data were collected from young people aged 14-16 years through the use of group and individual interviews in a school and community youth centre setting. Findings from this study question the saliency of expert-defined health-related risks to young people’s everyday lives. Young people in this study saw health as closely linked to ‘being happy’. Friendships and a sense of personal achievement were particularly important to participants’ health and well-being. When accounting for their participation in health-related practices identified as ‘risky’ in government policy – such as smoking, alcohol and substance use – young people emphasised the levels of pressure they experienced. Sources of pressure included arguments and bullying, school work, and negative stereotypes of young people in general. These areas indicated young people’s concerns that reach beyond the official prescriptions permeating current health policy.

  2. Increased relative risk of myelodysplastic syndrome in atomic bomb survivors

    International Nuclear Information System (INIS)

    Oda, Kenji; Kimura, Akiro; Matsuo, Tatsuki; Tomonaga, Masao; Kodama, Kazunori; Mabuchi, Kiyohiko

    1998-01-01

    It was investigated what blood disorders except leukemia increased the relative risk with dose dependency in atomic bomb survivors. Subjects were 217 patients of atomic bomb survivors in Hiroshima and Nagasaki, who had blood disorders except leukemia and died between 1950 and 1990. Their medical records were analyzed and their diagnoses were reevaluated. Sixteen cases were diagnosed as the aplastic anemia and 12 as the myelodysplastic syndrome (MDS). In the aplastic anemia, there was no correlation between the exposure dose and the mortality. In MDS, the excess relative risk (ERR)/bone marrow exposure dose of 1 Sv was very high (13.0). These results supports the hypothesis that MDS would be broken out by the clonal abnormality of the hematopoietic stem cell and radiation exposure could cause the appearance of the abnormal stem cell clone. (K.H.)

  3. Increased relative risk of myelodysplastic syndrome in atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Oda, Kenji [Hiroshima City Hospital (Japan); Kimura, Akiro; Matsuo, Tatsuki; Tomonaga, Masao; Kodama, Kazunori; Mabuchi, Kiyohiko

    1998-12-01

    It was investigated what blood disorders except leukemia increased the relative risk with dose dependency in atomic bomb survivors. Subjects were 217 patients of atomic bomb survivors in Hiroshima and Nagasaki, who had blood disorders except leukemia and died between 1950 and 1990. Their medical records were analyzed and their diagnoses were reevaluated. Sixteen cases were diagnosed as the aplastic anemia and 12 as the myelodysplastic syndrome (MDS). In the aplastic anemia, there was no correlation between the exposure dose and the mortality. In MDS, the excess relative risk (ERR)/bone marrow exposure dose of 1 Sv was very high (13.0). These results supports the hypothesis that MDS would be broken out by the clonal abnormality of the hematopoietic stem cell and radiation exposure could cause the appearance of the abnormal stem cell clone. (K.H.)

  4. Update on procedure-related risks for prenatal diagnosis techniques

    DEFF Research Database (Denmark)

    Tabor, Ann; Alfirevic, Zarko

    2010-01-01

    Introduction: As a consequence of the introduction of effective screening methods, the number of invasive prenatal diagnostic procedures is steadily declining. The aim of this review is to summarize the risks related to these procedures. Material and Methods: Review of the literature. Results: Data...... from randomised controlled trials as well as from systematic reviews and a large national registry study are consistent with a procedure-related miscarriage rate of 0.5-1.0% for amniocentesis as well as for chorionic villus sampling (CVS). In single-center studies performance may be remarkably good due...... not be performed before 15 + 0 weeks' gestation. CVS on the other hand should not be performed before 10 weeks' gestation due to a possible increase in risk of limb reduction defects. Discussion: Experienced operators have a higher success rate and a lower complication rate. The decreasing number of prenatal...

  5. Prospect relativity: how choice options influence decision under risk.

    Science.gov (United States)

    Stewart, Neil; Chater, Nick; Stott, Henry P; Reimers, Stian

    2003-03-01

    In many theories of decision under risk (e.g., expected utility theory, rank-dependent utility theory, and prospect theory), the utility of a prospect is independent of other options in the choice set. The experiments presented here show a large effect of the available options, suggesting instead that prospects are valued relative to one another. The judged certainty equivalent for a prospect is strongly influenced by the options available. Similarly, the selection of a preferred prospect is strongly influenced by the prospects available. Alternative theories of decision under risk (e.g., the stochastic difference model, multialternative decision field theory, and range frequency theory), where prospects are valued relative to one another, can provide an account of these context effects.

  6. Influence of βS-Globin Haplotypes and Hydroxyurea on Arginase I Levels in Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    J. A. Moreira

    2016-01-01

    Full Text Available Introduction. Sickle cell disease (SCD is characterized by hemoglobin S homozygosity, leading to hemolysis and vasoocclusion. The hemolysis releases arginase I, an enzyme that decreases the bioavailability of nitric oxide, worsening the symptoms. The different SCD haplotypes are related to clinical symptoms and varied hemoglobin F (HbF concentration. The aim of this study was to evaluate the impact of the βS gene haplotypes and HbF concentration on arginase I levels in SCD patients. Methods. Fifty SCD adult patients were enrolled in the study and 20 blood donors composed the control group. Arginase I was measured by ELISA. The βS haplotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. Statistical analyses were performed with GraphPad Prism program and the significance level was p<0.05. Results. Significant increase was observed in the arginase I levels in SCD patients compared to the control group (p<0.0001. The comparison between the levels of arginase I in three haplotypes groups showed a difference between the Bantu/Bantu × Bantu/Benin groups; Bantu/Bantu × Benin/Benin, independent of HU dosage. An inverse correlation with the arginase I levels and HbF concentration was observed. Conclusion. The results support the hypothesis that arginase I is associated with HbF concentration, also measured indirectly by the association with haplotypes.

  7. Deployment-related risk factors of low back pain

    DEFF Research Database (Denmark)

    Nissen, Lars Ravnborg; Marott, Jacob Louis; Gyntelberg, Finn

    2014-01-01

    Where much is known about the consequences of spinal and low back pain (LBP) during military deployments, there is lesser knowledge of risk factors for LBP among the deployed forces. The objective of this study was to identify deployment-related exposures associated with LBP. The study was a ques...... their subordinates and involve medical personnel, especially deployed physiotherapists, by giving advice to soldiers of different military occupational specialties on how to optimize ergonomics at work....

  8. Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Im, Kate M; Kirchhoff, Tomas; Wang, Xianshu

    2011-01-01

    Three founder mutations in BRCA1 and BRCA2 contribute to the risk of hereditary breast and ovarian cancer in Ashkenazi Jews (AJ). They are observed at increased frequency in the AJ compared to other BRCA mutations in Caucasian non-Jews (CNJ). Several authors have proposed that elevated allele...... the tools of statistical genomics to examine the likelihood of long-range LD at a deleterious locus in a population that faced a genetic bottleneck. We studied the genotypes of hundreds of women from a large international consortium of BRCA1 and BRCA2 mutation carriers and found that AJ women exhibited long......-range haplotypes compared to CNJ women. More than 50% of the AJ chromosomes with the BRCA1 185delAG mutation share an identical 2.1 Mb haplotype and nearly 16% of AJ chromosomes carrying the BRCA2 6174delT mutation share a 1.4 Mb haplotype. Simulations based on the best inference of Ashkenazi population demography...

  9. Some computer simulations based on the linear relative risk model

    International Nuclear Information System (INIS)

    Gilbert, E.S.

    1991-10-01

    This report presents the results of computer simulations designed to evaluate and compare the performance of the likelihood ratio statistic and the score statistic for making inferences about the linear relative risk mode. The work was motivated by data on workers exposed to low doses of radiation, and the report includes illustration of several procedures for obtaining confidence limits for the excess relative risk coefficient based on data from three studies of nuclear workers. The computer simulations indicate that with small sample sizes and highly skewed dose distributions, asymptotic approximations to the score statistic or to the likelihood ratio statistic may not be adequate. For testing the null hypothesis that the excess relative risk is equal to zero, the asymptotic approximation to the likelihood ratio statistic was adequate, but use of the asymptotic approximation to the score statistic rejected the null hypothesis too often. Frequently the likelihood was maximized at the lower constraint, and when this occurred, the asymptotic approximations for the likelihood ratio and score statistics did not perform well in obtaining upper confidence limits. The score statistic and likelihood ratio statistics were found to perform comparably in terms of power and width of the confidence limits. It is recommended that with modest sample sizes, confidence limits be obtained using computer simulations based on the score statistic. Although nuclear worker studies are emphasized in this report, its results are relevant for any study investigating linear dose-response functions with highly skewed exposure distributions. 22 refs., 14 tabs

  10. Mitochondrial haplotypes are not associated with mice selectively bred for high voluntary wheel running.

    Science.gov (United States)

    Wone, Bernard W M; Yim, Won C; Schutz, Heidi; Meek, Thomas H; Garland, Theodore

    2018-04-04

    Mitochondrial haplotypes have been associated with human and rodent phenotypes, including nonshivering thermogenesis capacity, learning capability, and disease risk. Although the mammalian mitochondrial D-loop is highly polymorphic, D-loops in laboratory mice are identical, and variation occurs elsewhere mainly between nucleotides 9820 and 9830. Part of this region codes for the tRNA Arg gene and is associated with mitochondrial densities and number of mtDNA copies. We hypothesized that the capacity for high levels of voluntary wheel-running behavior would be associated with mitochondrial haplotype. Here, we analyzed the mtDNA polymorphic region in mice from each of four replicate lines selectively bred for 54 generations for high voluntary wheel running (HR) and from four control lines (Control) randomly bred for 54 generations. Sequencing the polymorphic region revealed a variable number of adenine repeats. Single nucleotide polymorphisms (SNPs) varied from 2 to 3 adenine insertions, resulting in three haplotypes. We found significant genetic differentiations between the HR and Control groups (F st  = 0.779, p ≤ 0.0001), as well as among the replicate lines of mice within groups (F sc  = 0.757, p ≤ 0.0001). Haplotypes, however, were not strongly associated with voluntary wheel running (revolutions run per day), nor with either body mass or litter size. This system provides a useful experimental model to dissect the physiological processes linking mitochondrial, genomic SNPs, epigenetics, or nuclear-mitochondrial cross-talk to exercise activity. Copyright © 2018. Published by Elsevier B.V.

  11. Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques.

    Science.gov (United States)

    Semler, Matthew R; Wiseman, Roger W; Karl, Julie A; Graham, Michael E; Gieger, Samantha M; O'Connor, David H

    2017-11-13

    Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to infer Mane-A and Mane-B haplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313 Mane-A, Mane-B, and Mane-I sequences that defined 86 Mane-A and 106 Mane-B MHC-I haplotypes. Pacific Biosciences technology allows us to resolve these Mane-A and Mane-B haplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease.

  12. Modelling the genetic risk in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.

  13. The DAOA/G30 locus and affective disorders: haplotype based association study in a polydiagnostic approach

    Directory of Open Access Journals (Sweden)

    Knapp Michael

    2010-07-01

    Full Text Available Abstract Background The DAOA/G30 (D-amino acid oxidase activator gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, although there is no consensus about the specific risk alleles or haplotypes across studies. Methods In a case-control sample of German descent (affective psychosis: n = 248; controls: n = 188 we examined seven single nucleotide polymorphisms (SNPs around DAOA/G30 (rs3916966, rs1935058, rs2391191, rs1935062, rs947267, rs3918342, and rs9558575 for genetic association in a polydiagnostic approach (ICD 10; Leonhard's classification. Results No single marker showed evidence of overall association with affective disorder neither in ICD10 nor Leonhard's classification. Haplotype analysis revealed no association with recurrent unipolar depression or bipolar disorder according to ICD10, within Leonhard's classification manic-depression was associated with a 3-locus haplotype (rs2391191, rs1935062, and rs3916966; P = 0.022 and monopolar depression with a 5-locus combination at the DAOA/G30 core region (P = 0.036. Conclusion Our data revealed potential evidence for partially overlapping risk haplotypes at the DAOA/G30 locus in Leonhard's affective psychoses, but do not support a common genetic contribution of the DAOA/G30 gene complex to the pathogenesis of affective disorders.

  14. Multi-hazard risk analysis related to hurricanes

    Science.gov (United States)

    Lin, Ning

    Hurricanes present major hazards to the United States. Associated with extreme winds, heavy rainfall, and storm surge, landfalling hurricanes often cause enormous structural damage to coastal regions. Hurricane damage risk assessment provides the basis for loss mitigation and related policy-making. Current hurricane risk models, however, often oversimplify the complex processes of hurricane damage. This dissertation aims to improve existing hurricane risk assessment methodology by coherently modeling the spatial-temporal processes of storm landfall, hazards, and damage. Numerical modeling technologies are used to investigate the multiplicity of hazards associated with landfalling hurricanes. The application and effectiveness of current weather forecasting technologies to predict hurricane hazards is investigated. In particular, the Weather Research and Forecasting model (WRF), with Geophysical Fluid Dynamics Laboratory (GFDL)'s hurricane initialization scheme, is applied to the simulation of the wind and rainfall environment during hurricane landfall. The WRF model is further coupled with the Advanced Circulation (AD-CIRC) model to simulate storm surge in coastal regions. A case study examines the multiple hazards associated with Hurricane Isabel (2003). Also, a risk assessment methodology is developed to estimate the probability distribution of hurricane storm surge heights along the coast, particularly for data-scarce regions, such as New York City. This methodology makes use of relatively simple models, specifically a statistical/deterministic hurricane model and the Sea, Lake and Overland Surges from Hurricanes (SLOSH) model, to simulate large numbers of synthetic surge events, and conducts statistical analysis. The estimation of hurricane landfall probability and hazards are combined with structural vulnerability models to estimate hurricane damage risk. Wind-induced damage mechanisms are extensively studied. An innovative windborne debris risk model is

  15. Effects of the number of markers per haplotype and clustering of haplotypes on the accuracy of QTL mapping and prediction of genomic breeding values

    NARCIS (Netherlands)

    Calus, M.P.L.; Meuwissen, T.H.E.; Windig, J.J.; Knol, E.F.; Schrooten, C.; Vereijken, A.L.J.; Veerkamp, R.F.

    2009-01-01

    The aim of this paper was to compare the effect of haplotype definition on the precision of QTL-mapping and on the accuracy of predicted genomic breeding values. In a multiple QTL model using identity-by-descent (IBD) probabilities between haplotypes, various haplotype definitions were tested i.e.

  16. Relative radiological risks derived from different TENORM wastes in Malaysia.

    Science.gov (United States)

    Ismail, B; Teng, I L; Muhammad Samudi, Y

    2011-11-01

    In Malaysia technologically enhanced naturally occurring radioactive materials (TENORM) wastes are mainly the product of the oil and gas industry and mineral processing. Among these TENORM wastes are tin tailing, tin slag, gypsum and oil sludge. Mineral processing and oil and gas industries produce large volume of TENORM wastes that has become a radiological concern to the authorities. A study was carried out to assess the radiological risk related to workers working at these disposal sites and landfills as well as to the members of the public should these areas be developed for future land use. Radiological risk was assessed based on the magnitude of radiation hazard, effective dose rates and excess cancer risks. Effective dose rates and excess cancer risks were estimated using RESRAD 6.4 computer code. All data on the activity concentrations of NORM in wastes and sludges used in this study were obtained from the Atomic Energy Licensing Board, Malaysia, and they were collected over a period of between 5 and 10 y. Results obtained showed that there was a wide range in the total activity concentrations (TAC) of nuclides in the TENORM wastes. With the exception of tin slag and tin tailing-based TENORM wastes, all other TENORM wastes have TAC values comparable to that of Malaysia's soil. Occupational Effective Dose Rates estimated in all landfill areas were lower than the 20 mSv y(-1) permissible dose limit. The average Excess Cancer Risk Coefficient was estimated to be 2.77×10(-3) risk per mSv. The effective dose rates for residents living on gypsum and oil sludge-based TENORM wastes landfills were estimated to be lower than the permissible dose limit for members of the public, and was also comparable to that of the average Malaysia's ordinary soils. The average excess cancer risk coefficient was estimated to be 3.19×10(-3) risk per mSv. Results obtained suggest that gypsum and oil sludge-based TENORM wastes should be exempted from any radiological regulatory

  17. Relative radiological risks derived from different TENORM wastes in Malaysia

    International Nuclear Information System (INIS)

    Ismail, B.; Teng, I. L.; Muhammad samudi, Y.

    2011-01-01

    In Malaysia technologically enhanced naturally occurring radioactive materials (TENORM) wastes are mainly the product of the oil and gas industry and mineral processing. Among these TENORM wastes are tin tailing, tin slag, gypsum and oil sludge. Mineral processing and oil and gas industries produce large volume of TENORM wastes that has become a radiological concern to the authorities. A study was carried out to assess the radiological risk related to workers working at these disposal sites and landfills as well as to the members of the public should these areas be developed for future land use. Radiological risk was assessed based on the magnitude of radiation hazard, effective dose rates and excess cancer risks. Effective dose rates and excess cancer risks were estimated using RESRAD 6.4 computer code. All data on the activity concentrations of NORM in wastes and sludges used in this study were obtained from the Atomic Energy Licensing Board (Malaysia), and they were collected over a period of between 5 and 10 y. Results obtained showed that there was a wide range in the total activity concentrations (TAC) of nuclides in the TENORM wastes. With the exception of tin slag and tin tailing-based TENORM wastes, all other TENORM wastes have TAC values comparable to that of Malaysia's soil. Occupational Effective Dose Rates estimated in all landfill areas were lower than the 20 mSv y -1 permissible dose limit. The average Excess Cancer Risk Coefficient was estimated to be 2.77 x 10 -3 risk per mSv. The effective dose rates for residents living on gypsum and oil sludge-based TENORM wastes landfills were estimated to be lower than the permissible dose limit for members of the public, and was also comparable to that of the average Malaysia's ordinary soils. The average excess cancer risk coefficient was estimated to be 3.19 x 10 -3 risk per mSv. Results obtained suggest that gypsum and oil sludge-based TENORM wastes should be exempted from any radiological regulatory

  18. PTCH1 gene haplotype association with basal cell carcinoma after transplantation.

    Science.gov (United States)

    Begnini, A; Tessari, G; Turco, A; Malerba, G; Naldi, L; Gotti, E; Boschiero, L; Forni, A; Rugiu, C; Piaserico, S; Fortina, A B; Brunello, A; Cascone, C; Girolomoni, G; Gomez Lira, M

    2010-08-01

    Basal cell carcinoma (BCC) is 10 times more frequent in organ transplant recipients (OTRs) than in the general population. Factors in OTRs conferring increased susceptibility to BCC include ultraviolet radiation exposure, immunosuppression, viral infections such as human papillomavirus, phototype and genetic predisposition. The PTCH1 gene is a negative regulator of the hedgehog pathway, that provides mitogenic signals to basal cells in skin. PTCH1 gene mutations cause naevoid BCC syndrome, and contribute to the development of sporadic BCC and other types of cancers. Associations have been reported between PTCH1 polymorphisms and BCC susceptibility in nontransplanted individuals. To search for novel common polymorphisms in the proximal 5' regulatory region upstream of PTCH1 gene exon 1B, and to investigate the possible association of PTCH1 polymorphisms and haplotypes with BCC risk after organ transplantation. Three PTCH1 single nucleotide polymorphisms (rs2297086, rs2066836 and rs357564) were analysed by restriction fragment length polymorphism analysis in 161 northern Italian OTRs (56 BCC cases and 105 controls). Two regions of the PTCH1 gene promoter were screened by heteroduplex analysis in 30 cases and 30 controls. Single locus analysis showed no significant association. Haplotype T(1686)-T(3944) appeared to confer a significantly higher risk for BCC development (odds ratio 2.98, 95% confidence interval 2.55-3.48; P = 0.001). Two novel rare polymorphisms were identified at positions 176 and 179 of the 5'UTR. Two novel alleles of the -4 (CGG)(n) microsatellite were identified. No association of this microsatellite with BCC was observed. Haplotypes containing T(1686)-T(3944) alleles were shown to be associated with an increased BCC risk in our study population. These data appear to be of great interest for further investigations in a larger group of transplant individuals. Our results do not support the hypothesis that common polymorphisms in the proximal 5

  19. Associations of Polymorphisms in MTHFR Gene with the Risk of Age-Related Cataract in Chinese Han Population: A Genotype-Phenotype Analysis.

    Directory of Open Access Journals (Sweden)

    Xue-bin Wang

    Full Text Available Homocysteine (Hcy is a potential risk factor for age-related cataract (ARC. Methylenetetrahydrofolate reductase (MTHFR is the key enzyme for Hcy metabolism, and variants of MTHFR may affect MTHFR enzyme activity. This study mainly evaluated the associations between variants in MTHFR gene, plasma MTHFR enzyme activity, total Hcy (tHcy levels and ARC risk in Chinese population. Four single nucleotide polymorphisms (SNPs in MTHFR gene were genotyped using the high-resolution melting (HRM method in 502 ARC patients (mean age, 70.2 [SD, 9.0], 46.0% male and 890 healthy controls (mean age, 67.1 [SD, 11.1], 47.6% male. The plasma MTHFR activity, folic acid (FA, vitamins B12 and B6 levels were detected by enzyme-linked immunosorbent assays (ELISA. The plasma tHcy levels were measured by an automated enzymatic assay. After the Bonferroni correction, the minor allele T of SNP rs1801133 showed a significant association with an increased risk of overall ARC (OR = 1.26, P = 0.003. Consistent association was also found between SNP rs1801133 and cortical ARC risk (OR = 1.44, P = 0.003. Haplotype analyses revealed an adverse effect of the haplotype "C-A-T-C" (alleles in order of SNPs rs3737967, rs1801131, rs1801133 and rs9651118 on ARC risk (OR = 1.55, P = 0.003. Moreover, in a joint analysis of SNPs rs9651118 and rs1801133, subjects with two unfavorable genotypes had a 1.76-fold increased risk of ARC compared with the reference group, and a statistically significant dose-response trend (Ptrend = 0.001 was also observed. Further, in healthy controls and patients with cortical ARC, the allele T of SNP rs1801133 and the increasing number of unfavorable genotypes were significantly correlated with decreased MTHFR activity as well as increased tHcy levels. However, there was no significant association between FA, vitamins B12, B6 levels and MTHFR variants. Our data indicated that variants in MTHFR gene might individually and jointly influence susceptibility to ARC

  20. Association of ATG16L1 gene haplotype with inflammatory bowel disease in Indians.

    Directory of Open Access Journals (Sweden)

    Srinivasan Pugazhendhi

    Full Text Available Inflammatory bowel disease (IBD is characterized by multigenic inheritance. Defects in autophagy related genes are considered to show genetic heterogeneity between populations. We evaluated the association of several single nucleotide polymorphisms (SNPs in the autophagy related 16 like 1 (ATG16L1 gene with IBD in Indians. The ATG16L1 gene was genotyped for ten different SNPs using DNA extracted from peripheral blood of 234 patients with Crohn's disease (CD, 249 patients with ulcerative colitis (UC and 393 healthy controls The SNPs rs2241880, rs4663396, rs3792106, rs10210302, rs3792109, rs2241877, rs6737398, rs11682898, rs4663402 and rs4663421 were genotyped using the Sequenom MassArray platform. PLINK was used for the association analysis and pairwise linkage disequilibrium (LD values. Haplotype analysis was done using Haploview. All SNPs were in Hardy Weinberg equilibrium in cases and controls. The G allele at rs6737398 exhibited a protective association with both CD and UC. The T allele at rs4663402 and C allele at rs4663421 were positively associated with CD and UC. The T allele at rs2241877 exhibited protective association with UC only. The AA genotype at rs4663402 and the GG genotype at rs4663421 were protectively associated with both CD and UC. Haplotype analysis revealed that all the SNPs in tight LD (D' = 0.76-1.0 and organized in a single haplotype block. Haplotype D was positively associated with IBD (P = 5.8 x 10-6 for CD and 0.002 for UC. SNPs in ATG16L1 were associated with IBD in Indian patients. The relevance to management of individual patients requires further study.

  1. A new mathematical modeling for pure parsimony haplotyping problem.

    Science.gov (United States)

    Feizabadi, R; Bagherian, M; Vaziri, H R; Salahi, M

    2016-11-01

    Pure parsimony haplotyping (PPH) problem is important in bioinformatics because rational haplotyping inference plays important roles in analysis of genetic data, mapping complex genetic diseases such as Alzheimer's disease, heart disorders and etc. Haplotypes and genotypes are m-length sequences. Although several integer programing models have already been presented for PPH problem, its NP-hardness characteristic resulted in ineffectiveness of those models facing the real instances especially instances with many heterozygous sites. In this paper, we assign a corresponding number to each haplotype and genotype and based on those numbers, we set a mixed integer programing model. Using numbers, instead of sequences, would lead to less complexity of the new model in comparison with previous models in a way that there are neither constraints nor variables corresponding to heterozygous nucleotide sites in it. Experimental results approve the efficiency of the new model in producing better solution in comparison to two state-of-the art haplotyping approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Mineralocorticoid receptor haplotype, oral contraceptives and emotional information processing.

    Science.gov (United States)

    Hamstra, D A; de Kloet, E R; van Hemert, A M; de Rijk, R H; Van der Does, A J W

    2015-02-12

    Oral contraceptives (OCs) affect mood in some women and may have more subtle effects on emotional information processing in many more users. Female carriers of mineralocorticoid receptor (MR) haplotype 2 have been shown to be more optimistic and less vulnerable to depression. To investigate the effects of oral contraceptives on emotional information processing and a possible moderating effect of MR haplotype. Cross-sectional study in 85 healthy premenopausal women of West-European descent. We found significant main effects of oral contraceptives on facial expression recognition, emotional memory and decision-making. Furthermore, carriers of MR haplotype 1 or 3 were sensitive to the impact of OCs on the recognition of sad and fearful faces and on emotional memory, whereas MR haplotype 2 carriers were not. Different compounds of OCs were included. No hormonal measures were taken. Most naturally cycling participants were assessed in the luteal phase of their menstrual cycle. Carriers of MR haplotype 2 may be less sensitive to depressogenic side-effects of OCs. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Magnitudes and frequencies of earthquakes in relation to seismic risk

    International Nuclear Information System (INIS)

    Sharma, R.D.

    1989-01-01

    Estimating the frequencies of occurrence of earthquakes of different magnitudes on a regional basis is an important task in estimating seismic risk at a construction site. Analysis of global earthquake data provides an insight into the magnitudes frequency relationship in a statistical manner. It turns out that, whereas a linear relationship between the logarithm of earthquake occurrence rates and the corresponding earthquake magnitudes fits well in the magnitude range between 5 and 7, a second degree polynomial in M, the earthquake magnitude provides a better description of the frequencies of earthquakes in a much wider range of magnitudes. It may be possible to adopt magnitude frequency relation for regions, for which adequate earthquake data are not available, to carry out seismic risk calculations. (author). 32 refs., 8 tabs., 7 figs

  4. Founder haplotype analysis of Fanconi anemia in the Korean population finds common ancestral haplotypes for a FANCG variant.

    Science.gov (United States)

    Park, Joonhong; Kim, Myungshin; Jang, Woori; Chae, Hyojin; Kim, Yonggoo; Chung, Nack-Gyun; Lee, Jae-Wook; Cho, Bin; Jeong, Dae-Chul; Park, In Yang; Park, Mi Sun

    2015-05-01

    A common ancestral haplotype is strongly suggested in the Korean and Japanese patients with Fanconi anemia (FA), because common mutations have been frequently found: c.2546delC and c.3720_3724delAAACA of FANCA; c.307+1G>C, c.1066C>T, and c.1589_1591delATA of FANCG. Our aim in this study was to investigate the origin of these common mutations of FANCA and FANCG. We genotyped 13 FA patients consisting of five FA-A patients and eight FA-G patients from the Korean FA population. Microsatellite markers used for haplotype analysis included four CA repeat markers which are closely linked with FANCA and eight CA repeat markers which are contiguous with FANCG. As a result, Korean FA-A patients carrying c.2546delC or c.3720_3724delAAACA did not share the same haplotypes. However, three unique haplotypes carrying c.307+1G>C, c.1066C > T, or c.1589_1591delATA, that consisted of eight polymorphic loci covering a flanking region were strongly associated with Korean FA-G, consistent with founder haplotypes reported previously in the Japanese FA-G population. Our finding confirmed the common ancestral haplotypes on the origins of the East Asian FA-G patients, which will improve our understanding of the molecular population genetics of FA-G. To the best of our knowledge, this is the first report on the association between disease-linked mutations and common ancestral haplotypes in the Korean FA population. © 2015 John Wiley & Sons Ltd/University College London.

  5. MicroRNA Related Polymorphisms and Breast Cancer Risk

    Science.gov (United States)

    Khan, Sofia; Greco, Dario; Michailidou, Kyriaki; Milne, Roger L.; Muranen, Taru A.; Heikkinen, Tuomas; Aaltonen, Kirsimari; Dennis, Joe; Bolla, Manjeet K.; Liu, Jianjun; Hall, Per; Irwanto, Astrid; Humphreys, Keith; Li, Jingmei; Czene, Kamila; Chang-Claude, Jenny; Hein, Rebecca; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fletcher, Olivia; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Gibson, Lorna; Aitken, Zoe; Hopper, John L.; Tsimiklis, Helen; Bui, Minh; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Apicella, Carmel; Stone, Jennifer; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A.; van der Luijt, Rob B.; Meindl, Alfons; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Lichtner, Peter; Turnbull, Clare; Rahman, Nazneen; Chanock, Stephen J.; Hunter, David J.; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Schmidt, Marjanka K.; Broeks, Annegien; Veer, Laura J. V. a. n't.; Hogervorst, Frans B.; Fasching, Peter A.; Schrauder, Michael G.; Ekici, Arif B.; Beckmann, Matthias W.; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Benitez, Javier; Zamora, Pilar M.; Perez, Jose I. A.; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Pharoah, Paul D. P.; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Brown, Judith; Couch, Fergus J.; Wang, Xianshu; Vachon, Celine; Olson, Janet E.; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Mulot, Claire; Marme, Frederick; Burwinkel, Barbara; Schneeweiss, Andreas; Sohn, Christof; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Andrulis, Irene L.; Knight, Julia A.; Tchatchou, Sandrine; Mulligan, Anna Marie; Dörk, Thilo; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Anton-Culver, Hoda; Darabi, Hatef; Eriksson, Mikael; Garcia-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; van Asperen, Christi J.; Kristensen, Vessela N.; Slager, Susan; Toland, Amanda E.; Ambrosone, Christine B.; Yannoukakos, Drakoulis; Lindblom, Annika; Margolin, Sara; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Mariani, Paolo; Hooning, Maartje J.; Martens, John W. M.; Collée, J. Margriet; Jager, Agnes; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Giles, Graham G.; McLean, Catriona; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Mannermaa, Arto; Hamann, Ute; Chenevix-Trench, Georgia; Blomqvist, Carl; Aittomäki, Kristiina; Easton, Douglas F.; Nevanlinna, Heli

    2014-01-01

    Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88–0.96), rs1052532 (OR 0.97; 95% CI: 0.95–0.99), rs10719 (OR 0.97; 95% CI: 0.94–0.99), rs4687554 (OR 0.97; 95% CI: 0.95–0.99, and rs3134615 (OR 1.03; 95% CI: 1.01–1.05) located in the 3′ UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects. PMID:25390939

  6. MicroRNA related polymorphisms and breast cancer risk.

    Science.gov (United States)

    Khan, Sofia; Greco, Dario; Michailidou, Kyriaki; Milne, Roger L; Muranen, Taru A; Heikkinen, Tuomas; Aaltonen, Kirsimari; Dennis, Joe; Bolla, Manjeet K; Liu, Jianjun; Hall, Per; Irwanto, Astrid; Humphreys, Keith; Li, Jingmei; Czene, Kamila; Chang-Claude, Jenny; Hein, Rebecca; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fletcher, Olivia; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Gibson, Lorna; Aitken, Zoe; Hopper, John L; Tsimiklis, Helen; Bui, Minh; Makalic, Enes; Schmidt, Daniel F; Southey, Melissa C; Apicella, Carmel; Stone, Jennifer; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A; van der Luijt, Rob B; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Turnbull, Clare; Rahman, Nazneen; Chanock, Stephen J; Hunter, David J; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Schmidt, Marjanka K; Broeks, Annegien; Van't Veer, Laura J; Hogervorst, Frans B; Fasching, Peter A; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Benitez, Javier; Zamora, Pilar M; Perez, Jose I A; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Pharoah, Paul D P; Dunning, Alison M; Shah, Mitul; Luben, Robert; Brown, Judith; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Olson, Janet E; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Mulot, Claire; Marme, Frederick; Burwinkel, Barbara; Schneeweiss, Andreas; Sohn, Christof; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Andrulis, Irene L; Knight, Julia A; Tchatchou, Sandrine; Mulligan, Anna Marie; Dörk, Thilo; Bogdanova, Natalia V; Antonenkova, Natalia N; Anton-Culver, Hoda; Darabi, Hatef; Eriksson, Mikael; Garcia-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; van Asperen, Christi J; Kristensen, Vessela N; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Lindblom, Annika; Margolin, Sara; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Mariani, Paolo; Hooning, Maartje J; Martens, John W M; Collée, J Margriet; Jager, Agnes; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Giles, Graham G; McLean, Catriona; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Mannermaa, Arto; Hamann, Ute; Chenevix-Trench, Georgia; Blomqvist, Carl; Aittomäki, Kristiina; Easton, Douglas F; Nevanlinna, Heli

    2014-01-01

    Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

  7. MicroRNA related polymorphisms and breast cancer risk.

    Directory of Open Access Journals (Sweden)

    Sofia Khan

    Full Text Available Genetic variations, such as single nucleotide polymorphisms (SNPs in microRNAs (miRNA or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS. Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC. Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR 0.92; 95% confidence interval (CI: 0.88-0.96, rs1052532 (OR 0.97; 95% CI: 0.95-0.99, rs10719 (OR 0.97; 95% CI: 0.94-0.99, rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05 located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

  8. Risk of Cardiovascular Morbidity and Mortality in Relation to Temperature

    Science.gov (United States)

    Mathes, Robert; Ito, Kazuhiko; Matte, Thomas

    2013-01-01

    Objective To examine the effects of temperature on cardiovascular-related (CVD) morbidity and mortality among New York City (NYC) residents. Introduction Extreme temperatures are consistently shown to have an effect on CVD-related mortality [1, 2]. A large multi-city study of mortality demonstrated a cold-day and hot-day weather effect on CVD-related deaths, with the larger impact occurring on the coldest days [3]. In contrast, the association between weather and CVD-related morbidity is less clear [4, 5]. The purpose of this study is to characterize the effect of temperature on CVD-related emergency department (ED) visits, hospitalizations, and mortality on a large, heterogeneous population. Additionally, we conducted a sensitivity analysis to determine the impact of air pollutants, specifically fine particulates (PM2.5) and ozone (O3), along with temperature, on CVD outcomes. Methods We analyzed daily weather conditions, ED visits classified as CVD-related based on chief complaint text, hospitalizations, and natural cause deaths that occurred in NYC between 2002 and 2006. ED visits were obtained from data reported daily to the city health department for syndromic surveillance. Inpatient admissions were obtained from the Statewide Planning and Research Cooperative System, a data reporting system developed by New York State. Mortality data were obtained from the NYC Office of Vital Statistics. Data for PM2.5 and O3 were obtained from all available air quality monitors within the five boroughs of NYC. To estimate risk of CVD morbidity and mortality, we used generalized linear models using a Poisson distribution to calculate relative risks (RR) and 95% confidence intervals (CI). A non-linear distributed lag was used to model mean temperature in order to allow for its effect on the same day and on subsequent days. Models were fit separately for cold season (October through March) and warm season (April through September) given season may modify the effect on CVD

  9. Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA Levels

    Directory of Open Access Journals (Sweden)

    Selma M. Soyal

    2015-01-01

    Full Text Available The genomic region ~500 kb upstream of IRS1 has been implicated in insulin resistance, type 2 diabetes, adverse lipid profile, and cardiovascular risk. To gain further insight into this chromosomal region, we typed four SNPs in a cross-sectional cohort and subjects with type 2 diabetes recruited from the same geographic region. From 16 possible haplotypes, 6 haplotypes with frequencies >0.01 were observed. We identified one haplotype that was protective against insulin resistance (determined by HOMA-IR and fasting plasma insulin levels, type 2 diabetes, an adverse lipid profile, increased C-reactive protein, and asymptomatic atherosclerotic disease (assessed by intima media thickness of the common carotid arteries. BMI and total adipose tissue mass as well as visceral and subcutaneous adipose tissue mass did not differ between the reference and protective haplotypes. In 92 subjects, we observed an association of the protective haplotype with higher skeletal muscle mRNA levels of LOC646736, which is located in the same haplotype block as the informative SNPs and is mainly expressed in skeletal muscle, but only at very low levels in liver or adipose tissues. These data suggest a role for LOC646736 in human insulin resistance and warrant further studies on the functional effects of this locus.

  10. Threshold Evaluation of Emergency Risk Communication for Health Risks Related to Hazardous Ambient Temperature.

    Science.gov (United States)

    Liu, Yang; Hoppe, Brenda O; Convertino, Matteo

    2018-04-10

    Emergency risk communication (ERC) programs that activate when the ambient temperature is expected to cross certain extreme thresholds are widely used to manage relevant public health risks. In practice, however, the effectiveness of these thresholds has rarely been examined. The goal of this study is to test if the activation criteria based on extreme temperature thresholds, both cold and heat, capture elevated health risks for all-cause and cause-specific mortality and morbidity in the Minneapolis-St. Paul Metropolitan Area. A distributed lag nonlinear model (DLNM) combined with a quasi-Poisson generalized linear model is used to derive the exposure-response functions between daily maximum heat index and mortality (1998-2014) and morbidity (emergency department visits; 2007-2014). Specific causes considered include cardiovascular, respiratory, renal diseases, and diabetes. Six extreme temperature thresholds, corresponding to 1st-3rd and 97th-99th percentiles of local exposure history, are examined. All six extreme temperature thresholds capture significantly increased relative risks for all-cause mortality and morbidity. However, the cause-specific analyses reveal heterogeneity. Extreme cold thresholds capture increased mortality and morbidity risks for cardiovascular and respiratory diseases and extreme heat thresholds for renal disease. Percentile-based extreme temperature thresholds are appropriate for initiating ERC targeting the general population. Tailoring ERC by specific causes may protect some but not all individuals with health conditions exacerbated by hazardous ambient temperature exposure. © 2018 Society for Risk Analysis.

  11. Simulating the market coefficient of relative risk aversion

    Directory of Open Access Journals (Sweden)

    Samih Antoine Azar

    2014-12-01

    Full Text Available In this paper, expected utility, defined by a Taylor series expansion around expected wealth, is maximized. The coefficient of relative risk aversion (CRRA that is commensurate with a 100% investment in the risky asset is simulated. The following parameters are varied: the riskless return, the market standard deviation, the market stock premium, and the skewness and the kurtosis of the risky return. Both the high extremes and the low extremes are considered. With these figures, the upper bound of the market CRRA is 3.021 and the lower bound is 0.466. Log utility, which corresponds to a CRRA of 1, is not excluded.

  12. Grouping preprocess for haplotype inference from SNP and CNV data

    International Nuclear Information System (INIS)

    Shindo, Hiroyuki; Chigira, Hiroshi; Nagaoka, Tomoyo; Inoue, Masato; Kamatani, Naoyuki

    2009-01-01

    The method of statistical haplotype inference is an indispensable technique in the field of medical science. The authors previously reported Hardy-Weinberg equilibrium-based haplotype inference that could manage single nucleotide polymorphism (SNP) data. We recently extended the method to cover copy number variation (CNV) data. Haplotype inference from mixed data is important because SNPs and CNVs are occasionally in linkage disequilibrium. The idea underlying the proposed method is simple, but the algorithm for it needs to be quite elaborate to reduce the calculation cost. Consequently, we have focused on the details on the algorithm in this study. Although the main advantage of the method is accuracy, in that it does not use any approximation, its main disadvantage is still the calculation cost, which is sometimes intractable for large data sets with missing values.

  13. Grouping preprocess for haplotype inference from SNP and CNV data

    Energy Technology Data Exchange (ETDEWEB)

    Shindo, Hiroyuki; Chigira, Hiroshi; Nagaoka, Tomoyo; Inoue, Masato [Department of Electrical Engineering and Bioscience, School of Advanced Science and Engineering, Waseda University, 3-4-1, Okubo, Shinjuku-ku, Tokyo 169-8555 (Japan); Kamatani, Naoyuki, E-mail: masato.inoue@eb.waseda.ac.j [Institute of Rheumatology, Tokyo Women' s Medical University, 10-22, Kawada-cho, Shinjuku-ku, Tokyo 162-0054 (Japan)

    2009-12-01

    The method of statistical haplotype inference is an indispensable technique in the field of medical science. The authors previously reported Hardy-Weinberg equilibrium-based haplotype inference that could manage single nucleotide polymorphism (SNP) data. We recently extended the method to cover copy number variation (CNV) data. Haplotype inference from mixed data is important because SNPs and CNVs are occasionally in linkage disequilibrium. The idea underlying the proposed method is simple, but the algorithm for it needs to be quite elaborate to reduce the calculation cost. Consequently, we have focused on the details on the algorithm in this study. Although the main advantage of the method is accuracy, in that it does not use any approximation, its main disadvantage is still the calculation cost, which is sometimes intractable for large data sets with missing values.

  14. A haplotype-based study of lithium responding patients with bipolar affective disorder on the Faroe Islands

    DEFF Research Database (Denmark)

    Ewald, Henrik; Wang, August G; Vang, Maria

    1999-01-01

    , the Faroese population is perhaps the most valuable European population for genetic mapping of complex disease genes. The present study searched for haplotype sharing on chromosome 18 among eight lithium responding patients with bipolar affective disorder related, on average, 6.2 generations ago, using 30 DNA...

  15. Energy use and related risk management problems in CEE countries

    International Nuclear Information System (INIS)

    Ney, R.; Michna, J.; Ekmanis, J.; Zeltins, N.; Zebergs, V.

    2008-01-01

    Nowadays, the efficiency of energy use in the Central and East-European (CEE) countries is insufficient, being much lower than in the 'Old Europe'. The problem becomes increasingly pressing due to non-stop increasing prices of energy carriers (especially of crude oil). The authors trace the development of research activities in this sphere, classifying the revealed changes in parameters of energy consumption processes in particular time intervals into deterministic, probabilistic, and fuzzy. The paper presents a thorough analysis of decision-making in the energy management at its different levels normative, strategic, and operative. Particular attention is given to the management under uncertainty conditions - i.e. to the risk management. The most wanted research directions in this area proposed by the energy and environment policy (EEP) Center specially created for CEE countries concern management under risk connected with innovations, international activities, loss of reputation, etc.. The authors consider in detail the risk management with insufficient knowledge (non-knowledge) and under chaos. Much consideration is given to the scenario management and the game theory principles as related to the sphere of energy use. (Authors)

  16. Substance-related traffic-risk behaviors among college students

    Science.gov (United States)

    Arria, Amelia M.; Caldeira, Kimberly M.; Vincent, Kathryn B.; Garnier-Dykstra, Laura M.; O’Grady, Kevin E.

    2011-01-01

    Aims Drunk driving is a major public health concern, but drugged driving has received little attention. This study examines drugged driving and riding with a drugged driver in a college student sample, in terms of prevalence, age-related trends, race/sex differences, overlap with drunk driving, and risk for alcohol and marijuana dependence. Methods Students (N=1194) ages 19 to 22 were interviewed annually for three years about past-year frequency of drugged driving, riding with a drugged/drunk driver, drunk driving, access to a car, and alcohol/drug dependence. Annual follow-up rates were excellent (88% to 91%). Repeated measures analyses were conducted using generalized estimating equations (GEE). Results One in six (17%wt) 19-year-olds with access to a car drove drugged in the past year; prevalence remained stable through age 22. Drugged driving was more prevalent among males (pdrunk (ranges between 47% and 60%). Both drugged and drunk driving were independently associated with increased risk for alcohol dependence, holding constant age, sex, and race. Drunk driving did not add to the risk for marijuana dependence in the context of drugged driving. Conclusions The prevalence of drugged driving is similar to drunk driving among college students. Both are strongly associated with underlying alcohol and drug dependence. Prevention and treatment implications are discussed. PMID:21601379

  17. Genomic identification of founding haplotypes reveals the history of the selfing species Capsella rubella.

    Directory of Open Access Journals (Sweden)

    Yaniv Brandvain

    Full Text Available The shift from outcrossing to self-fertilization is among the most common evolutionary transitions in flowering plants. Until recently, however, a genome-wide view of this transition has been obscured by both a dearth of appropriate data and the lack of appropriate population genomic methods to interpret such data. Here, we present a novel population genomic analysis detailing the origin of the selfing species, Capsella rubella, which recently split from its outcrossing sister, Capsella grandiflora. Due to the recency of the split, much of the variation within C. rubella is also found within C. grandiflora. We can therefore identify genomic regions where two C. rubella individuals have inherited the same or different segments of ancestral diversity (i.e. founding haplotypes present in C. rubella's founder(s. Based on this analysis, we show that C. rubella was founded by multiple individuals drawn from a diverse ancestral population closely related to extant C. grandiflora, that drift and selection have rapidly homogenized most of this ancestral variation since C. rubella's founding, and that little novel variation has accumulated within this time. Despite the extensive loss of ancestral variation, the approximately 25% of the genome for which two C. rubella individuals have inherited different founding haplotypes makes up roughly 90% of the genetic variation between them. To extend these findings, we develop a coalescent model that utilizes the inferred frequency of founding haplotypes and variation within founding haplotypes to estimate that C. rubella was founded by a potentially large number of individuals between 50 and 100 kya, and has subsequently experienced a twenty-fold reduction in its effective population size. As population genomic data from an increasing number of outcrossing/selfing pairs are generated, analyses like the one developed here will facilitate a fine-scaled view of the evolutionary and demographic impact of the

  18. Y chromosome haplotype diversity of domestic sheep (Ovis aries) in northern Eurasia.

    Science.gov (United States)

    Zhang, Min; Peng, Wei-Feng; Yang, Guang-Li; Lv, Feng-Hua; Liu, Ming-Jun; Li, Wen-Rong; Liu, Yong-Gang; Li, Jin-Quan; Wang, Feng; Shen, Zhi-Qiang; Zhao, Sheng-Guo; Hehua, Eer; Marzanov, Nurbiy; Murawski, Maziek; Kantanen, Juha; Li, Meng-Hua

    2014-12-01

    Variation in two SNPs and one microsatellite on the Y chromosome was analyzed in a total of 663 rams representing 59 breeds from a large geographic range in northern Eurasia. SNPA-oY1 showed the highest allele frequency (91.55%) across the breeds, whereas SNPG-oY1 was present in only 56 samples. Combined genotypes established seven haplotypes (H4, H5, H6, H7, H8, H12 and H19). H6 dominated in northern Eurasia, and H8 showed the second-highest frequency. H4, which had been earlier reported to be absent in European breeds, was detected in one European breed (Swiniarka), whereas H7, which had been previously identified to be unique to European breeds, was present in two Chinese breeds (Ninglang Black and Large-tailed Han), one Buryatian (Transbaikal Finewool) and two Russian breeds (North Caucasus Mutton-Wool and Kuibyshev). H12, which had been detected only in Turkish breeds, was also found in Chinese breeds in this work. An overall low level of haplotype diversity (median h = 0.1288) was observed across the breeds with relatively higher median values in breeds from the regions neighboring the Near Eastern domestication center of sheep. H6 is the dominant haplotype in northwestern and eastern China, in which the haplotype distribution could be explained by the historical translocations of the H4 and H8 Y chromosomes to China via the Mongol invasions followed by expansions to northwestern and eastern China. Our findings extend previous results of sheep Y chromosomal genetic variability and indicate probably recent paternal gene flows between sheep breeds from distinct major geographic regions. © 2014 Stichting International Foundation for Animal Genetics.

  19. SNP frequency, haplotype structure and linkage disequilibrium in elite maize inbred lines

    Directory of Open Access Journals (Sweden)

    Smith Oscar

    2002-10-01

    Full Text Available Abstract Background Recent studies of ancestral maize populations indicate that linkage disequilibrium tends to dissipate rapidly, sometimes within 100 bp. We set out to examine the linkage disequilibrium and diversity in maize elite inbred lines, which have been subject to population bottlenecks and intense selection by breeders. Such population events are expected to increase the amount of linkage disequilibrium, but reduce diversity. The results of this study will inform the design of genetic association studies. Results We examined the frequency and distribution of DNA polymorphisms at 18 maize genes in 36 maize inbreds, chosen to represent most of the genetic diversity in U.S. elite maize breeding pool. The frequency of nucleotide changes is high, on average one polymorphism per 31 bp in non-coding regions and 1 polymorphism per 124 bp in coding regions. Insertions and deletions are frequent in non-coding regions (1 per 85 bp, but rare in coding regions. A small number (2–8 of distinct and highly diverse haplotypes can be distinguished at all loci examined. Within genes, SNP loci comprising the haplotypes are in linkage disequilibrium with each other. Conclusions No decline of linkage disequilibrium within a few hundred base pairs was found in the elite maize germplasm. This finding, as well as the small number of haplotypes, relative to neutral expectation, is consistent with the effects of breeding-induced bottlenecks and selection on the elite germplasm pool. The genetic distance between haplotypes is large, indicative of an ancient gene pool and of possible interspecific hybridization events in maize ancestry.

  20. HLA-G Haplotypes Are Differentially Associated with Asthmatic Features

    Directory of Open Access Journals (Sweden)

    Camille Ribeyre

    2018-02-01

    Full Text Available Human leukocyte antigen (HLA-G, a HLA class Ib molecule, interacts with receptors on lymphocytes such as T cells, B cells, and natural killer cells to influence immune responses. Unlike classical HLA molecules, HLA-G expression is not found on all somatic cells, but restricted to tissue sites, including human bronchial epithelium cells (HBEC. Individual variation in HLA-G expression is linked to its genetic polymorphism and has been associated with many pathological situations such as asthma, which is characterized by epithelium abnormalities and inflammatory cell activation. Studies reported both higher and equivalent soluble HLA-G (sHLA-G expression in different cohorts of asthmatic patients. In particular, we recently described impaired local expression of HLA-G and abnormal profiles for alternatively spliced isoforms in HBEC from asthmatic patients. sHLA-G dosage is challenging because of its many levels of polymorphism (dimerization, association with β2-microglobulin, and alternative splicing, thus many clinical studies focused on HLA-G single-nucleotide polymorphisms as predictive biomarkers, but few analyzed HLA-G haplotypes. Here, we aimed to characterize HLA-G haplotypes and describe their association with asthmatic clinical features and sHLA-G peripheral expression and to describe variations in transcription factor (TF binding sites and alternative splicing sites. HLA-G haplotypes were differentially distributed in 330 healthy and 580 asthmatic individuals. Furthermore, HLA-G haplotypes were associated with asthmatic clinical features showed. However, we did not confirm an association between sHLA-G and genetic, biological, or clinical parameters. HLA-G haplotypes were phylogenetically split into distinct groups, with each group displaying particular variations in TF binding or RNA splicing sites that could reflect differential HLA-G qualitative or quantitative expression, with tissue-dependent specificities. Our results, based on a

  1. Prion gene haplotypes of U.S. cattle

    Directory of Open Access Journals (Sweden)

    Harhay Gregory P

    2006-11-01

    Full Text Available Abstract Background Bovine spongiform encephalopathy (BSE is a fatal neurological disorder characterized by abnormal deposits of a protease-resistant isoform of the prion protein. Characterizing linkage disequilibrium (LD and haplotype networks within the bovine prion gene (PRNP is important for 1 testing rare or common PRNP variation for an association with BSE and 2 interpreting any association of PRNP alleles with BSE susceptibility. The objective of this study was to identify polymorphisms and haplotypes within PRNP from the promoter region through the 3'UTR in a diverse sample of U.S. cattle genomes. Results A 25.2-kb genomic region containing PRNP was sequenced from 192 diverse U.S. beef and dairy cattle. Sequence analyses identified 388 total polymorphisms, of which 287 have not previously been reported. The polymorphism alleles define PRNP by regions of high and low LD. High LD is present between alleles in the promoter region through exon 2 (6.7 kb. PRNP alleles within the majority of intron 2, the entire coding sequence and the untranslated region of exon 3 are in low LD (18.0 kb. Two haplotype networks, one representing the region of high LD and the other the region of low LD yielded nineteen different combinations that represent haplotypes spanning PRNP. The haplotype combinations are tagged by 19 polymorphisms (htSNPS which characterize variation within and across PRNP. Conclusion The number of polymorphisms in the prion gene region of U.S. cattle is nearly four times greater than previously described. These polymorphisms define PRNP haplotypes that may influence BSE susceptibility in cattle.

  2. Energy drinks and alcohol-related risk among young adults.

    Science.gov (United States)

    Caviness, Celeste M; Anderson, Bradley J; Stein, Michael D

    2017-01-01

    Energy drink consumption, with or without concurrent alcohol use, is common among young adults. This study sought to clarify risk for negative alcohol outcomes related to the timing of energy drink use. The authors interviewed a community sample of 481 young adults, aged 18-25, who drank alcohol in the last month. Past-30-day energy drink use was operationalized as no-use, use without concurrent alcohol, and concurrent use of energy drinks with alcohol ("within a couple of hours"). Negative alcohol outcomes included past-30-day binge drinking, past-30-day alcohol use disorder, and drinking-related consequences. Just over half (50.5%) reported no use of energy drinks,18.3% reported using energy drinks without concurrent alcohol use, and 31.2% reported concurrent use of energy drinks and alcohol. Relative to those who reported concurrent use of energy drinks with alcohol, and controlling for background characteristics and frequency of alcohol consumption, those who didn't use energy drinks and those who used without concurrent alcohol use had significantly lower binge drinking, negative consequences, and rates of alcohol use disorder (P energy drink without concurrent alcohol groups on any alcohol-related measure (P > .10 for all outcomes). Concurrent energy drink and alcohol use is associated with increased risk for negative alcohol consequences in young adults. Clinicians providing care to young adults could consider asking patients about concurrent energy drink and alcohol use as a way to begin a conversation about risky alcohol consumption while addressing 2 substances commonly used by this population.

  3. Haplotype analysis and linkage disequilibrium for DGAT1

    OpenAIRE

    Strucken, Eva M.; Rahmatalla, Siham; De Koning, Dirk-Jan; Brockmann, Gudrun A.

    2010-01-01

    This study focused on haplotype effects and linkage disequilibrium (LD) for the K232A locus and the promoter VNTR in the DGAT1 gene. Analyses were carried out in three German Holstein Frisian populations (including 492, 305, and 518 animals) for milk yield, milk fat and protein yield, and milk fat and protein content. We found that effects of the promoter VNTR were not significant and explain only a small amount of the variation of the QTL on BTA14. Haplotype effects were less significant tha...

  4. Mineralocorticoid receptor haplotype, estradiol, progesterone and emotional information processing.

    Science.gov (United States)

    Hamstra, Danielle A; de Kloet, E Ronald; Quataert, Ina; Jansen, Myrthe; Van der Does, Willem

    2017-02-01

    Carriers of MR-haplotype 1 and 3 (GA/CG; rs5522 and rs2070951) are more sensitive to the influence of oral contraceptives (OC) and menstrual cycle phase on emotional information processing than MR-haplotype 2 (CA) carriers. We investigated whether this effect is associated with estradiol (E2) and/or progesterone (P4) levels. Healthy MR-genotyped premenopausal women were tested twice in a counterbalanced design. Naturally cycling (NC) women were tested in the early-follicular and mid-luteal phase and OC-users during OC-intake and in the pill-free week. At both sessions E2 and P4 were assessed in saliva. Tests included implicit and explicit positive and negative affect, attentional blink accuracy, emotional memory, emotion recognition, and risky decision-making (gambling). MR-haplotype 2 homozygotes had higher implicit happiness scores than MR-haplotype 2 heterozygotes (p=0.031) and MR-haplotype 1/3 carriers (pemotion recognition test than MR-haplotype 1/3 (p=0.001). Practice effects were observed for most measures. The pattern of correlations between information processing and P4 or E2 differed between sessions, as well as the moderating effects of the MR genotype. In the first session the MR-genotype moderated the influence of P4 on implicit anxiety (sr=-0.30; p=0.005): higher P4 was associated with reduction in implicit anxiety, but only in MR-haplotype 2 homozygotes (sr=-0.61; p=0.012). In the second session the MR-genotype moderated the influence of E2 on the recognition of facial expressions of happiness (sr=-0.21; p=0.035): only in MR-haplotype 1/3 higher E2 was correlated with happiness recognition (sr=0.29; p=0.005). In the second session higher E2 and P4 were negatively correlated with accuracy in lag2 trials of the attentional blink task (pemotional information processing. This moderating effect may depend on the novelty of the situation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Trampoline related injuries in children: risk factors and radiographic findings.

    Science.gov (United States)

    Klimek, Peter Michael; Juen, David; Stranzinger, Enno; Wolf, Rainer; Slongo, Theddy

    2013-05-01

    Backyard trampolines are immensely popular among children, but are associated with an increase of trampoline-related injuries. The aim of this study was to evaluate radiographs of children with trampoline related injuries and to determine the risk factors. Between 2003 and 2009, 286 children under the age of 16 with backyard trampoline injuries were included in the study. The number of injuries increased from 13 patients in 2003 to 86 in 2009. The median age of the 286 patients was 7 years (range: 1-15 years). Totally 140 (49%) patients were males, and 146 (51%) females. Medical records and all available diagnostic imaging were reviewed. A questionnaire was sent to the parents to evaluate the circumstances of each injury, the type of trampoline, the protection equipment and the experience of the children using the trampoline. The study was approved by the Institutional Ethics Committee of the University Hospital of Bern. The questionnaires and radiographs of the 104 patients were available for evaluation. A fracture was sustained in 51 of the 104 patients. More than 75% of all patients sustaining injuries and in 90% of patients with fractures were jumping on the trampoline with other children at the time of the accident. The most common fractures were supracondylar humeral fractures (29%) and forearm fractures (25%). Fractures of the proximal tibia occurred especially in younger children between 2-5 years of age. Children younger than 5 years old are at risk for specific proximal tibia fractures ("Trampoline Fracture"). A child jumping simultaneously with other children has a higher risk of suffering from a fracture.

  6. Adding an alcohol-related risk score to an existing categorical risk classification for older adults: sensitivity to group differences.

    Science.gov (United States)

    Wilson, Sandra R; Fink, Arlene; Verghese, Shinu; Beck, John C; Nguyen, Khue; Lavori, Philip

    2007-03-01

    To evaluate a new alcohol-related risk score for research use. Using data from a previously reported trial of a screening and education system for older adults (Computerized Alcohol-Related Problems Survey), secondary analyses were conducted comparing the ability of two different measures of risk to detect post-intervention group differences: the original categorical outcome measure and a new, finely grained quantitative risk score based on the same research-based risk factors. Three primary care group practices in southern California. Six hundred sixty-five patients aged 65 and older. A previously calculated, three-level categorical classification of alcohol-related risk and a newly developed quantitative risk score. Mean post-intervention risk scores differed between the three experimental conditions: usual care, patient report, and combined report (Ptrinary risk classification. The additional clinical value of the risk score relative to the categorical measure needs to be determined.

  7. Nuclear fuel cycle risk assessment: survey and computer compilation of risk-related literature

    International Nuclear Information System (INIS)

    Yates, K.R.; Schreiber, A.M.; Rudolph, A.W.

    1982-10-01

    The US Nuclear Regulatory Commission has initiated the Fuel Cycle Risk Assessment Program to provide risk assessment methods for assistance in the regulatory process for nuclear fuel cycle facilities other than reactors. Both the once-through cycle and plutonium recycle are being considered. A previous report generated by this program defines and describes fuel cycle facilities, or elements, considered in the program. This report, the second from the program, describes the survey and computer compilation of fuel cycle risk-related literature. Sources of available information on the design, safety, and risk associated with the defined set of fuel cycle elements were searched and documents obtained were catalogued and characterized with respect to fuel cycle elements and specific risk/safety information. Both US and foreign surveys were conducted. Battelle's computer-based BASIS information management system was used to facilitate the establishment of the literature compilation. A complete listing of the literature compilation and several useful indexes are included. Future updates of the literature compilation will be published periodically. 760 annotated citations are included

  8. Perceptions of risk from workers in high risk industries with work related musculoskeletal disorders.

    Science.gov (United States)

    Hunter, D; Silverstein, B

    2014-01-01

    Work-related musculoskeletal disorders (WMSDs) remain a major occupational health problem, despite decades of research, outreach, and intervention. The aim of this study is to promote early identification and prevention of WMSDs by developing education and outreach materials grounded in interview data collected from workers that have recently filed for workers compensation (WC) for WMSDs. We conducted semi-structured telephone interviews with WC claimants (n=66) from high risk industries identified through the use of a Prevention Index (PI) in Washington state with WMSDs of the back, shoulder, hand/wrist, or knee. Perceptions regarding the degree of exposure to WMSD risk factors, the social construction of pain, and the potential to implement injury-prevention measures varied widely. Many workers dismissed their injuries as the result of "fluke" or "freak" occurrences and framed their exposure to risk factors for WMSDs as either inevitable or "just part of the job." Workers in high-risk industries for WMSDs described their work conditions in ways that suggested: (1) a lack of awareness of the potential for developing a WMSD, (2) a view of work-related pain as normal, and/or (3) a pattern of self-blame for WMSD onset. A paradigm that either asserts the inevitability of WMSDs or dismisses potential control measures presents both a significant barrier to injury prevention efforts as well as a major opportunity for future occupational health research.

  9. Autoantibodies to IA-2beta improve diabetes risk assessment in high-risk relatives

    DEFF Research Database (Denmark)

    Achenbach, P; Bonifacio, E; Williams, A J K

    2008-01-01

    -positive participants (median age 12.1 years; 57% male), 113 developed diabetes (5 year cumulative risk 56%), and 148 were also GADA-positive and IAA-positive (4Ab-positive). IA2betaA were detected in 137 (65%) ICA/IA2A-positive participants and were associated with an increased 5 year diabetes risk (IA2beta......A-positive 65 vs 39% in IA2betaA-negative, p=0.0002). The effect was most marked in 4Ab-positive relatives (72% vs 52%, p=0.003). Metabolic testing further refined risk assessment. Among 101 4Ab-positive relatives with IA2betaA, the 5 year risk was 94% in those with a low FPIR (vs 50% in those with a normal...... FPIR, p4Ab/IA2betaA-positive participants with a low FPIR was 1.5 years. Multivariate analysis confirmed IA2betaA status, antibody number, young...

  10. Risk Management in Supply Chain using Consistent Fuzzy Preference Relations

    OpenAIRE

    Ahmad Jafarnejad; Mehran Ebrahimi; Mohammad Ali Abbaszadeh; Seyed Mehdi Abtahi

    2014-01-01

    Nowadays, supply chains are exposed to numerous risks. Thus, to success in risky business environment, it is imperative for firms to systematically manage supply chain risks. Risk management is the identification, assessment, and prioritization of supply chain risks. The purpose of this paper is to propose a comprehensive approach to risk management in supply chains. Thus, by an appropriate review of the literature, supply chain risk sources are identified in six areas. Then, a CFPR method is...

  11. Evaluation of hip fracture risk in relation to fall direction.

    Science.gov (United States)

    Nankaku, Manabu; Kanzaki, Hideto; Tsuboyama, Tadao; Nakamura, Takashi

    2005-11-01

    The purpose of this study is to evaluate hip fracture risk in relation to fall direction, and to elucidate factors that influence the impact force in falls on the hip. Eight healthy volunteers performed deliberate falls in three directions (lateral, posterolateral and posterior) on a force platform covered by a mattress of 13 cm thickness. Fall descent motions and impact postures were examined by a three-dimensional analyzer. The maximum ground force reaction, velocity of the greater trochanter at impact, and activity of quadriceps and gluteus medius were measured. In all trials of lateral and posterolateral falls, but not of posterior falls, the subjects hit their greater trochanter directly on the mattress. The impact forces were between 2,000 N and 4,000 N. Posterolateral falls showed significantly higher velocity at impact than did posterior falls. The height and the lower limb length exhibited positive correlations with the impact force in all directions of fall. In the lateral fall, there was a positive correlation between the activity of quadriceps and the impact force. In view of the impact point, force, and velocity, the posterolateral fall seemed to carry the highest risk of hip fracture.

  12. Demographic And Risk Factors Related To Military Tuberculosis

    Directory of Open Access Journals (Sweden)

    M. Rasolinejad

    2006-05-01

    Full Text Available Background and Aim: Tuberculosis is one the major health care problems in developing countries. Miliary tuberculosis is induced by blood dissemination of multiple tubercle bacilli, the paramount importance of accurate diagnosis of military tuberculosis is because of its dismal outcome if untreated and the chance of cure if diagnosis happens early in the course of the disorder. In this study we describe the demographic and risk factors related to military tuberculosis, which enables us to control and reduce the incidence of military tuberculosis. This ultimately reduces the mortality and morbidity consistent with this disorder. Materials and Methods: we conducted a retrospective case control study, which compares 28 patients with military tuberculosis and 56 patients with pulmonary tuberculosis as control. We reviewed all the patients' documents registered between years 1994-2004, after extracting raw data we analyzed them with chi-square and Fisher exact tests. Results and Conclusion: We found that HIV (P< 0.05 infection and lack of BCG vaccination (P< 0.05 increases the number of military tuberculosis among our patients. In addition we did not find any other significant risk factor.

  13. Bayesian genomic selection: the effect of haplotype lenghts and priors

    DEFF Research Database (Denmark)

    Villumsen, Trine Michelle; Janss, Luc

    2009-01-01

    Breeding values for animals with marker data are estimated using a genomic selection approach where data is analyzed using Bayesian multi-marker association models. Fourteen model scenarios with varying haplotype lengths, hyper parameter and prior distributions were compared to find the scenario ...

  14. Direct chromosome-length haplotyping by single-cell sequencing

    NARCIS (Netherlands)

    Porubský, David; Sanders, Ashley D; van Wietmarschen, Niek; Falconer, Ester; Hills, Mark; Spierings, Diana C J; Bevova, Marianna R; Guryev, Victor; Lansdorp, Peter Michael

    Haplotypes are fundamental to fully characterize the diploid genome of an individual, yet methods to directly chart the unique genetic makeup of each parental chromosome are lacking. Here we introduce single-cell DNA template strand sequencing (Strand-seq) as a novel approach to phasing diploid

  15. Dense and accurate whole-chromosome haplotyping of individual genomes

    NARCIS (Netherlands)

    Porubsky, David; Garg, Shilpa; Sanders, Ashley D.; Korbel, Jan O.; Guryev, Victor; Lansdorp, Peter M.; Marschall, Tobias

    2017-01-01

    The diploid nature of the human genome is neglected in many analyses done today, where a genome is perceived as a set of unphased variants with respect to a reference genome. This lack of haplotype-level analyses can be explained by a lack of methods that can produce dense and accurate

  16. Geographical distribution of a specific mitochondrial haplotype of Zymoseptoria tritici

    Directory of Open Access Journals (Sweden)

    Sameh BOUKEF

    2014-01-01

    Full Text Available Severity of disease caused by the fungus Zymoseptoria tritici throughout world cereal growing regions has elicited much debate on the potential evolutionary mechanism conferring high adaptability of the pathogen to diverse climate conditions and different wheat hosts (Triticum durum and T. aestivum. Specific mitochondrial DNA sequence was used to investigate geographic distribution of the type 4 haplotype (mtRFLP4 within 1363 isolates of Z. tritici originating from 21 countries. The mtRFLP4 haplotype was detected from both durum and bread wheat hosts with greater frequency on durum wheat. The distribution of mtRFLP4 was limited to populations sampled from the Mediterranean and the Red Sea region. Greater frequencies of mtRFLP4 were found in Tunisia (87% and Algeria (60%. The haplotype was absent within European, Australian, North and South American populations except Argentina. While alternative hypotheses such as climatic adaptation could not be ruled out, it is postulated that mtRFLP4 originated in North Africa (e.g. Tunisia or Algeria as an adaptation to durum wheat as the prevailing cereal crop. The specialized haplotype has subsequently spread as indicated by lower frequency of occurrence in the surrounding Mediterranean countries and on bread wheat hosts.

  17. Association of specific haplotype of TNFα with Helicobacter pylori ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 87; Issue 3. Association of specific haplotype of TNF with Helicobacter pylori-mediated duodenal ulcer in eastern Indian population. Meenakshi Chakravorty Dipanjana Datta De Abhijit Choudhury Amal Santra Susanta Roychoudhury. Research Note Volume 87 Issue 3 ...

  18. A genomic portrait of haplotype diversity and signatures of selection in indigenous southern African populations.

    Directory of Open Access Journals (Sweden)

    Emile R Chimusa

    2015-03-01

    Full Text Available We report a study of genome-wide, dense SNP (∼ 900K and copy number polymorphism data of indigenous southern Africans. We demonstrate the genetic contribution to southern and eastern African populations, which involved admixture between indigenous San, Niger-Congo-speaking and populations of Eurasian ancestry. This finding illustrates the need to account for stratification in genome-wide association studies, and that admixture mapping would likely be a successful approach in these populations. We developed a strategy to detect the signature of selection prior to and following putative admixture events. Several genomic regions show an unusual excess of Niger-Kordofanian, and unusual deficiency of both San and Eurasian ancestry, which were considered the footprints of selection after population admixture. Several SNPs with strong allele frequency differences were observed predominantly between the admixed indigenous southern African populations, and their ancestral Eurasian populations. Interestingly, many candidate genes, which were identified within the genomic regions showing signals for selection, were associated with southern African-specific high-risk, mostly communicable diseases, such as malaria, influenza, tuberculosis, and human immunodeficiency virus/AIDs. This observation suggests a potentially important role that these genes might have played in adapting to the environment. Additionally, our analyses of haplotype structure, linkage disequilibrium, recombination, copy number variation and genome-wide admixture highlight, and support the unique position of San relative to both African and non-African populations. This study contributes to a better understanding of population ancestry and selection in south-eastern African populations; and the data and results obtained will support research into the genetic contributions to infectious as well as non-communicable diseases in the region.

  19. A genomic portrait of haplotype diversity and signatures of selection in indigenous southern African populations.

    Science.gov (United States)

    Chimusa, Emile R; Meintjies, Ayton; Tchanga, Milaine; Mulder, Nicola; Seoighe, Cathal; Seioghe, Cathal; Soodyall, Himla; Ramesar, Rajkumar

    2015-03-01

    We report a study of genome-wide, dense SNP (∼ 900K) and copy number polymorphism data of indigenous southern Africans. We demonstrate the genetic contribution to southern and eastern African populations, which involved admixture between indigenous San, Niger-Congo-speaking and populations of Eurasian ancestry. This finding illustrates the need to account for stratification in genome-wide association studies, and that admixture mapping would likely be a successful approach in these populations. We developed a strategy to detect the signature of selection prior to and following putative admixture events. Several genomic regions show an unusual excess of Niger-Kordofanian, and unusual deficiency of both San and Eurasian ancestry, which were considered the footprints of selection after population admixture. Several SNPs with strong allele frequency differences were observed predominantly between the admixed indigenous southern African populations, and their ancestral Eurasian populations. Interestingly, many candidate genes, which were identified within the genomic regions showing signals for selection, were associated with southern African-specific high-risk, mostly communicable diseases, such as malaria, influenza, tuberculosis, and human immunodeficiency virus/AIDs. This observation suggests a potentially important role that these genes might have played in adapting to the environment. Additionally, our analyses of haplotype structure, linkage disequilibrium, recombination, copy number variation and genome-wide admixture highlight, and support the unique position of San relative to both African and non-African populations. This study contributes to a better understanding of population ancestry and selection in south-eastern African populations; and the data and results obtained will support research into the genetic contributions to infectious as well as non-communicable diseases in the region.

  20. Literature search on risks related to ionizing radiations

    International Nuclear Information System (INIS)

    Abou Anoma, G.; Bijaoui, A.; Gauron, C.

    2013-09-01

    The authors propose a selection of information sources regarding risks related to ionizing radiations. They present knowledge bases which can be found on different Internet sites belonging to different bodies and agencies (IRSN, CEA, INRS, SFRP, CNRS, Radioprotection Cirkus, EDF) and in different books. They present information sources dealing with radionuclides which can be found in French and international Internet sites and in books, information sources concerning different professional activities and sectors (ASN, IRSN, INRS, medical-professional sheets proposed by the CISME, sheets proposed by the Labour Ministry and other bodies). It presents information sources dealing with radiological incidents, accidents and emergencies, dealing with radioactive wastes, with the legal European and French framework. Some additional tools of general or more detailed information are indicated (CIPR, IAEA, UNSCAR, IRPA, IRSN, SFRP, CEA, CEPN, Radiation Cirkus, books). Ways to get an updated search are indicated for different databases, as well as some practical services

  1. Relative risk perception for terrorism: implications for preparedness and risk communication.

    Science.gov (United States)

    Caponecchia, Carlo

    2012-09-01

    Terrorism presents a significant risk that is often approached at public policy, infrastructure, or emergency management level. Public perceptions of the likelihood of terrorist events, and how this may relate to individual preparedness, are not always extensively examined. The tendency to think that negative events are less likely to happen to oneself than to the average person is known as optimism bias. Optimism bias is relevant to perceptions of terrorism, because it is thought to be related to a reduction in precaution use. Using an online survey of 164 participants, this study aimed to determine whether Sydney residents thought they had a lower likelihood of experiencing terrorist events than other Australians. Significant optimism bias was observed for witnessing terrorist events, but not for personally experiencing terrorist events. In addition, Sydney residents tended to think that terrorist attacks were more likely to occur in Sydney than another major Australian city in the next five years. At the same time, household and workplace preparedness for terrorism was quite low, as was awareness of emergency strategies in the central business district. Perceptions of high likelihood of terrorism happening in one's own city, yet low preparedness present a challenge for risk communication and emergency management strategies. The diversity of possible terrorist targets, and the simple plans that can moderate the effects of a disaster may need to be emphasized in future anti-terrorism initiatives. © 2012 Society for Risk Analysis.

  2. Public relations in risk communication: risk pr. The importance of public relations for risk communication; Public Relations in der Risikokommunikation: Risiko-PR. Die Bedeutung von Public Relations fuer die Risikokommunikation

    Energy Technology Data Exchange (ETDEWEB)

    Lehmann, K.

    2001-07-01

    Risks have become a central problem of our time, as is reflected in concepts like 'society at risk' and 'anti-technological attitude', in group protest against risks and against those who cause them, and last but not least in the critical attitude of the media. Against this background, organisations must needs enter the public discussion and be able to communicate professionally and convincingly in order to ensure their own success and further existence. The book describes the basic problems of risk research and risk communications and discusses inhowfar, and how, public relations strategies and instruments can help here. [German] Risiken werden verstaerkt zum Problem unserer Zeit. Das belegen nicht nur Begriffe wie 'Risikogesellschaft' und 'Technikfeindlichkeit', die in letzter Zeit an Bedeutung gewonnen haben, sondern auch und vor allem nachhaltige Proteste von engagierten Gruppierungen gegen Risiken und deren Verursacher oder auch die kritische Berichterstattung der Medien. Vor diesem Hintergrund ist es fuer Organisationen erforderlich, in die oeffentliche Auseinandersetzung um Risiken einzusteigen und hier professionell und ueberzeugend zu kommunizieren, um den Organisationserfolg und Organisationsbestand zu sichern. Die vorliegende Arbeit beschreibt die Grundprobleme der Risikoforschung und Risikokommunikation und diskutiert, ob und inwieweit Public Relations bei der Loesung dieser Probleme helfen koennen, da insbesondere Public Relations gezielt Strategien und Instrumente nutzen, um beispielsweise den Wissensstand der Oeffentlichkeit zu verbessern und den Dialog mit relevanten Teiloeffentlichkeiten zu foerdern. (orig.)

  3. Binge drinking among adolescents: prevalence, risk practices and related variables.

    Science.gov (United States)

    Golpe, Sandra; Isorna, Manuel; Barreiro, Carmen; Braña, Teresa; Rial, Antonio

    2017-09-29

    According to the last Survey on Drug Use among Secondary School Students (ESTUDES 2014-2015), consumption levels of alcohol and other substances have decreased in the last years in Spain. However, available data on binge drinking remain worrying, given the negative consequences related with this pattern. The aim of this paper is to analyse binge drinking among adolescents, providing updated data on prevalence in addition to information about the consequences and some predictive factors of binge drinking. A correlational method was used for this purpose, comprised of administering a survey to Compulsory Secondary School, High School and Vocational Training students. Based on a sample of 3,419 Galician adolescents aged between 12 and 18 years (M = 14.57; SD = 1.76), the results show that binge drinking is a common and global practice, with few socio-demographic differences but related with a wide range of risk practices. Furthermore, variables such as consumption expectancies, consumption by family and friends, as well as curfew time and allowance money have been identified as interesting predictive factors that should be taken into account at the preventive level.

  4. Inflammation, insulin resistance, and diabetes--Mendelian randomization using CRP haplotypes points upstream.

    Directory of Open Access Journals (Sweden)

    Eric J Brunner

    2008-08-01

    Full Text Available Raised C-reactive protein (CRP is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables.We genotyped three tagging SNPs (CRP + 2302G > A; CRP + 1444T > C; CRP + 4899T > G in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study. Homeostasis model assessment-insulin resistance (HOMA-IR and hemoglobin A1c (HbA1c were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p = 0.52-0.92. The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p = 0.007-0.11. Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p = 0.25-0.88. Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls using three SNPs in tight linkage disequilibrium with our

  5. Influence of maternal depression on children's brooding rumination: Moderation by CRHR1 TAT haplotype.

    Science.gov (United States)

    Woody, Mary L; Kudinova, Anastacia Y; McGeary, John E; Knopik, Valerie S; Palmer, Rohan H C; Gibb, Brandon E

    2016-01-01

    There is growing evidence that brooding rumination plays a key role in the intergenerational transmission of major depressive disorder (MDD) and may be an endophenotype for depression risk. However, less is known about the mechanisms underlying this role. Therefore, the goal of the current study was to examine levels of brooding in children of mothers with a history of MDD (n = 129) compared to children of never depressed mothers (n = 126) and to determine whether the variation in a gene known to influence hypothalamic-pituitary-adrenal axis functioning--corticotropin-releasing hormone receptor 1 (CRHR1)--would moderate the link between maternal MDD and children's levels of brooding. We predicted children of mothers with a history of MDD would exhibit higher levels of brooding than children of mothers with no lifetime depression history but that this link would be stronger among children carrying no copies of the protective CRHR1 TAT haplotype. Our results supported these hypotheses and suggest that the development of brooding among children of depressed mothers, particularly children without the protective CRHR1 haplotype, may serve as an important mechanism of risk for the intergenerational transmission of depression.

  6. Eurasian otters, Lutra lutra, have a dominant mtDNA haplotype from the Iberian Peninsula to Scandinavia.

    Science.gov (United States)

    Ferrando, Ainhoa; Ponsà, Montserrat; Marmi, Josep; Domingo-Roura, Xavier

    2004-01-01

    The Eurasian otter, Lutra lutra, has a Palaearctic distribution and has suffered a severe decline throughout Europe during the last century. Previous studies in this and other mustelids have shown reduced levels of variability in mitochondrial DNA, although otter phylogeographic studies were restricted to central-western Europe. In this work we have sequenced 361 bp of the mtDNA control region in 73 individuals from eight countries and added our results to eight sequences available from GenBank and the literature. The range of distribution has been expanded in relation to previous works north towards Scandinavia, east to Russia and Belarus, and south to the Iberian Peninsula. We found a single dominant haplotype in 91.78% of the samples, and six more haplotypes deviating a maximum of two mutations from the dominant haplotype restricted to a single country. Variability was extremely low in western Europe but higher in eastern countries. This, together with the lack of phylogeographical structuring, supports the postglacial recolonization of Europe from a single refugium. The Eurasian otter mtDNA control region has a 220-bp variable minisatellite in Domain III that we sequenced in 29 otters. We found a total of 19 minisatellite haplotypes, but they showed no phylogenetic information.

  7. Events per variable for risk differences and relative risks using pseudo-observations

    DEFF Research Database (Denmark)

    Hansen, Stefan Nygaard; Andersen, Per Kragh; Parner, Erik Thorlund

    2014-01-01

    A method based on pseudo-observations has been proposed for direct regression modeling of functionals of interest with right-censored data, including the survival function, the restricted mean and the cumulative incidence function in competing risks. The models, once the pseudo-observations have...... been computed, can be fitted using standard generalized estimating equation software. Regression models can however yield problematic results if the number of covariates is large in relation to the number of events observed. Guidelines of events per variable are often used in practice. These rules...

  8. Osteoprotegerin CGA haplotype protection against cerebrovascular complications in anti-CCP negative patients with rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Fernanda Genre

    Full Text Available Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis.Three OPG gene variants (rs3134063, rs2073618 and rs3134069 were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression.No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31-0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04-0.78; p = 0.022, respectively.Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.

  9. Haplotype and genetic relationship of 27 Y-STR loci in Han population of Chaoshan area of China

    Directory of Open Access Journals (Sweden)

    Qing-hua TIAN

    2017-04-01

    Full Text Available Objective  To investigate the genetic polymorphisms of 27 Y-chromosomal short tandem repeats (Y-STR loci included in Yfiler® Plus kit in Han population of Chaoshan area, and explore the population genetic relationships and evaluate its application value on forensic medicine. Methods  By detecting 795 unrelated Chaoshan Han males with Yfiler® Plus kit, haplotype frequencies and population genetics parameters of the 27 Y-STR loci were statistically analyzed and compared with available data of other populations from different races and regions for analyzing the genetic distance and clustering relation of Chaoshan Han population. Results  Seven hundred and eighty-seven different haplotypes were observed in 795 unrelated male individuals, of which 779 haplotypes were unique, and 8 haplotypes occurred twice. The haplotype diversity (HD was 0.999975 with discriminative capacity (DC of 98.99%. The gene diversity (GD at the 27 Y-STR loci ranged from 0.3637(DYS391 to 0.9559(DYS385a/b. Comparing with Asian reference populations, the genetic distance (Rst between Chaoshan Han and Guangdong Han was the smallest (0.0036, while it was relatively larger between Chaoshan Han and Gansu Tibetan population (0.0935. The multi-dimensional scaling (MDS plot based on Rst values was similar to the results of clustering analysis. Conclusion  Multiplex detection of the 27 Y-STR loci reveals a highly polymorphic genetic distribution in Chaoshan Han population, which demonstrates the important significance of Yfiler® Plus kit for establishing a Y-STR database, studying population genetics, and for good practice in forensic medicine. DOI: 10.11855/j.issn.0577-7402.2017.03.08

  10. On accounting difficulties: Risks related to nuclear power

    International Nuclear Information System (INIS)

    Plot, Emmanuelle; Vidal, Olivier

    2014-01-01

    An extreme risk has a very slight probability but potentially heavy consequences. Despite the existence of three accountancy methods for dealing with them (provisions, contingent liabilities and insurance), the transposition of such risks into financial statements is based on a sequential analysis of both the probability of the risk happening and the ability to estimate the effects. This method keeps us from taking into account risks with a highly uncertain probability of occurrence, such as accidents at nuclear power plants - independently of the 'amount' at stake. As management reports from firms concerned by nuclear risks show, the diffusion of qualitative information does not offset this gap in bookkeeping

  11. On accounting difficulties: risks related to nuclear power

    International Nuclear Information System (INIS)

    Plot, E.; Vidal, O.

    2014-01-01

    An extreme risk has a very slight probability but potentially heavy consequences. Despite the existence of 3 accountancy methods for dealing with them (provisions, contingent liabilities and insurance), the transposition of such risks into financial statements is based on a sequential analysis of both the probability of the risk happening and the ability to estimate the effects. This method keeps us from taking into account risks with a highly uncertain probability of occurrence, such as accidents at nuclear power plants - independently of the 'amount' at stake. As management reports from firms concerned by nuclear risks show, the diffusion of qualitative information does not offset this gap in bookkeeping. (authors)

  12. Relative risk models of lung cancer in uranium miners

    Energy Technology Data Exchange (ETDEWEB)

    Tomasek, L [National Radiation Protection Institute, Prague (Czech Republic); Placek, V [Inst. for Expertises and Emergencies, Pribram-Kamenna (Czech Republic)

    1996-12-31

    The study population of the S cohort (studies of underground miners of uranium and other substances as the source of information on long term effects of exposure to radon and its progeny) involve uranium miners, that started underground work at the Jachymov and Horni Slavkov mines in the period 1978-1959, and had worked at least for four years. A total 4320 men satisfied these criteria. During the decade up to 1990, follow-up of the cohort mainly relied on the national population registry. In order to improve the follow-u, a series of additional checks were conducted: in the files of the Czech and Slovak Pensions Offices, by local enquires, and by direct correspondence. These additional efforts resulted in an increase of more than 10% in the numbers of known men to have died or emigrated. An exceptional feature of the S study is the large number of measurements of radon concentrations made in each mine-shaft (mean number per year and shaft was 223 in the period 1949-1960). Each man`s annual exposures to radon progeny in terms of working levels were estimated combining measurement data with men`s employment details. The excess relative risk models were used in the form RR = c(1 + ERR(w,x)), where ERR is excess relative risk, w and x denote exposure history and modifying variable, and c is an intercept term that allows the mortality rate for `unexposed` cohort to differ from that in the general population. The increased mortality (O/E=1.58; where O is observed and E is expected cases among collected death cases in the cohort) in the cohort, generally, somewhat lower ratios than one reflect the non-industrial character of the region, with the exception of lung cancer in man. The differences in the O/E ratios for lung cancer among the separate communities indicate that even in the situation of generally lower mortality, the dependence of lung cancer mortality on radon exposure cannot be excluded. 3 tabs., 6 refs.

  13. Role of MAPT mutations and haplotype in frontotemporal lobar degeneration in Northern Finland

    Directory of Open Access Journals (Sweden)

    Tuominen Hannu

    2008-12-01

    Full Text Available Abstract Background Frontotemporal lobar degeneration (FTLD consists of a clinically and neuropathologically heterogeneous group of syndromes affecting the frontal and temporal lobes of the brain. Mutations in microtubule-associated protein tau (MAPT, progranulin (PGRN and charged multi-vesicular body protein 2B (CHMP2B are associated with familial forms of the disease. The prevalence of these mutations varies between populations. The H1 haplotype of MAPT has been found to be closely associated with tauopathies and with sporadic FTLD. Our aim was to investigate MAPT mutations and haplotype frequencies in a clinical series of patients with FTLD in Northern Finland. Methods MAPT exons 1, 2 and 9–13 were sequenced in 59 patients with FTLD, and MAPT haplotypes were analysed in these patients, 122 patients with early onset Alzheimer's disease (eoAD and 198 healthy controls. Results No pathogenic mutations were found. The H2 allele frequency was 11.0% (P = 0.028 in the FTLD patients, 9.8% (P = 0.029 in the eoAD patients and 5.3% in the controls. The H2 allele was especially clustered in patients with a positive family history (P = 0.011 but did not lower the age at onset of the disease. The ApoE4 allele frequency was significantly increased in the patients with eoAD and in those with FTLD. Conclusion We conclude that although pathogenic MAPT mutations are rare in Northern Finland, the MAPT H2 allele may be associated with increased risks of FTLD and eoAD in the Finnish population.

  14. Haplotype analysis indicates an association between the DOPA decarboxylase (DDC) gene and nicotine dependence.

    Science.gov (United States)

    Ma, Jennie Z; Beuten, Joke; Payne, Thomas J; Dupont, Randolph T; Elston, Robert C; Li, Ming D

    2005-06-15

    DOPA decarboxylase (DDC; also known as L-amino acid decarboxylase; AADC) is involved in the synthesis of dopamine, norepinephrine and serotonin. Because the mesolimbic dopaminergic system is implicated in the reinforcing effects of many drugs, including nicotine, the DDC gene is considered a plausible candidate for involvement in the development of vulnerability to nicotine dependence (ND). Further, this gene is located within the 7p11 region that showed a 'suggestive linkage' to ND in our previous genome-wide scan in the Framingham Heart Study population. In the present study, we tested eight single nucleotide polymorphisms (SNPs) within DDC for association with ND, which was assessed by smoking quantity (SQ), the heaviness of smoking index (HSI) and the Fagerstrom test for ND (FTND) score, in a total of 2037 smokers and non-smokers from 602 nuclear families of African- or European-American (AA or EA, respectively) ancestry. Association analysis for individual SNPs using the PBAT-GEE program indicated that SNP rs921451 was significantly associated with two of the three adjusted ND measures in the EA sample (P=0.01-0.04). Haplotype-based association analysis revealed a protective T-G-T-G haplotype for rs921451-rs3735273-rs1451371-rs2060762 in the AA sample, which was significantly associated with all three adjusted ND measures after correction for multiple testing (min Z=-2.78, P=0.006 for HSI). In contrast, we found a high-risk T-G-T-G haplotype for a different SNP combination in the EA sample, rs921451-rs3735273-rs1451371-rs3757472, which showed a significant association after Bonferroni correction with the SQ and FTND score (max Z=2.73, P=0.005 for FTND). In summary, our findings provide the first evidence for the involvement of DDC in the susceptibility to ND and, further, reveal the racial specificity of its impact.

  15. Risk factors for age-related maculopathy in a 14-year follow-up study

    DEFF Research Database (Denmark)

    Buch, Helena; Vinding, Troels; la Cour, Morten

    2005-01-01

    To examine the association between potential risk factors and the 14-year incidence of age-related maculopathy (ARM).......To examine the association between potential risk factors and the 14-year incidence of age-related maculopathy (ARM)....

  16. Three Studies Point to Same Risk Gene for Age-Related Macular Degeneration

    Science.gov (United States)

    ... point to same risk gene for age-related macular degeneration NIH-funded research helps unravel the biology of ... rare, but powerful risk factor for age-related macular degeneration (AMD), a common cause of vision loss in ...

  17. A functional haplotype of NFKB1 influence susceptibility to oral cancer: a population-based and in vitro study.

    Science.gov (United States)

    Chen, Fa; Liu, Fengqiong; Yan, Lingjun; Lin, Lisong; Qiu, Yu; Wang, Jing; Wu, Junfeng; Bao, Xiaodan; Hu, Zhijian; Cai, Lin; He, Baochang

    2018-05-01

    Genetic variations of NF-κB and its inhibitor IκB genes and their biological mechanism in oral cancer were not well recognized. The purpose of this study was to evaluate the associations of polymorphisms in NFKB1 and NFKBIA with oral cancer susceptibility, and further explore their potential mechanism in vitro. First, the polymorphisms of NFKB1 and NFKBIA were genotyped through iPLEX Sequenom MassARRAY platform in a case-control study with 425 oral cancer patients and 485 healthy controls. Then, the function was explored by a luciferase reporter assay and an electrophoretic mobility shift assay (EMSA) in human tongue squamous cell carcinoma cell lines. The results indicated that NFKB1 rs28362491 Del/Del and rs72696119 G/G genotypes were associated with the risk of oral cancer, with a strong linkage disequilibrium (D' = 0.991, r 2  = 0.971). Moreover, DG haplotype of NFKB1 also showed a significant increased risk (OR = 1.25, 95% CI: 1.02-1.53, P = 0.030). Dual-luciferase reporter assays further revealed that the plasmids with DG or IG or DC haplotype transfected with Tca-8113 cells or CAL-27 cells had a lower luciferase expression than that with IC haplotype. EMSA demonstrated that 4-bp ATTG deletion in the promoter of NFKB1 abolished the binding site of transcription factor. Our preliminary findings suggest that the haplotype of rs28362491 and rs72696119 in NFKB1 could act as a novel genetic marker to predict oral cancer risk in the southeast of China, but much more extensive researches still need to be conducted. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  18. A novel haplotype of low-frequency variants in the aldosterone synthase gene among northern Han Chinese with essential hypertension.

    Science.gov (United States)

    Zhang, Hao; Li, Xueyan; Zhou, Li; Zhang, Keyong; Zhang, Qi; Li, Jingping; Wang, Ningning; Jin, Ming; Wu, Nan; Cong, Mingyu; Qiu, Changchun

    2017-09-01

    Low-frequency variants showed that there is more power to detect risk variants than to detect protective variants in complex diseases. Aldosterone plays an important role in the renin-angiotensin-aldosterone system, and aldosterone synthase catalyzes the speed-controlled steps of aldosterone biosynthesis. Polymorphisms of the aldosterone synthase gene (CYP11B2) have been reported to be associated with essential hypertension (EH). CYP11B2 polymorphisms such as -344T/C, have been extensively reported, but others are less well known. This study aimed to assess the association between human CYP11B2 and EH using a haplotype-based case-control study. A total of 1024 EH patients and 956 normotensive controls, which consist of north Han population peasants, were enrolled. Seven single nucleotide polymorphisms (SNPs) (rs28659182, rs10087214, rs73715282, rs542092383, rs4543, rs28491316, and rs7463212) covering the entire human CYP11B2 gene were genotyped as markers using the MassARRAY system. The major allele G frequency of rs542092383 was found to be risk against hypertension [odds ratio (OR) 3.478, 95% confidence interval (95% CI) 1.407-8.597, P = .004]. The AG genotype frequency of SNP rs542092383 was significantly associated with an increased risk of hypertension (OR 4.513, 95% CI 1.426-14.287, P = .010). In the haplotype-based case-control analysis, the frequency of the T-G-T haplotype was higher for EH patients than for controls (OR 5.729, 95% CI 1.889-17.371, P = .000495). All |D'| values of the seven SNPs were >0.9, and r values for rs28659182- rs10087214-rs28491316-rs7463212 SNPs were >0.8 and showed strong linkage intensity. Haplotype T-G-T may therefore be a useful genetic marker for EH.

  19. About some aspects of weather related risks in Spanish Agriculture

    Science.gov (United States)

    Anton, J. M.; Tarquis, A. M.; Grau, J. B.; Saa, A.; Diaz, M. C.

    2009-04-01

    aggressive floods in 1500-1800 era, and actual added trends of "climate change" are towards higher temperatures, less water and higher perturbations. These long term risks are rather poorly predictable and will be handled mostly by improvements in agriculture and also by social and economic adaptations, but at shorter delays and specific areas active policies are possible and exist. An agribusiness can set his production plans lowering his global risk. Sometimes it might use prudently some financial instruments, such as "orange juice futures". When using decision making models, some utility functions may consider that severe losses have higher effects than good profits, letting ranges for business margins for insurers to be limited by concurrence at correct levels. Correct availability of credits is necessary for bad periods, and also state policies for rare bad situations, concerning agribusiness survival and also alimentary safety. Insurance products are effective aids for a growing variety of well definite natural risks, such as in cases of hailstorm, that have probabilities of occurrence measurable from previous events data, and a variety of adequate professional models are continuously made for them. Related to Universidad Politecnica de Madrid the CEIGRAM institute has started recently and is involved in agricultural insurance, being connected with insurers through ENESA and AGROMUTUA. That world is active, important, evolving, and is regulated by diverse laws.

  20. Perception of radiation related risks among three population groups

    International Nuclear Information System (INIS)

    Mihai, L.T.; Milu, C.; Voicu, B.; Enachescu, D.

    2003-01-01

    A questionnaire survey was conducted among three groups that mainly differ in socioeconomic status and professional exposure to ionizing radiations. Seventy-seven (26.3%) of the respondents were professionally exposed to radiation, 35 (11.9%) were medical doctors without professional exposure and 177 (68.4%) belonged to the general population group. The level of anxiety toward radiation, expressed as a concernedness index, is significantly lower in people who are professionally exposed to radiation compared to medical doctors and general population (0.81±0.94, 1.42±1.21 and 1.72±1.34 respectively, p < 0.001). In a similar manner, concernedness index values varied with the education status, with lowest values among medical university graduates and highest among public school graduates (p < 0.001). Both university-graduated groups significantly differ from the non-university groups (p < 0.05). Knowledge about radiation and knowledge about emergency plans in nuclear accident/incident were also checked in relation with concernedness, the results confirming the hypothesis that better knowledge associates lower concernedness. The extent to which people accept the civil utilization of nuclear power is also related to concernedness and knowledge, significant associations having been found. The results suggest that a political decision in radiation matter requires a valid analysis of the public's understanding and acceptance. For that reason, it is important that radiological protection authorities develop new plans and materials for communicating with people, in order to improve knowledge upon ionizing radiation, irradiation risks and safety of nuclear energy application for civil purposes. (author)

  1. HLA alleles and haplotypes distribution in Dai population in Yunnan province, Southwest China.

    Science.gov (United States)

    Shi, L; Yao, Y F; Shi, L; Matsushita, M; Yu, L; Lin, Q K; Tao, Y F; Oka, T; Chu, J Y; Tokunaga, K

    2010-02-01

    Human leukocyte antigen (HLA) analysis would be a useful tool to trace the origin of modern humans. In this study, we provided the first four digital HLA-A, -B, -C and -DRB1 allele and haplotype data in the Dai ethnic population, which is a unique and representative Kam-Tai-speaking ethnic minority living in the Yunnan province of Southwestern China. Our results showed that the Dai population has unique HLA characteristic that are most closely related to the Southeastern Asia group and similar to the Kam-Tai speaking populations in China and Thailand.

  2. Risks and safety aspects related to PET/MR examinations

    International Nuclear Information System (INIS)

    Brix, Gunnar; Nekolla, Elke A.; Nosske, Dietmar; Griebel, Juergen

    2009-01-01

    The introduction of positron emission tomography (PET)/magnetic resonance (MR) systems into medical practice in the foreseeable future may not only lead to a gain in clinical diagnosis compared to PET/computed tomography (CT) imaging due to the superior soft-tissue contrast of the MR technology but can also substantially reduce exposure of patients to ionizing radiation. On the other hand, there are also risks and health effects associated with the use of diagnostic MR devices that have to be considered carefully. This review article summarizes biophysical and biological aspects, which are of relevance for the assessment of health effects related to the exposure of patients to both ionizing radiation in PET and magnetic and electromagnetic fields in MR. On this basis, some considerations concerning the justification and optimization of PET/MR examinations are presented - as far as this is possible at this very early stage. Current safety standards do not take into account synergistic effects of ionizing radiation and magnetic and electromagnetic fields. In the light of the developing PET/MR technology, there is an urgent need to investigate this aspect in more detail for exposure levels that will occur at PET/MR systems. (orig.)

  3. Concept analysis of risk in relation to coronary heart disease among Filipino-Americans.

    Science.gov (United States)

    Dalusung-Angosta, Alona

    2010-01-01

    To analyze the concept of risk in relation to coronary heart disease (CHD) among Filipino-Americans (FAs) and provide a new definition of risk. Published literature. This concept analysis provided a new meaning of risk in relation to CHD among FAs and shed light on further understanding of risk. Risk has been laced with negativity in health care, but based on the current literature, risk can be conceptualized in a positive perspective, especially in the area of chronic health disease such as CHD. However, further research is needed in the conceptualization of risk related to CHD for consistency, adequacy, and meaning. © 2010 Wiley Periodicals, Inc.

  4. Relations between radiation risks and radiation protection measuring techniques

    International Nuclear Information System (INIS)

    Herrmann, K.; Kraus, W.

    1975-10-01

    'Risk of damage' and 'exposure risk' are considered as components of the radiation risk. The influence of the 'exposure risk' on type and extent of radiation protection measurements is discussed with regard to different measuring tasks. Basing upon measuring results concerning the frequency of certain external and internal occupational exposures in the GDR, it has been shown that only a small fraction of the monitored persons are subjected to a high 'exposure risk'. As a consequence the following recommendations are given for discussion: (a) occupationally exposed persons with small 'exposure risk' should be monitored using only a long-term dosimeter (for instance a thermoluminescence dosimeter), (b) in the case of internal exposure the surface and, if necessary, air contamination should be controlled so strictly that routine measurements of internal contamination need not be performed. (author)

  5. Review of studies related to uncertainty in risk analsis

    International Nuclear Information System (INIS)

    Rish, W.R.; Marnicio, R.J.

    1988-08-01

    The Environmental Protection Agency's Office of Radiation Programs (ORP) is responsible for regulating on a national level the risks associated with technological sources of ionizing radiation in the environment. A critical activity of the ORP is analyzing and evaluating risk. The ORP believes that the analysis of uncertainty should be an integral part of any risk assessment; therefore, the ORP has initiated a project to develop framework for the treatment of uncertainty in risk analysis. Summaries of recent studies done in five areas of study are presented

  6. Review of studies related to uncertainty in risk analsis

    Energy Technology Data Exchange (ETDEWEB)

    Rish, W.R.; Marnicio, R.J.

    1988-08-01

    The Environmental Protection Agency's Office of Radiation Programs (ORP) is responsible for regulating on a national level the risks associated with technological sources of ionizing radiation in the environment. A critical activity of the ORP is analyzing and evaluating risk. The ORP believes that the analysis of uncertainty should be an integral part of any risk assessment; therefore, the ORP has initiated a project to develop framework for the treatment of uncertainty in risk analysis. Summaries of recent studies done in five areas of study are presented.

  7. Haplotype of platelet receptor P2RY12 gene is associated with residual clopidogrel on-treatment platelet reactivity.

    Science.gov (United States)

    Nie, Xiao-Yan; Li, Jun-Lei; Zhang, Yong; Xu, Yang; Yang, Xue-Li; Fu, Yu; Liang, Guang-Kai; Lu, Yun; Liu, Jian; Shi, Lu-Wen

    To investigate a possible association between common variations of the P2RY12 and the residual clopidogrel on-treatment platelet reactivity after adjusting for the influence of CYP2C19 tested by thromboelastography (TEG). One hundred and eighty patients with acute coronary syndrome (ACS) treated with clopidogrel and aspirin were included and platelet function was assessed by TEG. Five selected P2RY12 single nucleotide polymorphisms (SNPs; rs6798347, rs6787801, rs6801273, rs6785930, and rs2046934), which cover the common variations in the P2RY12 gene and its regulatory regions, and three CYP2C19 SNPs ( * 2, * 3, * 17) were genotyped and possible haplotypes were analyzed. The high on-treatment platelet reactivity (HTPR) prevalence defined by a platelet inhibition rate <30% by TEG in adenosine diphosphate (ADP)-channel was 69 (38.33%). Six common haplotypes were inferred from four of the selected P2RY12 SNPs (denoted H 0 to H 5 ) according to the linkage disequilibrium R square (except for rs2046934). Haplotype H 1 showed a significantly lower incidence of HTPR than the reference haplotype (H 0 ) in the total study population while haplotypes H 1 and H 2 showed significantly lower incidences of HTPR than H 0 in the nonsmoker subgroup after adjusting for CYP2C19 effects and demographic characteristics. rs2046934 (T744C) did not show any significant association with HTPR. The combination of common P2RY12 variations including regulatory regions rather than rs2046934 (T744C) that related to pharmacodynamics of clopidogrel in patients with ACS was independently associated with residual on-clopidogrel platelet reactivity. This is apart from the established association of the CYP2C19. This association seemed more important in the subgroup defined by smoking.

  8. H-PoP and H-PoPG: heuristic partitioning algorithms for single individual haplotyping of polyploids.

    Science.gov (United States)

    Xie, Minzhu; Wu, Qiong; Wang, Jianxin; Jiang, Tao

    2016-12-15

    Some economically important plants including wheat and cotton have more than two copies of each chromosome. With the decreasing cost and increasing read length of next-generation sequencing technologies, reconstructing the multiple haplotypes of a polyploid genome from its sequence reads becomes practical. However, the computational challenge in polyploid haplotyping is much greater than that in diploid haplotyping, and there are few related methods. This article models the polyploid haplotyping problem as an optimal poly-partition problem of the reads, called the Polyploid Balanced Optimal Partition model. For the reads sequenced from a k-ploid genome, the model tries to divide the reads into k groups such that the difference between the reads of the same group is minimized while the difference between the reads of different groups is maximized. When the genotype information is available, the model is extended to the Polyploid Balanced Optimal Partition with Genotype constraint problem. These models are all NP-hard. We propose two heuristic algorithms, H-PoP and H-PoPG, based on dynamic programming and a strategy of limiting the number of intermediate solutions at each iteration, to solve the two models, respectively. Extensive experimental results on simulated and real data show that our algorithms can solve the models effectively, and are much faster and more accurate than the recent state-of-the-art polyploid haplotyping algorithms. The experiments also show that our algorithms can deal with long reads and deep read coverage effectively and accurately. Furthermore, H-PoP might be applied to help determine the ploidy of an organism. https://github.com/MinzhuXie/H-PoPG CONTACT: xieminzhu@hotmail.comSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Haplotypes in the CRP Gene Associated with Increased BMI and Levels of CRP in Subjects with Type 2 Diabetes or Obesity from Southwestern Mexico

    Directory of Open Access Journals (Sweden)

    América Martínez-Calleja

    2012-01-01

    Full Text Available Objective. We evaluated the association between four polymorphisms in the CRP gene with circulating levels of C-reactive protein (CRP, type 2 diabetes (T2D, obesity, and risk score of coronary heart disease. Methods. We studied 402 individuals and classified them into four groups: healthy, obese, T2D obese, and T2D without obesity, from Guerrero, Southwestern Mexico. Blood levels of CRP, glucose, cholesterol, triglycerides, and leukocytes were measured. Genotyping was performed by PCR/RFLP, and the risk score for coronary heart disease was determined by the Framingham's methodology. Results. The TT genotype of SNP rs1130864 was associated with increased body mass index and T2D patients with obesity. We found that the haplotype 2 (TGAG was associated with increased levels of CRP (β=0.3; 95%CI: 0.1, 0.5; P=0.005 and haplotype 7 (TGGG with higher body mass index (BMI (β=0.2; 95%CI: 0.1, 0.3; P<0.001. The risk score for coronary heart disease was associated with increased levels of CRP, but not with any polymorphism or haplotype. Conclusions. The association between the TT genotype of SNP rs1130864 with obesity and the haplotype 7 with BMI may explain how obesity and genetic predisposition increase the risk of diseases such as T2D in the population of Southwestern Mexico.

  10. Genome-wide association study identifies shared risk loci common to two malignancies in golden retrievers.

    Directory of Open Access Journals (Sweden)

    Noriko Tonomura

    2015-02-01

    Full Text Available Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6% and hemangiosarcoma (20%. We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers.

  11. A Dynamic Programming Algorithm for the k-Haplotyping Problem

    Institute of Scientific and Technical Information of China (English)

    Zhen-ping Li; Ling-yun Wu; Yu-ying Zhao; Xiang-sun Zhang

    2006-01-01

    The Minimum Fragments Removal (MFR) problem is one of the haplotyping problems: given a set of fragments, remove the minimum number of fragments so that the resulting fragments can be partitioned into k classes of non-conflicting subsets. In this paper, we formulate the k-MFR problem as an integer linear programming problem, and develop a dynamic programming approach to solve the k-MFR problem for both the gapless and gap cases.

  12. RFLP's for the human pepsinogen A haplotypes (PGA)

    Energy Technology Data Exchange (ETDEWEB)

    Taggart, R T; Boudi, F B; Bell, G I

    1988-10-11

    PGA 101 is a 1340 bp cDNA clone containing exons 1-9 of the predicted human pepsinogen A coding sequence. Two distinct polymorphisms are detected with EcoRI and Bg1 II. Analysis with these enzymes provides for discrimination of the PGA haplotypes A, B, and C containing three, two and one PGA genes respectively. The PGA complex is located at 11q13. Mendelian inheritance was demonstrated in 20 families.

  13. Extended HLA-D region haplotype associated with celiac disease

    International Nuclear Information System (INIS)

    Howell, M.D.; Smith, J.R.; Austin, R.K.; Kelleher, D.; Nepom, G.T.; Volk, B.; Kagnoff, M.F.

    1988-01-01

    Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. The authors previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II β-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. They now report the isolation of this β-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP β-chain. This celiac disease-associated HLA-DP β-chain gene was flanked by HLA-DP α-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DPα-chain genes of celiac disease patients also were studied by RFLP analysis. Celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP α- and β-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion

  14. Extended HLA-D region haplotype associated with celiac disease

    Energy Technology Data Exchange (ETDEWEB)

    Howell, M.D.; Smith, J.R.; Austin, R.K.; Kelleher, D.; Nepom, G.T.; Volk, B.; Kagnoff, M.F.

    1988-01-01

    Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. The authors previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II ..beta..-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. They now report the isolation of this ..beta..-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP ..beta..-chain. This celiac disease-associated HLA-DP ..beta..-chain gene was flanked by HLA-DP ..cap alpha..-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DP..cap alpha..-chain genes of celiac disease patients also were studied by RFLP analysis. Celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP ..cap alpha..- and ..beta..-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion.

  15. Combinatorial aspects of genome rearrangements and haplotype networks

    OpenAIRE

    Labarre , Anthony

    2008-01-01

    The dissertation covers two problems motivated by computational biology: genome rearrangements, and haplotype networks. Genome rearrangement problems are a particular case of edit distance problems, where one seeks to transform two given objects into one another using as few operations as possible, with the additional constraint that the set of allowed operations is fixed beforehand; we are also interested in computing the corresponding distances between those objects, i.e. merely computing t...

  16. Reactor siting risk comparisons related to recommendations of NUREG-0625

    International Nuclear Information System (INIS)

    Barsell, A.W.; Dombek, F.S.; Orvis, D.D.

    1980-11-01

    This document evaluates how implementing the remote siting recommendations for nuclear reactors (NUREG-0625) made by the Siting Policy Task Force of the US Nuclear Regulatory Commission (NRC) can reduce potential public risk. The document analyzes how population density affects site-specific risk for both light water reactors (LWRs) and high-temperature gas-cooled reactors

  17. RELATIVE PROLIFERATION RISKS FOR NUCLEAR FUEL LEASING ARRANGEMENT

    International Nuclear Information System (INIS)

    CHENG, L.Y.; YUE, M.; BARI, R.A.

    2007-01-01

    The present study demonstrates a probabilistic approach to quantify the proliferation risks of fuel leasing and recycling. A Markov model approach is applied to evaluate the probability of proliferation success by diversion or theft. Proliferation risk is calculated as a product of the probability of success and the corresponding consequences

  18. Elderly Taiwanese's Intrinsic Risk Factors for Fall-related Injuries

    Directory of Open Access Journals (Sweden)

    In-Fun Li

    2016-09-01

    Conclusion: Elderly Taiwanese inpatients with existing intrinsic conditions of cancer, vertigo, and lower leg weakness were at high risk of falling, resulting in severe injuries. Additional research including controlled trials is necessary to further identify treatable, causal intrinsic risk factors for this elderly group.

  19. The effect of using genealogy-based haplotypes for genomic prediction.

    Science.gov (United States)

    Edriss, Vahid; Fernando, Rohan L; Su, Guosheng; Lund, Mogens S; Guldbrandtsen, Bernt

    2013-03-06

    Genomic prediction uses two sources of information: linkage disequilibrium between markers and quantitative trait loci, and additive genetic relationships between individuals. One way to increase the accuracy of genomic prediction is to capture more linkage disequilibrium by regression on haplotypes instead of regression on individual markers. The aim of this study was to investigate the accuracy of genomic prediction using haplotypes based on local genealogy information. A total of 4429 Danish Holstein bulls were genotyped with the 50K SNP chip. Haplotypes were constructed using local genealogical trees. Effects of haplotype covariates were estimated with two types of prediction models: (1) assuming that effects had the same distribution for all haplotype covariates, i.e. the GBLUP method and (2) assuming that a large proportion (π) of the haplotype covariates had zero effect, i.e. a Bayesian mixture method. About 7.5 times more covariate effects were estimated when fitting haplotypes based on local genealogical trees compared to fitting individuals markers. Genealogy-based haplotype clustering slightly increased the accuracy of genomic prediction and, in some cases, decreased the bias of prediction. With the Bayesian method, accuracy of prediction was less sensitive to parameter π when fitting haplotypes compared to fitting markers. Use of haplotypes based on genealogy can slightly increase the accuracy of genomic prediction. Improved methods to cluster the haplotypes constructed from local genealogy could lead to additional gains in accuracy.

  20. A unified framework for haplotype inference in nuclear families.

    Science.gov (United States)

    Iliadis, Alexandros; Anastassiou, Dimitris; Wang, Xiaodong

    2012-07-01

    Many large genome-wide association studies include nuclear families with more than one child (trio families), allowing for analysis of differences between siblings (sib pair analysis). Statistical power can be increased when haplotypes are used instead of genotypes. Currently, haplotype inference in families with more than one child can be performed either using the familial information or statistical information derived from the population samples but not both. Building on our recently proposed tree-based deterministic framework (TDS) for trio families, we augment its applicability to general nuclear families. We impose a minimum recombinant approach locally and independently on each multiple children family, while resorting to the population-derived information to solve the remaining ambiguities. Thus our framework incorporates all available information (familial and population) in a given study. We demonstrate that using all the constraints in our approach we can have gains in the accuracy as opposed to breaking the multiple children families to separate trios and resorting to a trio inference algorithm or phasing each family in isolation. We believe that our proposed framework could be the method of choice for haplotype inference in studies that include nuclear families with multiple children. Our software (tds2.0) is downloadable from www.ee.columbia.edu/∼anastas/tds. © 2012 The Authors Annals of Human Genetics © 2012 Blackwell Publishing Ltd/University College London.

  1. Sensation seeking related to varied definition of risk

    International Nuclear Information System (INIS)

    Dastol, O.U.; Drottz-Sjoberg, B.M.

    1998-01-01

    This pilot study is based on the assumption that the normal use of the word risk varies across subjects. It has been shown in previous risk perception studies that some people report their definition or normal use of the concept of risk as e.g. mainly probability, a combination of probability and consequences, mainly consequences, or due to the nature of the event (Drottz-Sjoeberg, 1991). Another field of research has developed measures for personality traits, i.e. facets of Sensation Seeking; Disinhibition, Thrill and Adventure Seeking, Experience Seeking, and Boredom Susceptibility (Zuckerman, 1994). The design of the present study involved three independent groups of first year psychology students (N=93). They were presented with one of three response formats regarding their normal use of the word risk, i.e. an open-ended format, separate ratings of four items suggesting a definition of risk on five-point scales, and one single five-point scale with the extremes labelled probability and consequences, and with their combination as the scale mid-point. The results showed, e.g. that the typical open-ended response to the personal definition of risk was 'danger', but among the responses were also 'chance', and 'outcome'. Another finding was that people who defined risk as 'outcome' and 'chance', using the open-ended format tended to score higher on the total Sensation Seeking Scale than those who defined risk as 'danger'. In addition, subjects who defined risk as the 'combination' of probability and consequences, using other response formats, also tended to score higher on the total Sensation Seeking Scale (SSS), especially as compared to those defining risk as the 'probability' of an event. (authors)

  2. Gender differences in the relations between work-related physical and psychosocial risk factors and musculoskeletal complaints

    NARCIS (Netherlands)

    Hooftman, W.E.; Poppel, M.N.M. van; Beek, A.J. van der; Bongers, P.M.; Mechelen, W. van

    2004-01-01

    Gender differences in the prevalence of musculoskeletal complaints might be explained by differences in the effect of exposure to work-related physical and psychosocial risk factors. A systematic review was conducted to examine gender differences in the relations between these risk factors and

  3. Risk of placental abruption in relation to migraines and headaches

    Directory of Open Access Journals (Sweden)

    Ananth Cande V

    2010-10-01

    Full Text Available Abstract Background Migraine, a common chronic-intermittent disorder of idiopathic origin characterized by severe debilitating headaches and autonomic nervous system dysfunction, and placental abruption, the premature separation of the placenta, share many common pathophysiological characteristics. Moreover, endothelial dysfunction, platelet activation, hypercoagulation, and inflammation are common to both disorders. We assessed risk of placental abruption in relation to maternal history of migraine before and during pregnancy in Peruvian women. Methods Cases were 375 women with pregnancies complicated by placental abruption, and controls were 368 women without an abruption. During in-person interviews conducted following delivery, women were asked if they had physician-diagnosed migraine, and they were asked questions that allowed headaches and migraine to be classified according to criteria established by the International Headache Society. Logistic regression procedures were used to calculate odds ratios (aOR and 95% confidence intervals (CI adjusted for confounders. Results Overall, a lifetime history of any headaches or migraine was associated with an increased odds of placental abruption (aOR = 1.60; 95% CI 1.16-2.20. A lifetime history of migraine was associated with a 2.14-fold increased odds of placental abruption (aOR = 2.14; 95% CI 1.22-3.75. The odds of placental abruption was 2.11 (95% CI 1.00-4.45 for migraineurs without aura; and 1.59 (95% 0.70-3.62 for migraineurs with aura. A lifetime history of tension-type headache was also increased with placental abruption (aOR = 1.61; 95% CI 1.01-2.57. Conclusions This study adds placental abruption to a growing list of pregnancy complications associated with maternal headache/migraine disorders. Nevertheless, prospective cohort studies are needed to more rigorously evaluate the extent to which migraines and/or its treatments are associated with the occurrence of placental abruption.

  4. Rapid DNA haplotyping using a multiplex heteroduplex approach: Application to Duchenne muscula dystrophy carrier detection

    Energy Technology Data Exchange (ETDEWEB)

    Prior, T.W.; Wenger, G.D.; Moore, J. [Ohio State Univ., Columbus, OH (United States)] [and others

    1994-09-01

    A new strategy has been developed for rapid haplotype analysis. It is based on an initial multiplex amplification of several polymorphic sites, followed by heteroduplex detection. Heteroduplexes formed between two different alleles are detected because they migrate differently than the corresponding homoduplexes in Hydrolink-MDE gel. The method is simple, rapid, does not depend on specific sequences such as restriction enzyme sites or CA boxes and does not require the use of isotope. This approach has been tested using 12 commonly occurring polymorphisms spanning the dystrophin gene as a model. We describe the use of the method to assign the carrier status of females in Duchenne muscular dystrophy (DMD) pedigrees. As a result of expanding the number of detectable polymorphisms throughout the dystrophin gene, we show how the method can easily be combined with dinucleotide analysis to improve the accuracy of carrier detection in the nondeletion cases. The technique is also shown to be used as an effective screen for improving carrier detection in several families with deletions. The finding of heterozygosity within the deletion identifies the at-risk female as a noncarrier. Using this method, we have identified and incorporated 3 new dystrophin polymorphisms (one of which in exon 16 is unique to African Americans). The method may be used other genetic diseases when mutations are unknown, or there are few dinucleotide markers in the gene proximity, or for the identification of haplotype backgrounds of mutant alleles.

  5. School-related risk factors for drunkenness among adolescents: risk factors differ between socio-economic groups

    DEFF Research Database (Denmark)

    Andersen, Anette; Holstein, Bjørn E; Due, Pernille

    2006-01-01

    Purpose: To examine, separately for boys and girls, whether socio-economic differences in drunkenness exist in adolescence, whether the level of exposure to school-related risk factors differ between socio-economic groups, and whether the relative contribution of school-related risk factors......) was measured by parental occupation. RESULTS: Among girls, exposures to school-related risk factors were more prevalent in lower socio-economic groups. Poor school satisfaction was associated with drunkenness among girls from high SEP, odds ratio (OR) = 2.98 (0.73-12.16). Among boys from high SEP autonomy...

  6. Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus.

    Directory of Open Access Journals (Sweden)

    Christopher G Bell

    2010-11-01

    Full Text Available Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D, focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip and absolute methylation values were estimated using a Bayesian algorithm (BATMAN. Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p = 9.40×10(-4, permutation p = 1.0×10(-3. Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p = 1.13×10(-7. Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM, encapsulates a Highly Conserved Non-Coding Element (HCNE that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases.

  7. The perception of risks related to electricity generation

    Energy Technology Data Exchange (ETDEWEB)

    Midden, C J; Daamen, D D; Verplanken, B

    1987-01-01

    Some of the key findings are discussed of psychological research on the perception of risks and attitudes with respect to the use of uranium and coal for electricity generation. It appears that attitudes are mostly not based on ideology but rather determined by a trade-off of expected risks and advantages. Lay estimates of probabilities are compared with expert judgements. In the last section attitudes of people living near existing or planned power plants are analyzed. Serious doubts are raised about the possibilities to give residents economic compensation for exposure to risks. 1 fig., 29 refs.

  8. Worldwide genealogy of Entamoeba histolytica: an overview to understand haplotype distribution and infection outcome.

    Science.gov (United States)

    Zermeño, Valeria; Ximénez, Cecilia; Morán, Patricia; Valadez, Alicia; Valenzuela, Olivia; Rascón, Edgar; Diaz, Daniel; Cerritos, René

    2013-07-01

    Although Entamoeba histolytica is one of the most prevalent intestinal parasites, how the different strains of this species are distributed all over the world and how different genotypes are associated with the infection outcome are yet to be fully understood. Recently, the use of a number of molecular markers has made the characterization of several genotypes in those regions with high incidence of amoebiasis possible. This work proposes the first genealogy of E. histolytica, with an haplotype network based on two tRNA gene-linked array of Short Tandem Repeats (STRs) reported until today, and 47 sequences from 39 new isolates of Mexican Amoebic Liver Abscesses (ALA) samples. One hundred and three sequences were obtained from D-A locus, their information about the geographic region of isolation as well as clinical diagnosis were also collected. One hundred and five sequences from N-K2 locus were also obtained as well as the region of isolation, but the information about clinical diagnosis was not available in all cases. The most abundant and widely distributed haplotype in the world is the one of E. histolytica HM1:IMSS strain. This was found in Mexico, Bangladesh, Japan, China and USA and is associated to symptomatic patients as well as asymptomatic cyst passers. Many other haplotypes were found only in a single country. Both genealogies suggest that there are no lineages within the networks that may be related to a particular geographic region or infection outcome. A concatenated analysis of the two molecular markers revealed 12 different combinations, which suggests the possibility of genetic recombination events. The present study is the first to propose a global genealogy of this species and suggests that there are still many genotypes to be discovered. The genotyping of new isolates will help to understand the great diversity and genetic structure of this parasite. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Critical review of methods for risk ranking of food related hazards, based on risks for human health

    DEFF Research Database (Denmark)

    van der Fels-Klerx, H. J.; van Asselt, E. D.; Raley, M.

    2018-01-01

    This study aimed to critically review methods for ranking risks related to food safety and dietary hazards on the basis of their anticipated human health impacts. A literature review was performed to identify and characterize methods for risk ranking from the fields of food, environmental science......, and the risk ranking method characterized. The methods were then clustered - based on their characteristics - into eleven method categories. These categories included: risk assessment, comparative risk assessment, risk ratio method, scoring method, cost of illness, health adjusted life years, multi......-criteria decision analysis, risk matrix, flow charts/decision trees, stated preference techniques and expert synthesis. Method categories were described by their characteristics, weaknesses and strengths, data resources, and fields of applications. It was concluded there is no single best method for risk ranking...

  10. The risk of cataract in relation to metal arc welding

    DEFF Research Database (Denmark)

    Slagor, Rebekka Michaelsen; Dornonville de la Cour, Morten; Bonde, Jens Peter

    2016-01-01

    .95–1.21] and the adjusted HR was 1.08 (95% CI 0.95–1.22). Age and diabetes were as expected strong risk factors. Conclusion: We found no increased risk of developing cataract among Danish metal welders who worked with arc welding from 1950–1985. This may be attributed to the effectiveness of personal safety equipment....... increases the risk of cataract. Method: We compared the risk of being diagnosed with cataract from 1987–2012 in a historic cohort of 4288 male metal arc welders against a reference group comprised of Danish skilled and unskilled male workers with similar age distribution. For the welders’ cohort...... adjusted for baseline data regarding age, diabetes, and social group. Results: There were 266 welders and 29 007 referents with a diagnosis and/or operation for cataract. The unadjusted HR for cataract comparing ever-welders with referents was 1.07 [95% confidence interval (95% CI) 0...

  11. Relation between Childhood Obesity and Adult Cardiovascular Risk

    Directory of Open Access Journals (Sweden)

    Darren M. Allcock

    2009-01-01

    Full Text Available The incidence of overweight and obesity is rising at an alarming pace in the pediatric population, just as in the adult population. The adult comorbidities associated with this risk factor are well-recognized and are being further elucidated continually. Additionally, we are gradually developing a better understanding of the risks of overweight and obesity among children while they are still young. However, there is now a growing body of evidence showing that childhood obesity not only leads all too frequently to adult obesity, but is in itself a risk factor for cardiometabolic syndrome and resultant cardiovascular risk in adulthood. If current trends continue, the problem of pediatric overweight and obesity will become of unmanageable proportions once these individuals reach adulthood. Future research efforts toward understanding this complex problem will need to focus on those overweight and obese children who later went on to change their metabolic course and become normal-weight adults.

  12. Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study.

    Science.gov (United States)

    Hardi, Hanaa; Melki, Rahma; Boughaleb, Zouhour; El Harroudi, Tijani; Aissaoui, Souria; Boukhatem, Noureddine

    2018-03-15

    Genetic determinants of breast cancer (BC) remained largely unknown in the majority of Moroccan patients. The purpose of this study was to explore the association of ERCC2 and MTHFR polymorphisms with genetic susceptibility to breast cancer in Moroccan population. We genotyped ERCC2 polymorphisms (rs1799793 (G934A) and rs13181 (A2251C)) and MTHFR polymorphisms (rs1801133 (C677T) and rs1801131 (A1298C)) using TaqMan SNP Genotyping Assays. Genotypes were compared in 151 BC cases and 156 population-matched controls. Allelic, genotypic and haplotype associations with the risk and clinicopathological features of BC were assessed using logistic regression analyses. ERCC2-rs1799793-AA genotype was associated with high risk of BC compared to wild type genotype (recessive model: OR: 2.90, 95% CI: 1.34-6.26, p = 0.0069) even after Bonferroni correction (p < 0,0125). MTHFR rs1801133-TT genotype was associated with increased risk of BC (recessive model, OR: 2.49, 95% CI: 1.17-5.29, p = 0.017) but the association turned insignificant after Bonferroni correction. For the rest of SNPs, no statistical associations to BC risk were detected. Significant association with clinical features was detected for MTHFR-rs1801133-TC genotype with early age at diagnosis and familial BC. Following Bonferroni correction, only association with familial BC remained significant. MTHFR-rs1801131-CC genotype was associated with sporadic BC. ERCC2-rs1799793-AA genotype correlated with ER+ and PR+ breast cancer. ERCC2-rs13181-CA genotype was significantly associated large tumors (T ≥ 3) in BC patients. None of these associations passed Bonferroni correction. Haplotype analysis showed that ERCC2 A-C haplotype was significantly associated with increased BC risk (OR: 3.71, 95% CI: 1.7-8.12, p = 0.0002 and p = 0.0008 before and after Bonferroni correction, respectively) and positive expression of ER and PR in BC patients. ERCC2 G-C haplotype was correlated with PR negative and

  13. Extent of Cropland and Related Soil Erosion Risk in Rwanda

    Directory of Open Access Journals (Sweden)

    Fidele Karamage

    2016-06-01

    Full Text Available Land conversion to cropland is one of the major causes of severe soil erosion in Africa. This study assesses the current cropland extent and the related soil erosion risk in Rwanda, a country that experienced the most rapid population growth and cropland expansion in Africa over the last decade. The land cover land use (LCLU map of Rwanda in 2015 was developed using Landsat-8 imagery. Based on the obtained LCLU map and the spatial datasets of precipitation, soil properties and elevation, the soil erosion rate of Rwanda was assessed at 30-m spatial resolution, using the Revised Universal Soil Loss Equation (RUSLE model. According to the results, the mean soil erosion rate was 250 t·ha−1·a−1 over the entire country, with a total soil loss rate of approximately 595 million tons per year. The mean soil erosion rate over cropland, which occupied 56% of the national land area, was estimated at 421 t·ha−1·a−1 and was responsible for about 95% of the national soil loss. About 24% of the croplands in Rwanda had a soil erosion rate larger than 300 t·ha−1·a−1, indicating their unsuitability for cultivation. With a mean soil erosion rate of 1642 t·ha−1·a−1, these unsuitable croplands were responsible for 90% of the national soil loss. Most of the unsuitable croplands are distributed in the Congo Nile Ridge, Volcanic Range mountain areas in the west and the Buberuka highlands in the north, regions characterized by steep slopes (>30% and strong rainfall. Soil conservation practices, such as the terracing cultivation method, are paramount to preserve the soil. According to our assessment, terracing alone could reduce the mean cropland soil erosion rate and the national soil loss by 79% and 75%, respectively. After terracing, only a small proportion of 7.6% of the current croplands would still be exposed to extreme soil erosion with a rate >300 t·ha−1·a−1. These irremediable cropland areas should be returned to mountain forest to

  14. Correlation between HLA haplotypes and the development of antidrug antibodies in a cohort of patients with rheumatic diseases

    Directory of Open Access Journals (Sweden)

    Benucci M

    2018-01-01

    Full Text Available Maurizio Benucci,1 Arianna Damiani,1 Francesca Li Gobbi,1 Francesca Bandinelli,1 Maria Infantino,2 Valentina Grossi,2 Mariangela Manfredi,2 Guillaume Noguier,3 Francesca Meacci2 1Rheumatology Unit, 2Immunology and Allergology Laboratory Unit, USL-Toscana Centro, Hospital S. Giovanni di Dio, Florence, Italy; 3Theradiag, Croissy Beaubourg, France Introduction: The aim of this study was to investigate the correlation between human leukocyte antigen (HLA haplotypes and the development of antidrug antibodies (ADAs in a cohort of patients with rheumatic diseases.Patients and methods: We evaluated the presence of ADAs in 248 patients with inflammatory rheumatic diseases after 6 months of treatment with anti-TNF drugs: 26 patients were treated with infliximab (IFX; three with rheumatoid arthritis [RA], 13 with ankylosing spondylitis [AS], 10 with psoriatic arthritis [PsA]; 83 treated with adalimumab (ADA; 24 with RA, 36 with AS, 23 with PsA; 88 treated with etanercept (ETA; 35 with RA, 27 with AS, 26 with PsA; 32 treated with certolizumab (CERT; 25 with RA, two with AS, five with PsA; and 19 treated with golimumab (GOL; three with RA, seven with AS, nine with PsA. Serum drug and ADA levels were determined using Lisa-Tracker Duo, the ADA-positive samples underwent an inhibition test, and the true-positive samples underwent genetic HLA typing. To have a homogeneous control population, we also performed genetic HLA typing of 11 ADA-negative patients.Results: After inhibition test, the frequency of ADAs was 2/26 patients treated with IFX (7.69%, 4/83 treated with ADA (4.81%, 0/88 treated with ETA (0%, 4/32 treated with CERT (12.5%, and 1/19 treated with GOL (5.26%. The frequency of HLA alleles in the examined patients was HLA-DRβ-11 0.636, HLA-DQ-03 0.636, and HLA-DQ-05 0.727. The estimated relative risks between the ADA-positive patients and the ADA-negative patients were HLA-DRβ-11 2.528 (95% CI 0.336–19.036, HLA-DQ-03 1.750 (95% CI 0.289–10

  15. Search for common haplotypes on chromosome 22q in patients with schizophrenia or bipolar disorder from the Faroe Islands

    DEFF Research Database (Denmark)

    Jorgensen, T H; Børglum, A D; Mors, O

    2002-01-01

    Chromosome 22q may harbor risk genes for schizophrenia and bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. Patients with schizophrenia and bipolar affective disorder from the Faroe...... Islands were typed for 35 evenly distributed polymorphic markers on 22q in a search for shared risk genes in the two disorders. No single marker was strongly associated with either disease, but five two-marker segments that cluster within two regions on the chromosome have haplotypes occurring...

  16. Evaluation of haplotype diversity of Achatina fulica (Lissachatina) [Bowdich] from Indian sub-continent by means of 16S rDNA sequence and its phylogenetic relationships with other global populations.

    Science.gov (United States)

    Ayyagari, Vijaya Sai; Sreerama, Krupanidhi

    2017-08-01

    Achatina fulica (Lissachatina fulica) is one of the most invasive species found across the globe causing a significant damage to crops, vegetables, and horticultural plants. This terrestrial snail is native to east Africa and spread to different parts of the world by introductions. India, a hot spot for biodiversity of several endemic gastropods, has witnessed an outburst of this snail population in several parts of the country posing a serious threat to crop loss and also to human health. With an objective to evaluate the genetic diversity of this snail, we have sampled this snail from different parts of India and analyzed its haplotype diversity by means of 16S rDNA sequence information. Apart from this, we have studied the phylogenetic relationships of the isolates sequenced in the present study in relation with other global populations by Bayesian and Maximum-likelihood approaches. Of the isolates sequenced, haplotype 'C' is the predominant one. A new haplotype 'S' from the state of Odisha was observed. The isolates sequenced in the present study clustered with its conspecifics from the Indian sub-continent. Haplotype network analyses were also carried out for studying the evolution of different haplotypes. It was observed that haplotype 'S' was associated with a Mauritius haplotype 'H', indicating the possibility of multiple introductions of A. fulica to India.

  17. Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population.

    Science.gov (United States)

    Fukushima-Uesaka, Hiromi; Saito, Yoshiro; Watanabe, Hidemi; Shiseki, Kisho; Saeki, Mayumi; Nakamura, Takahiro; Kurose, Kouichi; Sai, Kimie; Komamura, Kazuo; Ueno, Kazuyuki; Kamakura, Shiro; Kitakaze, Masafumi; Hanai, Sotaro; Nakajima, Toshiharu; Matsumoto, Kenji; Saito, Hirohisa; Goto, Yu-ichi; Kimura, Hideo; Katoh, Masaaki; Sugai, Kenji; Minami, Narihiro; Shirao, Kuniaki; Tamura, Tomohide; Yamamoto, Noboru; Minami, Hironobu; Ohtsu, Atsushi; Yoshida, Teruhiko; Saijo, Nagahiro; Kitamura, Yutaka; Kamatani, Naoyuki; Ozawa, Shogo; Sawada, Jun-ichi

    2004-01-01

    In order to identify single nucleotide polymorphisms (SNPs) and haplotype frequencies of CYP3A4 in a Japanese population, the distal enhancer and proximal promoter regions, all exons, and the surrounding introns were sequenced from genomic DNA of 416 Japanese subjects. We found 24 SNPs, including 17 novel ones: two in the distal enhancer, four in the proximal promoter, one in the 5'-untranslated region (UTR), seven in the introns, and three in the 3'-UTR. The most common SNP was c.1026+12G>A (IVS10+12G>A), with a 0.249 frequency. Four non-synonymous SNPs, c.554C>G (p.T185S, CYP3A4(*)16), c.830_831insA (p.E277fsX8, (*)6), c.878T>C (p.L293P, (*)18), and c.1088 C>T (p.T363M, (*)11) were found with frequencies of 0.014, 0.001, 0.028, and 0.002, respectively. No SNP was found in the known nuclear transcriptional factor-binding sites in the enhancer and promoter regions. Using these 24 SNPs, 16 haplotypes were unambiguously identified, and nine haplotypes were inferred by aid of an expectation-maximization-based program. In addition, using data from 186 subjects enabled a close linkage to be found between CYP3A4 and CYP3A5 SNPs, especially among the SNPs at c.1026+12 in CYP3A4 and c.219-237 (IVS3-237, a key SNP site for CYP3A5(*)3), c.865+77 (IVS9+77) and c.1523 in CYP3A5. This result suggested that CYP3A4 and CYP3A5 are within the same gene block. Haplotype analysis between CYP3A4 and CYP3A5 revealed several major haplotype combinations in the CYP3A4-CYP3A5 block. Our findings provide fundamental and useful information for genotyping CYP3A4 (and CYP3A5) in the Japanese, and probably Asian populations. Copyright 2003 Wiley-Liss, Inc.

  18. A prospective study of gait related risk factors for exercise-related lower leg pain.

    Science.gov (United States)

    Willems, T M; De Clercq, D; Delbaere, K; Vanderstraeten, G; De Cock, A; Witvrouw, E

    2006-01-01

    The purpose of this study was to determine prospectively gait related risk factors for exercise-related lower leg pain (ERLLP) in 400 physical education students. Static lower leg alignment was determined, and 3D gait kinematics combined with plantar pressure profiles were collected. After this evaluation, all sports injuries were registered by the same sports physician during the duration of the study. Forty six subjects developed ERLLP and 29 of them developed bilateral symptoms thus giving 75 symptomatic lower legs. Bilateral lower legs of 167 subjects who developed no injuries in the lower extremities served as controls. Cox regression analysis revealed that subjects who developed ERLLP had an altered running pattern before the injury compared to the controls and included (1) a significantly more central heel-strike, (2) a significantly increased pronation, accompanied with more pressure underneath the medial side of the foot, and (3) a significantly more lateral roll-off. These findings suggest that altered biomechanics play a role in the genesis of ERLLP and thus should be considered in prevention and rehabilitation.

  19. Assessment of credit risk based on fuzzy relations

    Science.gov (United States)

    Tsabadze, Teimuraz

    2017-06-01

    The purpose of this paper is to develop a new approach for an assessment of the credit risk to corporate borrowers. There are different models for borrowers' risk assessment. These models are divided into two groups: statistical and theoretical. When assessing the credit risk for corporate borrowers, statistical model is unacceptable due to the lack of sufficiently large history of defaults. At the same time, we cannot use some theoretical models due to the lack of stock exchange. In those cases, when studying a particular borrower given that statistical base does not exist, the decision-making process is always of expert nature. The paper describes a new approach that may be used in group decision-making. An example of the application of the proposed approach is given.

  20. Risks of multiple sclerosis in relatives of patients in Flanders, Belgium

    NARCIS (Netherlands)

    Carton, H; Vlietinck, R; Debruyne, J; DeKeyser, J; DHooghe, MB; Loos, R; Medaer, R; Truyen, L; Yee, IML; Sadovnick, AD

    Objectives - To calculate age adjusted risks for multiple sclerosis in relatives of Flemish patients with multiple sclerosis. Methods - Lifetime risks were calculated using the maximum likelihood approach. Results - Vital information was obtained on 674 probands with multiple sclerosis in Flanders

  1. Pushing and pulling in relation to musculoskeletal disorders : a review of risk factors

    NARCIS (Netherlands)

    Hoozemans, M J; Van Der Beek, Allard J.; Frings-Dresen, M. H. W.; Dijk, F.J.H.; van der Woude, L H

    The objective was to review the literature on risk factors for musculoskeletal disorders related to pushing and pulling. The risk factors have been described and evaluated from four perspectives: epidemiology, psychophysics, physiology, and biomechanics. Epidemiological studies have shown, based on

  2. Pushing and pulling in relation to musculoskeletal disorders: a review of risk factors

    NARCIS (Netherlands)

    Hoozemans, Marco; van der Beek, A.J.; Frings-Dresen, M.H.W.; Dijk, F.J.H.

    1998-01-01

    The objective was to review the literature on risk factors for musculoskeletal disorders related to pushing and pulling. The risk factors have been described and evaluated from four perspectives: epidemiology, psychophysics, physiology, and biomechanics. Epidemiological studies have shown, based on

  3. Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qian-fei; Liu, Xin; O' Connell, Jeff; Peng, Ze; Krauss, Ronald M.; Rainwater, David L.; VandeBerg, John L.; Rubin, Edward M.; Cheng, Jan-Fang; Pennacchio, Len A.

    2003-09-15

    Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however, whether independently arising polymorphisms in orthologous regions of non-human primates leads to similar variation in a quantitative trait found in both species. To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well established roles in influencing plasma HDL-cholesterol and triglyceride concentrations. Our extensive polymorphism analysis of this 68 kb gene cluster in 96 pedigreed baboons identified several haplotype blocks each with limited diversity, consistent with haplotype findings in humans. To determine whether baboons, like humans, also have particular haplotypes associated with lipid phenotypes, we genotyped 634 well characterized baboons using 16 haplotype tagging SNPs. Genetic analysis of single SNPs, as well as haplotypes, revealed an association of APOA5 and APOC3 variants with HDL cholesterol and triglyceride concentrations, respectively. Thus, independent variation in orthologous genomic intervals does associate with similar quantitative lipid traits in both species, supporting the possibility of uncovering human QTL genes in a highly controlled non-human primate model.

  4. Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation.

    Science.gov (United States)

    von Salomé, Jenny; Liu, Tao; Keihäs, Markku; Morak, Moni; Holinski-Feder, Elke; Berry, Ian R; Moilanen, Jukka S; Baert-Desurmont, Stéphanie; Lindblom, Annika; Lagerstedt-Robinson, Kristina

    2017-12-29

    Lynch syndrome (LS) predisposes to a spectrum of cancers and increases the lifetime risk of developing colorectal- or endometrial cancer to over 50%. Lynch syndrome is dominantly inherited and is caused by defects in DNA mismatch-repair genes MLH1, MSH2, MSH6 or PMS2, with the vast majority detected in MLH1 and MSH2. Recurrent LS-associated variants observed in apparently unrelated individuals, have either arisen de novo in different families due to mutation hotspots, or are inherited from a founder (a common ancestor) that lived several generations back. There are variants that recur in some populations while also acting as founders in other ethnic groups. Testing for founder mutations can facilitate molecular diagnosis of Lynch Syndrome more efficiently and more cost effective than screening for all possible mutations. Here we report a study of the missense mutation MLH1 c.2059C > T (p.Arg687Trp), a potential founder mutation identified in eight Swedish families and one Finnish family with Swedish ancestors. Haplotype analysis confirmed that the Finnish and Swedish families shared a haplotype of between 0.9 and 2.8 Mb. While MLH1 c.2059C > T exists worldwide, the Swedish haplotype was not found among mutation carriers from Germany or France, which indicates a common founder in the Swedish population. The geographic distribution of MLH1 c.2059C > T in Sweden suggests a single, ancient mutational event in the northern part of Sweden.

  5. Understanding the NSAID related risk of vascular events

    NARCIS (Netherlands)

    Vonkeman, Harald Erwin; Brouwers, Jacobus R.B.J.; van de Laar, Mart A F J

    2006-01-01

    Concern is growing about an increased risk of thrombotic events (including myocardial infarction and stroke) during the use of non-steroidal anti-inflammatory drugs (NSAIDs), in particular the so called selective cyclo-oxygenase-2 (COX 2) inhibitors. Although clinical trials give conflicting results

  6. Is parental age related to the risk of Alzheimer's disease

    NARCIS (Netherlands)

    C.M. van Duijn (Cornelia); W. Schulte (Wim); T.A. Tanja (Teun); R. Haaxma (Rob); A.J. Lameris; R.J. Saan; A. Hofman (Albert)

    1990-01-01

    textabstractAdvanced maternal and paternal age were investigated as putative risk factors for AD in 198 clinically diagnosed Alzheimer patients and in 198 randomly selected healthy controls. No significant differences in average age of fathers and of mothers at birth of the subject were observed.

  7. Advanced prostate cancer risk in relation to toenail selenium levels

    NARCIS (Netherlands)

    Geybels, M.S.; Verhage, B.A.J.; Schooten, F.J. van; Goldbohm, A.; Brandt, P.A. van den

    2013-01-01

    BACKGROUND: Selenium may prevent advanced prostate cancer (PCa), but most studies on this topic were conducted in populations with moderate to high selenium status. We investigated the association of toenail selenium, reflecting long-term selenium exposure, and advanced PCa risk in a population from

  8. Cancer risk in relation to serum copper levels.

    Science.gov (United States)

    Coates, R J; Weiss, N S; Daling, J R; Rettmer, R L; Warnick, G R

    1989-08-01

    A nested, matched case-control study was conducted to assess the relationship between serum levels of copper and the subsequent risk of cancer. One hundred thirty-three cases of cancer were identified during 1974-1984 among 5000 members of a northwest Washington State employee cohort from whom serum specimens had been previously obtained and stored. Two hundred forty-one controls were selected at random from the cohort and were matched to the cases on the basis of age, sex, race, and date of blood draw. Serum copper levels were measured by atomic absorption spectrometry. Risk of a subsequent diagnosis of cancer was positively associated with serum copper levels, but only among those cases diagnosed within 4 years of the time the serum specimens were collected. Among cases diagnosed more than 4 years after specimen collection, there was no consistent association between serum copper levels and risk. Adjustment for age, sex, race, occupational status, cigarette smoking, family history of cancer, alcohol consumption, and, among females, use of exogenous hormones had no appreciable effect on these relationships. The findings suggest that the presence of cancer may increase serum copper levels several years prior to its diagnosis. They are less supportive of the hypothesis that serum copper levels affect cancer risk.

  9. Radon - The management of the risk related to radon

    International Nuclear Information System (INIS)

    2010-01-01

    This leaflet briefly explains what radon is, where it comes from, and what it becomes. It indicates and briefly comments its concentrations in French departments, describes how radon can affect our health (lung cancer), describes how the risk can be reduced in buildings, and indicates the existing regulatory provisions

  10. HLA alleles and HLA-B27 haplotypes associated with susceptibility and severity of ankylosing spondylitis in a Portuguese population.

    Science.gov (United States)

    Pimentel-Santos, F M; Matos, M; Ligeiro, D; Mourão, A F; Ribeiro, C; Costa, J; Santos, H; Barcelos, A; Pinto, P; Cruz, M; Sousa, E; Santos, R A; Fonseca, J E; Trindade, H; Guedes-Pinto, H; Branco, J C

    2013-12-01

    Human leukocyte antigen (HLA)-B27 is the mostly known major histocompatibility complex (MHC) gene associated with ankylosing spondylitis (AS). Nonetheless, there is substantial evidence that other MHC genes appear to be associated with the disease, although it has not yet been established whether these associations are driven by direct associations or by linkage disequilibrium (LD) mechanisms. We aimed to investigate the contributions of HLA class I and II alleles and B27-haplotypes for AS in a case-control study. A total of 188 HLA-B27 AS cases and 189 HLA-B27 healthy controls were selected and typed for HLA class I and II by the Luminex polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. Allelic and haplotypic distributions were estimated by maximum likelihood method using Arlequin v3.11 and statistical analysis were performed by Stata10.1. No associations were found between non-HLA-B27 loci and AS susceptibility, but several associations were observed for phenotypic features of the disease. DRB1*08 was identified as a risk factor for uveitis and DQB1*04 seems to provide protection for AS severity (functional, metrological and radiological indexes). A*02/B27/C*02/DRB1*01/DQB1*05 [P<0.0001; odds ratio (OR) = 39.06; 95% confidence interval (CI) (2.34-651)] is the only haplotype that seems to confer susceptibility to AS. Moreover, the haplotype A*02/B27/C*01/DRB1*08/DQB1*04 seems to provide protection for disease functional and radiological repercussions. Our findings are compatible with the hypothesis that other genes within the HLA region besides HLA-B27 might play some role in AS susceptibility and severity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Review on risk factors related to lower back disorders at workplace

    Science.gov (United States)

    A' Tifah Jaffar, Nur; Nasrull Abdol Rahman, Mohd

    2017-08-01

    This review examines the evidence of the occurrence of risk exposure on work-related lower back disorders in the workplace. This review also investigates potential interactions between the risk factors in the workplace which include heavy physical work risk factor, static work postures risk factor, frequent bending and twisting risk factor, lifting risk factor, pushing and pulling risk factor, repetitive work risk factor, vibration risk factor, psychological and psychosocial risk factor that may be associated with symptoms of musculoskeletal disorders of lower back. These risk factors can reinforce each other and their influence can also be mediated by cultural or social factors. A systematic review of the literature was carried out by searching using databases and the searching strategy was used combined keyword for risk factors, work-related lower back disorders, heavy physical work, static work postures, frequent bending and twisting, lifting, pushing and pulling, repetitive work, vibration, psychological and psychosocial risk factor. A total of 67 articles were identified and reviewed. The risk factors identified that related for low back disorder are seven which are heavy physical work, static work postures, frequent bending and twisting, lifting, pushing and pulling, repetitive work, vibration, psychological and psychosocial risk factor and the level of evidence supporting the relationship with lower back disorders also described such as strong, moderate, insufficient, limited and no evidence. This result confirms that, existing of higher physical and psychosocial demand related to reported risk factors of low back disorders. The result also showed that previous reviews had evaluated relationship between risk factors of low back disorders and specific types of musculoskeletal disorders. This review also highlights the scarves evidence regarding some of the frequently reported risk factors for work related lower back disorders.

  12. Using prior risk-related knowledge to support risk management decisions: lessons learnt from a tunneling project.

    Science.gov (United States)

    Cárdenas, Ibsen Chivatá; Al-Jibouri, Saad S H; Halman, Johannes I M; van de Linde, Wim; Kaalberg, Frank

    2014-10-01

    The authors of this article have developed six probabilistic causal models for critical risks in tunnel works. The details of the models' development and evaluation were reported in two earlier publications of this journal. Accordingly, as a remaining step, this article is focused on the investigation into the use of these models in a real case study project. The use of the models is challenging given the need to provide information on risks that usually are both project and context dependent. The latter is of particular concern in underground construction projects. Tunnel risks are the consequences of interactions between site- and project-specific factors. Large variations and uncertainties in ground conditions as well as project singularities give rise to particular risk factors with very specific impacts. These circumstances mean that existing risk information, gathered from previous projects, is extremely difficult to use in other projects. This article considers these issues and addresses the extent to which prior risk-related knowledge, in the form of causal models, as the models developed for the investigation, can be used to provide useful risk information for the case study project. The identification and characterization of the causes and conditions that lead to failures and their interactions as well as their associated probabilistic information is assumed to be risk-related knowledge in this article. It is shown that, irrespective of existing constraints on using information and knowledge from past experiences, construction risk-related knowledge can be transferred and used from project to project in the form of comprehensive models based on probabilistic-causal relationships. The article also shows that the developed models provide guidance as to the use of specific remedial measures by means of the identification of critical risk factors, and therefore they support risk management decisions. Similarly, a number of limitations of the models are

  13. How to deal with Haplotype data: An Extension to the Conceptual Schema of the Human Genome

    Directory of Open Access Journals (Sweden)

    José Fabián Reyes Román

    2016-12-01

    Full Text Available The goal of this work is to describe the advantages of the application of Conceptual Modeling (CM in complex domains, such as genomics. Nowadays, the study and comprehension of the human genome is a major challenge due to its high level of complexity. The constant evolution in the genomic domain contributes to the generation of ever larger amounts of new data, which means that if we do not manage it correctly data quality could be compromised (i.e., problems related with heterogeneity and inconsistent data. In this paper, we propose the use of a Conceptual Schema of the Human Genome (CSHG, designed to understand and improve our ontological commitment to the domain and also extend (enrich this schema with the integration of a novel concept: Haplotypes. Our focus is on improving the understanding of the relationship between genotype and phenotype, since new findings show that this question is more complex than was originally thought. Here we present the first steps in our data management approach with haplotypes (variations, frequencies and populations and discuss the database evolution to support this data. Each new version in our conceptual schema (CS introduces changes to the underlying database structure that has essential and practical implications for better understanding and managing the relevant information. A solution based on conceptual models gives a clear definition of the domain with direct implications in the medical field (Precision Medicine, in which Genomic Information Systems (GeIS play a very important role.

  14. Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study

    Science.gov (United States)

    Purpose: Because foods provide many nutrients, which may interact with each other to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. Th...

  15. Characterizing users of new psychoactive substances using psychometric scales for risk-related behavior

    NARCIS (Netherlands)

    Vreeker, Annabel; van der Burg, Babette G.; van Laar, Margriet; Brunt, Tibor M.

    2017-01-01

    Studies investigating risk-related behavior in relation to new psychoactive substance (NPS) use are sparse. The current study investigated characteristics of NPS users by comparing risk-related behavior of NPS users to that of illicit drugs (ID) users and licit substances users and non-users (NLC)

  16. Quantitative trait loci and the relevance of phased haplotypes

    DEFF Research Database (Denmark)

    Gregersen, Vivi Raundahl

    Genetic control of different production traits and diseases within livestock has been of great interest since domenstication. SNPs have greatly facilitated the use of QTL studies in the search of genomic regions affecting different phenotypes. The studies have been conducted to identify regions...... underlying gentic control both as traditional linkage studies relying on genetic maps and as GWAS where an approach of phasing haplotypes within the QTL have been conducted to validate the regions. Overall, regions of interest have been identified for chronic pleuritis and osteochondrosis in addition to meat...... quality and boar taint in pigs, and for improved chees production within cows...

  17. A haplotype specific to North European wheat (Triticum aestivum L.)

    Czech Academy of Sciences Publication Activity Database

    Tsombalova, J.; Karafiátová, Miroslava; Vrána, Jan; Kubaláková, Marie; Peusa, H.; Jakobson, I.; Jarve, M.; Valárik, Miroslav; Doležel, Jaroslav; Jarve, K.

    2017-01-01

    Roč. 64, č. 4 (2017), s. 653-664 ISSN 0925-9864 R&D Projects: GA MŠk(CZ) LO1204; GA ČR(CZ) GA14-07164S Institutional support: RVO:61389030 Keywords : bread wheat * genetic diversity * polyploid wheat * introgression lines * molecular analysis * tetraploid wheat * hexaploid wheat * powdery mildew * spelta l. * map * Common wheat * Triticum aestivum L * Spelt * Triticum spelta L * Chromosome 4A * Zero alleles * Haplotype * Linkage disequilibrium Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 1.294, year: 2016

  18. The thickness and volume of LLETZ specimens can predict the relative risk of pregnancy-related morbidity.

    LENUS (Irish Health Repository)

    Khalid, S

    2012-05-01

    The aim of this study was to determine if the individual physical characteristics of the extirpated transformation zone after large loop excision of the transformation zone (LLETZ) might predict the relative risk of adverse obstetric outcome, specifically preterm labour (PTL).

  19. Disentangling the risk assessment and intimate partner violence relation: Estimating mediating and moderating effects.

    Science.gov (United States)

    Williams, Kirk R; Stansfield, Richard

    2017-08-01

    To manage intimate partner violence (IPV), the criminal justice system has turned to risk assessment instruments to predict if a perpetrator will reoffend. Empirically determining whether offenders assessed as high risk are those who recidivate is critical for establishing the predictive validity of IPV risk assessment instruments and for guiding the supervision of perpetrators. But by focusing solely on the relation between calculated risk scores and subsequent IPV recidivism, previous studies of the predictive validity of risk assessment instruments omitted mediating factors intended to mitigate the risk of this behavioral recidivism. The purpose of this study was to examine the mediating effects of such factors and the moderating effects of risk assessment on the relation between assessed risk (using the Domestic Violence Screening Instrument-Revised [DVSI-R]) and recidivistic IPV. Using a sample of 2,520 perpetrators of IPV, results revealed that time sentenced to jail and time sentenced to probation each significantly mediated the relation between DVSI-R risk level and frequency of reoffending. The results also revealed that assessed risk moderated the relation between these mediating factors and IPV recidivism, with reduced recidivism (negative estimated effects) for high-risk perpetrators but increased recidivism (positive estimate effects) for low-risk perpetrators. The implication is to assign interventions to the level of risk so that no harm is done. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Respiratory Health Symptoms among Schoolchildren in Relation to Possible Food-Related Risk and Protective Factors.

    Science.gov (United States)

    Wright, Caradee Y; Nkosi, Vusumuzi; Wichmann, Janine

    2018-03-13

    Respiratory health outcomes are among the top five causes of child morbidity and mortality around the world. We aimed to investigate possible food-related risk and protective factors for respiratory health outcomes in children. Structured questionnaires completed by primary caregivers of 10-year old children were used to collect information on demographics, socio-economic status, house characteristics and child respiratory health status. Upper (URIs) and Lower (LRIs) respiratory illnesses comprised hay fever, and wheezing, asthma and bronchitis, respectively. Eight hundred questionnaires were distributed, 648 retrieved and 420 completed in full (52.5% response rate). The hay fever 6-month prevalence was 22.4% and wheezing had the highest 6-month prevalence among the LRIs (13.8%). The majority of children ate vegetables (75.5%), fruit (69.3%) and chicken or fish (81.7%) regularly. Nearly half of the children (45.5%) regularly ate processed food. Eating processed food regularly was statistical significantly associated with wheeze (Adjusted Odds Ratio (OR) = 2.65; 95% CI: 1.38-5.08), hay fever (OR = 1.62; 95% CI: 1.09-2.64) and bronchitis (OR = 1.27; 95% CI: 1.06-2.56). The study found an association between regular consumption of processed foods and wheeze, hay fever and bronchitis among 10 year old children. The regular consumption of processed food plays a role in adverse respiratory health effects among children and healthy eating is emphasized.

  1. The evolution of risk perceptions related to bovine spongiform encephalopathy--Canadian consumer and producer behavior.

    Science.gov (United States)

    Yang, Jun; Goddard, Ellen

    2011-01-01

    In this study the dynamics of risk perceptions related to bovine spongiform encephalopathy (BSE) held by Canadian consumers and cow-calf producers were evaluated. Since the first domestic case of BSE in 2003, Canadian consumers and cow-calf producers have needed to make decisions on whether or not their purchasing/production behavior should change. Such changes in their behavior may relate to their levels of risk perceptions about BSE, risk perceptions that may be evolving over time and be affected by BSE media information available. An econometric analysis of the behavior of consumers and cow-calf producers might identify the impacts of evolving BSE risk perceptions. Risk perceptions related to BSE are evaluated through observed market behavior, an approach that differs from traditional stated preference approaches to eliciting risk perceptions at a particular point in time. BSE risk perceptions may be specified following a Social Amplification of Risk Framework (SARF) derived from sociology, psychology, and economics. Based on the SARF, various quality and quantity indices related to BSE media information are used as explanatory variables in risk perception equations. Risk perceptions are approximated using a predictive difference approach as defined by Liu et al. (1998). Results showed that Canadian consumer and cow-calf producer risk perceptions related to BSE have been amplified or attenuated by both quantity and quality of BSE media information. Government policies on risk communications need to address the different roles of BSE information in Canadian consumers' and cow-calf producers' behavior.

  2. Chronic and Acute Relational Risk Factors for Dating Aggression in Adolescence and Young Adulthood.

    Science.gov (United States)

    Collibee, Charlene; Furman, Wyndol

    2016-04-01

    Dating aggression is a prevalent and costly public health concern. Using a relational risk framework, this study examined acute and chronic relational risk factors (negative interactions, jealousy, support, and relationship satisfaction) and their effects on physical and psychological dating aggression. The study also examined the interaction between chronic and acute risk, allowing us to assess how changes in acute risk have differing effects depending on whether the individual is typically at higher chronic risk. A sample of 200 youth (100 female) completed seven waves of data, which spanned 9 years from middle adolescence to young adulthood (M age at Wave 1 = 15.83). Using hierarchical linear modeling, analyses revealed both acute (within-person) and chronic (between-person) levels in jealousy, negative interactions, and relationship satisfaction, were associated with physical and psychological dating aggression. Significant interactions between chronic and acute risk emerged in predicting physical aggression for negative interactions, jealousy, and relationship satisfaction such that those with higher levels of chronic risk are more vulnerable to increases in acute risk. These interactions between chronic and acute risk indicate that risk is not static, and dating aggression is particularly likely to occur at certain times for youth at high risk for dating aggression. Such periods of increased risk may provide opportunities for interventions to be particularly effective in preventing dating aggression or its consequences. Taken together, these findings provide support for the role of relational risk factors for dating aggression. They also underscore the importance of considering risk dynamically.

  3. Risk Perception Analysis Related To Existing Dams In Italy

    Science.gov (United States)

    Solimene, Pellegrino

    2013-04-01

    In the first part of this work, the progress of Italian National Rules about dams design, construction and operation are presented to highlight the strong connection existing between the promulgation of new decrees, as a consequence of a dam accidents, and the necessity to prevent further loss of lives and goods downstream. Following the Gleno Dam failure (1923), a special Ministerial Committee wrote out the first Regulations and made the proposal to establish, within the High Council of Public Works, a special department that become soon the "Dam Service", with the tasks of control and supervision about construction and operation phases of the dams and their reservoirs. A different definition of tasks and the structure of Dam Service were provided in accordance with law n° 183/1989, which transferred all the technical services to the Office of the Prime Minister; the aim was to join the Dam Office with the Department for National Technical Services, with the objective of increasing the knowledge of the territory and promoting the study on flood propagation downstream in case of operations on bottom outlet or hypothetical dam-break. In fact, population living downstream is not ready to accept any amount of risk because has not a good knowledge of the efforts of experts involved in dam safety, both from the operators and from the safety Authority. So it's important to optimize all the activities usually performed in a dam safety program and improve the emergency planning as a response to people's primary needs and feeling about safety from Civil Protection Authority. In the second part of the work, a definition of risk is provided as the relationship existing between probability of occurrence and loss, setting out the range within to plan for prevention (risk mitigation), thanks to the qualitative assessment of the minimum safety level that is suited to assign funds to plan for Civil Protection (loss mitigation). The basic meaning of the reliability of a zoned

  4. External cephalic version-related risks: a meta-analysis

    NARCIS (Netherlands)

    Grootscholten, K.; Kok, M.; Oei, S.G.; Mol, B.W.J.; Post, van der J.A.

    2008-01-01

    OBJECTIVE: To systematically review the literature on external cephalic version–related complications and to assess if the outcome of a version attempt is related to complications. DATA SOURCES: In March 2007 we searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials.

  5. External Cephalic Version-Related Risks A Meta-analysis

    NARCIS (Netherlands)

    Grootscholten, Kim; Kok, Marjolein; Oei, S. Guid; Mol, Ben W. J.; van der Post, Joris A.

    2008-01-01

    OBJECTIVE: To systematically review the literature on external cephalic version-related complications and to assess if the outcome of a version attempt is related to complications. DATA SOURCES: In March 2007 we searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials.

  6. Assessment of reduction in perception of nuclear risk related to perception of environmental risk

    International Nuclear Information System (INIS)

    Boemer, Veronica Araujo; Aquino, Afonso Rodrigues de

    2009-01-01

    This work presents a bibliographic research accomplished to evaluate the matter of reduction in risk perception, on people in general, that nuclear energy can show, for generation of electric power, face to perception of risk associated to environmental questions, as the global warming, from greenhouse effect, addressing the matter to the relevance of public acceptance for the development of new technologies. (author)

  7. Analysis of polymorphisms and haplotype structure of the human thymidylate synthase genetic region: a tool for pharmacogenetic studies.

    Directory of Open Access Journals (Sweden)

    Soma Ghosh

    Full Text Available 5-Fluorouracil (5FU, a widely used chemotherapeutic drug, inhibits the DNA replicative enzyme, thymidylate synthase (Tyms. Prior studies implicated a VNTR (variable numbers of tandem repeats polymorphism in the 5'-untranslated region (5'-UTR of the TYMS gene as a determinant of Tyms expression in tumors and normal tissues and proposed that these VNTR genotypes could help decide fluoropyrimidine dosing. Clinical associations between 5FU-related toxicity and the TYMS VNTR were reported, however, results were inconsistent, suggesting that additional genetic variation in the TYMS gene might influence Tyms expression. We thus conducted a detailed genetic analysis of this region, defining new polymorphisms in this gene including mononucleotide (poly A:T repeats and novel single nucleotide polymorphisms (SNPs flanking the VNTR in the TYMS genetic region. Our haplotype analysis of this region used data from both established and novel genetic variants and found nine SNP haplotypes accounting for more than 90% of the studied population. We observed non-exclusive relationships between the VNTR and adjacent SNP haplotypes, such that each type of VNTR commonly occurred on several haplotype backgrounds. Our results confirmed the expectation that the VNTR alleles exhibit homoplasy and lack the common ancestry required for a reliable marker of a linked adjacent locus that might govern toxicity. We propose that it may be necessary in a clinical trial to assay multiple types of genetic polymorphisms in the TYMS region to meaningfully model linkage of genetic markers to 5FU-related toxicity. The presence of multiple long (up to 26 nt, polymorphic monothymidine repeats in the promoter region of the sole human thymidylate synthetic enzyme is intriguing.

  8. Association of Hypoxia-Inducible Factor-2 Alpha Gene Polymorphisms with the Risk of Hepatitis B Virus-Related Liver Disease in Guangxi Chinese: A Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Liling Huang

    Full Text Available Hypoxia-inducible factor-2 alpha (HIF-2a plays a major role in the progression of disease, although the role of HIF-2α gene polymorphisms in hepatitis B virus (HBV-related diseases remains elusive. The aim of this study is to determine whether HIF-2a rs13419896 and rs6715787 single-nucleotide polymorphisms (SNPs are associated with susceptibility to chronic hepatitis B (CHB, liver cirrhosis (LC, or hepatocellular carcinoma (HCC.A case-control study of 107 patients with CHB, 83 patients with LC, 234 patients with HCC, and 224 healthy control subjects was carried out, and the HIF-2a rs13419896 and rs6715787 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP.No significant differences were observed in the genotype or allele frequency of two HIF-2a SNPs between the cases and controls (all p>0.05. However, in subgroup analysis by gender, the HIF-2a rs13419896 GA and AA genotypes were significantly associated with a risk of CHB (odds ratio [OR] = 3.565, 95% confidence interval [CI] = 1.123-11.314, p = 0.031 and OR = 12.506, 95% CI = 1.329-117.716, p = 0.027 in females, and the A allele of rs13419896 was associated with a risk of CHB (OR = 2.624, 95% CI = 1.244-5.537, p = 0.011 and LC (OR = 2.351, 95% CI = 1.002-5.518, p = 0.050 in females. The rs6715787 CG genotype polymorphism may contribute to a reduced risk of LC in the Guangxi Zhuang Chinese population (OR = 0.152, 95% CI = 0.028-0.807, p = 0.027, as determined via subgroup analysis by ethnicity. Moreover, binary logistic regression analyses that were adjusted by drinking status indicated that the AA genotype of rs13419896 may contribute to an increased risk of LC in the non-alcohol-drinking population (OR = 3.124, 95% CI = 1.091-8.947, p = 0.034. In haplotype analysis, GG haplotype was significantly associated with a reduced risk of LC (OR = 0.601, 95% CI = 0.419-0.862, p = 0.005.The HIF-2a rs13419896 polymorphism is associated with an increased

  9. Identifying Patterns in Extreme Precipitation Risk and the Related Impacts

    Science.gov (United States)

    Schroeer, K.; Tye, M. R.

    2017-12-01

    Extreme precipitation can harm human life and assets through flooding, hail, landslides, or debris flows. Flood risk assessments typically concentrate on river or mountain torrent channels, using water depth, flow velocity, and/or sediment deposition to quantify the risk. In addition, extreme events with high recurrence intervals are often the main focus. However, damages from short-term and localized convective showers often occur away from watercourses. Also, damages from more frequent small scale extremes, although usually less disastrous, can accumulate to considerable financial burdens. Extreme convective precipitation is expected to intensify in a warmer climate, and vulnerability patterns might change in tandem with changes in the character of precipitation and flood types. This has consequences for adaptation planners who want to establish effective protection measures and reduce the cost from natural hazards. Here we merge hydrological and exposure data to identify patterns of risk under varying synoptic conditions. Exposure is calculated from a database of 76k damage claims reported to the national disaster fund in 480 municipalities in south eastern Austria from 1990-2015. Hydrological data comprise sub-daily precipitation (59 gauges) and streamflow (62 gauges) observations. We use synoptic circulation types to identify typical precipitation patterns. They indicate the character of precipitation even if a gauge is not in close proximity, facilitating potential future research with regional climate model data. Results show that more claims are reported under synoptic conditions favouring convective precipitation (on average 1.5-3 times more than on other days). For agrarian municipalities, convective precipitation damages are among the costliest after long low-intensity precipitation events. In contrast, Alpine communities are particularly vulnerable to convective high-intensity rainfall. In addition to possible observational error, uncertainty is present

  10. Risk Management related to Privacy Policies of an Online Store

    Directory of Open Access Journals (Sweden)

    George Cristian Schin

    2016-07-01

    Full Text Available This paper seeks to explore the early warning alerts that NORSE system proposes to e-commerce merchants. The real time visibility to cyber-attacks empowers this intelligence tool with high capabilities to detect the threats that companies confront with. The fight against cyber-criminality should be reinforced globally, in the attempt to mitigate the risks and losses determined by attackers. By analysing two case studies, the article proposes a framework which can guide e-commerce merchants to integrate intelligent systems for threat detection. The managerial implications are obvious, equipping the leaders with tools to prevent both financial and knowledge loss.

  11. Risk assessment of cancer in relation with radon inhalation

    International Nuclear Information System (INIS)

    Timarche, M.; Laurier, D.; Baysson, H.; Catelinois, O.

    2004-01-01

    Several experimental studies have been studied in France in the field of low exposures to radon. The animal studies confirm the increase of ling cancer risk for exposures less than 100 units of exposures. A synthesis is actually running in the frame of an European programme coordinated by the Laboratory of epidemiology from the Institute of radiation protection and nuclear safety (I.R.S.N.). It will describe the different steps of the carcinogenesis brought into play during this chronic exposure at the level of bronchi epithelium by grouping the whole of data coming from the follow up of uranium miners and experimental studies

  12. Job related mortality risks of Hanford workers and their relation to cancer effects of measured doses of external radiation

    International Nuclear Information System (INIS)

    Kneale, G.W.; Mancuso, T.F.; Stewart, A.M.

    1984-01-01

    A continuation of the series by Mancuso, Stewart, and Kneale (MSK) on studies of cancer risks for radiation workers at Hanford is presented. It concentrates on the statistical problems posed by the need to estimate and control for job related mortality risks when there are several changes of occupation and no certainty about how different occupations are related to two socioeconomic factors which have strong health associations-namely, education and income. The final conclusion is that for tissues which are sensitive to cancer induced by radiation there is a risk of cancer for Hanford exposures whose dose response is curvilinear with long latency and increasing effect with increasing exposure age. (author)

  13. Updated listing of haplotypes at the human phenylalanine hydroxylase (PAH) locus

    Energy Technology Data Exchange (ETDEWEB)

    Eisensmith, R.C.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (United States))

    1992-12-01

    Analysis of mutant PAH chromosomes has identified approximately 60 different single-base substitutions and deletions within the PAH locus. Nearly all of these molecular lesions are in strong linkage disequilibrium with specific RFLP haplotypes in different ethnic populations. Thus, haplotype analysis is not only useful for diagnostic purposes but is proving to be a valuable tool in population genetic studies of the origin and spread of phenylketonuria alleles in human populations. PCR-based methods have been developed to detect six of the eight polymorphic restriction sites used for determination of RFLP haplotypes at the PAH locus. A table of the proposed expanded haplotypes is given.

  14. The effect of flight-related behaviour on the risk of venous thrombosis after air travel

    NARCIS (Netherlands)

    Schreijer, Anja J.M.; Cannegieter, Suzanne C.; Doggen, Catharina Jacoba Maria; Rosendaal, Frits R.

    2009-01-01

    In a case–control study including 11 033 participants (The Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study) on risk factors of venous thrombosis, we studied the effect of flight-related behaviour on the risk of venous thrombosis after air travel. Patients

  15. A risk-factor analysis of medical litigation judgments related to fall injuries in Korea.

    Science.gov (United States)

    Kim, Insook; Won, Seonae; Lee, Mijin; Lee, Won

    2018-01-01

    The aim of this study was to find out the risk factors through analysis of seven medical malpractice judgments related to fall injuries. The risk factors were analysed by using the framework that approaches falls from a systems perspective and comprised people, organisational or environmental factors, with each factor being comprised of subfactors. The risk factors found in each of the seven judgments were aggregated into one framework. The risk factors related to patients (i.e. the people factor) were age, pain, related disease, activities and functional status, urination state, cognitive function impairment, past history of fall, blood transfusion, sleep endoscopy state and uncooperative attitude. The risk factors related to the medical staff and caregivers (i.e. people factor) were observation negligence, no fall prevention activities and negligence in managing high-risk group for fall. Organisational risk factors were a lack of workforce, a lack of training, neglecting the management of the high-risk group, neglecting the management of caregivers and the absence of a fall prevention procedure. Regarding the environment, the risk factors were found to be the emergency room, chairs without a backrest and the examination table. Identifying risk factors is essential for preventing fall accidents, since falls are preventable patient-safety incidents. Falls do not happen as a result of a single risk factor. Therefore, a systems approach is effective to identify risk factors, especially organisational and environmental factors.

  16. Risk of infectious diseases among first-degree relatives of transplant recipients who develop CMV infection

    DEFF Research Database (Denmark)

    Ekenberg, C; Lodding, I P; Wareham, N E

    2017-01-01

    Transplant recipients are at high risk of cytomegalovirus (CMV) infection. Mechanisms explaining the variation in risk of infections are far from fully elucidated. We hypothesised that host genetics explains part of the variation in risk of infection and examined if relatives of recipients with C...

  17. Risk and sensitivity analysis in relation to external events

    International Nuclear Information System (INIS)

    Alzbutas, R.; Urbonas, R.; Augutis, J.

    2001-01-01

    This paper presents risk and sensitivity analysis of external events impacts on the safe operation in general and in particular the Ignalina Nuclear Power Plant safety systems. Analysis is based on the deterministic and probabilistic assumptions and assessment of the external hazards. The real statistic data are used as well as initial external event simulation. The preliminary screening criteria are applied. The analysis of external event impact on the NPP safe operation, assessment of the event occurrence, sensitivity analysis, and recommendations for safety improvements are performed for investigated external hazards. Such events as aircraft crash, extreme rains and winds, forest fire and flying parts of the turbine are analysed. The models are developed and probabilities are calculated. As an example for sensitivity analysis the model of aircraft impact is presented. The sensitivity analysis takes into account the uncertainty features raised by external event and its model. Even in case when the external events analysis show rather limited danger, the sensitivity analysis can determine the highest influence causes. These possible variations in future can be significant for safety level and risk based decisions. Calculations show that external events cannot significantly influence the safety level of the Ignalina NPP operation, however the events occurrence and propagation can be sufficiently uncertain.(author)

  18. Human health risk assessment related to cyanotoxins exposure.

    Science.gov (United States)

    Funari, Enzo; Testai, Emanuela

    2008-01-01

    This review focuses on the risk assessment associated with human exposure to cyanotoxins, secondary metabolites of an ubiquitous group of photosynthetic procariota. Cyanobacteria occur especially in eutrophic inland and coastal surface waters, where under favorable conditions they attain high densities and may form blooms and scums. Cyanotoxins can be grouped according to their biological effects into hepatotoxins, neurotoxins, cytotoxins, and toxins with irritating potential, also acting on the gastrointestinal system. The chemical and toxicological properties of the main cyanotoxins, relevant for the evaluation of possible risks for human health, are presented. Humans may be exposed to cyanotoxins via several routes, with the oral one being by far the most important, occurring by ingesting contaminated drinking water, food, some dietary supplements, or water during recreational activities. Acute and short-term toxic effects have been associated in humans with exposure to high levels of cyanotoxins in drinking and bathing waters. However, the chronic exposure to low cyanotoxin levels remains a critical issue. This article identifies the actual risky exposure scenarios, provides toxicologically derived reference values, and discusses open issues and research needs.

  19. HLA-haplotypes, anti- beta-cell antibodies: their role in prognostication of type 1 diabetes mellitus (results of 11-year observation

    Directory of Open Access Journals (Sweden)

    Elena Vital'evna Titovich

    2010-12-01

    Full Text Available The risk of type 1 diabetes mellitus (DM1 depends in the first place on the presence of predetermining HLA DR haplotypes, DQ genes, and specific autoantibodies.Aim. Prospective observation of DM1 risk groups (healthy sibs of DM patients for the elucidation of the role of genetic and autoimmune abnormalities in thedevelopment of DM1. Materials and methods. Predetermining and protective haplotypes (HLA-DRBI, DQ genes in combination with immunological markers (autoantibodiesto cytoplasmic structures of betbeta-cells (ICA, anti-insulin autoantibodies (IAA, anti-glutamate decarboxylase autoantibodies (GAD were studied in healthysibs of mean age 11.9?5.8 years selected from 143 discordant families of patients with DM1. In addition, a random sample of 599 DM1 patients (mean age7.5?6.2 years was enrolled for molecular genetic studies (HLA-DRBI-DG genes. The control group comprised 200 subjects. Results. DQAI*0501-DQB1+0201 (DQ2 and DQAI*0301-DQBI*0302 (DG8 haplotype heterozygosity creating the highest risk of DM1, the healthy sibswere divided into 3 risk groups. The high risk group 1 (DQ2/DQ8 included 23 (13.5% subjects, moderate risk group 2 (DQ2/X, DQ8/X 85 (59.7%, andlow risk group 3 (X/X; X - any haplotype besides DQ2, DQ8 63 (36.8%. The frequency of autoantibodies (AB of 2 or 3 species in group 1 was higher thanin groups 2 and 3 (26.1, 14.1, 11.1% respectively, p>0.05; 8.7, 2.4, 0%, p

  20. The evolutionary history of the DMRT3 'Gait keeper' haplotype.

    Science.gov (United States)

    Staiger, E A; Almén, M S; Promerová, M; Brooks, S; Cothran, E G; Imsland, F; Jäderkvist Fegraeus, K; Lindgren, G; Mehrabani Yeganeh, H; Mikko, S; Vega-Pla, J L; Tozaki, T; Rubin, C J; Andersson, L

    2017-10-01

    A previous study revealed a strong association between the DMRT3:Ser301STOP mutation in horses and alternate gaits as well as performance in harness racing. Several follow-up studies have confirmed a high frequency of the mutation in gaited horse breeds and an effect on gait quality. The aim of this study was to determine when and where the mutation arose, to identify additional potential causal mutations and to determine the coalescence time for contemporary haplotypes carrying the stop mutation. We utilized sequences from 89 horses representing 26 breeds to identify 102 SNPs encompassing the DMRT3 gene that are in strong linkage disequilibrium with the stop mutation. These 102 SNPs were genotyped in an additional 382 horses representing 72 breeds, and we identified 14 unique haplotypes. The results provided conclusive evidence that DMRT3:Ser301STOP is causal, as no other sequence polymorphisms showed an equally strong association to locomotion traits. The low sequence diversity among mutant chromosomes demonstrated that they must have diverged from a common ancestral sequence within the last 10 000 years. Thus, the mutation occurred either just before domestication or more likely some time after domestication and then spread across the world as a result of selection on locomotion traits. © 2017 Stichting International Foundation for Animal Genetics.

  1. Haplotypes and Sequence Variation in the Ovine Adiponectin Gene (ADIPOQ

    Directory of Open Access Journals (Sweden)

    Qing-Ming An

    2015-11-01

    Full Text Available The adiponectin gene (ADIPOQ plays an important role in energy homeostasis. In this study five separate regions (regions 1 to 5 of ovine ADIPOQ were analysed using PCR-SSCP. Four different PCR-SSCP patterns (A1-D1, A2-D2 were detected in region-1 and region-2, respectively, with seven and six SNPs being revealed. In region-3, three different patterns (A3-C3 and three SNPs were observed. Two patterns (A4-B4, A5-B5 and two and one SNPs were observed in region-4 and region-5, respectively. In total, nineteen SNPs were detected, with five of them in the coding region and two (c.46T/C and c.515G/A putatively resulting in amino acid changes (p.Tyr16His and p.Lys172Arg. In region-1, -2 and -3 of 316 sheep from eight New Zealand breeds, variants A1, A2 and A3 were the most common, although variant frequencies differed in the eight breeds. Across region-1 and region-3, nine haplotypes were identified and haplotypes A1-A3, A1-C3, B1-A3 and B1-C3 were most common. These results indicate that the ADIPOQ gene is polymorphic and suggest that further analysis is required to see if the variation in the gene is associated with animal production traits.

  2. Cancer Risks for Relatives of Children with Cancer

    International Nuclear Information System (INIS)

    Heath, J. A.; Smibert, E.; Algar, E. M.; Heath, J. A.; Dite, G. S.; Hopper, J. L.; Algar, E. M.

    2014-01-01

    We determined the extent and distribution of cancers in relatives of 379 children newly diagnosed with cancer. Family history was collected from 1,337 first-degree and 3,399 second-degree relatives and incidence compared with national age- and gender-specific rates. Overall, 14 children (3.7%) had a relative with a history of childhood cancer and 26 children (6.9%) had a first-degree relative with a history of cancer, with only one of these having an identifiable familial cancer syndrome. There was a higher than expected incidence of childhood cancer among first-degree relatives (parents and siblings) (standardized incidence ratio (SIR) 1.43; 95% CI 0.54-5.08). There was also a higher than expected incidence of adult cancers among first-degree relatives (SIR 1.45; 95% CI 0.93-2.21), particularly in females (SIR 1.82; 95% CI 1.26-3.39). The increased family cancer history in first-degree females was largely attributable to an effect in mothers (SIR 1.78; 95% CI 1.27-3.33). The gender-specific association was reflected in higher than expected incidence rates of breast cancer in both mothers (SIR 1.92; 95% CI 0.72-6.83) and aunts (SIR 1.64; 95% CI 0.98-2.94). These findings support the hypothesis that previously undetected familial cancer syndromes contribute to childhood cancer.

  3. Development of a relative risk model for evaluating ecological risk of water environment in the Haihe River Basin estuary area.

    Science.gov (United States)

    Chen, Qiuying; Liu, Jingling; Ho, Kin Chung; Yang, Zhifeng

    2012-03-15

    Ecological risk assessment for water environment is significant to water resource management of basin. Effective environmental management and systems restoration such as the Haihe River Basin require holistic understanding of the relative importance of various stressor-related impacts throughout the basin. As an effective technical tool for evaluating the ecological risk, relative risk model (RRM) was applied in regional scale successfully. In this study, the risk transfer from upstream of basin was considered and the RRM was developed through introducing the source-stressor-habitat exposure filter (SSH), the endpoint-habitat exposure filter (EH) and the stressor-endpoint effect filter (SE) to reflect the meaning of exposure and effect more explicit. Water environment which includes water quality, water quantity and aquatic ecosystems was selected as the assessment endpoints. We created a conceptual model which depicting potential and effect pathways from source to stressor to habitat to endpoint. The Haihe River Basin estuary (HRBE) was selected as the model case. The results showed that there were two low risk regions, one medium risk region and two high risk regions in the HRBE. The results also indicated that urbanization was the biggest source, the second was shipping and the third was industry, their risk scores are 5.65, 4.71 and 3.68 respectively. Furthermore, habitat destruction was the largest stressor with the risk scores (2.66), the second was oxygen consuming organic pollutants (1.75) and the third was pathogens (1.75). So these three stressors were the main influencing factors of the ecological pressure in the study area. For habitats, open waters (9.59) and intertidal mudflat were enduring the bigger pressure and should be taken considerable attention. Ecological service values damaged (30.54) and biodiversity decreased were facing the biggest risk pressure. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. ALPK1 genetic regulation and risk in relation to gout.

    Science.gov (United States)

    Ko, Albert Min-Shan; Tu, Hung-Pin; Liu, Tze-Tze; Chang, Jan-Gowth; Yuo, Chung-Yee; Chiang, Shang-Lun; Chang, Shun-Jen; Liu, Yu-Fan; Ko, Allen Min-Jen; Lee, Chien-Hung; Lee, Chi-Pin; Chang, Chung-Ming; Tsai, Shih-Feng; Ko, Ying-Chin

    2013-04-01

    The present study investigated whether single nucleotide polymorphisms (SNPs) in the alpha-protein kinase 1 (ALPK1) gene are associated with gout in aboriginal and Han Chinese Taiwanese. A total of 1351 aborigines from the community (511 cases and 840 controls) and 511 Han people from hospital (104 cases and 407 controls) were recruited. SNPs in potentially functional regions of the 38 genes within 4q25 were identified and genotypes determined by direct sequencing. Quantitation of blood ALPK1 mRNA expression levels and luciferase assay of gout-associated rs231253 pGL3-SNP constructs cotransfected with hsa-miR-519e were examined. We found that ALPK1 gene was the most determinant of gout. Three SNPs of rs11726117 M861T [C], rs231247 [G] and rs231253 [G] were most associated with gout risk [odd ratios (OR) ≥1.44, P ≤ 3.78 × 10(-6)) in aborigines. A replication set using Han people had risk at rs11726117 and rs231247 (OR ≥1.72, P ≤ 4.08 × 10(-3)). From pooled analysis (Breslow-Day test, P > 0.33) assuming an additive model, each increasing copy of the risk allele of rs11726117 [C], rs231247 [G] and rs231253 [G] showed significantly elevated OR for gout ≥1.42 (P ≥ 1.53 × 10(-6)). Consistently, the composite homozygous of linked 3 SNPs (versus wild-type, OR = 1.83, P = 8.21 × 10(-4)) had strong associations with ALPK1 mRNA expression. Luciferase showed reduced hybridization between hsa-miR-519e and construct carrying gout-associated rs231253 [G] than the wild-type [C] (P = 6.19 × 10(-4)). Our study found that a newly identified ALPK1 gene can effectively interfere with microRNA target recognition and modulates the mRNA expression; and the varying distribution of the implicated SNPs among cases and controls in the two studied populations suggests a significant role in gout susceptibility.

  5. The Privilege of Induction Avoidance and Calcineurin Inhibitors Withdrawal in 2 Haplotype HLA Matched White Kidney Transplantation.

    Science.gov (United States)

    Brifkani, Zaid; Brennan, Daniel C; Lentine, Krista L; Horwedel, Timothy A; Malone, Andrew F; Delos Santos, Rowena; Maw, Thin Thin; Alhamad, Tarek

    2017-03-01

    White recipients of 2-haplotype HLA-matched living kidney transplants are perceived to be of low immunologic risk. Little is known about the safety of induction avoidance and calcineurin inhibitor withdrawal in these patients. We reviewed our experience at a single center and compared it to Organ Procurement and Transplantation Network (OPTN) registry data and only included 2-haplotype HLA-matched white living kidney transplants recipients between 2000 and 2013. There were 56 recipients in a single center (where no induction was given) and 2976 recipients in the OPTN. Among the OPTN recipients, 1285 received no induction, 903 basiliximab, 608 thymoglobulin, and 180 alemtuzumab. First-year acute rejection rates were similar after induction-free transplantation among the center and induced groups nationally. Compared with induction-free transplantation in the national data, there was no decrease in graft failure risk over 13 years with use of basiliximab (adjusted hazard ratio [aHR], 0.86; confidence interval [CI], 0.68-1.08), Thymoglobulin (aHR, 0.92; CI, 0.7-1.21) or alemtuzumab (aHR, 1.18; CI, 0.72-1.93). Among induction-free recipients at the center, calcineurin inhibitor withdrawal at 1 year (n = 27) did not significantly impact graft failure risk (HR,1.62; CI, 0.38-6.89). This study may serve as a foundation for further studies to provide personalized, tailored, immunosuppression for this very low-risk population of kidney transplant patients.

  6. External cephalic version-related risks: a meta-analysis.

    Science.gov (United States)

    Grootscholten, Kim; Kok, Marjolein; Oei, S Guid; Mol, Ben W J; van der Post, Joris A

    2008-11-01

    To systematically review the literature on external cephalic version-related complications and to assess if the outcome of a version attempt is related to complications. In March 2007 we searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Studies reporting on complications from an external cephalic version attempt for singleton breech pregnancies after 36 weeks of pregnancy were selected. We calculated odds ratios (ORs) from studies that reported both on complications as well as on the position of the fetus immediately after the procedure. We found 84 studies, reporting on 12,955 version attempts that reported on external cephalic version-related complications. The pooled complication rate was 6.1% (95% CI 4.7-7.8), 0.24% for serious complications (95% confidence interval [CI] 0.17-0.34) and 0.35% for emergency cesarean deliveries (95% CI 0.26-0.47). Complications were not related to external cephalic version outcome (OR 1.2 (95% CI 0.93-1.7). External cephalic version is a safe procedure. Complications are not related to the fetal position after external cephalic version.

  7. Genomic association for sexual precocity in beef heifers using pre-selection of genes and haplotype reconstruction.

    Directory of Open Access Journals (Sweden)

    Luciana Takada

    Full Text Available Reproductive traits are of the utmost importance for any livestock farming, but are difficult to measure and to interpret since they are influenced by various factors. The objective of this study was to detect associations between known polymorphisms in candidate genes related to sexual precocity in Nellore heifers, which could be used in breeding programs. Records of 1,689 precocious and non-precocious heifers from farms participating in the Conexão Delta G breeding program were analyzed. A subset of single nucleotide polymorphisms (SNP located in the region of the candidate genes at a distance of up to 5 kb from the boundaries of each gene, were selected from the panel of 777,000 SNPs of the High-Density Bovine SNP BeadChip. Linear mixed models were used for statistical analysis of early heifer pregnancy, relating the trait with isolated SNPs or with haplotype groups. The model included the contemporary group (year and month of birth as fixed effect and parent of the animal (sire effect as random effect. The fastPHASE® and GenomeStudio® were used for reconstruction of the haplotypes and for analysis of linkage disequilibrium based on r2 statistics. A total of 125 candidate genes and 2,024 SNPs forming haplotypes were analyzed. Statistical analysis after Bonferroni correction showed that nine haplotypes exerted a significant effect (p<0.05 on sexual precocity. Four of these haplotypes were located in the Pregnancy-associated plasma protein-A2 gene (PAPP-A2, two in the Estrogen-related receptor gamma gene (ESRRG, and one each in the Pregnancy-associated plasma protein-A gene (PAPP-A, Kell blood group complex subunit-related family (XKR4 and mannose-binding lectin genes (MBL-1 genes. Although the present results indicate that the PAPP-A2, PAPP-A, XKR4, MBL-1 and ESRRG genes influence sexual precocity in Nellore heifers, further studies are needed to evaluate their possible use in breeding programs.

  8. Women and stroke patients are more at risk for fall- related injury among older persons

    Directory of Open Access Journals (Sweden)

    Sulistyowati Tuminah Darjoko

    2016-05-01

    Women and stroke sufferers were at higher risk of fall-related injury among older persons. Prevention of fall-related injury should be done by older persons through periodic control of their health condition.

  9. Aluminium: Food-related health risk assessment of the consumers

    Directory of Open Access Journals (Sweden)

    О.V. Bagryantseva

    2016-03-01

    Full Text Available Aluminum is the most abundant metal in the lithosphere, constituting 8 % of the earth's crust. Aluminum enters the food from the various objects of environment such as water, food contact materials (packaging materials, cooking vessels, aluminum-containing food additives. In raw food products the content of aluminum is less than 5.7 mg/kg of the product. Normally, aluminum is not practically found in a human body. However, within the last decade various toxic effects of aluminum on human body have been revealed, and they are able to cause the risk of various diseases. The analysis of the available data has demonstrated that the excessive entry of aluminum in human body with food items is associated first of all with the content of aluminum-containing food additives, as well as with the use of materials and products made of aluminum and its alloys intended for contact with food. High level of aluminum consumption has been also detected among children of all ages. At the same time, today, theprovisional tolerable weekly intake (PTWI of aluminum for children is not established. To reduce negative effect of aluminum on human body it is necessary to: * exclude from the list of Annex 2 of the Technical Regulations of the Customs Union "Requirements for Food Additives, Flavorings and Technological Aids” (TR TS 029/2012 the following food additives – potassium aluminum silicate (E555, bentonite (E558, sodium aluminum silicate (E554, potassium aluminum silicate (E555, calcium aluminum silicate (E556, aluminum silicate (kaolin (E559; * to develop requirements for the aluminum content in food products intended for children nutrition; * to obtain data on aluminum content in food items sold on the domestic market and to assess health risks to consumers.

  10. Age-Related Sensory Impairments and Risk of Cognitive Impairment

    Science.gov (United States)

    Fischer, Mary E; Cruickshanks, Karen J.; Schubert, Carla R; Pinto, Alex A; Carlsson, Cynthia M; Klein, Barbara EK; Klein, Ronald; Tweed, Ted S.

    2016-01-01

    Background/Objectives To evaluate the associations of sensory impairments with the 10-year risk of cognitive impairment. Previous work has primarily focused on the relationship between a single sensory system and cognition. Design The Epidemiology of Hearing Loss Study (EHLS) is a longitudinal, population-based study of aging in the Beaver Dam, WI community. Baseline examinations were conducted in 1993 and follow-up exams have been conducted every 5 years. Setting General community Participants EHLS members without cognitive impairment at EHLS-2 (1998–2000). There were 1,884 participants (mean age = 66.7 years) with complete EHLS-2 sensory data and follow-up information. Measurements Cognitive impairment was a Mini-Mental State Examination score of impairment was a pure-tone average of hearing thresholds (0.5, 1, 2 and 4 kHz) of > 25 decibel Hearing Level in either ear. Visual impairment was Pelli-Robson contrast sensitivity of impairment was a San Diego Odor Identification Test score of impairment were independently associated with cognitive impairment risk [Hearing: Hazard Ratio (HR) = 1.90, 95% Confidence Interval (C.I.) = 1.11, 3.26; Vision: HR = 2.05, 95% C.I. = 1.24, 3.38; Olfaction: HR = 3.92, 95% C.I. = 2.45, 6.26]. However, 85% with hearing impairment, 81% with visual impairment, and 76% with olfactory impairment did not develop cognitive impairment during follow-up. Conclusion The relationship between sensory impairment and cognitive impairment was not unique to one sensory system suggesting sensorineural health may be a marker of brain aging. The development of a combined sensorineurocognitive measure may be useful in uncovering mechanisms of healthy brain aging. PMID:27611845

  11. Critical review of methods for risk ranking of food-related hazards, based on risks for human health.

    Science.gov (United States)

    Van der Fels-Klerx, H J; Van Asselt, E D; Raley, M; Poulsen, M; Korsgaard, H; Bredsdorff, L; Nauta, M; D'agostino, M; Coles, D; Marvin, H J P; Frewer, L J

    2018-01-22

    This study aimed to critically review methods for ranking risks related to food safety and dietary hazards on the basis of their anticipated human health impacts. A literature review was performed to identify and characterize methods for risk ranking from the fields of food, environmental science and socio-economic sciences. The review used a predefined search protocol, and covered the bibliographic databases Scopus, CAB Abstracts, Web of Sciences, and PubMed over the period 1993-2013. All references deemed relevant, on the basis of predefined evaluation criteria, were included in the review, and the risk ranking method characterized. The methods were then clustered-based on their characteristics-into eleven method categories. These categories included: risk assessment, comparative risk assessment, risk ratio method, scoring method, cost of illness, health adjusted life years (HALY), multi-criteria decision analysis, risk matrix, flow charts/decision trees, stated preference techniques and expert synthesis. Method categories were described by their characteristics, weaknesses and strengths, data resources, and fields of applications. It was concluded there is no single best method for risk ranking. The method to be used should be selected on the basis of risk manager/assessor requirements, data availability, and the characteristics of the method. Recommendations for future use and application are provided.

  12. Optimal Consumption and Investment under Time-Varying Relative Risk Aversion

    DEFF Research Database (Denmark)

    Steffensen, Mogens

    2011-01-01

    We consider the continuous time consumption-investment problem originally formalized and solved by Merton in case of constant relative risk aversion. We present a complete solution for the case where relative risk aversion with respect to consumption varies with time, having in mind an investor...... with age-dependent risk aversion. This provides a new motivation for life-cycle investment rules. We study the optimal consumption and investment rules, in particular in the case where the relative risk aversion with respect to consumption is increasing with age....

  13. HLA Class II Allele, Haplotype, and Genotype Associations with Type 1 Diabetes in Benin: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Kaossarath A. Fagbemi

    2017-01-01

    Full Text Available Background. Several studies have reported the implication of HLA-DR/DQ loci in the susceptibility to type 1 diabetes (T1D. Since no such study has yet been performed in Benin, this pilot one aimed at assessing HLA class II allele, haplotype, and genotype associations with T1D. Material and Methods. Class II HLA genotyping was performed in 51 patients with T1D and 51 healthy unrelated controls by means of the PCR-SSP method. The diagnosis of T1D was set up according to American Diabetes Association criteria. Odds ratio (OR and its 95% confidence interval (95% CI were calculated to assess the associations between T1D and HLA alleles, haplotypes, and genotypes. Results. Participants were aged 1–24 years. T1D was significantly associated with DR3, DQA1∗05:01, DQB1∗02:01, and DR3-DR4. No significant associations were observed with DR4, DQB1∗03:02, and DQB1∗06:02. Conclusion. Certain HLA class II alleles, haplotypes, and genotypes were related to T1D and may be used as genetic susceptibility markers to T1D in Benin.

  14. Exploring gender perceptions of risk of HIV infection and related ...

    African Journals Online (AJOL)

    2016-08-15

    Aug 15, 2016 ... In order to close this gap, this study explored gender-related .... clubs are run by old people themselves in partnership with com- ... small samples of participants who are selected purposefully to .... felt uncomfortable with the topic under discussion or did not ..... African Medical Journal, 94(7), 537–543.

  15. Rationality on the rise: Why relative risk aversion increases with stake size

    OpenAIRE

    Fehr-Duda, Helga; Bruhin, Adrian; Epper, Thomas F.; Schubert, Renate

    2008-01-01

    How does risk tolerance vary with stake size? This important question cannot be adequately answered if framing effects, nonlinear probability weighting, and heterogeneity of preference types are neglected. We show that, contrary to gains, no coherent change in relative risk aversion is observed for losses. The increase in relative risk aversion over gains cannot be captured by the curvature of the utility function. It is driven predominantly by a change in probability weighting of a majority ...

  16. The influence of nuclear risk sense to atomic industry's public relation

    International Nuclear Information System (INIS)

    Biryukova, P.; Kazakevich, Yu.

    2001-01-01

    The goal of this report is estimation of the influence of sensing of nuclear risk to atomic industry's public relation. In this report the reasons of the negative relation to nuclear energetic owing to inadequate sensing of the risk dealing with this fields have been represented. (authors)

  17. Risk of Seizures in First Degree Relatives of Probands with Epilepsy ...

    African Journals Online (AJOL)

    Objective: To determine the risk of seizures in first degree relatives of epileptic patients. To relate the risk to several clinical characteristics in the probands. Such information is useful for genetic counselling. Methods: A prospective case-control study of 648 FDR of 88 probands attending the neurology out-patient clinic of a ...

  18. Relative risk analysis of several manufactured nanomaterials: an insurance industry context.

    Science.gov (United States)

    Robichaud, Christine Ogilvie; Tanzil, Dicksen; Weilenmann, Ulrich; Wiesner, Mark R

    2005-11-15

    A relative risk assessment is presented for the industrial fabrication of several nanomaterials. The production processes for five nanomaterials were selected for this analysis, based on their current or near-term potential for large-scale production and commercialization: single-walled carbon nanotubes, bucky balls (C60), one variety of quantum dots, alumoxane nanoparticles, and nano-titanium dioxide. The assessment focused on the activities surrounding the fabrication of nanomaterials, exclusive of any impacts or risks with the nanomaterials themselves. A representative synthesis method was selected for each nanomaterial based on its potential for scaleup. A list of input materials, output materials, and waste streams for each step of fabrication was developed and entered into a database that included key process characteristics such as temperature and pressure. The physical-chemical properties and quantities of the inventoried materials were used to assess relative risk based on factors such as volatility, carcinogenicity, flammability, toxicity, and persistence. These factors were first used to qualitatively rank risk, then combined using an actuarial protocol developed by the insurance industry for the purpose of calculating insurance premiums for chemical manufacturers. This protocol ranks three categories of risk relative to a 100 point scale (where 100 represents maximum risk): incident risk, normal operations risk, and latent contamination risk. Results from this analysis determined that relative environmental risk from manufacturing each of these five materials was comparatively low in relation to other common industrial manufacturing processes.

  19. Association of MMP-9 Haplotypes and TIMP-1 Polymorphism with Spontaneous Deep Intracerebral Hemorrhage in the Taiwan Population.

    Directory of Open Access Journals (Sweden)

    Wei-Min Ho

    Full Text Available Spontaneous deep intracerebral hemorrhage (SDICH is a devastating stroke subtype. The causes of SDICH are heterogeneous. Matrix metalloproteinase-9 (MMP-9, Gelantinase B has been shown to relate to stroke and the development of aneurysm and may increase risks of intracerebral hemorrhage. MMP activities are modulated by their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs. We analyzed the genetic variants of MMP-9 and TIMP-1 and SDICH susceptibility.Associations were tested by logistic regression or general linear models with adjusting for multiple covariables. Multiplicative terms between genes were applied to detect the interaction effects on SDICH. Permutation testing of 1,000 replicates was performed for empirical estimates.In the group of ≥65 years old (y/o, we found associations of SDICH with rs3787268 (Odds ratio [OR] = 0.48, 95% confidence interval [CI] 0.27 to 0.86, P = 0.01 and haplotype1 (Hap1 (OR = 0.48, 95% CI 0.26 to 0.86, P = 0.014. For TIMP1 gene, rs4898 was associated with SDICH in the elder male group (OR = 0.35, 95% CI 0.15 to 0.81, P = 0.015. In contrast, in the younger male group, there were associations of SDICH with rs2250889 (OR = 0.48, 95% CI 0.27 to 0.84, P = 0.01 and Hap3 (OR = 0.61, 95% CI 0.38 to 0.97, P = 0.04. We found significant genetic interaction between TIMP-1 and MMP-9 in SDICH susceptibility among younger male subjects (P = 0.004. In subjects carrying rs4898 minor allele, carriers with Hap3 had lower SDICH risk than non-carriers (OR = 0.19, 95% CI 0.07 to 0.51, P = 0.001. In addition, this study showed that when young males were exposed to alcohol, Hap3 was a protective factor of SDICH (OR = 0.06, 95% CI 0.01 to 0.27, P = 0.0002. In contrast, when they were exposed to smoke, Hap2 carriers had increased risk of SDICH (OR = 2.45, 95% CI 1.05 to 5.73, P = 0.04.This study showed modest to moderate effects of MMP-9 and TIMP-1 polymorphisms on SDICH risks with significant age differences

  20. Association of epidermal growth factor and epidermal growth factor receptor polymorphisms with the risk of hepatitis B virus-related hepatocellular carcinoma in the population of North China.

    Science.gov (United States)

    Wu, Jia; Zhang, Wei; Xu, Aiqiang; Zhang, Li; Yan, Tao; Li, Zhuo; Wu, Xiaopan; Zhu, Xilin; Ma, Juan; Li, Ke; Li, Hui; Liu, Ying

    2013-08-01

    Hepatocellular carcinoma (HCC) is a common solid malignant tumor occurring worldwide that leads to the third largest cause of death compared to other cancers. Genetic and environmental factors are involved in the pathogenesis of HCC. Epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) can stimulate the proliferation of epidermal and epithelial cells. The EGF signal pathway has a relationship with the growth of the embryo, tissue repairing, and tumorigenesis. In this study, 416 patients with hepatitis B virus infection (HBV)-related HCC and 645 individuals who had never been infected with HBV of the Chinese Han population were enrolled. Eight single-nucleotide polymorphisms (SNPs), whose minor allele frequency >20% in the EGF and EGFR genes, were genotyped to examine their associations with hepatocarcinogenesis. Genotyping experiments were carried out using TaqMan. There were significant differences in genotype distributions (p=0.005) and allele frequencies (p=0.001, odds ratio [OR]=1.43, 95% confidence interval [CI]=1.15-1.79) of rs11569017 in the EGF gene between the HCC and control groups. After binary logistic regression to determine independent factors for susceptibility to HCC under an additive model, rs11569017 was still independently associated with the susceptibility to HCC (p=0.021, OR=1.48, 95% CI=1.06-2.07), but no significant differences in other SNPs were found. Additionally, the haplotype T-G constructed by rs11569017 and rs4444903 of the EGF gene might increase the risk of HBV-related HCC (p=0.002, OR=1.44, 95% CI=1.15-1.82). The rs11569017 T allele was associated with susceptibility to HBV-related HCC.

  1. A common genetic variant in the neurexin superfamily member CNTNAP2 is associated with increased risk for selective mutism and social anxiety-related traits.

    Science.gov (United States)

    Stein, Murray B; Yang, Bao-Zhu; Chavira, Denise A; Hitchcock, Carla A; Sung, Sharon C; Shipon-Blum, Elisa; Gelernter, Joel

    2011-05-01

    Selective mutism (SM), considered an early-onset variant of social anxiety disorder, shares features of impaired social interaction and communication with autism spectrum disorders (ASDs) suggesting a possible shared pathophysiology. We examined association of a susceptibility gene, contactin-associated protein-like 2 (CNTNAP2), for ASDs and specific language impairment with SM and social anxiety-related traits. Sample 1 subjects were 99 nuclear families including 106 children with SM. Sample 2 subjects were young adults who completed measures of social interactional anxiety (n = 1028) and childhood behavioral inhibition (n = 920). Five single nucleotide polymorphisms in CNTNAP2 (including rs7794745 and rs2710102, previously associated with ASDs) were genotyped. Analyses revealed nominal significance (p = .018) for association of SM with rs2710102, which, with rs6944808, was part of a common haplotype associated with SM (permutation p = .022). Adjusting for sex and ancestral proportion, each copy of the rs2710102*a risk allele in the young adults was associated with increased odds of being >1 SD above the mean on the Social Interactional Anxiety Scale (odds ratio = 1.33, p = .015) and Retrospective Self-Report of Inhibition (odds ratio = 1.40, p = .010). Although association was found with rs2710102, the risk allele (a) for the traits studied here is the nonrisk allele for ASD and specific language impairment. These findings suggest a partially shared etiology between ASDs and SM and raise questions about which aspects of these syndromes are potentially influenced by CNTNAP2 and mechanism(s) by which these influences may be conveyed. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Chronic inflammatory state in sickle cell anemia patients is associated with HBB(*)S haplotype.

    Science.gov (United States)

    Bandeira, Izabel C J; Rocha, Lillianne B S; Barbosa, Maritza C; Elias, Darcielle B D; Querioz, José A N; Freitas, Max Vitor Carioca; Gonçalves, Romélia P

    2014-02-01

    The chronic inflammatory state in sickle cell anemia (SCA) is associated with several factors such as the following: endothelial damage; increased production of reactive oxygen species; hemolysis; increased expression of adhesion molecules by leukocytes, erythrocytes, and platelets; and increased production of proinflammatory cytokines. Genetic characteristics affecting the clinical severity of SCA include variations in the hemoglobin F (HbF) level, coexistence of alpha-thalassemia, and the haplotype associated with the HbS gene. The different haplotypes of SCA are Bantu, Benin, Senegal, Cameroon, and Arab-Indian. These haplotypes are associated with ethnic groups and also based on the geographical origin. Studies have shown that the Bantu haplotype is associated with higher incidence of clinical complications than the other haplotypes and is therefore considered to have the worst prognosis. This study aimed to evaluate the profile of the proinflammatory cytokines interleukin-6, tumor necrosis factor-α, and interleukin-17 in patients with SCA and also to assess the haplotypes associated with beta globin cluster S (HBB(*)S). We analyzed a total of 62 patients who had SCA and had been treated with hydroxyurea; they had received a dose ranging between 15 and 25 (20.0±0.6)mg/kg/day for 6-60 (18±3.4)months; their data were compared with those for 30 normal individuals. The presence of HbS was detected and the haplotypes of the beta S gene cluster were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our study demonstrated that SCA patients have increased inflammatory profile when compared to the healthy individuals. Further, analysis of the association between the haplotypes and inflammatory profile showed that the levels of IL-6 and TNF-α were greater in subjects with the Bantu/Bantu haplotype than in subjects with the Benin/Benin haplotype. The Bantu/Benin haplotype individuals had lower levels of cytokines than those with

  3. A haplotype regression approach for genetic evaluation using sequences from the 1000 bull genomes Project

    International Nuclear Information System (INIS)

    Lakhssassi, K.; González-Recio, O.

    2017-01-01

    Haplotypes from sequencing data may improve the prediction accuracy in genomic evaluations as haplotypes are in stronger linkage disequilibrium with quantitative trait loci than markers from SNP chips. This study focuses first, on the creation of haplotypes in a population sample of 450 Holstein animals, with full-sequence data from the 1000 bull genomes project; and second, on incorporating them into the whole genome prediction model. In total, 38,319,258 SNPs (and indels) from Next Generation Sequencing were included in the analysis. After filtering variants with minor allele frequency (MAF< 0.025) 13,912,326 SNPs were available for the haplotypes extraction with findhap.f90. The number of SNPs in the haploblocks was on average 924 SNP (166,552 bp). Unique haplotypes were around 97% in all chromosomes and were ignored leaving 153,428 haplotypes. Estimated haplotypes had a large contribution to the total variance of genomic estimated breeding values for kilogram of protein, Global Type Index, Somatic Cell Score and Days Open (between 32 and 99.9%). Haploblocks containing haplotypes with large effects were selected by filtering for each trait, haplotypes whose effect was larger/lower than the mean plus/minus 3 times the standard deviation (SD) and 1 SD above the mean of the haplotypes effect distribution. Results showed that filtering by 3 SD would not be enough to capture a large proportion of genetic variance, whereas filtering by 1 SD could be useful but model convergence should be considered. Additionally, sequence haplotypes were able to capture additional genetic variance to the polygenic effect for traits undergoing lower selection intensity like fertility and health traits.

  4. Genome-wide haplotype analysis of cis expression quantitative trait loci in monocytes.

    Directory of Open Access Journals (Sweden)

    Sophie Garnier

    Full Text Available In order to assess whether gene expression variability could be influenced by several SNPs acting in cis, either through additive or more complex haplotype effects, a systematic genome-wide search for cis haplotype expression quantitative trait loci (eQTL was conducted in a sample of 758 individuals, part of the Cardiogenics Transcriptomic Study, for which genome-wide monocyte expression and GWAS data were available. 19,805 RNA probes were assessed for cis haplotypic regulation through investigation of ~2,1 × 10(9 haplotypic combinations. 2,650 probes demonstrated haplotypic p-values >10(4-fold smaller than the best single SNP p-value. Replication of significant haplotype effects were tested for 412 probes for which SNPs (or proxies that defined the detected haplotypes were available in the Gutenberg Health Study composed of 1,374 individuals. At the Bonferroni correction level of 1.2 × 10(-4 (~0.05/412, 193 haplotypic signals replicated. 1000 G imputation was then conducted, and 105 haplotypic signals still remained more informative than imputed SNPs. In-depth analysis of these 105 cis eQTL revealed that at 76 loci genetic associations were compatible with additive effects of several SNPs, while for the 29 remaining regions data could be compatible with a more complex haplotypic pattern. As 24 of the 105 cis eQTL have previously been reported to be disease-associated loci, this work highlights the need for conducting haplotype-based and 1000 G imputed cis eQTL analysis before commencing functional studies at disease-associated loci.

  5. A haplotype regression approach for genetic evaluation using sequences from the 1000 bull genomes Project

    Energy Technology Data Exchange (ETDEWEB)

    Lakhssassi, K.; González-Recio, O.

    2017-07-01

    Haplotypes from sequencing data may improve the prediction accuracy in genomic evaluations as haplotypes are in stronger linkage disequilibrium with quantitative trait loci than markers from SNP chips. This study focuses first, on the creation of haplotypes in a population sample of 450 Holstein animals, with full-sequence data from the 1000 bull genomes project; and second, on incorporating them into the whole genome prediction model. In total, 38,319,258 SNPs (and indels) from Next Generation Sequencing were included in the analysis. After filtering variants with minor allele frequency (MAF< 0.025) 13,912,326 SNPs were available for the haplotypes extraction with findhap.f90. The number of SNPs in the haploblocks was on average 924 SNP (166,552 bp). Unique haplotypes were around 97% in all chromosomes and were ignored leaving 153,428 haplotypes. Estimated haplotypes had a large contribution to the total variance of genomic estimated breeding values for kilogram of protein, Global Type Index, Somatic Cell Score and Days Open (between 32 and 99.9%). Haploblocks containing haplotypes with large effects were selected by filtering for each trait, haplotypes whose effect was larger/lower than the mean plus/minus 3 times the standard deviation (SD) and 1 SD above the mean of the haplotypes effect distribution. Results showed that filtering by 3 SD would not be enough to capture a large proportion of genetic variance, whereas filtering by 1 SD could be useful but model convergence should be considered. Additionally, sequence haplotypes were able to capture additional genetic variance to the polygenic effect for traits undergoing lower selection intensity like fertility and health traits.

  6. Changes in Classes of Injury-Related Risks and Consequences of Risk-Level Drinking: a Latent Transition Analysis.

    Science.gov (United States)

    Cochran, Gerald; Field, Craig; Caetano, Raul

    2015-07-01

    Risk-level drinking, drinking and driving, and alcohol-related violence are risk factors that result in injuries. The current study sought to identify which subgroups of patients experience the most behavioral change following a brief intervention. A secondary analysis of data from a brief alcohol intervention study was conducted. The sample (N = 664) includes at-risk drinkers who experienced an injury and were admitted for care to a Level 1 trauma center. Injury-related items from the Short Inventory of Problems+6 were used to perform a latent transition analysis to describe class transitions participants experienced following discharge. Four classes emerged for the year before and after the current injury. Most individuals transitioned from higher-risk classes into those with lower risk. Some participants maintained risky profiles, and others increased risks and consequences. Drinking and driving remained a persistent problem among the study participants. Although a large portion of intervention recipients improved risks and consequences of alcohol use following discharge, more intensive intervention services may be needed for a subset of patients who showed little or no improvement.

  7. IGF-1, IGFBP-1, and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk: findings from the Breast and Prostate Cancer Cohort Consortium (BPC3.

    Directory of Open Access Journals (Sweden)

    Alpa V Patel

    2008-07-01

    Full Text Available IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-I and IGFBP-3 levels and breast cancer risk within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3. This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-I and 6,275 for circulating IGFBP-3 analyses comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the genes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP were selected to provide high coverage of common haplotypes; the haplotype structure was defined across four haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-I levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF levels does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women.

  8. Confusing Relative Risk with Absolute Risk Is Associated with More Enthusiastic Beliefs about the Value of Cancer Screening.

    Science.gov (United States)

    Caverly, Tanner J; Prochazka, Allan V; Binswanger, Ingrid A; Kutner, Jean S; Matlock, Daniel D

    2014-07-01

    Reviews of how data are presented in medical literature document that the benefit from an intervention is often exaggerated relative to the harm (e.g., relative risk for benefit and absolute risk for harm). Such mismatched presentations may create unwarranted enthusiasm, especially among those who misinterpret the statistics presented. The objective was to determine whether misinterpretation of risk data predicts enthusiasm for cancer screening. The authors administered a survey with 14 items assessing beliefs about cancer screening and 6 items measuring data interpretation ability. Multiple linear regression was used to evaluate the association between data interpretation and enthusiasm for cancer screening, with adjustment for gender and year graduated from medical school. Eighty-eight of 139 physicians at a state-wide professional meeting returned completed surveys (63% response rate). Lower data interpretation scores were associated with higher enthusiasm for cancer screening scores (P = 0.004) in the adjusted primary analysis. Confusing relative risk with absolute risk appeared to drive the overall association. Biased presentations of risk data could affect general beliefs about the value of cancer screening, especially among physicians who uncritically accept mismatched presentations of data. © The Author(s) 2014.

  9. Association of CAPN10 SNPs and haplotypes with polycystic ovary syndrome among South Indian Women.

    Directory of Open Access Journals (Sweden)

    Shilpi Dasgupta

    Full Text Available Polycystic Ovary Syndrome (PCOS is known to be characterized by metabolic disorder in which hyperinsulinemia and peripheral insulin resistance are central features. Given the physiological overlap between PCOS and type-2 diabetes (T2DM, and calpain 10 gene (CAPN10 being a strong candidate for T2DM, a number of studies have analyzed CAPN10 SNPs among PCOS women yielding contradictory results. Our study is first of its kind to investigate the association pattern of CAPN10 polymorphisms (UCSNP-44, 43, 56, 19 and 63 with PCOS among Indian women. 250 PCOS cases and 299 controls from Southern India were recruited for this study. Allele and genotype frequencies of the SNPs were determined and compared between the cases and controls. Results show significant association of UCSNP-44 genotype CC with PCOS (p = 0.007 with highly significant odds ratio when compared to TC (OR = 2.51, p = 0.003, 95% CI = 1.37-4.61 as well as TT (OR = 1.94, p = 0.016, 95% CI = 1.13-3.34. While the haplotype carrying the SNP-44 and SNP-19 variants (21121 exhibited a 2 fold increase in the risk for PCOS (OR = 2.37, p = 0.03, the haplotype containing SNP-56 and SNP-19 variants (11221 seems to have a protective role against PCOS (OR = 0.20, p = 0.004. Our results support the earlier evidence for a possible role of UCSNP-44 of the CAPN10 gene in the manifestation of PCOS.

  10. Novel CYP2E1 haplotype identified in a South African cohort

    Directory of Open Access Journals (Sweden)

    Laura J. Heathfield

    2014-09-01

    Full Text Available Alcohol abuse accounts for approximately 2.5 million deaths annually and is the third highest risk factor for disease and disability. Alcohol is metabolised by polymorphic enzymes and the status of an individual with respect to alcohol metabolising enzymes may have forensic relevance in post-mortems. Baseline frequencies of gene variants involved in alcohol metabolism need to be established to aid the identification of suitable population-specific polymorphisms to genotype during molecular autopsies. The principal alcohol metabolising enzymes include alcohol dehydrogenase (ADH, aldehyde dehydrogenase (ALDH and cytochrome P450 2E1 (CYP2E1. Six single nucleotide polymorphisms (SNPs – rs1229984G>A and rs2066702C>T in ADH1B, rs671G>A in ALDH2, and rs3813867G>C, rs2031920C>T and rs6413432T>A in CYP2E1 – were genotyped in 150 individuals from four South African populations: Xhosa, Zulu, South African white and South African coloured. Allele frequencies for each SNP in the four population groups were 0–10% for rs1229984A, 2–12% for rs2066702T, 0–2% for rs671A, 1–4% for rs3813867C, 0–1% for rs2031920T and 3–15% for rs6413432A. Haplotype analysis revealed a novel combination of three SNPs in CYP2E1 whose effects on alcohol metabolism need further investigation. Establishment of baseline frequencies adds to our knowledge of genetic variation in alcohol metabolising enzymes and additional research is required to determine the functional significance of this novel CYP2E1 haplotype.

  11. Anemia risk in relation to lead exposure in lead-related manufacturing

    Directory of Open Access Journals (Sweden)

    Nan-Hung Hsieh

    2017-05-01

    Full Text Available Abstract Background Lead-exposed workers may suffer adverse health effects under the currently regulated blood lead (BPb levels. However, a probabilistic assessment about lead exposure-associated anemia risk is lacking. The goal of this study was to examine the association between lead exposure and anemia risk among factory workers in Taiwan. Methods We first collated BPb and indicators of hematopoietic function data via health examination records that included 533 male and 218 female lead-exposed workers between 2012 and 2014. We used benchmark dose (BMD modeling to estimate the critical effect doses for detection of abnormal indicators. A risk-based probabilistic model was used to characterize the potential hazard of lead poisoning for job-specific workers by hazard index (HI. We applied Bayesian decision analysis to determine whether BMD could be implicated as a suitable BPb standard. Results Our results indicated that HI for total lead-exposed workers was 0.78 (95% confidence interval: 0.50–1.26 with risk occurrence probability of 11.1%. The abnormal risk of anemia indicators for male and female workers could be reduced, respectively, by 67–77% and 86–95% by adopting the suggested BPb standards of 25 and 15 μg/dL. Conclusions We conclude that cumulative exposure to lead in the workplace was significantly associated with anemia risk. This study suggests that current BPb standard needs to be better understood for the application of lead-exposed population protection in different scenarios to provide a novel standard for health management. Low-level lead exposure risk is an occupational and public health problem that should be paid more attention.

  12. Haplotype Diversity at Sub1 Locus and Allelic Distribution Among Rice Varieties of Tide and Flood Prone Areas of South-East Asia

    Directory of Open Access Journals (Sweden)

    A.S.M. Masuduzzaman

    2017-07-01

    Full Text Available Single nucleotide polymorphisms and restriction digestion-based haplotype variations among 160 flood prone rice varieties were analyzed with enzymes Alu I and Cac8 I to generate polymorphisms at Sub1A and Sub1C loci (conferring submergence tolerance, respectively. Haplotype associated with phenotype was used to study the haplotype variations at Sub1A and Sub1C loci and to determine their functional influence on submergence tolerance and stem elongation. Three patterns at Sub1A locus, Sub1A0 (null allele, Sub1A1 (does not cut and Sub1A2 (one SNP, and four patterns at Sub1C locus, Sub1C1, Sub1C2, Sub1C3 and Sub1C4, were generated. Both tolerant Sub1A1 and intolerant Sub1A2 had the same length, but the difference was presence of a restriction site in the Sub1A2, but absent at the Sub1A1. Further, two types of polymorphism were detected at the Sub1C, one included major length polymorphisms (165, 170 and 175 bp and the other was a single restriction site at different position. Eight haplotypes (different combinations of the two loci, A1C1, A1C2, A1C4, A2C2, A2C4, A0C2, A0C3 and A0C4, were detected among 160 varieties. Haplotype A1C1 was comparatively more related to haplotypes A1C2 and A1C4, having the same Sub1A allele, and these haplotypes were found only in Bangladeshi, Sri Lankan and Indian varieties. Most tolerant varieties in A1C1 haplotype showed slow elongation, having tolerant specific Sub1A1 and Sub1C1 alleles. Further, the varieties Madabaru and Kottamali (A2C2 also showed moderate level of tolerance without Sub1A1 allele. These varieties were different with FR13A and also suspected to carry different novel tolerant genes at other loci. These materials could be used for hybridization with Sub1 varieties for pyramiding additional tolerant specific alleles into a single genotype for improving submergence tolerance in rice.

  13. Two haplotype clusters of Echinococcus granulosus sensu stricto in northern Iraq (Kurdistan region) support the hypothesis of a parasite cradle in the Middle East.

    Science.gov (United States)

    Hassan, Zuber Ismael; Meerkhan, Azad Abdullah; Boufana, Belgees; Hama, Abdullah A; Ahmed, Bayram Dawod; Mero, Wijdan Mohammed Salih; Orsten, Serra; Interisano, Maria; Pozio, Edoardo; Casulli, Adriano

    2017-08-01

    Human cystic echinococcosis (CE) caused by Echinococcus granulosus s.s. is a major public health problem in Iraqi Kurdistan with a reported surgical incidence of 6.3 per 100,000 Arbil inhabitants. A total of 125 Echinococcus isolates retrieved from sheep, goats and cattle were used in this study. Our aim was to determine species/genotypes infecting livestock in Iraqi Kurdistan and examine intraspecific variation and population structure of Echinococcus granulosus s.s. in this region and relate it to that of other regions worldwide. Using nucleotide sequences of the mitochondrial cytochrome c oxidase subunit 1 (cox 1) we identified E. granulosus s.s. as the cause of hydatidosis in all examined animals. The haplotype network displayed a double-clustered topology with two main E. granulosus s.s. haplotypes, (KU05) and (KU33). The 'founder' haplotype (KU05) confirmed the presence of a common lineage of non-genetically differentiated populations as inferred by the low non-significant fixation index values. Overall diversity and neutrality indices indicated demographic expansion. We used E. granulosus s.s. nucleotide sequences from GenBank to draw haplotype networks for the Middle East (Iran, Jordan and Turkey), Europe (Albania, Greece, Italy, Romania and Spain), China, Mongolia, Russia, South America (Argentina, Brazil, Chile and Mexico) and Tunisia. Networks with two haplotype clusters like that reported here for Iraqi Kurdistan were seen for the Middle East, Europe, Mongolia, Russia and Tunisia using both 827bp and 1609bp cox1 nucleotide sequences, whereas a star-like network was observed for China and South America. We hypothesize that the double clustering seen at what is generally assumed to be the cradle of domestication may have emerged independently and dispersed from the Middle East to other regions and that haplotype (KU33) may be the main haplotype within a second cluster in the Middle East from where it has spread into Europe, Mongolia, Russia and North

  14. Youth at risk of physical inactivity may benefit more from activity-related support than youth not at risk

    Directory of Open Access Journals (Sweden)

    Schmalz Dorothy L

    2006-03-01

    Full Text Available Background This study examines whether associations between activity-related support and adolescents' physical activity differ for adolescents at high versus low risk of physical inactivity. Methods: Participants included 202 middle-school-aged girls (N = 92 and boys (N = 110. Physical activity was assessed using three self-report questionnaires. Activity-related support from mothers, fathers, siblings, and peers was assessed using the Activity Support Scale. Perceived sport competence was assessed using the Physical Activity Self Description Questionnaire. Participants' height and weight were measured and used to calculate their age- and sex-adjusted Body Mass Index percentile. Participants were classified as being at high risk for physical inactivity if they fulfilled two of the following three criteria: (1 overweight; (2 female; or (3 having low perceived sport competence. Results: Activity-related support from all sources was associated with higher levels of physical activity among adolescents. A stronger association between activity support and physical activity was found for adolescents at high risk for physical inactivity in comparison to adolescents at low risk. Conclusions: Findings from this study suggest that the activity-related support from family and friends may be an effective tool in promoting physical activity among youth at risk of physical inactivity.

  15. Risk of alcohol dependence: prevalence, related problems and socioeconomic factors

    Directory of Open Access Journals (Sweden)

    Juliana Gabrielle Martins-Oliveira

    2016-01-01

    Full Text Available Abstract The present study evaluated the possible alcohol dependence and related problems among adolescents and determined possible associations with socioeconomic factors and gender. A cross-sectional study was conducted with a representative sample of 936 adolescents aged 15 to 19 years enrolled at public and private schools in the city of Belo Horizonte, Brazil. Data related to alcohol consumption and associated problems were collected using the Alcohol Use Disorder Identification Test (AUDIT. The Social Vulnerability Index (SVI, mother's schooling and type of school were used to assess socioeconomic factors. Statistical analysis involved the chi-square test (p < 0.05 and Poisson regression. The prevalence of possible dependence was 16.4%, 52.1% reported concern of a family member regarding the adolescent's alcohol consumption. Female adolescents were less likely to exhibit possible dependence in comparison to males. Participants with living in a low vulnerability area were more likely to consume alcohol in comparison to those living in underprivileged areas. The results of the present study demonstrate that possible dependence was significantly associated with the male gender and low social vulnerability.

  16. Risk of abdominal aortic aneurysm (AAA) among male and female relatives of AAA patients.

    Science.gov (United States)

    van de Luijtgaarden, Koen M; Rouwet, Ellen V; Hoeks, Sanne E; Stolker, Robert J; Verhagen, Hence Jm; Majoor-Krakauer, Danielle

    2017-04-01

    Sex affects the presentation, treatment, and outcomes of abdominal aortic aneurysm (AAA). Although AAAs are less prevalent in women, at least in the general population, women with an AAA have a poorer prognosis in comparison to men. Sex differences in the genetic predisposition for aneurysm disease remain to be established. In this study we investigated the familial risk of AAA for women compared to men. All living AAA patients included in a 2004-2012 prospective database were invited to the multidisciplinary vascular/genetics outpatient clinic between 2009 and 2012 for assessment of family history using detailed questionnaires. AAA risk for male and female relatives was calculated separately and stratified by sex of the AAA patients. Families of 568 AAA patients were investigated and 22.5% of the patients had at least one affected relative. Female relatives had a 2.8-fold and male relatives had a 1.7-fold higher risk than the estimated sex-specific population risk. Relatives of female AAA patients had a higher aneurysm risk than relatives of male patients (9.0 vs 5.9%, p = 0.022), corresponding to 5.5- and 2.0-fold increases in aneurysm risk in the female and male relatives, respectively. The risk for aortic aneurysm in relatives of AAA patients is higher than expected from population risk. The excess risk is highest for the female relatives of AAA patients and for the relatives of female AAA patients. These findings endorse targeted AAA family screening for female and male relatives of all AAA patients.

  17. Perceived risk of prenatal diagnostic procedure-related miscarriage and Down syndrome among pregnant women.

    Science.gov (United States)

    Caughey, Aaron B; Washington, A Eugene; Kuppermann, Miriam

    2008-03-01

    The objective of the study was to identify correlates of perceived risk of carrying a Down syndrome-affected fetus or experiencing a procedure-related miscarriage among a diverse group of pregnant women. We conducted a cross-sectional survey of 1081 English-, Spanish-, or Chinese-speaking women receiving prenatal care in the San Francisco Bay area. Perceived risk of procedure-related miscarriage or carrying a Down syndrome-affected fetus was assessed using a linear rating scale from 0 (no risk) to 1 (high risk). Bivariate and multivariable analyses were used to explore associations between maternal characteristics including age, race/ethnicity, and socioeconomic status and perceived risks of carrying a Down syndrome-affected fetus or experiencing a procedure-related miscarriage. Women aged 35 years old or older had a higher perceived risk of Down syndrome than younger women (0.28 vs 0.22 on a scale from 0 to 1, P self-perceived health status (+0.08, P = .045). Latinas (+0.11, P = .008), women with an annual income less than $35,000 (+0.09, P = .003), and those who had difficulty conceiving (+0.09, P = .026) had higher perceived procedure-related miscarriage risk. Among women aged 35 years or older, perceived risk of carrying a Down syndrome-affected fetus was associated with the inclination to undergo prenatal diagnosis. Women's perceived risks of carrying a Down syndrome-affected fetus or having a procedure-related miscarriage are associated with numerous characteristics that have not been shown to be associated with the actual risks of these events. These perceived risks are associated with prenatal diagnostic test inclination. Understanding patients' risk perceptions and effectively communicating risk is critical to helping patients make informed decisions regarding use of invasive prenatal testing.

  18. Prevalence and risk factors related to preterm birth in Brazil

    Directory of Open Access Journals (Sweden)

    Maria do Carmo Leal

    2016-10-01

    Full Text Available Abstract Background The rate of preterm birth has been increasing worldwide, including in Brazil. This constitutes a significant public health challenge because of the higher levels of morbidity and mortality and long-term health effects associated with preterm birth. This study describes and quantifies factors affecting spontaneous and provider-initiated preterm birth in Brazil. Methods Data are from the 2011–2012 “Birth in Brazil” study, which used a national population-based sample of 23,940 women. We analyzed the variables following a three-level hierarchical methodology. For each level, we performed non-conditional multiple logistic regression for both spontaneous and provider-initiated preterm birth. Results The rate of preterm birth was 11.5 %, (95 % confidence 10.3 % to 12.9 % 60.7 % spontaneous - with spontaneous onset of labor or premature preterm rupture of membranes - and 39.3 % provider-initiated, with more than 90 % of the last group being pre-labor cesarean deliveries. Socio-demographic factors associated with spontaneous preterm birth were adolescent pregnancy, low total years of schooling, and inadequate prenatal care. Other risk factors were previous preterm birth (OR 3.74; 95 % CI 2.92–4.79, multiple pregnancy (OR 16.42; 95 % CI 10.56–25.53, abruptio placentae (OR 2.38; 95 % CI 1.27–4.47 and infections (OR 4.89; 95 % CI 1.72–13.88. In contrast, provider-initiated preterm birth was associated with private childbirth healthcare (OR 1.47; 95 % CI 1.09–1.97, advanced-age pregnancy (OR 1.27; 95 % CI 1.01–1.59, two or more prior cesarean deliveries (OR 1.64; 95 % CI 1.19–2.26, multiple pregnancy (OR 20.29; 95 % CI 12.58–32.72 and any maternal or fetal pathology (OR 6.84; 95 % CI 5.56–8.42. Conclusion The high proportion of provider-initiated preterm birth and its association with prior cesarean deliveries and all of the studied maternal/fetal pathologies suggest that a reduction of this type of

  19. Discovery, evaluation and distribution of haplotypes of the wheat Ppd-D1 gene.

    Science.gov (United States)

    Guo, Zhiai; Song, Yanxia; Zhou, Ronghua; Ren, Zhenglong; Jia, Jizeng

    2010-02-01

    Ppd-D1 is one of the most potent genes affecting the photoperiod response of wheat (Triticum aestivum). Only two alleles, insensitive Ppd-D1a and sensitive Ppd-D1b, were known previously, and these did not adequately explain the broad adaptation of wheat to photoperiod variation. In this study, five diagnostic molecular markers were employed to identify Ppd-D1 haplotypes in 492 wheat varieties from diverse geographic locations and 55 accessions of Aegilops tauschii, the D genome donor species of wheat. Six Ppd-D1 haplotypes, designated I-VI, were identified. Types II, V and VI were considered to be more ancient and types I, III and IV were considered to be derived from type II. The transcript abundances of the Ppd-D1 haplotypes showed continuous variation, being highest for haplotype I, lowest for haplotype III, and correlating negatively with varietal differences in heading time. These haplotypes also significantly affected other agronomic traits. The distribution frequency of Ppd-D1 haplotypes showed partial correlations with both latitudes and altitudes of wheat cultivation regions. The evolution, expression and distribution of Ppd-D1 haplotypes were consistent evidentially with each other. What was regarded as a pair of alleles in the past can now be considered a series of alleles leading to continuous variation.

  20. The putative oncogene Pim-1 in the mouse: its linkage and variation among t haplotypes.

    Science.gov (United States)

    Nadeau, J H; Phillips, S J

    1987-11-01

    Pim-1, a putative oncogene involved in T-cell lymphomagenesis, was mapped between the pseudo-alpha globin gene Hba-4ps and the alpha-crystallin gene Crya-1 on mouse chromosome 17 and therefore within the t complex. Pim-1 restriction fragment variants were identified among t haplotypes. Analysis of restriction fragment sizes obtained with 12 endonucleases demonstrated that the Pim-1 genes in some t haplotypes were indistinguishable from the sizes for the Pim-1b allele in BALB/c inbred mice. There are now three genes, Pim-1, Crya-1 and H-2 I-E, that vary among independently derived t haplotypes and that have indistinguishable alleles in t haplotypes and inbred strains. These genes are closely linked within the distal inversion of the t complex. Because it is unlikely that these variants arose independently in t haplotypes and their wild-type homologues, we propose that an exchange of chromosomal segments, probably through double crossingover, was responsible for indistinguishable Pim-1 genes shared by certain t haplotypes and their wild-type homologues. There was, however, no apparent association between variant alleles of these three genes among t haplotypes as would be expected if a single exchange introduced these alleles into t haplotypes. If these variant alleles can be shown to be identical to the wild-type allele, then lack of association suggests that multiple exchanges have occurred during the evolution of the t complex.

  1. Association between VEGF polymorphisms (936c/t, -460t/c and -634g/c) with haplotypes and coronary heart disease susceptibility.

    Science.gov (United States)

    Han, Xia; Liu, Lili; Niu, Jiamin; Yang, Jun; Zhang, Zengtang; Zhang, Zhiqiang

    2015-01-01

    Our aim was to investigate the association between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and coronary heart disease (CHD) susceptibility in Chinese Han population. 144 CHD patients and 150 healthy individuals were enrolled in the study. Three SNPs (936C/T, -460T/C and -634G/C) of VEGF were chose and then were genotyped with Sequenom time-of-flight mass spectrometry (TOFMS). Odds ratio (OR) with 95% confidence interval (CI) were used to evaluate the association of genotypes and haplotypes and CHD susceptibility. The frequencies of -460T/C CC genotype (13.6%) was found higher in the case group than that of control group (6.7%), which indicated that CC genotype was a risk factor for CHD (OR=2.50, 95% CI=1.10-5.68). Correspondently, the C allele appeared to increase the risk of CHD (OR=1.54, 95% CI=1.07-2.22). For -634G/C polymorphism, the risk of the CC genotype carrier for CHD increased 2.24 fold compared to the wild genotype. Moreover, -634G/CC allele was significantly associated with CHD susceptibility (OR=1.65, 95% CI=1.15-2.36). In addition, +936C/T CT genotype and C allele appeared to be a genetic-susceptibility factors for CHD (OR=2.43, 95% CI=1.44-4.10; OR=1.95, 95% CI=1.26-3.02). The haplotype analysis showed that T-C-T, C-C-C and C-G-C haplotypes all could increase the risk for CHD (OR: 2.43, 2.77 and 2.33). we concluded VEGF polymorphisms were associated with CHD susceptibility. Moreover, the haplotypes of T-C-T, C-C-C and C-G-C all could increase the risk for CHD.

  2. Analysis of Multiallelic CNVs by Emulsion Haplotype Fusion PCR.

    Science.gov (United States)

    Tyson, Jess; Armour, John A L

    2017-01-01

    Emulsion-fusion PCR recovers long-range sequence information by combining products in cis from individual genomic DNA molecules. Emulsion droplets act as very numerous small reaction chambers in which different PCR products from a single genomic DNA molecule are condensed into short joint products, to unite sequences in cis from widely separated genomic sites. These products can therefore provide information about the arrangement of sequences and variants at a larger scale than established long-read sequencing methods. The method has been useful in defining the phase of variants in haplotypes, the typing of inversions, and determining the configuration of sequence variants in multiallelic CNVs. In this description we outline the rationale for the application of emulsion-fusion PCR methods to the analysis of multiallelic CNVs, and give practical details for our own implementation of the method in that context.

  3. Visible Age-Related Signs and Risk of Ischemic Heart Disease in the General Population

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Frikke-Schmidt, Ruth; Schnohr, Peter

    2014-01-01

    developed MI. Presence of frontoparietal baldness, crown top baldness, earlobe crease, and xanthelasmata was associated with increased risk of IHD or MI after multifactorial adjustment for chronological age and well-known cardiovascular risk factors. The risk of IHD and MI increased stepwise with increasing...... risk of IHD and MI increased with increasing number of visible age-related signs. CONCLUSIONS: Male pattern baldness, earlobe crease, and xanthelasmata-alone or in combination-associate with increased risk of ischemic heart disease and myocardial infarction independent of chronological age and other...

  4. Suicide risk in relation to psychiatric hospitalization: evidence based on longitudinal registers

    DEFF Research Database (Denmark)

    Qin, Ping; Nordentoft, Merete

    2005-01-01

    history increases suicide risk relatively more in women than in men; and suicide risk is substantial for substance disorders and for multiple admissions in women but not in men. CONCLUSIONS: Suicide risk peaks in periods immediately after admission and discharge. The risk is particularly high in persons...... with affective disorders and in persons with short hospital treatment. These findings should lead to systematic evaluation of suicide risk among inpatients before discharge and corresponding outpatient treatment, and family support should be initiated immediately after the discharge...

  5. Risk factors related to heartburn in pregnant women attending the antenatal care clinic, Rajavithi Hospital.

    Science.gov (United States)

    Kovavisarach, Ekachai; Phromsila, Raweewan

    2012-08-01

    To determine the risk factors related to heartburn in pregnant women attending the antenatal care clinic, Rajavithi Hospital. Self-reporting questionnaire about demographic data and risk factors related to heartburn in those pregnant women between May 1 and July 31, 2010. Heartburn was found in 55 out of 452 pregnant women (12.2%). There were no significant differences in demographic characteristics and risk factors between the heartburn and non-heartburn groups. Consumption of alcoholic drinks was a reversely significant risk factor of heartburn (OR 0.11, CI 0.01 to 0.78) (p = 0.005). Heartburn was not uncommon, and no associated factors were demonstrated.

  6. Association of IL1B -511C/-31T haplotype and Helicobacter pylori vacA genotypes with gastric ulcer and chronic gastritis

    Directory of Open Access Journals (Sweden)

    Fernández-Tilapa Gloria

    2010-10-01

    Full Text Available Abstract Background The association between proinflammatory cytokine gene polymorphisms and gastric diseases related to Helicobacter pylori varies by population and geographic area. Our objective was to determine if the IL-1B -511 T>C and -31 C>T polymorphisms and H. pylori vacA genotypes are associated with risk of chronic gastritis and gastric ulcer in a Mexican population. Methods We conducted endoscopic studies in 128 patients with symptoms of dyspepsia. We took two biopsies from the body, antrum, or ulcer edge from each patient, and classified our histopathological findings according to the Sydney System. H. pylori infection and vacA genotyping were accomplished via PCR from total DNA of the gastric biopsies. We confirmed the presence of anti-H. pylori serum IgG and IgM in 102 control subjects. In both case subjects and control subjects, the IL-1B -511 T>C polymorphism was genotyped by PCR-RFLPs and the IL-1B -31 C>T polymorphism was genotyped by pyrosequencing. Results Sixty-two point seven (62.7% of the 102 control subjects were H. pylori-seropositive. Among the case subjects, 100 were diagnosed with chronic gastritis and 28 with gastric ulcer. We found that 77% of the patients with chronic gastritis and 85.7% of the patients with gastric ulcer were H. pylori-positive. The predominant H. pylori genotype was vacA s1m1 (58.4% and the most frequent subtype was vacA s1. The -511 TC, (rs16944 -511 T>C genotype and the -511C allele were associated with chronic gastritis (OR = 3.1, 95% CI = 1.4-6.8 and OR = 3.0, 95% CI = 1.4-6.0, respectively. The subjects carrying -31T (rs1143627 -31 C>T were found to be at a higher risk of having chronic gastritis (OR = 2.8, 95% CI = 1.3-5.8. The IL-1B -511C/-31T haplotype was associated with chronic gastritis (OR = 2.1, 95% CI = 1.2-3.8 but not with gastric ulcer. Conclusions The H. pylori vacA genotypes identified herein were similar to those reported for other regions of Mexico. The vacA s1m1 genotype was

  7. Lens aging in relation to nutritional determinants and possible risk factors for age-related cataract

    NARCIS (Netherlands)

    Berendschot, T.T.J.M.; Broekmans, W.M.R.; Klöpping-Ketelaars, I.A.A.; Kardinaal, A.F.M.; Poppel, G. van; Norren, D. van

    2002-01-01

    Objective: To investigate whether nutritional factors and possible risk factors for cataract influence the lens optical density (LOD). Design: Three hundred seventy-six subjects, aged 18 to 75 years, were recruited. In a cross-sectional design, serum was analyzed for lutein, zeaxanthin, vitamin C,

  8. Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico

    Directory of Open Access Journals (Sweden)

    José Ángel Cahua-Pablo

    2015-09-01

    Full Text Available Metabolic syndrome (MetS is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD. Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR = 2.9; p = 0.013 in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04. Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006. In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001. In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.

  9. Organelle DNA haplotypes reflect crop-use characteristics and geographic origins of Cannabis sativa.

    Science.gov (United States)

    Gilmore, Simon; Peakall, Rod; Robertson, James

    2007-10-25

    Comparative sequencing of cannabis individuals across 12 chloroplast and mitochondrial DNA loci revealed 7 polymorphic sites, including 5 length variable regions and 2 single nucleotide polymorphisms. Simple PCR assays were developed to assay these polymorphisms, and organelle DNA haplotypes were obtained for 188 cannabis individuals from 76 separate populations, including drug-type, fibre-type and wild populations. The haplotype data were analysed using parsimony, UPGMA and neighbour joining methods. Three haplotype groups were recovered by each analysis method, and these groups are suggestive of the crop-use characteristics and geographical origin of the populations, although not strictly diagnostic. We discuss the relationship between our haplotype data and taxonomic opinions of cannabis, and the implications of organelle DNA haplotyping to forensic investigations of cannabis.

  10. Risk-taking related to drug use: an application of the shift-to-risk design.

    Science.gov (United States)

    Deren, S; Des Jarlais, D C

    1977-01-01

    The utility of the shift-to-risk design for studying the influence of peer groups on drug taking was investigated. Two studies using this design with drug content were conducted, varying the level of information provided about a drug. Subjects were from two college classes consisting of 26 and 28 students. Results indicated that the specification of possible harmful drug effects which are somewhat minimal lead to a significantly greater willingness to recommend trying the drug. In addition, a tendency for a shift-to-caution was found. It was concluded that the shift-to-risk designwas useful for studying decision-making regarding drug use, and that both users and nonusers of drugs should be included in future research.

  11. Student nurse perceptions of risk in relation to international placements: a phenomenological research study.

    Science.gov (United States)

    Morgan, Debra A

    2012-11-01

    International nursing electives have been identified as a positive learning experience for students. However, whilst there are risks associated with international student placements in general, there is a scarcity of research specifically relating to student nurse's experiences of risk. This study aimed to investigate UK undergraduate student nurse experiences of risk during an international placement. A phenomenological methodology was applied and semi-structured interviews were conducted with student nurses who had recently returned from an international clinical placement abroad. Ten, second year student nurses, studying on a pre-registration diploma/BSc (Hons) Nursing Studies/Registered Nurse programme from one UK University participated in the study. Findings from the study highlighted that students felt that three types of risk existed; physical risk, clinical-professional risk and socio-cultural risk. Perceptions of risk were influenced by sociological theory relating to the concept of 'the other' and students attempted to reduce risk by employing strategies to reduce 'Otherness'. They also applied psychological theory relating to heuristics such as 'safety in numbers.' It also emerged from the study that exposure to perceived risk enhanced learning as students reported that it encouraged personal and professional development in particular and so assisted students in their move toward self-actualisation. It is suggested, and intended, that findings from this study can be applied to the preparation of students to further enhance their safety and learning experience during international placements abroad. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Management of the radon-related risk. Guide for local authorities. Guide for employers

    International Nuclear Information System (INIS)

    Struillou, Yves; Gupta, Olivier

    2017-01-01

    A first guide aims at being an aid to decision by specifying obligations of local authorities as owners of buildings open to public or as employers, but also at being a support for their health and social actions in terms of information on radon risk in housing. After a presentation of the risk related to radon (health risks, radon propagation, regulatory areas concerned by radon risk management in France), the report indicates the various obligations and mandatory actions for local authorities as building owner and as employer, and actions to be undertaken for existing and new buildings. Technical sheets are provided regarding radon detection, certifications, simple actions, technical diagnosis, remediation works, efficiency control of technical solutions, expert in radiation protection. The second guide aims at being an aid to decision by specifying obligations for employers in terms of management of radon-related risk to which some workers might be exposed, and at providing some good practice recommendations. After a presentation of the risk related to radon (health risks, radon propagation, regulatory areas concerned by radon risk management in France), the report addresses how to organise the radon-related risk management, how to measure radon in work places, how to interpret results and which actions to undertake. Technical sheets are provided regarding radon detection, certifications, simple actions, technical diagnosis, remediation works, efficiency control of technical solutions, expert in radiation protection

  13. Relative risk of visceral leishmaniasis in Brazil: a spatial analysis in urban area.

    Directory of Open Access Journals (Sweden)

    Valdelaine Etelvina Miranda de Araújo

    2013-11-01

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is a vector-borne disease whose factors involved in transmission are poorly understood, especially in more urban and densely populated counties. In Brazil, the VL urbanization is a challenge for the control program. The goals were to identify the greater risk areas for human VL and the risk factors involved in transmission. METHODOLOGY: This is an ecological study on the relative risk of human VL. Spatial units of analysis were the coverage areas of the Basic Health Units (146 small-areas of Belo Horizonte, Minas Gerais State, Brazil. Human VL cases, from 2007 to 2009 (n = 412, were obtained in the Brazilian Reportable Disease Information System. Bayesian approach was used to model the relative risk of VL including potential risk factors involved in transmission (canine infection, socioeconomic and environmental features and to identify the small-areas of greater risk to human VL. PRINCIPAL FINDINGS: The relative risk of VL was shown to be correlated with income, education, and the number of infected dogs per inhabitants. The estimates of relative risk of VL were higher than 1.0 in 54% of the areas (79/146. The spatial modeling highlighted 14 areas with the highest relative risk of VL and 12 of them are concentrated in the northern region of the city. CONCLUSIONS: The spatial analysis used in this study is useful for the identification of small-areas according to risk of human VL and presents operational applicability in control and surveillance program in an urban environment with an unequal spatial distribution of the disease. Thus the frequent monitoring of relative risk of human VL in small-areas is important to direct and prioritize the actions of the control program in urban environment, especially in big cities.

  14. Variations with time and age in the relative risks of solid cancer incidence after radiation exposure

    International Nuclear Information System (INIS)

    Little, M.P.; Muirhead, C.R.; de Vathaire, F.; Charles, M.W.

    1997-01-01

    The Japanese atomic bomb survivor cancer incidence dataset and data on five groups exposed to radiation for medical reasons in childhood are analysed and evidence found for a reduction in the radiation-induced relative risk of cancers other than leukaemia with increasing time since exposure and age at exposure. The rate of the reductions in relative risk with time since exposure are not significantly different for those exposed in childhood and for those exposed in adulthood, if adjustment is made for the effects on the relative risk of age at exposure. For those irradiated in childhood, there is a statistically significant annual reduction of 5.8% (95% Cl 2.8, 8.9) in excess relative risk, and there are no strong indications of inter-cohort heterogeniety in the speed of reduction of relative risk. After adjustment for the effects of age at exposure, there is a significant annual reduction of 3.6% (95% Cl 1.6, 5.6) in excess relative risk in all age-at-exposure groups. There are significant reductions of 5.2% (95% Cl 3.7, 6.8) in excess relative risk per year of age at exposure. There are statistically significant (P = 0.04) interactions between the exponential adjustments to the excess relative risk for age at exposure and time since exposure in the Japanese data, but no indications (P = 0.38) of such interactions when powers of time since exposure and attained age are used to adjust the excess relative risk, so that the fit of the model with power adjustments is to be preferred to that of the model with exponential adjustments. (author)

  15. Haplotype assembly in polyploid genomes and identical by descent shared tracts.

    Science.gov (United States)

    Aguiar, Derek; Istrail, Sorin

    2013-07-01

    Genome-wide haplotype reconstruction from sequence data, or haplotype assembly, is at the center of major challenges in molecular biology and life sciences. For complex eukaryotic organisms like humans, the genome is vast and the population samples are growing so rapidly that algorithms processing high-throughput sequencing data must scale favorably in terms of both accuracy and computational efficiency. Furthermore, current models and methodologies for haplotype assembly (i) do not consider individuals sharing haplotypes jointly, which reduces the size and accuracy of assembled haplotypes, and (ii) are unable to model genomes having more than two sets of homologous chromosomes (polyploidy). Polyploid organisms are increasingly becoming the target of many research groups interested in the genomics of disease, phylogenetics, botany and evolution but there is an absence of theory and methods for polyploid haplotype reconstruction. In this work, we present a number of results, extensions and generalizations of compass graphs and our HapCompass framework. We prove the theoretical complexity of two haplotype assembly optimizations, thereby motivating the use of heuristics. Furthermore, we present graph theory-based algorithms for the problem of haplotype assembly using our previously developed HapCompass framework for (i) novel implementations of haplotype assembly optimizations (minimum error correction), (ii) assembly of a pair of individuals sharing a haplotype tract identical by descent and (iii) assembly of polyploid genomes. We evaluate our methods on 1000 Genomes Project, Pacific Biosciences and simulated sequence data. HapCompass is available for download at http://www.brown.edu/Research/Istrail_Lab/. Supplementary data are available at Bioinformatics online.

  16. Polymorphism at Expressed DQ and DR Loci in Five Common Equine MHC Haplotypes

    Science.gov (United States)

    Miller, Donald; Tallmadge, Rebecca L.; Binns, Matthew; Zhu, Baoli; Mohamoud, Yasmin Ali; Ahmed, Ayeda; Brooks, Samantha A.; Antczak, Douglas F.

    2016-01-01

    The polymorphism of Major Histocompatibility Complex (MHC) class II DQ and DR genes in five common Equine Leukocyte Antigen (ELA) haplotypes was determined through sequencing of mRNA transcripts isolated from lymphocytes of eight ELA homozygous horses. Ten expressed MHC class II genes were detected in horses of the ELA-A3 haplotype carried by the donor horses of the equine Bacterial Artificial Chromosome (BAC) library and the reference genome sequence: four DR genes and six DQ genes. The other four ELA haplotypes contained at least eight expressed polymorphic MHC class II loci. Next Generation Sequencing (NGS) of genomic DNA of these four MHC haplotypes revealed stop codons in the DQA3 gene in the ELA-A2, ELA-A5, and ELA-A9 haplotypes. Few NGS reads were obtained for the other MHC class II genes that were not amplified in these horses. The amino acid sequences across haplotypes contained locus-specific residues, and the locus clusters produced by phylogenetic analysis were well supported. The MHC class II alleles within the five tested haplotypes were largely non-overlapping between haplotypes. The complement of equine MHC class II DQ and DR genes appears to be well conserved between haplotypes, in contrast to the recently described variation in class I gene loci between equine MHC haplotypes. The identification of allelic series of equine MHC class II loci will aid comparative studies of mammalian MHC conservation and evolution and may also help to interpret associations between the equine MHC class II region and diseases of the horse. PMID:27889800

  17. MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression.

    Science.gov (United States)

    Xu, Meixiang; Cross, Courtney E; Speidel, Jordan T; Abdel-Rahman, Sherif Z

    2016-10-01

    The O 6 -methylguanine-DNA methyltransferase (MGMT) protein removes O 6 -alkyl-guanine adducts from DNA. MGMT expression can thus alter the sensitivity of cells and tissues to environmental and chemotherapeutic alkylating agents. Previously, we defined the haplotype structure encompassing single nucleotide polymorphisms (SNPs) in the MGMT promoter/enhancer (P/E) region and found that haplotypes, rather than individual SNPs, alter MGMT promoter activity. The exact mechanism(s) by which these haplotypes exert their effect on MGMT promoter activity is currently unknown, but we noted that many of the SNPs comprising the MGMT P/E haplotypes are located within or in close proximity to putative transcription factor binding sites. Thus, these haplotypes could potentially affect transcription factor binding and, subsequently, alter MGMT promoter activity. In this study, we test the hypothesis that MGMT P/E haplotypes affect MGMT promoter activity by altering transcription factor (TF) binding to the P/E region. We used a promoter binding TF profiling array and a reporter assay to evaluate the effect of different P/E haplotypes on TF binding and MGMT expression, respectively. Our data revealed a significant difference in TF binding profiles between the different haplotypes evaluated. We identified TFs that consistently showed significant haplotype-dependent binding alterations (p ≤ 0.01) and revealed their role in regulating MGMT expression using siRNAs and a dual-luciferase reporter assay system. The data generated support our hypothesis that promoter haplotypes alter the binding of TFs to the MGMT P/E and, subsequently, affect their regulatory function on MGMT promoter activity and expression level.

  18. Plasmodium falciparum isolates from Angola show the StctVMNT haplotype in the pfcrt gene

    Science.gov (United States)

    2010-01-01

    Background Effective treatment remains a mainstay of malaria control, but it is unfortunately strongly compromised by drug resistance, particularly in Plasmodium falciparum, the most important human malaria parasite. Although P. falciparum chemoresistance is well recognized all over the world, limited data are available on the distribution and prevalence of pfcrt and pfmdr1 haplotypes that mediate resistance to commonly used drugs and that show distinct geographic differences. Methods Plasmodium falciparum-infected blood samples collected in 2007 at four municipalities of Luanda, Angola, were genotyped using PCR and direct DNA sequencing. Single nucleotide polymorphisms in the P. falciparum pfcrt and pfmdr1 genes were assessed and haplotype prevalences were determined. Results and Discussion The most prevalent pfcrt haplotype was StctVMNT (representing amino acids at codons 72-76). This result was unexpected, since the StctVMNT haplotype has previously been seen mainly in parasites from South America and India. The CVIET, CVMNT and CVINT drug-resistance haplotypes were also found, and one previously undescribed haplotype (CVMDT) was detected. Regarding pfmdr1, the most prevalent haplotype was YEYSNVD (representing amino acids at codons 86, 130, 184, 1034, 1042, 1109 and 1246). Wild haplotypes for pfcrt and pfmdr1 were uncommon; 3% of field isolates harbored wild type pfcrt (CVMNK), whereas 21% had wild type pfmdr1 (NEYSNVD). The observed predominance of the StctVMNT haplotype in Angola could be a result of frequent travel between Brazil and Angola citizens in the context of selective pressure of heavy CQ use. Conclusions The high prevalence of the pfcrt SVMNT haplotype and the pfmdr1 86Y mutation confirm high-level chloroquine resistance and might suggest reduced efficacy of amodiaquine in Angola. Further studies must be encouraged to examine the in vitro sensitivity of pfcrt SVMNT parasites to artesunate and amodiaquine for better conclusive data. PMID:20565881

  19. Effects of TMEM154 haplotypes 1 and 3 on susceptibility to ovine progressive pneumonia virus following natural exposure in sheep.

    Science.gov (United States)

    Leymaster, K A; Chitko-McKown, C G; Clawson, M L; Harhay, G P; Heaton, M P

    2013-11-01

    "1 1." These results are consistent with complete dominance of haplotype 3 relative to haplotype 1. The probability of infection at 9 mo of age for lambs with either diplotype "1 3" or "3 3" averaged 3.56 times that of lambs with diplotype "1 1." Genetic susceptibility to OPPV infection can be reduced by selection to increase the frequency of haplotype 1, resulting in a greater proportion of lambs with diplotype "1 1."

  20. Emotional reactions to alcohol-related words: Differences between low- and high-risk drinkers.

    Science.gov (United States)

    Gantiva, Carlos; Delgado, Rafael; Romo-González, Tania

    2015-11-01

    Research that has examined responses to alcohol-related words in drinkers has mostly linked such responses to memory, attentional, and perceptual bias. However, studies of emotional processing in alcoholics have not received much attention. The main goal of the present study was to identify the features and differences of emotional responses to alcohol-related words in low- and high-risk drinkers. A total of 149 low-risk drinkers and 125 high-risk drinkers evaluated five alcohol-related words and 15 words from the Affective Norms for English Words in the dimensions of valence, arousal, and dominance using the Self-Assessment Manikin. The results indicated that high-risk drinkers evaluated alcohol-related words as more appetitive and arousing. These results, together with findings in the attention and memory research literature, suggest that alcohol-related words can serve as conditioned cues in alcohol consumption. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Malaria in Africa: vector species' niche models and relative risk maps.

    Directory of Open Access Journals (Sweden)

    Alexander Moffett

    2007-09-01

    Full Text Available A central theoretical goal of epidemiology is the construction of spatial models of disease prevalence and risk, including maps for the potential spread of infectious disease. We provide three continent-wide maps representing the relative risk of malaria in Africa based on ecological niche models of vector species and risk analysis at a spatial resolution of 1 arc-minute (9 185 275 cells of approximately 4 sq km. Using a maximum entropy method we construct niche models for 10 malaria vector species based on species occurrence records since 1980, 19 climatic variables, altitude, and land cover data (in 14 classes. For seven vectors (Anopheles coustani, A. funestus, A. melas, A. merus, A. moucheti, A. nili, and A. paludis these are the first published niche models. We predict that Central Africa has poor habitat for both A. arabiensis and A. gambiae, and that A. quadriannulatus and A. arabiensis have restricted habitats in Southern Africa as claimed by field experts in criticism of previous models. The results of the niche models are incorporated into three relative risk models which assume different ecological interactions between vector species. The "additive" model assumes no interaction; the "minimax" model assumes maximum relative risk due to any vector in a cell; and the "competitive exclusion" model assumes the relative risk that arises from the most suitable vector for a cell. All models include variable anthrophilicity of vectors and spatial variation in human population density. Relative risk maps are produced from these models. All models predict that human population density is the critical factor determining malaria risk. Our method of constructing relative risk maps is equally general. We discuss the limits of the relative risk maps reported here, and the additional data that are required for their improvement. The protocol developed here can be used for any other vector-borne disease.

  2. Use-related risk analysis for medical devices based on improved FMEA.

    Science.gov (United States)

    Liu, Long; Shuai, Ma; Wang, Zhu; Li, Ping

    2012-01-01

    In order to effectively analyze and control use-related risk of medical devices, quantitative methodologies must be applied. Failure Mode and Effects Analysis (FMEA) is a proactive technique for error detection and risk reduction. In this article, an improved FMEA based on Fuzzy Mathematics and Grey Relational Theory is developed to better carry out user-related risk analysis for medical devices. As an example, the analysis process using this improved FMEA method for a certain medical device (C-arm X-ray machine) is described.

  3. Urban-hazard risk analysis: mapping of heat-related risks in the elderly in major Italian cities.

    Directory of Open Access Journals (Sweden)

    Marco Morabito

    Full Text Available Short-term impacts of high temperatures on the elderly are well known. Even though Italy has the highest proportion of elderly citizens in Europe, there is a lack of information on spatial heat-related elderly risks.Development of high-resolution, heat-related urban risk maps regarding the elderly population (≥ 65.A long time-series (2001-2013 of remote sensing MODIS data, averaged over the summer period for eleven major Italian cities, were downscaled to obtain high spatial resolution (100 m daytime and night-time land surface temperatures (LST. LST was estimated pixel-wise by applying two statistical model approaches: 1 the Linear Regression Model (LRM; 2 the Generalized Additive Model (GAM. Total and elderly population density data were extracted from the Joint Research Centre population grid (100 m from the 2001 census (Eurostat source, and processed together using "Crichton's Risk Triangle" hazard-risk methodology for obtaining a Heat-related Elderly Risk Index (HERI.The GAM procedure allowed for improved daytime and night-time LST estimations compared to the LRM approach. High-resolution maps of daytime and night-time HERI levels were developed for inland and coastal cities. Urban areas with the hazardous HERI level (very high risk were not necessarily characterized by the highest temperatures. The hazardous HERI level was generally localized to encompass the city-centre in inland cities and the inner area in coastal cities. The two most dangerous HERI levels were greater in the coastal rather than inland cities.This study shows the great potential of combining geospatial technologies and spatial demographic characteristics within a simple and flexible framework in order to provide high-resolution urban mapping of daytime and night-time HERI. In this way, potential areas for intervention are immediately identified with up-to-street level details. This information could support public health operators and facilitate coordination for heat-related

  4. Urban-hazard risk analysis: mapping of heat-related risks in the elderly in major Italian cities.

    Science.gov (United States)

    Morabito, Marco; Crisci, Alfonso; Gioli, Beniamino; Gualtieri, Giovanni; Toscano, Piero; Di Stefano, Valentina; Orlandini, Simone; Gensini, Gian Franco

    2015-01-01

    Short-term impacts of high temperatures on the elderly are well known. Even though Italy has the highest proportion of elderly citizens in Europe, there is a lack of information on spatial heat-related elderly risks. Development of high-resolution, heat-related urban risk maps regarding the elderly population (≥ 65). A long time-series (2001-2013) of remote sensing MODIS data, averaged over the summer period for eleven major Italian cities, were downscaled to obtain high spatial resolution (100 m) daytime and night-time land surface temperatures (LST). LST was estimated pixel-wise by applying two statistical model approaches: 1) the Linear Regression Model (LRM); 2) the Generalized Additive Model (GAM). Total and elderly population density data were extracted from the Joint Research Centre population grid (100 m) from the 2001 census (Eurostat source), and processed together using "Crichton's Risk Triangle" hazard-risk methodology for obtaining a Heat-related Elderly Risk Index (HERI). The GAM procedure allowed for improved daytime and night-time LST estimations compared to the LRM approach. High-resolution maps of daytime and night-time HERI levels were developed for inland and coastal cities. Urban areas with the hazardous HERI level (very high risk) were not necessarily characterized by the highest temperatures. The hazardous HERI level was generally localized to encompass the city-centre in inland cities and the inner area in coastal cities. The two most dangerous HERI levels were greater in the coastal rather than inland cities. This study shows the great potential of combining geospatial technologies and spatial demographic characteristics within a simple and flexible framework in order to provide high-resolution urban mapping of daytime and night-time HERI. In this way, potential areas for intervention are immediately identified with up-to-street level details. This information could support public health operators and facilitate coordination for heat-related

  5. Anxious and depressive symptoms in the French Asbestos-Related Diseases Cohort: risk factors and self-perception of risk.

    Science.gov (United States)

    Mounchetrou Njoya, Ibrahim; Paris, Christophe; Dinet, Jerome; Luc, Amandine; Lighezzolo-Alnot, Joelle; Pairon, Jean-Claude; Thaon, Isabelle

    2017-04-01

    Asbestos is known to be an independent risk factor for lung and pleural cancers. However, to date, little attention has been paid to the psychological effects of asbestos exposure among exposed subjects. The objectives of this study were to estimate the prevalence of anxious and depressive symptoms among >2000 French participants of the Asbestos-Related Diseases Cohort (ARDCO), 6 years after their inclusion, to identify the risk factors associated with those anxious and depressive symptoms and to evaluate the impact of the asbestos-risk perception. The ARDCO was constituted in four regions of France between October 2003 and December 2005, by including former asbestos workers. Between 2011 and 2012, participants of the ARDCO program were invited to undergo another chest CT scan 6 years after the previous scan. Participants were asked to complete questionnaires including asbestos exposure assessment, Hospital Anxiety and Depression Scale (HADS), asbestos-risk perception and self-perception of asbestos-related diseases. Among the 2225 participants, 2210 fully completed questionnaires were collected and analyzed. The prevalence of symptoms of probable anxiety and probable depression was 19.7% and 9.9%, respectively. The risk of anxious and depressive symptoms was independently associated with self-perception of the intensity of asbestos exposure, asbestos-risk perception and self-perception of asbestos-related diseases. The results obtained in this large study confirm that previously asbestos-exposed subjects are likely to develop anxious and depressive symptoms. Finally, implications related to the prevention of anxiety and depression among asbestos-exposed workers is discussed. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  6. Recovery of native genetic background in admixed populations using haplotypes, phenotypes, and pedigree information--using Cika cattle as a case breed.

    Directory of Open Access Journals (Sweden)

    Mojca Simčič

    Full Text Available The aim of this study was to obtain unbiased estimates of the diversity parameters, the population history, and the degree of admixture in Cika cattle which represents the local admixed breeds at risk of extinction undergoing challenging conservation programs. Genetic analyses were performed on the genome-wide Single Nucleotide Polymorphism (SNP Illumina Bovine SNP50 array data of 76 Cika animals and 531 animals from 14 reference populations. To obtain unbiased estimates we used short haplotypes spanning four markers instead of single SNPs to avoid an ascertainment bias of the BovineSNP50 array. Genome-wide haplotypes combined with partial pedigree and type trait classification show the potential to improve identification of purebred animals with a low degree of admixture. Phylogenetic analyses demonstrated unique genetic identity of Cika animals. Genetic distance matrix presented by rooted Neighbour-Net suggested long and broad phylogenetic connection between Cika and Pinzgauer. Unsupervised clustering performed by the admixture analysis and two-dimensional presentation of the genetic distances between individuals also suggest Cika is a distinct breed despite being similar in appearance to Pinzgauer. Animals identified as the most purebred could be used as a nucleus for a recovery of the native genetic background in the current admixed population. The results show that local well-adapted strains, which have never been intensively managed and differentiated into specific breeds, exhibit large haplotype diversity. They suggest a conservation and recovery approach that does not rely exclusively on the search for the original native genetic background but rather on the identification and removal of common introgressed haplotypes would be more powerful. Successful implementation of such an approach should be based on combining phenotype, pedigree, and genome-wide haplotype data of the breed of interest and a spectrum of reference breeds which

  7. Waterborne disease-related risk perceptions in the Sonora River basin, Mexico.

    Science.gov (United States)

    Morua, Agustin Robles; Halvorsen, Kathleen E; Mayer, Alex S

    2011-05-01

    Waterborne disease is estimated to cause about 10% of all diseases worldwide. However, related risk perceptions are not well understood, particularly in the developing world where waterborne disease is an enormous problem. We focus on understanding risk perceptions related to these issues in a region within northern Mexico. Our findings show how waterborne disease problems and solutions are understood in eight small communities along a highly contaminated river system. We found major differences in risk perceptions between health professionals, government officials, and lay citizens. Health professionals believed that a high level of human-waste-related risk existed within the region. Few officials and lay citizens shared this belief. In addition, few officials and lay citizens were aware of poor wastewater-management-related disease outbreaks and water contamination. Finally, aside from health professionals, a few interviewees understood the importance of basic hygiene and water treatment measures that could help to prevent disease. Our results add to the literature on environmentally-related risk perceptions in the developing world. We discuss recommendations for improving future human-wastewater-related risk communication within the region. © 2011 Society for Risk Analysis.

  8. Work Sectors with High Risk for Work-Related Musculoskeletal Disorders in Korean Men and Women

    OpenAIRE

    Jungsun Park; Yangho Kim; Boyoung Han

    2018-01-01

    Background: To identify work sectors with high risk for work-related musculoskeletal disorders (MSDs) in Korean men and women. Methods: We analyzed nationwide data to identify ergonomic risk factors in Korean employees. In particular, we analyzed data on exposure to five ergonomic risk factors (painful/tiring postures, lifting/moving heavy materials, standing/walking, repetitive hand/arm movements, and hand/arm vibration) according to employment sector, sex, and age, using the 2014 Fourth Kor...

  9. Reexamining the empirical relation between loan risk and collateral: The roles of collateral characteristics and types

    OpenAIRE

    Berger, Allen N.; Frame, Scott; Ioannidou, Vasso

    2011-01-01

    This paper offers a possible explanation for the conflicting empirical results in the literature concerning the relation between loan risk and collateral. Specifically, we posit that different economic characteristics or types of collateral pledges may be associated with the empirical dominance of the four different risk-collateral channels implied by economic theory. For our sample, collateral overall is associated with lower loan risk premiums and a higher probability of ex post loan nonper...

  10. Relative risk analysis in regulating the use of radiation-emitting medical devices. A preliminary application

    Energy Technology Data Exchange (ETDEWEB)

    Jones, E.D.; Banks, W.W.; Altenbach, T.J.; Fischer, L.E. [Lawrence Livermore National Lab., CA (United States)

    1995-09-01

    This report describes a preliminary application of an analysis approach for assessing relative risks in the use of radiation- emitting medical devices. Results are presented on human-initiated actions and failure modes that are most likely to occur in the use of the Gamma Knife, a gamma irradiation therapy device. This effort represents an initial step in a US Nuclear Regulatory Commission (NRC) plan to evaluate the potential role of risk analysis in regulating the use of nuclear medical devices. For this preliminary application of risk assessment, the focus was to develop a basic process using existing techniques for identifying the most likely risk contributors and their relative importance. The approach taken developed relative risk rankings and profiles that incorporated the type and quality of data available and could present results in an easily understood form. This work was performed by the Lawrence Livermore National Laboratory for the NRC.

  11. Patient clusters in acute, work-related back pain based on patterns of disability risk factors.

    Science.gov (United States)

    Shaw, William S; Pransky, Glenn; Patterson, William; Linton, Steven J; Winters, Thomas

    2007-02-01

    To identify subgroups of patients with work-related back pain based on disability risk factors. Patients with work-related back pain (N = 528) completed a 16-item questionnaire of potential disability risk factors before their initial medical evaluation. Outcomes of pain, functional limitation, and work disability were assessed 1 and 3 months later. A K-Means cluster analysis of 5 disability risk factors (pain, depressed mood, fear avoidant beliefs, work inflexibility, and poor expectations for recovery) resulted in 4 sub-groups: low risk (n = 182); emotional distress (n = 103); severe pain/fear avoidant (n = 102); and concerns about job accommodation (n = 141). Pain and disability outcomes at follow-up were superior in the low-risk group and poorest in the sever