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Sample records for addition genetic studies

  1. Genetic assessment of additional endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study.

    PubMed

    Greenwood, Tiffany A; Lazzeroni, Laura C; Calkins, Monica E; Freedman, Robert; Green, Michael F; Gur, Raquel E; Gur, Ruben C; Light, Gregory A; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Stone, William S; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L

    2016-01-01

    The Consortium on the Genetics of Schizophrenia Family Study (COGS-1) has previously reported our efforts to characterize the genetic architecture of 12 primary endophenotypes for schizophrenia. We now report the characterization of 13 additional measures derived from the same endophenotype test paradigms in the COGS-1 families. Nine of the measures were found to discriminate between schizophrenia patients and controls, were significantly heritable (31 to 62%), and were sufficiently independent of previously assessed endophenotypes, demonstrating utility as additional endophenotypes. Genotyping via a custom array of 1536 SNPs from 94 candidate genes identified associations for CTNNA2, ERBB4, GRID1, GRID2, GRIK3, GRIK4, GRIN2B, NOS1AP, NRG1, and RELN across multiple endophenotypes. An experiment-wide p value of 0.003 suggested that the associations across all SNPs and endophenotypes collectively exceeded chance. Linkage analyses performed using a genome-wide SNP array further identified significant or suggestive linkage for six of the candidate endophenotypes, with several genes of interest located beneath the linkage peaks (e.g., CSMD1, DISC1, DLGAP2, GRIK2, GRIN3A, and SLC6A3). While the partial convergence of the association and linkage likely reflects differences in density of gene coverage provided by the distinct genotyping platforms, it is also likely an indication of the differential contribution of rare and common variants for some genes and methodological differences in detection ability. Still, many of the genes implicated by COGS through endophenotypes have been identified by independent studies of common, rare, and de novo variation in schizophrenia, all converging on a functional genetic network related to glutamatergic neurotransmission that warrants further investigation. PMID:26597662

  2. Genetic assessment of additional endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study.

    PubMed

    Greenwood, Tiffany A; Lazzeroni, Laura C; Calkins, Monica E; Freedman, Robert; Green, Michael F; Gur, Raquel E; Gur, Ruben C; Light, Gregory A; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Stone, William S; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L

    2016-01-01

    The Consortium on the Genetics of Schizophrenia Family Study (COGS-1) has previously reported our efforts to characterize the genetic architecture of 12 primary endophenotypes for schizophrenia. We now report the characterization of 13 additional measures derived from the same endophenotype test paradigms in the COGS-1 families. Nine of the measures were found to discriminate between schizophrenia patients and controls, were significantly heritable (31 to 62%), and were sufficiently independent of previously assessed endophenotypes, demonstrating utility as additional endophenotypes. Genotyping via a custom array of 1536 SNPs from 94 candidate genes identified associations for CTNNA2, ERBB4, GRID1, GRID2, GRIK3, GRIK4, GRIN2B, NOS1AP, NRG1, and RELN across multiple endophenotypes. An experiment-wide p value of 0.003 suggested that the associations across all SNPs and endophenotypes collectively exceeded chance. Linkage analyses performed using a genome-wide SNP array further identified significant or suggestive linkage for six of the candidate endophenotypes, with several genes of interest located beneath the linkage peaks (e.g., CSMD1, DISC1, DLGAP2, GRIK2, GRIN3A, and SLC6A3). While the partial convergence of the association and linkage likely reflects differences in density of gene coverage provided by the distinct genotyping platforms, it is also likely an indication of the differential contribution of rare and common variants for some genes and methodological differences in detection ability. Still, many of the genes implicated by COGS through endophenotypes have been identified by independent studies of common, rare, and de novo variation in schizophrenia, all converging on a functional genetic network related to glutamatergic neurotransmission that warrants further investigation.

  3. Genetic association studies in complex disease: disentangling additional predisposing loci from associated neutral loci using a constrained - permutation approach.

    PubMed

    Spijker, G T; Nolte, I M; Jansen, R C; Te Meerman, G J

    2005-01-01

    In the process of genetically mapping a complex disease, the question may arise whether a certain polymorphism is the only causal variant in a region. A number of methods can answer this question, but unfortunately these methods are optimal for bi-allelic loci only. We wanted to develop a method that is more suited for multi-allelic loci, such as microsatellite markers. We propose the Additional Disease Loci Test (ADLT): the alleles at an additional locus are permuted within the subsample of haplotypes that have identical alleles at the predisposing locus. The hypothesis being tested is, whether the predisposing locus is the sole factor predisposing to the trait that is in LD with the additional locus under study. We applied ADLT to simulated datasets and a published dataset on Type 1 Diabetes, genotyped for microsatellite markers in the HLA-region. The method showed the expected number of false-positive results in the absence of additional loci, but proved to be more powerful than existing methods in the presence of additional disease loci. ADLT was especially superior in datasets with less LD or with multiple predisposing alleles. We conclude that the ADLT can be useful in identifying additional disease loci.

  4. Genetic predisposition to coronary heart disease and stroke using an additive genetic risk score: a population-based study in Greece

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To determine the extent to which the risk for incident coronary heart disease (CHD) increases in relation to a genetic risk score (GRS) that additively integrates the influence of high-risk alleles in nine documented single nucleotide polymorphisms (SNPs) for CHD, and to examine whether t...

  5. Additive influence of genetic predisposition and conventional risk factors in the incidence of coronary heart disease: a population-based study in Greece

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An additive genetic risk score (GRS) for coronary heart disease (CHD) has previously been associated with incident CHD in the population-based Greek European Prospective Investigation into Cancer and nutrition (EPIC) cohort. In this study, we explore GRS-‘environment’ joint actions on CHD for severa...

  6. Explaining additional genetic variation in complex traits

    PubMed Central

    Robinson, Matthew R.; Wray, Naomi R.; Visscher, Peter M.

    2015-01-01

    Genome-wide association studies (GWAS) have provided valuable insights into the genetic basis of complex traits, discovering >6000 variants associated with >500 quantitative traits and common complex diseases in humans. The associations identified so far represent only a fraction of those which influence phenotype, as there are likely to be very many variants across the entire frequency spectrum, each of which influences multiple traits, with only a small average contribution to the phenotypic variance. This presents a considerable challenge to further dissection of the remaining unexplained genetic variance within populations, which limits our ability to predict disease risk, identify new drug targets, improve and maintain food sources, and understand natural diversity. This challenge will be met within the current framework through larger sample size, better phenotyping including recording of non-genetic risk factors, focused study designs, and an integration of multiple sources of phenotypic and genetic information. The current evidence supports the application of quantitative genetic approaches, and we argue that one should retain simpler theories until simplicity can be traded for greater explanatory power. PMID:24629526

  7. Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: comparing meta and mega analytical approaches for data pooling

    PubMed Central

    Kochunov, Peter; Jahanshad, Neda; Sprooten, Emma; Nichols, Thomas E.; Mandl, René C.; Almasy, Laura; Booth, Tom; Brouwer, Rachel M.; Curran, Joanne E.; de Zubicaray, Greig I.; Dimitrova, Rali; Duggirala, Ravi; Fox, Peter T.; Hong, L. Elliot; Landman, Bennett A.; Lemaitre, Hervé; Lopez, Lorna; Martin, Nicholas G.; McMahon, Katie L.; Mitchell, Braxton D.; Olvera, Rene L.; Peterson, Charles P.; Starr, John M.; Sussmann, Jessika E.; Toga, Arthur W.; Wardlaw, Joanna M.; Wright, Margaret J.; Wright, Susan N.; Bastin, Mark E.; McIntosh, Andrew M.; Boomsma, Dorret I.; Kahn, René S.; den Braber, Anouk; de Geus, Eco JC; Deary, Ian J.; Hulshoff Pol, Hilleke E.; Williamson, Douglas E.; Blangero, John; van ’t Ent, Dennis; Thompson, Paul M.; Glahn, David C.

    2014-01-01

    Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9–85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large “mega-family”. We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability. PMID:24657781

  8. No Additional Prognostic Value of Genetic Information in the Prediction of Vascular Events after Cerebral Ischemia of Arterial Origin: The PROMISe Study

    PubMed Central

    Achterberg, Sefanja; Kappelle, L. Jaap; de Bakker, Paul I. W.; Traylor, Matthew; Algra, Ale

    2015-01-01

    Background Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, genetic information might improve performance of these risk models. Our aim was to develop and compare two models: one containing traditional vascular risk factors, the other also including genetic information. Methods and Results We studied 1020 patients with cerebral ischemia and genotyped them with the Illumina Immunochip. Median follow-up time was 6.5 years; the annual incidence of new ischemic events (primary outcome, n=198) was 3.0%. The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-ROC) of 0.65 (95% confidence interval 0.61-0.69). When we added a genetic risk score based on prioritized SNPs from a genome-wide association study of ischemic stroke (using summary statistics from the METASTROKE study which included 12389 cases and 62004 controls), the AUC-ROC remained the same. Similar results were found for the secondary outcome ischemic stroke. Conclusions We found no additional value of genetic information in a prognostic model for the risk of ischemic events in patients with cerebral ischemia of arterial origin. This is consistent with a complex, polygenic architecture, where many genes of weak effect likely act in concert to influence the heritable risk of an individual to develop (recurrent) vascular events. At present, genetic information cannot help clinicians to distinguish patients at high risk for recurrent vascular events. PMID:25906364

  9. Additive influence of genetic predisposition and conventional risk factors in the incidence of coronary heart disease: a population-based study in Greece

    PubMed Central

    Yiannakouris, Nikos; Katsoulis, Michail; Trichopoulou, Antonia; Ordovas, Jose M; Trichopoulos, Dimitrios

    2014-01-01

    Objectives An additive genetic risk score (GRS) for coronary heart disease (CHD) has previously been associated with incident CHD in the population-based Greek European Prospective Investigation into Cancer and nutrition (EPIC) cohort. In this study, we explore GRS-‘environment’ joint actions on CHD for several conventional cardiovascular risk factors (ConvRFs), including smoking, hypertension, type-2 diabetes mellitus (T2DM), body mass index (BMI), physical activity and adherence to the Mediterranean diet. Design A case–control study. Setting The general Greek population of the EPIC study. Participants and outcome measures 477 patients with medically confirmed incident CHD and 1271 controls participated in this study. We estimated the ORs for CHD by dividing participants at higher or lower GRS and, alternatively, at higher or lower ConvRF, and calculated the relative excess risk due to interaction (RERI) as a measure of deviation from additivity. Results The joint presence of higher GRS and higher risk ConvRF was in all instances associated with an increased risk of CHD, compared with the joint presence of lower GRS and lower risk ConvRF. The OR (95% CI) was 1.7 (1.2 to 2.4) for smoking, 2.7 (1.9 to 3.8) for hypertension, 4.1 (2.8 to 6.1) for T2DM, 1.9 (1.4 to 2.5) for lower physical activity, 2.0 (1.3 to 3.2) for high BMI and 1.5 (1.1 to 2.1) for poor adherence to the Mediterranean diet. In all instances, RERI values were fairly small and not statistically significant, suggesting that the GRS and the ConvRFs do not have effects beyond additivity. Conclusions Genetic predisposition to CHD, operationalised through a multilocus GRS, and ConvRFs have essentially additive effects on CHD risk. PMID:24500614

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

    PubMed Central

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

    2012-01-01

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

  11. Unnatural reactive amino acid genetic code additions

    DOEpatents

    Deiters, Alexander; Cropp, Ashton T; Chin, Jason W; Anderson, Christopher J; Schultz, Peter G

    2013-05-21

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  12. Unnatural reactive amino acid genetic code additions

    DOEpatents

    Deiters, Alexander; Cropp, T. Ashton; Chin, Jason W.; Anderson, J. Christopher; Schultz, Peter G.

    2014-08-26

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  13. Unnatural reactive amino acid genetic code additions

    SciTech Connect

    Deiters, Alexander; Cropp, T. Ashton; Chin, Jason W.; Anderson, J. Christopher; Schultz, Peter G.

    2011-02-15

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  14. Unnatural reactive amino acid genetic code additions

    SciTech Connect

    Deiters, Alexander; Cropp, T. Ashton; Chin, Jason W.; Anderson, J. Christopher; Schultz, Peter G.

    2011-08-09

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNAsyn-thetases, pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  15. Non-additive and Additive Genetic Effects on Extraversion in 3314 Dutch Adolescent Twins and Their Parents

    PubMed Central

    Rebollo-Mesa, Irene; Hudziak, James J.; Willemsen, Gonneke; Boomsma, Dorret I.

    2012-01-01

    The influence of non-additive genetic influences on personality traits has been increasingly reported in adult populations. Less is known, however, with respect to younger samples. In this study, we examine additive and non-additive genetic contributions to the personality trait of extraversion in 1,689 Dutch twin pairs, 1,505 mothers and 1,637 fathers of the twins. The twins were on average 15.5 years (range 12–18 years). To increase statistical power to detect non-additive genetic influences, data on extraversion were also collected in parents and simultaneously analyzed. Genetic modeling procedures incorporating age as a potential modifier of heritability showed significant influences of additive (20–23%) and non-additive genetic factors (31–33%) in addition to unshared environment (46–48%) for adolescents and for their parents. The additive genetic component was slightly and positively related to age. No significant sex differences were found for either extraversion means or for the magnitude of the genetic and environmental influences. There was no evidence of non-random mating for extraversion in the parental generation. Results show that in addition to additive genetic influences, extraversion in adolescents is influenced by non-additive genetic factors. PMID:18240014

  16. Additive and nonadditive genetic variation in avian personality traits.

    PubMed

    van Oers, K; Drent, P J; de Jong, G; van Noordwijk, A J

    2004-11-01

    Individuals of all vertebrate species differ consistently in their reactions to mildly stressful challenges. These typical reactions, described as personalities or coping strategies, have a clear genetic basis, but the structure of their inheritance in natural populations is almost unknown. We carried out a quantitative genetic analysis of two personality traits (exploration and boldness) and the combination of these two traits (early exploratory behaviour). This study was carried out on the lines resulting from a two-directional artificial selection experiment on early exploratory behaviour (EEB) of great tits (Parus major) originating from a wild population. In analyses using the original lines, reciprocal F(1) and reciprocal first backcross generations, additive, dominance, maternal effects ands sex-dependent expression of exploration, boldness and EEB were estimated. Both additive and dominant genetic effects were important determinants of phenotypic variation in exploratory behaviour and boldness. However, no sex-dependent expression was observed in either of these personality traits. These results are discussed with respect to the maintenance of genetic variation in personality traits, and the expected genetic structure of other behavioural and life history traits in general.

  17. Linkage of Type 2 Diabetes on Chromosome 9p24 in Mexican Americans: Additional Evidence from the Veterans Administration Genetic Epidemiology Study (VAGES)

    PubMed Central

    Farook, Vidya S.; Coletta, Dawn K.; Puppala, Sobha; Schneider, Jennifer; Chittoor, Geetha; Hu, Shirley L.; Winnier, Deidre A.; Norton, Luke; Dyer, Thomas D.; Arya, Rector; Cole, Shelley A.; Carless, Melanie; Göring, Harald H.; Almasy, Laura; Mahaney, Michael C.; Comuzzie, Anthony G.; Curran, Joanne E.; Blangero, John; Duggirala, Ravindranath; Lehman, Donna M.; Jenkinson, Christopher P.; DeFronzo, Ralph A.

    2014-01-01

    Objective Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage analysis to localize T2DM susceptibility loci in Mexican Americans. Methods We used the phenotypic and genotypic data from 1,122 Mexican American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). Genome-wide linkage analysis was performed, using the variance components approach. Data from two additional Mexican American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence. Results After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h2 = 0.62, P = 2.7 × 10−6). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region in SAFDGS also, we found the significant and increased linkage evidence (LOD = 4.3, empirical P = 1.0 × 10−5, genome-wide P = 1.6 × 10−3) for T2DM at the same chromosomal region when we performed genome-wide linkage analysis of the VAGES data combined with SAFHS and SAFDGS data. Conclusion Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies (GWASs) involving T2DM related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes. PMID:24060607

  18. Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

    PubMed Central

    2010-01-01

    Background Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. Methods A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG ≥ 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. Results We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-ε4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR

  19. Efficient Improvement of Silage Additives by Using Genetic Algorithms

    PubMed Central

    Davies, Zoe S.; Gilbert, Richard J.; Merry, Roger J.; Kell, Douglas B.; Theodorou, Michael K.; Griffith, Gareth W.

    2000-01-01

    The enormous variety of substances which may be added to forage in order to manipulate and improve the ensilage process presents an empirical, combinatorial optimization problem of great complexity. To investigate the utility of genetic algorithms for designing effective silage additive combinations, a series of small-scale proof of principle silage experiments were performed with fresh ryegrass. Having established that significant biochemical changes occur over an ensilage period as short as 2 days, we performed a series of experiments in which we used 50 silage additive combinations (prepared by using eight bacterial and other additives, each of which was added at six different levels, including zero [i.e., no additive]). The decrease in pH, the increase in lactate concentration, and the free amino acid concentration were measured after 2 days and used to calculate a “fitness” value that indicated the quality of the silage (compared to a control silage made without additives). This analysis also included a “cost” element to account for different total additive levels. In the initial experiment additive levels were selected randomly, but subsequently a genetic algorithm program was used to suggest new additive combinations based on the fitness values determined in the preceding experiments. The result was very efficient selection for silages in which large decreases in pH and high levels of lactate occurred along with low levels of free amino acids. During the series of five experiments, each of which comprised 50 treatments, there was a steady increase in the amount of lactate that accumulated; the best treatment combination was that used in the last experiment, which produced 4.6 times more lactate than the untreated silage. The additive combinations that were found to yield the highest fitness values in the final (fifth) experiment were assessed to determine a range of biochemical and microbiological quality parameters during full-term silage

  20. Additive and non-additive genetic components of the jack male life history in Chinook salmon (Oncorhynchus tshawytscha).

    PubMed

    Forest, Adriana R; Semeniuk, Christina A D; Heath, Daniel D; Pitcher, Trevor E

    2016-08-01

    Chinook salmon, Oncorhynchus tshawytscha, exhibit alternative reproductive tactics (ARTs) where males exist in two phenotypes: large "hooknose" males and smaller "jacks" that reach sexual maturity after only 1 year in seawater. The mechanisms that determine "jacking rate"-the rate at which males precociously sexually mature-are known to involve both genetics and differential growth rates, where individuals that become jacks exhibit higher growth earlier in life. The additive genetic components have been studied and it is known that jack sires produce significantly more jack offspring than hooknose sires, and vice versa. The current study was the first to investigate both additive and non-additive genetic components underlying jacking through the use of a full-factorial breeding design using all hooknose sires. The effect of dams and sires descendant from a marker-assisted broodstock program that identified "high performance" and "low performance" lines using growth- and survival-related gene markers was also studied. Finally, the relative growth of jack, hooknose, and female offspring was examined. No significant dam, sire, or interaction effects were observed in this study, and the maternal, additive, and non-additive components underlying jacking were small. Differences in jacking rates in this study were determined by dam performance line, where dams that originated from the low performance line produced significantly more jacks. Jack offspring in this study had a significantly larger body size than both hooknose males and females starting 1 year post-fertilization. This study provides novel information regarding the genetic architecture underlying ARTs in Chinook salmon that could have implications for the aquaculture industry, where jacks are not favoured due to their small body size and poor flesh quality. PMID:27450674

  1. Additive and non-additive genetic components of the jack male life history in Chinook salmon (Oncorhynchus tshawytscha).

    PubMed

    Forest, Adriana R; Semeniuk, Christina A D; Heath, Daniel D; Pitcher, Trevor E

    2016-08-01

    Chinook salmon, Oncorhynchus tshawytscha, exhibit alternative reproductive tactics (ARTs) where males exist in two phenotypes: large "hooknose" males and smaller "jacks" that reach sexual maturity after only 1 year in seawater. The mechanisms that determine "jacking rate"-the rate at which males precociously sexually mature-are known to involve both genetics and differential growth rates, where individuals that become jacks exhibit higher growth earlier in life. The additive genetic components have been studied and it is known that jack sires produce significantly more jack offspring than hooknose sires, and vice versa. The current study was the first to investigate both additive and non-additive genetic components underlying jacking through the use of a full-factorial breeding design using all hooknose sires. The effect of dams and sires descendant from a marker-assisted broodstock program that identified "high performance" and "low performance" lines using growth- and survival-related gene markers was also studied. Finally, the relative growth of jack, hooknose, and female offspring was examined. No significant dam, sire, or interaction effects were observed in this study, and the maternal, additive, and non-additive components underlying jacking were small. Differences in jacking rates in this study were determined by dam performance line, where dams that originated from the low performance line produced significantly more jacks. Jack offspring in this study had a significantly larger body size than both hooknose males and females starting 1 year post-fertilization. This study provides novel information regarding the genetic architecture underlying ARTs in Chinook salmon that could have implications for the aquaculture industry, where jacks are not favoured due to their small body size and poor flesh quality.

  2. Epistasis Is a Major Determinant of the Additive Genetic Variance in Mimulus guttatus

    PubMed Central

    Monnahan, Patrick J.; Kelly, John K.

    2015-01-01

    The influence of genetic interactions (epistasis) on the genetic variance of quantitative traits is a major unresolved problem relevant to medical, agricultural, and evolutionary genetics. The additive genetic component is typically a high proportion of the total genetic variance in quantitative traits, despite that underlying genes must interact to determine phenotype. This study estimates direct and interaction effects for 11 pairs of Quantitative Trait Loci (QTLs) affecting floral traits within a single population of Mimulus guttatus. With estimates of all 9 genotypes for each QTL pair, we are able to map from QTL effects to variance components as a function of population allele frequencies, and thus predict changes in variance components as allele frequencies change. This mapping requires an analytical framework that properly accounts for bias introduced by estimation errors. We find that even with abundant interactions between QTLs, most of the genetic variance is likely to be additive. However, the strong dependency of allelic average effects on genetic background implies that epistasis is a major determinant of the additive genetic variance, and thus, the population’s ability to respond to selection. PMID:25946702

  3. The contribution of additive genetic variation to personality variation: heritability of personality.

    PubMed

    Dochtermann, Ned A; Schwab, Tori; Sih, Andrew

    2015-01-01

    Individual animals frequently exhibit repeatable differences from other members of their population, differences now commonly referred to as 'animal personality'. Personality differences can arise, for example, from differences in permanent environmental effects--including parental and epigenetic contributors--and the effect of additive genetic variation. Although several studies have evaluated the heritability of behaviour, less is known about general patterns of heritability and additive genetic variation in animal personality. As overall variation in behaviour includes both the among-individual differences that reflect different personalities and temporary environmental effects, it is possible for personality to be largely genetically influenced even when heritability of behaviour per se is quite low. The relative contribution of additive genetic variation to personality variation can be estimated whenever both repeatability and heritability are estimated for the same data. Using published estimates to address this issue, we found that approximately 52% of animal personality variation was attributable to additive genetic variation. Thus, while the heritability of behaviour is often moderate or low, the heritability of personality is much higher. Our results therefore (i) demonstrate that genetic differences are likely to be a major contributor to variation in animal personality and (ii) support the phenotypic gambit: that evolutionary inferences drawn from repeatability estimates may often be justified.

  4. Perspectives: Why Study Human Genetics?

    ERIC Educational Resources Information Center

    Childs, Barton

    1983-01-01

    Reasons for studying human genetics are discussed. These include philosophical reasons, reasons of health, and social reasons. While content, interpretation, and emphasis of human genetics study will vary depending upon schools, teachers, and developmental stages of students, it is suggested that teachers address these three domains. (Author/JN)

  5. Genetic studies of substance abuse.

    PubMed

    Vanyukov, M M; Tarter, R E

    2000-05-01

    Genetic studies of substance abuse indicate that variation in the risk for the disorder in the population is contributed by differences in both individual genotypes and environment. Recent developments in genetics raise the possibility of disentangling the complex system of genotype-environment interaction that determines the development of the individual behavioral phenotype. This paper reviews the concepts, methods and results pertaining to genetic investigation of substance abuse.

  6. Genetic studies in primary gout

    PubMed Central

    Alvsaker, J. O.

    1968-01-01

    The plasma levels of the urate-binding α1-α2-globulin, as determined by its urate-binding capacity, have been recorded in 19 individuals from two gouty kindreds. A significantly reduced binding capacity, accounting for 13-30% of the mean value obtained in healthy, unrelated control subjects, was found in all cases of gout and in the single case of essential hyperuricemia included in the present study. In addition, six apparently healthy members of one of these kindreds also exhibited this characteristic. The distribution of the characteristic in three subsequent generations from this kindred further supported the hypothesis that the reduced binding capacity was inherited as an autosomal trait for which affected subjects were heterozygous. Based on the present observation, the mechanisms of inheritance in primary gout are discussed with special emphasis on the possible cooperation of genetic and environmental factors. Images PMID:4172458

  7. Very low levels of direct additive genetic variance in fitness and fitness components in a red squirrel population.

    PubMed

    McFarlane, S Eryn; Gorrell, Jamieson C; Coltman, David W; Humphries, Murray M; Boutin, Stan; McAdam, Andrew G

    2014-05-01

    A trait must genetically correlate with fitness in order to evolve in response to natural selection, but theory suggests that strong directional selection should erode additive genetic variance in fitness and limit future evolutionary potential. Balancing selection has been proposed as a mechanism that could maintain genetic variance if fitness components trade off with one another and has been invoked to account for empirical observations of higher levels of additive genetic variance in fitness components than would be expected from mutation-selection balance. Here, we used a long-term study of an individually marked population of North American red squirrels (Tamiasciurus hudsonicus) to look for evidence of (1) additive genetic variance in lifetime reproductive success and (2) fitness trade-offs between fitness components, such as male and female fitness or fitness in high- and low-resource environments. "Animal model" analyses of a multigenerational pedigree revealed modest maternal effects on fitness, but very low levels of additive genetic variance in lifetime reproductive success overall as well as fitness measures within each sex and environment. It therefore appears that there are very low levels of direct genetic variance in fitness and fitness components in red squirrels to facilitate contemporary adaptation in this population.

  8. Additive genetic variance in polyandry enables its evolution, but polyandry is unlikely to evolve through sexy or good sperm processes.

    PubMed

    Travers, L M; Simmons, L W; Garcia-Gonzalez, F

    2016-05-01

    Polyandry is widespread despite its costs. The sexually selected sperm hypotheses ('sexy' and 'good' sperm) posit that sperm competition plays a role in the evolution of polyandry. Two poorly studied assumptions of these hypotheses are the presence of additive genetic variance in polyandry and sperm competitiveness. Using a quantitative genetic breeding design in a natural population of Drosophila melanogaster, we first established the potential for polyandry to respond to selection. We then investigated whether polyandry can evolve through sexually selected sperm processes. We measured lifetime polyandry and offensive sperm competitiveness (P2 ) while controlling for sampling variance due to male × male × female interactions. We also measured additive genetic variance in egg-to-adult viability and controlled for its effect on P2 estimates. Female lifetime polyandry showed significant and substantial additive genetic variance and evolvability. In contrast, we found little genetic variance or evolvability in P2 or egg-to-adult viability. Additive genetic variance in polyandry highlights its potential to respond to selection. However, the low levels of genetic variance in sperm competitiveness suggest that the evolution of polyandry may not be driven by sexy sperm or good sperm processes.

  9. Additive genetic variance in polyandry enables its evolution, but polyandry is unlikely to evolve through sexy or good sperm processes.

    PubMed

    Travers, L M; Simmons, L W; Garcia-Gonzalez, F

    2016-05-01

    Polyandry is widespread despite its costs. The sexually selected sperm hypotheses ('sexy' and 'good' sperm) posit that sperm competition plays a role in the evolution of polyandry. Two poorly studied assumptions of these hypotheses are the presence of additive genetic variance in polyandry and sperm competitiveness. Using a quantitative genetic breeding design in a natural population of Drosophila melanogaster, we first established the potential for polyandry to respond to selection. We then investigated whether polyandry can evolve through sexually selected sperm processes. We measured lifetime polyandry and offensive sperm competitiveness (P2 ) while controlling for sampling variance due to male × male × female interactions. We also measured additive genetic variance in egg-to-adult viability and controlled for its effect on P2 estimates. Female lifetime polyandry showed significant and substantial additive genetic variance and evolvability. In contrast, we found little genetic variance or evolvability in P2 or egg-to-adult viability. Additive genetic variance in polyandry highlights its potential to respond to selection. However, the low levels of genetic variance in sperm competitiveness suggest that the evolution of polyandry may not be driven by sexy sperm or good sperm processes. PMID:26801640

  10. Very low levels of direct additive genetic variance in fitness and fitness components in a red squirrel population

    PubMed Central

    McFarlane, S Eryn; Gorrell, Jamieson C; Coltman, David W; Humphries, Murray M; Boutin, Stan; McAdam, Andrew G

    2014-01-01

    A trait must genetically correlate with fitness in order to evolve in response to natural selection, but theory suggests that strong directional selection should erode additive genetic variance in fitness and limit future evolutionary potential. Balancing selection has been proposed as a mechanism that could maintain genetic variance if fitness components trade off with one another and has been invoked to account for empirical observations of higher levels of additive genetic variance in fitness components than would be expected from mutation–selection balance. Here, we used a long-term study of an individually marked population of North American red squirrels (Tamiasciurus hudsonicus) to look for evidence of (1) additive genetic variance in lifetime reproductive success and (2) fitness trade-offs between fitness components, such as male and female fitness or fitness in high- and low-resource environments. “Animal model” analyses of a multigenerational pedigree revealed modest maternal effects on fitness, but very low levels of additive genetic variance in lifetime reproductive success overall as well as fitness measures within each sex and environment. It therefore appears that there are very low levels of direct genetic variance in fitness and fitness components in red squirrels to facilitate contemporary adaptation in this population. PMID:24963372

  11. The Evolution of Human Intelligence and the Coefficient of Additive Genetic Variance in Human Brain Size

    ERIC Educational Resources Information Center

    Miller, Geoffrey F.; Penke, Lars

    2007-01-01

    Most theories of human mental evolution assume that selection favored higher intelligence and larger brains, which should have reduced genetic variance in both. However, adult human intelligence remains highly heritable, and is genetically correlated with brain size. This conflict might be resolved by estimating the coefficient of additive genetic…

  12. Genetic studies in alcohol research

    SciTech Connect

    Karp, R.W.

    1994-12-15

    The National Institute on Alcohol Abuse and Alcoholism (NIAAA) supports research to elucidate the specific genetic factors, now largely unknown, which underlie susceptibility to alcoholism and its medical complications (including fetal alcohol syndrome). Because of the genetic complexity and heterogeneity of alcoholism, identification of the multiple underlying factors will require the development of new study designs and methods of analysis of data from human families. While techniques of genetic analysis of animal behavioral traits (e.g., targeted gene disruption, quantitative trait locus (QTL) mapping) are more powerful that those applicable to humans (e.g., linkage and allelic association studies), the validation of animal behaviors as models of aspects of human alcoholism has been problematic. Newly developed methods for mapping QTL influencing animal behavioral traits can not only permit analyses of human family data to be directly informed by the results of animal studies, but can also serve as a novel means of validating animal models of aspects of alcoholism. 55 refs.

  13. Parametric and Nonparametric Statistical Methods for Genomic Selection of Traits with Additive and Epistatic Genetic Architectures

    PubMed Central

    Howard, Réka; Carriquiry, Alicia L.; Beavis, William D.

    2014-01-01

    Parametric and nonparametric methods have been developed for purposes of predicting phenotypes. These methods are based on retrospective analyses of empirical data consisting of genotypic and phenotypic scores. Recent reports have indicated that parametric methods are unable to predict phenotypes of traits with known epistatic genetic architectures. Herein, we review parametric methods including least squares regression, ridge regression, Bayesian ridge regression, least absolute shrinkage and selection operator (LASSO), Bayesian LASSO, best linear unbiased prediction (BLUP), Bayes A, Bayes B, Bayes C, and Bayes Cπ. We also review nonparametric methods including Nadaraya-Watson estimator, reproducing kernel Hilbert space, support vector machine regression, and neural networks. We assess the relative merits of these 14 methods in terms of accuracy and mean squared error (MSE) using simulated genetic architectures consisting of completely additive or two-way epistatic interactions in an F2 population derived from crosses of inbred lines. Each simulated genetic architecture explained either 30% or 70% of the phenotypic variability. The greatest impact on estimates of accuracy and MSE was due to genetic architecture. Parametric methods were unable to predict phenotypic values when the underlying genetic architecture was based entirely on epistasis. Parametric methods were slightly better than nonparametric methods for additive genetic architectures. Distinctions among parametric methods for additive genetic architectures were incremental. Heritability, i.e., proportion of phenotypic variability, had the second greatest impact on estimates of accuracy and MSE. PMID:24727289

  14. Additive genetic variance and developmental plasticity in growth trajectories in a wild cooperative mammal.

    PubMed

    Huchard, E; Charmantier, A; English, S; Bateman, A; Nielsen, J F; Clutton-Brock, T

    2014-09-01

    Individual variation in growth is high in cooperative breeders and may reflect plastic divergence in developmental trajectories leading to breeding vs. helping phenotypes. However, the relative importance of additive genetic variance and developmental plasticity in shaping growth trajectories is largely unknown in cooperative vertebrates. This study exploits weekly sequences of body mass from birth to adulthood to investigate sources of variance in, and covariance between, early and later growth in wild meerkats (Suricata suricatta), a cooperative mongoose. Our results indicate that (i) the correlation between early growth (prior to nutritional independence) and adult mass is positive but weak, and there are frequent changes (compensatory growth) in post-independence growth trajectories; (ii) among parameters describing growth trajectories, those describing growth rate (prior to and at nutritional independence) show undetectable heritability while associated size parameters (mass at nutritional independence and asymptotic mass) are moderately heritable (0.09 ≤ h(2) < 0.3); and (iii) additive genetic effects, rather than early environmental effects, mediate the covariance between early growth and adult mass. These results reveal that meerkat growth trajectories remain plastic throughout development, rather than showing early and irreversible divergence, and that the weak effects of early growth on adult mass, an important determinant of breeding success, are partly genetic. In contrast to most cooperative invertebrates, the acquisition of breeding status is often determined after sexual maturity and strongly impacted by chance in many cooperative vertebrates, who may therefore retain the ability to adjust their morphology to environmental changes and social opportunities arising throughout their development, rather than specializing early.

  15. Additive genetic variance and developmental plasticity in growth trajectories in a wild cooperative mammal.

    PubMed

    Huchard, E; Charmantier, A; English, S; Bateman, A; Nielsen, J F; Clutton-Brock, T

    2014-09-01

    Individual variation in growth is high in cooperative breeders and may reflect plastic divergence in developmental trajectories leading to breeding vs. helping phenotypes. However, the relative importance of additive genetic variance and developmental plasticity in shaping growth trajectories is largely unknown in cooperative vertebrates. This study exploits weekly sequences of body mass from birth to adulthood to investigate sources of variance in, and covariance between, early and later growth in wild meerkats (Suricata suricatta), a cooperative mongoose. Our results indicate that (i) the correlation between early growth (prior to nutritional independence) and adult mass is positive but weak, and there are frequent changes (compensatory growth) in post-independence growth trajectories; (ii) among parameters describing growth trajectories, those describing growth rate (prior to and at nutritional independence) show undetectable heritability while associated size parameters (mass at nutritional independence and asymptotic mass) are moderately heritable (0.09 ≤ h(2) < 0.3); and (iii) additive genetic effects, rather than early environmental effects, mediate the covariance between early growth and adult mass. These results reveal that meerkat growth trajectories remain plastic throughout development, rather than showing early and irreversible divergence, and that the weak effects of early growth on adult mass, an important determinant of breeding success, are partly genetic. In contrast to most cooperative invertebrates, the acquisition of breeding status is often determined after sexual maturity and strongly impacted by chance in many cooperative vertebrates, who may therefore retain the ability to adjust their morphology to environmental changes and social opportunities arising throughout their development, rather than specializing early. PMID:24962704

  16. Estimation of Additive, Dominance, and Imprinting Genetic Variance Using Genomic Data

    PubMed Central

    Lopes, Marcos S.; Bastiaansen, John W. M.; Janss, Luc; Knol, Egbert F.; Bovenhuis, Henk

    2015-01-01

    Traditionally, exploration of genetic variance in humans, plants, and livestock species has been limited mostly to the use of additive effects estimated using pedigree data. However, with the development of dense panels of single-nucleotide polymorphisms (SNPs), the exploration of genetic variation of complex traits is moving from quantifying the resemblance between family members to the dissection of genetic variation at individual loci. With SNPs, we were able to quantify the contribution of additive, dominance, and imprinting variance to the total genetic variance by using a SNP regression method. The method was validated in simulated data and applied to three traits (number of teats, backfat, and lifetime daily gain) in three purebred pig populations. In simulated data, the estimates of additive, dominance, and imprinting variance were very close to the simulated values. In real data, dominance effects account for a substantial proportion of the total genetic variance (up to 44%) for these traits in these populations. The contribution of imprinting to the total phenotypic variance of the evaluated traits was relatively small (1–3%). Our results indicate a strong relationship between additive variance explained per chromosome and chromosome length, which has been described previously for other traits in other species. We also show that a similar linear relationship exists for dominance and imprinting variance. These novel results improve our understanding of the genetic architecture of the evaluated traits and shows promise to apply the SNP regression method to other traits and species, including human diseases. PMID:26438289

  17. [Food additives and genetically modified food--a risk for allergic patients?].

    PubMed

    Wüthrich, B

    1999-04-01

    Adverse reactions to food and food additives must be classified according to pathogenic criteria. It is necessary to strictly differentiate between an allergy, triggered by a substance-specific immunological mechanism, and an intolerance, in which no specific immune reaction can be established. In contrast to views expressed in the media, by laymen and patients, adverse reactions to additives are less frequent than is believed. Due to frequently "alternative" methods of examination, an allergy to food additives is often wrongly blamed as the cause of a wide variety of symptoms and illness. Diagnosing an allergy or intolerance to additives normally involves carrying out double-blind, placebo-controlled oral provocation tests with food additives. Allergic reactions to food additives occur particularly against additives which are organic in origin. In principle, it is possible that during the manufacture of genetically modified plants and food, proteins are transferred which potentially create allergies. However, legislation exists both in the USA (Federal Drug Administration, FDA) and in Switzerland (Ordinance on the approval process for GM food, GM food additives and GM accessory agents for processing) which require a careful analysis before a genetically modified product is launched, particularly where foreign genes are introduced. Products containing genetically modified organisms (GMO) as additives must be declared. In addition, the source of the foreign protein must be identified. The "Round-up ready" (RR) soya flour introduced in Switzerland is no different from natural soya flour in terms of its allergenic potential. Genetically modified food can be a blessing for allergic individuals if gene technology were to succeed in removing the allergen (e.g. such possibilities exist for rice). The same caution shown towards genetically modified food might also be advisable for foreign food in our diet. Luckily, the immune system of the digestive tract in healthy people

  18. [Food additives and genetically modified food--a risk for allergic patients?].

    PubMed

    Wüthrich, B

    1999-04-01

    Adverse reactions to food and food additives must be classified according to pathogenic criteria. It is necessary to strictly differentiate between an allergy, triggered by a substance-specific immunological mechanism, and an intolerance, in which no specific immune reaction can be established. In contrast to views expressed in the media, by laymen and patients, adverse reactions to additives are less frequent than is believed. Due to frequently "alternative" methods of examination, an allergy to food additives is often wrongly blamed as the cause of a wide variety of symptoms and illness. Diagnosing an allergy or intolerance to additives normally involves carrying out double-blind, placebo-controlled oral provocation tests with food additives. Allergic reactions to food additives occur particularly against additives which are organic in origin. In principle, it is possible that during the manufacture of genetically modified plants and food, proteins are transferred which potentially create allergies. However, legislation exists both in the USA (Federal Drug Administration, FDA) and in Switzerland (Ordinance on the approval process for GM food, GM food additives and GM accessory agents for processing) which require a careful analysis before a genetically modified product is launched, particularly where foreign genes are introduced. Products containing genetically modified organisms (GMO) as additives must be declared. In addition, the source of the foreign protein must be identified. The "Round-up ready" (RR) soya flour introduced in Switzerland is no different from natural soya flour in terms of its allergenic potential. Genetically modified food can be a blessing for allergic individuals if gene technology were to succeed in removing the allergen (e.g. such possibilities exist for rice). The same caution shown towards genetically modified food might also be advisable for foreign food in our diet. Luckily, the immune system of the digestive tract in healthy people

  19. Additive and nonadditive genetic variances for milk yield, fertility, and lifetime performance traits of dairy cattle.

    PubMed

    Fuerst, C; Sölkner, J

    1994-04-01

    Additive and nonadditive genetic variances were estimated for yield traits and fertility for three subsequent lactations and for lifetime performance traits of purebred and crossbred dairy cattle populations. Traits were milk yield, energy-corrected milk yield, fat percentage, protein percentage, calving interval, length of productive life, and lifetime FCM of purebred Simmental, Simmental including crossbreds, and Braunvieh crossed with Brown Swiss. Data files ranged from 66,740 to 375,093 records. An approach based on pedigree information for sire and maternal grandsire was used and included additive, dominance, and additive by additive genetic effects. Variances were estimated using the tildehat approximation to REML. Heritability estimated without nonadditive effects in the model was overestimated, particularly in presence of additive by additive variance. Dominance variance was important for most traits; for the lifetime performance traits, dominance was clearly higher than additive variance. Additive by additive variance was very high for milk yield and energy-corrected milk yield, especially for data including crossbreds. Effect of inbreeding was low in most cases. Inclusion of nonadditive effects in genetic evaluation models might improve estimation of additive effects and may require consideration for dairy cattle breeding programs.

  20. Genetic rearrangements of six wheat-agropyron cristatum 6P addition lines revealed by molecular markers.

    PubMed

    Han, Haiming; Bai, Li; Su, Junji; Zhang, Jinpeng; Song, Liqiang; Gao, Ainong; Yang, Xinming; Li, Xiuquan; Liu, Weihua; Li, Lihui

    2014-01-01

    Agropyron cristatum (L.) Gaertn. (2n = 4x = 28, PPPP) not only is cultivated as pasture fodder but also could provide many desirable genes for wheat improvement. It is critical to obtain common wheat-A. cristatum alien disomic addition lines to locate the desired genes on the P genome chromosomes. Comparative analysis of the homoeologous relationships between the P genome chromosome and wheat genome chromosomes is a key step in transferring different desirable genes into common wheat and producing the desired alien translocation line while compensating for the loss of wheat chromatin. In this study, six common wheat-A. cristatum disomic addition lines were produced and analyzed by phenotypic examination, genomic in situ hybridization (GISH), SSR markers from the ABD genomes and STS markers from the P genome. Comparative maps, six in total, were generated and demonstrated that all six addition lines belonged to homoeologous group 6. However, chromosome 6P had undergone obvious rearrangements in different addition lines compared with the wheat chromosome, indicating that to obtain a genetic compensating alien translocation line, one should recombine alien chromosomal regions with homoeologous wheat chromosomes. Indeed, these addition lines were classified into four types based on the comparative mapping: 6PI, 6PII, 6PIII, and 6PIV. The different types of chromosome 6P possessed different desirable genes. For example, the 6PI type, containing three addition lines, carried genes conferring high numbers of kernels per spike and resistance to powdery mildew, important traits for wheat improvement. These results may prove valuable for promoting the development of conventional chromosome engineering techniques toward molecular chromosome engineering. PMID:24595330

  1. Evolvability of individual traits in a multivariate context: partitioning the additive genetic variance into common and specific components.

    PubMed

    McGuigan, Katrina; Blows, Mark W

    2010-07-01

    Genetic covariation among multiple traits will bias the direction of evolution. Although a trait's phenotypic context is crucial for understanding evolutionary constraints, the evolutionary potential of one (focal) trait, rather than the whole phenotype, is often of interest. The extent to which a focal trait can evolve independently depends on how much of the genetic variance in that trait is unique. Here, we present a hypothesis-testing framework for estimating the genetic variance in a focal trait that is independent of variance in other traits. We illustrate our analytical approach using two Drosophila bunnanda trait sets: a contact pheromone system comprised of cuticular hydrocarbons (CHCs), and wing shape, characterized by relative warps of vein position coordinates. Only 9% of the additive genetic variation in CHCs was trait specific, suggesting individual traits are unlikely to evolve independently. In contrast, most (72%) of the additive genetic variance in wing shape was trait specific, suggesting relative warp representations of wing shape could evolve independently. The identification of genetic variance in focal traits that is independent of other traits provides a way of studying the evolvability of individual traits within the broader context of the multivariate phenotype.

  2. Do Health Professionals Need Additional Competencies for Stratified Cancer Prevention Based on Genetic Risk Profiling?

    PubMed Central

    Chowdhury, Susmita; Henneman, Lidewij; Dent, Tom; Hall, Alison; Burton, Alice; Pharoah, Paul; Pashayan, Nora; Burton, Hilary

    2015-01-01

    There is growing evidence that inclusion of genetic information about known common susceptibility variants may enable population risk-stratification and personalized prevention for common diseases including cancer. This would require the inclusion of genetic testing as an integral part of individual risk assessment of an asymptomatic individual. Front line health professionals would be expected to interact with and assist asymptomatic individuals through the risk stratification process. In that case, additional knowledge and skills may be needed. Current guidelines and frameworks for genetic competencies of non-specialist health professionals place an emphasis on rare inherited genetic diseases. For common diseases, health professionals do use risk assessment tools but such tools currently do not assess genetic susceptibility of individuals. In this article, we compare the skills and knowledge needed by non-genetic health professionals, if risk-stratified prevention is implemented, with existing competence recommendations from the UK, USA and Europe, in order to assess the gaps in current competences. We found that health professionals would benefit from understanding the contribution of common genetic variations in disease risk, the rationale for a risk-stratified prevention pathway, and the implications of using genomic information in risk-assessment and risk management of asymptomatic individuals for common disease prevention. PMID:26068647

  3. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  4. Genome-Enabled Estimates of Additive and Nonadditive Genetic Variances and Prediction of Apple Phenotypes Across Environments.

    PubMed

    Kumar, Satish; Molloy, Claire; Muñoz, Patricio; Daetwyler, Hans; Chagné, David; Volz, Richard

    2015-12-01

    The nonadditive genetic effects may have an important contribution to total genetic variation of phenotypes, so estimates of both the additive and nonadditive effects are desirable for breeding and selection purposes. Our main objectives were to: estimate additive, dominance and epistatic variances of apple (Malus × domestica Borkh.) phenotypes using relationship matrices constructed from genome-wide dense single nucleotide polymorphism (SNP) markers; and compare the accuracy of genomic predictions using genomic best linear unbiased prediction models with or without including nonadditive genetic effects. A set of 247 clonally replicated individuals was assessed for six fruit quality traits at two sites, and also genotyped using an Illumina 8K SNP array. Across several fruit quality traits, the additive, dominance, and epistatic effects contributed about 30%, 16%, and 19%, respectively, to the total phenotypic variance. Models ignoring nonadditive components yielded upwardly biased estimates of additive variance (heritability) for all traits in this study. The accuracy of genomic predicted genetic values (GEGV) varied from about 0.15 to 0.35 for various traits, and these were almost identical for models with or without including nonadditive effects. However, models including nonadditive genetic effects further reduced the bias of GEGV. Between-site genotypic correlations were high (>0.85) for all traits, and genotype-site interaction accounted for <10% of the phenotypic variability. The accuracy of prediction, when the validation set was present only at one site, was generally similar for both sites, and varied from about 0.50 to 0.85. The prediction accuracies were strongly influenced by trait heritability, and genetic relatedness between the training and validation families.

  5. Genome-Enabled Estimates of Additive and Nonadditive Genetic Variances and Prediction of Apple Phenotypes Across Environments

    PubMed Central

    Kumar, Satish; Molloy, Claire; Muñoz, Patricio; Daetwyler, Hans; Chagné, David; Volz, Richard

    2015-01-01

    The nonadditive genetic effects may have an important contribution to total genetic variation of phenotypes, so estimates of both the additive and nonadditive effects are desirable for breeding and selection purposes. Our main objectives were to: estimate additive, dominance and epistatic variances of apple (Malus × domestica Borkh.) phenotypes using relationship matrices constructed from genome-wide dense single nucleotide polymorphism (SNP) markers; and compare the accuracy of genomic predictions using genomic best linear unbiased prediction models with or without including nonadditive genetic effects. A set of 247 clonally replicated individuals was assessed for six fruit quality traits at two sites, and also genotyped using an Illumina 8K SNP array. Across several fruit quality traits, the additive, dominance, and epistatic effects contributed about 30%, 16%, and 19%, respectively, to the total phenotypic variance. Models ignoring nonadditive components yielded upwardly biased estimates of additive variance (heritability) for all traits in this study. The accuracy of genomic predicted genetic values (GEGV) varied from about 0.15 to 0.35 for various traits, and these were almost identical for models with or without including nonadditive effects. However, models including nonadditive genetic effects further reduced the bias of GEGV. Between-site genotypic correlations were high (>0.85) for all traits, and genotype-site interaction accounted for <10% of the phenotypic variability. The accuracy of prediction, when the validation set was present only at one site, was generally similar for both sites, and varied from about 0.50 to 0.85. The prediction accuracies were strongly influenced by trait heritability, and genetic relatedness between the training and validation families. PMID:26497141

  6. Study Identifies Genetic Subtypes of Crohn's Disease

    MedlinePlus

    ... medlineplus.gov/news/fullstory_161499.html Study Identifies Genetic Subtypes of Crohn's Disease Findings may help explain ... disease appears to have at least two distinct genetic subtypes, which could explain why the condition is ...

  7. Studies in genetic discrimination. Final progress report

    SciTech Connect

    Not Available

    1994-06-01

    We have screened 1006 respondents in a study of genetic discrimination. Analysis of these responses has produced evidence of the range of institutions engaged in genetic discrimination and demonstrates the impact of this discrimination on the respondents to the study. We have found that both ignorance and policy underlie genetic discrimination and that anti-discrimination laws are being violated.

  8. Additional EIPC Study Analysis. Final Report

    SciTech Connect

    Hadley, Stanton W; Gotham, Douglas J.; Luciani, Ralph L.

    2014-12-01

    Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations were developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 14 topics was developed for further analysis. This paper brings together the earlier interim reports of the first 13 topics plus one additional topic into a single final report.

  9. Toxicological safety assessment of genetically modified Bacillus thuringiensis with additional N-acyl homoserine lactonase gene.

    PubMed

    Peng, Donghai; Zhou, Chenfei; Chen, Shouwen; Ruan, Lifang; Yu, Ziniu; Sun, Ming

    2008-01-01

    The aim of the present study is to evaluate the toxicology safety to mammals of a genetically modified (GM) Bacillus thuringiensis with an additional N-acyl homoserine lactones gene (aiiA), which possesses insecticidal activity together with restraint of bacterial pathogenicity and is intended for use as a multifunctional biopesticide. Safety assessments included an acute oral toxicity test and 28-d animal feeding study in Wistar rats, primary eye and dermal irritation in Zealand White rabbits, and delayed contact hypersensitivity in guinea pigs. Tests were conducted using spray-dried powder preparation. This GM product showed toxicity neither in oral acute toxicity test nor in 28-d animal feeding test at a dose of 5,000 mg/kg body weight. During the animal feeding test, there were no significant differences in growth, food and water consumption, hematology, blood biochemical indices, organ weights, and histopathology finding between rats in controls and tested groups. Tested animals in primary eye and dermal irritation and delayed contact hypersensitivity test were also devoid of any toxicity compared to controls. All the above results demonstrated that the GM based multifunctional B. thuringiensis has low toxicity and low eye and dermal irritation and would not cause hypersensitivity to laboratory mammals and therefore could be regarded as safe for use as a pesticide.

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

    PubMed Central

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

    2016-01-01

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

  11. Genetics in Practice: A Template for Interactive Case Studies.

    ERIC Educational Resources Information Center

    Edwards, Erin; Walker, Andy; Bergeson, Kathleen; Louviere, John; Robinson, Kris; Higgins, Joseph; Harris, Charles

    2001-01-01

    Describes the development of a template for interactive case studies that was used for an online continuing medical education course on genetics for health care providers. Discusses goals of the template system, including the production of additional case studies with no additional programming costs and easy updating capabilities. (LRW)

  12. Genetic linkage analysis to identify a gene required for the addition of phosphoethanolamine to meningococcal lipopolysaccharide.

    PubMed

    Tang, Christoph M; Stroud, Dave; Mackinnon, Fiona; Makepeace, Katherine; Plested, Joyce; Moxon, E Richard; Chalmers, Ronald

    2002-02-01

    Lipopolysaccharide (LPS) is important for the virulence of Neisseria meningitidis, and is the target of immune responses. We took advantage of a monoclonal antibody (Mab B5) that recognises phosphoethanolamine (PEtn) attached to the inner core of meningococcal LPS to identify genes required for the addition of PEtn to LPS. Insertional mutants that lost Mab B5 reactivity were isolated and characterised, but failed to yield genes directly responsible for PEtn substitution. Subsequent genetic linkage analysis was used to define a region of DNA containing a single intact open reading frame which is sufficient to confer B5 reactivity to a B5 negative meningococcal isolate. The results provide an initial characterisation of the genetic basis of a key, immunodominant epitope of meningococcal LPS.

  13. Structure Property Studies for Additively Manufactured Parts

    SciTech Connect

    Milenski, Helen M; Schmalzer, Andrew Michael; Kelly, Daniel

    2015-08-17

    Since the invention of modern Additive Manufacturing (AM) processes engineers and designers have worked hard to capitalize on the unique building capabilities that AM allows. By being able to customize the interior fill of parts it is now possible to design components with a controlled density and customized internal structure. The creation of new polymers and polymer composites allow for even greater control over the mechanical properties of AM parts. One of the key reasons to explore AM, is to bring about a new paradigm in part design, where materials can be strategically optimized in a way that conventional subtractive methods cannot achieve. The two processes investigated in my research were the Fused Deposition Modeling (FDM) process and the Direct Ink Write (DIW) process. The objectives of the research were to determine the impact of in-fill density and morphology on the mechanical properties of FDM parts, and to determine if DIW printed samples could be produced where the filament diameter was varied while the overall density remained constant.

  14. Effect of multiplicative and additive noise on genetic transcriptional regulatory mechanism

    NASA Astrophysics Data System (ADS)

    Liu, Xue-Mei; Xie, Hui-Zhang; Liu, Liang-Gang; Li, Zhi-Bing

    2009-02-01

    A multiplicative noise and an additive noise are introduced in the kinetic model of Smolen-Baxter-Byrne [P. Smolen, D.A. Baxter, J.H. Byrne, Amer. J. Physiol. Cell. Physiol. 274 (1998) 531], in which the expression of gene is controlled by protein concentration of transcriptional activator. The Fokker-Planck equation is solved and the steady-state probability distribution is obtained numerically. It is found that the multiplicative noise converts the bistability to monostability that can be regarded as a noise-induced transition. The additive noise reduces the transcription efficiency. The correlation between the multiplicative noise and the additive noise works as a genetic switch and regulates the gene transcription effectively.

  15. Additive genetic variation for tolerance to estrogen pollution in natural populations of Alpine whitefish (Coregonus sp., Salmonidae)

    PubMed Central

    Brazzola, Gregory; Chèvre, Nathalie; Wedekind, Claus

    2014-01-01

    The evolutionary potential of natural populations to adapt to anthropogenic threats critically depends on whether there exists additive genetic variation for tolerance to the threat. A major problem for water-dwelling organisms is chemical pollution, and among the most common pollutants is 17α-ethinylestradiol (EE2), the synthetic estrogen that is used in oral contraceptives and that can affect fish at various developmental stages, including embryogenesis. We tested whether there is variation in the tolerance to EE2 within Alpine whitefish. We sampled spawners from two species of different lakes, bred them in vitro in a full-factorial design each, and studied growth and mortality of embryos. Exposure to EE2 turned out to be toxic in all concentrations we tested (≥1 ng/L). It reduced embryo viability and slowed down embryogenesis. We found significant additive genetic variation in EE2-induced mortality in both species, that is, genotypes differed in their tolerance to estrogen pollution. We also found maternal effects on embryo development to be influenced by EE2, that is, some maternal sib groups were more susceptible to EE2 than others. In conclusion, the toxic effects of EE2 were strong, but both species demonstrated the kind of additive genetic variation that is necessary for an evolutionary response to this type of pollution. PMID:25553069

  16. Additive genetic variation for tolerance to estrogen pollution in natural populations of Alpine whitefish (Coregonus sp., Salmonidae).

    PubMed

    Brazzola, Gregory; Chèvre, Nathalie; Wedekind, Claus

    2014-11-01

    The evolutionary potential of natural populations to adapt to anthropogenic threats critically depends on whether there exists additive genetic variation for tolerance to the threat. A major problem for water-dwelling organisms is chemical pollution, and among the most common pollutants is 17α-ethinylestradiol (EE2), the synthetic estrogen that is used in oral contraceptives and that can affect fish at various developmental stages, including embryogenesis. We tested whether there is variation in the tolerance to EE2 within Alpine whitefish. We sampled spawners from two species of different lakes, bred them in vitro in a full-factorial design each, and studied growth and mortality of embryos. Exposure to EE2 turned out to be toxic in all concentrations we tested (≥1 ng/L). It reduced embryo viability and slowed down embryogenesis. We found significant additive genetic variation in EE2-induced mortality in both species, that is, genotypes differed in their tolerance to estrogen pollution. We also found maternal effects on embryo development to be influenced by EE2, that is, some maternal sib groups were more susceptible to EE2 than others. In conclusion, the toxic effects of EE2 were strong, but both species demonstrated the kind of additive genetic variation that is necessary for an evolutionary response to this type of pollution. PMID:25553069

  17. GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics

    PubMed Central

    Ledda, Mirko; Kutalik, Zoltán; Souza Destito, Maria C.; Souza, Milena M.; Cirillo, Cintia A.; Zamboni, Amabilene; Martin, Nathalie; Morya, Edgard; Sameshima, Koichi; Beckmann, Jacques S.; le Coutre, Johannes; Bergmann, Sven; Genick, Ulrich K.

    2014-01-01

    Human perception of bitterness displays pronounced interindividual variation. This phenotypic variation is mirrored by equally pronounced genetic variation in the family of bitter taste receptor genes. To better understand the effects of common genetic variations on human bitter taste perception, we conducted a genome-wide association study on a discovery panel of 504 subjects and a validation panel of 104 subjects from the general population of São Paulo in Brazil. Correction for general taste-sensitivity allowed us to identify a SNP in the cluster of bitter taste receptors on chr12 (10.88– 11.24 Mb, build 36.1) significantly associated (best SNP: rs2708377, P = 5.31 × 10−13, r2 = 8.9%, β = −0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This association overlaps with—but is statistically distinct from—the previously identified SNP rs10772420 influencing the perception of quinine bitterness that falls in the same bitter taste cluster. We replicated this association to quinine perception (P = 4.97 × 10−37, r2 = 23.2%, β = 0.25, s.e. = 0.020) and additionally found the effect of this genetic locus to be concentration specific with a strong impact on the perception of low, but no impact on the perception of high concentrations of quinine. Our study, thus, furthers our understanding of the complex genetic architecture of bitter taste perception. PMID:23966204

  18. GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics.

    PubMed

    Ledda, Mirko; Kutalik, Zoltán; Souza Destito, Maria C; Souza, Milena M; Cirillo, Cintia A; Zamboni, Amabilene; Martin, Nathalie; Morya, Edgard; Sameshima, Koichi; Beckmann, Jacques S; le Coutre, Johannes; Bergmann, Sven; Genick, Ulrich K

    2014-01-01

    Human perception of bitterness displays pronounced interindividual variation. This phenotypic variation is mirrored by equally pronounced genetic variation in the family of bitter taste receptor genes. To better understand the effects of common genetic variations on human bitter taste perception, we conducted a genome-wide association study on a discovery panel of 504 subjects and a validation panel of 104 subjects from the general population of São Paulo in Brazil. Correction for general taste-sensitivity allowed us to identify a SNP in the cluster of bitter taste receptors on chr12 (10.88- 11.24 Mb, build 36.1) significantly associated (best SNP: rs2708377, P = 5.31 × 10(-13), r(2) = 8.9%, β = -0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This association overlaps with-but is statistically distinct from-the previously identified SNP rs10772420 influencing the perception of quinine bitterness that falls in the same bitter taste cluster. We replicated this association to quinine perception (P = 4.97 × 10(-37), r(2) = 23.2%, β = 0.25, s.e. = 0.020) and additionally found the effect of this genetic locus to be concentration specific with a strong impact on the perception of low, but no impact on the perception of high concentrations of quinine. Our study, thus, furthers our understanding of the complex genetic architecture of bitter taste perception.

  19. Planning additional drilling campaign using two-space genetic algorithm: A game theoretical approach

    NASA Astrophysics Data System (ADS)

    Kumral, Mustafa; Ozer, Umit

    2013-03-01

    Grade and tonnage are the most important technical uncertainties in mining ventures because of the use of estimations/simulations, which are mostly generated from drill data. Open pit mines are planned and designed on the basis of the blocks representing the entire orebody. Each block has different estimation/simulation variance reflecting uncertainty to some extent. The estimation/simulation realizations are submitted to mine production scheduling process. However, the use of a block model with varying estimation/simulation variances will lead to serious risk in the scheduling. In the medium of multiple simulations, the dispersion variances of blocks can be thought to regard technical uncertainties. However, the dispersion variance cannot handle uncertainty associated with varying estimation/simulation variances of blocks. This paper proposes an approach that generates the configuration of the best additional drilling campaign to generate more homogenous estimation/simulation variances of blocks. In other words, the objective is to find the best drilling configuration in such a way as to minimize grade uncertainty under budget constraint. Uncertainty measure of the optimization process in this paper is interpolation variance, which considers data locations and grades. The problem is expressed as a minmax problem, which focuses on finding the best worst-case performance i.e., minimizing interpolation variance of the block generating maximum interpolation variance. Since the optimization model requires computing the interpolation variances of blocks being simulated/estimated in each iteration, the problem cannot be solved by standard optimization tools. This motivates to use two-space genetic algorithm (GA) approach to solve the problem. The technique has two spaces: feasible drill hole configuration with minimization of interpolation variance and drill hole simulations with maximization of interpolation variance. Two-space interacts to find a minmax solution

  20. FEMALE AND MALE GENETIC EFFECTS ON OFFSPRING PATERNITY: ADDITIVE GENETIC (CO)VARIANCES IN FEMALE EXTRA-PAIR REPRODUCTION AND MALE PATERNITY SUCCESS IN SONG SPARROWS (MELOSPIZA MELODIA)

    PubMed Central

    Reid, Jane M; Arcese, Peter; Keller, Lukas F; Losdat, Sylvain

    2014-01-01

    Ongoing evolution of polyandry, and consequent extra-pair reproduction in socially monogamous systems, is hypothesized to be facilitated by indirect selection stemming from cross-sex genetic covariances with components of male fitness. Specifically, polyandry is hypothesized to create positive genetic covariance with male paternity success due to inevitable assortative reproduction, driving ongoing coevolution. However, it remains unclear whether such covariances could or do emerge within complex polyandrous systems. First, we illustrate that genetic covariances between female extra-pair reproduction and male within-pair paternity success might be constrained in socially monogamous systems where female and male additive genetic effects can have opposing impacts on the paternity of jointly reared offspring. Second, we demonstrate nonzero additive genetic variance in female liability for extra-pair reproduction and male liability for within-pair paternity success, modeled as direct and associative genetic effects on offspring paternity, respectively, in free-living song sparrows (Melospiza melodia). The posterior mean additive genetic covariance between these liabilities was slightly positive, but the credible interval was wide and overlapped zero. Therefore, although substantial total additive genetic variance exists, the hypothesis that ongoing evolution of female extra-pair reproduction is facilitated by genetic covariance with male within-pair paternity success cannot yet be definitively supported or rejected either conceptually or empirically. PMID:24724612

  1. Female and male genetic effects on offspring paternity: additive genetic (co)variances in female extra-pair reproduction and male paternity success in song sparrows (Melospiza melodia).

    PubMed

    Reid, Jane M; Arcese, Peter; Keller, Lukas F; Losdat, Sylvain

    2014-08-01

    Ongoing evolution of polyandry, and consequent extra-pair reproduction in socially monogamous systems, is hypothesized to be facilitated by indirect selection stemming from cross-sex genetic covariances with components of male fitness. Specifically, polyandry is hypothesized to create positive genetic covariance with male paternity success due to inevitable assortative reproduction, driving ongoing coevolution. However, it remains unclear whether such covariances could or do emerge within complex polyandrous systems. First, we illustrate that genetic covariances between female extra-pair reproduction and male within-pair paternity success might be constrained in socially monogamous systems where female and male additive genetic effects can have opposing impacts on the paternity of jointly reared offspring. Second, we demonstrate nonzero additive genetic variance in female liability for extra-pair reproduction and male liability for within-pair paternity success, modeled as direct and associative genetic effects on offspring paternity, respectively, in free-living song sparrows (Melospiza melodia). The posterior mean additive genetic covariance between these liabilities was slightly positive, but the credible interval was wide and overlapped zero. Therefore, although substantial total additive genetic variance exists, the hypothesis that ongoing evolution of female extra-pair reproduction is facilitated by genetic covariance with male within-pair paternity success cannot yet be definitively supported or rejected either conceptually or empirically.

  2. Genetic Breeding and Diversity of the Genus Passiflora: Progress and Perspectives in Molecular and Genetic Studies

    PubMed Central

    Cerqueira-Silva, Carlos Bernard M.; Jesus, Onildo N.; Santos, Elisa S. L.; Corrêa, Ronan X.; Souza, Anete P.

    2014-01-01

    Despite the ecological and economic importance of passion fruit (Passiflora spp.), molecular markers have only recently been utilized in genetic studies of this genus. In addition, both basic genetic researches related to population studies and pre-breeding programs of passion fruit remain scarce for most Passiflora species. Considering the number of Passiflora species and the increasing use of these species as a resource for ornamental, medicinal, and food purposes, the aims of this review are the following: (i) to present the current condition of the passion fruit crop; (ii) to quantify the applications and effects of using molecular markers in studies of Passiflora; (iii) to present the contributions of genetic engineering for passion fruit culture; and (iv) to discuss the progress and perspectives of this research. Thus, the present review aims to summarize and discuss the relationship between historical and current progress on the culture, breeding, and molecular genetics of passion fruit. PMID:25196515

  3. Genetic breeding and diversity of the genus Passiflora: progress and perspectives in molecular and genetic studies.

    PubMed

    Cerqueira-Silva, Carlos Bernard M; Jesus, Onildo N; Santos, Elisa S L; Corrêa, Ronan X; Souza, Anete P

    2014-01-01

    Despite the ecological and economic importance of passion fruit (Passiflora spp.), molecular markers have only recently been utilized in genetic studies of this genus. In addition, both basic genetic researches related to population studies and pre-breeding programs of passion fruit remain scarce for most Passiflora species. Considering the number of Passiflora species and the increasing use of these species as a resource for ornamental, medicinal, and food purposes, the aims of this review are the following: (i) to present the current condition of the passion fruit crop; (ii) to quantify the applications and effects of using molecular markers in studies of Passiflora; (iii) to present the contributions of genetic engineering for passion fruit culture; and (iv) to discuss the progress and perspectives of this research. Thus, the present review aims to summarize and discuss the relationship between historical and current progress on the culture, breeding, and molecular genetics of passion fruit. PMID:25196515

  4. Genetic and Epigenetic Changes in Oilseed Rape (Brassica napus L.) Extracted from Intergeneric Allopolyploid and Additions with Orychophragmus

    PubMed Central

    Gautam, Mayank; Dang, Yanwei; Ge, Xianhong; Shao, Yujiao; Li, Zaiyun

    2016-01-01

    Allopolyploidization with the merger of the genomes from different species has been shown to be associated with genetic and epigenetic changes. But the maintenance of such alterations related to one parental species after the genome is extracted from the allopolyploid remains to be detected. In this study, the genome of Brassica napus L. (2n = 38, genomes AACC) was extracted from its intergeneric allohexaploid (2n = 62, genomes AACCOO) with another crucifer Orychophragmus violaceus (2n = 24, genome OO), by backcrossing and development of alien addition lines. B. napus-type plants identified in the self-pollinated progenies of nine monosomic additions were analyzed by the methods of amplified fragment length polymorphism, sequence-specific amplified polymorphism, and methylation-sensitive amplified polymorphism. They showed modifications to certain extents in genomic components (loss and gain of DNA segments and transposons, introgression of alien DNA segments) and DNA methylation, compared with B. napus donor. The significant differences in the changes between the B. napus types extracted from these additions likely resulted from the different effects of individual alien chromosomes. Particularly, the additions which harbored the O. violaceus chromosome carrying dominant rRNA genes over those of B. napus tended to result in the development of plants which showed fewer changes, suggesting a role of the expression levels of alien rRNA genes in genomic stability. These results provided new cues for the genetic alterations in one parental genome that are maintained even after the genome becomes independent. PMID:27148282

  5. Genetic and Epigenetic Changes in Oilseed Rape (Brassica napus L.) Extracted from Intergeneric Allopolyploid and Additions with Orychophragmus.

    PubMed

    Gautam, Mayank; Dang, Yanwei; Ge, Xianhong; Shao, Yujiao; Li, Zaiyun

    2016-01-01

    Allopolyploidization with the merger of the genomes from different species has been shown to be associated with genetic and epigenetic changes. But the maintenance of such alterations related to one parental species after the genome is extracted from the allopolyploid remains to be detected. In this study, the genome of Brassica napus L. (2n = 38, genomes AACC) was extracted from its intergeneric allohexaploid (2n = 62, genomes AACCOO) with another crucifer Orychophragmus violaceus (2n = 24, genome OO), by backcrossing and development of alien addition lines. B. napus-type plants identified in the self-pollinated progenies of nine monosomic additions were analyzed by the methods of amplified fragment length polymorphism, sequence-specific amplified polymorphism, and methylation-sensitive amplified polymorphism. They showed modifications to certain extents in genomic components (loss and gain of DNA segments and transposons, introgression of alien DNA segments) and DNA methylation, compared with B. napus donor. The significant differences in the changes between the B. napus types extracted from these additions likely resulted from the different effects of individual alien chromosomes. Particularly, the additions which harbored the O. violaceus chromosome carrying dominant rRNA genes over those of B. napus tended to result in the development of plants which showed fewer changes, suggesting a role of the expression levels of alien rRNA genes in genomic stability. These results provided new cues for the genetic alterations in one parental genome that are maintained even after the genome becomes independent. PMID:27148282

  6. Characterizing the ADHD Phenotype for Genetic Studies

    ERIC Educational Resources Information Center

    Stevenson, Jim; Asherson, Phil; Hay, David; Levy, Florence; Swanson, Jim; Thapar, Anita; Willcutt, Erik

    2005-01-01

    The genetic study of ADHD has made considerable progress. Further developments in the field will be reliant in part on identifying the most appropriate phenotypes for genetic analysis. The use of both categorical and dimensional measures of symptoms related to ADHD has been productive. The use of multiple reporters is a valuable feature of the…

  7. Addition of restriction fragment length polymorphism markers to the genetic linkage map of Brassica rapa L. (syn. campestris).

    PubMed

    Panigrahi, Jogeswar; Patnaik, Anjana; Kole, Phullara; Koleb, Chitta ranjan

    2009-01-01

    Genetic linkage analysis of 151 restriction fragment length polymorphism (RFLP) loci, that included eight new loci, detected by the six probes in the present study, and four trait loci including seed colour, leaf pubescence, resistance to white rust caused by Albugo candida race-2 (AC-2) and race-7 (AC-7) employing the MAPMAKER/EXP 3.0 programme led to the development of 10 linkage groups (LGs) spanning over 44.4 centiMorgan (cM) to 130.4 cM containing 9 to 22 loci and two short LGs with two or three marker loci in Brassica rapa. The enriched map covers 993.1 cM of B. rapa genome with an average marker interval of 6.41. Eight new RFLP loci occupied new map positions on five linkage groups, LG 2, 3, 6, 8 and 9. Addition of these RFLP loci led to appreciable changes in the corresponding linkage groups and resulted in an increase of the total map length by 102.8 cM and of the marker interval by 0.35 cM. Interval mapping by using the computer programme MAPMAKER/ QTL 1.1 for scanning the genetic map led to the detection of one major quantitative trait locus (QTL) in LG 4 and one minor QTL in LG 8 governing resistance to AC-7. Both QTLs contributed 7.89 to the interaction phenotype (IP) score with 96.3% genetic variation. The multi-locus model suggested additive gene action with 96.8% genetic variation.

  8. Heritability of heterozygosity offers a new way of understanding why dominant gene action contributes to additive genetic variance.

    PubMed

    Nietlisbach, Pirmin; Hadfield, Jarrod D

    2015-07-01

    Whenever allele frequencies are unequal, nonadditive gene action contributes to additive genetic variance and therefore the resemblance between parents and offspring. The reason for this has not been easy to understand. Here, we present a new single-locus decomposition of additive genetic variance that may give greater intuition about this important result. We show that the contribution of dominant gene action to parent-offspring resemblance only depends on the degree to which the heterozygosity of parents and offspring covary. Thus, dominant gene action only contributes to additive genetic variance when heterozygosity is heritable. Under most circumstances this is the case because individuals with rare alleles are more likely to be heterozygous, and because they pass rare alleles to their offspring they also tend to have heterozygous offspring. When segregating alleles are at equal frequency there are no rare alleles, the heterozygosities of parents and offspring are uncorrelated and dominant gene action does not contribute to additive genetic variance. PMID:26100570

  9. Contributions of genetic studies to clinical psychiatry.

    PubMed

    Abe, K; Oda, N

    1991-12-01

    Recent twin and family studies have demonstrated a genetic factor in Gilles de la Tourette syndrome, some cases of infantile autism, enuresis, specific reading disability, sleepwalking, night terrors, common fears and anxiety. Family studies have been used to elucidate the nosological relationship of psychiatric disorders; e.g. anorexia nervosa (to affective disorder), Gilles de la Tourette syndrome, and sleeptalking. Advances in biochemical genetics and in enzyme polymorphisms suggest that there are wide individual variations in the adverse effects of drugs and that dosage should be tailored to the individual patient. Recently molecular genetic methods have been introduced to psychiatry, but a major breakthrough in this field appears to be still years away.

  10. Genetic and molecular genetic studies of murine and human lupus.

    PubMed

    Steinberg, A D; Klinman, D M; Kastner, D L; Seldin, M F; Gause, W C; Scribner, C L; Britten, J L; Siegel, J N; Mountz, J D

    1987-06-01

    Mice and humans with systemic lupus erythematosus (SLE) have been studied with regard to cellular, genetic and molecular genetic abnormalities. B cell hyperactivity and autoantibody production are the hallmarks of this illness. In humans with SLE, there is increased stem cell, B cell precursor and B cell proliferation. The same is true of NZB mice. In lpr/lpr and gld/gld mice, marked expansion of a subpopulation of T cells allows extrathymic terminal T cell maturation and secondary B cell hyperactivity. Androgens suppress these processes and polyclonal immune activators accelerate them. Three types of genes are identified: inducing genes, accelerating genes and background genes. These give rise to abnormal expression of various cellular oncogenes, T cell receptor genes and immunoglobulin genes. The data suggest that abnormal immune regulation plays a critical role in the development of SLE, with polyclonal B cell activation being common to both mice and humans with SLE. Different genetic and cellular abnormalities underlie the ultimate syndrome, the common denominator, generalized autoimmunity, that we call SLE.

  11. A Genome-Wide Association Analysis Reveals Epistatic Cancellation of Additive Genetic Variance for Root Length in Arabidopsis thaliana.

    PubMed

    Lachowiec, Jennifer; Shen, Xia; Queitsch, Christine; Carlborg, Örjan

    2015-01-01

    Efforts to identify loci underlying complex traits generally assume that most genetic variance is additive. Here, we examined the genetics of Arabidopsis thaliana root length and found that the genomic narrow-sense heritability for this trait in the examined population was statistically zero. The low amount of additive genetic variance that could be captured by the genome-wide genotypes likely explains why no associations to root length could be found using standard additive-model-based genome-wide association (GWA) approaches. However, as the broad-sense heritability for root length was significantly larger, and primarily due to epistasis, we also performed an epistatic GWA analysis to map loci contributing to the epistatic genetic variance. Four interacting pairs of loci were revealed, involving seven chromosomal loci that passed a standard multiple-testing corrected significance threshold. The genotype-phenotype maps for these pairs revealed epistasis that cancelled out the additive genetic variance, explaining why these loci were not detected in the additive GWA analysis. Small population sizes, such as in our experiment, increase the risk of identifying false epistatic interactions due to testing for associations with very large numbers of multi-marker genotypes in few phenotyped individuals. Therefore, we estimated the false-positive risk using a new statistical approach that suggested half of the associated pairs to be true positive associations. Our experimental evaluation of candidate genes within the seven associated loci suggests that this estimate is conservative; we identified functional candidate genes that affected root development in four loci that were part of three of the pairs. The statistical epistatic analyses were thus indispensable for confirming known, and identifying new, candidate genes for root length in this population of wild-collected A. thaliana accessions. We also illustrate how epistatic cancellation of the additive genetic variance

  12. A Genome-Wide Association Analysis Reveals Epistatic Cancellation of Additive Genetic Variance for Root Length in Arabidopsis thaliana

    PubMed Central

    Lachowiec, Jennifer; Shen, Xia; Queitsch, Christine; Carlborg, Örjan

    2015-01-01

    Efforts to identify loci underlying complex traits generally assume that most genetic variance is additive. Here, we examined the genetics of Arabidopsis thaliana root length and found that the genomic narrow-sense heritability for this trait in the examined population was statistically zero. The low amount of additive genetic variance that could be captured by the genome-wide genotypes likely explains why no associations to root length could be found using standard additive-model-based genome-wide association (GWA) approaches. However, as the broad-sense heritability for root length was significantly larger, and primarily due to epistasis, we also performed an epistatic GWA analysis to map loci contributing to the epistatic genetic variance. Four interacting pairs of loci were revealed, involving seven chromosomal loci that passed a standard multiple-testing corrected significance threshold. The genotype-phenotype maps for these pairs revealed epistasis that cancelled out the additive genetic variance, explaining why these loci were not detected in the additive GWA analysis. Small population sizes, such as in our experiment, increase the risk of identifying false epistatic interactions due to testing for associations with very large numbers of multi-marker genotypes in few phenotyped individuals. Therefore, we estimated the false-positive risk using a new statistical approach that suggested half of the associated pairs to be true positive associations. Our experimental evaluation of candidate genes within the seven associated loci suggests that this estimate is conservative; we identified functional candidate genes that affected root development in four loci that were part of three of the pairs. The statistical epistatic analyses were thus indispensable for confirming known, and identifying new, candidate genes for root length in this population of wild-collected A. thaliana accessions. We also illustrate how epistatic cancellation of the additive genetic variance

  13. A rangewide population genetic study of trumpeter swans

    USGS Publications Warehouse

    Oyler-McCance, S.J.; Ransler, F.A.; Berkman, L.K.; Quinn, T.W.

    2007-01-01

    For management purposes, the range of naturally occurring trumpeter swans (Cygnus buccinator) has been divided into two populations, the Pacific Coast Population (PP) and the Rocky Mountain Population (RMP). Little is known about the distribution of genetic variation across the species' range despite increasing pressure to make difficult management decisions regarding the two populations and flocks within them. To address this issue, we used rapidly evolving genetic markers (mitochondrial DNA sequence and 17 nuclear microsatellite loci) to elucidate the underlying genetic structure of the species. Data from both markers revealed a significant difference between the PP and RMP with the Yukon Territory as a likely area of overlap. Additionally, we found that the two populations have somewhat similar levels of genetic diversity (PP is slightly higher) suggesting that the PP underwent a population bottleneck similar to a well-documented one in the RMP. Both genetic structure and diversity results reveal that the Tri-State flock, a suspected unique, non-migratory flock, is not genetically different from the Canadian flock of the RMP and need not be treated as a unique population from a genetic standpoint. Finally, trumpeter swans appear to have much lower mitochondrial DNA variability than other waterfowl studied thus far which may suggest a previous, species-wide bottleneck. ?? 2007 Springer Science+Business Media, Inc.

  14. Australian empirical study into genetic discrimination.

    PubMed

    Otlowski, Margaret F; Taylor, Sandra D; Barlow-Stewart, Kristine K

    2002-01-01

    This paper outlines a major empirical study that is being undertaken by an interdisciplinary team into genetic discrimination in Australia. The 3-year study will examine the nature and extent of this newly emerging phenomenon across the perspectives of consumers, third parties, and the legal system and will analyze its social and legal dimensions. Although the project is confined to Australia, it is expected that the outcomes will have significance for the wider research community as this is the most substantial study of its kind to be undertaken to date into genetic discrimination. PMID:12394353

  15. A Study of Additional Costs of Second Language Instruction.

    ERIC Educational Resources Information Center

    McEwen, Nelly

    A study was conducted whose primary aim was to identify and explain additional costs incurred by Alberta, Canada school jurisdictions providing second language instruction in 1980. Additional costs were defined as those which would not have been incurred had the second language program not been in existence. Three types of additional costs were…

  16. [Questions safety and tendency of using genetically modified microorganisms in food, food additives and food derived].

    PubMed

    Khovaev, A A

    2008-01-01

    In this article analysis questions of using genetically modified microorganisms in manufacture food production, present new GMM used in manufacture -food ferments; results of medical biological appraisal/ microbiological and genetic expert examination/ of food, getting by use microorganisms or there producents with indication modern of control methods.

  17. Recruiting American Indian Women for a Genetic Epidemiology Study

    PubMed Central

    Nadeau, M.; Best, L.

    2010-01-01

    Due to previous negative experiences, some American Indian communities are distrustful of research in general and genetic research in particular. The Turtle Mountain Community College was awarded a National Institutes of Health (NIH) grant with 3 aims: (1) to study possible genetic influences on pre-eclampsia, (2) to encourage tribal college students to consider biomedical careers and (3) to develop the local research infrastructure. Retrospectively identified case (91) and control (188) participants were recruited into Phase I over a 3-year period and additional participants (71) were concurrently recruited from a prenatal clinic into a prospective case/control study, Phase II. This paper describes some of the challenges and solutions we encountered in the process of recruiting American Indian participants into a genetic epidemiologic study. PMID:20616521

  18. WONOEP appraisal: new genetic approaches to study epilepsy

    PubMed Central

    Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A.; Grisar, Thierry; Gilby, Krista L.; Vinet, Jonathan; Kadam, Shilpa D.; Becker, Albert J.

    2014-01-01

    Objective New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming and optogenetic manipulations within epileptic networks are progressively unravelling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiological impacts of mutations in epilepsy-associated genes on a multilayer level, from cells to circuits. Methods This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy in Quebec, Canada. Results Next-generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and have revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell-types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knockdown approaches, are enabling functional validation with exquisite cell-type and temporal specificity. In addition, optogenetics, using cell-type specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. Genetically-encoded cell-type labeling is also providing new means to assess the role of the non-neuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next-generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and non

  19. The future for genetic studies in reproduction

    PubMed Central

    Montgomery, G.W.; Zondervan, K.T.; Nyholt, D.R.

    2014-01-01

    Genetic factors contribute to risk of many common diseases affecting reproduction and fertility. In recent years, methods for genome-wide association studies (GWAS) have revolutionized gene discovery for common traits and diseases. Results of GWAS are documented in the Catalog of Published Genome-Wide Association Studies at the National Human Genome Research Institute and report over 70 publications for 32 traits and diseases associated with reproduction. These include endometriosis, uterine fibroids, age at menarche and age at menopause. Results that pass appropriate stringent levels of significance are generally well replicated in independent studies. Examples of genetic variation affecting twinning rate, infertility, endometriosis and age at menarche demonstrate that the spectrum of disease-related variants for reproductive traits is similar to most other common diseases. GWAS ‘hits’ provide novel insights into biological pathways and the translational value of these studies lies in discovery of novel gene targets for biomarkers, drug development and greater understanding of environmental factors contributing to disease risk. Results also show that genetic data can help define sub-types of disease and co-morbidity with other traits and diseases. To date, many studies on reproductive traits have used relatively small samples. Future genetic marker studies in large samples with detailed phenotypic and clinical information will yield new insights into disease risk, disease classification and co-morbidity for many diseases associated with reproduction and infertility. PMID:23982303

  20. Additional records of metazoan parasites from Caribbean marine mammals, including genetically identified anisakid nematodes.

    PubMed

    Colón-Llavina, Marlene M; Mignucci-Giannoni, Antonio A; Mattiucci, Simonetta; Paoletti, Michela; Nascetti, Giuseppe; Williams, Ernest H

    2009-10-01

    Studies of marine mammal parasites in the Caribbean are scarce. An assessment for marine mammal endo- and ectoparasites from Puerto Rico and the Virgin Islands, but extending to other areas of the Caribbean, was conducted between 1989 and 1994. The present study complements the latter and enhances identification of anisakid nematodes using molecular markers. Parasites were collected from 59 carcasses of stranded cetaceans and manatees from 1994 to 2006, including Globicephala macrorhynchus, Kogia breviceps, Kogia sima, Lagenodelphis hosei, Mesoplodon densirostris, Peponocephala electra, Stenella longirostris, Steno bredanensis, Trichechus manatus. Tursiops truncatus, and Ziphius cavirostris. Sixteen species of endoparasitic helminthes were morphologically identified, including two species of acanthocephalans (Bolbosoma capitatum, Bolbosoma vasculosum), nine species of nematodes (Anisakis sp., Anisakis brevispiculata, Anisakis paggiae, Anisakis simplex, Anisakis typica, Anisakis ziphidarium, Crassicauda anthonyi, Heterocheilus tunicatus, Pseudoterranova ceticola), two species of cestodes (Monorygma grimaldi, Phyllobothrium delphini), and three species of trematodes (Chiorchis groschafti, Pulmonicola cochleotrema, Monoligerum blairi). The nematodes belonging to the genus Anisakis recovered in some stranded animals were genetically identified to species level based on their sequence analysis of mitochondrial DNA (629 bp of mtDNA cox 2). A total of five new host records and six new geographic records are presented. PMID:19582477

  1. Additional records of metazoan parasites from Caribbean marine mammals, including genetically identified anisakid nematodes.

    PubMed

    Colón-Llavina, Marlene M; Mignucci-Giannoni, Antonio A; Mattiucci, Simonetta; Paoletti, Michela; Nascetti, Giuseppe; Williams, Ernest H

    2009-10-01

    Studies of marine mammal parasites in the Caribbean are scarce. An assessment for marine mammal endo- and ectoparasites from Puerto Rico and the Virgin Islands, but extending to other areas of the Caribbean, was conducted between 1989 and 1994. The present study complements the latter and enhances identification of anisakid nematodes using molecular markers. Parasites were collected from 59 carcasses of stranded cetaceans and manatees from 1994 to 2006, including Globicephala macrorhynchus, Kogia breviceps, Kogia sima, Lagenodelphis hosei, Mesoplodon densirostris, Peponocephala electra, Stenella longirostris, Steno bredanensis, Trichechus manatus. Tursiops truncatus, and Ziphius cavirostris. Sixteen species of endoparasitic helminthes were morphologically identified, including two species of acanthocephalans (Bolbosoma capitatum, Bolbosoma vasculosum), nine species of nematodes (Anisakis sp., Anisakis brevispiculata, Anisakis paggiae, Anisakis simplex, Anisakis typica, Anisakis ziphidarium, Crassicauda anthonyi, Heterocheilus tunicatus, Pseudoterranova ceticola), two species of cestodes (Monorygma grimaldi, Phyllobothrium delphini), and three species of trematodes (Chiorchis groschafti, Pulmonicola cochleotrema, Monoligerum blairi). The nematodes belonging to the genus Anisakis recovered in some stranded animals were genetically identified to species level based on their sequence analysis of mitochondrial DNA (629 bp of mtDNA cox 2). A total of five new host records and six new geographic records are presented.

  2. The modified ultrasound pattern sum score mUPSS as additional diagnostic tool for genetically distinct hereditary neuropathies.

    PubMed

    Grimm, Alexander; Rasenack, Maria; Athanasopoulou, Ioanna M; Dammeier, Nele Maria; Lipski, Christina; Wolking, Stefan; Vittore, Debora; Décard, Bernhard F; Axer, Hubertus

    2016-02-01

    The objective of this study is to evaluate the nerve ultrasound characteristics in genetically distinct inherited neuropathies, the value of the modified ultrasound pattern sum score (mUPSS) to differentiate between the subtypes and the correlation of ultrasound with nerve conduction studies (NCS), disease duration and severity. All patients underwent a standardized neurological examination, ultrasound, and NCS. In addition, genetic testing was performed. Consequently, mUPSS was applied, which is a sum-score of cross-sectional areas (CSA) at predefined anatomical points in different nerves. 31 patients were included (10xCharcot-Marie-Tooth (CMT)1a, 3xCMT1b, 3xCMTX, 9xCMT2, 6xHNPP [Hereditary neuropathy with liability to pressure palsies]). Generalized, homogeneous nerve enlargement and significantly increased UPS scores emphasized the diagnosis of demyelinating neuropathy, particularly CMT1a and CMT1b. The amount of enlargement did not depend on disease duration, symptom severity, height and weight. In CMTX the nerves were enlarged, as well, however, only in the roots and lower limbs, most prominent in men. In CMT2 no significant enlargement was detectable. In HNPP the CSA values were increased at entrapped sites, and not elsewhere. However, a distinction from CMT1, which also showed enlarged CSA values at entrapment sites, was only possible by calculating the entrapment ratios and entrapment score. The mUPSS allowed distinction between CMT1a (increased UPS scores, entrapment ratios <1.0) and HNPP (low UPS scores, entrapment ratios >1.4), while CMT1b and CMTX showed intermediate UPS types and entrapment ratios <1.0. Although based on few cases, ultrasound revealed consistent and homogeneous nerve alteration in certain inherited neuropathies. The modified UPSS is a quantitative tool, which may provide useful information for diagnosis, differentiation and follow-up evaluation in addition to NCS and molecular testing.

  3. Genetic variation and prediction of additive and nonadditive genetic effects for six carcass traits in an Angus-Brahman multibreed herd.

    PubMed

    Elzo, M A; West, R L; Johnson, D D; Wakeman, D L

    1998-07-01

    Estimates of covariances and sire expected progeny differences of additive and nonadditive genetic effects for six carcass traits were obtained using records from 486 straightbred and crossbred steers from 121 sires born between 1989 and 1995 in the Angus-Brahman multibreed herd of the University of Florida. Steers were slaughtered at a similar carcass composition end point. Covariances were estimated by REML procedures, using a generalized expectation-maximization algorithm applied to multibreed populations. Straightbred and crossbred estimates of heritabilities and additive genetic correlations were within ranges found in the literature for steers slaughtered on an age- or weight-constant basis for hot carcass weight, longissimus muscle area, and shear force but equal to or less than the lower bound of these ranges for fat-related traits. Maximum values of interactibilities (i.e., ratios of nonadditive variances to phenotypic variances in the F1) and nonadditive genetic correlations were smaller than heritabilities and additive genetic correlations in straightbreds and crossbred groups. Sire additive and total direct genetic predictions for longissimus muscle area, marbling, and shear force tended to decrease with the fraction of Brahman alleles, whereas those for hot carcass weight and fat thickness over the longissimus were higher, and those for kidney fat were lower in straightbreds and F1 than in other crossbred groups. Nonadditive genetic predictions were similar across sire groups of all Angus and Brahman fractions. These results suggest that slaughtering steers on a similar carcass composition basis reduces variability of fat-related traits while retaining variability for non-fat-related traits comparable to slaughtering steers on a similar age or weight basis. Selection for carcass traits within desirable (narrow) ranges and slaughter of steers at similar compositional end point seems to be a good combination to help produce meat products of consistent

  4. Genetic variation and prediction of additive and nonadditive genetic effects for six carcass traits in an Angus-Brahman multibreed herd.

    PubMed

    Elzo, M A; West, R L; Johnson, D D; Wakeman, D L

    1998-07-01

    Estimates of covariances and sire expected progeny differences of additive and nonadditive genetic effects for six carcass traits were obtained using records from 486 straightbred and crossbred steers from 121 sires born between 1989 and 1995 in the Angus-Brahman multibreed herd of the University of Florida. Steers were slaughtered at a similar carcass composition end point. Covariances were estimated by REML procedures, using a generalized expectation-maximization algorithm applied to multibreed populations. Straightbred and crossbred estimates of heritabilities and additive genetic correlations were within ranges found in the literature for steers slaughtered on an age- or weight-constant basis for hot carcass weight, longissimus muscle area, and shear force but equal to or less than the lower bound of these ranges for fat-related traits. Maximum values of interactibilities (i.e., ratios of nonadditive variances to phenotypic variances in the F1) and nonadditive genetic correlations were smaller than heritabilities and additive genetic correlations in straightbreds and crossbred groups. Sire additive and total direct genetic predictions for longissimus muscle area, marbling, and shear force tended to decrease with the fraction of Brahman alleles, whereas those for hot carcass weight and fat thickness over the longissimus were higher, and those for kidney fat were lower in straightbreds and F1 than in other crossbred groups. Nonadditive genetic predictions were similar across sire groups of all Angus and Brahman fractions. These results suggest that slaughtering steers on a similar carcass composition basis reduces variability of fat-related traits while retaining variability for non-fat-related traits comparable to slaughtering steers on a similar age or weight basis. Selection for carcass traits within desirable (narrow) ranges and slaughter of steers at similar compositional end point seems to be a good combination to help produce meat products of consistent

  5. Genetics, Genome-Wide Association Studies, and Menarche.

    PubMed

    Witchel, Selma Feldman

    2016-07-01

    Puberty is characterized by maturation of the hypothalamic-pituitary-gonadal axis, development of secondary sexual features, increased linear growth velocity, maturation of the epiphyses limiting additional growth, and achievement of menarche. The age at menarche appears to have a significant genetic component. With the advent of genome-wide association studies (GWASs), the genome has been interrogated to find associations between specific loci and age at menarche. It is apparent that multiple genetic loci, epigenetic mechanisms, and environmental factors modulate this biological event crucial for reproductive competence.

  6. Genetics, Genome-Wide Association Studies, and Menarche.

    PubMed

    Witchel, Selma Feldman

    2016-07-01

    Puberty is characterized by maturation of the hypothalamic-pituitary-gonadal axis, development of secondary sexual features, increased linear growth velocity, maturation of the epiphyses limiting additional growth, and achievement of menarche. The age at menarche appears to have a significant genetic component. With the advent of genome-wide association studies (GWASs), the genome has been interrogated to find associations between specific loci and age at menarche. It is apparent that multiple genetic loci, epigenetic mechanisms, and environmental factors modulate this biological event crucial for reproductive competence. PMID:27513021

  7. Set-based tests for genetic association in longitudinal studies.

    PubMed

    He, Zihuai; Zhang, Min; Lee, Seunggeun; Smith, Jennifer A; Guo, Xiuqing; Palmas, Walter; Kardia, Sharon L R; Diez Roux, Ana V; Mukherjee, Bhramar

    2015-09-01

    Genetic association studies with longitudinal markers of chronic diseases (e.g., blood pressure, body mass index) provide a valuable opportunity to explore how genetic variants affect traits over time by utilizing the full trajectory of longitudinal outcomes. Since these traits are likely influenced by the joint effect of multiple variants in a gene, a joint analysis of these variants considering linkage disequilibrium (LD) may help to explain additional phenotypic variation. In this article, we propose a longitudinal genetic random field model (LGRF), to test the association between a phenotype measured repeatedly during the course of an observational study and a set of genetic variants. Generalized score type tests are developed, which we show are robust to misspecification of within-subject correlation, a feature that is desirable for longitudinal analysis. In addition, a joint test incorporating gene-time interaction is further proposed. Computational advancement is made for scalable implementation of the proposed methods in large-scale genome-wide association studies (GWAS). The proposed methods are evaluated through extensive simulation studies and illustrated using data from the Multi-Ethnic Study of Atherosclerosis (MESA). Our simulation results indicate substantial gain in power using LGRF when compared with two commonly used existing alternatives: (i) single marker tests using longitudinal outcome and (ii) existing gene-based tests using the average value of repeated measurements as the outcome.

  8. Genetic studies in the Amish community.

    PubMed

    Patton, Michael A

    2005-01-01

    The Amish community was established in Pennsylvania, Ohio and Indiana. They form a distinct and biologically isolated community by virtue of their strong cultural and religious beliefs. This paper outlines aspects of the Amish culture and reviews some of the recent genetic studies that have been undertaken in this community. PMID:16096212

  9. The Multi-allelic Genetic Architecture of a Variance-Heterogeneity Locus for Molybdenum Concentration in Leaves Acts as a Source of Unexplained Additive Genetic Variance.

    PubMed

    Forsberg, Simon K G; Andreatta, Matthew E; Huang, Xin-Yuan; Danku, John; Salt, David E; Carlborg, Örjan

    2015-11-01

    Genome-wide association (GWA) analyses have generally been used to detect individual loci contributing to the phenotypic diversity in a population by the effects of these loci on the trait mean. More rarely, loci have also been detected based on variance differences between genotypes. Several hypotheses have been proposed to explain the possible genetic mechanisms leading to such variance signals. However, little is known about what causes these signals, or whether this genetic variance-heterogeneity reflects mechanisms of importance in natural populations. Previously, we identified a variance-heterogeneity GWA (vGWA) signal for leaf molybdenum concentrations in Arabidopsis thaliana. Here, fine-mapping of this association reveals that the vGWA emerges from the effects of three independent genetic polymorphisms that all are in strong LD with the markers displaying the genetic variance-heterogeneity. By revealing the genetic architecture underlying this vGWA signal, we uncovered the molecular source of a significant amount of hidden additive genetic variation or "missing heritability". Two of the three polymorphisms underlying the genetic variance-heterogeneity are promoter variants for Molybdate transporter 1 (MOT1), and the third a variant located ~25 kb downstream of this gene. A fourth independent association was also detected ~600 kb upstream of MOT1. Use of a T-DNA knockout allele highlights Copper Transporter 6; COPT6 (AT2G26975) as a strong candidate gene for this association. Our results show that an extended LD across a complex locus including multiple functional alleles can lead to a variance-heterogeneity between genotypes in natural populations. Further, they provide novel insights into the genetic regulation of ion homeostasis in A. thaliana, and empirically confirm that variance-heterogeneity based GWA methods are a valuable tool to detect novel associations of biological importance in natural populations.

  10. The Multi-allelic Genetic Architecture of a Variance-Heterogeneity Locus for Molybdenum Concentration in Leaves Acts as a Source of Unexplained Additive Genetic Variance

    PubMed Central

    Forsberg, Simon K. G.; Andreatta, Matthew E.; Huang, Xin-Yuan; Danku, John; Salt, David E.; Carlborg, Örjan

    2015-01-01

    Genome-wide association (GWA) analyses have generally been used to detect individual loci contributing to the phenotypic diversity in a population by the effects of these loci on the trait mean. More rarely, loci have also been detected based on variance differences between genotypes. Several hypotheses have been proposed to explain the possible genetic mechanisms leading to such variance signals. However, little is known about what causes these signals, or whether this genetic variance-heterogeneity reflects mechanisms of importance in natural populations. Previously, we identified a variance-heterogeneity GWA (vGWA) signal for leaf molybdenum concentrations in Arabidopsis thaliana. Here, fine-mapping of this association reveals that the vGWA emerges from the effects of three independent genetic polymorphisms that all are in strong LD with the markers displaying the genetic variance-heterogeneity. By revealing the genetic architecture underlying this vGWA signal, we uncovered the molecular source of a significant amount of hidden additive genetic variation or “missing heritability”. Two of the three polymorphisms underlying the genetic variance-heterogeneity are promoter variants for Molybdate transporter 1 (MOT1), and the third a variant located ~25 kb downstream of this gene. A fourth independent association was also detected ~600 kb upstream of MOT1. Use of a T-DNA knockout allele highlights Copper Transporter 6; COPT6 (AT2G26975) as a strong candidate gene for this association. Our results show that an extended LD across a complex locus including multiple functional alleles can lead to a variance-heterogeneity between genotypes in natural populations. Further, they provide novel insights into the genetic regulation of ion homeostasis in A. thaliana, and empirically confirm that variance-heterogeneity based GWA methods are a valuable tool to detect novel associations of biological importance in natural populations. PMID:26599497

  11. Study on thermal effects & sulfurized additives, in lubricating greases

    NASA Astrophysics Data System (ADS)

    Shah, Ami Atul

    Lithium Base grease constitutes about 50% of market. The greases are developed to be able to work in multiple working conditions and have longer working life. Greases with extreme pressure additives and anti-wear additives have been developed as a solution to many of the applications. These developed greases are tested under ASTM D2266 testing conditions to meet the requirements. The actual working conditions, although, differ than the real testing conditions. The loading, speed and temperature conditions can be more harsh, or fluctuating in nature. The cyclic nature of the parameters cannot be directly related to the test performance. For this purpose studies on the performance under spectrum loading, variable speed and fluctuating temperature must be performed. This study includes tests to understand the effect of thermal variation on some of the most commonly used grease additives that perform well under ASTM D2266 testing conditions. The studied additives include most widely used industrial extreme pressure additive MoS2. Performance of ZDDP which is trying to replace MoS2 in its industrial applications has also been studied. The tests cover study of extreme pressure, anti-wear and friction modifier additives to get a general idea on the effects of thermal variation in three areas. Sulphur is the most common extreme pressure additive. Sulphur based MoS 2 is extensively used grease additive. Study to understand the tribological performance of this additive through wear testing and SEM/EDX studies has been done. This performance is also studied for other metallic sulfides like WS2 and sulphur based organic compound. The aim is to study the importance of the type of bond that sulphur shares in its additive's structure on its performance. The MoS2 film formation is found to be on the basis of the FeS formation on the substrate and protection through sacrificial monolayer deposition of the MoS2 sheared structure. The free Mo then tends to oxidise. An attempt to

  12. 29 CFR 2590.702-1 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40, or at age 30 for those with increased risk for breast cancer, including individuals with BRCA1 or... evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for the mammogram is paid. This policy is applied uniformly to...

  13. 26 CFR 54.9802-3T - Additional requirements prohibiting discrimination based on genetic information (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... increased risk for breast cancer, including individuals with BRCA1 or BRCA2 gene mutations. B is 33 years... reimbursement. Following an established policy, the plan asks B for evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for...

  14. 29 CFR 2590.702-1 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40, or at age 30 for those with increased risk for breast cancer, including individuals with BRCA1 or... evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for the mammogram is paid. This policy is applied uniformly to...

  15. 29 CFR 2590.702-1 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40, or at age 30 for those with increased risk for breast cancer, including individuals with BRCA1 or... evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for the mammogram is paid. This policy is applied uniformly to...

  16. 45 CFR 146.122 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 40, or at age 30 for those with increased risk for breast cancer, including individuals with BRCA1 or... evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for the mammogram is paid. This policy is applied uniformly to...

  17. 26 CFR 54.9802-3T - Additional requirements prohibiting discrimination based on genetic information (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... increased risk for breast cancer, including individuals with BRCA1 or BRCA2 gene mutations. B is 33 years... reimbursement. Following an established policy, the plan asks B for evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for...

  18. 45 CFR 146.122 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 40, or at age 30 for those with increased risk for breast cancer, including individuals with BRCA1 or... evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for the mammogram is paid. This policy is applied uniformly to...

  19. 26 CFR 54.9802-3T - Additional requirements prohibiting discrimination based on genetic information (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... increased risk for breast cancer, including individuals with BRCA1 or BRCA2 gene mutations. B is 33 years... reimbursement. Following an established policy, the plan asks B for evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for...

  20. 29 CFR 2590.702-1 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40, or at age 30 for those with increased risk for breast cancer, including individuals with BRCA1 or... evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for the mammogram is paid. This policy is applied uniformly to...

  1. 29 CFR 2590.702-1 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40, or at age 30 for those with increased risk for breast cancer, including individuals with BRCA1 or... evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for the mammogram is paid. This policy is applied uniformly to...

  2. 26 CFR 54.9802-3T - Additional requirements prohibiting discrimination based on genetic information (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... increased risk for breast cancer, including individuals with BRCA1 or BRCA2 gene mutations. B is 33 years... reimbursement. Following an established policy, the plan asks B for evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for...

  3. 26 CFR 54.9802-3T - Additional requirements prohibiting discrimination based on genetic information (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... increased risk for breast cancer, including individuals with BRCA1 or BRCA2 gene mutations. B is 33 years... reimbursement. Following an established policy, the plan asks B for evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for...

  4. 45 CFR 146.122 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 40, or at age 30 for those with increased risk for breast cancer, including individuals with BRCA1 or... evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for the mammogram is paid. This policy is applied uniformly to...

  5. 45 CFR 146.122 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 40, or at age 30 for those with increased risk for breast cancer, including individuals with BRCA1 or... evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for the mammogram is paid. This policy is applied uniformly to...

  6. 45 CFR 146.122 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 40, or at age 30 for those with increased risk for breast cancer, including individuals with BRCA1 or... evidence of increased risk of breast cancer, such as the results of a genetic test or a family history of breast cancer, before the claim for the mammogram is paid. This policy is applied uniformly to...

  7. Quantitative genetic study of the adaptive process.

    PubMed

    Shaw, R G; Shaw, F H

    2014-01-01

    The additive genetic variance with respect to absolute fitness, VA(W), divided by mean absolute fitness, , sets the rate of ongoing adaptation. Fisher's key insight yielding this quantitative prediction of adaptive evolution, known as the Fundamental Theorem of Natural Selection, is well appreciated by evolutionists. Nevertheless, extremely scant information about VA(W) is available for natural populations. Consequently, the capacity for fitness increase via natural selection is unknown. Particularly in the current context of rapid environmental change, which is likely to reduce fitness directly and, consequently, the size and persistence of populations, the urgency of advancing understanding of immediate adaptive capacity is extreme. We here explore reasons for the dearth of empirical information about VA(W), despite its theoretical renown and critical evolutionary role. Of these reasons, we suggest that expectations that VA(W) is negligible, in general, together with severe statistical challenges of estimating it, may largely account for the limited empirical emphasis on it. To develop insight into the dynamics of VA(W) in a changing environment, we have conducted individual-based genetically explicit simulations. We show that, as optimizing selection on a trait changes steadily over generations, VA(W) can grow considerably, supporting more rapid adaptation than would the VA(W) of the base population. We call for direct evaluation of VA(W) and in support of prediction of rates adaptive evolution, and we advocate for the use of aster modeling as a rigorous basis for achieving this goal.

  8. Genetic studies in chronic kidney disease: interpretation and clinical applicability.

    PubMed

    Witasp, Anna; Nordfors, Louise; Carrero, Juan Jesus; Luttropp, Karin; Lindholm, Bengt; Schalling, Martin; Stenvinkel, Peter

    2012-01-01

    The tools of modern molecular biology are evolving rapidly, resulting in vastly more efficient approaches to illuminating human genetic variations and their effects on common multifactorial disorders such as chronic kidney disease (CKD). Indeed, candidate gene association studies and genome-wide association studies (GWASs) have generated novel genetic variants in previously unrecognized biological pathways, highlighting disease mechanisms with a potential role in CKD etiology, morbidity and mortality. Nephrologists now need to find ways to make use of these advancements and meet the increasingly stringent requirements for valid study design, data handling and interpretation of genetic studies. Adding to our prior article in this journal, which introduced the basics of genotype-phenotype association studies in CKD, this second article focuses on how to ascertain robust and reproducible findings by applying adequate methodological and statistical approaches to genotype-phenotype studies in CKD populations. Moreover, this review will briefly discuss genotype-based risk prediction, pharmacotherapy, drug target identification and individualized treatment solutions, specifically highlighting potentially important findings in CKD patients. This increased knowledge will hopefully facilitate the exciting transition from conventional clinical medicine to gene-based medicine. However, before this can be accomplished, unsolved issues regarding the complex human genetic architecture as well technical and clinically oriented obstacles will have to be overcome. Additionally, new policies and standardized risk evaluations for genetic testing in the clinical setting will have to be established to guarantee that CKD patients are provided with high-quality genotype-guided counseling that will help to improve their poor outcomes.

  9. Human genetic mapping studies using single sperm typing

    SciTech Connect

    Hubert, R.S.

    1993-01-01

    Sperm typing is a powerful technique that uses the polymerase chain reaction (PCR) to analyze DNA sequences within single sperm cells in order to construct genetic maps. This methodology was used to estimate the recombination fraction between D3S2 and D3S2 which was found to be 0.28 (95% CI = 0.20-0.36). Pedigree analysis was unable to determine genetic distance between these two markers due to their low informativeness. We also showed that dinucleotide and tetranucleotide repeat polymorphisms can be analyzed in single cells without using radioactivity or denaturing gels. This provides a rich new source of DANA polymorphisms for genetic mapping by sperm typing. In addition, an approach that uses the sperm typing methodology is described that can define the physical boundaries of meiotic recombination hotspots. The hotspot at 4p16.3 near the Huntington disease gene was localized to an interval between D4S10 and D4S126. These studies demonstrated the usefulness of sperm typing as a tool for the study of human genetic.

  10. Controlling false discoveries in genetic studies.

    PubMed

    van den Oord, Edwin J C G

    2008-07-01

    A false discovery occurs when a researcher concludes that a marker is involved in the etiology of the disease whereas in reality it is not. In genetic studies the risk of false discoveries is very high because only few among the many markers that can be tested will have an effect on the disease. In this article, we argue that it may be best to use methods for controlling false discoveries that would introduce the same ratio of false discoveries divided by all rejected tests into the literature regardless of systematic differences between studies. After a brief discussion of traditional "multiple testing" methods, we show that methods that control the false discovery rate (FDR) may be more suitable to achieve this goal. These FDR methods are therefore discussed in more detail. Instead of merely testing for main effects, it may be important to search for gene-environment/covariate interactions, gene-gene interactions or genetic variants affecting disease subtypes. In the second section, we point out the challenges involved in controlling false discoveries in such searches. The final section discusses the role of replication studies for eliminating false discoveries and the complexities associated with the definition of what constitutes a replication and the design of these studies.

  11. A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease.

    PubMed

    Holmans, Peter; Moskvina, Valentina; Jones, Lesley; Sharma, Manu; Vedernikov, Alexey; Buchel, Finja; Saad, Mohamad; Sadd, Mohamad; Bras, Jose M; Bettella, Francesco; Nicolaou, Nayia; Simón-Sánchez, Javier; Mittag, Florian; Gibbs, J Raphael; Schulte, Claudia; Durr, Alexandra; Guerreiro, Rita; Hernandez, Dena; Brice, Alexis; Stefánsson, Hreinn; Majamaa, Kari; Gasser, Thomas; Heutink, Peter; Wood, Nicholas W; Martinez, Maria; Singleton, Andrew B; Nalls, Michael A; Hardy, John; Morris, Huw R; Williams, Nigel M

    2013-03-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1-2% in people >60 and 3-4% in people >80. Genome-wide association (GWA) studies have now implicated significant evidence for association in at least 18 genomic regions. We have studied a large PD-meta analysis and identified a significant excess of SNPs (P < 1 × 10(-16)) that are associated with PD but fall short of the genome-wide significance threshold. This result was independent of variants at the 18 previously implicated regions and implies the presence of additional polygenic risk alleles. To understand how these loci increase risk of PD, we applied a pathway-based analysis, testing for biological functions that were significantly enriched for genes containing variants associated with PD. Analysing two independent GWA studies, we identified that both had a significant excess in the number of functional categories enriched for PD-associated genes (minimum P = 0.014 and P = 0.006, respectively). Moreover, 58 categories were significantly enriched for associated genes in both GWA studies (P < 0.001), implicating genes involved in the 'regulation of leucocyte/lymphocyte activity' and also 'cytokine-mediated signalling' as conferring an increased susceptibility to PD. These results were unaltered by the exclusion of all 178 genes that were present at the 18 genomic regions previously reported to be strongly associated with PD (including the HLA locus). Our findings, therefore, provide independent support to the strong association signal at the HLA locus and imply that the immune-related genetic susceptibility to PD is likely to be more widespread in the genome than previously appreciated.

  12. Genetic and environmental influences on impulsivity: A meta-analysis of twin, family and adoption studies

    PubMed Central

    Bezdjian, Serena; Baker, Laura A.; Tuvblad, Catherine

    2011-01-01

    A meta-analysis of twin, family and adoption studies was conducted to estimate the magnitude of genetic and environmental influences on impulsivity. The best fitting model for 41 key studies (58 independent samples from 14 month old infants to adults; N = 27,147) included equal proportions of variance due to genetic (0.50) and non-shared environmental (0.50) influences, with genetic effects being both additive (0.38) and non-additive (0.12). Shared environmental effects were unimportant in explaining individual differences in impulsivity. Age, sex, and study design (twin vs. adoption) were all significant moderators of the magnitude of genetic and environmental influences on impulsivity. The relative contribution of genetic effects (broad sense heritability) and unique environmental effects were also found to be important throughout development from childhood to adulthood. Total genetic effects were found to be important for all ages, but appeared to be strongest in children. Analyses also demonstrated that genetic effects appeared to be stronger in males than in females. Method of assessment (laboratory tasks vs. questionnaires), however, was not a significant moderator of the genetic and environmental influences on impulsivity. These results provide a structured synthesis of existing behavior genetic studies on impulsivity by providing a clearer understanding of the relative genetic and environmental contributions in impulsive traits through various stages of development. PMID:21889436

  13. The Etruscans: A Population-Genetic Study

    PubMed Central

    Vernesi, Cristiano; Caramelli, David; Dupanloup, Isabelle; Bertorelle, Giorgio; Lari, Martina; Cappellini, Enrico; Moggi-Cecchi, Jacopo; Chiarelli, Brunetto; Castrì, Loredana; Casoli, Antonella; Mallegni, Francesco; Lalueza-Fox, Carles; Barbujani, Guido

    2004-01-01

    The origins of the Etruscans, a non-Indo-European population of preclassical Italy, are unclear. There is broad agreement that their culture developed locally, but the Etruscans’ evolutionary and migrational relationships are largely unknown. In this study, we determined mitochondrial DNA sequences in multiple clones derived from bone samples of 80 Etruscans who lived between the 7th and the 3rd centuries b.c. In the first phase of the study, we eliminated all specimens for which any of nine tests for validation of ancient DNA data raised the suspicion that either degradation or contamination by modern DNA might have occurred. On the basis of data from the remaining 30 individuals, the Etruscans appeared as genetically variable as modern populations. No significant heterogeneity emerged among archaeological sites or time periods, suggesting that different Etruscan communities shared not only a culture but also a mitochondrial gene pool. Genetic distances and sequence comparisons show closer evolutionary relationships with the eastern Mediterranean shores for the Etruscans than for modern Italian populations. All mitochondrial lineages observed among the Etruscans appear typically European or West Asian, but only a few haplotypes were found to have an exact match in a modern mitochondrial database, raising new questions about the Etruscans’ fate after their assimilation into the Roman state. PMID:15015132

  14. Combining genetic association study designs: a GWAS case study.

    PubMed

    Estus, Janice L; Fardo, David W

    2013-01-01

    Genome-wide association studies (GWAS) explore the relationship between genome variability and disease susceptibility with either population- or family-based data. Here, we have evaluated the utility of combining population- and family-based statistical association tests and have proposed a method for reducing the burden of multiple testing. Unrelated singleton and parent-offspring trio cases and controls from the Genetics of Kidneys in Diabetes (GoKinD) study were analyzed for genetic association with diabetic nephropathy (DN) in type 1 diabetics (T1D). The Cochran-Armitage test for trend and the family-based association test were employed using either unrelated cases and controls or trios, respectively. In addition to combining single nucleotide polymorphism (SNP) p-values across these tests via Fisher's method, we employed a novel screening approach to rank SNPs based on conditional power for more efficient testing. Using either the population-based or family-based subset alone predictably limited resolution to detect DN SNPs. For 384,197 SNPs passing quality control (QC), none achieved strict genome-wide significance (1.4 × 10(-7)) using 1171 singletons (577/594 cases/controls) or 1738 pooled singletons and offspring probands (841/897). Similarly, none of the 352,004 SNPs passing QC in 567 family trios (264/303 case/control proband trios) reached genome-wide significance. Testing the top 10 SNPs ranked using aggregated conditional power resulted in two SNPs reaching genome-wide significance, rs11645147 on chromosome 16 (p = 1.74 × 10(-4) < 0.05/10 = 0.005) and rs7866522 on chromosome 9 (p = 0.0033). Efficient usage of mixed designs incorporating both unrelated and family-based data may help to uncover associations otherwise difficult to detect in the presence of massive multiple testing corrections. Capitalizing on the strengths of both types while using screening approaches may be useful especially in light of large-scale, next-generation sequencing and rare

  15. Combining genetic association study designs: a GWAS case study

    PubMed Central

    Estus, Janice L.; Fardo, David W.

    2013-01-01

    Genome-wide association studies (GWAS) explore the relationship between genome variability and disease susceptibility with either population- or family-based data. Here, we have evaluated the utility of combining population- and family-based statistical association tests and have proposed a method for reducing the burden of multiple testing. Unrelated singleton and parent-offspring trio cases and controls from the Genetics of Kidneys in Diabetes (GoKinD) study were analyzed for genetic association with diabetic nephropathy (DN) in type 1 diabetics (T1D). The Cochran-Armitage test for trend and the family-based association test were employed using either unrelated cases and controls or trios, respectively. In addition to combining single nucleotide polymorphism (SNP) p-values across these tests via Fisher's method, we employed a novel screening approach to rank SNPs based on conditional power for more efficient testing. Using either the population-based or family-based subset alone predictably limited resolution to detect DN SNPs. For 384,197 SNPs passing quality control (QC), none achieved strict genome-wide significance (1.4 × 10−7) using 1171 singletons (577/594 cases/controls) or 1738 pooled singletons and offspring probands (841/897). Similarly, none of the 352,004 SNPs passing QC in 567 family trios (264/303 case/control proband trios) reached genome-wide significance. Testing the top 10 SNPs ranked using aggregated conditional power resulted in two SNPs reaching genome-wide significance, rs11645147 on chromosome 16 (p = 1.74 × 10−4 < 0.05/10 = 0.005) and rs7866522 on chromosome 9 (p = 0.0033). Efficient usage of mixed designs incorporating both unrelated and family-based data may help to uncover associations otherwise difficult to detect in the presence of massive multiple testing corrections. Capitalizing on the strengths of both types while using screening approaches may be useful especially in light of large-scale, next-generation sequencing and rare

  16. Benchmark Study of Industrial Needs for Additive Manufacturing in Finland

    NASA Astrophysics Data System (ADS)

    Lindqvist, Markku; Piili, Heidi; Salminen, Antti

    Additive manufacturing (AM) is a modern way to produce parts for industrial use. Even though the technical knowledge and research of AM processes are strong in Finland, there are only few industrial applications. Aim of this study is to collect practical knowledge of companies who are interested in industrial use of AM, especially in South-Eastern Finland. Goal of this study is also to investigate demands and requirements of applications for industrial use of AM in this area of Finland. It was concluded, that two of the reasons prohibiting wider industrial use of AM in Finland, are wrong expectations against this technology as well as lack of basic knowledge of possibilities of the technology. Especially, it was noticed that strong 3D-hype is even causing misunderstandings. Nevertheless, the high-level industrial know-how in the area, built around Finnish lumber industry is a strong foundation for the additive manufacturing technology.

  17. Study Suggests Genetic Link to Middle Ear Infections

    MedlinePlus

    ... medlineplus.gov/news/fullstory_161378.html Study Suggests Genetic Link to Middle Ear Infections They're the ... News) -- Researchers say they've found a potential genetic link to a child's higher risk of middle ...

  18. Electrostatic Levitation for Studies of Additive Manufactured Materials

    NASA Technical Reports Server (NTRS)

    SanSoucie, Michael P.; Rogers, Jan R.; Tramel, Terri

    2014-01-01

    The electrostatic levitation (ESL) laboratory at NASA's Marshall Space Flight Center is a unique facility for investigators studying high temperature materials. The laboratory boasts two levitators in which samples can be levitated, heated, melted, undercooled, and resolidified. Electrostatic levitation minimizes gravitational effects and allows materials to be studied without contact with a container or instrumentation. The lab also has a high temperature emissivity measurement system, which provides normal spectral and normal total emissivity measurements at use temperature. The ESL lab has been instrumental in many pioneering materials investigations of thermophysical properties, e.g., creep measurements, solidification, triggered nucleation, and emissivity at high temperatures. Research in the ESL lab has already led to the development of advanced high temperature materials for aerospace applications, coatings for rocket nozzles, improved medical and industrial optics, metallic glasses, ablatives for reentry vehicles, and materials with memory. Modeling of additive manufacturing materials processing is necessary for the study of their resulting materials properties. In addition, the modeling of the selective laser melting processes and its materials property predictions are also underway. Unfortunately, there is very little data for the properties of these materials, especially of the materials in the liquid state. Some method to measure thermophysical properties of additive manufacturing materials is necessary. The ESL lab is ideal for these studies. The lab can provide surface tension and viscosity of molten materials, density measurements, emissivity measurements, and even creep strength measurements. The ESL lab can also determine melting temperature, surface temperatures, and phase transition temperatures of additive manufactured materials. This presentation will provide background on the ESL lab and its capabilities, provide an approach to using the ESL

  19. Genetic prerequisites for additive or synergistic actions of 5-fluorocytosine and fluconazole in baker's yeast.

    PubMed

    Paluszynski, John P; Klassen, Roland; Meinhardt, Friedhelm

    2008-10-01

    During applications of 5-fluorocytosine (5FC) and fluconazole (FLC), additive or synergistic action may even occur when primary resistance to 5FC is established. Here, we analysed conjoint drug action in Saccharomyces cerevisiae strains deficient in genes known to be essential for 5FC or FLC function. Despite clear primary resistance, residual 5FC activity and additive 5FC+FLC action in cells lacking cytosine permease (Fcy2p) or uracil phosphoribosyl transferase (Fur1p) were detected. In contrast, Deltafcy1 mutants, lacking cytosine deaminase, became entirely resistant to 5FC, concomitantly losing 5FC+FLC additivity. Disruption of the orotate phosphoribosyltransferase gene (URA5) in the wild-type led to low-level 5FC tolerance, while an alternative orotate phosphoribosyltransferase, encoded by URA10, contributed to 5FC toxicity only in the Deltaura5 background. Remarkably, combination of Deltaura5 and Deltafur1 resulted in complete 5FC resistance. Thus, yeast orotate phosphoribosyltransferases are involved in 5FC metabolism. Similarly, disruption of the ergosterol Delta(5,6)-desaturase-encoding gene ERG3 resulted only in partial resistance to FLC, and concomitantly a synergistic effect with 5FC became evident. Full resistance to FLC occurred in Deltaerg3 Deltaerg11 double mutants and, simultaneously, synergism or even an additive effect with FLC and 5FC was no longer discernible. Since the majority of spontaneously occurring resistant yeast clones displayed residual sensitivity to either 5FC or FLC and those strains responded to combined drug treatment in a predictable manner, careful resistance profiling based on the findings reported here may help to address yeast infections by combined application of antimycotic compounds.

  20. The genetics of alcoholism: identifying specific genes through family studies.

    PubMed

    Edenberg, Howard J; Foroud, Tatiana

    2006-09-01

    Alcoholism is a complex disorder with both genetic and environmental risk factors. Studies in humans have begun to elucidate the genetic underpinnings of the risk for alcoholism. Here we briefly review strategies for identifying individual genes in which variations affect the risk for alcoholism and related phenotypes, in the context of one large study that has successfully identified such genes. The Collaborative Study on the Genetics of Alcoholism (COGA) is a family-based study that has collected detailed phenotypic data on individuals in families with multiple alcoholic members. A genome-wide linkage approach led to the identification of chromosomal regions containing genes that influenced alcoholism risk and related phenotypes. Subsequently, single nucleotide polymorphisms (SNPs) were genotyped in positional candidate genes located within the linked chromosomal regions, and analyzed for association with these phenotypes. Using this sequential approach, COGA has detected association with GABRA2, CHRM2 and ADH4; these associations have all been replicated by other researchers. COGA has detected association to additional genes including GABRG3, TAS2R16, SNCA, OPRK1 and PDYN, results that are awaiting confirmation. These successes demonstrate that genes contributing to the risk for alcoholism can be reliably identified using human subjects.

  1. A Study of Additive Noise Model for Robust Speech Recognition

    NASA Astrophysics Data System (ADS)

    Awatade, Manisha H.

    2011-12-01

    A model of how speech amplitude spectra are affected by additive noise is studied. Acoustic features are extracted based on the noise robust parts of speech spectra without losing discriminative information. An existing two non-linear processing methods, harmonic demodulation and spectral peak-to-valley ratio locking, are designed to minimize mismatch between clean and noisy speech features. Previously studied methods, including peak isolation [1], do not require noise estimation and are effective in dealing with both stationary and non-stationary noise.

  2. Microwave sanitization of color additives used in cosmetics: feasibility study.

    PubMed

    Jasnow, S B; Smith, J L

    1975-08-01

    Microwave exposure has been explored as a method of microbiologically sanitizing color additives used in cosmetic products. Selected microbiologically unacceptable cosmetic color additives, D&C red no. 7 Ca lake (certified synthetic organic color), carmine (natural organic color not subject to certification), and chromium hydroxide green (inorganic color not subject to certification), were submitted to microwave exposure. Gram-negative bacteria were eliminated, as verified by enrichment procedures, and levels of gram-positive bacteria were reduced. Generally, analytical and dermal safety studies indicated no significant alterations in physical, chemical, and toxicological properties of the colors. Sanitization was also successfully performed on other colors (D&C red no. 9 Ba lake, D&C red no. 12 Ba lake, D&C green no. 5, and FD&C red no. 4); initial physical and chemical tests were satisfactory. Results indicated that this method of sanitization is feasible and warrants further investigation.

  3. BIG FROG WILDERNESS STUDY AREA AND ADDITIONS, TENNESSEE AND GEORGIA.

    USGS Publications Warehouse

    Slack, John F.; Gazdik, Gertrude C.

    1984-01-01

    A mineral-resource survey was made of the Big Frog Wilderness Study Area and additions, Tennessee-Georgia. Geochemical sampling found traces of gold, zinc, copper, and arsenic in rocks, stream sediments, and panned concentrates, but not in sufficient quantities to indicate the presence of deposits of these metals. The results of the survey indicate that there is little promise for the occurrence of metallic mineral deposits within the study area. The only apparent resources are nonmetallic commodities including rock suitable for construction materials, and small amounts of sand and gravel; however, these commodities are found in abundance outside the study area. A potential may exist for oil and natural gas at great depths, but this cannot be evaluated by the present study.

  4. Recommended Protocol for Round Robin Studies in Additive Manufacturing

    PubMed Central

    Moylan, Shawn; Brown, Christopher U.; Slotwinski, John

    2016-01-01

    One way to improve confidence and encourage proliferation of additive manufacturing (AM) technologies and parts is by generating more high quality data describing the performance of AM processes and parts. Many in the AM community see round robin studies as a way to generate large data sets while distributing the cost among the participants, thereby reducing the cost to individual users. The National Institute of Standards and Technology (NIST) has conducted and participated in several of these AM round robin studies. While the results of these studies are interesting and informative, many of the lessons learned in conducting these studies concern the logistics and methods of the study and unique issues presented by AM. Existing standards for conducting interlaboratory studies of measurement methods, along with NIST’s experience, form the basis for recommended protocols for conducting AM round robin studies. The role of round robin studies in AM qualification, some of the limitations of round robin studies, and the potential benefit of less formal collaborative experiments where multiple factors, AM machine being only one, are varied simultaneously are also discussed. PMID:27274602

  5. Molecular genetic system for regenerative studies using newts.

    PubMed

    Hayashi, Toshinori; Yokotani, Naoki; Tane, Shoji; Matsumoto, Akira; Myouga, Ayumi; Okamoto, Mitsumasa; Takeuchi, Takashi

    2013-02-01

    Urodele newts have the remarkable capability of organ regeneration, and have been used as a unique experimental model for more than a century. However, the mechanisms underlying regulation of the regeneration are not well understood, and gene functions in particular remain largely unknown. To elucidate gene function in regeneration, molecular genetic analyses are very powerful. In particular, it is important to establish transgenic or knockout (mutant) lines, and systematically cross these lines to study the functions of the genes. In fact, such systems have been developed for other vertebrate models. However, there is currently no experimental model system using molecular genetics for newt regenerative research due to difficulties with respect to breeding newts in the laboratory. Here, we show that the Iberian ribbed newt (Pleurodeles waltl) has outstanding properties as a laboratory newt. We developed conditions under which we can obtain a sufficient number and quality of eggs throughout the year, and shortened the period required for sexual maturation from 18 months to 6 months. In addition, P. waltl newts are known for their ability, like other newts, to regenerate various tissues. We revealed that their ability to regenerate various organs is equivalent to that of Japanese common newts. We also developed a method for efficient transgenesis. These studies demonstrate that P. waltl newts are a suitable model animal for analysis of regeneration using molecular genetics. Establishment of this experimental model will enable us to perform comparable studies using these newts and other vertebrate models.

  6. Molecular Genetic Studies of Complex Phenotypes

    PubMed Central

    Marian, A.J.

    2012-01-01

    The approach to molecular genetic studies of complex phenotypes has evolved considerably during the recent years. The candidate gene approach, restricted to analysis of a few single nucleotide polymorphisms (SNPs) in a modest number of cases and controls, has been supplanted by the unbiased approach of Genome-Wide Association Studies (GWAS), wherein a large number of tagger SNPs are typed in a large number of individuals. GWAS, which are designed upon the common disease- common variant hypothesis (CD-CV), have identified a large number of SNPs and loci for complex phenotypes. However, alleles identified through GWAS are typically not causative but rather in linkage disequilibrium (LD) with the true causal variants. The common alleles, which may not capture the uncommon and rare variants, account only for a fraction of heritability of the complex traits. Hence, the focus is being shifted to rare variants – common disease (RV-CD) hypothesis, surmising that rare variants exert large effect sizes on the phenotype. In conjunctional with this conceptual shift technological advances in DNA sequencing techniques have dramatically enhanced whole genome or whole exome sequencing capacity. The sequencing approach affords identification of not only the rare but also the common variants. The approach – whether used in complementation with GWAS or as a stand-alone approach - could define the genetic architecture of the complex phenotypes. Robust phenotyping and large-scale sequencing studies are essential to extract the information content of the vast number of DNA sequence variants (DSVs) in the genome. To garner meaningful clinical information and link the genotype to a phenotype, identification and characterization of a very large number of causal fields beyond the information content of DNA sequence variants would be necessary. This review provides an update on the current progress and limitations in identifying DSVs that are associated with phenotypic effects. PMID

  7. A genetic study of affective disorders.

    PubMed

    Smeraldi, E; Negri, F; Melica, A M

    1977-11-01

    First and second degree relatives of 99 probands with affective disorders (49 unipolar and 50 bipolar subjects) were studied. The high risk values obtained for affective disorders were shown to be compatible with those found by other authors, although the prevalence of the illness in the population of Lombardy appears to be much lower than in other countries. Very low rates of suicide and alcoholism were found in our sample. Data obtained by analysis of the affected pairs of relatives rule out the hypothesis of a dominant X-linked gene if the bipolar and the unipolar forms are considered genetically separated entities. Results compatible with a polygenic condition, partially shared by bipolar patients, were found using Slater's and Smith & Falconer's methods. Our data, however, cannot rule out the dominant hypothesis. PMID:596231

  8. Making intelligent systems team players: Additional case studies

    NASA Technical Reports Server (NTRS)

    Malin, Jane T.; Schreckenghost, Debra L.; Rhoads, Ron W.

    1993-01-01

    Observations from a case study of intelligent systems are reported as part of a multi-year interdisciplinary effort to provide guidance and assistance for designers of intelligent systems and their user interfaces. A series of studies were conducted to investigate issues in designing intelligent fault management systems in aerospace applications for effective human-computer interaction. The results of the initial study are documented in two NASA technical memoranda: TM 104738 Making Intelligent Systems Team Players: Case Studies and Design Issues, Volumes 1 and 2; and TM 104751, Making Intelligent Systems Team Players: Overview for Designers. The objective of this additional study was to broaden the investigation of human-computer interaction design issues beyond the focus on monitoring and fault detection in the initial study. The results of this second study are documented which is intended as a supplement to the original design guidance documents. These results should be of interest to designers of intelligent systems for use in real-time operations, and to researchers in the areas of human-computer interaction and artificial intelligence.

  9. Addition of molecular methods to mutation studies with Drosophila melanogaster

    SciTech Connect

    Lee, W.R. )

    1989-01-01

    For 80 years, Drosophila melanogaster has been used as a major tool in analyzing Mendelian genetics. By using chromosome inversions that suppress crossing over, geneticists have developed a large number of stocks for mutation analysis. These stocks permit numerous tests for specific locus mutations, lethals at multiple loci on any chromosome, chromosome exchanges, insertions, and deletions. The entire genome can be manipulated for a degree of genetic control not found in other germ-line systems. Recombinant DNA techniques now permit analysis of mutations to the nucleotide level. By combining classical genetic analysis with recombinant DNA techniques, it is possible to analyze mutations that range from chromosome aberrations and multilocus deficiencies to single nucleotide transitions.

  10. Additive genetic and heterosis effects in crosses among cattle breeds of British, European and Zebu origin.

    PubMed

    Peacock, F M; Koger, M; Olson, T A; Crockett, J R

    1981-05-01

    Breed and heterosis effects for maternal and calf components for weaning traits were measured in the progeny of Angus (A), Brahman (B) and Charolais (C) sires mated to A, B, C and reciprocal AB, AC and BC dams. Additive breed effects for the calf component for weaning weight were -3.0 +/- 3.2, -26.6 +/- 3.1 and 29.6 +/- 3.3 kg for A, B and C, respectively. Corresponding maternal breed effects were -1.7 +/- 2.4, 7.8 +/- 2.3 and -6.1 +/- 2.6 kilograms. Heterosis effects on weaning weight for the calf component were 21.2 +/- 3.6 for AB, 1.4 +/- 3.7 for AC and 16.5 +/- 3.4 for BC crosses, while heterosis levels for the maternal component were 28.9 +/- 2.7 for AB, 16.5 +/- 3.2 for AC and 18.7 +/- 2.9 kg for BC dams. The corresponding estimates for condition scores tended to parallel those for weaning weight. Approximate relative production efficiency rates were computed for the different mating groups as (calf weight divided by cow weight) x weaning rate. These values were .34 for purebred matings, .36 for purebred dams raising F1 calves, .40 for F1 cows raising backcross calves and .43 for F1 dams raising three breed crossbred calves.

  11. Additive genetic variation in resistance traits of an exotic pine species: little evidence for constraints on evolution of resistance against native herbivores

    PubMed Central

    Moreira, X; Zas, R; Sampedro, L

    2013-01-01

    The apparent failure of invasions by alien pines in Europe has been explained by the co-occurrence of native pine congeners supporting herbivores that might easily recognize the new plants as hosts. Previous studies have reported that exotic pines show reduced tolerance and capacity to induce resistance to those native herbivores. We hypothesize that limited genetic variation in resistance to native herbivores and the existence of evolutionary trade-offs between growth and resistance could represent additional potential constraints on the evolution of invasiveness of exotic pines outside their natural range. In this paper, we examined genetic variation for constitutive and induced chemical defences (measured as non-volatile resin in the stem and total phenolics in the needles) and resistance to two major native generalist herbivores of pines in cafeteria bioassays (the phloem-feeder Hylobius abietis and the defoliator Thaumetopoea pityocampa) using half-sib families drawn from a sample of the population of Pinus radiata introduced to Spain in the mid-19th century. We found (i) significant genetic variation, with moderate-to-high narrow-sense heritabilities for both the production of constitutive non-volatile resin and induced total phenolics, and for constitutive resistance against T. pityocampa in bioassays, (ii) no evolutionary trade-offs between plant resistance and growth traits or between the production of different quantitative chemical defences and (iii) a positive genetic correlation between constitutive resistance to the two studied herbivores. Overall, results of our study indicate that the exotic pine P. radiata has limited genetic constraints on the evolution of resistance against herbivores in its introduced range, suggesting that, at least in terms of interactions with these enemies, this pine species has potential to become invasive in the future. PMID:23232833

  12. Biological detoxification of the mycotoxin deoxynivalenol and its use in genetically engineered crops and feed additives.

    PubMed

    Karlovsky, Petr

    2011-08-01

    Deoxynivalenol (DON) is the major mycotoxin produced by Fusarium fungi in grains. Food and feed contaminated with DON pose a health risk to humans and livestock. The risk can be reduced by enzymatic detoxification. Complete mineralization of DON by microbial cultures has rarely been observed and the activities turned out to be unstable. The detoxification of DON by reactions targeting its epoxide group or hydroxyl on carbon 3 is more feasible. Microbial strains that de-epoxidize DON under anaerobic conditions have been isolated from animal digestive system. Feed additives claimed to de-epoxidize trichothecenes enzymatically are on the market but their efficacy has been disputed. A new detoxification pathway leading to 3-oxo-DON and 3-epi-DON was discovered in taxonomically unrelated soil bacteria from three continents; the enzymes involved remain to be identified. Arabidopsis, tobacco, wheat, barley, and rice were engineered to acetylate DON on carbon 3. In wheat expressing DON acetylation activity, the increase in resistance against Fusarium head blight was only moderate. The Tri101 gene from Fusarium sporotrichioides was used; Fusarium graminearum enzyme which possesses higher activity towards DON would presumably be a better choice. Glycosylation of trichothecenes occurs in plants, contributing to the resistance of wheat to F. graminearum infection. Marker-assisted selection based on the trichothecene-3-O-glucosyltransferase gene can be used in breeding for resistance. Fungal acetyltransferases and plant glucosyltransferases targeting carbon 3 of trichothecenes remain promising candidates for engineering resistance against Fusarium head blight. Bacterial enzymes catalyzing oxidation, epimerization, and less likely de-epoxidation of DON may extend this list in future.

  13. Evolutionary genetics in wild primates: combining genetic approaches with field studies of natural populations

    PubMed Central

    Tung, Jenny; Alberts, Susan C; Wray, Gregory A

    2010-01-01

    Ecological and evolutionary studies of wild primates hold important keys to understanding both the shared characteristics of primate biology and the genetic and phenotypic differences that make specific lineages, including our own, unique. Although complementary genetic research on nonhuman primates has long been of interest, recent technological and methodological advances now enable functional and population genetic studies in an unprecedented manner. In the past several years, novel genetic data sets have revealed new information about the demographic history of primate populations and the genetics of adaptively important traits. In combination with the rich history of behavioral, ecological, and physiological work on natural primate populations, genetic approaches promise to provide a compelling picture of primate evolution in the past and in the present day. PMID:20580115

  14. RAMSEYS DRAFT WILDERNESS STUDY AREA AND ADDITION, VIRGINIA.

    USGS Publications Warehouse

    Lesure, Frank G.; Mory, Peter C.

    1984-01-01

    Mineral-resource surveys of the Ramseys Draft Wilderness Study Area and adjoining roadless area addition in George Washington National Forest in the western valley and ridge province, Augusta and Highland Counties, Virginia, were done. The surveys outlined three small areas containing anomalous amounts of copper, lead, and zinc related to stratabound red-bed copper mineralization, but these occurrences are not large and are not considered as having mineral-resource potential. The area contains abundant sandstone suitable for construction materials and shale suitable for making brick, tile, and other low-grade ceramic products, but these commodities occur in abundance outside the wilderness study area. Structural conditions are probably favorable for the accumulation of natural gas, but exploratory drilling has not been done sufficiently near the area to evaluate the gas potential.

  15. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  16. Implementation of the Realized Genomic Relationship Matrix to Open-Pollinated White Spruce Family Testing for Disentangling Additive from Nonadditive Genetic Effects.

    PubMed

    Gamal El-Dien, Omnia; Ratcliffe, Blaise; Klápště, Jaroslav; Porth, Ilga; Chen, Charles; El-Kassaby, Yousry A

    2016-03-01

    The open-pollinated (OP) family testing combines the simplest known progeny evaluation and quantitative genetics analyses as candidates' offspring are assumed to represent independent half-sib families. The accuracy of genetic parameter estimates is often questioned as the assumption of "half-sibling" in OP families may often be violated. We compared the pedigree- vs. marker-based genetic models by analysing 22-yr height and 30-yr wood density for 214 white spruce [Picea glauca (Moench) Voss] OP families represented by 1694 individuals growing on one site in Quebec, Canada. Assuming half-sibling, the pedigree-based model was limited to estimating the additive genetic variances which, in turn, were grossly overestimated as they were confounded by very minor dominance and major additive-by-additive epistatic genetic variances. In contrast, the implemented genomic pairwise realized relationship models allowed the disentanglement of additive from all nonadditive factors through genetic variance decomposition. The marker-based models produced more realistic narrow-sense heritability estimates and, for the first time, allowed estimating the dominance and epistatic genetic variances from OP testing. In addition, the genomic models showed better prediction accuracies compared to pedigree models and were able to predict individual breeding values for new individuals from untested families, which was not possible using the pedigree-based model. Clearly, the use of marker-based relationship approach is effective in estimating the quantitative genetic parameters of complex traits even under simple and shallow pedigree structure.

  17. Implementation of the Realized Genomic Relationship Matrix to Open-Pollinated White Spruce Family Testing for Disentangling Additive from Nonadditive Genetic Effects

    PubMed Central

    Gamal El-Dien, Omnia; Ratcliffe, Blaise; Klápště, Jaroslav; Porth, Ilga; Chen, Charles; El-Kassaby, Yousry A.

    2016-01-01

    The open-pollinated (OP) family testing combines the simplest known progeny evaluation and quantitative genetics analyses as candidates’ offspring are assumed to represent independent half-sib families. The accuracy of genetic parameter estimates is often questioned as the assumption of “half-sibling” in OP families may often be violated. We compared the pedigree- vs. marker-based genetic models by analysing 22-yr height and 30-yr wood density for 214 white spruce [Picea glauca (Moench) Voss] OP families represented by 1694 individuals growing on one site in Quebec, Canada. Assuming half-sibling, the pedigree-based model was limited to estimating the additive genetic variances which, in turn, were grossly overestimated as they were confounded by very minor dominance and major additive-by-additive epistatic genetic variances. In contrast, the implemented genomic pairwise realized relationship models allowed the disentanglement of additive from all nonadditive factors through genetic variance decomposition. The marker-based models produced more realistic narrow-sense heritability estimates and, for the first time, allowed estimating the dominance and epistatic genetic variances from OP testing. In addition, the genomic models showed better prediction accuracies compared to pedigree models and were able to predict individual breeding values for new individuals from untested families, which was not possible using the pedigree-based model. Clearly, the use of marker-based relationship approach is effective in estimating the quantitative genetic parameters of complex traits even under simple and shallow pedigree structure. PMID:26801647

  18. Implementation of the Realized Genomic Relationship Matrix to Open-Pollinated White Spruce Family Testing for Disentangling Additive from Nonadditive Genetic Effects.

    PubMed

    Gamal El-Dien, Omnia; Ratcliffe, Blaise; Klápště, Jaroslav; Porth, Ilga; Chen, Charles; El-Kassaby, Yousry A

    2016-03-01

    The open-pollinated (OP) family testing combines the simplest known progeny evaluation and quantitative genetics analyses as candidates' offspring are assumed to represent independent half-sib families. The accuracy of genetic parameter estimates is often questioned as the assumption of "half-sibling" in OP families may often be violated. We compared the pedigree- vs. marker-based genetic models by analysing 22-yr height and 30-yr wood density for 214 white spruce [Picea glauca (Moench) Voss] OP families represented by 1694 individuals growing on one site in Quebec, Canada. Assuming half-sibling, the pedigree-based model was limited to estimating the additive genetic variances which, in turn, were grossly overestimated as they were confounded by very minor dominance and major additive-by-additive epistatic genetic variances. In contrast, the implemented genomic pairwise realized relationship models allowed the disentanglement of additive from all nonadditive factors through genetic variance decomposition. The marker-based models produced more realistic narrow-sense heritability estimates and, for the first time, allowed estimating the dominance and epistatic genetic variances from OP testing. In addition, the genomic models showed better prediction accuracies compared to pedigree models and were able to predict individual breeding values for new individuals from untested families, which was not possible using the pedigree-based model. Clearly, the use of marker-based relationship approach is effective in estimating the quantitative genetic parameters of complex traits even under simple and shallow pedigree structure. PMID:26801647

  19. Methodological considerations in the study of genetic discrimination.

    PubMed

    Treloar, Susan; Taylor, Sandra; Otlowski, Margaret; Barlow-Stewart, Kristine; Stranger, Mark; Chenoweth, Kellie

    2004-01-01

    The potential significance and dimensions of genetic discrimination have been described extensively in published literature, but epidemiological and verified case data are limited. Obtaining unbiased data from individuals about discrimination which has been based on erroneous or unjustifiable assumptions about their genetic predispositions poses unique challenges. Through review and discussion of research literature, we identify methodological considerations for collecting valid epidemiological data on genetic discrimination from individuals in the community; in particular, we consider issues which relate to sampling, selection and response. We identify issues to promote sound study design, with particular attention to verification of genetic discrimination, and highlight the importance of clinical and genetic knowledge of complex genotype-phenotype relationships.

  20. Genetic association studies in drug-induced liver injury.

    PubMed

    Daly, Ann K; Day, Chris P

    2009-11-01

    Genetic studies on drug-induced liver injury (DILI) have proved challenging, both because of their rarity and their difficulty in replicating observed effects. However, significant progress has now been achieved by both candidate-gene and genome-wide association studies. These two approaches are considered in detail, together with examples of DILI due to specific drugs where consistent associations have been reported. Particular consideration is given to associations between antituberculosis drug-related liver injury and the "slow acetylator" genotype for N-acetyltransferase 2, amoxicillin/clavulanate-related liver injury, and the human leukocyte antigen (HLA) class II DRB1*1501 allele and flucloxacillin-related injury and the HLA class I B*5701 allele. Although these associations are drug-specific, the possibility that additional, more general susceptibility genes for DILI exist requires further investigation, ideally by genome-wide association studies involving international collaboration. The possibility of interethnic variation in susceptibility to DILI also requires further study.

  1. Evolution of the additive genetic variance-covariance matrix under continuous directional selection on a complex behavioural phenotype.

    PubMed

    Careau, Vincent; Wolak, Matthew E; Carter, Patrick A; Garland, Theodore

    2015-11-22

    Given the pace at which human-induced environmental changes occur, a pressing challenge is to determine the speed with which selection can drive evolutionary change. A key determinant of adaptive response to multivariate phenotypic selection is the additive genetic variance-covariance matrix ( G: ). Yet knowledge of G: in a population experiencing new or altered selection is not sufficient to predict selection response because G: itself evolves in ways that are poorly understood. We experimentally evaluated changes in G: when closely related behavioural traits experience continuous directional selection. We applied the genetic covariance tensor approach to a large dataset (n = 17 328 individuals) from a replicated, 31-generation artificial selection experiment that bred mice for voluntary wheel running on days 5 and 6 of a 6-day test. Selection on this subset of G: induced proportional changes across the matrix for all 6 days of running behaviour within the first four generations. The changes in G: induced by selection resulted in a fourfold slower-than-predicted rate of response to selection. Thus, selection exacerbated constraints within G: and limited future adaptive response, a phenomenon that could have profound consequences for populations facing rapid environmental change.

  2. Evolution of the additive genetic variance-covariance matrix under continuous directional selection on a complex behavioural phenotype.

    PubMed

    Careau, Vincent; Wolak, Matthew E; Carter, Patrick A; Garland, Theodore

    2015-11-22

    Given the pace at which human-induced environmental changes occur, a pressing challenge is to determine the speed with which selection can drive evolutionary change. A key determinant of adaptive response to multivariate phenotypic selection is the additive genetic variance-covariance matrix ( G: ). Yet knowledge of G: in a population experiencing new or altered selection is not sufficient to predict selection response because G: itself evolves in ways that are poorly understood. We experimentally evaluated changes in G: when closely related behavioural traits experience continuous directional selection. We applied the genetic covariance tensor approach to a large dataset (n = 17 328 individuals) from a replicated, 31-generation artificial selection experiment that bred mice for voluntary wheel running on days 5 and 6 of a 6-day test. Selection on this subset of G: induced proportional changes across the matrix for all 6 days of running behaviour within the first four generations. The changes in G: induced by selection resulted in a fourfold slower-than-predicted rate of response to selection. Thus, selection exacerbated constraints within G: and limited future adaptive response, a phenomenon that could have profound consequences for populations facing rapid environmental change. PMID:26582016

  3. Experimental Study of Additives on Viscosity biodiesel at Low Temperature

    NASA Astrophysics Data System (ADS)

    Fajar, Berkah; Sukarno

    2015-09-01

    An experimental investigation was performed to find out the viscosity of additive and biodiesel fuel mixture in the temperature range from 283 K to 318 K. Solutions to reduce the viscosity of biodiesel is to add the biodiesel with some additive. The viscosity was measured using a Brookfield Rheometer DV-II. The additives were the generic additive (Diethyl Ether/DDE) and the commercial additive Viscoplex 10-330 CFI. Each biodiesel blends had a concentration of the mixture: 0.0; 0.25; 0.5; 0.75; 1.0; and 1.25% vol. Temperature of biodiesel was controlled from 40°C to 0°C. The viscosity of biodiesel and additive mixture at a constant temperature can be approximated by a polynomial equation and at a constant concentration by exponential equation. The optimum mixture is at 0.75% for diethyl ether and 0.5% for viscoplex.

  4. Selection of homogeneous populations for genetic study: the Portugal genetics of psychosis project.

    PubMed

    Pato, C N; Azevedo, M H; Pato, M T; Kennedy, J L; Coelho, I; Dourado, A; Macedo, A; Valente, J; Ferreira, C P; Madeira, J; Gago da Camara, J; Moniz, M; Correia, C

    1997-05-31

    Molecular genetic studies of psychiatric disorders must face the possibility that despite the significant contribution of genetic factors to the expression of syndromes like schizophrenia, these syndromes may be a heterogeneous collection of genetic and non-genetic illnesses. These illnesses may be etiologically distinct from each other and still share many clinical features in common. Linkage studies of families with multiple affected members tend to favor the selection of genetic forms of a syndrome but can still represent a heterogeneous set of different genetic illnesses. To limit the potential genetic heterogeneity of a study sample, we selected a population that was geographically isolated and was historically relatively genetically homogeneous. We then assessed the relative level of homogeneity utilizing a surname analysis of the population of the Azores, mainland Portugal, rural USA, and urban USA. The average number of families with the same last name corrected for population size in the Azores is 30.88, in Coimbra it is 21.42, compared to 1.13 in a rural American population and 0.38 in an urban American population. The results of this analysis indicate that the Azores have the highest degree of homogeneity, and mainland Portugal has a high degree of homogeneity.

  5. Emerging Trends in Behavioral Genetic Studies of Child Temperament

    PubMed Central

    Saudino, Kimberly J.; Micalizzi, Lauren

    2015-01-01

    In this article, we describe three emerging trends in the application of behavioral genetic methods to the study of temperament. The trends—using multiple methods to assess temperament, considering contextual influences on temperament, and evaluating the structure of temperament—have been well studied in the phenotypic literature, but adding a behavioral genetic perspective can enrich our understanding of temperament. We review recent behavioral genetic research in each of these areas and discuss its implications. PMID:26417384

  6. Statistical Analysis in Genetic Studies of Mental Illnesses

    PubMed Central

    Zhang, Heping

    2011-01-01

    Identifying the risk factors for mental illnesses is of significant public health importance. Diagnosis, stigma associated with mental illnesses, comorbidity, and complex etiologies, among others, make it very challenging to study mental disorders. Genetic studies of mental illnesses date back at least a century ago, beginning with descriptive studies based on Mendelian laws of inheritance. A variety of study designs including twin studies, family studies, linkage analysis, and more recently, genomewide association studies have been employed to study the genetics of mental illnesses, or complex diseases in general. In this paper, I will present the challenges and methods from a statistical perspective and focus on genetic association studies. PMID:21909187

  7. Additive Manufacturing in Production: A Study Case Applying Technical Requirements

    NASA Astrophysics Data System (ADS)

    Ituarte, Iñigo Flores; Coatanea, Eric; Salmi, Mika; Tuomi, Jukka; Partanen, Jouni

    Additive manufacturing (AM) is expanding the manufacturing capabilities. However, quality of AM produced parts is dependent on a number of machine, geometry and process parameters. The variability of these parameters affects the manufacturing drastically and therefore standardized processes and harmonized methodologies need to be developed to characterize the technology for end use applications and enable the technology for manufacturing. This research proposes a composite methodology integrating Taguchi Design of Experiments, multi-objective optimization and statistical process control, to optimize the manufacturing process and fulfil multiple requirements imposed to an arbitrary geometry. The proposed methodology aims to characterize AM technology depending upon manufacturing process variables as well as to perform a comparative assessment of three AM technologies (Selective Laser Sintering, Laser Stereolithography and Polyjet). Results indicate that only one machine, laser-based Stereolithography, was feasible to fulfil simultaneously macro and micro level geometrical requirements but mechanical properties were not at required level. Future research will study a single AM system at the time to characterize AM machine technical capabilities and stimulate pre-normative initiatives of the technology for end use applications.

  8. Genetics

    MedlinePlus

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  9. Functional-mixed effects models for candidate genetic mapping in imaging genetic studies.

    PubMed

    Lin, Ja-An; Zhu, Hongtu; Mihye, Ahn; Sun, Wei; Ibrahim, Joseph G

    2014-12-01

    The aim of this paper is to develop a functional-mixed effects modeling (FMEM) framework for the joint analysis of high-dimensional imaging data in a large number of locations (called voxels) of a three-dimensional volume with a set of genetic markers and clinical covariates. Our FMEM is extremely useful for efficiently carrying out the candidate gene approaches in imaging genetic studies. FMEM consists of two novel components including a mixed effects model for modeling nonlinear genetic effects on imaging phenotypes by introducing the genetic random effects at each voxel and a jumping surface model for modeling the variance components of the genetic random effects and fixed effects as piecewise smooth functions of the voxels. Moreover, FMEM naturally accommodates the correlation structure of the genetic markers at each voxel, while the jumping surface model explicitly incorporates the intrinsically spatial smoothness of the imaging data. We propose a novel two-stage adaptive smoothing procedure to spatially estimate the piecewise smooth functions, particularly the irregular functional genetic variance components, while preserving their edges among different piecewise-smooth regions. We develop weighted likelihood ratio tests and derive their exact approximations to test the effect of the genetic markers across voxels. Simulation studies show that FMEM significantly outperforms voxel-wise approaches in terms of higher sensitivity and specificity to identify regions of interest for carrying out candidate genetic mapping in imaging genetic studies. Finally, FMEM is used to identify brain regions affected by three candidate genes including CR1, CD2AP, and PICALM, thereby hoping to shed light on the pathological interactions between these candidate genes and brain structure and function.

  10. Optimal Trend Tests for Genetic Association Studies of Heterogeneous Diseases.

    PubMed

    Lee, Wen-Chung

    2016-06-09

    The Cochran-Armitage trend test is a standard procedure in genetic association studies. It is a directed test with high power to detect genetic effects that follow the gene-dosage model. In this paper, the author proposes optimal trend tests for genetic association studies of heterogeneous diseases. Monte-Carlo simulations show that the power gain of the optimal trend tests over the conventional Cochran-Armitage trend test is striking when the genetic effects are heterogeneous. The easy-to-use R 3.1.2 software (R Foundation for Statistical Computing, Vienna, Austria) code is provided. The optimal trend tests are recommended for routine use.

  11. A new dawn for genetic association studies in multiple sclerosis.

    PubMed

    Kantarci, Orhun H

    2016-08-01

    Before the genomics technology revolution allowed us to do genome-wide science, genetics research relied on our limited knowledge about a subject to generate hypothesis and candidate genes to study. Despite the level of naiveté, several associations with susceptibility to a complex disease such as multiple sclerosis (MS) were discovered. Of these, HLA-DRB1 and IL7R (1) stand out as being confirmed and refined early by the genome-wide association studies (GWAS) that followed.(2) Despite the expense and gargantuan efforts, these GWAS have successfully led to the discovery of more than 100 additional genes, albeit with smaller effect sizes, that contribute to MS susceptibility.(3) This list keeps growing, but it comes with no surprise that most of these genes identified the immune system as one large candidate for MS susceptibility. PMID:27540593

  12. Replication of a gene-environment interaction Via Multimodel inference: additive-genetic variance in adolescents' general cognitive ability increases with family-of-origin socioeconomic status.

    PubMed

    Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

    2015-03-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES-an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research. PMID:25539975

  13. Replication of a Gene-Environment Interaction via Multimodel Inference: Additive-Genetic Variance in Adolescents’ General Cognitive Ability Increases with Family-of-Origin Socioeconomic Status

    PubMed Central

    Kirkpatrick, Robert M.; McGue, Matt; Iacono, William G.

    2015-01-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES—an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research. PMID:25539975

  14. Replication of a gene-environment interaction Via Multimodel inference: additive-genetic variance in adolescents' general cognitive ability increases with family-of-origin socioeconomic status.

    PubMed

    Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

    2015-03-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES-an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research.

  15. A "Genetic Study" of the Galaxy

    NASA Astrophysics Data System (ADS)

    2006-09-01

    Looking in detail at the composition of stars with ESO's VLT, astronomers are providing a fresh look at the history of our home galaxy, the Milky Way. They reveal that the central part of our Galaxy formed not only very quickly but also independently of the rest. "For the first time, we have clearly established a 'genetic difference' between stars in the disc and the bulge of our Galaxy," said Manuela Zoccali, lead author of the paper presenting the results in the journal Astronomy and Astrophysics [1]. "We infer from this that the bulge must have formed more rapidly than the disc, probably in less than a billion years and when the Universe was still very young." ESO PR Photo 34a/06 ESO PR Photo 34a/06 The Field around Baade's Window The Milky Way is a spiral galaxy, having pinwheel-shaped arms of gas, dust, and stars lying in a flattened disc, and extending directly out from a spherical nucleus of stars in the central region. The spherical nucleus is called a bulge, because it bulges out from the disc. While the disc of our Galaxy is made up of stars of all ages, the bulge contains old stars dating from the time the galaxy formed, more than 10 billion years ago. Thus, studying the bulge allows astronomers to know more about how our Galaxy formed. To do this, an international team of astronomers [2] analysed in detail the chemical composition of 50 giant stars in four different areas of the sky towards the Galactic bulge. They made use of the FLAMES/UVES spectrograph on ESO's Very Large Telescope to obtain high-resolution spectra. The chemical composition of stars carries the signature of the enrichment processes undergone by the interstellar matter up to the moment of their formation. It depends on the previous history of star formation and can thus be used to infer whether there is a 'genetic link' between different stellar groups. In particular, comparison between the abundance of oxygen and iron in stars is very illustrative. Oxygen is predominantly produced in

  16. The severity of retinal pathology in homozygous Crb1rd8/rd8 mice is dependent on additional genetic factors.

    PubMed

    Luhmann, Ulrich F O; Carvalho, Livia S; Holthaus, Sophia-Martha Kleine; Cowing, Jill A; Greenaway, Simon; Chu, Colin J; Herrmann, Philipp; Smith, Alexander J; Munro, Peter M G; Potter, Paul; Bainbridge, James W B; Ali, Robin R

    2015-01-01

    Understanding phenotype-genotype correlations in retinal degeneration is a major challenge. Mutations in CRB1 lead to a spectrum of autosomal recessive retinal dystrophies with variable phenotypes suggesting the influence of modifying factors. To establish the contribution of the genetic background to phenotypic variability associated with the Crb1(rd8/rd8) mutation, we compared the retinal pathology of Crb1(rd8/rd8)/J inbred mice with that of two Crb1(rd8/rd8) lines backcrossed with C57BL/6JOlaHsd mice. Topical endoscopic fundal imaging and scanning laser ophthalmoscopy fundus images of all three Crb1(rd8/rd8) lines showed a significant increase in the number of inferior retinal lesions that was strikingly variable between the lines. Optical coherence tomography, semithin, ultrastructural morphology and assessment of inflammatory and vascular marker by immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction revealed that the lesions were associated with photoreceptor death, Müller and microglia activation and telangiectasia-like vascular remodelling-features that were stable in the inbred, variable in the second, but virtually absent in the third Crb1(rd8/rd8) line, even at 12 months of age. This suggests that the Crb1(rd8/rd8) mutation is necessary, but not sufficient for the development of these degenerative features. By whole-genome SNP analysis of the genotype-phenotype correlation, a candidate region on chromosome 15 was identified. This may carry one or more genetic modifiers for the manifestation of the retinal pathology associated with mutations in Crb1. This study also provides insight into the nature of the retinal vascular lesions that likely represent a clinical correlate for the formation of retinal telangiectasia or Coats-like vasculopathy in patients with CRB1 mutations that are thought to depend on such genetic modifiers.

  17. Medical Genetics and the First Studies of the Genetics of Populations in Mexico.

    PubMed

    Barahona, Ana

    2016-09-01

    Following World War II (WWII), there was a new emphasis within genetics on studying the genetic composition of populations. This probably had a dual source in the growing strength of evolutionary biology and the new international interest in understanding the effects of radiation on human populations, following the atomic bombings in Japan. These global concerns were shared by Mexican physicians. Indeed, Mexico was one of the leading centers of this trend in human genetics. Three leading players in this story were Mario Salazar Mallén, Adolfo Karl, and Rubén Lisker. Their trajectories and the international networks in human genetics that were established after WWII, paved the way for the establishment of medical and population genetics in Mexico. Salazar Mallén's studies on the distribution and characterization of ABO blood groups in indigenous populations were the starting point while Karl's studies on the distribution of abnormal hemoglobin in Mexican indigenous populations showed the relationships observed in other laboratories at the time. It was Lisker's studies, however, that were instrumental in the development of population genetics in the context of national public policies for extending health care services to the Mexican population. In particular, he conducted studies on Mexican indigenous groups contributing to the knowledge of the biological diversity of human populations according to international trends that focused on the variability of human populations in terms of genetic frequencies. From the start, however, Lisker was as committed to the reconstruction of shared languages and practices as he was to building networks of collaboration in order to guarantee the necessary groundwork for establishing the study of the genetics of human populations in Mexico. This study also allows us to place Mexican science within a global context in which connected narratives describe the interplay between global trends and national contexts. PMID:27601615

  18. Medical Genetics and the First Studies of the Genetics of Populations in Mexico.

    PubMed

    Barahona, Ana

    2016-09-01

    Following World War II (WWII), there was a new emphasis within genetics on studying the genetic composition of populations. This probably had a dual source in the growing strength of evolutionary biology and the new international interest in understanding the effects of radiation on human populations, following the atomic bombings in Japan. These global concerns were shared by Mexican physicians. Indeed, Mexico was one of the leading centers of this trend in human genetics. Three leading players in this story were Mario Salazar Mallén, Adolfo Karl, and Rubén Lisker. Their trajectories and the international networks in human genetics that were established after WWII, paved the way for the establishment of medical and population genetics in Mexico. Salazar Mallén's studies on the distribution and characterization of ABO blood groups in indigenous populations were the starting point while Karl's studies on the distribution of abnormal hemoglobin in Mexican indigenous populations showed the relationships observed in other laboratories at the time. It was Lisker's studies, however, that were instrumental in the development of population genetics in the context of national public policies for extending health care services to the Mexican population. In particular, he conducted studies on Mexican indigenous groups contributing to the knowledge of the biological diversity of human populations according to international trends that focused on the variability of human populations in terms of genetic frequencies. From the start, however, Lisker was as committed to the reconstruction of shared languages and practices as he was to building networks of collaboration in order to guarantee the necessary groundwork for establishing the study of the genetics of human populations in Mexico. This study also allows us to place Mexican science within a global context in which connected narratives describe the interplay between global trends and national contexts.

  19. Health studies indicate MTBE is safe gasoline additive

    SciTech Connect

    Anderson, E.V.

    1993-09-01

    Implementation of the oxygenated fuels program by EPA in 39 metropolitan areas, including Fairbanks and Anchorage, Alaska, in the winter of 1992, encountered some unexpected difficulties. Complaints of headaches, dizziness, nausea, and irritated eyes started in Fairbanks, jumped to Anchorage, and popped up in various locations in the lower 48 states. The suspected culprit behind these complaints was the main additive for oxygenation of gasoline is methyl tert-butyl ether (MTBE). A test program, hastily organized in response to these complaints, has indicated that MTBE is a safe gasoline additive. However, official certification of the safety of MTBE is still awaited.

  20. Genetic Counseling of Adults with Williams Syndrome: A First Study

    PubMed Central

    Farwig, Katrina; Harmon, Amanda G.; Fontana, Kristina M.; Mervis, Carolyn B.; Morris, Colleen A.

    2010-01-01

    We report on a study of genetic counseling to 43 adults with Williams syndrome (WS). Participants were initially asked what they knew about how WS occurs. Genetic counseling was provided with a focus on the basic genetics of WS, recurrence risk, and on participants’ attitudes toward socio-cultural topics. Forty nine % indicated they would be okay or happy if their baby had WS, 44% said they would be sad or upset, and 5% were unsure. The sad/upset group was significantly older than the okay/happy group and a significantly higher proportion of the former group indicated they did not plan to have children. During the post counseling session participants were questioned to determine if they recalled the facts previously presented. Eighy one % correctly gave the odds that their child would have WS. Fifty three % considered the 50-50 odds to be a high chance. After genetic counseling, 61% were able to state something that had been taught, and 88% indicated they would want to test their baby for WS before birth. Ninety eight% would recommend genetic counseling to others. Findings indicate that based on the type of genetic counseling provided in this study, the majority of individuals with WS—a genetic disorder associated with intellectual disability but with relative strengths in (concrete) language and in verbal rote memory—are able to learn simple facts about the genetics of WS and are eager to respond to socio-cultural questions regarding topics typically included in genetic counseling sessions. PMID:20425790

  1. Genetic susceptibility to male infertility: news from genome-wide association studies.

    PubMed

    Aston, K I

    2014-05-01

    A thorough understanding of the genetic basis of male infertility has eluded researchers in spite of significant efforts to identify novel genetic causes of the disease, particularly over the past decade. Approximately half of male factor infertility cases have no known cause; however, it is likely that the majority of idiopathic male factor infertility cases have some unidentified genetic basis. Well-established genetic causes of male infertility are limited to Y chromosome microdeletions and Klinefelter's syndrome, together accounting for 10-20% of cases of severe spermatogenic failure. In addition to these, several genetic polymorphisms have been demonstrated to be significantly associated with male infertility. The discovery of new genetic associations with male infertility has been hampered by two primary factors. First, most studies are underpowered because of insufficient sample size and ethnic and phenotypic heterogeneity. Second, most studies evaluate a single gene, an approach that is very inefficient in the context of male infertility, considering that many hundreds of genes are involved in the process of testicular development and spermatogenesis. Significant recent advances in microarray and next-generation sequencing technologies have enabled the application of whole-genome approaches to the study of male infertility. We recently performed a pilot genome-wide association study (GWAS) for severe spermatogenic failure, and several additional male infertility GWAS have since been published. More recently, genomic microarray tools have been applied to the association of copy number variants with male infertility. These studies are beginning to shed additional light on the genetic architecture of male infertility, and whole-genome studies have proven effective in identifying novel genetic causes of the disease. This review will discuss some of the recent findings of these whole-genome studies as well as future directions for this research that will likely

  2. Genetically modified mouse models in studies of luteinising hormone action.

    PubMed

    Huhtaniemi, Ilpo; Ahtiainen, Petteri; Pakarainen, Tomi; Rulli, Susana B; Zhang, Fu-Ping; Poutanen, Matti

    2006-06-27

    Numerous genetically modified mouse models have recently been developed for the study of the pituitary-gonadal interactions. They include spontaneous or engineered knockouts (KO) of the gonadotrophin-releasing hormone (GnRH) and its receptor, the gonadotrophin common-alpha(Calpha), luteinising hormone (LH) beta and follicle-stimulating hormone (FSH) beta subunits, and the two gonadotrophin receptors (R), LHR and FSHR. In addition, there are also transgenic (TG) mice overexpressing gonadotrophin subunits and producing supraphysiological levels of these hormones. These models have offered relevant phenocopies for similar mutations in humans and to a great extent expanded our knowledge on normal and pathological functions of the hypothalamic-pituitary-gonadal (HPG) axis. The purpose of this article is to review some of our recent findings on two such mouse models, the LHR KO mouse (LuRKO), and the hCG overexpressing TG mouse (hCG+).

  3. Kinetic study of additions of dialkylmagnesium compounds to a cycloprene

    SciTech Connect

    Watkins, E.K.; Richey, H.G. Jr.

    1992-11-01

    Reaction of Et{sub 2}Mg and spiro[2.4]hept-1-ene (1) in tetahydrofuran followed by hydrolysis furnishes mainly 1-ethylspiro[2.4]heptane (3); when hydrolysis is with D{sub 2}O, {ge}98% of this (Z)-1-ethylspirol[2.4]heptane-2-d (4). Some metalation of 1 and formation of higher molecular weight products incorporating two or three molecules of 1 also take place. Formation of 3 is first order in 1 and in Et{sub 2}Mg, and at 35.47{degrees}C the rate constant is 1.2 x 10{sup -5} L M{sup -1}s{sup -1}. Under the same conditions, the rate of addition (1.5 x 10{sup -5} L M{sup -1}{sub s}{sup -1}). Under the same conditions, the rate of addition (1.5 x 10{sup -5} L mol{sup -1} {sub s}{sup -1}) of the Grignard reagent prepared from EtBr is similar. Reactions of 1 with Me{sub 2}Mg, I-Pr{sub 2}Mg, and t-Bu{sub 2}Mg. Added Fe(acac){sub 3} increases the rate of formation of 3 from reactions of 1 with either Et{sub 2}Mg or the Grignard reagent prepared from EtBr, but additional products also are formed. 55 refs., 2 tabs.

  4. Genetic and Environmental Influences on Disordered Eating: An Adoption Study

    PubMed Central

    Klump, Kelly L.; Suisman, Jessica L.; Burt, S. Alexandra; McGue, Matt; Iacono, William G.

    2009-01-01

    Twin studies indicate significant genetic, but little shared environmental, influences on eating disorders. However, critics argue that study limitations constrain the conclusions that can be drawn. Adoption studies avoid many of these limitations, but to date, no adoption studies of eating pathology have been conducted. The current study was the first adoption study to examine genetic/environmental effects for disordered eating. Participants included 123 adopted and 56 biological female sibling pairs. Disordered eating (i.e., overall eating pathology, body dissatisfaction, weight preoccupation, binge eating) was assessed using the Minnesota Eating Behaviors Survey. Biometric model-fitting indicated significant genetic influences (59–82%) on all forms of disordered eating, with nonshared environmental factors accounting for the remaining variance. Shared environmental factors did not contribute significantly to any disordered eating symptom. Our findings bolster those from twin studies and provide critical evidence of significant genetic effects on disordered eating symptoms. PMID:19899849

  5. Genetic studies of freshwater turtle and tortoises: a review of the past 70 years

    USGS Publications Warehouse

    FitzSimmons, Nancy N.; Hart, Kristen M.

    2007-01-01

    Powerful molecular techniques have been developed over many decades for resolving genetic relationships, population genetic structure, patterns of gene flow, mating systems, and the amount of genetic diversity in animals. Genetic studies of turtles were among the earliest and the rapid application of new genetic tools and analytical techniques is still apparent in the literature on turtles. At present, of the 198 freshwater turtles and tortoises that are listed as not extinct by the IUCN Red List, 69 species worldwide are listed as endangered or critically endangered, and an additional 56 species are listed as vulnerable. Of the ca. 300 species of the freshwater turtles and tortoises in the world, ca. 42% are considered to be facing a high risk extinction, and there is a need to focus intense conservation attention on these species. This includes a need to (i) assess our current state of knowledge regarding the application of genetics to studies of freshwater turtles and tortoises and (ii) determine future research directions. Here, we review all available published studies for the past 70 years that were written in English and used genetic markers (e.g. karyotypes, allozymes, DNA loci) to better understand the biology of freshwater turtles and tortoises. We review the types of studies conducted in relation to the species studied and quantify the countries where the studies were performed. We rack the changing use of different genetic markers through time and report on studies focused on aspects of molecular evolution within turtle genomes. We address the usefulness of particular genetic markers to answer phylogenetic questions and present data comparing population genetic structure and mating systems across species. We draw specific attention to whether authors have considered issues to turtle conservation in their research or provided new insights that have been translated into recommendations for conservation management.

  6. Metabolic Profiles and Genetic Diversity of Denitrifying Communities in Activated Sludge after Addition of Methanol or Ethanol†

    PubMed Central

    Hallin, Sara; Throbäck, Ingela Noredal; Dicksved, Johan; Pell, Mikael

    2006-01-01

    External carbon sources can enhance denitrification rates and thus improve nitrogen removal in wastewater treatment plants. The effects of adding methanol and ethanol on the genetic and metabolic diversity of denitrifying communities in activated sludge were compared using a pilot-scale plant with two parallel lines. A full-scale plant receiving the same municipal wastewater, but without external carbon source addition, was the reference. Metabolic profiles obtained from potential denitrification rates with 10 electron donors showed that the denitrifying communities altered their preferences for certain compounds after supplementation with methanol or ethanol and that methanol had the greater impact. Clone libraries of nirK and nirS genes, encoding the two different nitrite reductases in denitrifiers, revealed that methanol also increased the diversity of denitrifiers of the nirS type, which indicates that denitrifiers favored by methanol were on the rise in the community. This suggests that there might be a niche differentiation between nirS and nirK genotypes during activated sludge processes. The composition of nirS genotypes also varied greatly among all samples, whereas the nirK communities were more stable. The latter was confirmed by denaturing gradient gel electrophoresis of nirK communities on all sampling occasions. Our results support earlier hypotheses that the compositions of denitrifier communities change during predenitrification processes when external carbon sources are added, although no severe effect could be observed from an operational point of view. PMID:16885297

  7. A genetic study of Wilson's disease in the United Kingdom.

    PubMed

    Coffey, Alison J; Durkie, Miranda; Hague, Stephen; McLay, Kirsten; Emmerson, Jennifer; Lo, Christine; Klaffke, Stefanie; Joyce, Christopher J; Dhawan, Anil; Hadzic, Nedim; Mieli-Vergani, Giorgina; Kirk, Richard; Elizabeth Allen, K; Nicholl, David; Wong, Siew; Griffiths, William; Smithson, Sarah; Giffin, Nicola; Taha, Ali; Connolly, Sally; Gillett, Godfrey T; Tanner, Stuart; Bonham, Jim; Sharrack, Basil; Palotie, Aarno; Rattray, Magnus; Dalton, Ann; Bandmann, Oliver

    2013-05-01

    Previous studies have failed to identify mutations in the Wilson's disease gene ATP7B in a significant number of clinically diagnosed cases. This has led to concerns about genetic heterogeneity for this condition but also suggested the presence of unusual mutational mechanisms. We now present our findings in 181 patients from the United Kingdom with clinically and biochemically confirmed Wilson's disease. A total of 116 different ATP7B mutations were detected, 32 of which are novel. The overall mutation detection frequency was 98%. The likelihood of mutations in genes other than ATP7B causing a Wilson's disease phenotype is therefore very low. We report the first cases with Wilson's disease due to segmental uniparental isodisomy as well as three patients with three ATP7B mutations and three families with Wilson's disease in two consecutive generations. We determined the genetic prevalence of Wilson's disease in the United Kingdom by sequencing the entire coding region and adjacent splice sites of ATP7B in 1000 control subjects. The frequency of all single nucleotide variants with in silico evidence of pathogenicity (Class 1 variant) was 0.056 or 0.040 if only those single nucleotide variants that had previously been reported as mutations in patients with Wilson's disease were included in the analysis (Class 2 variant). The frequency of heterozygote, putative or definite disease-associated ATP7B mutations was therefore considerably higher than the previously reported occurrence of 1:90 (or 0.011) for heterozygote ATP7B mutation carriers in the general population (P < 2.2 × 10(-16) for Class 1 variants or P < 5 × 10(-11) for Class 2 variants only). Subsequent exclusion of four Class 2 variants without additional in silico evidence of pathogenicity led to a further reduction of the mutation frequency to 0.024. Using this most conservative approach, the calculated frequency of individuals predicted to carry two mutant pathogenic ATP7B alleles is 1:7026 and thus still

  8. From genetic studies to precision medicine in alcohol dependence.

    PubMed

    Sun, Yan; Zhang, Yan; Wang, Fan; Sun, Yankun; Shi, Jie; Lu, Lin

    2016-04-01

    Genetic factors contribute to more than 50% of the variation in the vulnerability to alcohol dependence (AD). Although significant advances have been made in medications for AD, these medications do not work for all people. Precise tailoring of medicinal strategies for individual alcoholic patients is needed to achieve optimal outcomes. This review updates the most promising information on genetic variants in AD, which may be useful for improving diagnostic, therapeutic, and monitoring strategies. We describe genetic candidates of various neurotransmitter and enzyme systems. In addition to biological and allelic associations with AD, genetic effects on AD-related phenotypes and treatment responses have also been described. Gene-gene and gene-environment interactions have been considered. Potential applications of genomewide and epigenetic approaches for identifying genetic biomarkers of AD have been discussed. Overall, the application of genetic findings in precision medicine for AD will likely involve an integrated approach that distinguishes effect sizes of specific genetic predictors with regard to sex, pharmacotherapy, ethnicity, and AD-related aspects and considers gene-gene and gene-environment interactions. Our work may pave the way toward more precise treatment for AD that could ultimately improve clinical management and interventions. PMID:26580132

  9. Public culture and public understanding of genetics: a focus group study.

    PubMed

    Bates, Benjamin R

    2005-01-01

    As the role of genetic science in everyday life has grown, policymakers have become concerned about Americans' understandings of this science. Much effort has been devoted to formal schooling, but less attention has been paid to the role of public culture in shaping public understanding of genetics. Research into public cultural messages about genetics has claimed that the public is likely to adopt problematic accounts, but few studies have explored the public's articulation of these messages. This study is based on 25 focus groups convened to explore the lay public's understanding of genetics. The study found that the public processed a greater variety of messages than assumed by previous researchers, including documentaries, non-science-fiction films, and popular television in addition to previous researchers' focus on science fiction and news media. The study also found that the public does not process the messages through the linear, transmission model assumed by previous research. The public processes messages about genetics complexly and critically. On the basis of these findings, the study suggests that researchers should include a greater variety of texts about genetics in their research and attend more fully to audience processing in addition to content analyses of these texts. PMID:15822248

  10. Additive transgene expression and genetic introgression in multiple green-fluorescent protein transgenic crop x weed hybrid generations.

    PubMed

    Halfhill, M D; Millwood, R J; Weissinger, A K; Warwick, S I; Stewart, C N

    2003-11-01

    The level of transgene expression in crop x weed hybrids and the degree to which crop-specific genes are integrated into hybrid populations are important factors in assessing the potential ecological and agricultural risks of gene flow associated with genetic engineering. The average transgene zygosity and genetic structure of transgenic hybrid populations change with the progression of generations, and the green fluorescent protein (GFP) transgene is an ideal marker to quantify transgene expression in advancing populations. The homozygous T(1) single-locus insert GFP/ Bacillus thuringiensis (Bt) transgenic canola ( Brassica napus, cv Westar) with two copies of the transgene fluoresced twice as much as hemizygous individuals with only one copy of the transgene. These data indicate that the expression of the GFP gene was additive, and fluorescence could be used to determine zygosity status. Several hybrid generations (BC(1)F(1), BC(2)F(1)) were produced by backcrossing various GFP/Bt transgenic canola ( B. napus, cv Westar) and birdseed rape ( Brassica rapa) hybrid generations onto B. rapa. Intercrossed generations (BC(2)F(2) Bulk) were generated by crossing BC(2)F(1) individuals in the presence of a pollinating insect ( Musca domestica L.). The ploidy of plants in the BC(2)F(2) Bulk hybrid generation was identical to the weedy parental species, B. rapa. AFLP analysis was used to quantify the degree of B. napus introgression into multiple backcross hybrid generations with B. rapa. The F(1) hybrid generations contained 95-97% of the B. napus-specific AFLP markers, and each successive backcross generation demonstrated a reduction of markers resulting in the 15-29% presence in the BC(2)F(2) Bulk population. Average fluorescence of each successive hybrid generation was analyzed, and homozygous canola lines and hybrid populations that contained individuals homozygous for GFP (BC(2)F(2) Bulk) demonstrated significantly higher fluorescence than hemizygous hybrid

  11. Additive transgene expression and genetic introgression in multiple green-fluorescent protein transgenic crop x weed hybrid generations.

    PubMed

    Halfhill, M D; Millwood, R J; Weissinger, A K; Warwick, S I; Stewart, C N

    2003-11-01

    The level of transgene expression in crop x weed hybrids and the degree to which crop-specific genes are integrated into hybrid populations are important factors in assessing the potential ecological and agricultural risks of gene flow associated with genetic engineering. The average transgene zygosity and genetic structure of transgenic hybrid populations change with the progression of generations, and the green fluorescent protein (GFP) transgene is an ideal marker to quantify transgene expression in advancing populations. The homozygous T(1) single-locus insert GFP/ Bacillus thuringiensis (Bt) transgenic canola ( Brassica napus, cv Westar) with two copies of the transgene fluoresced twice as much as hemizygous individuals with only one copy of the transgene. These data indicate that the expression of the GFP gene was additive, and fluorescence could be used to determine zygosity status. Several hybrid generations (BC(1)F(1), BC(2)F(1)) were produced by backcrossing various GFP/Bt transgenic canola ( B. napus, cv Westar) and birdseed rape ( Brassica rapa) hybrid generations onto B. rapa. Intercrossed generations (BC(2)F(2) Bulk) were generated by crossing BC(2)F(1) individuals in the presence of a pollinating insect ( Musca domestica L.). The ploidy of plants in the BC(2)F(2) Bulk hybrid generation was identical to the weedy parental species, B. rapa. AFLP analysis was used to quantify the degree of B. napus introgression into multiple backcross hybrid generations with B. rapa. The F(1) hybrid generations contained 95-97% of the B. napus-specific AFLP markers, and each successive backcross generation demonstrated a reduction of markers resulting in the 15-29% presence in the BC(2)F(2) Bulk population. Average fluorescence of each successive hybrid generation was analyzed, and homozygous canola lines and hybrid populations that contained individuals homozygous for GFP (BC(2)F(2) Bulk) demonstrated significantly higher fluorescence than hemizygous hybrid

  12. A genetic study of male sexual orientation.

    PubMed

    Bailey, J M; Pillard, R C

    1991-12-01

    Homosexual male probands with monozygotic cotwins, dizygotic cotwins, or adoptive brothers were recruited using homophile publications. Sexual orientation of relatives was assessed either by asking relatives directly, or when this was impossible, asking the probands. Of the relatives whose sexual orientation could be rated, 52% (29/56) of monozygotic cotwins, 22% (12/54) of dizygotic cotwins, and 11% (6/57) of adoptive brothers were homosexual. Heritabilities were substantial under a wide range of assumptions about the population base rate of homosexuality and ascertainment bias. However, the rate of homosexuality among nontwin biological siblings, as reported by probands, 9.2% (13/142), was significantly lower than would be predicted by a simple genetic hypothesis and other published reports. A proband's self-reported history of childhood gender non-conformity did not predict homosexuality in relatives in any of the three subsamples. Thus, childhood gender nonconformity does not appear to be an indicator of genetic loading for homosexuality. Cotwins from concordant monozygotic pairs were very similar for childhood gender nonconformity.

  13. Confounding and heterogeneity in genetic association studies with admixed populations.

    PubMed

    Liu, Jinghua; Lewinger, Juan Pablo; Gilliland, Frank D; Gauderman, W James; Conti, David V

    2013-02-15

    Association studies among admixed populations pose many challenges including confounding of genetic effects due to population substructure and heterogeneity due to different patterns of linkage disequilibrium (LD). We use simulations to investigate controlling for confounding by indicators of global ancestry and the impact of including a covariate for local ancestry. In addition, we investigate the use of an interaction term between a single-nucleotide polymorphism (SNP) and local ancestry to capture heterogeneity in SNP effects. Although adjustment for global ancestry can control for confounding, additional adjustment for local ancestry may increase power when the induced admixture LD is in the opposite direction as the LD in the ancestral population. However, if the induced LD is in the same direction, there is the potential for reduced power because of overadjustment. Furthermore, the inclusion of a SNP by local ancestry interaction term can increase power when there is substantial differential LD between ancestry populations. We examine these approaches in genome-wide data using the University of Southern California's Children's Health Study investigating asthma risk. The analysis highlights rs10519951 (P = 8.5 × 10(-7)), a SNP lacking any evidence of association from a conventional analysis (P = 0.5).

  14. Autism and genetics: Clinical approach and association study with two markers of HRAS gene

    SciTech Connect

    Herault, J.; Petit, E.; Cherpi, C.

    1995-08-14

    Twin studies and familial aggregation studies indicate that genetic factors could play a role in infantile autism. In an earlier study, we identified a possible positive association between autism and a c-Harvey-ras (HRAS) oncogene marker at the 3{prime} end of the coding region. In an attempt to confirm this finding, we studied a larger population, well-characterized clinically and genetically. We report a positive association between autism and two HRAS markers, the 3{prime} marker used in the initial study and an additional marker in exon 1. 46 refs., 1 fig., 2 tabs.

  15. NMR relaxometry study of plaster mortar with polymer additives

    SciTech Connect

    Jumate, E.; Manea, D.; Moldovan, D.; Fechete, R.

    2013-11-13

    The cement mixed with water forms a plastic paste or slurry which stiffness in time and finally hardens into a resistant stone. The addition of sand aggregates, polymers (Walocel) and/or calcium carbonate will modify dramatically the final mortar mechanic and thermal properties. The hydration processes can be observed using the 1D NMR measurements of transverse T{sub 2} relaxation times distributions analysed by a Laplace inversion algorithm. These distributions were obtained for mortar pasta measured at 2 hours after preparation then at 3, 7 and 28 days after preparation. Multiple components are identified in the T{sub 2} distributions. These can be associated with the proton bounded chemical or physical to the mortar minerals characterized by a short T{sub 2} relaxation time and to water protons in pores with three different pore sizes as observed from SEM images. The evaporation process is faster in the first hours after preparation, while the mortar hydration (bonding of water molecules to mortar minerals) can be still observed after days or months from preparation. Finally, the mechanic resistance was correlated with the transverse T{sub 2} relaxation rates corresponding to the bound water.

  16. [A study on origin of genetic ethics problem and countermeasure].

    PubMed

    Cheng, Yan-Ping

    2008-03-01

    The genetic ethical problem is one of problems which are the most disputable or difficult to resolve perfectly in the fields of life science. In these years the research for the problems is being concentrated on the types of genetic ethical problem and the ways to resolve them. But the systematic research for origin of genetic ethical problem is rare to be known. Thus it seems to be short of theoretical support to bring forward corresponding countermeasure. In this paper we focus on the evolving germ of genetic ethical problem and its evolving rule from the twofold views of human biological evolution and cultural evolution. A human being is a double offspring with biological evolution and cultural evolution . And he is a species which has both biological and cultural attribute on the earth. Through comparing and studying human biological evolution , cultural evolution, and characteristics of both biological attribute and cultural attribute, we bring forward a viewpoint that all ethical problems originate from a conflict originating from interplay of human biological evolution and cultural evolution. We intend to seek for the gist of theory and practice in order to research for genetic ethical problem and put forward some corresponding countermeasures. At the same time we'll advance a series of corresponding countermeasures of genetic ethical problem. The final aim in the paper is that not only some of our opinions will be admitted, but also through learning and understanding genetic ethical problem and its origin, the decision-makers and investigators in genetics field will be promoted to have more sense of fate and responsibility , so that the average public are able to misunderstand less and understand more for studying and genetics applying. We all work hard for genetics career to make it in healthy and continuing development and give a lot of happiness to human beings.

  17. Additive genetic variation in resistance of Nile tilapia (Oreochromis niloticus) to Streptococcus iniae and S. agalactiae capsular type Ib: is genetic resistance correlated?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Streptococcus (S.) iniae and S. agalactiae are both economically important Gram positive bacterial pathogens affecting the globally farmed tilapia (Oreochromis spp.). Historically control of these bacteria in tilapia culture has included biosecurity, therapeutants and vaccination strategies. Genet...

  18. Genetic studies of Unverricht-Luendborg disease

    SciTech Connect

    Lafreniere, R.G.; Dube, M.P.; Rouleau, G.A.

    1994-09-01

    Unverricht-Luendborg disease (ULD) is a progressive myoclonus epilepsy with an age of onset between 6 and 13 years, myoclonic jerks that progressively worsen, and mental deterioration. ULD shows an autosomal recessive mode of inheritance. The ULD gene has been genetically linked to 21q22.3, and more recently estimated to lie within 0.3 cM of the markers PFKL, D21S25, and D21S154, based on linkage disequilibrium. We have previously identified eight families affected with ULD and shown linkage to 21q22.3. In our efforts to identify the metabolic basis of the disease, we have identified several other families with ULD and are testing them for linkage to 21q22.3 We are also constructing a cosmid and YAC contig of the candidate EPM1 region in 21q22.3 and are in the process of identifying candidate genes therefrom.

  19. [The application of genetic risk score in genetic studies of complex human diseases].

    PubMed

    Dayan, Niu; Weili, Yan

    2015-12-01

    Complex diseases such as cardiovascular disease, type 2 diabetes, essential hypertension, asthma, obesity and cancer have spread across the globe and become the predominant cause of death. There are growing concerns over the role of genetic susceptibility in pathogenesis of complex diseases. However, the related susceptibility genes and sequence variations are still unknown. To elucidate the genetic basis of complex diseases, researchers have identified a large number of genetic variants associated with complex diseases through genome-wide association studies (GWAS) and candidate gene studies recently. The identification of these causal and/or associated variants promotes the development of approaches for complex diseases prediction and prevention. Genetic risk score (GRS), an emerging method for exploring correlation between single nucleotide polymorphisms (SNPs) and clinical phenotypes of complex diseases, integrates weak effects of multiple SNPs and dramatically enhances predictability of complex diseases by gene polymorphisms. This method has been applied successfully in genetic studies of many complex diseases. Here we focus on the introduction of the computational methods and evaluation criteria of GRS, enumerate a series of achievements through GRS application, discuss some limitations during application, and finally prospect the future of GRS.

  20. Incorporating Hardy-Weinberg Equilibrium Law to Enhance the Association Strength for Ordinal Trait Genetic Study.

    PubMed

    Zhang, Wei; Li, Qizhai

    2016-03-01

    The conventional method to examine whether genetic variants are associated with the ordinal traits is the proportional odds model. Such analyses are often conducted by assuming an additive genetic mode of inheritance. However, how the genetic variants influence the risk of occurrence of a disease is impossible to know in practice. Using an improper model might result in a low-power test, thus it reduces the probability of detecting the deleterious genetic markers. To address these concerns, we propose a two-phase procedure (TPP) for ordinal trait genetic studies. In the first phase, we used a linear combination to weight the Hardy-Weinberg equilibrium tests in case groups and formed an omnibus test to classify the genetic models. Then based on the chosen model, the corresponding score test was used to identify the associations. To control the false positive rate, we derived the joint distribution of the test used for selecting the genetic model and that used for identifying the associations. We also obtained the closed forms of two other robust tests, MAX3 and CHI2. Extensive computer simulations were carried out and the results showed that the true selection rates of genetic models are satisfactory and the proposed TPP is more robust than MAX3 and CHI2. Finally, we demonstrated the advantage of our proposed method by applying it to analyse the antibody reactivity to cyclic citrullinated peptides data.

  1. Incorporating Hardy-Weinberg Equilibrium Law to Enhance the Association Strength for Ordinal Trait Genetic Study.

    PubMed

    Zhang, Wei; Li, Qizhai

    2016-03-01

    The conventional method to examine whether genetic variants are associated with the ordinal traits is the proportional odds model. Such analyses are often conducted by assuming an additive genetic mode of inheritance. However, how the genetic variants influence the risk of occurrence of a disease is impossible to know in practice. Using an improper model might result in a low-power test, thus it reduces the probability of detecting the deleterious genetic markers. To address these concerns, we propose a two-phase procedure (TPP) for ordinal trait genetic studies. In the first phase, we used a linear combination to weight the Hardy-Weinberg equilibrium tests in case groups and formed an omnibus test to classify the genetic models. Then based on the chosen model, the corresponding score test was used to identify the associations. To control the false positive rate, we derived the joint distribution of the test used for selecting the genetic model and that used for identifying the associations. We also obtained the closed forms of two other robust tests, MAX3 and CHI2. Extensive computer simulations were carried out and the results showed that the true selection rates of genetic models are satisfactory and the proposed TPP is more robust than MAX3 and CHI2. Finally, we demonstrated the advantage of our proposed method by applying it to analyse the antibody reactivity to cyclic citrullinated peptides data. PMID:26626859

  2. Genetic Association Studies in Lumbar Disc Degeneration: A Systematic Review

    PubMed Central

    Eskola, Pasi J.; Lemmelä, Susanna; Kjaer, Per; Solovieva, Svetlana; Männikkö, Minna; Tommerup, Niels; Lind-Thomsen, Allan; Husgafvel-Pursiainen, Kirsti; Cheung, Kenneth M. C.; Chan, Danny

    2012-01-01

    Objective Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans. Methods A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology Network for information published between 1990–2011 addressing genes and lumbar disc degeneration. Two investigators independently identified studies to determine inclusion, after which they performed data extraction and analysis. The level of cumulative genetic association evidence was analyzed according to The HuGENet Working Group guidelines. Results Fifty-two studies were included for review. Forty-eight studies reported at least one positive association between a genetic marker and lumbar disc degeneration. The phenotype definition of lumbar disc degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with a weak level of evidence. The level of evidence was moderate for ASPN (D-repeat), COL11A1 (rs1676486), GDF5 (rs143383), SKT (rs16924573), THBS2 (rs9406328) and MMP9 (rs17576). Conclusions Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Clear definition of lumbar disc degeneration phenotypes and large population-based cohorts are needed. An international consortium is needed to standardize genetic association studies in relation to disc degeneration. PMID:23185509

  3. A behavioral genetic study of the overlap between personality and parenting.

    PubMed

    Spinath, Frank M; O'Connor, Thomas G

    2003-10-01

    The current study had three aims. The first was to examine the covariation between personality of parents and parenting behaviors. The second aim was to examine the genetic and environmental influences on parenting behaviors. The third aim was to examine the extent to which the association between personality and parenting was mediated by genetic and environmental factors. Personality (Five Factor Model, NEO-FFI) and parenting data were collected as part of a larger German study of 300 adult twin pairs (GOSAT). The current paper analyzes data on a subset of the 300 twin pairs from the GOSAT sample who were concordant for having children (n=98 pairs or 196 individuals). Results indicated modest overlap between personality and parenting. In addition, univariate behavioral genetic analyses indicated moderate genetic influence on select parenting dimensions. Results also indicated that the moderate phenotypic covariation between personality and parenting was attributed largely to nongenetic factors. Implications of the findings for research on parenting and personality are considered.

  4. Additional EIPC Study Analysis: Interim Report on High Priority Topics

    SciTech Connect

    Hadley, Stanton W

    2013-11-01

    Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations were developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 13 topics was developed for further analysis; this paper discusses the first five.

  5. Additional studies for the spectrophotometric measurement of iodine in water

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Previous work in iodine spectroscopy is briefly reviewed. Continued studies of the direct spectrophotometric determination of aqueous iodine complexed with potassium iodide show that free iodine is optimally determined at the isosbestic point for these solutions. The effects on iodine determinations of turbidity and chemical substances (in trace amounts) is discussed and illustrated. At the levels tested, iodine measurements are not significantly altered by such substances. A preliminary design for an on-line, automated iodine monitor with eventual capability of operating also as a controller was analyzed and developed in detail with respect single beam colorimeter operating at two wavelengths (using a rotating filter wheel). A flow-through sample cell allows the instrument to operate continuously, except for momentary stop flow when measurements are made. The timed automatic cycling of the system may be interrupted whenever desired, for manual operation. An analog output signal permits controlling an iodine generator.

  6. A systematic study of genetic algorithms with genotype editing

    SciTech Connect

    Huang, C. F.; Rocha, L. M.

    2004-01-01

    This paper presents our systematic study on an RNA-editing computational model of Genetic Algorithms (GA). This model is constructed based on several genetic editing characteristics that are gleaned from the RNA editing system as observed in several organisms. We have expanded the traditional Genetic Algorithm with artificial editing mechanisms as proposed by [15]. The incorporation of editing mechanisms provides a means for artificial agents with genetic descriptions to gain greater phenotypic plasticity, which may be environmentally regulated. The systematic study of this RNA-editing model has shed some light into the evolutionary implications of RNA editing and how to select proper RNA editors for design of more robust GAS. The results will also show promising applications to complex real-world problems. We expect that the framework proposed will both facilitate determining the evolutionary role of RNA editing in biology, and advance the current state of research in Evolutionary Computation.

  7. Genetically engineered humanized mouse models for preclinical antibody studies.

    PubMed

    Proetzel, Gabriele; Wiles, Michael V; Roopenian, Derry C

    2014-04-01

    The use of genetic engineering has vastly improved our capabilities to create animal models relevant in preclinical research. With the recent advances in gene-editing technologies, it is now possible to very rapidly create highly tunable mouse models as needs arise. Here, we provide an overview of genetic engineering methods, as well as the development of humanized neonatal Fc receptor (FcRn) models and their use for monoclonal antibody in vivo studies.

  8. Molecular Genetic Strategies in the Study of Corticohippocampal Circuits.

    PubMed

    Angelakos, Christopher C; Abel, Ted

    2015-07-01

    The first reproductively viable genetically modified mice were created in 1982 by Richard Palmiter and Ralph Brinster (Palmiter RD, Brinster RL, Hammer RE, Trumbauer ME, Rosenfeld MG, Birnberg NC, Evans RM. 1982. Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature 300: 611-615). In the subsequent 30 plus years, numerous ground-breaking technical advancements in genetic manipulation have paved the way for improved spatially and temporally targeted research. Molecular genetic studies have been especially useful for probing the molecules and circuits underlying how organisms learn and remember—one of the most interesting and intensively investigated questions in neuroscience research. Here, we discuss selected genetic tools, focusing on corticohippocampal circuits and their implications for understanding learning and memory. PMID:26134320

  9. Genetically Engineered Mouse Models for Studying Inflammatory Bowel Disease

    PubMed Central

    Mizoguchi, Atsushi; Takeuchi, Takahito; Himuro, Hidetomo; Okada, Toshiyuki; Mizoguchi, Emiko

    2015-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that is mediated by very complex mechanisms controlled by genetic, immune, and environmental factors. More than 74 kinds of genetically engineered mouse strains have been established since 1993 for studying IBD. Although mouse models cannot fully reflect human IBD, they have provided significant contributions for not only understanding the mechanism, but also developing new therapeutic means for IBD. Indeed, 20 kinds of genetically engineered mouse models carry the susceptibility genes identified in human IBD, and the functions of some other IBD susceptibility genes have also been dissected out using mouse models. Cutting-edge technologies such as cell-specific and inducible knockout systems, which were recently employed to mouse IBD models, have further enhanced the ability of investigators to provide important and unexpected rationales for developing new therapeutic strategies for IBD. In this review article, we briefly introduce 74 kinds of genetically engineered mouse models that spontaneously develop intestinal inflammation. PMID:26387641

  10. Genetic studies among endogamous groups of Saraswats in Western India.

    PubMed

    Bhatia, H M; Shanbhag, S R; Baxi, A J; Bapat, J; Sathe, M S; Sharma, R S; Kabeer, H; Bharucha, Z S; Surlacar, L

    1976-01-01

    Three groups of Saraswat Brahmans in Western India and a group of Goan Catholics ethnologically related to Saraswats were studied for various genetic markers. Saraswats have higher A than B with an Rh(D)-negative incidence ranging from 10 to 17%. All the groups have low incidence of G-6-PD deficiency (up to 1%). Incidence of thalassaemia trait ranges from 1 to 6%. Gm(1) was present in 85-87%. Intergroup differences suggest genetic closeness between the various groups with genetic distance ranging from 0.8 to 1.5. Genetic relationship between Goan Catholics and Chitrapur Saraswats confirms the ethnological and historical evidence of relationship between the two groups.

  11. Multivariate analysis in a genetic divergence study of Psidium guajava.

    PubMed

    Nogueira, A M; Ferreira, M F S; Guilhen, J H S; Ferreira, A

    2014-01-01

    The family Myrtaceae is widespread in the Atlantic Forest and is well-represented in the Espírito Santo State in Brazil. In the genus Psidium of this family, guava (Psidium guajava L.) is the most economically important species. Guava is widely cultivated in tropical and subtropical countries; however, the widespread cultivation of only a small number of guava tree cultivars may cause the genetic vulnerability of this crop, making the search for promising genotypes in natural populations important for breeding programs and conservation. In this study, the genetic diversity of 66 guava trees sampled in the southern region of Espírito Santo and in Caparaó, MG, Brazil were evaluated. A total of 28 morphological descriptors (11 quantitative and 17 multicategorical) and 18 microsatellite markers were used. Principal component, discriminant and cluster analyses, descriptive analyses, and genetic diversity analyses using simple sequence repeats were performed. Discrimination of accessions using molecular markers resulted in clustering of genotypes of the same origin, which was not observed using morphological data. Genetic diversity was detected between and within the localities evaluated, regardless of the methodology used. Genetic differentiation among the populations using morphological and molecular data indicated the importance of the study area for species conservation, genetic erosion estimation, and exploitation in breeding programs. PMID:25526187

  12. Multivariate analysis in a genetic divergence study of Psidium guajava.

    PubMed

    Nogueira, A M; Ferreira, M F S; Guilhen, J H S; Ferreira, A

    2014-12-18

    The family Myrtaceae is widespread in the Atlantic Forest and is well-represented in the Espírito Santo State in Brazil. In the genus Psidium of this family, guava (Psidium guajava L.) is the most economically important species. Guava is widely cultivated in tropical and subtropical countries; however, the widespread cultivation of only a small number of guava tree cultivars may cause the genetic vulnerability of this crop, making the search for promising genotypes in natural populations important for breeding programs and conservation. In this study, the genetic diversity of 66 guava trees sampled in the southern region of Espírito Santo and in Caparaó, MG, Brazil were evaluated. A total of 28 morphological descriptors (11 quantitative and 17 multicategorical) and 18 microsatellite markers were used. Principal component, discriminant and cluster analyses, descriptive analyses, and genetic diversity analyses using simple sequence repeats were performed. Discrimination of accessions using molecular markers resulted in clustering of genotypes of the same origin, which was not observed using morphological data. Genetic diversity was detected between and within the localities evaluated, regardless of the methodology used. Genetic differentiation among the populations using morphological and molecular data indicated the importance of the study area for species conservation, genetic erosion estimation, and exploitation in breeding programs.

  13. A comparative phylogenetic study of genetics and folk music.

    PubMed

    Pamjav, Horolma; Juhász, Zoltán; Zalán, Andrea; Németh, Endre; Damdin, Bayarlkhagva

    2012-04-01

    Computer-aided comparison of folk music from different nations is one of the newest research areas. We were intrigued to have identified some important similarities between phylogenetic studies and modern folk music. First of all, both of them use similar concepts and representation tools such as multidimensional scaling for modelling relationship between populations. This gave us the idea to investigate whether these connections are merely accidental or if they mirror population migrations from the past. We raised the question; does the complex structure of musical connections display a clear picture and can this system be interpreted by the genetic analysis? This study is the first to systematically investigate the incidental genetic background of the folk music context between different populations. Paternal (42 populations) and maternal lineages (56 populations) were compared based on Fst genetic distances of the Y chromosomal and mtDNA haplogroup frequencies. To test this hypothesis, the corresponding musical cultures were also compared using an automatic overlap analysis of parallel melody styles for 31 Eurasian nations. We found that close musical relations of populations indicate close genetic distances (<0.05) with a probability of 82%. It was observed that there is a significant correlation between population genetics and folk music; maternal lineages have a more important role in folk music traditions than paternal lineages. Furthermore, the combination of these disciplines establishing a new interdisciplinary research field of "music-genetics" can be an efficient tool to get a more comprehensive picture on the complex behaviour of populations in prehistoric time.

  14. Genetic Counseling for Indigenous Australians: an Exploratory Study from the Perspective of Genetic Health Professionals.

    PubMed

    Kowal, Emma; Gallacher, Lyndon; Macciocca, Ivan; Sahhar, Margaret

    2015-08-01

    Indigenous populations are thought to have particularly low levels of access to genetic health services, and cultural issues may be a contributing factor. This article presents the findings of the first study of genetic health service provision to Indigenous Australians. This qualitative study aimed to identify elements of culturally-competent genetic health service provision in Indigenous Australian contexts. Twelve semi-structured interviews were conducted with genetic counselors and clinical geneticists from around Australia who had delivered services to Indigenous Australians. Participants were asked to describe their experiences and identify any collective cultural needs of Indigenous clients, as well as comment on specific training and resources they had received or used. Interviews were audio-recorded and transcribed with thematic analysis conducted on the data. The findings show that participants were reluctant to generalize the needs of Indigenous peoples. Some participants asserted that Indigenous peoples have needs that differ from the general population, while others felt that there were no collective cultural needs, instead advocating an individualized approach. Being flexible and practical, taking time to build rapport, recognizing different family structures and decision-making processes, as well as socio-economic disadvantage were all identified as important factors in participants' interactions with Indigenous clients. Indigenous support workers and hospital liaison officers were seen as valuable resources for effective service provision. The implications of this study for training and practice are discussed.

  15. The Minnesota Adoption Studies: genetic differences and malleability.

    PubMed

    Scarr, S; Weinberg, R A

    1983-04-01

    In 1974 we launched 2 large adoption studies for 2 quite different purposes. The Transracial Adoption Study was designed to test the hypothesis that black and interracial children reared by white families perform on IQ and school achievement tests as well as other adoptees because they are reared in the culture of the tests and the schools. In addition, transracial families provided a sample with large numbers of adopted and natural children in the same families. Sources of individual differences among siblings could be studied without fear of possible differences between adoptive families and those with their own children. The Adolescent Adoption Study was designed to assess the cumulative impact of differences among family environments at the end of the child-rearing period. All of the children were adopted in the first year of life and averaged 18.5 years at the time of the study. A comparison sample of families with their own adolescents was also studied. Black and interracial children scored as well on IQ tests as adoptees in other studies. Individual differences among them, however, were more related to differences among their biological than adoptive parents, whether they lived together or not. Young siblings were found to be intellectually quite similar, whether genetically related or not. Adolescents' IQ test scores were similar to those of their parents and siblings only if they were biologically related. Our interpretation of these results is that younger children are more influenced by differences among their family environments than older adolescents, who are freer to seek their own niches.

  16. Consent for genetic research in the Framingham Heart Study.

    PubMed

    Levy, Daniel; Splansky, Greta Lee; Strand, Nicolle K; Atwood, Larry D; Benjamin, Emelia J; Blease, Susan; Cupples, L Adrienne; D'Agostino, Ralph B; Fox, Caroline S; Kelly-Hayes, Margaret; Koski, Greg; Larson, Martin G; Mutalik, Karen M; Oberacker, Elizabeth; O'Donnell, Christopher J; Sutherland, Patrice; Valentino, Maureen; Vasan, Ramachandran S; Wolf, Philip A; Murabito, Joanne M

    2010-05-01

    Extensive efforts have been aimed at understanding the genetic underpinnings of complex diseases that affect humans. Numerous genome-wide association studies have assessed the association of genes with human disease, including the Framingham Heart Study (FHS), which genotyped 550,000 SNPs in 9,000 participants. The success of such efforts requires high rates of consent by participants, which is dependent on ethical oversight, communications, and trust between research participants and investigators. To study this we calculated percentages of participants who consented to collection of DNA and to various uses of their genetic information in two FHS cohorts between 2002 and 2009. The data included rates of consent for providing a DNA sample, creating an immortalized cell line, conducting research on various genetic conditions including those that might be considered sensitive, and for notifying participants of clinically significant genetic findings were above 95%. Only with regard to granting permission to share DNA or genetic findings with for-profit companies was the consent rate below 95%. We concluded that the FHS has maintained high rates of retention and consent for genetic research that has provided the scientific freedom to establish collaborations and address a broad range of research questions. We speculate that our high rates of consent have been achieved by establishing frequent and open communications with participants that highlight extensive oversight procedures. Our approach to maintaining high consent rates via ethical oversight of genetic research and communication with study participants is summarized in this report and should be of help to other studies engaged in similar types of research. Published 2010 Wiley-Liss, Inc. PMID:20425830

  17. Deaf Adults' Reasons for Genetic Testing Depend on Cultural Affiliation: Results from a Prospective, Longitudinal Genetic Counseling and Testing Study

    ERIC Educational Resources Information Center

    Boudreault, Patrick; Baldwin, Erin E.; Fox, Michelle; Dutton, Loriel; Tullis, LeeElle; Linden, Joyce; Kobayashi, Yoko; Zhou, Jin; Sinsheimer, Janet S.; Sininger, Yvonne; Grody, Wayne W.; Palmer, Christina G. S.

    2010-01-01

    This article examines the relationship between cultural affiliation and deaf adults' motivations for genetic testing for deafness in the first prospective, longitudinal study to examine the impact of genetic counseling and genetic testing on deaf adults and the deaf community. Participants (n = 256), classified as affiliating with hearing, Deaf,…

  18. The expanding phenotypic spectra of kidney diseases: insights from genetic studies.

    PubMed

    Stokman, Marijn F; Renkema, Kirsten Y; Giles, Rachel H; Schaefer, Franz; Knoers, Nine V A M; van Eerde, Albertien M

    2016-08-01

    Next-generation sequencing (NGS) has led to the identification of previously unrecognized phenotypes associated with classic kidney disease genes. In addition to improving diagnostics for genetically heterogeneous diseases and enabling a faster rate of gene discovery, NGS has enabled an expansion and redefinition of nephrogenetic disease categories. Findings from these studies raise the question of whether disease diagnoses should be made on clinical grounds, on genetic evidence or a combination thereof. Here, we discuss the major kidney disease-associated genes and gene categories for which NGS has expanded the phenotypic spectrum. For example, COL4A3-5 genes, which are classically associated with Alport syndrome, are now understood to also be involved in the aetiology of focal segmental glomerulosclerosis. DGKE, which is associated with nephrotic syndrome, is also mutated in patients with atypical haemolytic uraemic syndrome. We examine how a shared genetic background between diverse clinical phenotypes can provide insight into the function of genes and novel links with essential pathophysiological mechanisms. In addition, we consider genetic and epigenetic factors that contribute to the observed phenotypic heterogeneity of kidney diseases and discuss the challenges in the interpretation of genetic data. Finally, we discuss the implications of the expanding phenotypic spectra associated with kidney disease genes for clinical practice, genetic counselling and personalized care, and present our recommendations for the use of NGS-based tests in routine nephrology practice.

  19. Complex approaches to study complex trait genetics in multiple sclerosis.

    PubMed

    Kálmán, Bernadette

    2014-09-30

    Multiple sclerosis (MS) is a complex trait disorder defined by several genes and their interactions with environmental factors. A comprehensive exploration of the susceptibility variants had not been feasible until recently when new developments in biotechnology and bioinformatics made possible sequencing of the whole human genome, cataloguing of nucleotide variants and alignments of these variants in haplotypes. Earlier observations from epidemiological, candidate gene and linkage studies provided ample evidence to support a complex genetic determination of MS. New biotechnology and bioinformatics resources have been recently applied to further successful explorations of the disease. These efforts were paralleled by more careful and reliable ascertainments of disease phenotypes, collaborations among specialized centers to generate sufficient sample size and involvement of clinician-scientists capable of working both on the clinical and scientific study sides. Data obtained from the whole genome association studies (GWAS) elevated our understanding of MS genetics to a new level by identifying an extensive list of genetic determinants. Pathway analyses of MS-associated variants provided evidence to support the immune etiology of the disease. Future research will likely explore how environmental factors interact with the genome, and contribute to the abnormal immune activation and inflammation. This review summarizes the outcomes of MS genetic explorations including those of recent GWAS, and highlights practical consequences of genetic and genomic studies by pointing out as to how the derived data facilitate further elucidation of MS pathogenesis. A better understanding of disease processes is necessary for future advancements in therapeutics and the development of disease prevention strategies.

  20. Major study commencing into genetic discrimination in Australia.

    PubMed

    Otlowski, Margaret F; Taylor, Sandra D; Barlow-Stewart, Kristine K

    2002-08-01

    This article describes a nationwide empirical study that will be undertaken during the next three years into the newly emerging phenomenon of genetic discrimination. In particular, the study aims to investigate the nature and extent of genetic discrimination in Australia across three key perspectives: consumers, third parties and the legal system. Further, the study aims to examine the social and legal implications of genetic discrimination, with a view to making recommendations for use in the Australian legal and policy context. It is anticipated that the data produced from this multifaceted investigation will assist in identifying areas where legal or other reforms are required. It will contribute significant baseline data for facilitating ongoing assessment of the nature and extent of the problem, as well as for longitudinal evaluation of the impact and effectiveness of any reforms which may be introduced in the future to address the issue. PMID:12242882

  1. Does Childhood Anxiety Evoke Maternal Control? A Genetically Informed Study

    ERIC Educational Resources Information Center

    Eley, Thalia C.; Napolitano, Maria; Lau, Jennifer Y. F.; Gregory, Alice M.

    2010-01-01

    Background: Despite theoretical and empirical support for an association between maternal control and child anxiety, few studies have examined the origins of this association. Furthermore, none use observer-ratings of maternal control within a genetically informative design. This study addressed three questions: 1) do children who experience…

  2. Functional genetic studies of the tarnished plant bug

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The tarnished plant bug (TPB), Lygus lineolaris (Palisot de Beuvois) has become a primary pest of cotton in the Mississippi Delta. To identify new techological and genetic methods to control TPB, studies have begun to focus on genes expressed by the insect. Initial studies on interference of transcr...

  3. Genetic linkage study of bipolar disorder and the serotonin transporter

    SciTech Connect

    Kelsoe, J.R.; Morison, M.; Mroczkowski-Parker, Z.; Bergesch, P.; Rapaport, M.H.; Mirow, A.L.

    1996-04-09

    The serotonin transporter (HTT) is an important candidate gene for the genetic transmission of bipolar disorder. It is the site of action of many antidepressants, and plays a key role in the regulation of serotonin neurotransmission. Many studies of affectively ill patients have found abnormalities in serotonin metabolism, and dysregulation of the transporter itself. The human serotonin transporter has been recently cloned and mapped to chromosome 17. We have identified a PstI RFLP at the HTT locus, and here report our examination of this polymorphism for possible linkage to bipolar disorder. Eighteen families were examined from three populations: the Old Order Amish, Iceland, and the general North American population. In addition to HTT, three other microsatellite markers were examined, which span an interval known to contain HTT. Linkage analyses were conducted under both dominant and recessive models, as well as both narrow (bipolar only) and broad (bipolar + recurrent unipolar) diagnostic models. Linkage could be excluded to HTT under all models examined. Linkage to the interval spanned by the microsatellites was similarly excluded under the dominant models. In two individual families, maximum lod scores of 1.02 and 0.84 were obtained at D17S798 and HTT, respectively. However, these data overall do not support the presence of a susceptibility locus for bipolar disorder near the serotonin transporter. 20 refs., 2 tabs.

  4. Why Is Studying the Genetics of Intelligence So Controversial?

    PubMed

    Tabery, James

    2015-01-01

    From the very beginning, studies of the nature and nurture of intelligence have been closely associated with an interest in intervening, and those interventions have been surrounded by controversy. The nature of those controversies has not always been the same, however. Since the mid-nineteenth century, when Francis Galton imagined a science that would assess the extent to which a trait like "genius" was due to nature or due to nurture, science and technology have changed dramatically, and so have the interventions that have been envisioned in light of those developments. A scientist today can search for particular stretches of DNA and assess whether differences in those stretches are associated with differences in a human trait of interest; a genetic counselor today can genetically test an individual (be it an embryo, fetus, newborn, child, or adult) and provide information about what that genetic result means, allowing for interventions that can range from terminating a pregnancy to prescribing chemotherapy. So when one asks a question like, "Why is studying the genetics of intelligence controversial?," it is important to realize up front that the answer will be, "It can be controversial for a variety of different reasons, and those reasons have evolved over time." The purpose of this essay is to provide a survey of the controversies that surround genetic studies of intelligence. With the survey in place, I will then draw out several lessons both for scientists who study the genetics of intelligence as well as for science studies scholars (bioethicists, philosophers, historians, sociologists) who reflect and comment on the controversies surrounding that research. PMID:26413953

  5. Why Is Studying the Genetics of Intelligence So Controversial?

    PubMed

    Tabery, James

    2015-01-01

    From the very beginning, studies of the nature and nurture of intelligence have been closely associated with an interest in intervening, and those interventions have been surrounded by controversy. The nature of those controversies has not always been the same, however. Since the mid-nineteenth century, when Francis Galton imagined a science that would assess the extent to which a trait like "genius" was due to nature or due to nurture, science and technology have changed dramatically, and so have the interventions that have been envisioned in light of those developments. A scientist today can search for particular stretches of DNA and assess whether differences in those stretches are associated with differences in a human trait of interest; a genetic counselor today can genetically test an individual (be it an embryo, fetus, newborn, child, or adult) and provide information about what that genetic result means, allowing for interventions that can range from terminating a pregnancy to prescribing chemotherapy. So when one asks a question like, "Why is studying the genetics of intelligence controversial?," it is important to realize up front that the answer will be, "It can be controversial for a variety of different reasons, and those reasons have evolved over time." The purpose of this essay is to provide a survey of the controversies that surround genetic studies of intelligence. With the survey in place, I will then draw out several lessons both for scientists who study the genetics of intelligence as well as for science studies scholars (bioethicists, philosophers, historians, sociologists) who reflect and comment on the controversies surrounding that research.

  6. Reverse Genetics System for Studying Human Rhinovirus Infections

    PubMed Central

    Lee, Wai-Ming; Wang, Wensheng; Bochkov, Yury A; Lee, Iris

    2015-01-01

    SUMMARY Human rhinovirus (HRV) contains a 7.2 Kb messenger-sense RNA genome which is the template for reproducing progeny viruses after it enters the cytoplasm of a host cell. Reverse genetics refers to the regeneration of progeny viruses from an artificial cDNA copy of the RNA genome of an RNA virus. It has been a powerful molecular genetic tool for studying HRV and other RNA viruses because the artificial DNA stage makes it practical to introduce specific mutations into the viral RNA genome. This chapter uses HRV-16 as the model virus to illustrate the strategy and the methods for constructing and cloning the artificial cDNA copy of a full-length HRV genome, identifying the infectious cDNA clone isolates, and selecting the most vigorous cDNA clone isolate to serve as the standard parental clone for future molecular genetic study of the virus. PMID:25261313

  7. The Genetic and Environmental Contributions to Internet Use and Associations With Psychopathology: A Twin Study.

    PubMed

    Long, Elizabeth C; Verhulst, Brad; Neale, Michael C; Lind, Penelope A; Hickie, Ian B; Martin, Nicholas G; Gillespie, Nathan A

    2016-02-01

    Excessive internet use has been linked to psychopathology. Therefore, understanding the genetic and environmental risks underpinning internet use and their relation to psychopathology is important. This study aims to explore the genetic and environmental etiology of internet use measures and their associations with internalizing disorders and substance use disorders. The sample included 2,059 monozygotic (MZ) and dizygotic (DZ) young adult twins from the Brisbane Longitudinal Twin Study (BLTS). Younger participants reported more frequent internet use, while women were more likely to use the internet for interpersonal communication. Familial aggregation in 'frequency of internet use' was entirely explained by additive genetic factors accounting for 41% of the variance. Familial aggregation in 'frequency of use after 11 pm', 'using the internet to contact peers', and 'using the internet primarily to access social networking sites' was attributable to varying combinations of additive genetic and shared environmental factors. In terms of psychopathology, there were no significant associations between internet use measures and major depression (MD), but there were positive significant associations between 'frequency of internet use' and 'frequency of use after 11 pm' with social phobia (SP). 'Using the internet to contact peers' was positively associated with alcohol abuse, whereas 'using the internet to contact peers' and 'using the internet primarily to access social networking sites' were negatively associated with cannabis use disorders and nicotine symptoms. Individual differences in internet use can be attributable to varying degrees of genetic and environmental risks. Despite some significant associations of small effect, variation in internet use appears mostly unrelated to psychopathology.

  8. Current status and prospects for the study of Nicotiana genomics, genetics, and nicotine biosynthesis genes.

    PubMed

    Wang, Xuewen; Bennetzen, Jeffrey L

    2015-02-01

    Nicotiana, a member of the Solanaceae family, is one of the most important research model plants, and of high agricultural and economic value worldwide. To better understand the substantial and rapid research progress with Nicotiana in recent years, its genomics, genetics, and nicotine gene studies are summarized, with useful web links. Several important genetic maps, including a high-density map of N. tabacum consisting of ~2,000 markers published in 2012, provide tools for genetics research. Four whole genome sequences are from allotetraploid species, including N. benthamiana in 2012, and three N. tabacum cultivars (TN90, K326, and BX) in 2014. Three whole genome sequences are from diploids, including progenitors N. sylvestris and N. tomentosiformis in 2013 and N. otophora in 2014. These and additional studies provide numerous insights into genome evolution after polyploidization, including changes in gene composition and transcriptome expression in N. tabacum. The major genes involved in the nicotine biosynthetic pathway have been identified and the genetic basis of the differences in nicotine levels among Nicotiana species has been revealed. In addition, other progress on chloroplast, mitochondrial, and NCBI-registered projects on Nicotiana are discussed. The challenges and prospects for genomic, genetic and application research are addressed. Hence, this review provides important resources and guidance for current and future research and application in Nicotiana.

  9. Genetic studies in pediatric ITP: outlook, feasibility and requirements

    PubMed Central

    Bergmann, Anke K.; Grace, Rachael F.; Neufeld, Ellis J.

    2010-01-01

    The genomic revolution in medicine has not escaped attention of clinicians and scientists involved in medical management and research studies of immune thrombocytopenic purpura (ITP). In principle, ITP biology and care will benefit greatly from modern methods to understand the patterns of gene expression and genetic markers associated with fundamental parameters of the disease including predictors of remission; risk factors for severity; determinants of response to various therapies; and possibly biological sub-types. However, applying modern genetics to ITP carries severe challenges: (i) achieving adequate sample sizes is a fundamental problem because ITP is rare (and in pediatric ITP, chronic cases constitute only about 1/4 of the total); (ii) familial transmission of childhood ITP is so rare that a convincing pedigree requires consideration of other immunologic or hematologic disorders; (iii) ITP is probably biologically heterogeneous, based on clinical observations, immunological studies and animal models. Here we review the advantages and disadvantages of potential genetic approaches. Sufficient information is available to set reasonable bounds on which genetic analyses of ITP are feasible, and how they are most likely to be accomplished. The highest priority is for accurate phenotypes to compare to genetic analyses. Several registries worldwide hold promise for accomplishing this goal. PMID:20309691

  10. Dioecy, more than monoecy, affects plant spatial genetic structure: the case study of Ficus

    PubMed Central

    Nazareno, Alison G; Alzate-Marin, Ana L; Pereira, Rodrigo Augusto S

    2013-01-01

    In this analysis, we attempt to understand how monoecy and dioecy drive spatial genetic structure (SGS) in plant populations. For this purpose, plants of the genus Ficus were used as a comparative model due to their particular characteristics, including high species diversity, variation in life histories, and sexual systems. One of the main issues we assessed is whether dioecious fig tree populations are more spatially genetically structured than monoecious populations. Using the Sp statistic, which allows for quantitative comparisons among different studies, we compared the extent of SGS between monoecious and dioecious Ficus species. To broaden our conclusions we used published data on an additional 27 monoecious and dioecious plant species. Furthermore, genetic diversity analyses were performed for two monoecious Ficus species using 12 microsatellite markers in order to strengthen our conclusions about SGS. Our results show that dioecy, more than monoecy, significantly contributes to SGS in plant populations. On average, the estimate of Sp was six times higher for dioecious Ficus species than monoecious Ficus species and it was two times higher in dioecious than monoecious plant species. Considering these results, we emphasize that the long-distance pollen dispersal mechanism in monoecious Ficus species seems to be the dominant factor in determining weak spatial genetic structure, high levels of genetic diversity, and lack of inbreeding. Although Ficus constitute a model species to study SGS, a more general comparison encompassing a wider range of plants is required in order to better understand how sexual systems affect genetic structure. PMID:24223285

  11. [Studies on genetic relationship of Dioscorea].

    PubMed

    Huang, Han-han; Li, Xia; Gao, Wen-yuan; Xiao, Pei-gen

    2015-09-01

    Based on the results of the morphologic studies on genus Dioscorea, the paper summarized the entire chemical constituent that isolated from this genus and analyzed it with the methods of chemotaxonomy. The rules of the chemical constituent and pharmacodynamic effects were analyzed. Seventeen species which belong to Sect. Stenophora Uline of Dioscorea contain steroidal sapogenin. Other species with different main components such as polysaccharide and tannin have have different effects. This chemotaxonomic view point will conduce to establish a phylogeny of the genus Dioscorea.

  12. PGD for cystic fibrosis patients and couples at risk of an additional genetic disorder combined with 24-chromosome aneuploidy testing.

    PubMed

    Rechitsky, Svetlana; Verlinsky, Oleg; Kuliev, Anver

    2013-05-01

    Preimplantation genetic diagnosis (PGD) for inherited disorders is presently applied for more than 300 different conditions. The most frequent PGD indication is cystic fibrosis (CF), the largest series of which is reviewed here, totalling 404 PGD cycles. This involved testing for 52 different CFTR mutations with almost half of the cases (195/404 cycles) performed for ΔF508 mutation, one-quarter (103/404 cycles) for six other frequent mutations and only a few for the remaining 45 CFTR mutations. There were 44 PGD cycles performed for 25 CF-affected homozygous or double-heterozygous CF patients (18 male and seven female partners), which involved testing simultaneously for three mutations, resulting in birth of 13 healthy CF-free children and no misdiagnosis. PGD was also performed for six couples at a combined risk of producing offspring with CF and another genetic disorder. Concomitant testing for CFTR and other mutations resulted in birth of six healthy children, free of both CF and another genetic disorder in all but one cycle. A total of 96 PGD cycles for CF were performed with simultaneous aneuploidy testing, including microarray-based 24-chromosome analysis, as a comprehensive PGD for two or more conditions in the same biopsy material.

  13. [Felines: an alternative in genetic toxicology studies?].

    PubMed

    Zamora-Perez, Ana; Gómez-Meda, Belinda C; Ramos-Ibarra, Maria L; Batista-González, Cecilia M; Luna-Aguirre, Jaime; González-Rodríguez, Andrés; Rodríguez-Avila, José L; Zúñiga-González, Guillermo M

    2008-06-01

    The micronuclei (MN) test carry out in peripheral blood is fast, simple, economic and it is used to detect genotoxic environmental agents. MN are fragments of chromosomes or complete chromosomes remaining in the cytoplasm after cell division, which increase when organisms are exposed to genotoxic agents. Therefore, species with the highest values of spontaneous micronucleated erythrocytes (MNE) are the most suitable to be potentials biomonitor of micronucleogenic agents, using a drop of blood. Nine species of Felines that present spontaneous MNE in peripheral blood are shown. From these species, the cat has been previously proven, with positive results and also lion (Panthera leo), yaguaroundi (Felis yagoaroundi), lynx (Lynx ruffus), jaguar (Panthera onca), puma (Puma concolor), tiger (Panthera tigris), ocelote (Felis padalis) and leopard (Panthera pardus) display spontaneous MNE, and with this characteristic this Family can be propose like a potential group to be used in toxicogenetic studies.

  14. Potential Genetic Risk Factors for Chronic TMD: Genetic Associations from the OPPERA Case Control Study

    PubMed Central

    Smith, Shad B.; Maixner, Dylan; Greenspan, Joel; Dubner, Ron; Fillingim, Roger; Ohrbach, Richard; Knott, Charles; Slade, Gary; Bair, Eric; Gibson, Dustin G.; Zaykin, Dmitri V.; Weir, Bruce; Maixner, William; Diatchenko, Luda

    2011-01-01

    Genetic factors play a role in the etiology of persistent pain conditions, putatively by modulating underlying processes such as nociceptive sensitivity, psychological well-being, inflammation, and autonomic response. However, to date, only a few genes have been associated with temporomandibular disorders (TMD). This study evaluated 358 genes involved in pain processes, comparing allelic frequencies between 166 cases with chronic TMD and 1442 controls enrolled in the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study cooperative agreement. To enhance statistical power, 182 TMD cases and 170 controls from a similar study were included in the analysis. Genotyping was performed using the Pain Research Panel, an Affymetrix gene chip representing 3295 single nucleotide polymorphisms, including ancestry-informative markers that were used to adjust for population stratification. Adjusted associations between genetic markers and TMD case status were evaluated using logistic regression. The OPPERA findings provided evidence supporting previously-reported associations between TMD and two genes: HTR2A and COMT. Other genes were revealed as potential new genetic risk factors for TMD, including NR3C1, CAMK4, CHRM2, IFRD1, and GRK5. While these findings need to be replicated in independent cohorts, the genes potentially represent important markers of risk for TMD and they identify potential targets for therapeutic intervention. PMID:22074755

  15. STrengthening the REporting of Genetic Association studies (STREGA) – an extension of the STROBE statement

    PubMed Central

    Little, Julian; Higgins, Julian PT; Ioannidis, John PA; Moher, David; Gagnon, France; von Elm, Erik; Khoury, Muin J; Cohen, Barbara; Davey-Smith, George; Grimshaw, Jeremy; Scheet, Paul; Gwinn, Marta; Williamson, Robin E; Zou, Guang Yong; Hutchings, Kim; Johnson, Candice Y; Tait, Valerie; Wiens, Miriam; Golding, Jean; van Duijn, Cornelia; McLaughlin, John; Paterson, Andrew; Wells, George; Fortier, Isabel; Freedman, Matthew; Zecevic, Maja; King, Richard; Infante-Rivard, Claire; Stewart, Alex; Birkett, Nick

    2009-01-01

    Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of OBservational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy–Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed, but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct or analysis. PMID:19297801

  16. The study of relatedness and genetic diversity in cranes

    USGS Publications Warehouse

    Gee, G.F.; Dessauer, H.C.; Longmire, J.; Briles, W.E.; Simon, R.C.; Wood, Don A.

    1992-01-01

    The U.S. Fish and Wildlife Service (Service) is responsible for recovery of endangered species in the wild and, when necessary, maintenance in captivity. These programs provide an immediate measure of insurance against extinction. A prerequisite inherent in all of these programs is the preservation of enough genetic diversity to maintain a viable population and to maintain the capacity of the population to respond to change. Measures of genetic diversity examine polymorphic genes that are not influenced by selection pressures. Examples of these techniques and those used to determine relatedness are discussed. Studies of genetic diversity, electrophoresis of blood proteins, relatedness, blood typing, and restriction fragment length polymorphisms which are being used by the Patuxent Wildlife Research Center are discussed in detail.

  17. Studies on the Pathophysiology and Genetic Basis of Migraine

    PubMed Central

    Gasparini, Claudia F; Sutherland, Heidi G.; Griffiths, Lyn R

    2013-01-01

    Migraine is a neurological disorder that affects the central nervous system causing painful attacks of headache. A genetic vulnerability and exposure to environmental triggers can influence the migraine phenotype. Migraine interferes in many facets of people’s daily life including employment commitments and their ability to look after their families resulting in a reduced quality of life. Identification of the biological processes that underlie this relatively common affliction has been difficult because migraine does not have any clearly identifiable pathology or structural lesion detectable by current medical technology. Theories to explain the symptoms of migraine have focused on the physiological mechanisms involved in the various phases of headache and include the vascular and neurogenic theories. In relation to migraine pathophysiology the trigeminovascular system and cortical spreading depression have also been implicated with supporting evidence from imaging studies and animal models. The objective of current research is to better understand the pathways and mechanisms involved in causing pain and headache to be able to target interventions. The genetic component of migraine has been teased apart using linkage studies and both candidate gene and genome-wide association studies, in family and case-control cohorts. Genomic regions that increase individual risk to migraine have been identified in neurological, vascular and hormonal pathways. This review discusses knowledge of the pathophysiology and genetic basis of migraine with the latest scientific evidence from genetic studies. PMID:24403849

  18. GESDB: a platform of simulation resources for genetic epidemiology studies.

    PubMed

    Yao, Po-Ju; Chung, Ren-Hua

    2016-01-01

    Computer simulations are routinely conducted to evaluate new statistical methods, to compare the properties among different methods, and to mimic the observed data in genetic epidemiology studies. Conducting simulation studies can become a complicated task as several challenges can occur, such as the selection of an appropriate simulation tool and the specification of parameters in the simulation model. Although abundant simulated data have been generated for human genetic research, currently there is no public database designed specifically as a repository for these simulated data. With the lack of such a database, for similar studies, similar simulations may have been repeated, which resulted in redundant work. Thus, we created an online platform, the Genetic Epidemiology Simulation Database (GESDB), for simulation data sharing and discussion of simulation techniques for genetic epidemiology studies. GESDB consists of a database for storing simulation scripts, simulated data and documentation from published articles as well as a discussion forum, which provides a platform for discussion of the simulated data and exchanging simulation ideas. Moreover, summary statistics such as the simulation tools that are most commonly used and datasets that are most frequently downloaded are provided. The statistics will be informative for researchers to choose an appropriate simulation tool or select a common dataset for method comparisons. GESDB can be accessed at http://gesdb.nhri.org.twDatabase URL: http://gesdb.nhri.org.tw. PMID:27242038

  19. GESDB: a platform of simulation resources for genetic epidemiology studies.

    PubMed

    Yao, Po-Ju; Chung, Ren-Hua

    2016-01-01

    Computer simulations are routinely conducted to evaluate new statistical methods, to compare the properties among different methods, and to mimic the observed data in genetic epidemiology studies. Conducting simulation studies can become a complicated task as several challenges can occur, such as the selection of an appropriate simulation tool and the specification of parameters in the simulation model. Although abundant simulated data have been generated for human genetic research, currently there is no public database designed specifically as a repository for these simulated data. With the lack of such a database, for similar studies, similar simulations may have been repeated, which resulted in redundant work. Thus, we created an online platform, the Genetic Epidemiology Simulation Database (GESDB), for simulation data sharing and discussion of simulation techniques for genetic epidemiology studies. GESDB consists of a database for storing simulation scripts, simulated data and documentation from published articles as well as a discussion forum, which provides a platform for discussion of the simulated data and exchanging simulation ideas. Moreover, summary statistics such as the simulation tools that are most commonly used and datasets that are most frequently downloaded are provided. The statistics will be informative for researchers to choose an appropriate simulation tool or select a common dataset for method comparisons. GESDB can be accessed at http://gesdb.nhri.org.twDatabase URL: http://gesdb.nhri.org.tw.

  20. GESDB: a platform of simulation resources for genetic epidemiology studies

    PubMed Central

    Yao, Po-Ju; Chung, Ren-Hua

    2016-01-01

    Computer simulations are routinely conducted to evaluate new statistical methods, to compare the properties among different methods, and to mimic the observed data in genetic epidemiology studies. Conducting simulation studies can become a complicated task as several challenges can occur, such as the selection of an appropriate simulation tool and the specification of parameters in the simulation model. Although abundant simulated data have been generated for human genetic research, currently there is no public database designed specifically as a repository for these simulated data. With the lack of such a database, for similar studies, similar simulations may have been repeated, which resulted in redundant work. Thus, we created an online platform, the Genetic Epidemiology Simulation Database (GESDB), for simulation data sharing and discussion of simulation techniques for genetic epidemiology studies. GESDB consists of a database for storing simulation scripts, simulated data and documentation from published articles as well as a discussion forum, which provides a platform for discussion of the simulated data and exchanging simulation ideas. Moreover, summary statistics such as the simulation tools that are most commonly used and datasets that are most frequently downloaded are provided. The statistics will be informative for researchers to choose an appropriate simulation tool or select a common dataset for method comparisons. GESDB can be accessed at http://gesdb.nhri.org.tw. Database URL: http://gesdb.nhri.org.tw PMID:27242038

  1. Population genetic study among the Orange Asli (Semai Senoi) of Malaysia: Malayan aborigines.

    PubMed

    Saha, N; Mak, J W; Tay, J S; Liu, Y; Tan, J A; Low, P S; Singh, M

    1995-02-01

    A population genetic study was undertaken to provide gene frequency data on the additional blood genetic markers in the Semai and to estimate the genetic relations between the Semai and their neighboring and linguistically related populations by genetic distance and principal components analyses. Altogether 10 polymorphic and 7 monomorphic blood genetic markers (plasma proteins and red cell enzymes) were studied in a group of 349 Senoi Semai from 11 aboriginal settlements (villages) in the Pahang State of western Malaysia. Both the red cell glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (PGD) loci reveal the presence of polymorphic frequencies of a nondeficient slow allele at the G6PD locus and a fast allele at the PGD locus. The Semai are characterized by high prevalences of ahaptoglobinemia and G6PD deficiency, high frequencies of HP*1, HB*E, RH*R1, ACP*C, GLO1*1, PGM1*2+, and GC*1F and corresponding low frequencies of ABO*A, HbCoSp, HB*B0, TF*D, CHI, and GC*2. Genetic distance analyses by both cluster and principal components models were performed between the Semai and 14 other populations (Malay; Javanese; Khmer; Veddah; Tamils of Malaysia, Sri Lanka, and India; Sinhalese; Oraon; Toda and Irula of India; Chinese; Japanese; Koreans) on the basis of 30 alleles at 7 polymorphic loci. A more detailed analysis using 53 alleles at 13 polymorphic loci with 10 populations was carried out. Both analyses give genetic evidence of a close relationship between the Semai and the Khmer of Cambodia. Furthermore, the Semai are more closely related to the Javanese than to their close neighbors--the Malay, Chinese, and Tamil Indians. There is no evidence for close genetic relationship between the Semai and the Veddah or other Indian tribes. The evidence fits well with the linguistic relationship of the Semai with the Mon-Khmer branch of the Austro-Asiatic language family.

  2. Genetic studies on the Cayo Santiago rhesus macaques: A review of 40 years of research.

    PubMed

    Widdig, Anja; Kessler, Matthew J; Bercovitch, Fred B; Berard, John D; Duggleby, Christine; Nürnberg, Peter; Rawlins, Richard G; Sauermann, Ulrike; Wang, Qian; Krawczak, Michael; Schmidtke, Jörg

    2016-01-01

    Genetic studies not only contribute substantially to our current understanding of the natural variation in behavior and health in many species, they also provide the basis of numerous in vivo models of human traits. Despite the many challenges posed by the high level of biological and social complexity, a long lifespan and difficult access in the field, genetic studies of primates are particularly rewarding because of the close evolutionary relatedness of these species to humans. The free-ranging rhesus macaque (Macaca mulatta) population on Cayo Santiago (CS), Puerto Rico, provides a unique resource in this respect because several of the abovementioned caveats are of either minor importance there, or lacking altogether, thereby allowing long-term genetic research in a primate population under constant surveillance since 1956. This review summarizes more than 40 years of genetic research carried out on CS, from early blood group typing and the genetic characterization of skeletal material via population-wide paternity testing with DNA fingerprints and short tandem repeats (STRs) to the analysis of the highly polymorphic DQB1 locus within the major histocompatibility complex (MHC). The results of the paternity studies also facilitated subsequent studies of male dominance and other factors influencing male reproductive success, of male reproductive skew, paternal kin bias, and mechanisms of paternal kin recognition. More recently, the CS macaques have been the subjects of functional genetic and gene expression analyses and have played an important role in behavioral and quantitative genetic studies. In addition, the CS colony has been used as a natural model for human adult-onset macular degeneration, glaucoma, and circadian rhythm disorder. Our review finishes off with a discussion of potential future directions of research on CS, including the transition from STRs to single nucleotide polymorphism (SNP) typing and whole genome sequencing. PMID:26031601

  3. A systematic molecular genetic approach to study mammalian germline development

    PubMed Central

    Abe, Kuniya; Ko, Minoru S. H.; MacGregor, Grant R.

    2011-01-01

    It is difficult to study gene expression in mammalian embryonic germ cells as PGCs constitute only a minor proportion of the mouse embryo. We have overcome this problem by using a novel combination of established molecular and transgenic approaches. A line of mice has been generated in which the cells of the germ lineage express the β-galactosidase reporter gene during embryogenesis. Using this line, germ cells have been purified to near homogeneity from embryos at discrete stages during germline development by use of a stain for β-gal activity and a fluorescence activated cell sorter. Subsequently, cDNA libraries have been constructed from each germ cell population using a modified lone-linker PCR strategy. These combined cDNA libraries represent genes expressed in PGCs during mammalian germline development. To facilitate a molecular genetic approach to studying mammalian germline development, these cDNA libraries will be pooled to form an arrayed, addressed reference embryonic germ cell cDNA library. In parallel with large-scale cDNA sequencing efforts, genes that are differentially expressed in germ cells will be identified by screening the reference library with probes generated by subtractive hybridization. Complementary DNAs identified using this approach will be analyzed by sequencing, database comparison, genomic mapping and in situ hybridization to ascertain the potential functional importance of each gene to germline development. In addition to providing a wealth of novel information regarding patterns of gene expression during mammalian germline development, these results will form the basis for future experiments to determine the function of these genes in this process. PMID:9853837

  4. Brazilian studies on the genetics of Schistosoma mansoni

    PubMed Central

    Gentile, Rosana; Oliveira, Guilherme

    2009-01-01

    The parasite Schistosoma is known to exhibit variations among species, strains and genera, such as, the levels of infectivity, pathogenicity and immunogenicity. These factors may differ among parasite populations according to the local epidemiological conditions. Diversity observed in S. mansoni from different geographical regions or within individuals of the same region can be determined by differences in the genotype of each parasite strain. However, until recently, finding adequate genetic markers to investigate infectivity or other epidemiological characteristics of a transmission area proved difficult. Several studies have been conducted to evaluate the genetic variability of S. mansoni, using different techniques. Intraspecific variability was observed in morphological characters, isoenzyme studies, mtDNA, ribosomal gene probes, RAPD and microsatellites. The sequencing of the S. mansoni genome was the most important achievement concerning genetic approaches to the study of this parasite and may improve the development of drugs, vaccines and diagnostics of schistosomiasis. The knowledge of the genetic structure of schistosome populations in relation to epidemiological data and host variability is essential for the understanding of the epidemiology of the disease and the design of control strategies. PMID:18831955

  5. Quantitative genetic analysis of cellular adhesion molecules: the Fels Longitudinal Study.

    PubMed

    Lee, Miryoung; Czerwinski, Stefan A; Choh, Audrey C; Demerath, Ellen W; Sun, Shumei S; Chumlea, Wm C; Towne, Bradford; Siervogel, Roger M

    2006-03-01

    Circulating concentrations of inflammatory markers predict cardiovascular disease (CVD) risk and are closely associated with obesity. However, little is known concerning genetic influences on serum levels of inflammatory markers. In this study, we estimated the heritability (h2) of soluble cellular adhesion molecule (sCAM) concentrations and examined the correlational architecture between different sCAMs. The study population included 234 men and 270 women aged 18-76 years, belonging to 121 families participating in the Fels Longitudinal Study. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sESEL-1) and P-selectin (sPSEL-1) were assayed using commercially available kits. A variance components-based maximum likelihood method was used to estimate the h2 of the different serum inflammatory markers while simultaneously adjusting for the effects of known CVD risk factors, such as age and smoking. Additionally, we used bivariate extensions of these methods to estimate genetic and random environmental correlations among sCAMs. Levels of sCAMs were significantly heritable: h2=0.24+/-0.10 for sICAM-1, h2=0.22+/-0.10 for sVCAM-1, h2=0.50+/-0.11 for sESEL-1, and h2=0.46+/-0.10 for sPSEL-1. In addition, a significant genetic correlation (rho(G)=0.63) was found between sICAM-1 and sVCAM-1 indicating some degree of shared genetic control. In the Fels Longitudinal Study, the levels of four sCAMs are significantly influenced by genetic effects, and sICAM-1 shares a common genetic background with sVCAM-1.

  6. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  7. Study design in genetic epidemiology: theoretical and practical considerations.

    PubMed

    Whittemore, A S; Nelson, L M

    1999-01-01

    Recent advances in molecular genetics have created new opportunities and challenges for genetic epidemiologists. Here we review some of the issues that arise when designing a study involving the genetic epidemiology of chronic diseases of late onset, such as cancer. We discuss two considerations that influence the choice of design. The first consideration is the study's goals. We describe the goals of identifying new susceptibility genes for a disease, of estimating important characteristics of known genes, and of learning how to prevent the disease in the genetically susceptible. We indicate how these goals affect the choice of design and present some guidelines for choosing designs that effectively address them. The second consideration is the set of practical constraints to successfully conducting the research. These contraints include problems of potential selection bias, reduced response rates, problems particular to family registries, problems particular to the cultures of various ethnic groups, and ethical issues. We indicate how these constraints affect the choice of design and discuss ways to deal with them. PMID:10854488

  8. Genetic and ecological studies of animals in Chernobyl and Fukushima.

    PubMed

    Mousseau, Timothy A; Møller, Anders P

    2014-01-01

    Recent advances in genetic and ecological studies of wild animal populations in Chernobyl and Fukushima have demonstrated significant genetic, physiological, developmental, and fitness effects stemming from exposure to radioactive contaminants. The few genetic studies that have been conducted in Chernobyl generally show elevated rates of genetic damage and mutation rates. All major taxonomic groups investigated (i.e., birds, bees, butterflies, grasshoppers, dragonflies, spiders, mammals) displayed reduced population sizes in highly radioactive parts of the Chernobyl Exclusion Zone. In Fukushima, population censuses of birds, butterflies, and cicadas suggested that abundances were negatively impacted by exposure to radioactive contaminants, while other groups (e.g., dragonflies, grasshoppers, bees, spiders) showed no significant declines, at least during the first summer following the disaster. Insufficient information exists for groups other than insects and birds to assess effects on life history at this time. The differences observed between Fukushima and Chernobyl may reflect the different times of exposure and the significance of multigenerational mutation accumulation in Chernobyl compared to Fukushima. There was considerable variation among taxa in their apparent sensitivity to radiation and this reflects in part life history, physiology, behavior, and evolutionary history. Interestingly, for birds, population declines in Chernobyl can be predicted by historical mitochondrial DNA base-pair substitution rates that may reflect intrinsic DNA repair ability.

  9. Genetic studies in chronic kidney disease: basic concepts.

    PubMed

    Nordfors, Louise; Luttropp, Karin; Carrero, Juan Jesus; Witasp, Anna; Stenvinkel, Peter; Lindholm, Bengt; Schalling, Martin

    2012-01-01

    In spite of extensive research resulting in major advances in renal care including technological improvements of dialysis, the poor outcome of chronic kidney disease patients has only marginally been improved since the 1980s. It has thus become clear that new strategies are needed to move forward. There are now great expectations that increased knowledge about genetic characteristics combined with other biological markers will identify pathophysiological pathways involved in the initiation and progression of renal damage and that this in turn will help define tools for early disease intervention and personalized treatment strategies. Already, new methodologies have made it possible to study the heritable component of many kidney diseases, and it is probable that DNA-based diagnostics will be performed on a regular basis for many conditions in the near future. This article discusses basic genetic concepts and highlights some of the novel approaches available for genome-wide genetic analyses. We hope that it may serve as an introduction to the research field of what we call "nephrogenetics." A second article in this series will focus on the interpretation and evaluation of genetic association studies and how to make use of this information to improve patient care and outcomes.

  10. Physiological basis of tolerance to complete submergence in rice involves genetic factors in addition to the SUB1 gene.

    PubMed

    Singh, Sudhanshu; Mackill, David J; Ismail, Abdelbagi M

    2014-01-01

    Recurring floods in Asia cause poor crop establishment. Yields decline drastically when plants are completely submerged for a few days. Traditional rice cultivars predominate because they have acquired moderate tolerance to flooding but they carry the penalty of inherently lower grain yields. In contrast, modern high-yielding varieties are highly susceptible to flooding. Cultivars with tolerance to complete submergence were recently developed in the background of popular varieties by transferring the submergence tolerance gene SUBMERGENCE1 (SUB1) from the highly tolerant Indian landrace FR13A. The present study evaluated three pairs of Sub1 near-isogenic lines (NILs) together with FR13A and two of its submergence-tolerant derivatives under field conditions to assess the survival and growth processes occurring during submergence and recovery that are associated with SUB1. Under control conditions, the NILs showed similar growth and biomass accumulation, indicating that SUB1 had no apparent effects. Submergence substantially decreased biomass accumulation but with greater reduction in the genotypes lacking SUB1, particularly when submergence was prolonged for 17 days. When submerged, the lines lacking SUB1 showed greater elongation and lower or negative biomass accumulation. Sub1 lines maintained higher chlorophyll concentrations during submergence and lost less non-structural carbohydrates (NSC) after submergence. This indicates that the introgression of SUB1 resulted in better regulation of NSC during submergence and that high pre-submergence NSC is not essential for the submergence tolerance conferred by SUB1. During recovery, chlorophyll degradation was faster in genotypes lacking SUB1 and any surviving plants showed poorer and delayed emergence of tillers and leaves. Sub1 lines restored new leaf and tiller production faster. During submergence, FR13A showed not only slower leaf elongation but also accumulated extra biomass and was able to recover faster than Sub

  11. Comparison of participant information and informed consent forms of five European studies in genetic isolated populations.

    PubMed

    Mascalzoni, Deborah; Janssens, A Cecile J W; Stewart, Alison; Pramstaller, Peter; Gyllensten, Ulf; Rudan, Igor; van Duijn, Cornelia M; Wilson, James F; Campbell, Harry; Quillan, Ruth M C

    2010-03-01

    Family-based research in genetically isolated populations is an effective approach for identifying loci influencing variation in disease traits. In common with all studies in humans, those in genetically isolated populations need ethical approval; however, existing ethical frameworks may be inadequate to protect participant privacy and confidentiality and to address participants' information needs in such populations. Using the ethical-legal guidelines of the Council for International Organizations of Medical Sciences (CIOMS) as a template, we compared the participant information leaflets and consent forms of studies in five European genetically isolated populations to identify additional information that should be incorporated into information leaflets and consent forms to guarantee satisfactorily informed consent. We highlight the additional information that participants require on the research purpose and the reasons why their population was chosen; on the potential risks and benefits of participation; on the opportunities for benefit sharing; on privacy; on the withdrawal of consent and on the disclosure of genetic data. This research raises some important issues that should be addressed properly and identifies relevant types of information that should be incorporated into information leaflets for this type of study.

  12. Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes

    ERIC Educational Resources Information Center

    Loo, Sandra K.; Shtir, Corina; Doyle, Alysa E.; Mick, Eric; McGough, James J.; McCracken, James; Biederman, Joseph; Smalley, Susan L.; Cantor, Rita M.; Faraone, Stephen V.; Nelson, Stanley F.

    2012-01-01

    Objective: The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability. Method: We performed a genome-wide association analysis with a dense set of 1 million single-nucleotide polymorphisms (SNPs) and quantitative intelligence scores within an ancestrally…

  13. Genetic studies of the Roma (Gypsies): a review

    PubMed Central

    Kalaydjieva, Luba; Gresham, David; Calafell, Francesc

    2001-01-01

    Background Data provided by the social sciences as well as genetic research suggest that the 8-10 million Roma (Gypsies) who live in Europe today are best described as a conglomerate of genetically isolated founder populations. The relationship between the traditional social structure observed by the Roma, where the Group is the primary unit, and the boundaries, demographic history and biological relatedness of the diverse founder populations appears complex and has not been addressed by population genetic studies. Results Recent medical genetic research has identified a number of novel, or previously known but rare conditions, caused by private founder mutations. A summary of the findings, provided in this review, should assist diagnosis and counselling in affected families, and promote future collaborative research. The available incomplete epidemiological data suggest a non-random distribution of disease-causing mutations among Romani groups. Conclusion Although far from systematic, the published information indicates that medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe. Reported carrier rates for some Mendelian disorders are in the range of 5 -15%, sufficient to justify newborn screening and early treatment, or community-based education and carrier testing programs for disorders where no therapy is currently available. To be most productive, future studies of the epidemiology of single gene disorders should take social organisation and cultural anthropology into consideration, thus allowing the targeting of public health programs and contributing to the understanding of population structure and demographic history of the Roma. PMID:11299048

  14. Plants with genetically modified events combined by conventional breeding: an assessment of the need for additional regulatory data.

    PubMed

    Pilacinski, W; Crawford, A; Downey, R; Harvey, B; Huber, S; Hunst, P; Lahman, L K; MacIntosh, S; Pohl, M; Rickard, C; Tagliani, L; Weber, N

    2011-01-01

    Crop varieties with multiple GM events combined by conventional breeding have become important in global agriculture. The regulatory requirements in different countries for such products vary considerably, placing an additional burden on regulatory agencies in countries where the submission of additional data is required and delaying the introduction of innovative products to meet agricultural needs. The process of conventional plant breeding has predictably provided safe food and feed products both historically and in the modern era of plant breeding. Thus, previously approved GM events that have been combined by conventional plant breeding and contain GM traits that are not likely to interact in a manner affecting safety should be considered to be as safe as their conventional counterparts. Such combined GM event crop varieties should require little, if any, additional regulatory data to meet regulatory requirements.

  15. A Global Population Genetic Study of Pantala flavescens.

    PubMed

    Troast, Daniel; Suhling, Frank; Jinguji, Hiroshi; Sahlén, Göran; Ware, Jessica

    2016-01-01

    Among terrestrial arthropods, the dragonfly species Pantala flavescens is remarkable due to their nearly global distribution and extensive migratory ranges; the largest of any known insect. Capable of migrating across oceans, the potential for high rates of gene flow among geographically distant populations is significant. It has been hypothesized that P. flavescens may be a global panmictic population but no sufficient genetic evidence has been collected thus far. Through a population genetic analysis of P. flavescens samples from North America, South America, and Asia, the current study aimed to examine the extent at which gene flow is occurring on a global scale and discusses the implications of the genetic patterns we uncovered on population structure and genetic diversity of the species. This was accomplished using PCR-amplified cytochrome oxidase one (CO1) mitochondrial DNA data to reconstruct phylogenetic trees, a haplotype network, and perform molecular variance analyses. Our results suggested high rates of gene flow are occurring among all included geographic regions; providing the first significant evidence that Pantala flavescens should be considered a global panmictic population. PMID:26934181

  16. A Global Population Genetic Study of Pantala flavescens

    PubMed Central

    Troast, Daniel; Suhling, Frank; Jinguji, Hiroshi; Sahlén, Göran; Ware, Jessica

    2016-01-01

    Among terrestrial arthropods, the dragonfly species Pantala flavescens is remarkable due to their nearly global distribution and extensive migratory ranges; the largest of any known insect. Capable of migrating across oceans, the potential for high rates of gene flow among geographically distant populations is significant. It has been hypothesized that P. flavescens may be a global panmictic population but no sufficient genetic evidence has been collected thus far. Through a population genetic analysis of P. flavescens samples from North America, South America, and Asia, the current study aimed to examine the extent at which gene flow is occurring on a global scale and discusses the implications of the genetic patterns we uncovered on population structure and genetic diversity of the species. This was accomplished using PCR-amplified cytochrome oxidase one (CO1) mitochondrial DNA data to reconstruct phylogenetic trees, a haplotype network, and perform molecular variance analyses. Our results suggested high rates of gene flow are occurring among all included geographic regions; providing the first significant evidence that Pantala flavescens should be considered a global panmictic population. PMID:26934181

  17. Comparative use of InDel and SSR markers in deciphering the interspecific structure of cultivated citrus genetic diversity: a perspective for genetic association studies.

    PubMed

    García-Lor, Andrés; Luro, François; Navarro, Luis; Ollitrault, Patrick

    2012-01-01

    Genetic stratification associated with domestication history is a key parameter for estimating the pertinence of genetic association study within a gene pool. Previous molecular and phenotypic studies have shown that most of the diversity of cultivated citrus results from recombination between three main species: C. medica (citron), C. reticulata (mandarin) and C. maxima (pummelo). However, the precise contribution of each of these basic species to the genomes of secondary cultivated species, such as C. sinensis (sweet orange), C. limon (lemon), C. aurantium (sour orange), C. paradisi (grapefruit) and recent hybrids is unknown. Our study focused on: (1) the development of insertion-deletion (InDel) markers and their comparison with SSR markers for use in genetic diversity and phylogenetic studies; (2) the analysis of the contributions of basic taxa to the genomes of secondary species and modern cultivars and (3) the description of the organisation of the Citrus gene pool, to evaluate how genetic association studies should be done at the cultivated Citrus gene pool level. InDel markers appear to be better phylogenetic markers for tracing the contributions of the three ancestral species, whereas SSR markers are more useful for intraspecific diversity analysis. Most of the genetic organisation of the Citrus gene pool is related to the differentiation between C. reticulata, C. maxima and C. medica. High and generalised LD was observed, probably due to the initial differentiation between the basic species and a limited number of interspecific recombinations. This structure precludes association genetic studies at the genus level without developing additional recombinant populations from interspecific hybrids. Association genetic studies should also be affordable at intraspecific level in a less structured pool such as C. reticulata. PMID:22160318

  18. Spitting for Science: Danish High School Students Commit to a Large-Scale Self-Reported Genetic Study

    PubMed Central

    Athanasiadis, Georgios; Jørgensen, Frank G.; Cheng, Jade Y.; Kjærgaard, Peter C.; Schierup, Mikkel H.; Mailund, Thomas

    2016-01-01

    Scientific outreach delivers science to the people. But it can also deliver people to the science. In this work, we report our experience from a large-scale public engagement project promoting genomic literacy among Danish high school students with the additional benefit of collecting data for studying the genetic makeup of the Danish population. Not only did we confirm that students have a great interest in their genetic past, but we were also gratified to see that, with the right motivation, adolescents can provide high-quality data for genetic studies. PMID:27571202

  19. Spitting for Science: Danish High School Students Commit to a Large-Scale Self-Reported Genetic Study.

    PubMed

    Athanasiadis, Georgios; Jørgensen, Frank G; Cheng, Jade Y; Kjærgaard, Peter C; Schierup, Mikkel H; Mailund, Thomas

    2016-01-01

    Scientific outreach delivers science to the people. But it can also deliver people to the science. In this work, we report our experience from a large-scale public engagement project promoting genomic literacy among Danish high school students with the additional benefit of collecting data for studying the genetic makeup of the Danish population. Not only did we confirm that students have a great interest in their genetic past, but we were also gratified to see that, with the right motivation, adolescents can provide high-quality data for genetic studies. PMID:27571202

  20. Synthesis and assessment of date palm genetic diversity studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A thorough assessment of genetic diversity and population differentiation of Phoenix dactylifera are critical for its dynamic conservation and sustainable utilization of its genetic diversity. Estimates of genetic diversity based on phenotypic, biochemical and molecular markers; and fruit quality tr...

  1. A Snapshot of Functional Genetic Studies in Medicago truncatula.

    PubMed

    Kang, Yun; Li, Minguye; Sinharoy, Senjuti; Verdier, Jerome

    2016-01-01

    In the current context of food security, increase of plant protein production in a sustainable manner represents one of the major challenges of agronomic research, which could be partially resolved by increased cultivation of legume crops. Medicago truncatula is now a well-established model for legume genomic and genetic studies. With the establishment of genomics tools and mutant populations in M. truncatula, it has become an important resource to answer some of the basic biological questions related to plant development and stress tolerance. This review has an objective to overview a decade of genetic studies in this model plant from generation of mutant populations to nowadays. To date, the three biological fields, which have been extensively studied in M. truncatula, are the symbiotic nitrogen fixation, the seed development, and the abiotic stress tolerance, due to their significant agronomic impacts. In this review, we summarize functional genetic studies related to these three major biological fields. We integrated analyses of a nearly exhaustive list of genes into their biological contexts in order to provide an overview of the forefront research advances in this important legume model plant. PMID:27555857

  2. A Snapshot of Functional Genetic Studies in Medicago truncatula

    PubMed Central

    Kang, Yun; Li, Minguye; Sinharoy, Senjuti; Verdier, Jerome

    2016-01-01

    In the current context of food security, increase of plant protein production in a sustainable manner represents one of the major challenges of agronomic research, which could be partially resolved by increased cultivation of legume crops. Medicago truncatula is now a well-established model for legume genomic and genetic studies. With the establishment of genomics tools and mutant populations in M. truncatula, it has become an important resource to answer some of the basic biological questions related to plant development and stress tolerance. This review has an objective to overview a decade of genetic studies in this model plant from generation of mutant populations to nowadays. To date, the three biological fields, which have been extensively studied in M. truncatula, are the symbiotic nitrogen fixation, the seed development, and the abiotic stress tolerance, due to their significant agronomic impacts. In this review, we summarize functional genetic studies related to these three major biological fields. We integrated analyses of a nearly exhaustive list of genes into their biological contexts in order to provide an overview of the forefront research advances in this important legume model plant. PMID:27555857

  3. The Brazilian Xavante Indians revisited: new protein genetic studies.

    PubMed

    Salzano, F M; Franco, M H; Weimer, T A; Callegari-Jacques, S M; Mestriner, M A; Hutz, M H; Flowers, N M; Santos, R V; Coimbra, C E

    1997-09-01

    A total of 94 individuals from the Xavante village of Rio das Mortes were variously studied in relation to 28 protein genetic systems. No variation was observed for 15 of them, in accordance with previous studies. Of the remaining 13, four (Rh, Duffy, acid phosphatase, and GC) showed significant departures from the averages obtained in 32 other South American Indian populations. If studies performed in the 1960s are considered, there is indication that no significant changes in this village's gene pool has occurred in the last 30 years. Comparison with two other Xavante populations included nine systems with variation, and for three of them (MNSs, Rh, and Duffy) significant differences were found. Genetically the Rio das Mortes are closer to the São Marcos than to the Simões Lopes Xavantes. A dendrogram considering 25 genetic systems and 33 South American Indian populations was constructed. There the Xavante were grouped together, in two neighboring clusters, with three other tribes who speak Ge languages, But these clusters also present populations who speak other languages, and the reproducibility of the tree is low. South American Indians, at least with this set of markers, do not seem to be clearly classified into defined subgroups.

  4. Homogeneous case subgroups increase power in genetic association studies.

    PubMed

    Traylor, Matthew; Markus, Hugh; Lewis, Cathryn M

    2015-06-01

    Genome-wide association studies of clinically defined cases against controls have transformed our understanding of the genetic causes of many diseases. However, there are limitations to the simple clinical definitions used in these studies, and GWAS analyses are beginning to explore more refined phenotypes in subgroups of the existing data sets. These analyses are often performed ad hoc without considering the power requirements to justify such analyses. Here we derive expressions for the relative power of such subgroup analyses and determine the genotypic relative risks (GRRs) required to achieve equivalent power to a full analysis for relevant scenarios. We show that only modest increases in GRRs may be required to offset the reduction in power from analysing fewer cases, implying that analyses of more genetically homogenous case subgroups may have the potential to identify further associations. We find that, for lower genotypic relative risks in the full sample, subgroup analyses of more homogeneous cases have relatively more power than for higher index genotypic relative risks and that this effect is stronger for rare as opposed to common variants. As GWA studies are likely to have now identified the majority of SNPs with stronger effects, these results strongly advocate a renewed effort to identify phenotypically homogeneous disease groups, in which power to detect genetic variants with small effects will be greater. These results suggest that analysis of case subsets could be a powerful strategy to uncover some of the hidden heritability for common complex disorders, particularly in identifying rarer variants of modest effect.

  5. Genetic association study of Dickkopf-1 and sclerostin genes with paget disease of bone.

    PubMed

    Beauregard, Mariejka; Gagnon, Edith; Guay-Bélanger, Sabrina; Siris, Ethel S; Morissette, Jean; Brown, Jacques P; Michou, Laëtitia

    2013-11-01

    Increased expression of DKK1 gene was reported in pagetic osteoblasts and stromal cells, and increased serum levels of DKK1 and SOST proteins were reported in patients with Paget disease of bone (PDB). This study aimed at identifying rare genetic variants of the DKK1 and SOST genes and at testing for genetic association with PDB in the French-Canadian population. Exons, promoters, and exon-intron junctions of these genes were sequenced in patients with PDB and healthy controls. An association study of Tag SNPs of both genes was also performed in 239 pagetic patients and 297 healthy individuals. Three rare variants were identified in this study, all located in the DKK1 gene: one variant in the second exon leading to alteration in a highly conserved amino acid (p.R120L), one in the 5'-untranslated region (-50 C/A), and one in a splice site of intron 1 (IVS1 184 T/C), although none of these rare variants were associated with PDB. A genetic association of a Tag SNP of the DKK1 gene was found: the G allele of rs1569198 was significantly decreased in patients in comparison to controls (42 vs. 49 %, uncorrected P = 0.03, OR = 0.77, 95 % CI 0.61-0.98). In conclusion, this study identified three rare genetic variants in DKK1 in the French-Canadian population. In addition, a weak genetic association of a common variant of DKK1, rs1569198, which is located on a predicted new acceptor site for splicing of this gene, was observed in PDB, whereas no rare variant or genetic association was found in the SOST gene.

  6. Genome-wide Association Study of Dermatomyositis Reveals Genetic Overlap with other Autoimmune Disorders

    PubMed Central

    Miller, Frederick W.; Cooper, Robert G.; Vencovsky, Jiri; Rider, Lisa G.; Danko, Katalin; Wedderburn, Lucy R.; Lundberg, Ingrid E.; Pachman, Lauren M.; Reed, Ann M.; Ytterberg, Steven R.; Padyukov, Leonid; Selva-O’Callaghan, Albert; Radstake, Timothy; Isenberg, David A.; Chinoy, Hector; Ollier, William E. R.; O’Hanlon, Terrance P.; Peng, Bo; Lee, Annette; Lamb, Janine A.; Chen, Wei; Amos, Christopher I.; Gregersen, Peter K.

    2014-01-01

    Objective To identify new genetic associations with juvenile and adult dermatomyositis (DM). Methods We performed a genome-wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1178) and controls (n = 4724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM. Results Compared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS-level significance (P < 5x10−8) at 80 genotyped SNPs. An analysis of 141 non-MHC SNPs previously associated with autoimmune diseases showed that three SNPs linked with three genes were associated with DM, with a false discovery rate (FDR) < 0.05. These genes were phospholipase C like 1 (PLCL1, rs6738825, FDR=0.00089), B lymphoid tyrosine kinase (BLK, rs2736340, FDR=0.00031), and chemokine (C-C motif) ligand 21 (CCL21, rs951005, FDR=0.0076). None of these genes was previously reported to be associated with DM. Conclusion Our findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non-MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches. PMID:23983088

  7. [Genetic predisposition and Pediatric Acute Respiratory Distress Syndrome: New tools for genetic study].

    PubMed

    Erranz, M Benjamín; Wilhelm, B Jan; Riquelme, V Raquel; Cruces, R Pablo

    2015-01-01

    Acute respiratory distress syndrome (ARDS) is the most severe form of respiratory failure. Theoretically, any acute lung condition can lead to ARDS, but only a small percentage of individuals actually develop the disease. On this basis, genetic factors have been implicated in the risk of developing ARDS. Based on the pathophysiology of this disease, many candidate genes have been evaluated as potential modifiers in patient, as well as in animal models, of ARDS. Recent experimental data and clinical studies suggest that variations of genes involved in key processes of tissue, cellular and molecular lung damage may influence susceptibility and prognosis of ARDS. However, the pathogenesis of pediatric ARDS is complex, and therefore, it can be expected that many genes might contribute. Genetic variations such as single nucleotide polymorphisms and copy-number variations are likely associated with susceptibility to ARDS in children with primary lung injury. Genome-wide association (GWA) studies can objectively examine these variations, and help identify important new genes and pathogenetic pathways for future analysis. This approach might also have diagnostic and therapeutic implications, such as predicting patient risk or developing a personalized therapeutic approach to this serious syndrome.

  8. Study of wood plastic composite in the presence of nitrogen containing additives

    NASA Astrophysics Data System (ADS)

    Ali, K. M. Idriss; Khan, Mubarak A.; Husain, M. M.

    1994-10-01

    Effect of nitrogen-containing additives in the study of wood plastic composites of MMA with simul and mango wood of Bangladesh has been investigated. Nine different additives were used and the additives containing carboamide group induce the highest tensile strength to the composite.

  9. Genetic Diversity and Association Studies in US Hispanic/Latino Populations: Applications in the Hispanic Community Health Study/Study of Latinos

    PubMed Central

    Conomos, Matthew P.; Laurie, Cecelia A.; Stilp, Adrienne M.; Gogarten, Stephanie M.; McHugh, Caitlin P.; Nelson, Sarah C.; Sofer, Tamar; Fernández-Rhodes, Lindsay; Justice, Anne E.; Graff, Mariaelisa; Young, Kristin L.; Seyerle, Amanda A.; Avery, Christy L.; Taylor, Kent D.; Rotter, Jerome I.; Talavera, Gregory A.; Daviglus, Martha L.; Wassertheil-Smoller, Sylvia; Schneiderman, Neil; Heiss, Gerardo; Kaplan, Robert C.; Franceschini, Nora; Reiner, Alex P.; Shaffer, John R.; Barr, R. Graham; Kerr, Kathleen F.; Browning, Sharon R.; Browning, Brian L.; Weir, Bruce S.; Avilés-Santa, M. Larissa; Papanicolaou, George J.; Lumley, Thomas; Szpiro, Adam A.; North, Kari E.; Rice, Ken; Thornton, Timothy A.; Laurie, Cathy C.

    2016-01-01

    US Hispanic/Latino individuals are diverse in genetic ancestry, culture, and environmental exposures. Here, we characterized and controlled for this diversity in genome-wide association studies (GWASs) for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We simultaneously estimated population-structure principal components (PCs) robust to familial relatedness and pairwise kinship coefficients (KCs) robust to population structure, admixture, and Hardy-Weinberg departures. The PCs revealed substantial genetic differentiation within and among six self-identified background groups (Cuban, Dominican, Puerto Rican, Mexican, and Central and South American). To control for variation among groups, we developed a multi-dimensional clustering method to define a “genetic-analysis group” variable that retains many properties of self-identified background while achieving substantially greater genetic homogeneity within groups and including participants with non-specific self-identification. In GWASs of 22 biomedical traits, we used a linear mixed model (LMM) including pairwise empirical KCs to account for familial relatedness, PCs for ancestry, and genetic-analysis groups for additional group-associated effects. Including the genetic-analysis group as a covariate accounted for significant trait variation in 8 of 22 traits, even after we fit 20 PCs. Additionally, genetic-analysis groups had significant heterogeneity of residual variance for 20 of 22 traits, and modeling this heteroscedasticity within the LMM reduced genomic inflation for 19 traits. Furthermore, fitting an LMM that utilized a genetic-analysis group rather than a self-identified background group achieved higher power to detect previously reported associations. We expect that the methods applied here will be useful in other studies with multiple ethnic groups, admixture, and relatedness. PMID:26748518

  10. Genetic and environmental influences on individual differences in attitudes toward homosexuality: an Australian twin study.

    PubMed

    Verweij, Karin J H; Shekar, Sri N; Zietsch, Brendan P; Eaves, Lindon J; Bailey, J Michael; Boomsma, Dorret I; Martin, Nicholas G

    2008-05-01

    Previous research has shown that many heterosexuals hold negative attitudes toward homosexuals and homosexuality (homophobia). Although a great deal of research has focused on the profile of homophobic individuals, this research provides little theoretical insight into the aetiology of homophobia. To examine genetic and environmental influences on variation in attitudes toward homophobia, we analysed data from 4,688 twins who completed a questionnaire concerning sexual behaviour and attitudes, including attitudes toward homosexuality. Results show that, in accordance with literature, males have significantly more negative attitudes toward homosexuality than females and non-heterosexuals are less homophobic than heterosexuals. In contrast with some earlier findings, age had no significant effect on the homophobia scores in this study. Genetic modelling showed that variation in homophobia scores could be explained by additive genetic (36%), shared environmental (18%) and unique environmental factors (46%). However, corrections based on previous findings show that the shared environmental estimate may be almost entirely accounted for as extra additive genetic variance arising from assortative mating for homophobic attitudes. The results suggest that variation in attitudes toward homosexuality is substantially inherited, and that social environmental influences are relatively minor.

  11. Unraveling the genetic etiology of adult antisocial behavior: a genome-wide association study.

    PubMed

    Tielbeek, Jorim J; Medland, Sarah E; Benyamin, Beben; Byrne, Enda M; Heath, Andrew C; Madden, Pamela A F; Martin, Nicholas G; Wray, Naomi R; Verweij, Karin J H

    2012-01-01

    Crime poses a major burden for society. The heterogeneous nature of criminal behavior makes it difficult to unravel its causes. Relatively little research has been conducted on the genetic influences of criminal behavior. The few twin and adoption studies that have been undertaken suggest that about half of the variance in antisocial behavior can be explained by genetic factors. In order to identify the specific common genetic variants underlying this behavior, we conduct the first genome-wide association study (GWAS) on adult antisocial behavior. Our sample comprised a community sample of 4816 individuals who had completed a self-report questionnaire. No genetic polymorphisms reached genome-wide significance for association with adult antisocial behavior. In addition, none of the traditional candidate genes can be confirmed in our study. While not genome-wide significant, the gene with the strongest association (p-value = 8.7×10(-5)) was DYRK1A, a gene previously related to abnormal brain development and mental retardation. Future studies should use larger, more homogeneous samples to disentangle the etiology of antisocial behavior. Biosocial criminological research allows a more empirically grounded understanding of criminal behavior, which could ultimately inform and improve current treatment strategies. PMID:23077488

  12. Unraveling the Genetic Etiology of Adult Antisocial Behavior: A Genome-Wide Association Study

    PubMed Central

    Tielbeek, Jorim J.; Medland, Sarah E.; Benyamin, Beben; Byrne, Enda M.; Heath, Andrew C.; Madden, Pamela A. F.; Martin, Nicholas G.; Wray, Naomi R.; Verweij, Karin J. H.

    2012-01-01

    Crime poses a major burden for society. The heterogeneous nature of criminal behavior makes it difficult to unravel its causes. Relatively little research has been conducted on the genetic influences of criminal behavior. The few twin and adoption studies that have been undertaken suggest that about half of the variance in antisocial behavior can be explained by genetic factors. In order to identify the specific common genetic variants underlying this behavior, we conduct the first genome-wide association study (GWAS) on adult antisocial behavior. Our sample comprised a community sample of 4816 individuals who had completed a self-report questionnaire. No genetic polymorphisms reached genome-wide significance for association with adult antisocial behavior. In addition, none of the traditional candidate genes can be confirmed in our study. While not genome-wide significant, the gene with the strongest association (p-value = 8.7×10−5) was DYRK1A, a gene previously related to abnormal brain development and mental retardation. Future studies should use larger, more homogeneous samples to disentangle the etiology of antisocial behavior. Biosocial criminological research allows a more empirically grounded understanding of criminal behavior, which could ultimately inform and improve current treatment strategies. PMID:23077488

  13. Genetic Influences on Blood Pressure Response to the Cold Pressor Test: Results from the HAPI Heart Study

    PubMed Central

    Roy-Gagnon, Marie-Hélène; Weir, Matthew R.; Sorkin, John D.; Ryan, Kathleen A.; Sack, Paul A.; Hines, Scott; Bielak, Lawrence F.; Peyser, Patricia A.; Post, Wendy; Mitchell, Braxton D.; Shuldiner, Alan R.; Douglas, Julie A.

    2012-01-01

    Blood pressure (BP) response to the cold pressor test (CPT) has been found to predict the development of hypertension and cardiovascular disease in prospective studies. However, the determinants of BP response to the CPT, including the role of genetic factors, are largely unknown. Additionally, to our knowledge, no study has examined the genetics of BP recovery from the CPT, including whether shared genetic factors influence both reactivity and recovery. As part of the Heredity and Phenotype Intervention (HAPI) Heart Study, we administered a 2½-minute hand CPT to 835 participants from 18 extended Amish families. We estimated the heritability of BP reactivity and recovery (measured by the incremental area under the curve) and the genetic correlations between baseline, reactivity, and recovery BP phenotypes. After adjustment for relevant covariates, including baseline BP, the heritability estimates for both systolic BP (SBP) and diastolic BP (DBP) reactivity and recovery differed significantly from zero (P<0.01), with 12–25% of the total variation in BP response attributable to additive genetic effects. The genetic correlations between baseline DBP and response phenotypes were not significantly different from 0, while the genetic correlation between DBP reactivity and recovery (0.74) was significantly different from 0 and one (P<0.005). The genetic correlation between SBP reactivity and recovery was similar (0.81, P<0.05). We conclude that, independent of baseline BP, BP response to the CPT is heritable, and that both shared and unshared genetic factors influence BP reactivity and recovery, thus stressing the importance of identifying genetic variants that influence both traits. PMID:18327083

  14. Study of genetic direct search algorithms for function optimization

    NASA Technical Reports Server (NTRS)

    Zeigler, B. P.

    1974-01-01

    The results are presented of a study to determine the performance of genetic direct search algorithms in solving function optimization problems arising in the optimal and adaptive control areas. The findings indicate that: (1) genetic algorithms can outperform standard algorithms in multimodal and/or noisy optimization situations, but suffer from lack of gradient exploitation facilities when gradient information can be utilized to guide the search. (2) For large populations, or low dimensional function spaces, mutation is a sufficient operator. However for small populations or high dimensional functions, crossover applied in about equal frequency with mutation is an optimum combination. (3) Complexity, in terms of storage space and running time, is significantly increased when population size is increased or the inversion operator, or the second level adaptation routine is added to the basic structure.

  15. A powerful and robust test in genetic association studies.

    PubMed

    Cheng, Kuang-Fu; Lee, Jen-Yu

    2014-01-01

    There are several well-known single SNP tests presented in the literature for detecting gene-disease association signals. Having in place an efficient and robust testing process across all genetic models would allow a more comprehensive approach to analysis. Although some studies have shown that it is possible to construct such a test when the variants are common and the genetic model satisfies certain conditions, the model conditions are too restrictive and in general difficult to verify. In this paper, we propose a powerful and robust test without assuming any model restrictions. Our test is based on the selected 2 × 2 tables derived from the usual 2 × 3 table. By signals from these tables, we show through simulations across a wide range of allele frequencies and genetic models that this approach may produce a test which is almost uniformly most powerful in the analysis of low- and high-frequency variants. Two cancer studies are used to demonstrate applications of the proposed test. PMID:24969671

  16. A Novel Lung Disease Phenotype Adjusted for Mortality Attrition for Cystic Fibrosis Genetic Modifier Studies

    PubMed Central

    Taylor, Chelsea; Commander, Clayton W.; Collaco, Joseph M.; Strug, Lisa J.; Li, Weili; Wright, Fred A.; Webel, Aaron D.; Pace, Rhonda G.; Stonebraker, Jaclyn R.; Naughton, Kathleen; Dorfman, Ruslan; Sandford, Andrew; Blackman, Scott M.; Berthiaume, Yves; Paré, Peter; Drumm, Mitchell L.; Zielenski, Julian; Durie, Peter; Cutting, Garry R.; Knowles, Michael R.; Corey, Mary

    2011-01-01

    SUMMARY Genetic studies of lung disease in Cystic Fibrosis are hampered by the lack of a severity measure that accounts for chronic disease progression and mortality attrition. Further, combining analyses across studies requires common phenotypes that are robust to study design and patient ascertainment. Using data from the North American Cystic Fibrosis Modifier Consortium (Canadian Consortium for CF Genetic Studies, Johns Hopkins University CF Twin and Sibling Study, and University of North Carolina/Case Western Reserve University Gene Modifier Study), the authors calculated age-specific CF percentile values of FEV1 which were adjusted for CF age-specific mortality data. The phenotype was computed for 2061 patients representing the Canadian CF population, 1137 extreme phenotype patients in the UNC/Case Western study, and 1323 patients from multiple CF sib families in the CF Twin and Sibling Study. Despite differences in ascertainment and median age, our phenotype score was distributed in all three samples in a manner consistent with ascertainment differences, reflecting the lung disease severity of each individual in the underlying population. The new phenotype score was highly correlated with the previously recommended complex phenotype, but the new phenotype is more robust for shorter follow-up and for extreme ages. A disease progression and mortality adjusted phenotype reduces the need for stratification or additional covariates, increasing statistical power and avoiding possible distortions. This approach will facilitate large scale genetic and environmental epidemiological studies which will provide targeted therapeutic pathways for the clinical benefit of patients with CF. PMID:21462361

  17. Functional Analysis of the Human Genome:. Study of Genetic Disease

    NASA Astrophysics Data System (ADS)

    Tsui, Lap-Chee

    2003-04-01

    I will divide my remarks into 3 parts. First, I will give a brief summary of the Human Genome Project. Second, I will describe our work on human chromosome 7 to illustrate how we could contribute to the Project and disease research. Third, I would like to bring across the argument that study of genetic disease is an integral component of the Human Genome Project. In particular, I will use cystic fibrosis as an example to elaborate why I consider disease study is a part of functional genomics.

  18. The Genetic and Environmental Contributions to Internet Use and Associations With Psychopathology: A Twin Study

    PubMed Central

    Long, Elizabeth C.; Verhulst, Brad; Neale, Michael C.; Lind, Penelope A.; Hickie, Ian B.; Martin, Nicholas G.; Gillespie, Nathan A.

    2016-01-01

    Excessive internet use has been linked to psychopathology. Therefore, understanding the genetic and environmental risks underpinning internet use and their relation to psychopathology is important. This study aims to explore the genetic and environmental etiology of internet use measures and their associations with internalizing disorders and substance use disorders. The sample included 2,059 monozygotic (MZ) and dizygotic (DZ) young adult twins from the Brisbane Longitudinal Twin Study (BLTS). Younger participants reported more frequent internet use, while women were more likely to use the internet for interpersonal communication. Familial aggregation in ‘frequency of internet use’ was entirely explained by additive genetic factors accounting for 41% of the variance. Familial aggregation in ‘frequency of use after 11 pm’, ‘using the internet to contact peers’, and ‘using the internet primarily to access social networking sites’ was attributable to varying combinations of additive genetic and shared environmental factors. In terms of psychopathology, there were no significant associations between internet use measures and major depression (MD), but there were positive significant associations between ‘frequency of internet use’ and ‘frequency of use after 11 pm’ with social phobia (SP). ‘Using the internet to contact peers’ was positively associated with alcohol abuse, whereas ‘using the internet to contact peers’ and ‘using the internet primarily to access social networking sites’ were negatively associated with cannabis use disorders and nicotine symptoms. Individual differences in internet use can be attributable to varying degrees of genetic and environmental risks. Despite some significant associations of small effect, variation in internet use appears mostly unrelated to psychopathology. PMID:26693596

  19. The Genetic and Environmental Contributions to Internet Use and Associations With Psychopathology: A Twin Study.

    PubMed

    Long, Elizabeth C; Verhulst, Brad; Neale, Michael C; Lind, Penelope A; Hickie, Ian B; Martin, Nicholas G; Gillespie, Nathan A

    2016-02-01

    Excessive internet use has been linked to psychopathology. Therefore, understanding the genetic and environmental risks underpinning internet use and their relation to psychopathology is important. This study aims to explore the genetic and environmental etiology of internet use measures and their associations with internalizing disorders and substance use disorders. The sample included 2,059 monozygotic (MZ) and dizygotic (DZ) young adult twins from the Brisbane Longitudinal Twin Study (BLTS). Younger participants reported more frequent internet use, while women were more likely to use the internet for interpersonal communication. Familial aggregation in 'frequency of internet use' was entirely explained by additive genetic factors accounting for 41% of the variance. Familial aggregation in 'frequency of use after 11 pm', 'using the internet to contact peers', and 'using the internet primarily to access social networking sites' was attributable to varying combinations of additive genetic and shared environmental factors. In terms of psychopathology, there were no significant associations between internet use measures and major depression (MD), but there were positive significant associations between 'frequency of internet use' and 'frequency of use after 11 pm' with social phobia (SP). 'Using the internet to contact peers' was positively associated with alcohol abuse, whereas 'using the internet to contact peers' and 'using the internet primarily to access social networking sites' were negatively associated with cannabis use disorders and nicotine symptoms. Individual differences in internet use can be attributable to varying degrees of genetic and environmental risks. Despite some significant associations of small effect, variation in internet use appears mostly unrelated to psychopathology. PMID:26693596

  20. Type I error rates for testing genetic drift with phenotypic covariance matrices: a simulation study.

    PubMed

    Prôa, Miguel; O'Higgins, Paul; Monteiro, Leandro R

    2013-01-01

    Studies of evolutionary divergence using quantitative genetic methods are centered on the additive genetic variance-covariance matrix (G) of correlated traits. However, estimating G properly requires large samples and complicated experimental designs. Multivariate tests for neutral evolution commonly replace average G by the pooled phenotypic within-group variance-covariance matrix (W) for evolutionary inferences, but this approach has been criticized due to the lack of exact proportionality between genetic and phenotypic matrices. In this study, we examined the consequence, in terms of type I error rates, of replacing average G by W in a test of neutral evolution that measures the regression slope between among-population variances and within-population eigenvalues (the Ackermann and Cheverud [AC] test) using a simulation approach to generate random observations under genetic drift. Our results indicate that the type I error rates for the genetic drift test are acceptable when using W instead of average G when the matrix correlation between the ancestral G and P is higher than 0.6, the average character heritability is above 0.7, and the matrices share principal components. For less-similar G and P matrices, the type I error rates would still be acceptable if the ratio between the number of generations since divergence and the effective population size (t/N(e)) is smaller than 0.01 (large populations that diverged recently). When G is not known in real data, a simulation approach to estimate expected slopes for the AC test under genetic drift is discussed.

  1. Bayesian semiparametric meta-analysis for genetic association studies.

    PubMed

    De Iorio, Maria; Newcombe, Paul J; Tachmazidou, Ioanna; Verzilli, Claudio J; Whittaker, John C

    2011-07-01

    We present a Bayesian semiparametric model for the meta-analysis of candidate gene studies with a binary outcome. Such studies often report results from association tests for different, possibly study-specific and non-overlapping genetic markers in the same genetic region. Meta-analyses of the results at each marker in isolation are seldom appropriate as they ignore the correlation that may exist between markers due to linkage disequilibrium (LD) and cannot assess the relative importance of variants at each marker. Also such marker-wise meta-analyses are restricted to only those studies that have typed the marker in question, with a potential loss of power. A better strategy is one which incorporates information about the LD between markers so that any combined estimate of the effect of each variant is corrected for the effect of other variants, as in multiple regression. Here we develop a Bayesian semiparametric model which models the observed genotype group frequencies conditional to the case/control status and uses pairwise LD measurements between markers as prior information to make posterior inference on adjusted effects. The approach allows borrowing of strength across studies and across markers. The analysis is based on a mixture of Dirichlet processes model as the underlying semiparametric model. Full posterior inference is performed through Markov chain Monte Carlo algorithms. The approach is demonstrated on simulated and real data. PMID:21400586

  2. Genetic Geostatistical Framework for Spatial Analysis of Fine-Scale Genetic Heterogeneity in Modern Populations: Results from the KORA Study

    PubMed Central

    Diaz-Lacava, A. N.; Walier, M.; Holler, D.; Steffens, M.; Gieger, C.; Furlanello, C.; Lamina, C.; Wichmann, H. E.; Becker, T.

    2015-01-01

    Aiming to investigate fine-scale patterns of genetic heterogeneity in modern humans from a geographic perspective, a genetic geostatistical approach framed within a geographic information system is presented. A sample collected for prospective studies in a small area of southern Germany was analyzed. None indication of genetic heterogeneity was detected in previous analysis. Socio-demographic and genotypic data of German citizens were analyzed (212 SNPs; n = 728). Genetic heterogeneity was evaluated with observed heterozygosity (HO). Best-fitting spatial autoregressive models were identified, using socio-demographic variables as covariates. Spatial analysis included surface interpolation and geostatistics of observed and predicted patterns. Prediction accuracy was quantified. Spatial autocorrelation was detected for both socio-demographic and genetic variables. Augsburg City and eastern suburban areas showed higher HO values. The selected model gave best predictions in suburban areas. Fine-scale patterns of genetic heterogeneity were observed. In accordance to literature, more urbanized areas showed higher levels of admixture. This approach showed efficacy for detecting and analyzing subtle patterns of genetic heterogeneity within small areas. It is scalable in number of loci, even up to whole-genome analysis. It may be suggested that this approach may be applicable to investigate the underlying genetic history that is, at least partially, embedded in geographic data. PMID:26258132

  3. Genetic parameters and genome-wide association study of hyperpigmentation of the visceral peritoneum in chickens

    PubMed Central

    2013-01-01

    Background Hyperpigmentation of the visceral peritoneum (HVP) has recently garnered much attention in the poultry industry because of the possible risk to the health of affected animals and the damage it causes to the appearance of commercial chicken carcasses. However, the heritable characters of HVP remain unclear. The objective of this study was to investigate the genetic parameters of HVP by genome-wide association study (GWAS) in chickens. Results HVP was found to be influenced by genetic factors, with a heritability score of 0.33. HVP had positive genetic correlations with growth and carcass traits, such as leg muscle weight (rg = 0.34), but had negative genetic correlations with immune traits, such as the antibody response to Newcastle disease virus (rg = −0.42). The GWAS for HVP using 39,833 single nucleotide polymorphisms indicated the genetic factors associated with HVP displayed an additive effect rather than a dominance effect. In addition, we determined that three genomic regions, involving the 50.5–54.0 Mb region of chicken (Gallus gallus) chromosome 1 (GGA1), the 58.5–60.5 Mb region of GGA1, and the 10.5–12.0 Mb region of GGA20, were strongly associated (P < 6.28 × 10-7) with HVP in chickens. Variants in these regions explained >50% of additive genetic variance for HVP. This study also confirmed that expression of BMP7, which codes for a bone morphogenetic protein and is located in one of the candidate regions, was significantly higher in the visceral peritoneum of Huiyang Beard chickens with HVP than in that of chickens without pigmentation (P < 0.05). Conclusions HVP is a quantitative trait with moderate heritability. Genomic variants resulting in HVP were identified on GGA1 and GGA20, and expression of the BMP7 gene appears to be upregulated in HVP-affected chickens. Findings from this study should be used as a basis for further functional validation of candidate genes involved in HVP. PMID:23679099

  4. A genetic study of the human low-voltage electroencephalogram.

    PubMed

    Anokhin, A; Steinlein, O; Fischer, C; Mao, Y; Vogt, P; Schalt, E; Vogel, F

    1992-01-01

    The studied phenotype, the low-voltage electroencephalogram (LVEEG), is characterized by the absence of an alpha rhythm from the resting EEG. In previous studies, evidence was found for a simple autosomal-dominant mode of inheritance of the LVEEG. Such a polymorphism in brain function can be used as a research model for the stepwise elucidation of the molecular mechanism involved in those aspects of neuronal activity that are reflected in the EEG. Linkage with the variable number of tandem repeats (VNTR) marker CMM6 (D20S19) and localization of an LVEEG (EEGV1) gene on 20q have previously been reported, and genetic heterogeneity has been demonstrated. This latter result has been corroborated by studying new marker (MS214). The phenotype of the LVEEG is described here in greater detail. Its main characteristic is the absence of rhythmic alpha activity, especially in occipital leads, whereas other wave forms such as beta or theta waves may be present. Analysis of 17 new families (some of them large), together with 60 previously described nuclear families, supports the genetic hypothesis of an autosomal-dominant mode of inheritance. Problems connected with the analysis of linkage heterogeneity, exclusion mapping, and the study of multipoint linkage are discussed. A possible explanation of the localization of LVEEG in the close vicinity of another gene influencing synchronization of the normal EEG, the gene for benign neonatal epilepsie, is given.

  5. The Tourette International Collaborative Genetics (TIC Genetics) study, finding the genes causing Tourette syndrome: objectives and methods.

    PubMed

    Dietrich, Andrea; Fernandez, Thomas V; King, Robert A; State, Matthew W; Tischfield, Jay A; Hoekstra, Pieter J; Heiman, Gary A

    2015-02-01

    Tourette syndrome (TS) is a neuropsychiatric disorder characterized by recurrent motor and vocal tics, often accompanied by obsessive-compulsive disorder and/or attention-deficit/hyperactivity disorder. While the evidence for a genetic contribution is strong, its exact nature has yet to be clarified fully. There is now mounting evidence that the genetic risks for TS include both common and rare variants and may involve complex multigenic inheritance or, in rare cases, a single major gene. Based on recent progress in many other common disorders with apparently similar genetic architectures, it is clear that large patient cohorts and open-access repositories will be essential to further advance the field. To that end, the large multicenter Tourette International Collaborative Genetics (TIC Genetics) study was established. The goal of the TIC Genetics study is to undertake a comprehensive gene discovery effort, focusing both on familial genetic variants with large effects within multiply affected pedigrees and on de novo mutations ascertained through the analysis of apparently simplex parent-child trios with non-familial tics. The clinical data and biomaterials (DNA, transformed cell lines, RNA) are part of a sharing repository located within the National Institute for Mental Health Center for Collaborative Genomics Research on Mental Disorders, USA, and will be made available to the broad scientific community. This resource will ultimately facilitate better understanding of the pathophysiology of TS and related disorders and the development of novel therapies. Here, we describe the objectives and methods of the TIC Genetics study as a reference for future studies from our group and to facilitate collaboration between genetics consortia in the field of TS.

  6. A novel set of single-copy nuclear DNA markers for the genetic study of Salicaceae.

    PubMed

    Du, S H; Wang, Z S; Zhang, J G

    2014-07-04

    Species of Populus are widely distributed worldwide, playing a significant role in both ecology and economy. However, the lack of single-copy nuclear markers limits knowledge about the phylogeny and population genetics of this genus. In the present study, primer pairs of 15 single-copy nuclear markers were developed through bioinformatic methods based on complete genomic sequences of Populus trichocarpa and Salix arbutifolia. Twenty individuals of Populus davidiana Dode and Salix matsudana Koidz were used to evaluate the basic application of these markers with respect to marker length and diversity indices, respectively. The utility of single-copy nuclear markers is anticipated to facilitate further studies about the phylogeny, population genetics, and phylogeography of this genus, in addition to providing information about the evolutionary dynamics of Salicaceae.

  7. COAGULASE-NEGATIVE MUTANTS OF STAPHYLOCOCCUS AUREUS: GENETIC STUDIES.

    PubMed

    KORMAN, R Z

    1963-09-01

    Korman, Ruth Z. (Cornell University, Ithaca, N.Y.). Coagulase-negative mutants of Staphylococcus aureus: genetic studies. J. Bacteriol. 86:363-369. 1963.-The behavior in mutation and transduction of pleiotropic coagulase-negative mutants of Staphylococcus aureus PS 53 (NCTC 8511) was analyzed. Coagulase-positive colonies were recovered, as well as a novel phenotype resistant to some cell-wall inhibitors and differing in sugar fermentation pattern. The hypothesis that the coagulase-negative strains differ from the original propagating strain in the structure or organization of the cell wall is discussed.

  8. Muscle channelopathies and critical points in functional and genetic studies

    PubMed Central

    Jurkat-Rott, Karin; Lehmann-Horn, Frank

    2005-01-01

    Muscle channelopathies are caused by mutations in ion channel genes, by antibodies directed against ion channel proteins, or by changes of cell homeostasis leading to aberrant splicing of ion channel RNA or to disturbances of modification and localization of channel proteins. As ion channels constitute one of the only protein families that allow functional examination on the molecular level, expression studies of putative mutations have become standard in confirming that the mutations cause disease. Functional changes may not necessarily prove disease causality of a putative mutation but could be brought about by a polymorphism instead. These problems are addressed, and a more critical evaluation of the underlying genetic data is proposed. PMID:16075040

  9. Studies of genetic transformation of higher plants using irradiated pollen

    SciTech Connect

    Chyi, Y.S.

    1984-01-01

    Pandey has reported extensively on an unusual genetic phenomenon he called egg transformation. When compatible pollen was treated wth genetically lethal dosage of ..gamma..-radiation (100,000 rad), and used as mentor pollen to overcome selfincompatibility of several Nicotiana species, some genetic characters were found to be transferred from the radiation killed pollen to nonhybrid progeny. Observed transformants were fertile, cytogenetically normal, and had maternal phenotypes except for those specific traits transferred from the donors. Heavily irradiated pollen was believed to discharge its radiation-fragmented DNA (chromatin) into the embryo sac and bring about the transformation of the egg. The frequency of gene transfer was reported to be over 50%, and happened for all three characters Pandey studied - self incompatible specificities, flower color, and pollen color. Plant species studied were tomato, pea, apple, rapeseed, and Nicotiana species, including various stocks from Dr. Pandey. Treatments included pollinations with soley irradiated donor pollen, with a mixture of irradiated donor and normal self pollen, with a mixture of normal donor and self pollen, and double pollinations with irradiated donor pollen and normal self pollen, using different time intervals to separate the two pollinations. A total of 6210 pollinations were made, and 17,522 seedlings representing 87,750 potential transformational events were screened. In no case was an unambiguous transformant recovered. This research was unable to confirm or expand upon the findings of Dr. Pandey, or elucidate the mechanisms underlying such phenomena. Alternative explanations for Pandey's data were postulated. This approach to gene transfer by using irradiated pollen appears to be of little practical use to plant breeders.

  10. 7 CFR 1710.253 - Engineering and cost studies-addition of generation capacity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Engineering and cost studies-addition of generation... TO ELECTRIC LOANS AND GUARANTEES Construction Work Plans and Related Studies § 1710.253 Engineering... engineering and cost studies as specified by RUS. The studies shall cover a period from the beginning of...

  11. 7 CFR 1710.253 - Engineering and cost studies-addition of generation capacity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 11 2011-01-01 2011-01-01 false Engineering and cost studies-addition of generation... TO ELECTRIC LOANS AND GUARANTEES Construction Work Plans and Related Studies § 1710.253 Engineering... engineering and cost studies as specified by RUS. The studies shall cover a period from the beginning of...

  12. 7 CFR 1710.253 - Engineering and cost studies-addition of generation capacity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 11 2013-01-01 2013-01-01 false Engineering and cost studies-addition of generation... TO ELECTRIC LOANS AND GUARANTEES Construction Work Plans and Related Studies § 1710.253 Engineering... engineering and cost studies as specified by RUS. The studies shall cover a period from the beginning of...

  13. 7 CFR 1710.253 - Engineering and cost studies-addition of generation capacity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 11 2014-01-01 2014-01-01 false Engineering and cost studies-addition of generation... TO ELECTRIC LOANS AND GUARANTEES Construction Work Plans and Related Studies § 1710.253 Engineering... engineering and cost studies as specified by RUS. The studies shall cover a period from the beginning of...

  14. 7 CFR 1710.253 - Engineering and cost studies-addition of generation capacity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 11 2012-01-01 2012-01-01 false Engineering and cost studies-addition of generation... TO ELECTRIC LOANS AND GUARANTEES Construction Work Plans and Related Studies § 1710.253 Engineering... engineering and cost studies as specified by RUS. The studies shall cover a period from the beginning of...

  15. Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study

    PubMed Central

    Matullo, Giuseppe; Guarrera, Simonetta; Betti, Marta; Fiorito, Giovanni; Ferrante, Daniela; Voglino, Floriana; Cadby, Gemma; Di Gaetano, Cornelia; Rosa, Fabio; Russo, Alessia; Hirvonen, Ari; Casalone, Elisabetta; Tunesi, Sara; Padoan, Marina; Giordano, Mara; Aspesi, Anna; Casadio, Caterina; Ardissone, Francesco; Ruffini, Enrico; Betta, Pier Giacomo; Libener, Roberta; Guaschino, Roberto; Piccolini, Ezio; Neri, Monica; Musk, Arthur W. B.; de Klerk, Nicholas H.; Hui, Jennie; Beilby, John; James, Alan L.; Creaney, Jenette; Robinson, Bruce W.; Mukherjee, Sutapa; Palmer, Lyle J.; Mirabelli, Dario; Ugolini, Donatella; Bonassi, Stefano; Magnani, Corrado; Dianzani, Irma

    2013-01-01

    Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5–17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2–3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52–95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos. PMID:23626673

  16. Genetic-Quantitative Study of the First-Service Pregnancy Probability of Murrah Heifers.

    PubMed

    Fernandes, P B; Marques, K O; de Araujo Neto, F R; de Oliveira, D P; Hurtado-Lugo, N A; Aspilcueta-Borquis, R R; Tonhati, H

    2016-06-01

    Because of the importance of reproduction in stock breeding systems, it is necessary to find selection criteria that increase reproductive efficiency. The aim of this study was to estimate genetic parameters for the probability of conception on first service (PROB) in Murrah heifers, and its association with other traits of economic interest [age at first calving (AFC), service period, calving interval and milk yield at 270 days], with the purpose of evaluating their use as selection criteria. Reproductive information and first lactation records of 1200 Murrah heifers were used to perform two-trait analyses between PROB and the other characteristics. Bayesian inference was used to estimate the variance components, considering PROB as threshold and the other as linear factors. The results demonstrate that this trait has heritability of 0.15, indicating the possibility of a genetic gain by using it for selection. With respect to the genetic correlation estimates, the only high-magnitude association was with AFC (-0.899), which is the current criterion indicating sexual precocity of females. In the light of the parameters estimated, the first-service pregnancy rate is an alternative for indication of sexual precocity, although presenting a smaller genetic gain than the current standard AFC. Nevertheless, additional research should be conducted regarding this trait to assess the economic importance of its use in dairy buffalo production systems. PMID:27117537

  17. Biochemical and Molecular Genetic Studies on Biosilica Morphogenesis in Diatoms

    NASA Astrophysics Data System (ADS)

    Kroger, N.; Poulsen, N.

    2006-12-01

    Diatoms are a large group of unicellular microalgae encased by silica cell walls that exhibit species-specific micro-and nanopatterns. Previously, we have characterized from diatoms unique phosphoproteins (termed silaffins) and unusually long polyamine chains (termed LCPA), which have both been implicated in biosilica formation. While the chemical structures of LCPA are largely conserved among different diatom species, the silaffins exhibit extensive structural variations. In vitro studies on the silica formation activities of silaffins and LCPA from the diatom Thalassiosira pseudonana indicate that silica morphogenesis is primarily determined by silaffins rather than LCPA. Recently, the complete genome sequence of T. pseudonana has become available, which for the first time opens the door to employ functional genomic approaches for studying the mechanism of silica biomineralization. To this end we have established the first genetic transformation system for T. pseudonana, which will be instrumental for analyzing the functions of silaffins in vivo, and for identifying new components of the diatom silica forming machinery. Here we describe the current knowledge on the structures and properties of silaffins and LCPA, the methods for genetic manipulation of T. pseudonana, and the first experimental steps towards functional genomics in diatoms.

  18. Experimental studies on some genetic effects of marine pollution

    NASA Astrophysics Data System (ADS)

    Battaglia, B.; Bisol, P. M.; Rodinò, E.

    1980-03-01

    Following the results of a series of investigations carried out to estimate the degree of marine pollution by utilizing certain marine filter feeders, such as the blue mussel Mytilus galloprovincialis, research has been planned to detect possible genetic effects of pollutants, with special attention to those acting at the population level. The possible selective role of pollutants has been studied both in natural ( Mytilus) and in experimental ( Tisbe holothuriae) populations by utilizing some electrophoretically-detected gene-enzyme systems as genetic markers. For some of the seven polymorphic loci studied in Mytilus (AP, LAP, 6-PGD, IDHs, IDHm, PGI, PGM) significant changes in gene frequencies have been detected which can be related to the degree of pollution in the sampling areas. In the more polluted areas these changes were accompanied by a decrease in the frequency of heterozygotes. Similar changes in gene frequencies also occurred in laboratory populations of the copepod Tisbe, reared under various experimental conditions. In particular, certain alleles of two loci, PGI-1 and AP-1, exhibited an increase in frequency, especially in populations cultured at various levels of oil pollution. This trend appeared more significant for the locus PGI. The fact that equilibria are reached and that the less favoured alleles are nevertheless maintained in the populations, even at extremely low frequencies, suggests the balanced nature of these enzyme polymorphisms. The significance of the above findings is briefly discussed.

  19. Children of the atomic bomb survivors: A genetic study

    SciTech Connect

    Neel, J.V.; Schull, W.J.

    1991-01-01

    This volume represents the results of over 40 years of study of the latent health effects on the survivors of the atomic bomb blasts. Planning for this research began in 1946 and data collection has been ongoing since 1948. The work represents the efforts of both US and Japanese agencies and presents 13 papers which the editors believe represent the best scientific information related to the genetic effects of radiation exposure. In general, the results presented here indicate that radiation exposure effects on reproductive cells are less than previously thought. The paper contained here examine that question in light of effects on pregnancy outcome, sex ratio, congenital defects, and early mortality of children. The papers also present helpful comparison of these results with the results seen in experimental radiation studies with animals. For anyone interested in the risks associated with radiation studies, this book represents a vital collection of information.

  20. Recommendations for using standardised phenotypes in genetic association studies.

    PubMed

    Naylor, Melissa G; Weiss, Scott T; Lange, Christoph

    2009-07-01

    Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity). These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

  1. Methods to Study Metastasis in Genetically Modified Mice.

    PubMed

    Kabeer, Farhia; Beverly, Levi J; Darrasse-Jèze, Guillaume; Podsypanina, Katrina

    2016-02-01

    Metastasis is often modeled by xenotransplantation of cell lines in immunodeficient mice. A wealth of information about tumor cell behavior in the new environment is obtained from these efforts. Yet by design, this approach is "tumor-centric," as it focuses on cell-autonomous determinants of human tumor dissemination in mouse tissues, in effect using the animal body as a sophisticated "Petri dish" providing nutrients and support for tumor growth. Transgenic or gene knockout mouse models of cancer allow the study of tumor spread as a systemic disease and offer a complimentary approach for studying the natural history of cancer. This introduction is aimed at describing the overall methodological approach to studying metastasis in genetically modified mice, with a particular focus on using animals with regulated expression of potent human oncogenes in the breast. PMID:26832689

  2. Inherited neuromyotonia: a clinical and genetic study of a family.

    PubMed

    Falace, Antonio; Striano, Pasquale; Manganelli, Fiore; Coppola, Antonietta; Striano, Salvatore; Minetti, Carlo; Zara, Federico

    2007-01-01

    Neuromyotonia is a disorder of peripheral nerve hyperexcitability characterized by myokymia, muscle cramps and stiffness, delayed muscle relaxation after contraction (pseudomyotonia), and hyperhidrosis, associated with well described spontaneous electromyographic features. It is usually an acquired disorder associated with autoantibodies against neuronal voltage-gated potassium channels. However, mutations of KCNA1, encoding the K(+) channel subunit hKv1.1, have been reported in rare families with neuromyotonia, and mutations in KCNQ2, encoding voltage-gated potassium M channel subunit, in families with benign neonatal seizures and myokymia. We report a three-generation family with inherited neuromyotonia without evidence of immunological involvement. Genetic study excluded mutations in KCNA1, KCNA2, KCNA6 and KCNQ2 genes. Our study does not completely exclude the involvement of other genes encoding ion channels subunits in the pathogenesis of this disorder. Further studies of familial cases will shed light on the molecular basis of inherited neuromyotonia. PMID:17140792

  3. Do Other People's Plights Matter? A Genetically Informed Twin Study of the Role of Social Context in the Link between Peer Victimization and Children's Aggression and Depression Symptoms

    ERIC Educational Resources Information Center

    Brendgen, Mara; Vitaro, Frank; Barker, Edward D.; Girard, Alain; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2013-01-01

    Using a genetically informed design, this study examined the additive and interactive effects of genetic risk, personal peer victimization experiences, and peer victimization experienced by others on children's aggression and depression symptoms. Of major interest was whether these effects varied depending on whether or not the victimized others…

  4. The Case of the "Tainted" Taco Shells: A Case Study on Genetically Modified Foods

    ERIC Educational Resources Information Center

    Taylor, Ann T. S.

    2004-01-01

    This case study introduces students to the use of genetically modified foods. Students learn how genetically modified plants are made, and then they read primary literature papers to evaluate the environmental, economic, and health issues. (Contains 2 figures.)

  5. Genetic counselor perceptions of genetic counseling session goals: a validation study of the reciprocal-engagement model.

    PubMed

    Hartmann, Julianne E; Veach, Patricia McCarthy; MacFarlane, Ian M; LeRoy, Bonnie S

    2015-04-01

    Although some researchers have attempted to define genetic counseling practice goals, no study has obtained consensus about the goals from a large sample of genetic counselors. The Reciprocal-Engagement Model (REM; McCarthy Veach, Bartels & LeRoy, 2007) articulates 17 goals of genetic counseling practice. The present study investigated whether these goals could be generalized as a model of practice, as determined by a larger group of clinical genetic counselors. Accordingly, 194 genetic counselors were surveyed regarding their opinions about the importance of each goal and their perceptions of how frequently they achieve each goal. Mean importance ratings suggest they viewed every goal as important. Factor analysis of the 17 goals yielded four factors: Understanding and Appreciation, Support and Guidance, Facilitative Decision-Making, and Patient-Centered Education. Patient-Centered Education and Facilitative Decision-Making goals received the highest mean importance ratings. Mean frequency ratings were consistently lower than importance ratings, suggesting genetic counseling goals may be difficult to achieve and/or not applicable in all situations. A number of respondents provided comments about the REM goals that offer insight into factors related to implementing the goals in clinical practice. This study presents preliminary evidence concerning the validity of the goals component of the REM.

  6. Exogenous Visual Orienting Is Associated with Specific Neurotransmitter Genetic Markers: A Population-Based Genetic Association Study

    PubMed Central

    Lundwall, Rebecca A.; Guo, Dong-Chuan; Dannemiller, James L.

    2012-01-01

    Background Currently, there is a sense that the spatial orienting of attention is related to genotypic variations in cholinergic genes but not to variations in dopaminergic genes. However, reexamination of associations with both cholinergic and dopaminergic genes is warranted because previous studies used endogenous rather than exogenous cues and costs and benefits were not analyzed separately. Examining costs (increases in response time following an invalid pre-cue) and benefits (decreases in response time following a valid pre-cue) separately could be important if dopaminergic genes (implicated in disorders such as attention deficit disorder) independently influence the different processes of orienting (e.g., disengage, move, engage). Methodology/Principal Findings We tested normal subjects (N = 161) between 18 and 61 years. Participants completed a computer task in which pre-cues preceded the presence of a target. Subjects responded (with a key press) to the location of the target (right versus left of fixation). The cues could be valid (i.e., appear where the target would appear) or invalid (appear contralateral to where the target would appear). DNA sequencing assays were performed on buccal cells to genotype known genetic markers and these were examined for association with task scores. Here we show significant associations between visual orienting and genetic markers (on COMT, DAT1, and APOE; R2s from 4% to 9%). Conclusions/Significance One measure in particular – the response time cost of a single dim, invalid cue – was associated with dopaminergic markers on COMT and DAT1. Additionally, variations of APOE genotypes based on the ε2/ε3/ε4 alleles were also associated with response time differences produced by simultaneous cues with unequal luminances. We conclude that individual differences in visual orienting are related to several dopaminergic markers as well as to a cholinergic marker. These results challenge the view that orienting is not

  7. DNA fingerprinting secondary transfer from different skin areas: Morphological and genetic studies.

    PubMed

    Zoppis, Silvia; Muciaccia, Barbara; D'Alessio, Alessio; Ziparo, Elio; Vecchiotti, Carla; Filippini, Antonio

    2014-07-01

    The correct identification of the biological samples under analysis is crucial in forensic investigation in that it represents the pivotal issue attesting that the resulting genetic profiles are fully reliable in terms of weight of the evidence. The study reported herein shows that "touch DNA" secondary transfer is indeed possible from person to person and, in turn, from person to object depending on the specific sebaceous or non-sebaceous skin area previously touched. In addition, we demonstrate the presence of fragmented single stranded DNA specifically immunodetected in the vast majority of cells forming the sebaceous gland but not in the epidermis layers, strongly indicating that sebaceous fluid represents an important vector responsible for DNA transfer. In view of our results, forensic investigations need to take into account that the propensity to leave behind genetic material through contact could depend from the individual ability to shed sebaceous fluid on the skin surface.

  8. Warranted concerns, warranted outlooks: a focus group study of public understandings of genetic research.

    PubMed

    Bates, Benjamin R; Lynch, John A; Bevan, Jennifer L; Condit, Celeste M

    2005-01-01

    This paper discusses how the American public accounts for the concerns that they have about genetic research and the benefits that they foresee. We develop a general framework for discussing public claims about genetic technology based on Stephen Toulmin's model of warrants in argumentation. After a review of the results from public opinion polls about genetic research, we present a focus group study of public understandings of genetics. We outline the warrants, or publicly accepted "good reasons", that this group offers for accepting some aspects of genetic technology and for rejecting other aspects. The warrants presented by the public in their discussion of genetic research indicate that the public has a complex, informed understanding of genetic research, albeit a non-technical one. The paper concludes with a discussion of the importance of public participation in debates over genetic research and the ways that researchers and policymakers could adapt to public concerns about genetics.

  9. Study of the genetic diversity and structure of a natural population of Nectandra megapotamica (Spreng.) Mez. using RAPD markers.

    PubMed

    Costa, L S; Reiniger, L R S; Heinzmann, B M; Amaral, L P; Serrote, C M L

    2015-01-01

    Nectandra megapotamica (Spreng.) Mez. is a tree species that naturally occurs in the Atlantic Forest, Brazil. The aim of this study was to evaluate the genetic diversity and structure of a natural population of 12 N. megapotamica individuals using random amplified polymorphic DNA markers. Eleven primers were used in this study, producing 81 bands, of which 98.99% were polymorphic. Analysis using STRUCTURE defined three different clusters (K = 3), results that were consistent with those of principal coordinates analysis. Both Nei's genetic diversity (h = 0.33) and Shannon's diversity index (I = 0.49) were relatively high. Analysis of molecular variance indicated that 24.89% of the genetic variability was among clusters, while the remaining 75.11% was within clusters. The Mantel test showed a weak correlation between genetic and geographic distances (r = 0.25, P = 0.105). Overall, the results revealed high levels of genetic diversity within clusters and high genetic differentiation among clusters without any spatial pattern of genetic variability. In addition, gene flow was independent of the geographical distribution and was compatible with the hierarchical island model. PMID:26782488

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

    PubMed Central

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

    1988-01-01

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

  11. Clinicopathological and genetic study of early-onset demyelinating neuropathy.

    PubMed

    Parman, Yesim; Battaloglu, Esra; Baris, Ibrahim; Bilir, Birdal; Poyraz, Mürüvvet; Bissar-Tadmouri, Nisrine; Williams, Anna; Ammar, Nadia; Nelis, Eva; Timmerman, Vincent; De Jonghe, Peter; Najafov, Ayaz; Necefov, Ayaz; Deymeer, Feza; Serdaroglu, Piraye; Brophy, Peter J; Said, G

    2004-11-01

    Autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT4), Dejerine-Sottas disease and congenital hypomyelinating neuropathy are variants of hereditary demyelinating neuropathy of infancy, a genetically heterogeneous group of disorders. To explore the spectrum of early-onset demyelinating neuropathies further, we studied the clinicopathological and genetic aspects of 20 patients born to unaffected parents. In 19 families out of 20, consanguinity between the parents or presence of an affected sib suggested autosomal recessive transmission. Screening of various genes known to be involved in CMT4 revealed six mutations of which five are novel. Four of these novel mutations occurred in the homozygous state and include: one in GDAP1, one in MTMR2, one in PRX and one in KIAA1985. One patient was heterozygous for a novel MTMR2 mutation and still another was homozygous for the founder mutation, R148X, in NDRG1. All patients tested negative for mutations in EGR2. Histopathological examination of nerve biopsy specimens showed a severe, chronic demyelinating neuropathy, with onion bulb formation, extensive demyelination of isolated fibres and axon loss. We did not discern a specific pattern of histopathology that could be correlated to mutations in a particular gene. PMID:15469949

  12. The Relevance of HLA Sequencing in Population Genetics Studies

    PubMed Central

    Sanchez-Mazas, Alicia

    2014-01-01

    Next generation sequencing (NGS) is currently being adapted by different biotechnological platforms to the standard typing method for HLA polymorphism, the huge diversity of which makes this initiative particularly challenging. Boosting the molecular characterization of the HLA genes through efficient, rapid, and low-cost technologies is expected to amplify the success of tissue transplantation by enabling us to find donor-recipient matching for rare phenotypes. But the application of NGS technologies to the molecular mapping of the MHC region also anticipates essential changes in population genetic studies. Huge amounts of HLA sequence data will be available in the next years for different populations, with the potential to change our understanding of HLA variation in humans. In this review, we first explain how HLA sequencing allows a better assessment of the HLA diversity in human populations, taking also into account the methodological difficulties it introduces at the statistical level; secondly, we show how analyzing HLA sequence variation may improve our comprehension of population genetic relationships by facilitating the identification of demographic events that marked human evolution; finally, we discuss the interest of both HLA and genome-wide sequencing and genotyping in detecting functionally significant SNPs in the MHC region, the latter having also contributed to the makeup of the HLA molecular diversity observed today. PMID:25126587

  13. A multiple phenotype imputation method for genetic studies

    PubMed Central

    Dahl, Andrew; Iotchkova, Valentina; Baud, Amelie; Johansson, Åsa; Gyllensten, Ulf; Soranzo, Nicole; Mott, Richard; Kranis, Andreas; Marchini, Jonathan

    2016-01-01

    Genetic association studies have yielded a wealth of biologic discoveries. However, these have mostly analyzed one trait and one SNP at a time, thus failing to capture the underlying complexity of these datasets. Joint genotype-phenotype analyses of complex, high-dimensional datasets represent an important way to move beyond simple GWAS with great potential. The move to high-dimensional phenotypes will raise many new statistical problems. In this paper we address the central issue of missing phenotypes in studies with any level of relatedness between samples. We propose a multiple phenotype mixed model and use a computationally efficient variational Bayesian algorithm to fit the model. On a variety of simulated and real datasets from a range of organisms and trait types, we show that our method outperforms existing state-of-the-art methods from the statistics and machine learning literature and can boost signals of association. PMID:26901065

  14. [The study of tomato fruit weight quantitative trait locus and its application in genetics teaching].

    PubMed

    Wang, Haiyan

    2015-08-01

    The classical research cases, which have greatly promoted the development of genetics in history, can be combined with the content of courses in genetics teaching to train students' ability of scientific thinking and genetic analysis. The localization and clone of gene controlling tomato fruit weight is a pioneer work in quantitative trait locus (QTL) studies and represents a complete process of QTL research in plants. Application of this integrated case in genetics teaching, which showed a wonderful process of scientific discovery and the fascination of genetic research, has inspired students' interest in genetics and achieved a good teaching effect.

  15. Additive-dominance genetic model analyses for late-maturity alpha-amylase activity in a bread wheat factorial crossing population.

    PubMed

    Rasul, Golam; Glover, Karl D; Krishnan, Padmanaban G; Wu, Jixiang; Berzonsky, William A; Ibrahim, Amir M H

    2015-12-01

    Elevated level of late maturity α-amylase activity (LMAA) can result in low falling number scores, reduced grain quality, and downgrade of wheat (Triticum aestivum L.) class. A mating population was developed by crossing parents with different levels of LMAA. The F2 and F3 hybrids and their parents were evaluated for LMAA, and data were analyzed using the R software package 'qgtools' integrated with an additive-dominance genetic model and a mixed linear model approach. Simulated results showed high testing powers for additive and additive × environment variances, and comparatively low powers for dominance and dominance × environment variances. All variance components and their proportions to the phenotypic variance for the parents and hybrids were significant except for the dominance × environment variance. The estimated narrow-sense heritability and broad-sense heritability for LMAA were 14 and 54%, respectively. High significant negative additive effects for parents suggest that spring wheat cultivars 'Lancer' and 'Chester' can serve as good general combiners, and that 'Kinsman' and 'Seri-82' had negative specific combining ability in some hybrids despite of their own significant positive additive effects, suggesting they can be used as parents to reduce LMAA levels. Seri-82 showed very good general combining ability effect when used as a male parent, indicating the importance of reciprocal effects. High significant negative dominance effects and high-parent heterosis for hybrids demonstrated that the specific hybrid combinations; Chester × Kinsman, 'Lerma52' × Lancer, Lerma52 × 'LoSprout' and 'Janz' × Seri-82 could be generated to produce cultivars with significantly reduced LMAA level.

  16. Protecting genetic materials and genetic information: a case study of Guthrie Cards in Victoria.

    PubMed

    Lawson, C; Smith, R

    2001-11-01

    The authors are privileged to have been provided with correspondence about a dispute over the ongoing storage of genetic material (as Guthrie Cards) in Victoria. The correspondence details confusion over the roles of government and the private sector service provider in accounting for the storage, use and destruction of these stored genetic materials collected as part of a government public health program. The purpose in publishing this account is to highlight the present inadequacies in current practices and the ongoing potential for a crisis in the management of collected genetic materials through a lack of appropriate regulation, transparency and accountability. The article suggests measures to remedy some of the existing inadequacies in contractual arrangements and recommends that the government retain ownership and control of both the genetic materials and the derived information to ensure some accountability in the present legal environment.

  17. Excitotoxic food additives--relevance of animal studies to human safety.

    PubMed

    Olney, J W

    1984-01-01

    Evidence is reviewed supporting the view that excitotoxic food additives pose a significant hazard to the developing nervous system of young children. The following points are stressed: (1) although blood-brain barriers protect most central neurons from excitotoxins, certain brain regions lack such protection (a characteristic common to all vertebrate species); (2) regardless of species, it requires only a transient increase in blood excitotoxin levels for neurons in unprotected brain regions to be "silently" destroyed; (3) humans may be at particularly high risk for this kind of brain damage, since ingestion of a given amount of excitotoxin causes much higher blood excitotoxin levels in humans than in other species; (4) in addition to the heightened risk on a species basis, risk may be further increased for certain consumer sub-populations due to youth, disease or genetic factors; (5) despite these reasons for maintaining a wide margin of safety in the use of excitotoxins in foods, no safety margin is currently being observed, i.e., a comparative evaluation of animal (extensive) and human (limited) data supports the conclusion that excitotoxins, as used in foods today, may produce blood elevations high enough to cause damage to the nervous system of young children, damage which is not detectable at the time of occurrence but which may give rise to subtle disturbances in neuroendocrine function in adolescence and/or adulthood.

  18. Genetic studies in relation to kuru: an overview.

    PubMed

    Goldfarb, L G; Cervenakova, L; Gajdusek, D C

    2004-06-01

    Kuru is a subacute neurodegenerative disease presenting with limb ataxia, dysarthria, and a shivering tremor. The disease progress to complete motor and mental incapacity and death within 6 to 24 months. Neuropathologically, a typical pattern of neuronal loss, astrocytic and microglial proliferation, characteristic "kuru-type" amyloid plaques, and PrP deposits in the cerebral cortex and cerebellum are observed. Kuru is the prototype of a group of human transmissible spongiform encephalopathies (TSEs), or "prion" diseases, that include hereditary, sporadic and infectious forms. The latest member of this group, the variant Creutzfeldt-Jakob disease (vCJD), linked to transmission of bovine spongiform encephalopathy (BSE) to humans, shows features similar to kuru. Kuru has emerged at the beginning of the 1900s in a small indigenous population of New-Guinean Eastern Highlands, reached epidemic proportions in the mid-1950s and disappeared progressively in the latter half of the century to complete absence at the end of the 1990s. Early studies made infection, the first etiologic assumption, seem unlikely and led to a hypothesis that kuru might be a genetically determined or genetically mediated illness. After transmissibility of kuru had been discovered and all major epidemiologic phenomena adequately explained by the spread of an infectious agent with long incubation period through the practice of cannibalism, the pattern of occurrence still continued to suggest a role for genetic predisposition. Recent studies indicate that individuals homozygous for Methionine at a polymorphic position 129 of the prion protein were preferentially affected during the kuru epidemic. The carriers of the alternative 129Met/Val and 129Val/Val genotypes had a longer incubation period and thus developed disease at a later age and at a later stage of the epidemic. Observations made during the kuru epidemic are helpful in the understanding of the current vCJD outbreak, and vice versa clinical

  19. Studies of jet fuel additives using the quartz crystal microbalance and pressure monitoring at 140 C

    SciTech Connect

    Zabarnick, S.; Grinstead, R.R. . Aerospace Mechanics Div./KL-463)

    1994-11-01

    Recent advances in jet aircraft and engine technology have placed an ever increasing heat load on the aircraft. The bulk of this excess heat is absorbed by the aircraft fuel, as jet fuel is used as the primary coolant for the numerous heat sources. The quartz crystal microbalance (QCM) and pressure monitoring are used for the evaluation of jet fuel additives for the improvement of jet fuel thermal stability. The mechanisms of additive behavior are determined by measuring the time-dependent deposition with the QCM and oxidation by pressure measurements. Studies at various additive concentrations permits the determination of optimum additive concentrations. Additive packages made of mixtures of antioxidants, detergent/dispersants, and metal deactivators are shown to yield good improvements in thermal stability over a wide range of jet fuel types.

  20. Evolutionary triangulation: informing genetic association studies with evolutionary evidence.

    PubMed

    Huang, Minjun; Graham, Britney E; Zhang, Ge; Harder, Reed; Kodaman, Nuri; Moore, Jason H; Muglia, Louis; Williams, Scott M

    2016-01-01

    Genetic studies of human diseases have identified many variants associated with pathogenesis and severity. However, most studies have used only statistical association to assess putative relationships to disease, and ignored other factors for evaluation. For example, evolution is a factor that has shaped disease risk, changing allele frequencies as human populations migrated into and inhabited new environments. Since many common variants differ among populations in frequency, as does disease prevalence, we hypothesized that patterns of disease and population structure, taken together, will inform association studies. Thus, the population distributions of allelic risk variants should reflect the distributions of their associated diseases. Evolutionary Triangulation (ET) exploits this evolutionary differentiation by comparing population structure among three populations with variable patterns of disease prevalence. By selecting populations based on patterns where two have similar rates of disease that differ substantially from a third, we performed a proof of principle analysis for this method. We examined three disease phenotypes, lactase persistence, melanoma, and Type 2 diabetes mellitus. We show that for lactase persistence, a phenotype with a simple genetic architecture, ET identifies the key gene, lactase. For melanoma, ET identifies several genes associated with this disease and/or phenotypes related to it, such as skin color genes. ET was less obviously successful for Type 2 diabetes mellitus, perhaps because of the small effect sizes in known risk loci and recent environmental changes that have altered disease risk. Alternatively, ET may have revealed new genes involved in conferring disease risk for diabetes that did not meet nominal GWAS significance thresholds. We also compared ET to another method used to filter for phenotype associated genes, population branch statistic (PBS), and show that ET performs better in identifying genes known to associate with

  1. Evolutionary triangulation: informing genetic association studies with evolutionary evidence.

    PubMed

    Huang, Minjun; Graham, Britney E; Zhang, Ge; Harder, Reed; Kodaman, Nuri; Moore, Jason H; Muglia, Louis; Williams, Scott M

    2016-01-01

    Genetic studies of human diseases have identified many variants associated with pathogenesis and severity. However, most studies have used only statistical association to assess putative relationships to disease, and ignored other factors for evaluation. For example, evolution is a factor that has shaped disease risk, changing allele frequencies as human populations migrated into and inhabited new environments. Since many common variants differ among populations in frequency, as does disease prevalence, we hypothesized that patterns of disease and population structure, taken together, will inform association studies. Thus, the population distributions of allelic risk variants should reflect the distributions of their associated diseases. Evolutionary Triangulation (ET) exploits this evolutionary differentiation by comparing population structure among three populations with variable patterns of disease prevalence. By selecting populations based on patterns where two have similar rates of disease that differ substantially from a third, we performed a proof of principle analysis for this method. We examined three disease phenotypes, lactase persistence, melanoma, and Type 2 diabetes mellitus. We show that for lactase persistence, a phenotype with a simple genetic architecture, ET identifies the key gene, lactase. For melanoma, ET identifies several genes associated with this disease and/or phenotypes related to it, such as skin color genes. ET was less obviously successful for Type 2 diabetes mellitus, perhaps because of the small effect sizes in known risk loci and recent environmental changes that have altered disease risk. Alternatively, ET may have revealed new genes involved in conferring disease risk for diabetes that did not meet nominal GWAS significance thresholds. We also compared ET to another method used to filter for phenotype associated genes, population branch statistic (PBS), and show that ET performs better in identifying genes known to associate with

  2. Genetic Studies on Diabetic Microvascular Complications: Focusing on Genome-Wide Association Studies

    PubMed Central

    Kwak, Soo Heon

    2015-01-01

    Diabetes is a common metabolic disorder with a worldwide prevalence of 8.3% and is the leading cause of visual loss, end-stage renal disease and amputation. Recently, genome-wide association studies (GWASs) have identified genetic risk factors for diabetic microvascular complications of retinopathy, nephropathy, and neuropathy. We summarized the recent findings of GWASs on diabetic microvascular complications and highlighted the challenges and our opinion on future directives. Five GWASs were conducted on diabetic retinopathy, nine on nephropathy, and one on neuropathic pain. The majority of recent GWASs were underpowered and heterogeneous in terms of study design, inclusion criteria and phenotype definition. Therefore, few reached the genome-wide significance threshold and the findings were inconsistent across the studies. Recent GWASs provided novel information on genetic risk factors and the possible pathophysiology of diabetic microvascular complications. However, further collaborative efforts to standardize phenotype definition and increase sample size are necessary for successful genetic studies on diabetic microvascular complications. PMID:26194074

  3. Familial Scheuermann disease: a genetic and linkage study.

    PubMed Central

    McKenzie, L; Sillence, D

    1992-01-01

    Scheuermann juvenile kyphosis or Scheuermann disease is the most frequent cause of kyphosis in adolescence. However, the natural history and genetic basis is still unknown. Reports of identical radiological changes in monozygotic twins, sib recurrence, and transmission over three generations suggest underlying heritability. In this study, 12 probands were referred to us. Upon radiological examination of the proband's parents and sibs, seven were shown to have familial Scheuermann disease with an autosomal dominant pattern of inheritance. Of the remaining five probands, four had chromosomal anomalies. The three largest pedigrees were subjected to linkage analysis with three candidate genes: Duffy, COL1A1, and COL1A2. Linkage of Scheuermann disease was excluded with Duffy (lod score = -2.195 at theta = 0.10) and COL1A2 (lod score = -2.750 at theta = 0.05) in these families. Images PMID:1552543

  4. Mismatches in genetic markers in a large family study.

    PubMed Central

    Ashton, G C

    1980-01-01

    The Hawaii Family Study of Cognition provided an opportunity to investigate the frequency and implications of non-agreement, or mismatches, between observed and expected genetic marker phenotypes of husbands, wives, and children. Mismatch data from 68 families in which one or both spouses were known not to be a biological parent were used to determine the rate of undeclared nonparentage in 1,748 families in which conventional relationships were claimed. Two independent approaches gave consistent estimates, suggesting that approximately 2.3% of the 2,839 tested children from these families were probably the result of infidelity, concealed adoption, or another event. About two-thirds of the mismatches detected were probably due to properties of the techniques employed. PMID:6930820

  5. Blinders, phenotype, and fashionable genetic analysis: a critical examination of the current state of epilepsy genetic studies.

    PubMed

    Greenberg, David A; Subaran, Ryan

    2011-01-01

    Although it is accepted that idiopathic generalized epilepsy (IGE) is strongly, if not exclusively, influenced by genetic factors, there is little consensus on what those genetic influences may be, except for one point of agreement: epilepsy is a "channelopathy." This point of agreement has continued despite the failure of studies investigating channel genes to demonstrate the primacy of their influence on IGE expression. The belief is sufficiently entrenched that the more important issues involving phenotype definition, data collection, methods of analysis, and the interpretation of results have become subordinate to it. The goal of this article is to spark discussion of where the study of epilepsy genetics has been and where it is going, suggesting we may never get there if we continue on the current road. We use the long history of psychiatric genetic studies as a mirror and starting point to illustrate that only when we expand our outlook on how to study the genetics of the epilepsies, consider other mechanisms that could lead to epilepsy susceptibility, and, especially, focus on the critical problem of phenotype definition, will the major influences on common epilepsy begin to be understood. PMID:21219301

  6. Epistatic study reveals two genetic interactions in blood pressure regulation

    PubMed Central

    2013-01-01

    Background Although numerous candidate gene and genome-wide association studies have been performed on blood pressure, a small number of regulating genetic variants having a limited effect have been identified. This phenomenon can partially be explained by possible gene-gene/epistasis interactions that were little investigated so far. Methods We performed a pre-planned two-phase investigation: in phase 1, one hundred single nucleotide polymorphisms (SNPs) in 65 candidate genes were genotyped in 1,912 French unrelated adults in order to study their two-locus combined effects on blood pressure (BP) levels. In phase 2, the significant epistatic interactions observed in phase 1 were tested in an independent population gathering 1,755 unrelated European adults. Results Among the 9 genetic variants significantly associated with systolic and diastolic BP in phase 1, some may act through altering the corresponding protein levels: SNPs rs5742910 (Padjusted≤0.03) and rs6046 (Padjusted =0.044) in F7 and rs1800469 (Padjusted ≤0.036) in TGFB1; whereas some may be functional through altering the corresponding protein structure: rs1800590 (Padjusted =0.028, SE=0.088) in LPL and rs2228570 (Padjusted ≤9.48×10-4) in VDR. The two epistatic interactions found for systolic and diastolic BP in the discovery phase: VCAM1 (rs1041163) * APOB (rs1367117), and SCGB1A1 (rs3741240) * LPL (rs1800590), were tested in the replication population and we observed significant interactions on DBP. In silico analyses yielded putative functional properties of the SNPs involved in these epistatic interactions trough the alteration of corresponding protein structures. Conclusions These findings support the hypothesis that different pathways and then different genes may act synergistically in order to modify BP. This could highlight novel pathophysiologic mechanisms underlying hypertension. PMID:23298194

  7. Population genetic studies in the genomic sequencing era

    PubMed Central

    CHEN, Hua

    2015-01-01

    Recent advances in high-throughput sequencing technologies have revolutionized the field of population genetics. Data now routinely contain genomic level polymorphism information, and the low cost of DNA sequencing enables researchers to investigate tens of thousands of subjects at a time. This provides an unprecedented opportunity to address fundamental evolutionary questions, while posing challenges on traditional population genetic theories and methods. This review provides an overview of the recent methodological developments in the field of population genetics, specifically methods used to infer ancient population history and investigate natural selection using large-sample, large-scale genetic data. Several open questions are also discussed at the end of the review. PMID:26228473

  8. Evaluating Drugs and Food Additives for Public Use: A Case Studies Approach.

    ERIC Educational Resources Information Center

    Merritt, Sheridan V.

    1980-01-01

    Described is a case study used in an introductory college biology course that provides a basis for generating debate on an issue concerning the regulation of controversial food additives and prescription drugs. The case study contained within this article deals with drug screening, specifically with information related to thalidomide. (CS)

  9. Studying genetic research participants: lessons from the "Learning About Research in North Carolina" study.

    PubMed

    Corbie-Smith, Giselle; Blumenthal, Connie; Henderson, Gail; Garrett, Joanne; Bussey-Jones, Jada; Moloney, Mairead; Sandler, Robert S; Lloyd, Stacey W; Dorrance, Jessica; Darter, Jane

    2008-08-01

    Given the prohibitive cost of recruiting large and diverse populations for genetic explorations in cancer research, there has been a call for genetic studies to engage existing cohorts of research participants. This strategy could lead to more efficient recruitment and potentially result in significant advances in the understanding of cancer etiology and treatment. The Learning About Research in North Carolina (LeARN) study responded to the National Human Genome Research Institute interest in research on how study participants from diverse populations who had participated in genetic research perceived the risks and benefits of participating in combined epidemiologic-genetic research, how well they understand the purpose of the research and the uses to which the research results may be put, and how involvement in such research affects perceptions of disease causality. In this article, we give an overview of the LeARN study, summarizing the methods we used, challenges we encountered, and lessons learned about recruiting participants who have previously participated in genetic research.

  10. GENETIC AND ENVIRONMENTAL EFFECTS ON BODY MASS INDEX DURING ADOLESCENCE: A PROSPECTIVE STUDY AMONG FINNISH TWINS

    PubMed Central

    Lajunen, Hanna-Reetta; Kaprio, Jaakko; Keski-Rahkonen, Anna; Rose, Richard J.; Pulkkinen, Lea; Rissanen, Aila; Silventoinen, Karri

    2009-01-01

    Objective To study genetic and environmental factors affecting body mass index (BMI) and BMI phenotypic correlations across adolescence. Design Prospective, population-based, twin cohort study. Subjects and methods We used twin modeling in 2413 monozygotic and same-sex and opposite-sex dizygotic Finnish twin pairs born in 1983–1987 and assessed by self-report questionnaires at 11–12, 14, and 17 years. Results Heritability of BMI was estimated to be 0.58–0.69 among 11–12- and 14-year-old boys and girls, 0.83 among 17-year-old boys and 0.74 among girls. Common environmental effects shared by siblings were 0.15–0.24 among 11–12- and 14-year-old boys and girls but no longer discernible at 17 y. Unique environmental effects were 0.15–0.23. Additive genetic factors explained 90–96% of the BMI phenotypic correlations across adolescence, whereas unique environmental factors explained the rest. Common environment had no effect on BMI phenotypic correlations. Conclusions The genetic contribution to BMI is strong during adolescence, and it mainly explains BMI phenotypic correlations across adolescence. Common environmental factors have an effect on BMI during early adolescence, but that effect disappears by late adolescence. PMID:19337205

  11. What's in a name; Genetic structure in Solanum section Petota studied using population-genetic tools

    PubMed Central

    2011-01-01

    Background The taxonomy and systematic relationships among species of Solanum section Petota are complicated and the section seems overclassified. Many of the presumed (sub)species from South America are very similar and they are able to exchange genetic material. We applied a population genetic approach to evaluate support for subgroups within this material, using AFLP data. Our approach is based on the following assumptions: (i) accessions that may exchange genetic material can be analyzed as if they are part of one gene pool, and (ii) genetic differentiation among species is expected to be higher than within species. Results A dataset of 566 South-American accessions (encompassing 89 species and subspecies) was analyzed in two steps. First, with the program STRUCTURE 2.2 in an 'unsupervised' procedure, individual accessions were assigned to inferred clusters based on genetic similarity. The results showed that the South American members of section Petota could be arranged in 16 clusters of various size and composition. Next, the accessions within the clusters were grouped by maximizing the partitioning of genetic diversity among subgroups (i.e., maximizing Fst values) for all available individuals of the accessions (2767 genotypes). This two-step approach produced an optimal partitioning into 44 groups. Some of the species clustered as genetically distinct groups, either on their own, or combined with one or more other species. However, accessions of other species were distributed over more than one cluster, and did not form genetically distinct units. Conclusions We could not find any support for 43 species (almost half of our dataset). For 28 species some level of support could be found varying from good to weak. For 18 species no conclusions could be drawn as the number of accessions included in our dataset was too low. These molecular data should be combined with data from morphological surveys, with geographical distribution data, and with information from

  12. Genetic Studies of Stuttering in a Founder Population

    PubMed Central

    Wittke-Thompson, Jacqueline K.; Ambrose, Nicoline; Yairi, Ehud; Roe, Cheryl; Cook, Edwin H.; Ober, Carole; Cox, Nancy J.

    2007-01-01

    Genome-wide linkage and association analyses were conducted to identify genetic determinants of stuttering in a founder population in which 48 individuals affected with stuttering are connected in a single 232-person genealogy. A novel approach was devised to account for all necessary relationships to enable multipoint linkage analysis. Regions with nominal evidence for linkage were found on chromosomes 3 (P=0.013, 208.8 centiMorgans (cM)), 13 (P=0.012, 52.6 cM), and 15 (P=0.02, 100 cM). Regions with nominal evidence for association with stuttering that overlapped with a linkage signal are located on chromosomes 3 (P=0.0047, 195 cM), 9 (P=0.0067, 46.5 cM), and 13 (P=0.0055, 52.6 cM). We also conducted the first meta-analysis for stuttering using results from linkage studies in the Hutterites and The Illinois International Genetics of Stuttering Project and identified regions with nominal evidence for linkage on chromosomes 2 (P=0.013, 180–195 cM) and 5 (P=0.0051, 105–120 cM; P=0.015, 120–135 cM). None of the linkage signals detected in the Hutterite sample alone, or in the meta-analysis, meet genome-wide criteria for significance, although some of the stronger signals overlap linkage mapping signals previously reported for other speech and language disorders. PMID:17276504

  13. Study raises questions about measurement of 'additionality,'or maintaining domestic health spending amid foreign donations.

    PubMed

    Garg, Charu C; Evans, David B; Dmytraczenko, Tania; Izazola-Licea, José-Antonio; Tangcharoensathien, Viroj; Ejeder, Tessa Tan-Torres

    2012-02-01

    Donor nations and philanthropic organizations increasingly require that funds provided for a specific health priority such as HIV should supplement domestic spending on that priority-a concept known as "additionality." We investigated the "additionality" concept using data from Honduras, Rwanda, and Thailand, and we found that the three countries increased funding for HIV in response to increased donor funding. In contrast, the study revealed that donors, faced with increased Global Fund resources for HIV in certain countries, tended to decrease their funding for HIV or shift funds for use in non-HIV health areas. More broadly, we found many problems in the measurement and interpretation of additionality. These findings suggest that it would be preferable for donors and countries to agree on how best to use available domestic and external funds to improve population health, and to develop better means of tracking outcomes, than to try to develop more sophisticated methods to track additionality.

  14. Multilocus Sequence Typing for Studying Genetic Relationships among Yersinia Species

    PubMed Central

    Kotetishvili, Mamuka; Kreger, Arnold; Wauters, Georges; Morris, J. Glenn; Sulakvelidze, Alexander; Stine, O. Colin

    2005-01-01

    The intra- and interspecies genetic relationships of 58 strains representing all currently known species of the genus Yersinia were examined by multilocus sequence typing (MLST), using sequence data from 16S RNA, glnA, gyrB, recA, and Y-HSP60 loci. Yersinia aldovae, Y. bercovieri, Y. intermedia, Y. pestis, Y. pseudotuberculosis, Y. rohdei, and Y. ruckeri were genetically more homogeneous than were Y. enterocolitica, Y. frederiksenii, Y. kristensenii, and Y. mollaretii. The MLST data concerning the genetic relatedness within and among various species of Yersinia support the idea that Y. pestis and Y. pseudotuberculosis are two lineages within the same species rather than two distinct species. Y. ruckeri is the genetically most distant species within the genus. There was evidence of O-antigen switching and genetic recombination within and among various species of Yersinia. The genetic relatedness data obtained by MLST of the four housekeeping genes and 16S RNA agreed in most, but not all, instances. MLST was better suited for determining genetic relatedness among yersiniae than was 16S RNA analysis. Some strains of Y. frederiksenii and Y. kristensenii are genetically less related to other strains within those species, compared to strains of all other species within the genus. The taxonomic standing of these strains should be further examined because they may represent currently unrecognized Yersinia species. PMID:15956383

  15. Multilocus sequence typing for studying genetic relationships among Yersinia species.

    PubMed

    Kotetishvili, Mamuka; Kreger, Arnold; Wauters, Georges; Morris, J Glenn; Sulakvelidze, Alexander; Stine, O Colin

    2005-06-01

    The intra- and interspecies genetic relationships of 58 strains representing all currently known species of the genus Yersinia were examined by multilocus sequence typing (MLST), using sequence data from 16S RNA, glnA, gyrB, recA, and Y-HSP60 loci. Yersinia aldovae, Y. bercovieri, Y. intermedia, Y. pestis, Y. pseudotuberculosis, Y. rohdei, and Y. ruckeri were genetically more homogeneous than were Y. enterocolitica, Y. frederiksenii, Y. kristensenii, and Y. mollaretii. The MLST data concerning the genetic relatedness within and among various species of Yersinia support the idea that Y. pestis and Y. pseudotuberculosis are two lineages within the same species rather than two distinct species. Y. ruckeri is the genetically most distant species within the genus. There was evidence of O-antigen switching and genetic recombination within and among various species of Yersinia. The genetic relatedness data obtained by MLST of the four housekeeping genes and 16S RNA agreed in most, but not all, instances. MLST was better suited for determining genetic relatedness among yersiniae than was 16S RNA analysis. Some strains of Y. frederiksenii and Y. kristensenii are genetically less related to other strains within those species, compared to strains of all other species within the genus. The taxonomic standing of these strains should be further examined because they may represent currently unrecognized Yersinia species.

  16. A novel genetic framework for studying response to artificial selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Response to selection is fundamental to plant breeding. To gain insight into the genetic basis of response to selection, we propose a new experimental genetic framework to simultaneously map loci controlling specific traits associated with population improvement and characterize the allele frequenc...

  17. Exploring Genetic and Environmental Effects in Dysphonia: A Twin Study

    ERIC Educational Resources Information Center

    Simberg, Susanna; Santtila, Pekka; Soveri, Anna; Varjonen, Markus; Sala, Eeva; Sandnabba, N. Kenneth

    2009-01-01

    Purpose: To explore the existence of genetic effects as well as the interaction between potential genetic effects and a voice-demanding occupation on dysphonia. Method: One thousand seven hundred and twenty-eight Finnish twins (555 male; 1,173 female) born between 1961 and 1989 completed a questionnaire concerning vocal symptoms and occupation.…

  18. Hamartomatous polyps - a clinical and molecular genetic study.

    PubMed

    Jelsig, Anne Marie

    2016-08-01

    Hamartomatous polyps (HPs) in the gastrointestinal (GI) tract are rare compared to other types of GI polyps, yet they are the most common type of polyp in children. The symptoms are usually rectal bleeding, abdominal pain, obstipation, anaemia, and/or small bowel obstruction. The polyps are typically removed concurrently with endoscopy when located in the colon, rectum, or stomach, whereas polyps in the small bowel are removed during push-enteroscopy, device-assisted enteroscopy, or by surgery. HPs can be classified as juvenile polyps or Peutz-Jeghers polyps based on their histopathological appearance. Patients with one or a few juvenile polyps are usually not offered clinical follow-up as the polyp(s) are considered not to harbour any malignant potential. Nevertheless, it is important to note that juvenile polyps and HPs are also found in patients with hereditary hamartomatous polyposis syndromes (HPS). Patients with HPS have an increased risk of cancer, recurrences of polyps, and extraintestinal complications. The syndromes are important to diagnose, as patients should be offered surveillance from childhood or early adolescence. The syndromes include juvenile polyposis syndrome, Peutz-Jeghers syndrome, and the PTEN hamartoma tumour syndrome. Currently, the HPS diagnoses are based on clinical criteria and are often assisted with genetic testing as candidate genes have been described for each syndrome. This thesis is based on six scientific papers. The overall aim of the studies was to expand the knowledge on clinical course and molecular genetics in patients with HPs and HPS, and to investigate research participants' attitude towards the results of extensive genetic testing.   Paper I: In the first paper we investigated the occurrence, anatomic distribution, and other demographics of juvenile polyps in the colon and rectum in Denmark in 1995-2014. Based on the Danish Pathology Data Bank we found that 1772 patients had 2108 JPs examined in the period, and we

  19. SHEEP MOUNTAIN WILDERNESS STUDY AREA AND CUCAMONGA WILDERNESS AND ADDITIONS, CALIFORNIA.

    USGS Publications Warehouse

    Evans, James G.; Ridenour, James

    1984-01-01

    The Sheep Mountain Wilderness Study Area and Cucamonga Wilderness and additions encompass approximately 104 sq mi of the eastern San Gabriel Mountains, Los Angeles and San Bernardino Counties, California. A mineral survey indicates areas of probable and substantiated tungsten and gold resource potential for parts of the Sheep Mountain Wilderness Study Area and an area of probable tungsten and gold resource potential in the Cucamonga Wilderness and additions. The rugged topography, withdrawal of lands from mineral entry to protect watershed, and restricted entry of lands during periods of high fire danger have contributed to the continuing decline in mineral exploration. The geologic setting precludes the presence of energy resources.

  20. Influence of Polarization on Carbohydrate Hydration: A Comparative Study Using Additive and Polarizable Force Fields.

    PubMed

    Pandey, Poonam; Mallajosyula, Sairam S

    2016-07-14

    Carbohydrates are known to closely modulate their surrounding solvent structures and influence solvation dynamics. Spectroscopic investigations studying far-IR regions (below 1000 cm(-1)) have observed spectral shifts in the libration band (around 600 cm(-1)) of water in the presence of monosaccharides and polysaccharides. In this paper, we use molecular dynamics simulations to gain atomistic insight into carbohydrate-water interactions and to specifically highlight the differences between additive (nonpolarizable) and polarizable simulations. A total of six monosaccharide systems, α and β anomers of glucose, galactose, and mannose, were studied using additive and polarizable Chemistry at HARvard Macromolecular Mechanics (CHARMM) carbohydrate force fields. Solvents were modeled using three additive water models TIP3P, TIP4P, and TIP5P in additive simulations and polarizable water model SWM4 in polarizable simulations. The presence of carbohydrate has a significant effect on the microscopic water structure, with the effects being pronounced for proximal water molecules. Notably, disruption of the tetrahedral arrangement of proximal water molecules was observed due to the formation of strong carbohydrate-water hydrogen bonds in both additive and polarizable simulations. However, the inclusion of polarization resulted in significant water-bridge occupancies, improved ordered water structures (tetrahedral order parameter), and longer carbohydrate-water H-bond correlations as compared to those for additive simulations. Additionally, polarizable simulations also allowed the calculation of power spectra from the dipole-dipole autocorrelation function, which corresponds to the IR spectra. From the power spectra, we could identify spectral signatures differentiating the proximal and bulk water structures, which could not be captured from additive simulations. PMID:27266974

  1. A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population

    PubMed Central

    Zhao, Shan-Chao; Ren, Guoping; Yu, Yongwei; Wu, Yudong; Wu, Ji; Xue, Yao; Zhou, Bo; Zhang, Yanling; Xu, Xingxing; Li, Jie; He, Weiyang; Benlloch, Sara; Ross-Adams, Helen; Chen, Li; Li, Jucong; Hong, Yingqia; Kote-Jarai, Zsofia; Cui, Xingang; Hou, Jianguo; Guo, Jianming; Xu, Lei; Yin, Changjun; Zhou, Yuanping; Neal, David E.; Oliver, Tim; Cao, Guangwen; Zhang, Zhengdong; Easton, Douglas F.; Chelala, Claude; Olama, Ali Amin Al; Eeles, Rosalind A.; Zhang, Hongwei; Lu, Yong-Jie

    2016-01-01

    Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer. PMID:26881390

  2. Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course.

    PubMed

    Graff, Mariaelisa; Ngwa, Julius S; Workalemahu, Tsegaselassie; Homuth, Georg; Schipf, Sabine; Teumer, Alexander; Völzke, Henry; Wallaschofski, Henri; Abecasis, Goncalo R; Edward, Lakatta; Francesco, Cucca; Sanna, Serena; Scheet, Paul; Schlessinger, David; Sidore, Carlo; Xiao, Xiangjun; Wang, Zhaoming; Chanock, Stephen J; Jacobs, Kevin B; Hayes, Richard B; Hu, Frank; Van Dam, Rob M; Crout, Richard J; Marazita, Mary L; Shaffer, John R; Atwood, Larry D; Fox, Caroline S; Heard-Costa, Nancy L; White, Charles; Choh, Audrey C; Czerwinski, Stefan A; Demerath, Ellen W; Dyer, Thomas D; Towne, Bradford; Amin, Najaf; Oostra, Ben A; Van Duijn, Cornelia M; Zillikens, M Carola; Esko, Tõnu; Nelis, Mari; Nikopensius, Tit; Metspalu, Andres; Strachan, David P; Monda, Keri; Qi, Lu; North, Kari E; Cupples, L Adrienne; Gordon-Larsen, Penny; Berndt, Sonja I

    2013-09-01

    Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P < 5.0 × 10⁻⁸) near FTO (P = 3.72 × 10⁻²³), TMEM18 (P = 3.24 × 10⁻¹⁷), MC4R (P = 4.41 × 10⁻¹⁷), TNNI3K (P = 4.32 × 10⁻¹¹), SEC16B (P = 6.24 × 10⁻⁹), GNPDA2 (P = 1.11 × 10⁻⁸) and POMC (P = 4.94 × 10⁻⁸) as well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 × 10⁻⁵ after conditioning on the established single-nucleotide polymorphism at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 18-90) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with older adults (P < 0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different ages.

  3. Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course

    PubMed Central

    Graff, Mariaelisa; Ngwa, Julius S.; Workalemahu, Tsegaselassie; Homuth, Georg; Schipf, Sabine; Teumer, Alexander; Völzke, Henry; Wallaschofski, Henri; Abecasis, Goncalo R.; Edward, Lakatta; Francesco, Cucca; Sanna, Serena; Scheet, Paul; Schlessinger, David; Sidore, Carlo; Xiao, Xiangjun; Wang, Zhaoming; Chanock, Stephen J.; Jacobs, Kevin B.; Hayes, Richard B.; Hu, Frank; Van Dam, Rob M.; Crout, Richard J.; Marazita, Mary L.; Shaffer, John R; Atwood, Larry D.; Fox, Caroline S.; Heard-Costa, Nancy L.; White, Charles; Choh, Audrey C.; Czerwinski, Stefan A.; Demerath, Ellen W.; Dyer, Thomas D.; Towne, Bradford; Amin, Najaf; Oostra, Ben A.; Van Duijn, Cornelia M.; Zillikens, M. Carola; Esko, Tõnu; Nelis, Mari; Nikopensius, Tit; Metspalu, Andres; Strachan, David P.; Monda, Keri; Qi, Lu; North, Kari E.; Cupples, L. Adrienne; Gordon-Larsen, Penny; Berndt, Sonja I.

    2013-01-01

    Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P < 5.0 × 10−8) near FTO (P = 3.72 × 10−23), TMEM18 (P = 3.24 × 10−17), MC4R (P = 4.41 × 10−17), TNNI3K (P = 4.32 × 10−11), SEC16B (P = 6.24 × 10−9), GNPDA2 (P = 1.11 × 10−8) and POMC (P = 4.94 × 10−8) as well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 × 10−5 after conditioning on the established single-nucleotide polymorphism at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 18–90) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with older adults (P < 0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different ages. PMID:23669352

  4. Rate of evolutionary change in cranial morphology of the marsupial genus Monodelphis is constrained by the availability of additive genetic variation

    PubMed Central

    Porto, Arthur; Sebastião, Harley; Pavan, Silvia Eliza; VandeBerg, John L.; Marroig, Gabriel; Cheverud, James M.

    2015-01-01

    We tested the hypothesis that the rate of marsupial cranial evolution is dependent on the distribution of genetic variation in multivariate space. To do so, we carried out a genetic analysis of cranial morphological variation in laboratory strains of Monodelphis domestica and used estimates of genetic covariation to analyze the morphological diversification of the Monodelphis brevicaudata species group. We found that within-species genetic variation is concentrated in only a few axes of the morphospace and that this strong genetic covariation influenced the rate of morphological diversification of the brevicaudata group, with between-species divergence occurring fastest when occurring along the genetic line of least resistance. Accounting for the geometric distribution of genetic variation also increased our ability to detect the selective regimen underlying species diversification, with several instances of selection only being detected when genetic covariances were taken into account. Therefore, this work directly links patterns of genetic covariation among traits to macroevolutionary patterns of morphological divergence. Our findings also suggest that the limited distribution of Monodelphis species in morphospace is the result of a complex interplay between the limited dimensionality of available genetic variation and strong stabilizing selection along two major axes of genetic variation. PMID:25818173

  5. Rate of evolutionary change in cranial morphology of the marsupial genus Monodelphis is constrained by the availability of additive genetic variation.

    PubMed

    Porto, A; Sebastião, H; Pavan, S E; VandeBerg, J L; Marroig, G; Cheverud, J M

    2015-04-01

    We tested the hypothesis that the rate of marsupial cranial evolution is dependent on the distribution of genetic variation in multivariate space. To do so, we carried out a genetic analysis of cranial morphological variation in laboratory strains of Monodelphis domestica and used estimates of genetic covariation to analyse the morphological diversification of the Monodelphis brevicaudata species group. We found that within-species genetic variation is concentrated in only a few axes of the morphospace and that this strong genetic covariation influenced the rate of morphological diversification of the brevicaudata group, with between-species divergence occurring fastest when occurring along the genetic line of least resistance. Accounting for the geometric distribution of genetic variation also increased our ability to detect the selective regimen underlying species diversification, with several instances of selection only being detected when genetic covariances were taken into account. Therefore, this work directly links patterns of genetic covariation among traits to macroevolutionary patterns of morphological divergence. Our findings also suggest that the limited distribution of Monodelphis species in morphospace is the result of a complex interplay between the limited dimensionality of available genetic variation and strong stabilizing selection along two major axes of genetic variation.

  6. A molecular genetic study of autism and related phenotypes in extended pedigrees

    PubMed Central

    2013-01-01

    Background Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. Methods We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. Results Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas 'repetitive behavior’, showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. Conclusions These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears

  7. Genetic Diversity in Gorkhas: an Autosomal STR Study

    PubMed Central

    Preet, Kiran; Malhotra, Seema; Shrivastava, Pankaj; Jain, Toshi; Rawat, Shweta; Varte, L. Robert; Singh, Sayar; Singh, Inderjeet; Sarkar, Soma

    2016-01-01

    Genotyping of highly polymorphic autosomal short tandem repeat (STR) markers is a potent tool for elucidating genetic diversity. In the present study, fifteen autosomal STR markers were analyzed in unrelated healthy male Gorkha individuals (n = 98) serving in the Indian Army by using AmpFlSTR Identifiler Plus PCR Amplification Kit. In total, 138 alleles were observed with corresponding allele frequencies ranging from 0.005 to 0.469. The studied loci were in Hardy-Weinberg Equilibrium (HWE). Heterozygosity ranged from 0.602 to 0.867. The most polymorphic locus was Fibrinogen Alpha (FGA) chain which was also the most discriminating locus as expected. Neighbor Joining (NJ) tree and principal component analysis (PCA) plot clustered the Gorkhas with those of Nepal and other Tibeto-Burman population while lowlander Indian population formed separate cluster substantiating the closeness of the Gorkhas with the Tibeto-Burman linguistic phyla. Furthermore, the dataset of STR markers obtained in the study presents a valuable information source of STR DNA profiles from personnel for usage in disaster victim identification in military exigencies and adds to the Indian database of military soldiers and military hospital repository. PMID:27580933

  8. Genetic, Genomic and Epigenomic Studies of Balkan Endemic Nephropathy (Ben).

    PubMed

    Staneva, Rada G; Balabanski, L; Dimova, I; Rukova, B; Hadjidekova, S; Dimitrov, P; Simeonov, V; Ivanov, S; Vagarova, R; Malinov, M; Cukuranovic, R; Stefanovic, V; Polenakovic, M; Djonov, V; Galabov, A; Toncheva, D

    2015-01-01

    BEN is a primary, chronic tubulointerstitial nephritis characterized with chronic anemia, absence of edema, xantoderma, normal blood pressure and normal findings on the fundus oculi. The disease is distributed in restricted areas in Bulgaria, Romania, Croatia, Bosnia, Former Yugoslavia. Despite numerous studies on genetic and environmental factors and their possible involvement in BEN, its etiopathogenesis still remains elusive. Our recent study aim to elucidate the possible epigenetic component in BEN development. Whole genome DNA array methylation analysis was applied to compare the methylation profiles of male and female BEN patients from endemic regions in Bulgaria and Serbia and healthy controls. All three most prominent candidate genes with aberrations in the epigenetic profile discovered with this study are involved in the inflammatory/immune processes and oncogenesis. These data are in concordance with the reported pathological alterations in BEN. This research supports the role of epigenetic changes in BEN pathology. Exome sequencing of 22.000 genes with Illumina Nextera Exome Enrichment Kit revealed three mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients which encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN. PMID:27442376

  9. Genetic Diversity in Gorkhas: an Autosomal STR Study.

    PubMed

    Preet, Kiran; Malhotra, Seema; Shrivastava, Pankaj; Jain, Toshi; Rawat, Shweta; Varte, L Robert; Singh, Sayar; Singh, Inderjeet; Sarkar, Soma

    2016-01-01

    Genotyping of highly polymorphic autosomal short tandem repeat (STR) markers is a potent tool for elucidating genetic diversity. In the present study, fifteen autosomal STR markers were analyzed in unrelated healthy male Gorkha individuals (n = 98) serving in the Indian Army by using AmpFlSTR Identifiler Plus PCR Amplification Kit. In total, 138 alleles were observed with corresponding allele frequencies ranging from 0.005 to 0.469. The studied loci were in Hardy-Weinberg Equilibrium (HWE). Heterozygosity ranged from 0.602 to 0.867. The most polymorphic locus was Fibrinogen Alpha (FGA) chain which was also the most discriminating locus as expected. Neighbor Joining (NJ) tree and principal component analysis (PCA) plot clustered the Gorkhas with those of Nepal and other Tibeto-Burman population while lowlander Indian population formed separate cluster substantiating the closeness of the Gorkhas with the Tibeto-Burman linguistic phyla. Furthermore, the dataset of STR markers obtained in the study presents a valuable information source of STR DNA profiles from personnel for usage in disaster victim identification in military exigencies and adds to the Indian database of military soldiers and military hospital repository. PMID:27580933

  10. Comparative study of electrolyte additives using electrochemical impedance spectroscopy on symmetric cells

    NASA Astrophysics Data System (ADS)

    Petibon, R.; Sinha, N. N.; Burns, J. C.; Aiken, C. P.; Ye, Hui; VanElzen, Collette M.; Jain, Gaurav; Trussler, S.; Dahn, J. R.

    2014-04-01

    The effect of various electrolyte additives and additive combinations added to a 1 M LiPF6 EC:EMC electrolyte on the positive and negative electrodes surface of 1 year old wound LiCoO2/graphite cells and Li[Ni0.4Mn0.4Co0.2])O2/graphite cells was studied using electrochemical impedance spectroscopy (EIS) on symmetric cells. The additives tested were: vinylene carbonate (VC), trimethoxyboroxine (TMOBX), fluoroethylene carbonate (FEC), lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), and H2O alone or in combination. In general, compared to control electrolyte, the additives tested reduced the impedance of the positive electrode and increased the impedance of the negative electrode with the exception of LiTFSI in Li[Ni0.4Mn0.4Co0.2]O2/graphite wound cells. Higher charge voltage led to higher positive electrode impedance, with the exception of 2%VC + 2% FEC, and 2% LiTFSI. In some cases, some additives when mixed with another controlled the formation of the SEI at one electrode, and shared the formation of the SEI at one electrode when mixed with a different additive.

  11. Genetic Determinants for Promoter Hypermethylation in the Lungs of Smokers: A Candidate Gene-Based Study

    PubMed Central

    Leng, Shuguang; Stidley, Christine A.; Liu, Yushi; Edlund, Christopher K.; Willink, Randall P.; Han, Younghun; Landi, Maria Teresa; Thun, Michael; Picchi, Maria A.; Bruse, Shannon E.; Crowell, Richard E.; Van Den Berg, David; Caporaso, Neil E.; Amos, Christopher I.; Siegfried, Jill M.; Tesfaigzi, Yohannes; Gilliland, Frank D.; Belinsky, Steven A.

    2011-01-01

    The detection of tumor suppressor gene promoter methylation in sputum-derived exfoliated cells predicts early lung cancer. Here we identified genetic determinants for this epigenetic process and examined their biological effects on gene regulation. A two-stage approach involving discovery and replication was employed to assess the association between promoter hypermethylation of a 12-gene panel and common variation in 40 genes involved in carcinogen metabolism, regulation of methylation, and DNA damage response in members of the Lovelace Smokers Cohort (n=1434). Molecular validation of three identified variants was conducted using primary bronchial epithelial cells. Association of study-wide significance (P<8.2×10−5) was identified for rs1641511, rs3730859, and rs1883264 in TP53, LIG1, and BIK, respectively. These SNPs were significantly associated with altered expression of the corresponding genes in primary bronchial epithelial cells. In addition, rs3730859 in LIG1 was also moderately associated with increased risk for lung cancer among Caucasian smokers. Together, our findings suggest that genetic variation in DNA replication and apoptosis pathways impacts the propensity for gene promoter hypermethylation in the aerodigestive tract of smokers. The incorporation of genetic biomarkers for gene promoter hypermethylation with clinical and somatic markers may improve risk assessment models for lung cancer. PMID:22139380

  12. Generating Scenarios of Addition and Subtraction: A Study of Japanese University Students

    ERIC Educational Resources Information Center

    Kinda, Shigehiro

    2013-01-01

    Students are presented with problems involving three scenario types of addition and subtraction in elementary mathematics: one dynamic ("Change") and two static ("Combine, Compare"). Previous studies have indicated that the dynamic type is easier for school children, whereas the static types are more difficult and comprehended only gradually…

  13. Experimental study of combustion of decane, dodecane and hexadecane with polymeric and nano-particle additives

    NASA Astrophysics Data System (ADS)

    Ghamari, Mohsen; Ratner, Albert

    2015-11-01

    Recent studies have shown that adding combustible nano-particles could have promising effects on increasing burning rate of liquid fuels. Combustible nano-particles could enhance the heat conduction and mixing within the droplet. Polymers have also higher burning rate than regular hydrocarbon fuels because of having the flame closer to the droplet surface. Therefore adding polymeric additive could have the potential to increase the burning rate. In this study, combustion of stationary fuel droplets of n-Decane, n-Dodecane and n-Hexadecane doped with different percentages of a long chain polymer and also a very fine nano carbon was examined and compared with the pure hydrocarbon behavior. In contrast with hydrocarbon droplets with no polymer addition, several zones of combustion including a slow and steady burning zone, a strong swelling zone and a final fast and fairly steady combustion zone were also detected. In addition, increasing polymer percentage resulted in a more extended swelling zone and shorter slow burning zone in addition to a shorter total burning time. Addition of nano-particles also resulted in an overall increased burning rate and shortened burning time which is due to enhanced heat conduction within the droplet.

  14. Mental addition in bilinguals: an FMRI study of task-related and performance-related activation.

    PubMed

    Lin, Jo-Fu Lotus; Imada, Toshiaki; Kuhl, Patricia K

    2012-08-01

    Behavioral studies show that bilinguals are slower and less accurate when performing mental calculation in their nondominant (second; L2) language than in their dominant (first; L1) language. However, little is known about the neural correlates associated with the performance differences observed between bilinguals' 2 languages during arithmetic processing. To address the cortical activation differences between languages, the current study examined task-related and performance-related brain activation during mental addition when problems were presented auditorily in participants' L1 and L2. Eleven Chinese-English bilinguals heard 2-digit addition problems that required exact or approximate calculations. Functional magnetic resonance imaging results showed that auditorily presented multidigit addition in bilinguals activates bilateral inferior parietal and inferior frontal regions in both L1 and L2. Language differences were observed in the form of greater activation for L2 exact addition in the left inferior frontal area. A negative correlation between brain activation and behavioral performance during mental addition in L2 was observed in the left inferior parietal area. Current results provide further evidence for the effects of language-specific experience on arithmetic processing in bilinguals at the cortical level.

  15. Genetic regulation of inflammation-mediated activation of haemostasis: family-based approaches in population studies.

    PubMed

    Vohnout, B; Gianfagna, F; Lorenzet, R; Cerletti, C; de Gaetano, G; Donati, M B; Iacoviello, L

    2011-11-01

    Blood coagulation and inflammation play a key role in atherosclerosis and thrombosis. Candidate gene and genome wide association studies have identified potential specific genes that might have a causal role in these pathogenic processes. The analysis of quantitative traits is more powerful as they are closer to direct gene action than disease phenotypes. Thus linkage-based studies on extended families might be useful both to estimate the heritability and to map the genetic loci responsible for the regulation of the trait. Family-based studies may estimate high heritability for thrombosis and quantitative traits regarding both platelet aggregation and blood coagulation. Some specific loci relevant to thrombosis have been identified, with some of them showing a direct pleiotropic effect on the risk of thrombosis. Haemostasis factors can be activated by inflammatory stimuli. Fibrinogen level is genetically correlated with C-reactive protein levels with a link for both traits on chromosomes 12 and 21. Genes related to prostanoid biosynthesis, involved both in inflammation and thrombosis, show high heritability levels in both enzyme expression and prostanoid production. Considering that few large family-based linkage studies have as yet been performed on haemostasis and inflammation-related traits, additional studies are highly needed. We are performing a family-based linkage study on large pedigrees (750 subjects from 23 families with juvenile myocardial infarction and 31 control families), to identify genes responsible for quantitative traits involved in the pathway progressively going from inflammation to haemostasis, cell activation, thrombus formation and cardiovascular events.

  16. Simulating a base population in honey bee for molecular genetic studies

    PubMed Central

    2012-01-01

    Background Over the past years, reports have indicated that honey bee populations are declining and that infestation by an ecto-parasitic mite (Varroa destructor) is one of the main causes. Selective breeding of resistant bees can help to prevent losses due to the parasite, but it requires that a robust breeding program and genetic evaluation are implemented. Genomic selection has emerged as an important tool in animal breeding programs and simulation studies have shown that it yields more accurate breeding value estimates, higher genetic gain and low rates of inbreeding. Since genomic selection relies on marker data, simulations conducted on a genomic dataset are a pre-requisite before selection can be implemented. Although genomic datasets have been simulated in other species undergoing genetic evaluation, simulation of a genomic dataset specific to the honey bee is required since this species has a distinct genetic and reproductive biology. Our software program was aimed at constructing a base population by simulating a random mating honey bee population. A forward-time population simulation approach was applied since it allows modeling of genetic characteristics and reproductive behavior specific to the honey bee. Results Our software program yielded a genomic dataset for a base population in linkage disequilibrium. In addition, information was obtained on (1) the position of markers on each chromosome, (2) allele frequency, (3) χ2 statistics for Hardy-Weinberg equilibrium, (4) a sorted list of markers with a minor allele frequency less than or equal to the input value, (5) average r2 values of linkage disequilibrium between all simulated marker loci pair for all generations and (6) average r2 value of linkage disequilibrium in the last generation for selected markers with the highest minor allele frequency. Conclusion We developed a software program that takes into account the genetic and reproductive biology specific to the honey bee and that can be used to

  17. Genetic analysis of tolerance to infections using random regressions: a simulation study.

    PubMed

    Kause, Antti

    2011-08-01

    Tolerance to infections is the ability of a host to limit the impact of a given pathogen burden on host performance. This simulation study demonstrated the merit of using random regressions to estimate unbiased genetic variances for tolerance slope and its genetic correlations with other traits, which could not be obtained using the previously implemented statistical methods. Genetic variance in tolerance was estimated as genetic variance in regression slopes of host performance along an increasing pathogen burden level. Random regressions combined with covariance functions allowed genetic variance for host performance to be estimated at any point along the pathogen burden trajectory, providing a novel means to analyse infection-induced changes in genetic variation of host performance. Yet, the results implied that decreasing family size as well as a non-zero environmental or genetic correlation between initial host performance before infection and pathogen burden led to biased estimates for tolerance genetic variance. In both cases, genetic correlation between tolerance slope and host performance in a pathogen-free environment became artificially negative, implying a genetic trade-off when it did not exist. Moreover, recording a normally distributed pathogen burden as a threshold trait is not a realistic way of obtaining unbiased estimates for tolerance genetic variance. The results show that random regressions are suitable for the genetic analysis of tolerance, given suitable data structure collected either under field or experimental conditions. PMID:21767462

  18. Genetic Influences on Brain Developmental Trajectories on Neuroimaging Studies: From Infancy to Young Adulthood

    PubMed Central

    Douet, Vanessa; Chang, Linda; Cloak, Christine; Ernst, Thomas

    2013-01-01

    Human brain development has been studied intensively with neuroimaging. However, little is known about how genes influence developmental brain trajectories, even though a significant number of genes (about 10,000, or approximately one-third) in the human genome are expressed primarily in the brain and during brain development. Interestingly, in addition to showing differential expression among tissues, many genes are differentially expressed across the ages (e.g., antagonistic pleiotropy). Age-specific gene expression plays an important role in several critical events in brain development, including neuronal cell migration, synaptogenesis and neurotransmitter receptor specificity, as well as in aging and neurodegenerative disorders (e.g., Alzheimer disease or amyotrophic lateral sclerosis). In addition, the majority of psychiatric and mental disorders are polygenic, and many have onsets during childhood and adolescence. In this review, we summarize the major findings from neuroimaging studies that link genetics with brain development, from infancy to young adulthood. Specifically, we focus on the heritability of brain structures across the ages, age-related genetic influences on brain development and sex-specific developmental trajectories. PMID:24077983

  19. Sequential neural processes in abacus mental addition: an EEG and FMRI case study.

    PubMed

    Ku, Yixuan; Hong, Bo; Zhou, Wenjing; Bodner, Mark; Zhou, Yong-Di

    2012-01-01

    Abacus experts are able to mentally calculate multi-digit numbers rapidly. Some behavioral and neuroimaging studies have suggested a visuospatial and visuomotor strategy during abacus mental calculation. However, no study up to now has attempted to dissociate temporally the visuospatial neural process from the visuomotor neural process during abacus mental calculation. In the present study, an abacus expert performed the mental addition tasks (8-digit and 4-digit addends presented in visual or auditory modes) swiftly and accurately. The 100% correct rates in this expert's task performance were significantly higher than those of ordinary subjects performing 1-digit and 2-digit addition tasks. ERPs, EEG source localizations, and fMRI results taken together suggested visuospatial and visuomotor processes were sequentially arranged during the abacus mental addition with visual addends and could be dissociated from each other temporally. The visuospatial transformation of the numbers, in which the superior parietal lobule was most likely involved, might occur first (around 380 ms) after the onset of the stimuli. The visuomotor processing, in which the superior/middle frontal gyri were most likely involved, might occur later (around 440 ms). Meanwhile, fMRI results suggested that neural networks involved in the abacus mental addition with auditory stimuli were similar to those in the visual abacus mental addition. The most prominently activated brain areas in both conditions included the bilateral superior parietal lobules (BA 7) and bilateral middle frontal gyri (BA 6). These results suggest a supra-modal brain network in abacus mental addition, which may develop from normal mental calculation networks.

  20. "Genetic Engineering" Gains Momentum (Science/Society Case Study).

    ERIC Educational Resources Information Center

    Moore, John W.; Moore, Elizabeth A., Eds.

    1980-01-01

    Reviews the benefits and hazards of genetic engineering, or "recombinant-DNA" research. Recent federal safety rules issued by NIH which ease the strict prohibitions on recombinant-DNA research are explained. (CS)

  1. [Study on tests of genetics experiments in universities].

    PubMed

    Jie, He; Hao, Zhang; Lili, Zhang

    2015-03-01

    Based on the present situation and the development of experiment tests in universities, we introduced a reform in tests of genetics experiments. According to the teaching goals and course contents of genetics experiment, the tests of genetics experiments contain four aspects on the performance of students: the adherence to the experimental procedures, the depth of participation in experiment, the quality of experiment report, and the mastery of experiment principles and skills, which account for 10 %, 20 %, 40 % and 30 % in the total scores, respectively. All four aspects were graded quantitatively. This evaluation system has been tested in our experiment teaching. The results suggest that it has an effect on the promotion of teaching in genetics experiments.

  2. Raman spectroscopic study of a genetically altered kidney cell

    NASA Astrophysics Data System (ADS)

    Joshi, Joel; Garcia, Francisco; Centeno, Silvia P.; Joshi, N. V.

    2008-02-01

    A Raman spectroscopic investigation of a genetically altered Human Embryonic Kidney Cell (HEK293) along with a pathologically normal cell has been carried out by a conventional method. The genetic alteration was carried out with a standard protocol by using a Green Fluorescence Protein (GFP). Raman spectra show that there are dramatic differences between the spectrum obtained from a genetically altered cell and that obtained from a pathologically normal cell. The former shows three broad bands; meanwhile the latter shows several sharp peaks corresponding to the ring vibrational modes of Phen, GFP and DNA. The present analysis provides an indication that the force field near Phen located at 64, 65 and 66 was altered during the genetic transformation. The Raman spectrum could be a direct experimental evidence for substantial modifications triggered due to the expression of specific genes.

  3. Genetic transformation: a tool to study protein targeting in diatoms.

    PubMed

    Kroth, Peter G

    2007-01-01

    Diatoms are unicellular photoautotrophic eukaryotes that play an important role in ecology by fixing large amounts of CO2 in the oceans. Because they evolved by secondary endocytobiosis-- a process of uptake of a eukaryotic alga into another eukaryotic cell--they have a rather unusual cell biology and genetic constitution. Because the preparation of organelles is rather difficult as a result of the cytosolic structures, genetic transformation and expression of preproteins fused to green fluorescent protein (GFP) became one of the major tools to analyze subcellular localization of proteins in diatoms. Meanwhile several groups successfully attempted to develop genetic transformation protocols for diatoms. These methods are based on "biolistic" DNA delivery via a particle gun and allow the introduction and expression of foreign genes in the algae. Here a protocol for the genetic transformation of the diatom Phaeodactylum tricornutum is described as well as the subsequent characterization of the transformants. PMID:17951693

  4. Phenotype-Based Genetic Association Studies (PGAS)-Towards Understanding the Contribution of Common Genetic Variants to Schizophrenia Subphenotypes.

    PubMed

    Ehrenreich, Hannelore; Nave, Klaus-Armin

    2014-01-01

    Neuropsychiatric diseases ranging from schizophrenia to affective disorders and autism are heritable, highly complex and heterogeneous conditions, diagnosed purely clinically, with no supporting biomarkers or neuroimaging criteria. Relying on these "umbrella diagnoses", genetic analyses, including genome-wide association studies (GWAS), were undertaken but failed to provide insight into the biological basis of these disorders. "Risk genotypes" of unknown significance with low odds ratios of mostly <1.2 were extracted and confirmed by including ever increasing numbers of individuals in large multicenter efforts. Facing these results, we have to hypothesize that thousands of genetic constellations in highly variable combinations with environmental co-factors can cause the individual disorder in the sense of a final common pathway. This would explain why the prevalence of mental diseases is so high and why mutations, including copy number variations, with a higher effect size than SNPs, constitute only a small part of variance. Elucidating the contribution of normal genetic variation to (disease) phenotypes, and so re-defining disease entities, will be extremely labor-intense but crucial. We have termed this approach PGAS ("phenotype-based genetic association studies"). Ultimate goal is the definition of biological subgroups of mental diseases. For that purpose, the GRAS (Göttingen Research Association for Schizophrenia) data collection was initiated in 2005. With >3000 phenotypical data points per patient, it comprises the world-wide largest currently available schizophrenia database (N > 1200), combining genome-wide SNP coverage and deep phenotyping under highly standardized conditions. First PGAS results on normal genetic variants, relevant for e.g., cognition or catatonia, demonstrated proof-of-concept. Presently, an autistic subphenotype of schizophrenia is being defined where an unfortunate accumulation of normal genotypes, so-called pro-autistic variants of

  5. Microstructural Study Of Zinc Hot Dip Galvanized Coatings with Titanium Additions In The Zinc Melt

    NASA Astrophysics Data System (ADS)

    Konidaris, S.; Pistofidis, N.; Vourlias, G.; Pavlidou, E.; Stergiou, A.; Stergioudis, G.; Polychroniadis, E. K.

    2007-04-01

    Zinc hot-dip galvanizing is a method for protecting iron and steel against corrosion. Galvanizing with pure Zn or Zn with additions like Ni, Al, Pb and Bi has been extensively studied, but there is a lack of scientific information about other additions. The present work examines the effect of a 0.5 wt% Ti addition in the Zn melt. The samples were exposed to accelerated corrosion in a salt spray chamber (SSC). The microstructure and chemical composition of the coatings were determined by Optical Microscopy, XRD and SEM associated with an EDS Analyzer. The results indicate that the coatings have a typical morphology, while Zn-Ti phases were also detected.

  6. A synchrotron study of microstructure gradient in laser additively formed epitaxial Ni-based superalloy.

    PubMed

    Xue, Jiawei; Zhang, Anfeng; Li, Yao; Qian, Dan; Wan, Jingchun; Qi, Baolu; Tamura, Nobumichi; Song, Zhongxiao; Chen, Kai

    2015-01-01

    Laser additive forming is considered to be one of the promising techniques to repair single crystal Ni-based superalloy parts to extend their life and reduce the cost. Preservation of the single crystalline nature and prevention of thermal mechanical failure are two of the most essential issues for the application of this technique. Here we employ synchrotron X-ray microdiffraction to evaluate the quality in terms of crystal orientation and defect distribution of a Ni-based superalloy DZ125L directly formed by a laser additive process rooted from a single crystalline substrate of the same material. We show that a disorientation gradient caused by a high density of geometrically necessary dislocations and resultant subgrains exists in the interfacial region between the epitaxial and stray grains. This creates a potential relationship of stray grain formation and defect accumulation. The observation offers new directions on the study of performance control and reliability of the laser additive manufactured superalloys. PMID:26446425

  7. A synchrotron study of microstructure gradient in laser additively formed epitaxial Ni-based superalloy

    SciTech Connect

    Xue, Jiawei; Zhang, Anfeng; Li, Yao; Qian, Dan; Wan, Jingchun; Qi, Baolu; Tamura, Nobumichi; Song, Zhongxiao; Chen, Kai

    2015-10-08

    Laser additive forming is considered to be one of the promising techniques to repair single crystal Ni-based superalloy parts to extend their life and reduce the cost. Preservation of the single crystalline nature and prevention of thermal mechanical failure are two of the most essential issues for the application of this technique. Here we employ synchrotron X-ray microdiffraction to evaluate the quality in terms of crystal orientation and defect distribution of a Ni-based superalloy DZ125L directly formed by a laser additive process rooted from a single crystalline substrate of the same material. We show that a disorientation gradient caused by a high density of geometrically necessary dislocations and resultant subgrains exists in the interfacial region between the epitaxial and stray grains. This creates a potential relationship of stray grain formation and defect accumulation. In conclusion, the observation offers new directions on the study of performance control and reliability of the laser additive manufactured superalloys.

  8. A synchrotron study of microstructure gradient in laser additively formed epitaxial Ni-based superalloy

    PubMed Central

    Xue, Jiawei; Zhang, Anfeng; Li, Yao; Qian, Dan; Wan, Jingchun; Qi, Baolu; Tamura, Nobumichi; Song, Zhongxiao; Chen, Kai

    2015-01-01

    Laser additive forming is considered to be one of the promising techniques to repair single crystal Ni-based superalloy parts to extend their life and reduce the cost. Preservation of the single crystalline nature and prevention of thermal mechanical failure are two of the most essential issues for the application of this technique. Here we employ synchrotron X-ray microdiffraction to evaluate the quality in terms of crystal orientation and defect distribution of a Ni-based superalloy DZ125L directly formed by a laser additive process rooted from a single crystalline substrate of the same material. We show that a disorientation gradient caused by a high density of geometrically necessary dislocations and resultant subgrains exists in the interfacial region between the epitaxial and stray grains. This creates a potential relationship of stray grain formation and defect accumulation. The observation offers new directions on the study of performance control and reliability of the laser additive manufactured superalloys. PMID:26446425

  9. Summary of Previous Chamber or Controlled Anthrax Studies and Recommendations for Possible Additional Studies

    SciTech Connect

    Piepel, Gregory F.; Amidan, Brett G.; Morrow, Jayne B.

    2010-12-29

    This report and an associated Excel file(a) summarizes the investigations and results of previous chamber and controlled studies(b) to characterize the performance of methods for collecting, storing and/or transporting, extracting, and analyzing samples from surfaces contaminated by Bacillus anthracis (BA) or related simulants. This report and the Excel are the joint work of the Pacific Northwest National Laboratory (PNNL) and the National Institute of Standards and Technology (NIST) for the Department of Homeland Security, Science and Technology Directorate. The report was originally released as PNNL-SA-69338, Rev. 0 in November 2009 with limited distribution, but was subsequently cleared for release with unlimited distribution in this Rev. 1. Only minor changes were made to Rev. 0 to yield Rev. 1. A more substantial update (including summarizing data from other studies and more condensed summary tables of data) is underway

  10. Studies of levels of biogenic amines in meat samples in relation to the content of additives.

    PubMed

    Jastrzębska, Aneta; Kowalska, Sylwia; Szłyk, Edward

    2016-01-01

    The impact of meat additives on the concentration of biogenic amines and the quality of meat was studied. Fresh white and red meat samples were fortified with the following food additives: citric and lactic acids, disodium diphosphate, sodium nitrite, sodium metabisulphite, potassium sorbate, sodium chloride, ascorbic acid, α-tocopherol, propyl 3,4,5-trihydroxybenzoate (propyl gallate) and butylated hydroxyanisole. The content of spermine, spermidine, putrescine, cadaverine, histamine, tyramine, tryptamine and 2-phenylethylamine was determined by capillary isotachophoretic methods in meat samples (fresh and fortified) during four days of storage at 4°C. The results were applied to estimate the impact of the tested additives on the formation of biogenic amines in white and red meat. For all tested meats, sodium nitrite, sodium chloride and disodium diphosphate showed the best inhibition. However, cadaverine and putrescine were characterised by the biggest changes in concentration during the storage time of all the additives. Based on the presented data for the content of biogenic amines in meat samples analysed as a function of storage time and additives, we suggest that cadaverine and putrescine have a significant impact on meat quality. PMID:26515667

  11. Studies of levels of biogenic amines in meat samples in relation to the content of additives.

    PubMed

    Jastrzębska, Aneta; Kowalska, Sylwia; Szłyk, Edward

    2016-01-01

    The impact of meat additives on the concentration of biogenic amines and the quality of meat was studied. Fresh white and red meat samples were fortified with the following food additives: citric and lactic acids, disodium diphosphate, sodium nitrite, sodium metabisulphite, potassium sorbate, sodium chloride, ascorbic acid, α-tocopherol, propyl 3,4,5-trihydroxybenzoate (propyl gallate) and butylated hydroxyanisole. The content of spermine, spermidine, putrescine, cadaverine, histamine, tyramine, tryptamine and 2-phenylethylamine was determined by capillary isotachophoretic methods in meat samples (fresh and fortified) during four days of storage at 4°C. The results were applied to estimate the impact of the tested additives on the formation of biogenic amines in white and red meat. For all tested meats, sodium nitrite, sodium chloride and disodium diphosphate showed the best inhibition. However, cadaverine and putrescine were characterised by the biggest changes in concentration during the storage time of all the additives. Based on the presented data for the content of biogenic amines in meat samples analysed as a function of storage time and additives, we suggest that cadaverine and putrescine have a significant impact on meat quality.

  12. Studying circadian rhythm and sleep using genetic screens in Drosophila.

    PubMed

    Axelrod, Sofia; Saez, Lino; Young, Michael W

    2015-01-01

    The power of Drosophila melanogaster as a model organism lies in its ability to be used for large-scale genetic screens with the capacity to uncover the genetic basis of biological processes. In particular, genetic screens for circadian behavior, which have been performed since 1971, allowed researchers to make groundbreaking discoveries on multiple levels: they discovered that there is a genetic basis for circadian behavior, they identified the so-called core clock genes that govern this process, and they started to paint a detailed picture of the molecular functions of these clock genes and their encoded proteins. Since the discovery that fruit flies sleep in 2000, researchers have successfully been using genetic screening to elucidate the many questions surrounding this basic animal behavior. In this chapter, we briefly recall the history of circadian rhythm and sleep screens and then move on to describe techniques currently employed for mutagenesis and genetic screening in the field. The emphasis lies on comparing the newer approaches of transgenic RNA interference (RNAi) to classical forms of mutagenesis, in particular in their application to circadian behavior and sleep. We discuss the different screening approaches in light of the literature and published and unpublished sleep and rhythm screens utilizing ethyl methanesulfonate mutagenesis and transgenic RNAi from our lab.

  13. Population genetic studies revealed local adaptation in a high gene-flow marine fish, the small yellow croaker (Larimichthys polyactis).

    PubMed

    Wang, Le; Liu, Shufang; Zhuang, Zhimeng; Guo, Liang; Meng, Zining; Lin, Haoran

    2013-01-01

    The genetic differentiation of many marine fish species is low. Yet local adaptation may be common in marine fish species as the vast and changing marine environment provides more chances for natural selection. Here, we used anonymous as well as known protein gene linked microsatellites and mitochondrial DNA to detect the population structure of the small yellow croaker (Larimichthys polyactis) in the Northwest Pacific marginal seas. Among these loci, we detected at least two microsatellites, anonymous H16 and HSP27 to be clearly under diversifying selection in outlier tests. Sequence cloning and analysis revealed that H16 was located in the intron of BAHCC1 gene. Landscape genetic analysis showed that H16 mutations were significantly associated with temperature, which further supported the diversifying selection at this locus. These marker types presented different patterns of population structure: (i) mitochondrial DNA phylogeny showed no evidence of genetic divergence and demonstrated only one glacial linage; (ii) population differentiation using putatively neutral microsatellites presented a pattern of high gene flow in the L. polyactis. In addition, several genetic barriers were identified; (iii) the population differentiation pattern revealed by loci under diversifying selection was rather different from that revealed by putatively neutral loci. The results above suggest local adaptation in the small yellow croaker. In summary, population genetic studies based on different marker types disentangle the effects of demographic history, migration, genetic drift and local adaptation on population structure and also provide valuable new insights for the design of management strategies in L. polyactis.

  14. Genetic Models for the Study of Luteinizing Hormone Receptor Function

    PubMed Central

    Narayan, Prema

    2015-01-01

    The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is essential for fertility in men and women. LHCGR binds luteinizing hormone (LH) as well as the highly homologous chorionic gonadotropin. Signaling from LHCGR is required for steroidogenesis and gametogenesis in males and females and for sexual differentiation in the male. The importance of LHCGR in reproductive physiology is underscored by the large number of naturally occurring inactivating and activating mutations in the receptor that result in reproductive disorders. Consequently, several genetically modified mouse models have been developed for the study of LHCGR function. They include targeted deletion of LH and LHCGR that mimic inactivating mutations in hormone and receptor, expression of a constitutively active mutant in LHCGR that mimics activating mutations associated with familial male-limited precocious puberty and transgenic models of LH and hCG overexpression. This review summarizes the salient findings from these models and their utility in understanding the physiological and pathological consequences of loss and gain of function in LHCGR signaling. PMID:26483755

  15. Genetic study of host factors in gastrocarcinogenesis in rats.

    PubMed

    Morino, K; Ohgaki, H; Matsukura, N; Kawachi, T; Sugimura, T

    1982-01-01

    The effects of genetic factors on gastrocarcinogenesis in rats were studied by giving 83 micrograms/ml of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking-water to ACI strain rats, Buffalo strain rats, and their F1 hybrid rats for eight months. Animals were sacrificed on the 505th experimental day and examined histologically. The incidences of gastric carcinoma were as follows (no. of carcinoma-bearing rats/no. of effective animals): ACI rats, 86% (12/14) of males and 53% (9/17) of females; Buffalo rats, 19% (3/16) of males and 0% (0/13) of females; F1 hybrids between ACI and Buffalo rats, 23% (7/30) of males and 3% (1/32) of females. The incidence of gastric carcinoma in F1 hybrids was significantly lower than that in ACI rats but not significantly different from that in Buffalo rats. These results suggest that resistance to gastrocarcinogenesis by MNNG is an autosomally dominant trait.

  16. A genome-wide Asian genetic map and ethnic comparison: The GENDISCAN study

    PubMed Central

    Ju, Young Seok; Park, Hansoo; Lee, Mi Kyeong; Kim, Jong-Il; Sung, Joohon; Cho, Sung-Il; Seo, Jeong-Sun

    2008-01-01

    Background Genetic maps provide specific positions of genetic markers, which are required for performing genetic studies. Linkage analyses of Asian families have been performed with Caucasian genetic maps, since appropriate genetic maps of Asians were not available. Different ethnic groups may have different recombination rates as a result of genomic variations, which would generate misspecification of the genetic map and reduce the power of linkage analyses. Results We constructed the genetic map of a Mongolian population in Asia with CRIMAP software. This new map, called the GENDISCAN map, is based on genotype data collected from 1026 individuals of 73 large Mongolian families, and includes 1790 total and 1500 observable meioses. The GENDISCAN map provides sex-averaged and sex-specific genetic positions of 1039 microsatellite markers in Kosambi centimorgans (cM) with physical positions. We also determined 95% confidence intervals of genetic distances of the adjacent marker intervals. Genetic lengths of the whole genome, chromosomes and adjacent marker intervals are compared with those of Rutgers Map v.2, which was constructed based on Caucasian populations (Centre d'Etudes du Polymorphisme Humain (CEPH) and Icelandic families) by mapping methods identical to those of the GENDISCAN map, CRIMAP software and the Kosambi map function. Mongolians showed approximately 1.9 fewer recombinations per meiosis than Caucasians. As a result, genetic lengths of the whole genome and chromosomes of the GENDISCAN map are shorter than those of Rutgers Map v.2. Thirty-eight marker intervals differed significantly between the Mongolian and Caucasian genetic maps. Conclusion The new GENDISCAN map is applicable to the genetic study of Asian populations. Differences in the genetic distances between the GENDISCAN and Caucasian maps could facilitate elucidation of genomic variations between different ethnic groups. PMID:19025666

  17. Genetic Studies of Quantitative MCI and AD Phenotypes in ADNI: Progress, Opportunities, and Plans

    PubMed Central

    Saykin, Andrew J.; Shen, Li; Yao, Xiaohui; Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Ramanan, Vijay K.; Foroud, Tatiana M.; Faber, Kelly M.; Sarwar, Nadeem; Munsie, Leanne M.; Hu, Xiaolan; Soares, Holly D.; Potkin, Steven G.; Thompson, Paul M.; Kauwe, John S.K.; Kaddurah-Daouk, Rima; Green, Robert C.; Toga, Arthur W.; Weiner, Michael W.

    2015-01-01

    INTRODUCTION Genetic data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) has been crucial in advancing the understanding of AD pathophysiology. Here we provide an update on sample collection, scientific progress and opportunities, conceptual issues, and future plans. METHODS Lymphoblastoid cell lines and DNA and RNA samples from blood have been collected and banked, and data and biosamples have been widely disseminated. To date, APOE genotyping, genome-wide association study (GWAS), and whole exome and whole genome sequencing (WES, WGS) data have been obtained and disseminated. RESULTS ADNI genetic data have been downloaded thousands of times and over 300 publications have resulted, including reports of large scale GWAS by consortia to which ADNI contributed. Many of the first applications of quantitative endophenotype association studies employed ADNI data, including some of the earliest GWAS and pathway-based studies of biospecimen and imaging biomarkers, as well as memory and other clinical/cognitive variables. Other contributions include some of the first WES and WGS data sets and reports in healthy controls, MCI, and AD. DISCUSSION Numerous genetic susceptibility and protective markers for AD and disease biomarkers have been identified and replicated using ADNI data, and have heavily implicated immune, mitochondrial, cell cycle/fate, and other biological processes. Early sequencing studies suggest that rare and structural variants are likely to account for significant additional phenotypic variation. Longitudinal analyses of transcriptomic, proteomic, metabolomic, and epigenomic changes will also further elucidate dynamic processes underlying preclinical and prodromal stages of disease. Integration of this unique collection of multi-omics data within a systems biology framework will help to separate truly informative markers of early disease mechanisms and potential novel therapeutic targets from the vast background of less relevant biological

  18. Heritability of personality: A meta-analysis of behavior genetic studies.

    PubMed

    Vukasović, Tena; Bratko, Denis

    2015-07-01

    The aim of this meta-analysis was to systematize available findings in the field of personality heritability and test for possible moderator effects of study design, type of personality model, and gender on heritability estimates. Study eligibility criteria were: personality model, behavior genetic study design, self-reported data, essential statistical indicators, and independent samples. A total of 134 primary studies with 190 potentially independent effect sizes were identified. After exclusion of studies that did not meet inclusion criteria and/or met 1 of the exclusion criteria, the final sample included 62 independent effect sizes, representing more than 100,000 participants of both genders and all ages. Data analyses were performed using the random-effects model, software program R package metafor. The average effect size was .40, indicating that 40% of individual differences in personality were due to genetic, while 60% are due to environmental influences. After correction for possible publication bias the conclusion was unaltered. Additional analyses showed that personality model and gender were not significant moderators of personality heritability estimate, while study design was a significant moderator with twin studies showing higher estimates, .47, compared to family and adoption studies, .22. Personality model also was not a significant moderator of heritability estimates for neuroticism or extraversion, 2 personality traits contained in most personality trait theories and/or models. This study is the first to empirically test and confirm moderator effect of study design on heritability estimates in the field of personality. Limitations of the study, as well as suggestion for future studies, are discussed. (PsycINFO Database Record

  19. A Study of Aluminum Combustion in Solids, Powders, Foams, Additively-Manufactured Lattices, and Composites

    NASA Astrophysics Data System (ADS)

    Black, James; Trammell, Norman; Batteh, Jad; Curran, Nicholas; Rogers, John; Littrell, Donald

    2015-06-01

    This study examines the fireball characteristics, blast parameters, and combustion efficiency of explosively-shocked aluminum-based materials. The materials included structural and non-structural aluminum forms - such as solid cylinders, foams, additively-manufactured lattices, and powders - and some polytetrafluoroethylene-aluminum (PTFE-Al) composites. The materials were explosively dispersed in a small blast chamber, and the blast properties and products were measured with pressure transducers, thermocouples, slow and fast ultraviolet/visible spectrometers, and high-speed video.

  20. Spectra-temporal patterns underlying mental addition: an ERP and ERD/ERS study.

    PubMed

    Ku, Yixuan; Hong, Bo; Gao, Xiaorong; Gao, Shangkai

    2010-03-12

    Functional neuroimaging data have shown that mental calculation involves fronto-parietal areas that are composed of different subsystems shared with other cognitive functions such as working memory and language. Event-related potential (ERP) analysis has also indicated sequential information changes during the calculation process. However, little is known about the dynamic properties of oscillatory networks in this process. In the present study, we applied both ERP and event-related (de-)synchronization (ERS/ERD) analyses to EEG data recorded from normal human subjects performing tasks for sequential visual/auditory mental addition. Results in the study indicate that the late positive components (LPCs) can be decomposed into two separate parts. The earlier element LPC1 (around 360ms) reflects the computing attribute and is more prominent in calculation tasks. The later element LPC2 (around 590ms) indicates an effect of number size and appears larger only in a more complex 2-digit addition task. The theta ERS and alpha ERD show modality-independent frontal and parietal differential patterns between the mental addition and control groups, and discrepancies are noted in the beta ERD between the 2-digit and 1-digit mental addition groups. The 2-digit addition (both visual and auditory) results in similar beta ERD patterns to the auditory control, which may indicate a reliance on auditory-related resources in mental arithmetic, especially with increasing task difficulty. These results coincide with the theory of simple calculation relying on the visuospatial process and complex calculation depending on the phonological process. PMID:20105450

  1. Shared and Unique Genetic and Environmental Influences on Binge Eating and Night Eating: A Swedish Twin Study

    PubMed Central

    Root, Tammy L.; Thornton, Laura; Lindroos, Ann Karin; Stunkard, Albert J.; Lichtenstein, Paul; Pedersen, Nancy L.; Rasmussen, Finn; Bulik, Cynthia M.

    2009-01-01

    We applied twin methodology to female and male twin pairs to further understand the nature of the relation between two behaviors associated with eating disorders—binge eating (BE) and night eating (NE) in an effort to determine the extent of overlap of genetic and environmental factors influencing liability to these behaviors. We calculated heritability estimates for males and females for each behavior and applied bivariate twin modeling to the female data to estimate the genetic and environmental correlation between these two traits. Data on BE and NE were derived from the Swedish Twin Study of Adults: Genes and Environment (STAGE) of the Swedish Twin Registry (STR; N = 11604). Prevalence estimates revealed sex differences with females more likely to endorse BE and males more likely to endorse NE. In males, we were only able to estimate univariate heritabilities due to small sample sizes: The heritability for BE was .74 [95% CI = (0.36, 0.93)] and for NE was .44 [95% CI = (0.24, 0.61)]. The best fitting bivariate model for females included additive genetic and unique environmental factors as well as the genetic correlation between BE and NE. Heritability estimates were 0.70 [95% CI = (0.26, 0.77)] for BE and 0.35 [95% CI = (0.17, 0.52)] for NE. The genetic correlation, 0.66 [95% CI = (0.48, 0.96)] suggests considerable overlap in the genetic factors influencing liability to BE and NE. In females, there is considerable overlap in the genetic factors that contribute to these traits, but the incomplete overlap allows for the influence of independent genetic and environmental factors as well. BE and NE in females are therefore best conceptualized as related but not identical traits. PMID:20188292

  2. Shared and unique genetic and environmental influences on binge eating and night eating: a Swedish twin study.

    PubMed

    Root, Tammy L; Thornton, Laura M; Lindroos, Ann Karin; Stunkard, Albert J; Lichtenstein, Paul; Pedersen, Nancy L; Rasmussen, Finn; Bulik, Cynthia M

    2010-04-01

    We applied twin methodology to female and male twin pairs to further understand the nature of the relation between two behaviors associated with eating disorders-binge eating (BE) and night eating (NE) in an effort to determine the extent of overlap of genetic and environmental factors influencing liability to these behaviors. We calculated heritability estimates for males and females for each behavior and applied bivariate twin modeling to the female data to estimate the genetic and environmental correlation between these two traits. Data on BE and NE were derived from the Swedish Twin study of Adults: Genes and Environment (STAGE) of the Swedish Twin Registry (STR; N=11,604). Prevalence estimates revealed sex differences with females more likely to endorse BE and males more likely to endorse NE. In males, we were only able to estimate univariate heritabilities due to small sample sizes: The heritability for BE was 0.74 [95% CI=(0.36, 0.93)] and for NE was 0.44 [95% CI=(0.24, 0.61)]. The best fitting bivariate model for females included additive genetic and unique environmental factors as well as the genetic correlation between BE and NE. Heritability estimates were 0.70 [95% CI=(0.26, 0.77)] for BE and 0.35 [95% CI=(0.17, 0.52)] for NE. The genetic correlation, 0.66 [95% CI=(0.48, 0.96)] suggests considerable overlap in the genetic factors influencing liability to BE and NE. In females, there is considerable overlap in the genetic factors that contribute to these traits, but the incomplete overlap allows for the influence of independent genetic and environmental factors as well. BE and NE in females are therefore best conceptualized as related but not identical traits.

  3. Shared and unique genetic and environmental influences on binge eating and night eating: a Swedish twin study.

    PubMed

    Root, Tammy L; Thornton, Laura M; Lindroos, Ann Karin; Stunkard, Albert J; Lichtenstein, Paul; Pedersen, Nancy L; Rasmussen, Finn; Bulik, Cynthia M

    2010-04-01

    We applied twin methodology to female and male twin pairs to further understand the nature of the relation between two behaviors associated with eating disorders-binge eating (BE) and night eating (NE) in an effort to determine the extent of overlap of genetic and environmental factors influencing liability to these behaviors. We calculated heritability estimates for males and females for each behavior and applied bivariate twin modeling to the female data to estimate the genetic and environmental correlation between these two traits. Data on BE and NE were derived from the Swedish Twin study of Adults: Genes and Environment (STAGE) of the Swedish Twin Registry (STR; N=11,604). Prevalence estimates revealed sex differences with females more likely to endorse BE and males more likely to endorse NE. In males, we were only able to estimate univariate heritabilities due to small sample sizes: The heritability for BE was 0.74 [95% CI=(0.36, 0.93)] and for NE was 0.44 [95% CI=(0.24, 0.61)]. The best fitting bivariate model for females included additive genetic and unique environmental factors as well as the genetic correlation between BE and NE. Heritability estimates were 0.70 [95% CI=(0.26, 0.77)] for BE and 0.35 [95% CI=(0.17, 0.52)] for NE. The genetic correlation, 0.66 [95% CI=(0.48, 0.96)] suggests considerable overlap in the genetic factors influencing liability to BE and NE. In females, there is considerable overlap in the genetic factors that contribute to these traits, but the incomplete overlap allows for the influence of independent genetic and environmental factors as well. BE and NE in females are therefore best conceptualized as related but not identical traits. PMID:20188292

  4. Studies on Monitoring and Tracking Genetic Resources: An Executive Summary

    PubMed Central

    Garrity, George M.; Thompson, Lorraine M.; Ussery, David W.; Paskin, Norman; Baker, Dwight; Desmeth, Philippe; Schindel, D.E.; Ong, P.S.

    2009-01-01

    The principles underlying fair and equitable sharing of benefits derived from the utilization of genetic resources are set out in Article 15 of the UN Convention on Biological Diversity, which stipulate that access to genetic resources is subject to the prior informed consent of the country where such resources are located and to mutually agreed terms regarding the sharing of benefits that could be derived from such access. One issue of particular concern for provider countries is how to monitor and track genetic resources once they have left the provider country and enter into use in a variety of forms. This report was commissioned to provide a detailed review of advances in DNA sequencing technologies, as those methods apply to identification of genetic resources, and the use of globally unique persistent identifiers for persistently linking to data and other forms of digital documentation that is linked to individual genetic resources. While the report was written for an audience with a mixture of technical, legal, and policy backgrounds it is relevant to the genomics community as it is an example of downstream application of genomics information. PMID:21304641

  5. Identification of CSK as a systemic sclerosis genetic risk factor through Genome Wide Association Study follow-up

    PubMed Central

    Martin, Jose-Ezequiel; Broen, Jasper C.; Carmona, F. David; Teruel, Maria; Simeon, Carmen P.; Vonk, Madelon C.; van ‘t Slot, Ruben; Rodriguez-Rodriguez, Luis; Vicente, Esther; Fonollosa, Vicente; Ortego-Centeno, Norberto; González-Gay, Miguel A.; García-Hernández, Francisco J.; de la Peña, Paloma García; Carreira, Patricia; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; van Riel, Piet L.C.M.; Kreuter, Alexander; Witte, Torsten; Riemekasten, Gabriella; Airo, Paolo; Scorza, Raffaella; Lunardi, Claudio; Hunzelmann, Nicolas; Distler, Jörg H.W.; Beretta, Lorenzo; van Laar, Jacob; Chee, Meng May; Worthington, Jane; Herrick, Ariane; Denton, Christopher; Tan, Filemon K.; Arnett, Frank C.; Assassi, Shervin; Fonseca, Carmen; Mayes, Maureen D.; Radstake, Timothy R.D.J.; Koeleman, Bobby P.C.; Martin, Javier

    2012-01-01

    Systemic sclerosis (SSc) is complex autoimmune disease affecting the connective tissue; influenced by genetic and environmental components. Recently, we performed the first successful genome-wide association study (GWAS) of SSc. Here, we perform a large replication study to better dissect the genetic component of SSc. We selected 768 polymorphisms from the previous GWAS and genotyped them in seven replication cohorts from Europe. Overall significance was calculated for replicated significant SNPs by meta-analysis of the replication cohorts and replication-GWAS cohorts (3237 cases and 6097 controls). Six SNPs in regions not previously associated with SSc were selected for validation in another five independent cohorts, up to a total of 5270 SSc patients and 8326 controls. We found evidence for replication and overall genome-wide significance for one novel SSc genetic risk locus: CSK [P-value = 5.04 × 10−12, odds ratio (OR) = 1.20]. Additionally, we found suggestive association in the loci PSD3 (P-value = 3.18 × 10−7, OR = 1.36) and NFKB1 (P-value = 1.03 × 10−6, OR = 1.14). Additionally, we strengthened the evidence for previously confirmed associations. This study significantly increases the number of known putative genetic risk factors for SSc, including the genes CSK, PSD3 and NFKB1, and further confirms six previously described ones. PMID:22407130

  6. Frontiers of torenia research: innovative ornamental traits and study of ecological interaction networks through genetic engineering

    PubMed Central

    2013-01-01

    Advances in research in the past few years on the ornamental plant torenia (Torenia spps.) have made it notable as a model plant on the frontier of genetic engineering aimed at studying ornamental characteristics and pest control in horticultural ecosystems. The remarkable advantage of torenia over other ornamental plant species is the availability of an easy and high-efficiency transformation system for it. Unfortunately, most of the current torenia research is still not very widespread, because this species has not become prominent as an alternative to other successful model plants such as Arabidopsis, snapdragon and petunia. However, nowadays, a more global view using not only a few selected models but also several additional species are required for creating innovative ornamental traits and studying horticultural ecosystems. We therefore introduce and discuss recent research on torenia, the family Scrophulariaceae, for secondary metabolite bioengineering, in which global insights into horticulture, agriculture and ecology have been advanced. Floral traits, in torenia particularly floral color, have been extensively studied by manipulating the flavonoid biosynthetic pathways in flower organs. Plant aroma, including volatile terpenoids, has also been genetically modulated in order to understand the complicated nature of multi-trophic interactions that affect the behavior of predators and pollinators in the ecosystem. Torenia would accordingly be of great use for investigating both the variation in ornamental plants and the infochemical-mediated interactions with arthropods. PMID:23803155

  7. A twin and molecular genetics study of sleep paralysis and associated factors.

    PubMed

    Denis, Dan; French, Christopher C; Rowe, Richard; Zavos, Helena M S; Nolan, Patrick M; Parsons, Michael J; Gregory, Alice M

    2015-08-01

    Sleep paralysis is a relatively common but under-researched phenomenon. In this paper we examine prevalence in a UK sample and associations with candidate risk factors. This is the first study to investigate the heritability of sleep paralysis in a twin sample and to explore genetic associations between sleep paralysis and a number of circadian expressed single nucleotide polymorphisms. Analyses are based on data from the Genesis1219 twin/sibling study, a community sample of twins/siblings from England and Wales. In total, data from 862 participants aged 22-32 years (34% male) were used in the study. This sample consisted of monozygotic and dizygotic twins and siblings. It was found that self-reports of general sleep quality, anxiety symptoms and exposure to threatening events were all associated independently with sleep paralysis. There was moderate genetic influence on sleep paralysis (53%). Polymorphisms in the PER2 gene were associated with sleep paralysis in additive and dominant models of inheritance-although significance was not reached once a Bonferroni correction was applied. It is concluded that factors associated with disrupted sleep cycles appear to be associated with sleep paralysis. In this sample of young adults, sleep paralysis was moderately heritable. Future work should examine specific polymorphisms associated with differences in circadian rhythms and sleep homeostasis further in association with sleep paralysis.

  8. A twin and molecular genetics study of sleep paralysis and associated factors.

    PubMed

    Denis, Dan; French, Christopher C; Rowe, Richard; Zavos, Helena M S; Nolan, Patrick M; Parsons, Michael J; Gregory, Alice M

    2015-08-01

    Sleep paralysis is a relatively common but under-researched phenomenon. In this paper we examine prevalence in a UK sample and associations with candidate risk factors. This is the first study to investigate the heritability of sleep paralysis in a twin sample and to explore genetic associations between sleep paralysis and a number of circadian expressed single nucleotide polymorphisms. Analyses are based on data from the Genesis1219 twin/sibling study, a community sample of twins/siblings from England and Wales. In total, data from 862 participants aged 22-32 years (34% male) were used in the study. This sample consisted of monozygotic and dizygotic twins and siblings. It was found that self-reports of general sleep quality, anxiety symptoms and exposure to threatening events were all associated independently with sleep paralysis. There was moderate genetic influence on sleep paralysis (53%). Polymorphisms in the PER2 gene were associated with sleep paralysis in additive and dominant models of inheritance-although significance was not reached once a Bonferroni correction was applied. It is concluded that factors associated with disrupted sleep cycles appear to be associated with sleep paralysis. In this sample of young adults, sleep paralysis was moderately heritable. Future work should examine specific polymorphisms associated with differences in circadian rhythms and sleep homeostasis further in association with sleep paralysis. PMID:25659590

  9. The Admixture Structure and Genetic Variation of the Archipelago of Cape Verde and Its Implications for Admixture Mapping Studies

    PubMed Central

    Beleza, Sandra; Campos, Joana; Lopes, Jailson; Araújo, Isabel Inês; Hoppfer Almada, Ana; e Silva, António Correia; Parra, Esteban J.; Rocha, Jorge

    2012-01-01

    Recently admixed populations offer unique opportunities for studying human history and for elucidating the genetic basis of complex traits that differ in prevalence between human populations. Historical records, classical protein markers, and preliminary genetic data indicate that the Cape Verde islands in West Africa are highly admixed and primarily descended from European males and African females. However, little is known about the variation in admixture levels, admixture dynamics and genetic diversity across the islands, or about the potential of Cape Verde for admixture mapping studies. We have performed a detailed analysis of phenotypic and genetic variation in Cape Verde based on objective skin color measurements, socio-economic status (SES) evaluations and data for 50 autosomal, 34 X-chromosome, and 21 non-recombinant Y-chromosome (NRY) markers in 845 individuals from six islands of the archipelago. We find extensive genetic admixture between European and African ancestral populations (mean West African ancestry = 0.57, sd = 0.08), with individual African ancestry proportions varying considerably among the islands. African ancestry proportions calculated with X and Y-chromosome markers confirm that the pattern of admixture has been sex-biased. The high-resolution NRY-STRs reveal additional patterns of variation among the islands that are most consistent with differentiation after admixture. The differences in the autosomal admixture proportions are clearly evident in the skin color distribution across the islands (Pearson r = 0.54, P-value<2e–16). Despite this strong correlation, there are significant interactions between SES and skin color that are independent of the relationship between skin color and genetic ancestry. The observed distributions of admixture, genetic variation and skin color and the relationship of skin color with SES relate to historical and social events taking place during the settlement history of Cape Verde, and have

  10. Unravelling fears of genetic discrimination: an exploratory study of Dutch HCM families in an era of genetic non-discrimination acts.

    PubMed

    Geelen, Els; Horstman, Klasien; Marcelis, Carlo L M; Doevendans, Pieter A; Van Hoyweghen, Ine

    2012-10-01

    Since the 1990s, many countries in Europe and the United States have enacted genetic non-discrimination legislation to prevent people from deferring genetic tests for fear that insurers or employers would discriminate against them based on that information. Although evidence for genetic discrimination exists, little is known about the origins and backgrounds of fears of discrimination and how it affects decisions for uptake of genetic testing. The aim of this article is to gain a better understanding of these fears and its possible impact on the uptake of testing by studying the case of hypertrophic cardiomyopathy (HCM). In a qualitative study, we followed six Dutch extended families involved in genetic testing for HCM for three-and-a-half years. Semi-structured interviews were conducted with 57 members of these families. Based on the narratives of the families, we suggest that fears of discrimination have to be situated in the broader social and life-course context of family and kin. We describe the processes in which families developed meaningful interpretations of genetic discrimination and how these interpretations affected family members' decisions to undergo genetic testing. Our findings show that fears of genetic discrimination do not so much stem from the opportunity of genetic testing but much more from earlier experiences of discrimination of diseased family members. These results help identify the possible limitations of genetic non-discrimination regulations and provide direction to clinicians supporting their clients as they confront issues of genetic testing and genetic discrimination.

  11. Genetic and Environmental Influences on Neuroimaging Phenotypes: A Meta-Analytical Perspective on Twin Imaging Studies

    PubMed Central

    Blokland, Gabriella A. M.; de Zubicaray, Greig I.; McMahon, Katie L.; Wright, Margaret J.

    2014-01-01

    Because brain structure and function are affected in neurological and psychiatric disorders, it is important to disentangle the sources of variation in these phenotypes. Over the past 15 years, twin studies have found evidence for both genetic and environmental influences on neuroimaging phenotypes, but considerable variation across studies makes it difficult to draw clear conclusions about the relative magnitude of these influences. Here we performed the first meta-analysis of structural MRI data from 48 studies on >1,250 twin pairs, and diffusion tensor imaging data from 10 studies on 444 twin pairs. The proportion of total variance accounted for by genes (A), shared environment (C), and unshared environment (E), was calculated by averaging A, C, and E estimates across studies from independent twin cohorts and weighting by sample size. The results indicated that additive genetic estimates were significantly different from zero for all meta-analyzed phenotypes, with the exception of fractional anisotropy (FA) of the callosal splenium, and cortical thickness (CT) of the uncus, left parahippocampal gyrus, and insula. For many phenotypes there was also a significant influence of C. We now have good estimates of heritability for many regional and lobar CT measures, in addition to the global volumes. Confidence intervals are wide and number of individuals small for many of the other phenotypes. In conclusion, while our meta-analysis shows that imaging measures are strongly influenced by genes, and that novel phenotypes such as CT measures, FA measures, and brain activation measures look especially promising, replication across independent samples and demographic groups is necessary. PMID:22856370

  12. Use of Longitudinal Data in Genetic Studies in the Genome-wide Association Studies Era: Summary of Group 14

    PubMed Central

    Kerner, Berit; North, Kari E; Fallin, M Daniele

    2010-01-01

    Participants analyzed actual and simulated longitudinal data from the Framingham Heart Study for various metabolic and cardiovascular traits. The genetic information incorporated into these investigations ranged from selected single-nucleotide polymorphisms to genome-wide association arrays. Genotypes were incorporated using a broad range of methodological approaches including conditional logistic regression, linear mixed models, generalized estimating equations, linear growth curve estimation, growth modeling, growth mixture modeling, population attributable risk fraction based on survival functions under the proportional hazards models, and multivariate adaptive splines for the analysis of longitudinal data. The specific scientific questions addressed by these different approaches also varied, ranging from a more precise definition of the phenotype, bias reduction in control selection, estimation of effect sizes and genotype associated risk, to direct incorporation of genetic data into longitudinal modeling approaches and the exploration of population heterogeneity with regard to longitudinal trajectories. The group reached several overall conclusions: 1) The additional information provided by longitudinal data may be useful in genetic analyses. 2) The precision of the phenotype definition as well as control selection in nested designs may be improved, especially if traits demonstrate a trend over time or have strong age-of-onset effects. 3) Analyzing genetic data stratified for high-risk subgroups defined by a unique development over time could be useful for the detection of rare mutations in common multi-factorial diseases. 4) Estimation of the population impact of genomic risk variants could be more precise. The challenges and computational complexity demanded by genome-wide single-nucleotide polymorphism data were also discussed. PMID:19924713

  13. Genetic moderation of stability in attachment security from early childhood to age 18 years: A replication study.

    PubMed

    Raby, K Lee; Roisman, Glenn I; Booth-LaForce, Cathryn

    2015-11-01

    A longstanding question for attachment theory and research is whether genetically based characteristics of the child influence the development of attachment security and its stability over time. This study attempted to replicate and extend recent findings indicating that the developmental stability of attachment security is moderated by oxytocin receptor (OXTR) genetic variants. Using longitudinal data from over 550 individuals, there was no evidence that OXTR rs53576 moderated the association between attachment security during early childhood and overall coherence of mind ("security") during the Adult Attachment Interview at age 18 years. Additional analyses involving a second commonly investigated OXTR variant (rs2254298) and indices of individuals' dismissing and preoccupied attachment states of mind also failed to provide robust evidence for oxytonergic moderation of the stability in attachment security across development. The discussion focuses on research strategies for investigating genetic contributions to attachment security across the life span.

  14. A Genetically Informed Study of the Intergenerational Transmission of Marital Instability

    ERIC Educational Resources Information Center

    D'Onofrio, Brian M.; Turkheimer, Eric; Emery, Robert E.; Harden, K. Paige; Slutske, Wendy S.; Heath, Andrew C.; Madden, Pamela A. F.; Martin, Nicholas G.

    2007-01-01

    Environmental or genetic influences, or both could account for the increased risk of divorce among the offspring of separated parents. Previous studies have used covariates to statistically control for confounds, but the present research is the first genetically informed study of the topic. The investigation used the Children of Twins Design with…

  15. Genetic and environmental influences on spontaneous micronuclei frequencies in children and adults: a twin study.

    PubMed

    Jones, Kimberly H; York, Timothy P; Juusola, Jane; Ferreira-Gonzalez, Andrea; Maes, Hermine H; Jackson-Cook, Colleen

    2011-11-01

    The primary aim of this study was to quantify genetic and environmental influences on the frequency of spontaneously occurring micronuclei in children and adults. To meet this aim, a total of 63 male and female twin pairs and 19 singletons (145 individuals) were evaluated, ranging in age from 7 to 85 years. Micronuclei frequencies significantly increased with age for both genders (r = 0.49, P < 0.001), with the lowest and highest rates being seen in the 7- to 9 (mean = 0.56%, SD = .28) and 60- to 69-year-olds (mean = 2.12%, SD = 1.0), respectively. This age effect was significantly more pronounced in females than males (P = 0.017). In addition to the main effect of age, the completion of puberty in either gender (P = 0.036) and menopause in females (P = 0.024) was associated with a significant increase in micronuclei frequencies. Genetic model fitting indicated that influences from both additive genetic (65.2% of variance) and unique environmental (34.8% of variance) sources best explained the observed micronuclei frequencies in monozygotic and dizygotic twin pairs. Self-reported health conditions associated with an increased frequency of micronuclei included a history of allergies (P < 0.007) and migraines (P = 0.026). Multivitamin use was also associated with increased micronuclei frequencies (P = 0.004). In contrast, significantly lower micronuclei frequencies were associated with arthritis (P = 0.002), as well as consuming fruit (P = 0.014), green, leafy vegetables (P < 0.001) and/or folate-enriched bread (P = 0.035). A sex-specific effect, resulting in a significantly increased frequency of micronuclei with tobacco usage, was observed for females (but not males). Gender differences also moderated the impact of vitamin D and calcium consumption. In conclusion, the frequency of spontaneously arising micronuclei in humans is a complex trait, being influenced by both heritable genetic and environmental components. Recognition of factors contributing to baseline

  16. Genetic vectors as a tool in association studies: definitions and application for study of rheumatoid arthritis.

    PubMed

    Sandalov, Igor; Padyukov, Leonid

    2015-01-01

    To identify putative relations between different genetic factors in the human genome in the development of common complex disease, we mapped the genetic data to an ensemble of spin chains and analysed the data as a quantum system. Each SNP is considered as a spin with three states corresponding to possible genotypes. The combined genotype represents a multispin state, described by the product of individual-spin states. Each person is characterized by a single genetic vector (GV) and individuals with identical GVs comprise the GV group. This consolidation of genotypes into GVs provides integration of multiple genetic variants for a single statistical test and excludes ambiguity of biological interpretation known for allele and haplotype associations. We analyzed two independent cohorts, with 2633 rheumatoid arthritis cases and 2108 healthy controls, and data for 6 SNPs from the HTR2A locus plus shared epitope allele. We found that GVs based on selected markers are highly informative and overlap for 98.3% of the healthy population between two cohorts. Interestingly, some of the GV groups contain either only controls or only cases, thus demonstrating extreme susceptibility or protection features. By using this new approach we confirmed previously detected univariate associations and demonstrated the most efficient selection of SNPs for combined analyses for functional studies. PMID:25834811

  17. A biochemical and genetic study of Leishmania donovani pyruvate kinase.

    PubMed

    Sandoval, Will; Isea, Raúl; Rodriguez, Evelyn; Ramirez, Jose Luis

    2008-11-15

    Here we present a biochemical and molecular biology study of the enzyme pyruvate kinase (PYK) from the parasitic protozoa Leishmania donovani. The PYK gene was cloned, mutagenised and over expressed and its kinetic parameters determined. Like in other kinetoplastids, L. donovani PYK is allosterically stimulated by the effector fructose 2,6 biphosphate and not by fructose 1,6 biphosphate. When the putative effector binding site of L. donovani PYK was mutagenised, we obtained two mutants with extreme kinetic behavior: Lys453Leu, which retained a sigmoidal kinetics and was little affected by the effector; and His480Gln, which deployed a hyperbolic kinetics that was not changed by the addition of the effector. Molecular Dynamics (MD) studies revealed that the mutations not only altered the effector binding site of L. donovani PYK but also changed the folding of its domain C. PMID:18725273

  18. Effect of Exogenous Phytase Addition on Soil Phosphatase Activities: a Fluorescence Spectroscopy Study.

    PubMed

    Yang, Xiao-zhu; Chen, Zhen-hua; Zhang, Yu-lan; Chen, Li-jun

    2015-05-01

    The utilization of organic phosphorus (P) has directly or indirectly improved after exogenous phytase was added to soil. However, the mechanism by which exogenous phytase affected the soil phosphatases (phosphomonoesterase and phosphodiesterase) activities was not clear. The present work was aimed to study red soil, brown soil and cinnamon soil phosphomonoesterase (acid and alkaline) (AcP and AlP) and phosphodiesterase (PD) activities responding to the addition of exogenous phytase (1 g phytase/50 g air dry soil sample) based on the measurements performed via a fluorescence detection method combined with 96 microplates using a TECAN Infinite 200 Multi-Mode Microplate Reader. The results indicated that the acid phosphomonoesterase activity was significantly enhanced in red soil (p≤0. 01), while it was significantly reduced in cinnamon soil; alkaline phosphomonoesterase activity was significantly enhanced in cinnamon soil (p≤ 0. 01), while it was significantly reduced in red soil; phosphodiesterase activity was increased in three soils but it was significantly increased in brown soil (p≤0. 01) after the addition of exogenous phytase. The activities still remained strong after eight days in different soils, which indicated that exogenous phytase addition could be enhance soil phosphatases activities effectively. This effect was not only related to soil properties, such as pH and phosphorus forms, but might also be related to the excreted enzyme amount of the stimulating microorganism. Using fluorescence spectroscopy to study exogenous phytase addition influence on soil phosphatase activities was the first time at home and abroad. Compared with the conventional spectrophotometric method, the fluorescence microplate method is an accurate, fast and simple to use method to determine the relationships among the soil phosphatases activities.

  19. Informed consent, participation in, and withdrawal from a population based cohort study involving genetic analysis

    PubMed Central

    Matsui, K; Kita, Y; Ueshima, H

    2005-01-01

    Design: Descriptive analyses. Setting and participants: The study evaluated two non-genetic subcohorts comprising 3166 people attending for a health checkup during 2002, and two genetic subcohorts comprising 2195 people who underwent a checkup during 2003. Main outcome measurements: Analysis endpoints were differences in participation rates between the non-genetic and genetic subcohorts, differences between providing non-extensive and extensive preliminary information, and changes in participation status between baseline and at 6 months. Results: Participation rates in the genetic subcohorts were 4·7–9·3% lower than those in the non-genetic subcohorts. The odds ratios (OR) of participation in genetic research were between 0·60 and 0·77, and the OR for withdrawal from the research was over 7·70; providing preliminary extensive information about genetic research reduced the withdrawal risks (OR 0·15 for all dependent variables) but worsened participation rates (OR 0·63–0·74). Conclusions: The general population responded sceptically towards genetic research. It is crucial that genetic researchers utilise an informative and educational consent process worthy of public trust. PMID:15994356

  20. Genetic Studies of Stuttering in a Founder Population

    ERIC Educational Resources Information Center

    Wittke-Thompson, Jacqueline K.; Ambrose, Nicoline; Yairi, Ehud; Roe, Cheryl; Cook, Edwin H.; Ober, Carole; Cox, Nancy J.

    2007-01-01

    Genome-wide linkage and association analyses were conducted to identify genetic determinants of stuttering in a founder population in which 48 individuals affected with stuttering are connected in a single 232-person genealogy. A novel approach was devised to account for all necessary relationships to enable multipoint linkage analysis. Regions…

  1. What Can the Study of Genetics Offer to Educators?

    ERIC Educational Resources Information Center

    Thomas, Michael S. C.; Kovas, Yulia; Meaburn, Emma L.; Tolmie, Andrew

    2015-01-01

    This article explores the potential contribution of modern genetic methods and findings to education. It is familiar to hear that the "gene" for this or that behavior has been discovered, or that certain skills are "highly heritable." Can this help educators? To explore this question, we describe the methods used to relate…

  2. Genetic determinants of bone mass in adults. A twin study.

    PubMed Central

    Pocock, N A; Eisman, J A; Hopper, J L; Yeates, M G; Sambrook, P N; Eberl, S

    1987-01-01

    The relative importance of genetic factors in determining bone mass in different parts of the skeleton is poorly understood. Lumbar spine and proximal femur bone mineral density and forearm bone mineral content were measured by photon absorptiometry in 38 monozygotic and 27 dizygotic twin pairs. Bone mineral density was significantly more highly correlated in monozygotic than in dizygotic twins for the spine and proximal femur and in the forearm of premenopausal twin pairs, which is consistent with significant genetic contributions to bone mass at all these sites. The lesser genetic contribution to proximal femur and distal forearm bone mass compared with the spine suggests that environmental factors are of greater importance in the aetiology of osteopenia of the hip and wrist. This is the first demonstration of a genetic contribution to bone mass of the spine and proximal femur in adults and confirms similar findings of the forearm. Furthermore, bivariate analysis suggested that a single gene or set of genes determines bone mass at all sites. PMID:3624485

  3. Ninos Desaparecidos: A Case Study about Genetics and Human Rights.

    ERIC Educational Resources Information Center

    Chamany, Katayoun

    2001-01-01

    Provides information on the experiences of 50 children displaced during Argentina's "dirty war" of the 1970s who underwent DNA and protein analysis and subsequently were reunited with their biological families. Considers not only genetic evidence but the moral, political, and emotional dimensions of these children's stories as well. (Contains 19…

  4. Genetic Simulation Tools for Post-Genome Wide Association Studies of Complex Diseases

    PubMed Central

    Amos, Christopher I.; Bafna, Vineet; Hauser, Elizabeth R.; Hernandez, Ryan D.; Li, Chun; Liberles, David A.; McAllister, Kimberly; Moore, Jason H.; Paltoo, Dina N.; Papanicolaou, George J.; Peng, Bo; Ritchie, Marylyn D.; Rosenfeld, Gabriel; Witte, John S.

    2014-01-01

    Genetic simulation programs are used to model data under specified assumptions to facilitate the understanding and study of complex genetic systems. Standardized data sets generated using genetic simulation are essential for the development and application of novel analytical tools in genetic epidemiology studies. With continuing advances in high-throughput genomic technologies and generation and analysis of larger, more complex data sets, there is a need for updating current approaches in genetic simulation modeling. To provide a forum to address current and emerging challenges in this area, the National Cancer Institute (NCI) sponsored a workshop, entitled “Genetic Simulation Tools for Post-Genome Wide Association Studies of Complex Diseases” at the National Institutes of Health (NIH) in Bethesda, Maryland on March 11-12, 2014. The goals of the workshop were to: (i) identify opportunities, challenges and resource needs for the development and application of genetic simulation models; (ii) improve the integration of tools for modeling and analysis of simulated data; and (iii) foster collaborations to facilitate development and applications of genetic simulation. During the course of the meeting the group identified challenges and opportunities for the science of simulation, software and methods development, and collaboration. This paper summarizes key discussions at the meeting, and highlights important challenges and opportunities to advance the field of genetic simulation. PMID:25371374

  5. Genetic simulation tools for post-genome wide association studies of complex diseases.

    PubMed

    Chen, Huann-Sheng; Hutter, Carolyn M; Mechanic, Leah E; Amos, Christopher I; Bafna, Vineet; Hauser, Elizabeth R; Hernandez, Ryan D; Li, Chun; Liberles, David A; McAllister, Kimberly; Moore, Jason H; Paltoo, Dina N; Papanicolaou, George J; Peng, Bo; Ritchie, Marylyn D; Rosenfeld, Gabriel; Witte, John S; Gillanders, Elizabeth M; Feuer, Eric J

    2015-01-01

    Genetic simulation programs are used to model data under specified assumptions to facilitate the understanding and study of complex genetic systems. Standardized data sets generated using genetic simulation are essential for the development and application of novel analytical tools in genetic epidemiology studies. With continuing advances in high-throughput genomic technologies and generation and analysis of larger, more complex data sets, there is a need for updating current approaches in genetic simulation modeling. To provide a forum to address current and emerging challenges in this area, the National Cancer Institute (NCI) sponsored a workshop, entitled "Genetic Simulation Tools for Post-Genome Wide Association Studies of Complex Diseases" at the National Institutes of Health (NIH) in Bethesda, Maryland on March 11-12, 2014. The goals of the workshop were to (1) identify opportunities, challenges, and resource needs for the development and application of genetic simulation models; (2) improve the integration of tools for modeling and analysis of simulated data; and (3) foster collaborations to facilitate development and applications of genetic simulation. During the course of the meeting, the group identified challenges and opportunities for the science of simulation, software and methods development, and collaboration. This paper summarizes key discussions at the meeting, and highlights important challenges and opportunities to advance the field of genetic simulation.

  6. The Unexplained Female Predominance of Systemic Lupus Erythematosus: Clues from Genetic and Cytokine Studies

    PubMed Central

    Weckerle, Corinna E.

    2010-01-01

    Despite recent progress in the understanding of systemic lupus erythematosus (SLE), the striking 9:1 female to male ratio of disease incidence remains largely unexplained. In addition, peak SLE incidence rates occur during the early reproductive years in women. Studies which illuminate potential causes underlying this sex difference and characteristic onset during the reproductive years have the potential to fundamentally advance our understanding of disease pathogenesis in SLE. Similarly, progress in this area will likely inform human reproductive immunology. Studies of sex hormone function in the immune system are of obvious importance; however, it seems likely that many other types of sex-related genetic and immunological differences will contribute to SLE. In this review, we will focus on recent work in sex-related differences in cytokine pathways and genetics of these pathways as they relate to SLE pathogenesis. It seems quite possible that many of these sex-related differences could be important to reproductive fitness, which may explain the conservation of these immune system features and the observed female predominance of SLE. PMID:20063186

  7. Genetic approaches for studying myiasis-causing flies: molecular markers and mitochondrial genomics.

    PubMed

    de Azeredo-Espin, Ana Maria Lima; Lessinger, Ana Cláudia

    2006-01-01

    "Myiasis-causing flies" is a generic term that includes species from numerous dipteran families, mainly Calliphoridae and Oestridae, of which blowflies, screwworm flies and botflies are among the most important. This group of flies is characterized by the ability of their larvae to develop in animal flesh. When the host is a live vertebrate, such parasitism by dipterous larvae is known as primary myiasis. Myiasis-causing flies can be classified as saprophagous (free-living species), facultative or obligate parasites. Many of these flies are of great medical and veterinary importance in Brazil because of their role as key livestock insect-pests and vectors of pathogens, in addition to being considered important legal evidence in forensic entomology. The characterization of myiasis-causing flies using molecular markers to study mtDNA (by RFLP) and nuclear DNA (by RAPD and microsatellite) has been used to identify the evolutionary mechanisms responsible for specific patterns of genetic variability. These approaches have been successfully used to analyze the population structures of the New World screwworm fly Cochliomyia hominivorax and the botfly Dermatobia hominis. In this review, various aspects of the organization, evolution and potential applications of the mitochondrial genome of myiasis-causing flies in Brazil, and the analysis of nuclear markers in genetic studies of populations, are discussed.

  8. Strategies for genetic study of hearing loss in the Brazilian northeastern region

    PubMed Central

    Melo, Uirá S; Santos, Silvana; Cavalcanti, Hannalice G; Andrade, Wagner T; Dantas, Vitor G; Rosa, Marine RD; Mingroni-Netto, Regina C

    2014-01-01

    The overall aim of this study was to estimate the contribution of genetic factors to the etiology of hearing loss (HL) in two counties in the Brazilian northeastern region. A cross-sectional study, based on the key informant approach (KI) was conducted in Queimadas and Gado Bravo counties (Paraíba, Northeast Brazil). The sample consisted of 182 patients with HL. Genetic screening of the most frequent mutations associated with HL was performed for all samples. DFNB1 mutations were the most frequently found in both counties. The c.35delG mutation was detected in homozygosis in seven non-syndromic probands in Queimadas (7/76, 9.2%) and only a single homozygote with this mutation was found in Gado Bravo (1/44, 2.3%). We also detected the del(GJB6-D13S1854) mutation in non-syndromic probands from Gado Bravo (2/44, 4.5%). The c.189C>A (p.TyrY63*) mutation in the CLRN1 gene was detected in homozygosis in 21/23 Usher syndrome patients from Gado Bravo and it was not found in Queimadas. Cases with probable genetic etiology contributed approximately to half of HL probands in each county (54.6% in Gado Bravo and 45.7% in Queimadas). We confirm the importance of DFNB1 locus to non-syndromic HL but we show that the frequency of mutations in the northeastern region differs somewhat from those reported in southeastern Brazil and other populations. In addition, the extremely high frequency of individuals with Usher syndrome with c.189C>A variation in CLRN1 indicates the need for a specific screening of this mutation. PMID:24596593

  9. Genetic variation of piperidine alkaloids in Pinus ponderosa: a common garden study

    PubMed Central

    Gerson, Elizabeth A.; Kelsey, Rick G.; St Clair, J. Bradley

    2009-01-01

    Background and Aims Previous measurements of conifer alkaloids have revealed significant variation attributable to many sources, environmental and genetic. The present study takes a complementary and intensive, common garden approach to examine genetic variation in Pinus ponderosa var. ponderosa alkaloid production. Additionally, this study investigates the potential trade-off between seedling growth and alkaloid production, and associations between topographic/climatic variables and alkaloid production. Methods Piperidine alkaloids were quantified in foliage of 501 nursery seedlings grown from seed sources in west-central Washington, Oregon and California, roughly covering the western half of the native range of ponderosa pine. A nested mixed model was used to test differences among broad-scale regions and among families within regions. Alkaloid concentrations were regressed on seedling growth measurements to test metabolite allocation theory. Likewise, climate characteristics at the seed sources were also considered as explanatory variables. Key Results Quantitative variation from seedling to seedling was high, and regional variation exceeded variation among families. Regions along the western margin of the species range exhibited the highest alkaloid concentrations, while those further east had relatively low alkaloid levels. Qualitative variation in alkaloid profiles was low. All measures of seedling growth related negatively to alkaloid concentrations on a natural log scale; however, coefficients of determination were low. At best, annual height increment explained 19·4 % of the variation in ln(total alkaloids). Among the climate variables, temperature range showed a negative, linear association that explained 41·8 % of the variation. Conclusions Given the wide geographic scope of the seed sources and the uniformity of resources in the seedlings' environment, observed differences in alkaloid concentrations are evidence for genetic regulation of alkaloid

  10. Informed consent for human genetic and genomic studies: a systematic review.

    PubMed

    Khan, A; Capps, B J; Sum, M Y; Kuswanto, C N; Sim, K

    2014-09-01

    As genetic and genomic studies grow in scale, there are ethical concerns related to the collection and use of genetic information. The emergence of large public databases potentially redefine the terms of participation in genetic and genomic research, and suggests the changing application of traditional ethical principles such as privacy or consent. For this study, we wanted to see whether such developments are reflected in the informed consent processes in human genetic and genomic studies. Therefore, we performed a systematic review of the empirical studies that examined informed consent involving large genetic databases in human genetic and genomic studies, grouped the identified issues related to the different stakeholders (including subjects, researchers, and institutional review boards) and discussed the limitations and implications of these findings. Major themes related to the place of bioethical considerations, procured tissues, people involved, process of informed consent and study procedures. Frequently raised issues included confidentiality of participants, documentation of informed consent, public attitudes, future use of participant samples or data, and disclosure of results. Awareness and attention to these bioethical issues as well as assiduousness in managing these concerns in genetic/genomic research would further strengthen and safeguard the rights, safety and well-being of genetic research participants.

  11. Genetic linkage studies in autosomal recessive retinitis pigmentosa

    SciTech Connect

    Mansfield, D.C.; Teague, P.W.; Barber, A.

    1994-09-01

    Autosomal recessive retinitis pigmentosa (arRP) is a severe retinal dystrophy characterized by night blindness, progressive constriction of the visual fields and loss of central vision in the fourth or fifth decades. The frequency of this form of retinitis pigmentosa (RP) varies in different populations. Mutations within the rhodopsin, cyclic GMP phosphodiesterase-{beta} subunit and cGMP-gated channel genes have been reported in some arRP families. The genetic loci responsible for the majority of cases have yet to be identified. Genetic heterogeneity is likely to be extensive. In order to minimize the amount of genetic heterogenity, a set of arRP families was ascertained within the South-Central Sardinian population, in which 81% of families with a known mode of inheritance show an autosomal recessive form of RP. The Sardinian population is an ethnic {open_quotes}outlier{close_quotes}, having remained relatively isolated from mainland and other cultures. Genetic linkage data has been obtained in a set of 11 Sardinian arRP kindreds containing 26 affected members. Under the assumption of genetic homogeneity, no evidence of linkage was found in the arRP kindreds using 195 markers, which excluded 62% of the genome (Z<-2). Positive lod scores were obtained with D14S80 which showed no recombination in a subset of 5 families. Heterogeneity testing using D14S80 and arRP showed no significant evidence of heterogeneity (p=0.18) but evidence of linkage ({chi}{sup 2}=3.64, p=0.028). We are currently screening the neural retina-specific leucine zipper gene (NRL) in 14q11 for mutations as a candidate locus.

  12. A synchrotron study of microstructure gradient in laser additively formed epitaxial Ni-based superalloy

    DOE PAGES

    Xue, Jiawei; Zhang, Anfeng; Li, Yao; Qian, Dan; Wan, Jingchun; Qi, Baolu; Tamura, Nobumichi; Song, Zhongxiao; Chen, Kai

    2015-10-08

    Laser additive forming is considered to be one of the promising techniques to repair single crystal Ni-based superalloy parts to extend their life and reduce the cost. Preservation of the single crystalline nature and prevention of thermal mechanical failure are two of the most essential issues for the application of this technique. Here we employ synchrotron X-ray microdiffraction to evaluate the quality in terms of crystal orientation and defect distribution of a Ni-based superalloy DZ125L directly formed by a laser additive process rooted from a single crystalline substrate of the same material. We show that a disorientation gradient caused bymore » a high density of geometrically necessary dislocations and resultant subgrains exists in the interfacial region between the epitaxial and stray grains. This creates a potential relationship of stray grain formation and defect accumulation. In conclusion, the observation offers new directions on the study of performance control and reliability of the laser additive manufactured superalloys.« less

  13. Couples Counseling in Alzheimer's Disease: Additional Clinical Findings from a Novel Intervention Study.

    PubMed

    Auclair, Ursula; Epstein, Cynthia; Mittelman, Mary

    2009-04-01

    This article describes the clinical findings of a study designed to assess the benefit of counseling for couples, one of whom is in the early stage of Alzheimer's disease (AD). We previously reported our findings based on the first 12 couples that enrolled in the study. Based on the treatment of 30 additional couples, we have refined our treatment strategy to include concepts of Gestalt Therapy and Transactional Analysis and identified prevalent issues of concern to this cohort. The study design has remained as described in the earlier article (Epstein et al., 2006), and has proven to be appropriate to meet the goals of this intervention as indicated by our clinical experience and feedback from the participating couples. Case vignettes demonstrate how to conduct the sessions so that the experience of each member of the dyad is validated, while acknowledging the differential impact of the disease on them. PMID:19865591

  14. [Cancer pharmacogenetics: study of genetically determined variations on cancer susceptibility due to xenobiotic exposure].

    PubMed

    Quiñones, Luis; Lee, Kuen; Varela F, Nelson; Escala, Mario; García, Karen; Godoy, Loreto; Castro, Andrés; Soto, Jorge; Saavedra, Iván; Cáceres, Dante

    2006-04-01

    Pharmacogenetics is the study of genetically determined variations in the response to drugs and toxic agents, and their implications on disease. Recently, the discipline has acquired great relevancy due to the development of non-invasive molecular techniques that identify genetic variants in human beings. There is also a need to explain the individual differences in susceptibility to drug actions and disease risk. Genetic variants can modify the magnitude of a pharmacologic effect, toxicity threshold, secondary effects and drug interactions. There are approximately thirty families of drug-metabolizing enzymes with genetic variants that cause functional alterations and variations in pharmacologic activity. We summarize the general knowledge about genetic variants of biotransformation enzymes, their relationship with cancer risk and the role of ethnicity. Cancer pharmacogenetics is another promising and exciting research area that will explain why people with an almost identical group of genes, have a different susceptibility to cancer, whose etiology has genetic and environmental components.

  15. Addition of fluoride to pit and fissure sealants--a feasibility study.

    PubMed

    Swartz, M L; Phillips, R W; Norman, R D; Elliason, S; Rhodes, B F; Clark, H E

    1976-01-01

    The data obtained in this in vitro study indicate that contact with pit and fissure sealants to which NaF has been added in amounts ranging from 2 to 5% substantially increases the fluoride content of the enamel and reduces its solubility in acid. The properties of the materials do not seem to be impaired by the addition of fluoride in these amounts. It thus appears that this approach to providing a backup anticariogenic mechanism may, indeed, be feasible. However, further investigation must be done to confirm the anticariogenic effect and to establish the most efficacious means of fluoride incorporation in the materials.

  16. The impact of information order on intentions to undergo predictive genetic testing: an experimental study.

    PubMed

    Morrison, Val; Henderson, Bethan J; Taylor, Caroline; A'Ch Dafydd, Nonn; Unwin, Abbie

    2010-10-01

    As predictive genetic testing availability increases so does our need to understand factors associated with test uptake. This study tests whether the order positive and negative information about genetic testing for breast cancer is presented in affects intention to take a genetic test. Eighty-four women were randomly allocated into three groups: (1) positive then negative information; (2) negative then positive information; and (3) a control group. A significant effect was found in relation to perceived risk, attitudes towards genetic testing, perceived disadvantages of testing and intention. Our findings point to a primacy effect, whereby information presented first has the greatest effect.

  17. Personalized prostate cancer screening among men with high risk genetic predisposition- study protocol for a prospective cohort study

    PubMed Central

    2014-01-01

    Background Prostate cancer screening among the general population is highly debatable. Nevertheless, screening among high-risk groups is appealing. Prior data suggests that men carrying mutations in the BRCA1& 2 genes may be at increased risk of developing prostate cancer. Additionally, they appear to develop prostate cancer at a younger age and with a more aggressive course. However, prior studies did not systematically perform prostate biopsies and thus cannot determine the true prevalence of prostate cancer in this population. Methods This will be a prospective diagnostic trial of screening for prostate cancer among men with genetic predisposition. The target population is males (40–70 year old) carrying a BRCA1 and/or BRCA2 germ line mutation. They will be identified via our Genetic counseling unit. All men after signing an informed consent will undergo the following tests: PSA, free to total PSA, MRI of prostate and prostate biopsy. The primary endpoint will be to estimate the prevalence, stage and grade of prostate cancer in this population. Additionally, the study aims to estimate the impact of these germ line mutations on benign prostatic hyperplasia. Furthermore, this study aims to create a bio-bank of tissue, urine and serum of this unique cohort for future investigations. Finally, this study will identify an inception cohort for future interventional studies of primary and secondary prevention. Discussion The proposed research is highly translational and focuses not only on the clinical results, but on the future specimens that will be used to advance our understanding of prostate cancer patho-physiology. Most importantly, these high-risk germ-line mutation carriers are ideal candidates for primary and secondary prevention initiatives. Trial registration ClinicalTrials.gov: NCT02053805. PMID:25047061

  18. Genetic Complexity of Episodic Memory: A Twin Approach to Studies of Aging

    PubMed Central

    Kremen, William S.; Spoon, Kelly M.; Jacobson, Kristen C.; Vasilopoulos, Terrie; McCaffery, Jeanne M.; Panizzon, Matthew S.; Franz, Carol E.; Vuoksimaa, Eero; Xian, Hong; Rana, Brinda K.; Toomey, Rosemary; McKenzie, Ruth; Lyons, Michael J.

    2016-01-01

    Episodic memory change is a central issue in cognitive aging, and understanding that process will require elucidation of its genetic underpinnings. A key limiting factor in genetically informed research on memory has been lack of attention to genetic and phenotypic complexity, as if “memory is memory” and all well-validated assessments are essentially equivalent. Here we applied multivariate twin models to data from late-middle-aged participants in the Vietnam Era Twin Study of Aging to examine the genetic architecture of 6 measures from 3 standard neuropsychological tests: the California Verbal Learning Test-2, and Wechsler Memory Scale-III Logical Memory (LM) and Visual Reproductions (VR). An advantage of the twin method is that it can estimate the extent to which latent genetic influences are shared or independent across different measures before knowing which specific genes are involved. The best-fitting model was a higher order common pathways model with a heritable higher order general episodic memory factor and three test-specific subfactors. More importantly, substantial genetic variance was accounted for by genetic influences that were specific to the latent LM and VR subfactors (28% and 30%, respectively) and independent of the general factor. Such unique genetic influences could partially account for replication failures. Moreover, if different genes influence different memory phenotypes, they could well have different age-related trajectories. This approach represents an important step toward providing critical information for all types of genetically informative studies of aging and memory. PMID:24956007

  19. Designing and implementing sample and data collection for an international genetics study: the Type 1 Diabetes Genetics Consortium (T1DGC)

    PubMed Central

    Hilner, Joan E; Perdue, Letitia H; Sides, Elizabeth G; Pierce, June J; Wägner, Ana M; Aldrich, Alan; Loth, Amanda; Albret, Lotte; Wagenknecht, Lynne E; Nierras, Concepcion; Akolkar, Beena

    2010-01-01

    Background and Purpose The Type 1 Diabetes Genetics Consortium (T1DGC) is an international project whose primary aims are to: (a) discover genes that modify type 1 diabetes risk; and (b) expand upon the existing genetic resources for type 1 diabetes research. The initial goal was to collect 2500 affected sibling pair (ASP) families worldwide. Methods T1DGC was organized into four regional networks (Asia-Pacific, Europe, North America, and the United Kingdom) and a Coordinating Center. A Steering Committee, with representatives from each network, the Coordinating Center, and the funding organizations, was responsible for T1DGC operations. The Coordinating Center, with regional network representatives, developed study documents and data systems. Each network established laboratories for: DNA extraction and cell line production; human leukocyte antigen genotyping; and autoantibody measurement. Samples were tracked from the point of collection, processed at network laboratories and stored for deposit at National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repositories. Phenotypic data were collected and entered into the study database maintained by the Coordinating Center. Results T1DGC achieved its original ASP recruitment goal. In response to research design changes, the T1DGC infrastructure also recruited trios, cases, and controls. Results of genetic analyses have identified many novel regions that affect susceptibility to type 1 diabetes. T1DGC created a resource of data and samples that is accessible to the research community. Limitations Participation in T1DGC was declined by some countries due to study requirements for the processing of samples at network laboratories and/or final deposition of samples in NIDDK Central Repositories. Re-contact of participants was not included in informed consent templates, preventing collection of additional samples for functional studies. Conclusions T1DGC implemented a distributed

  20. Novel Approaches to Studying the Genetic Basis of Cerebellar Development

    PubMed Central

    Sajan, Samin A.; Waimey, Kathryn E.

    2010-01-01

    The list of genes that when mutated cause disruptions in cerebellar development is rapidly increasing. The study of both spontaneous and engineered mouse mutants has been essential to this progress, as it has revealed much of our current understanding of the developmental processes required to construct the mature cerebellum. Improvements in brain imaging, such as magnetic resonance imaging (MRI) and the emergence of better classification schemes for human cerebellar malformations, have recently led to the identification of a number of genes which cause human cerebellar disorders. In this review we argue that synergistic approaches combining classical molecular techniques, genomics, and mouse models of human malformations will be essential to fuel additional discoveries of cerebellar developmental genes and mechanisms. PMID:20387026

  1. Genetic Determinants of Age-Related Macular Degeneration in Diverse Populations From the PAGE Study

    PubMed Central

    Restrepo, Nicole A.; Spencer, Kylee L.; Goodloe, Robert; Garrett, Tiana A.; Heiss, Gerardo; Bůžková, Petra; Jorgensen, Neal; Jensen, Richard A.; Matise, Tara C.; Hindorff, Lucia A.; Klein, Barbara E. K.; Klein, Ronald; Wong, Tien Y.; Cheng, Ching-Yu; Cornes, Belinda K.; Tai, E.-Shyong; Ritchie, Marylyn D.; Haines, Jonathan L.; Crawford, Dana C.

    2014-01-01

    Purpose. Substantial progress has been made in identifying susceptibility variants for AMD in European populations; however, few studies have been conducted to understand the role these variants play in AMD risk in diverse populations. The present study aims to examine AMD risk across diverse populations in known and suspected AMD complement factor and lipid-related loci. Methods. Targeted genotyping was performed across study sites for AMD and lipid trait-associated single nucleotide polymorphism (SNPs). Genetic association tests were performed at individual sites and then meta-analyzed using logistic regression assuming an additive genetic model stratified by self-described race/ethnicity. Participants included cases with early or late AMD and controls with no signs of AMD as determined by fundus photography. Populations included in this study were European Americans, African Americans, Mexican Americans, and Singaporeans from the Population Architecture using Genomics and Epidemiology (PAGE) study. Results. Index variants of AMD, rs1061170 (CFH) and rs10490924 (ARMS2), were associated with AMD at P = 3.05 × 10−8 and P = 6.36 × 10−6, respectively, in European Americans. In general, none of the major AMD index variants generalized to our non-European populations with the exception of rs10490924 in Mexican Americans at an uncorrected P value < 0.05. Four lipid-associated SNPS (LPL rs328, TRIB1 rs6987702, CETP rs1800775, and KCTD10/MVK rs2338104) were associated with AMD in African Americans and Mexican Americans (P < 0.05), but these associations did not survive strict corrections for multiple testing. Conclusions. While most associations did not generalize in the non-European populations, variants within lipid-related genes were found to be associated with AMD. This study highlights the need for larger well-powered studies in non-European populations. PMID:25205864

  2. Genetics, society, and decisions

    SciTech Connect

    Kowles, R.V.

    1985-01-01

    This book provides a conceptual understanding of the biology of genes and also gives current events and controversies in the field. Basic transmission genetics, molecular genetics, and population genetics are covered, with additional discussions relating to such topics as agriculture, aging, forensic science, genetic counseling, gene splicing, and recombinant DNA. Low level radiation and its effects, drugs and heredity, IQ, heredity and racial variation, and creationism versus evolution are also described. ''Billboard'' style diagrams visually explain important concepts. Boldfaced key terms are defined within the text and in a comprehensive glossary. Selected readings, discussion questions and problems, and excellent chapter summaries further aid study.

  3. A water soluble additive to suppress respirable dust from concrete-cutting chainsaws: a case study.

    PubMed

    Summers, Michael P; Parmigiani, John P

    2015-01-01

    Respirable dust is of particular concern in the construction industry because it contains crystalline silica. Respirable forms of silica are a severe health threat because they heighten the risk of numerous respirable diseases. Concrete cutting, a common work practice in the construction industry, is a major contributor to dust generation. No studies have been found that focus on the dust suppression of concrete-cutting chainsaws, presumably because, during normal operation water is supplied continuously and copiously to the dust generation points. However, there is a desire to better understand dust creation at low water flow rates. In this case study, a water-soluble surfactant additive was used in the chainsaw's water supply. Cutting was performed on a free-standing concrete wall in a covered outdoor lab with a hand-held, gas-powered, concrete-cutting chainsaw. Air was sampled at the operator's lapel, and around the concrete wall to simulate nearby personnel. Two additive concentrations were tested (2.0% and 0.2%), across a range of fluid flow rates (0.38-3.8 Lpm [0.1-1.0 gpm] at 0.38 Lpm [0.1 gpm] increments). Results indicate that when a lower concentration of additive is used exposure levels increase. However, all exposure levels, once adjusted for 3 hours of continuous cutting in an 8-hour work shift, are below the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) of 5 mg/m(3). Estimates were made using trend lines to predict the fluid flow rates that would cause respirable dust exposure to exceed both the OSHA PEL and the American Conference of Governmental Industrial Hygienists (ACGIH®) threshold limit value (TLV).

  4. The apt/6-Methylpurine Counterselection System and Its Applications in Genetic Studies of the Hyperthermophilic Archaeon Sulfolobus islandicus

    PubMed Central

    Bi, Hongkai; Whitaker, Rachel J.

    2016-01-01

    ABSTRACT Sulfolobus islandicus serves as a model for studying archaeal biology as well as linking novel biology to evolutionary ecology using functional population genomics. In the present study, we developed a new counterselectable genetic marker in S. islandicus to expand the genetic toolbox for this species. We show that resistance to the purine analog 6-methylpurine (6-MP) in S. islandicus M.16.4 is due to the inactivation of a putative adenine phosphoribosyltransferase encoded by M164_0158 (apt). The application of the apt gene as a novel counterselectable marker was first illustrated by constructing an unmarked α-amylase deletion mutant. Furthermore, the 6-MP counterselection feature was employed in a forward (loss-of-function) mutation assay to reveal the profile of spontaneous mutations in S. islandicus M.16.4 at the apt locus. Moreover, the general conservation of apt genes in the crenarchaea suggests that the same strategy can be broadly applied to other crenarchaeal model organisms. These results demonstrate that the apt locus represents a new tool for genetic manipulation and sequence analysis of the hyperthermophilic crenarchaeon S. islandicus. IMPORTANCE Currently, the pyrEF/5-fluoroorotic acid (5-FOA) counterselection system remains the sole counterselection marker in crenarchaeal genetics. Since most Sulfolobus mutants constructed by the research community were derived from genetic hosts lacking the pyrEF genes, the pyrEF/5-FOA system is no longer available for use in forward mutation assays. Demonstration of the apt/6-MP counterselection system for the Sulfolobus model renders it possible to again study the mutation profiles in mutants that have already been constructed by the use of strains with a pyrEF-deficient background. Furthermore, additional counterselectable markers will allow us to conduct more sophisticated genetic studies, i.e., investigate mechanisms of chromosomal DNA transfer and quantify recombination frequencies among S

  5. Magneto-optical study of uranium additions to amorphous TbxFe1 - x

    NASA Astrophysics Data System (ADS)

    Dillon, J. F., Jr.; van Dover, R. B.; Hong, M.; Gyorgy, E. M.; Albiston, S. D.

    1987-02-01

    Recent reports of huge magneto-optical Kerr rotations in certain crystalline metallic uranium compounds prompted a study of the magnetic and magneto-optical effects of uranium additions to a rare-earth transition metal amorphous alloy. Using variable composition samples, the polar Kerr effect at a small spot (e.g., 0.5 mm diam) was measured as field, temperature, and composition were varied. Points on the Curie line and the edges of the compensation region were determined from these observations. The compositions studied included (TbxFe1-x)1-yUy with 0.125≤x≤0.550 and y=0.0, 0.04, 0.07, 0.16. The addition of uranium to TbxFe1-x depresses the TC of Tb-rich material much more strongly than that of Tb-poor material. The compensation region does not shift at all with increasing y. It appears that uranium does not contribute to the magnetization of these amorphous alloys, nor does it significantly affect the magneto-optical effects.

  6. Exposing College Students to Exercise: The Training Interventions and Genetics of Exercise Response (TIGER) Study

    ERIC Educational Resources Information Center

    Sailors, Mary H.; Jackson, Andrew S.; McFarlin, Brian K.; Turpin, Ian; Ellis, Kenneth J.; Foreyt, John P.; Hoelscher, Deanna M.; Bray, Molly S.

    2010-01-01

    Objective: The Training Interventions and Genetics of Exercise Response (TIGER) study is an exercise program designed to introduce sedentary college students to regular physical activity and to identify genetic factors that influence response to exercise. Participants: A multiracial/ethnic cohort (N = 1,567; 39% male), age 18 to 35 years,…

  7. Genetic thinking in the study of social relationships: Five points of entry

    PubMed Central

    Reiss, David

    2014-01-01

    For nearly a generation, researchers studying human behavioral development have combined genetically informed research designs with careful measures of social relationships: parenting, sibling relationships, peer relationships, marital processes, social class stratifications and patterns of social engagement in the elderly. In what way have these genetically informed studies altered the construction and testing of social theories of human development? We consider five points where genetic thinking is taking hold. First, genetic findings suggest an alternative scenario for explaining social data. Associations between measures of the social environment and human development may be due to genes that influence both. Second, genetic studies add to other prompts to study the early developmental origins of current social phenomena in mid-life and beyond. Third, genetic analyses promise to bring to the surface understudied social systems, such as sibling relationships, that have an impact on human development independent of genotype. Fourth, genetic analyses anchor in neurobiology individual differences in resilience and sensitivity to both adverse and favorable social environments. Finally, genetic analyses increase the utility of laboratory simulations of human social processes and of animal models. PMID:25419225

  8. Clusters of Concepts in Molecular Genetics: A Study of Swedish Upper Secondary Science Students' Understanding

    ERIC Educational Resources Information Center

    Gericke, Niklas; Wahlberg, Sara

    2013-01-01

    To understand genetics, students need to be able to explain and draw connections between a large number of concepts. The purpose of the study reported herein was to explore the way upper secondary science students reason about concepts in molecular genetics in order to understand protein synthesis. Data were collected by group interviews. Concept…

  9. Are Endophenotypes Based on Measures of Executive Functions Useful for Molecular Genetic Studies of ADHD?

    ERIC Educational Resources Information Center

    Doyle, Alysa E.; Faraone, Stephen V.; Seidman, Larry J.; Willcutt, Erik G.; Nigg, Joel T.; Waldman, Irwin D.; Pennington, Bruce F.; Peart, Joanne; Biederman, Joseph

    2005-01-01

    Background: Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or…

  10. Exposing college students to exercise: the training interventions and genetics of exercise response (TIGER) study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Training Interventions and Genetics of Exercise Response (TIGER) study is an exercise program designed to introduce sedentary college students to regular physical activity and to identify genetic factors that influence response to exercise. A multiracial/ethnic cohort (N = 1,567; 39% male), age ...

  11. Examining Genetic and Environmental Effects on Social Aggression: A Study of 6-Year-Old Twins

    ERIC Educational Resources Information Center

    Brendgen, Mara; Dionne, Ginette; Girard, Alain; Boivin, Michel; Vitaro, Frank; Prusse, Daniel

    2005-01-01

    Using a genetic design of 234 six-year-old twins, this study examined (a) the contribution of genes and environment to social versus physical aggression, and (b) whether the correlation between social and physical aggression can be explained by similar genetic or environmental factors or by a directional link between the phenotypes. For social…

  12. Genetic analysis of metabolic polymorphisms in molecular epidemiological studies: social and ethical implications.

    PubMed

    Hainaut, P; Vähäkangas, K

    1999-01-01

    The use of genetic biomarkers in epidemiological studies raises specific social and ethical issues related to the selection of molecular markers and methods of analysis, obtaining participation, the storage of biological samples and their linkage with individual data, the disclosure of information and the publication of results. Several of these issues are similar to those associated with the use of any type of biomarker in epidemiology. Other problems are specifically related to the use of genetic material and the perception that genetic information raises special concerns regarding privacy, risk of abuse and psychosocial impact in this chapter we define how genetic studies performed in the context of molecular epidemiological studies (genetic analysis) differ from genetic screening or genetic testing conducted in a clinical or public health context We then examine the ethical implications of this distinction and describe how general ethical principles may apply to genetic analysis in the area of molecular epidemiology. In particular we discuss specific questions such as those of obtaining participation, working with archival samples and communicating results. We advocate an approach whereby ethical issues are tackled as an intrinsic part of study design; this requires broad discussion with all the parties involved.

  13. Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

    PubMed Central

    2011-01-01

    Background Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. Methods CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. Results None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value < 0.05 in EPICOLON stage 1 [rs698 in ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive), rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive), rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant), and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs

  14. Heritability and Molecular-Genetic Basis of Resting EEG Activity: A Genome-Wide Association Study

    PubMed Central

    Malone, Stephen M.; Burwell, Scott J.; Vaidyanathan, Uma; Miller, Michael B.; McGue, Matt; Iacono, William G.

    2014-01-01

    Several EEG parameters are potential endophenotypes for different psychiatric disorders. The present study consists of a comprehensive behavioral- and molecular-genetic analysis of such parameters in a large community sample (N = 4,026) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric heritability estimates ranged from .49 to .85, with a median of .78. The additive effect of all SNPs (SNP heritability) varied across electrodes. Although individual SNPs were not significantly associated with EEG parameters, several genes were associated with delta power. We also obtained an association between the GABRA2 gene and beta power (p < .014), consistent with findings reported by others, although this did not survive Bonferroni correction. If EEG parameters conform to a largely polygenic model of inheritance, larger sample sizes will be required to detect individual variants reliably. PMID:25387704

  15. Characterization studies on the additives mixed L-arginine phosphate monohydrate (LAP) crystals

    NASA Astrophysics Data System (ADS)

    Haja Hameed, A. S.; Karthikeyan, C.; Ravi, G.; Rohani, S.

    2011-04-01

    L-arginine phosphate monohydrate (LAP), potassium thiocyanate (KSCN) mixed LAP (LAP:KSCN) and sodium sulfite (Na 2SO 3) mixed LAP (LAP:Na 2SO 3) single crystals were grown by slow cooling technique. The effect of microbial contamination and coloration on the growth solutions was studied. The crystalline powders of the grown crystals were examined by X-ray diffraction and the lattice parameters of the crystals were estimated. From the FTIR spectroscopic analysis, various functional group frequencies associated with the crystals were assigned. Vickers microhardness studies were done on {1 0 0} faces for pure and additives mixed LAP crystals. From the preliminary surface second harmonic generation (SHG) results, it was found that the SHG intensity at (1 0 0) face of LAP:KSCN crystal was much stronger than that of pure LAP.

  16. The guanidine and maleic acid (1:1) complex. The additional theoretical and experimental studies

    NASA Astrophysics Data System (ADS)

    Drozd, Marek; Dudzic, Damian

    2012-04-01

    On the basis of experimental literature data the theoretical studies for guanidinium and maleic acid complex with using DFT method are performed. In these studies the experimental X-ray data for two different forms of investigated crystal were used. During the geometry optimization process one equilibrium structure was found, only. According to this result the infrared spectrum for one theoretical molecule was calculated. On the basis of potential energy distribution (PED) analysis the clear-cut assignments of observed bands were performed. For the calculated molecule with energy minimum the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were obtained and graphically illustrated. The energy difference (GAP) between HOMO and LUMO was analyzed. Additionally, the nonlinear properties of this molecule were calculated. The α and β (first and second order) hyperpolarizability values are obtained. On the basis of these results the title crystal was classified as new second order NLO generator.

  17. [Genetic heterogeneity of osteogenesis imperfecta. Study of 6 cases].

    PubMed

    Olivares, J L; Hernández, M C; Bueno, M

    1986-09-01

    Osteogenesis imperfecta one of the most common disorders of connective tissue, has been known for centuries. The most characteristic alterations which define it are: osteoporosis, osseous fragility with multiple fractures, blue sclerae, deafness and imperfect dentinogenesis. Important advances in the biochemical, anatomopathological, genetic, therapeutic and prophylactic fields have resulted in a great present-day interest in this disease. In this work we report six cases of osteogenesis imperfecta according to the current classification and we review the most outstanding aspects. PMID:3789548

  18. Progress in Genetic Studies of Pain and Analgesia

    PubMed Central

    LaCroix-Fralish, Michael L.

    2009-01-01

    Interindividual variability in pain sensitivity and the response to analgesic manipulations remains a considerable clinical challenge as well as an area of intense scientific investigation. Techniques in this field have matured rapidly so that much relevant data have emerged only in the past few years. Our increasing understanding of the genetic mediation of these biological phenomena have nonetheless revealed their surprising complexity. This review provides a comprehensive picture and critical analysis of the field and its prospects. PMID:18834308

  19. Prazosin addition to fluvoxamine: A preclinical study and open clinical trial in OCD.

    PubMed

    Feenstra, Matthijs G P; Klompmakers, André; Figee, Martijn; Fluitman, Sjoerd; Vulink, Nienke; Westenberg, Herman G M; Denys, Damiaan

    2016-02-01

    The efficacy of selective serotonin reuptake inhibitors (SRIs) in psychiatric disorders may be "augmented" through the addition of atypical antipsychotic drugs. A synergistic increase in dopamine (DA) release in the prefrontal cortex has been suggested to underlie this augmentation effect, though the mechanism of action is not clear yet. We used in vivo microdialysis in rats to study DA release following the administration of combinations of fluvoxamine (10 mg/kg) and quetiapine (10 mg/kg) with various monoamine-related drugs. The results confirmed that the selective 5-HT1A antagonist WAY-100635 (0.05 mg/kg) partially blocked the fluvoxamine-quetiapine synergistic effect (maximum DA increase dropped from 325% to 214%). A novel finding is that the α1-adrenergic blocker prazosin (1 mg/kg), combined with fluvoxamine, partially mimicked the effect of augmentation (maximum DA increase 205%; area-under-the-curve 163%). As this suggested that prazosin augmentation might be tested in a clinical study, we performed an open clinical trial of prazosin 20 mg addition to SRI in therapy-resistant patients with obsessive-compulsive disorder applying for neurosurgery. A small, non-significant reduction in Yale Brown Obsessive Compulsive Scale (Y-BOCS) scores was observed in 10 patients and one patient was classified as a responder with a reduction in Y-BOCS scores of more than 25%. We suggest that future clinical studies augmenting SRIs with an α1-adrenergic blocker in less treatment resistant cases should be considered. The clinical trial "Prazosin in combination with a serotonin reuptake inhibitor for patients with Obsessive Compulsive disorder: an open label study" was registered at 24/05/2011 under trial number ISRCTN61562706: http://www.controlled-trials.com/ISRCTN61562706. PMID:26712326

  20. Human genetic studies in areas of high natural radiation. VIII. Genetic load not related to radiation.

    PubMed Central

    Freire-Maia, A; Krieger, H

    1975-01-01

    The genetic load disclosed by inbreeding has been analyzed in a multiple regression model for a population involving several localities in the state of Espírito Santo, Brazil. The inbreeding load has been estimated for number of pregnancies, abortions, stillbirths, children born alive, anomalies in general, sex ratio, infant mortality, post-infant mortality, and sterility and infertility of the couple. There was no evidence of either maternal or paternal inbreeding effects on the variables analyzed. The effect of inbreeding of the zygote was significant only for anomalies in general (B = 2.29 +/- 0.45) and infant mortality (B = 3.19 +/- 1.39). The latter result must be accepted with caution because of the many environmental causes affecting infant mortality. The B/A ratio suggested a predominantly mutational load for anomalies in general (B/A = 25), but with respect to infant mortality (B/A = 6), the ratio is regarded as an underestimate because of the environmental contribution to A and therefore not supportive of the segregational interpretation. PMID:803018

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

    PubMed

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

    2009-03-01

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

  2. Empirical Bayes scan statistics for detecting clusters of disease risk variants in genetic studies.

    PubMed

    McCallum, Kenneth J; Ionita-Laza, Iuliana

    2015-12-01

    Recent developments of high-throughput genomic technologies offer an unprecedented detailed view of the genetic variation in various human populations, and promise to lead to significant progress in understanding the genetic basis of complex diseases. Despite this tremendous advance in data generation, it remains very challenging to analyze and interpret these data due to their sparse and high-dimensional nature. Here, we propose novel applications and new developments of empirical Bayes scan statistics to identify genomic regions significantly enriched with disease risk variants. We show that the proposed empirical Bayes methodology can be substantially more powerful than existing scan statistics methods especially so in the presence of many non-disease risk variants, and in situations when there is a mixture of risk and protective variants. Furthermore, the empirical Bayes approach has greater flexibility to accommodate covariates such as functional prediction scores and additional biomarkers. As proof-of-concept we apply the proposed methods to a whole-exome sequencing study for autism spectrum disorders and identify several promising candidate genes.

  3. Great bustard population structure in central Spain: concordant results from genetic analysis and dispersal study.

    PubMed

    Martín, Carlos A; Alonso, Juan C; Alonso, Javier; Pitra, Christian; Lieckfeldt, Dietmar

    2002-01-22

    We found significant sex differences in the mtDNA genetic structure and dispersal patterns of great bustards in a population of 11 breeding groups, "leks", in central Spain. The analysis of genetic distances showed that the female population was divided into three groups of leks separated by ca. 50 km, whereas male haplotypes were randomly distributed among leks. Genetic distances among pairs of leks were positively correlated with geographical distances in females but not in males. While female haplotype distributions were homogeneous among leks at close distances, differences in male genetic structure were highly variable even between two close leks. These results from genetic analyses were concordant with those from a radiotracking study on natal dispersal. Natal dispersal distances were higher in males than in females. Also, the frequency of movement of a female between two leks was positively correlated with their genetic affinity and geographical proximity. In males, the frequency of movement was correlated with geographical proximity but not with genetic affinity. Males dispersed among genetically unrelated leks, contributing to keep nuclear genetic diversity in the population, whereas females tended to be philopatric. These results suggest that isolation-by-distance influences the distribution of maternal lineages at a regional level. PMID:11798426

  4. Great bustard population structure in central Spain: concordant results from genetic analysis and dispersal study.

    PubMed

    Martín, Carlos A; Alonso, Juan C; Alonso, Javier; Pitra, Christian; Lieckfeldt, Dietmar

    2002-01-22

    We found significant sex differences in the mtDNA genetic structure and dispersal patterns of great bustards in a population of 11 breeding groups, "leks", in central Spain. The analysis of genetic distances showed that the female population was divided into three groups of leks separated by ca. 50 km, whereas male haplotypes were randomly distributed among leks. Genetic distances among pairs of leks were positively correlated with geographical distances in females but not in males. While female haplotype distributions were homogeneous among leks at close distances, differences in male genetic structure were highly variable even between two close leks. These results from genetic analyses were concordant with those from a radiotracking study on natal dispersal. Natal dispersal distances were higher in males than in females. Also, the frequency of movement of a female between two leks was positively correlated with their genetic affinity and geographical proximity. In males, the frequency of movement was correlated with geographical proximity but not with genetic affinity. Males dispersed among genetically unrelated leks, contributing to keep nuclear genetic diversity in the population, whereas females tended to be philopatric. These results suggest that isolation-by-distance influences the distribution of maternal lineages at a regional level.

  5. Reporting genetic results in research studies: summary and recommendations of an NHLBI working group.

    PubMed

    Bookman, Ebony B; Langehorne, Aleisha A; Eckfeldt, John H; Glass, Kathleen C; Jarvik, Gail P; Klag, Michael; Koski, Greg; Motulsky, Arno; Wilfond, Benjamin; Manolio, Teri A; Fabsitz, Richard R; Luepker, Russell V

    2006-05-15

    Prospective epidemiologic studies aid in identifying genetic variants associated with diseases, health risks, and physiologic traits. These genetic variants may eventually be measured clinically for purposes of diagnosis, prognosis, and treatment. As evidence of the potential clinical value of such information accrues, research studies face growing pressure to report these results to study participants or their physicians, even before sufficient evidence is available to support widespread screening of asymptomatic persons. There is thus a need to begin to develop consensus on whether and when genetic findings should be reported to participants in research studies. The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group on Reporting Genetic Results in Research Studies to discuss if, when, and how genetic information should be reported to study participants. The Working Group concluded that genetic test results should be reported to study participants when the associated risk for the disease is significant; the disease has important health implications such as premature death or substantial morbidity or has significant reproductive implications; and proven therapeutic or preventive interventions are available. Finally, the Working Group recommended procedures for reporting genetic research results and encouraged increased efforts to create uniform guidelines for this activity.

  6. A combined toxicity study of zinc oxide nanoparticles and vitamin C in food additives

    NASA Astrophysics Data System (ADS)

    Wang, Yanli; Yuan, Lulu; Yao, Chenjie; Ding, Lin; Li, Chenchen; Fang, Jie; Sui, Keke; Liu, Yuanfang; Wu, Minghong

    2014-11-01

    At present, safety evaluation standards for nanofood additives are made based on the toxic effects of a single additive. Since the size, surface properties and chemical nature influence the toxicity of nanomaterials, the toxicity may have dramatically changed when nanomaterials are used as food additives in a complex system. Herein, we investigated the combined toxicity of zinc oxide nanoparticles (ZnO NPs) and vitamin C (Vc, ascorbic acid). The results showed that Vc increased the cytotoxicity significantly compared with that of the ZnO only NPs. When the cells were exposed to ZnO NPs at a concentration less than 15 mg L-1, or to Vc at a concentration less than 300 mg L-1, there was no significant cytotoxicity, both in the case of gastric epithelial cell line (GES-1) and neural stem cells (NSCs). However, when 15 mg L-1 of ZnO NPs and 300 mg L-1 of Vc were introduced to cells together, the cell viability decreased sharply indicating significant cytotoxicity. Moreover, the significant increase in toxicity was also shown in the in vivo experiments. The dose of the ZnO NPs and Vc used in the in vivo study was calculated according to the state of food and nutrition enhancer standard. After repeated oral exposure to ZnO NPs plus Vc, the injury of the liver and kidneys in mice has been indicated by the change of these indices. These findings demonstrate that the synergistic toxicity presented in a complex system is essential for the toxicological evaluation and safety assessment of nanofood.At present, safety evaluation standards for nanofood additives are made based on the toxic effects of a single additive. Since the size, surface properties and chemical nature influence the toxicity of nanomaterials, the toxicity may have dramatically changed when nanomaterials are used as food additives in a complex system. Herein, we investigated the combined toxicity of zinc oxide nanoparticles (ZnO NPs) and vitamin C (Vc, ascorbic acid). The results showed that Vc increased the

  7. Impact of contacting study authors to obtain additional data for systematic reviews: diagnostic accuracy studies for hepatic fibrosis

    PubMed Central

    2014-01-01

    Background Seventeen of 172 included studies in a recent systematic review of blood tests for hepatic fibrosis or cirrhosis reported diagnostic accuracy results discordant from 2 × 2 tables, and 60 studies reported inadequate data to construct 2 × 2 tables. This study explores the yield of contacting authors of diagnostic accuracy studies and impact on the systematic review findings. Methods Sixty-six corresponding authors were sent letters requesting additional information or clarification of data from 77 studies. Data received from the authors were synthesized with data included in the previous review, and diagnostic accuracy sensitivities, specificities, and positive and likelihood ratios were recalculated. Results Of the 66 authors, 68% were successfully contacted and 42% provided additional data for 29 out of 77 studies (38%). All authors who provided data at all did so by the third emailed request (ten authors provided data after one request). Authors of more recent studies were more likely to be located and provide data compared to authors of older studies. The effects of requests for additional data on the conclusions regarding the utility of blood tests to identify patients with clinically significant fibrosis or cirrhosis were generally small for ten out of 12 tests. Additional data resulted in reclassification (using median likelihood ratio estimates) from less useful to moderately useful or vice versa for the remaining two blood tests and enabled the calculation of an estimate for a third blood test for which previously the data had been insufficient to do so. We did not identify a clear pattern for the directional impact of additional data on estimates of diagnostic accuracy. Conclusions We successfully contacted and received results from 42% of authors who provided data for 38% of included studies. Contacting authors of studies evaluating the diagnostic accuracy of serum biomarkers for hepatic fibrosis and cirrhosis in hepatitis C patients

  8. Disorders of sex development: a genetic study of patients in a multidisciplinary clinic.

    PubMed

    Laino, Luigi; Majore, Silvia; Preziosi, Nicoletta; Grammatico, Barbara; De Bernardo, Carmelilia; Scommegna, Salvatore; Rapone, Anna Maria; Marrocco, Giacinto; Bottillo, Irene; Grammatico, Paola

    2014-12-01

    Sex development is a process under genetic control directing both the bi-potential gonads to become either a testis or an ovary, and the consequent differentiation of internal ducts and external genitalia. This complex series of events can be altered by a large number of genetic and non-genetic factors. Disorders of sex development (DSD) are all the medical conditions characterized by an atypical chromosomal, gonadal, or phenotypical sex. Incomplete knowledge of the genetic mechanisms involved in sex development results in a low probability of determining the molecular definition of the genetic defect in many of the patients. In this study, we describe the clinical, cytogenetic, and molecular study of 88 cases with DSD, including 29 patients with 46,XY and disorders in androgen synthesis or action, 18 with 46,XX and disorders in androgen excess, 17 with 46,XY and disorders of gonadal (testicular) development, 11 classified as 46,XX other, eight with 46,XX and disorders of gonadal (ovarian) development, and five with sex chromosome anomalies. In total, we found a genetic variant in 56 out of 88 of them, leading to the clinical classification of every patient, and we outline the different steps required for a coherent genetic testing approach. In conclusion, our results highlight the fact that each category of DSD is related to a large number of different DNA alterations, thus requiring multiple genetic studies to achieve a precise etiological diagnosis for each patient.

  9. Disorders of sex development: a genetic study of patients in a multidisciplinary clinic

    PubMed Central

    Laino, Luigi; Majore, Silvia; Preziosi, Nicoletta; Grammatico, Barbara; De Bernardo, Carmelilia; Scommegna, Salvatore; Rapone, Anna Maria; Marrocco, Giacinto; Bottillo, Irene; Grammatico, Paola

    2014-01-01

    Sex development is a process under genetic control directing both the bi-potential gonads to become either a testis or an ovary, and the consequent differentiation of internal ducts and external genitalia. This complex series of events can be altered by a large number of genetic and non-genetic factors. Disorders of sex development (DSD) are all the medical conditions characterized by an atypical chromosomal, gonadal, or phenotypical sex. Incomplete knowledge of the genetic mechanisms involved in sex development results in a low probability of determining the molecular definition of the genetic defect in many of the patients. In this study, we describe the clinical, cytogenetic, and molecular study of 88 cases with DSD, including 29 patients with 46,XY and disorders in androgen synthesis or action, 18 with 46,XX and disorders in androgen excess, 17 with 46,XY and disorders of gonadal (testicular) development, 11 classified as 46,XX other, eight with 46,XX and disorders of gonadal (ovarian) development, and five with sex chromosome anomalies. In total, we found a genetic variant in 56 out of 88 of them, leading to the clinical classification of every patient, and we outline the different steps required for a coherent genetic testing approach. In conclusion, our results highlight the fact that each category of DSD is related to a large number of different DNA alterations, thus requiring multiple genetic studies to achieve a precise etiological diagnosis for each patient. PMID:25248670

  10. A study of pyrazines in cigarettes and how additives might be used to enhance tobacco addiction

    PubMed Central

    Alpert, Hillel R; Agaku, Israel T; Connolly, Gregory N

    2016-01-01

    Background Nicotine is known as the drug that is responsible for the addicted behaviour of tobacco users, but it has poor reinforcing effects when administered alone. Tobacco product design features enhance abuse liability by (A) optimising the dynamic delivery of nicotine to central nervous system receptors, and affecting smokers’ withdrawal symptoms, mood and behaviour; and (B) effecting conditioned learning, through sensory cues, including aroma, touch and visual stimulation, to create perceptions of pending nicotine reward. This study examines the use of additives called ‘pyrazines’, which may enhance abuse potential, their introduction in ‘lights’ and subsequently in the highly market successful Marlboro Lights (Gold) cigarettes and eventually many major brands. Methods We conducted internal tobacco industry research using online databases in conjunction with published scientific literature research, based on an iterative feedback process. Results Tobacco manufacturers developed the use of a range of compounds, including pyrazines, in order to enhance ‘light’ cigarette products’ acceptance and sales. Pyrazines with chemosensory and pharmacological effects were incorporated in the first ‘full-flavour, low-tar’ product achieving high market success. Such additives may enhance dependence by helping to optimise nicotine delivery and dosing and through cueing and learned behaviour. Conclusions Cigarette additives and ingredients with chemosensory effects that promote addiction by acting synergistically with nicotine, increasing product appeal, easing smoking initiation, discouraging cessation or promoting relapse should be regulated by the US Food and Drug Administration. Current models of tobacco abuse liability could be revised to include more explicit roles with regard to non-nicotine constituents that enhance abuse potential. PMID:26063608

  11. A combined toxicity study of zinc oxide nanoparticles and vitamin C in food additives.

    PubMed

    Wang, Yanli; Yuan, Lulu; Yao, Chenjie; Ding, Lin; Li, Chenchen; Fang, Jie; Sui, Keke; Liu, Yuanfang; Wu, Minghong

    2014-12-21

    At present, safety evaluation standards for nanofood additives are made based on the toxic effects of a single additive. Since the size, surface properties and chemical nature influence the toxicity of nanomaterials, the toxicity may have dramatically changed when nanomaterials are used as food additives in a complex system. Herein, we investigated the combined toxicity of zinc oxide nanoparticles (ZnO NPs) and vitamin C (Vc, ascorbic acid). The results showed that Vc increased the cytotoxicity significantly compared with that of the ZnO only NPs. When the cells were exposed to ZnO NPs at a concentration less than 15 mg L(-1), or to Vc at a concentration less than 300 mg L(-1), there was no significant cytotoxicity, both in the case of gastric epithelial cell line (GES-1) and neural stem cells (NSCs). However, when 15 mg L(-1) of ZnO NPs and 300 mg L(-1) of Vc were introduced to cells together, the cell viability decreased sharply indicating significant cytotoxicity. Moreover, the significant increase in toxicity was also shown in the in vivo experiments. The dose of the ZnO NPs and Vc used in the in vivo study was calculated according to the state of food and nutrition enhancer standard. After repeated oral exposure to ZnO NPs plus Vc, the injury of the liver and kidneys in mice has been indicated by the change of these indices. These findings demonstrate that the synergistic toxicity presented in a complex system is essential for the toxicological evaluation and safety assessment of nanofood.

  12. Rate constants of hydroperoxyl radical addition to cyclic nitrones: a DFT study.

    PubMed

    Villamena, Frederick A; Merle, John K; Hadad, Christopher M; Zweier, Jay L

    2007-10-01

    Nitrones are potential synthetic antioxidants against the reduction of radical-mediated oxidative damage in cells and as analytical reagents for the identification of HO2* and other such transient species. In this work, the PCM/B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) and PCM/mPW1K/6-31+G(d,p) density functional theory (DFT) methods were employed to predict the reactivity of HO2* with various functionalized nitrones as spin traps. The calculated second-order rate constants and free energies of reaction at both levels of theory were in the range of 100-103 M-1 s-1 and 1 to -12 kcal mol-1, respectively, and the rate constants for some nitrones are on the same order of magnitude as those observed experimentally. The trend in HO2* reactivity to nitrones could not be explained solely on the basis of the relationship of the theoretical positive charge densities on the nitronyl-C, with their respective ionization potentials, electron affinities, rate constants, or free energies of reaction. However, various modes of intramolecular H-bonding interaction were observed at the transition state (TS) structures of HO2* addition to nitrones. The presence of intramolecular H-bonding interactions in the transition states were predicted and may play a significant role toward a facile addition of HO2* to nitrones. In general, HO2* addition to ethoxycarbonyl- and spirolactam-substituted nitrones, as well as those nitrones without electron-withdrawing substituents, such as 5,5-dimethyl-pyrroline N-oxide (DMPO) and 5-spirocyclopentyl-pyrroline N-oxide (CPPO), are most preferred compared to the methylcarbamoyl-substituted nitrones. This study suggests that the use of specific spin traps for efficient trapping of HO2* could pave the way toward improved radical detection and antioxidant protection. PMID:17845014

  13. Additional follow-up telephone counselling and initial smoking relapse: a longitudinal, controlled study

    PubMed Central

    Wu, Lei; He, Yao; Jiang, Bin; Zuo, Fang; Liu, Qinghui; Zhang, Li; Zhou, Changxi

    2016-01-01

    Objectives Smoking cessation services can help smokers to quit; however, many smoking relapse cases occur over time. Initial relapse prevention should play an important role in achieving the goal of long-term smoking cessation. Several studies have focused on the effect of extended telephone support in relapse prevention, but the conclusions remain conflicting. Design and setting From October 2008 to August 2013, a longitudinal, controlled study was performed in a large general hospital of Beijing. Participants The smokers who sought treatment at our smoking cessation clinic were non-randomised and divided into 2 groups: face-to-face individual counselling group (FC group), and face-to-face individual counselling plus telephone follow-up counselling group (FCF group). No pharmacotherapy was offered. Outcomes The timing of initial smoking relapse was compared between FC and FCF groups. Predictors of initial relapse were investigated during the first 180 days, using the Cox proportional hazards model. Results Of 547 eligible male smokers who volunteered to participate, 457 participants (117 in FC group and 340 in FCF group) achieved at least 24 h abstinence. The majority of the lapse episodes occurred during the first 2 weeks after the quit date. Smokers who did not receive the follow-up telephone counselling (FC group) tended to relapse to smoking earlier than those smokers who received the additional follow-up telephone counselling (FCF group), and the log-rank test was statistically significant (p=0.003). A Cox regression model showed that, in the FCF group, being married, and having a lower Fagerström test score, normal body mass index and doctor-diagnosed tobacco-related chronic diseases, were significantly independent protective predictors of smoking relapse. Conclusions Within the limitations of this study, it can be concluded that additional follow-up telephone counselling might be an effective strategy in preventing relapse. Further research is still

  14. Study of mandible reconstruction using a fibula flap with application of additive manufacturing technology

    PubMed Central

    2014-01-01

    Background This study aimed to establish surgical guiding techniques for completing mandible lesion resection and reconstruction of the mandible defect area with fibula sections in one surgery by applying additive manufacturing technology, which can reduce the surgical duration and enhance the surgical accuracy and success rate. Methods A computer assisted mandible reconstruction planning (CAMRP) program was used to calculate the optimal cutting length and number of fibula pieces and design the fixtures for mandible cutting, registration, and arrangement of the fibula segments. The mandible cutting and registering fixtures were then generated using an additive manufacturing system. The CAMRP calculated the optimal fibula cutting length and number of segments based on the location and length of the defective portion of the mandible. The mandible cutting jig was generated according to the boundary surface of the lesion resection on the mandible STL model. The fibular cutting fixture was based on the length of each segment, and the registered fixture was used to quickly arrange the fibula pieces into the shape of the defect area. In this study, the mandibular lesion was reconstructed using registered fibular sections in one step, and the method is very easy to perform. Results and conclusion The application of additive manufacturing technology provided customized models and the cutting fixtures and registered fixtures, which can improve the efficiency of clinical application. This study showed that the cutting fixture helped to rapidly complete lesion resection and fibula cutting, and the registered fixture enabled arrangement of the fibula pieces and allowed completion of the mandible reconstruction in a timely manner. Our method can overcome the disadvantages of traditional surgery, which requires a long and different course of treatment and is liable to cause error. With the help of optimal cutting planning by the CAMRP and the 3D printed mandible resection jig and

  15. Toxicogenomics concepts and applications to study hepatic effects of food additives and chemicals

    SciTech Connect

    Stierum, Rob . E-mail: stierum@voeding.tno.nl; Heijne, Wilbert; Kienhuis, Anne; Ommen, Ben van; Groten, John

    2005-09-01

    Transcriptomics, proteomics and metabolomics are genomics technologies with great potential in toxicological sciences. Toxicogenomics involves the integration of conventional toxicological examinations with gene, protein or metabolite expression profiles. An overview together with selected examples of the possibilities of genomics in toxicology is given. The expectations raised by toxicogenomics are earlier and more sensitive detection of toxicity. Furthermore, toxicogenomics will provide a better understanding of the mechanism of toxicity and may facilitate the prediction of toxicity of unknown compounds. Mechanism-based markers of toxicity can be discovered and improved interspecies and in vitro-in vivo extrapolations will drive model developments in toxicology. Toxicological assessment of chemical mixtures will benefit from the new molecular biological tools. In our laboratory, toxicogenomics is predominantly applied for elucidation of mechanisms of action and discovery of novel pathway-supported mechanism-based markers of liver toxicity. In addition, we aim to integrate transcriptome, proteome and metabolome data, supported by bioinformatics to develop a systems biology approach for toxicology. Transcriptomics and proteomics studies on bromobenzene-mediated hepatotoxicity in the rat are discussed. Finally, an example is shown in which gene expression profiling together with conventional biochemistry led to the discovery of novel markers for the hepatic effects of the food additives butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole.

  16. Resources allocation in healthcare for cancer: a case study using generalised additive mixed models.

    PubMed

    Musio, Monica; Sauleau, Erik A; Augustin, Nicole H

    2012-11-01

    Our aim is to develop a method for helping resources re-allocation in healthcare linked to cancer, in order to replan the allocation of providers. Ageing of the population has a considerable impact on the use of health resources because aged people require more specialised medical care due notably to cancer. We propose a method useful to monitor changes of cancer incidence in space and time taking into account two age categories, according to healthcar general organisation. We use generalised additive mixed models with a Poisson response, according to the methodology presented in Wood, Generalised additive models: an introduction with R. Chapman and Hall/CRC, 2006. Besides one-dimensional smooth functions accounting for non-linear effects of covariates, the space-time interaction can be modelled using scale invariant smoothers. Incidence data collected by a general cancer registry between 1992 and 2007 in a specific area of France is studied. Our best model exhibits a strong increase of the incidence of cancer along time and an obvious spatial pattern for people more than 70 years with a higher incidence in the central band of the region. This is a strong argument for re-allocating resources for old people cancer care in this sub-region. PMID:23242683

  17. Covalent binding of aniline to humic substances. 2. 15N NMR studies of nucleophilic addition reactions

    USGS Publications Warehouse

    Thorn, K.A.; Pettigrew, P.J.; Goldenberg, W.S.; Weber, E.J.

    1996-01-01

    Aromatic amines are known to undergo covalent binding with humic substances in the environment. Although previous studies have examined reaction conditions and proposed mechanisms, there has been no direct spectroscopic evidence for the covalent binding of the amines to the functional groups in humic substances. In order to further elucidate the reaction mechanisms, the Suwannee River and IHSS soil fulvic and humic acids were reacted with 15N-labeled aniline at pH 6 and analyzed using 15N NMR spectrometry. Aniline underwent nucleophilic addition reactions with the quinone and other carbonyl groups in the samples and became incorporated in the form of anilinohydroquinone, anilinoquinone, anilide, imine, and heterocyclic nitrogen, the latter comprising 50% or more of the bound amine. The anilide and anilinohydroquinone nitrogens were determined to be susceptible to chemical exchange by ammonia. In the case of Suwannee River fulvic acid, reaction under anoxic conditions and pretreatment with sodium borohydride or hydroxylamine prior to reaction under oxic conditions resulted in a decrease in the proportion of anilinohydroquinone nitrogen incorporated. The relative decrease in the incorporation of anilinohydroquinone nitrogen with respect to anilinoquinone nitrogen under anoxic conditions suggested that inter- or intramolecular redox reactions accompanied the nucleophilic addition reactions.

  18. Studies on the reuse of waste printed circuit board as an additive for cement mortar.

    PubMed

    Ban, Bong-Chan; Song, Jong-Yoon; Lim, Joong-Yeon; Wang, Soo-Kyoon; An, Kwang-Guk; Kim, Dong-Su

    2005-01-01

    The recent development in electronic industries has generated a drastic increase in production of printed circuit boards (PCB). Accordingly, the amount of waste PCB from electronic productions and waste electronics and its environmental impact such as soil and groundwater contamination have become a great concern. This study aims to propose a method for reuse of waste PCB as an additive for cement mortar. Although the expansibility of waste PCB powder finer than 0.08 mm in water was observed to be greater than 2.0%, the maximum expansion rates in water for 0.08 to approximately 0.15 and 0.15 to approximately 0.30 mm sized PCB powders were less than 2.0%, which satisfied the necessary condition as an alternative additive for cement mortar in place of sand. The difference in the compressive strength of standard mortar and waste PCB added mortar was observed to be less than 10% and their difference was expected to be smaller after prolonged aging. The durability of waste PCB added cement mortar was also examined through dry/wet conditioning cyclic tests and acidic/alkaline conditioning tests. From the tests, both weight and compressive strength of cement mortar were observed to be recovered with aging. The leaching test for heavy metals from waste PCB added mortar showed that no heavy metal ions such as copper, lead, or cadmium were detected in the leachate, which resulted from fixation effect of the cement hydrates.

  19. Assessment of Nano Cellulose from Peach Palm Residue as Potential Food Additive: Part II: Preliminary Studies.

    PubMed

    Andrade, Dayanne Regina Mendes; Mendonça, Márcia Helena; Helm, Cristiane Vieira; Magalhães, Washington L E; de Muniz, Graciela Ines Bonzon; Kestur, Satyanarayana G

    2015-09-01

    High consumption of dietary fibers in the diet is related to the reduction of the risk of non-transmitting of chronic diseases, prevention of the constipation etc. Rich diets in dietary fibers promote beneficial effects for the metabolism. Considering the above and recognizing the multifaceted advantages of nano materials, there have been many attempts in recent times to use the nano materials in the food sector including as food additive. However, whenever new product for human and animal consumption is developed, it has to be tested for their effectiveness regarding improvement in the health of consumers, safety aspects and side effects. However, before it is tried with human beings, normally such materials would be assessed through biological tests on a living organism to understand its effect on health condition of the consumer. Accordingly, based on the authors' finding reported in a previous paper, this paper presents body weight, biochemical (glucose, cholesterol and lipid profile in blood, analysis of feces) and histological tests carried out with biomass based cellulose nano fibrils prepared by the authors for its possible use as food additive. Preliminary results of the study with mice have clearly brought out potential of these fibers for the said purpose. PMID:26344977

  20. Resources allocation in healthcare for cancer: a case study using generalised additive mixed models.

    PubMed

    Musio, Monica; Sauleau, Erik A; Augustin, Nicole H

    2012-11-01

    Our aim is to develop a method for helping resources re-allocation in healthcare linked to cancer, in order to replan the allocation of providers. Ageing of the population has a considerable impact on the use of health resources because aged people require more specialised medical care due notably to cancer. We propose a method useful to monitor changes of cancer incidence in space and time taking into account two age categories, according to healthcar general organisation. We use generalised additive mixed models with a Poisson response, according to the methodology presented in Wood, Generalised additive models: an introduction with R. Chapman and Hall/CRC, 2006. Besides one-dimensional smooth functions accounting for non-linear effects of covariates, the space-time interaction can be modelled using scale invariant smoothers. Incidence data collected by a general cancer registry between 1992 and 2007 in a specific area of France is studied. Our best model exhibits a strong increase of the incidence of cancer along time and an obvious spatial pattern for people more than 70 years with a higher incidence in the central band of the region. This is a strong argument for re-allocating resources for old people cancer care in this sub-region.

  1. Mechanisms on electrical breakdown strength increment of polyethylene by aromatic carbonyl compounds addition: a theoretical study.

    PubMed

    Zhang, Hui; Shang, Yan; Wang, Xuan; Zhao, Hong; Han, Baozhong; Li, Zesheng

    2013-12-01

    A theoretical investigation is accomplished on the mechanisms of electrical breakdown strength increment of polyethylene at the atomic and molecular levels. It is found that the addition of aromatic carbonyl compounds as voltage stabilizers is one of the important factors for increasing electrical breakdown strength of polyethylene, as the additives can trap hot electrons, obtain energy of hot electrons, and transform the aliphatic cation to relatively stable aromatic cation to prevent the degradation of the polyethylene matrix. The HOMO-LUMO energy gaps (E(g)), the ionization potentials (IPs), and electron affinities (EAs) at the ground states of a series of aromatic carbonyl compounds are obtained at the B3LYP/6-311+G(d,p) level. The theoretical results are in good agreement with the available experimental findings, show that 2,4-dioctyloxybenzophenone (Bzo) and 4,4'-didodecyloxybenzil (Bd) molecules can effectively increase the electrical breakdown strength when they are doped into polyethylene because of their much smaller E g values than all the other studied aromatic carbonyl molecules and excellent compatibility with polymers matrix.

  2. Development of structural MR brain imaging protocols to study genetics and maturation

    PubMed Central

    Kochunov, Peter; Davis, M. Duff

    2009-01-01

    Structural imaging research offers excellent translational benefits when non-human primate (NHP) models are employed. In this paper, we will discuss the development of anatomical MR imaging protocols for two important applications of structural imaging in NHP: studies of genetic variability in brain morphology and longitudinal imaging of fetal brain maturation trends. In contrast with imaging studies of adult humans, structural imaging in the NHP is challenging due to a comparatively small brain size (2-200 fold smaller volume, depending on the species). This difference in size is further accentuated in NHP studies of brain development, in which fetal brain volumes are 10-50% of their adult size. The sizes of cortical gyri and sulci scale allometrically with brain size. Thus, achieving spatial sampling that is comparable to that of high-quality human studies (∼1.0 mm3) requires a brain-size-adjusted reduction in the sampling volumes of from 500-to-150 microns3. Imaging at this spatial resolution while maintaining sufficient contrast and signal to noise ratio necessitates the development of specialized MRI protocols. Here we discuss our strategy to optimize the protocol parameters for two commonly available structural imaging sequences: MPRAGE and TrueFisp. In addition, computational tools developed for the analysis of human structural images were applied to the NHP studies. These included removal of non-brain tissues, correction for RF inhomogeneity, spatial normalization, building of optimized target brain and analysis of cerebral gyrification and individual cortical variability. Finally, recent findings in the genetics of cerebral gyrification and tracking of maturation trends in the fetal, newborn and adult brain are described PMID:19665566

  3. Study on Friction and Wear Properties of Silver Matrix Brush Material with Different Additives

    NASA Astrophysics Data System (ADS)

    Chen, Xiaoli; Wang, Wenfang; Hong, Yu; Wu, Yucheng

    2013-07-01

    Friction and wear processes of AgCuX (G, CF and AlN) composites-CuAgV alloy friction pair and effects of different additive content in silver based composite on friction and wear behavior are studied in this paper. The microstructure of the brush wear surface is observed by SEM. The results show that when graphite content is up to 9 wt.%, Ag-Cu-CF-G composite exhibits the best wear properties; when the content of aluminum nitride is up to 0.5 wt.%, Ag-Cu-AlN-G composites has the most comprehensive performance. The wear loss of both composites arises with the increase of both pressure and speed, but when speed reaches a critical value, the increased amplitude of wear loss tends to be steady.

  4. Comparative study of dimensional accuracy of different impression techniques using addition silicone impression material.

    PubMed

    Penaflor, C F; Semacio, R C; De Las Alas, L T; Uy, H G

    1998-01-01

    This study compared dimensional accuracy of the single, double with spacer, double with cut-out and double mix impression technique using addition silicone impression material. A typhodont containing Ivorine teeth model with six (6) full-crown tooth preparations were used as the positive control. Two stone replication models for each impression technique were made as test materials. Accuracy of the techniques were assessed by measuring four dimensions on the stone dies poured from the impression of the Ivorine teeth model. Results indicated that most of the measurements for the height, width and diameter slightly decreased and a few increased compared with the Ivorine teeth model. The double with cut-out and double mix technique presents the least difference from the master model as compared to the two latter impression techniques. PMID:10202524

  5. Study of cadmium, zinc and lead biosorption by orange wastes using the subsequent addition method.

    PubMed

    Pérez-Marín, A B; Ballester, A; González, F; Blázquez, M L; Muñoz, J A; Sáez, J; Zapata, V Meseguer

    2008-11-01

    The biosorption of several metals (Cd2+, Zn2+ and Pb2+) by orange wastes has been investigated in binary systems. Multicomponent sorption isotherms were obtained using an original procedure, similar to that proposed by Pagnanelli et al. [Pagnanelli, F., Petrangeli, M.P., Toro, L., Trifoni, M., Veglio, F., 2001a. Biosorption of metal ions on Arthrobacter sp.: biomass characterization and biosorption modelling. Environ. Sci. Technol. 34, 2773-2778] for monoelement systems, known as subsequent addition method (SAM). Experimental sorption data were analysed using an extended multicomponent Langmuir equation. The maximum sorption uptake was approximately 0.25mmol/g for the three binary systems studied. The reliability of the proposed procedure for obtaining the equilibrium data in binary systems was verified by means of a statistical F-test. PMID:18440805

  6. Spectroscopic studies of nucleic acid additions during seed-mediated growth of gold nanoparticles

    PubMed Central

    Tapp, Maeling; Sullivan, Rick; Dennis, Patrick; Naik, Rajesh R.

    2015-01-01

    The effect of adding nucleic acids to gold seeds during the growth stage of either nanospheres or nanorods was investigated using UV-Vis spectroscopy to reveal any oligonucleotide base or structure-specific effects on nanoparticle growth kinetics or plasmonic signatures. Spectral data indicate that the presence of DNA duplexes during seed ageing drastically accelerated nanosphere growth while the addition of single-stranded polyadenine at any point during seed ageing induces nanosphere aggregation. For seeds added to a gold nanorod growth solution, single-stranded polythymine induces a modest blue-shift in the longitudinal peak wavelength. Moreover, a particular sequence comprised of 50% thymine bases was found to induce a faster, more dramatic blue-shift in the longitudinal peak wavelength compared to any of the homopolymer incubation cases. Monomeric forms of the nucleic acids, however, do not yield discernable spectral differences in any of the gold suspensions studied. PMID:25960601

  7. Rapid identification of color additives, using the C18 cartridge: collaborative study.

    PubMed

    Young, M L

    1988-01-01

    Nine laboratories collaboratively studied a method for the separation and identification of the 7 permitted FD&C color additives (Red Nos. 3 and 40; Blue Nos. 1 and 2; Yellow Nos. 5 and 6; Green No. 3) and the banned FD&C Red No. 2 in foods. The method is based on use of a commercial C18 cartridge and spectrophotometry or thin layer chromatography. Collaborators analyzed 5 commercial products (noodles, candy, carbonated soda, flavored gelatin, and powdered drink) and 2 dye mixtures (one containing FD&C Red Nos. 2, 3, and 40; the other containing FD&C Green No. 3 and Red No. 3). All of the colors were identified with little or no difficulty by 8 collaborators. The method has been adopted official first action.

  8. Genetic causes of intellectual disability in a birth cohort: A population‐based study

    PubMed Central

    Riegel, Mariluce; Segal, Sandra L.; Félix, Têmis M.; Barros, Aluísio J. D.; Santos, Iná S.; Matijasevich, Alicia; Giugliani, Roberto; Black, Maureen

    2015-01-01

    Intellectual disability affects approximately 1–3% of the population and can be caused by genetic and environmental factors. Although many studies have investigated the etiology of intellectual disability in different populations, few studies have been performed in middle‐income countries. The present study estimated the prevalence of genetic causes related to intellectual disability in a cohort of children from a city in south Brazil who were followed from birth. Children who showed poor performance in development and intelligence tests at the ages of 2 and 4 were included. Out of 4,231 liveborns enrolled in the cohort, 214 children fulfilled the inclusion criteria. A diagnosis was established in approximately 90% of the children evaluated. Genetic causes were determined in 31 of the children and 19 cases remained unexplained even after extensive investigation. The overall prevalence of intellectual disability in this cohort due to genetic causes was 0.82%. Because this study was nested in a cohort, there were a large number of variables related to early childhood and the likelihood of information bias was minimized by collecting information with a short recall time. This study was not influenced by selection bias, allowing identification of intellectual disability and estimation of the prevalence of genetic causes in this population, thereby increasing the possibility of providing appropriate management and/or genetic counseling. © 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. PMID:25728503

  9. Human genetics studies: the case for group rights.

    PubMed

    Underkuffler, Laura S

    2007-01-01

    In this essay, the author focuses on an underlying theoretical issue which she believes seriously affects our collective response to the idea of group rights in the genetic-control context. That issue is to what extent are our responses to claims of group rights hampered by our bringing to the table (consciously or unconsciously) a model which is structured to acknowledge only individual concerns? Put another way, to what extent are our objections to group rights in this context a product of our inability (or refusal) to imagine the idea of group rights, rather than the product of truly substantive concerns?

  10. Parameterization of interatomic potential by genetic algorithms: A case study

    SciTech Connect

    Ghosh, Partha S. Arya, A.; Dey, G. K.; Ranawat, Y. S.

    2015-06-24

    A framework for Genetic Algorithm based methodology is developed to systematically obtain and optimize parameters for interatomic force field functions for MD simulations by fitting to a reference data base. This methodology is applied to the fitting of ThO{sub 2} (CaF{sub 2} prototype) – a representative of ceramic based potential fuel for nuclear applications. The resulting GA optimized parameterization of ThO{sub 2} is able to capture basic structural, mechanical, thermo-physical properties and also describes defect structures within the permissible range.

  11. Study of triallyl phosphate as an electrolyte additive for high voltage lithium-ion cells

    NASA Astrophysics Data System (ADS)

    Xia, J.; Madec, L.; Ma, L.; Ellis, L. D.; Qiu, W.; Nelson, K. J.; Lu, Z.; Dahn, J. R.

    2015-11-01

    The role of triallyl phosphate as an electrolyte additive in Li(Ni0.42Mn0.42Co0.16)O2/graphite pouch cells was studied using ex-situ gas measurements, ultra high precision coulometry, automated storage experiments, electrochemical impedance spectroscopy, long-term cycling and X-ray photoelectron spectroscopy. Cells containing triallyl phosphate produced less gas during formation, cycling and storage than control cells. The use of triallyl phosphate led to higher coulombic efficiency and smaller charge endpoint capacity slippage during ultra high precision charger testing. Cells containing triallyl phosphate showed smaller potential drop during 500 h storage at 40 °C and 60 °C and the voltage drop decreased as the triallyl phosphate content in the electrolyte increased. However, large amounts of triallyl phosphate (>3% by weight in the electrolyte) led to large impedance after cycling and storage. Symmetric cell studies showed large amounts of triallyl phosphate (5% or more) led to significant impedance increase at both negative and positive electrodes. X-ray photoelectron spectroscopy studies suggested that the high impedance came from the polymerization of triallyl phosphate molecules which formed thick solid electrolyte interphase films at the surfaces of both negative and positive electrodes. An optimal amount of 2%-3% triallyl phosphate led to better capacity retention during long term cycling.

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

    PubMed Central

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

    2012-01-01

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

  13. Genetic thromobophilia in pregnancy: a case-control study among North Indian women.

    PubMed

    Kaur, Lovejeet; Puri, Manju; Kaushik, Shweta; Sachdeva, Mohinder Pal; Trivedi, Shubha Sagar; Saraswathy, Kallur Nava

    2013-02-01

    In the present study, an attempt is made to understand the role of genetic thrombophilias i.e. MTHFR C677T and FVL in the causation of various pregnancy complications like pregnancy induced hypertension (PIH), recurrent abortions, intra-uterine growth retardation (IUGR) and intra-uterine death on the whole and also individually along with the comparative assessment of pathophysiological basis of various pregnancy complications via the genetic proximities. One thousand and eleven (1,011) women of reproductive age group were recruited in the present study comprising various complications and controls. Recruitment criteria for all the pregnancy complications and controls was made and followed strictly. MTHFR C677T and FVL mutation detection was done in all the subjects. Vegetarianism was found to be significant risk factors for all the pregnancy complications and also when assessed individually. With respect to MTHFR C677T polymorphism, higher frequency of 677T allele was found among controls as compared to cases. 677T allele was found to pose decreased risk for various pregnancy complications on the whole and also individually. On adjusting the diet, regression analysis revealed no risk of mutant allele (T) for various pregnancy complications. FVL homozygous mutants were found to be absent among controls. In conclusion, the present study depicts dietary pattern as one of the most important factors in demonstrating the role of MTHFR C677T in various pregnancy complications and is indicative of a relatively deleterious effect of double dose of FVL in the presently studied population. Additionally, these polymorphisms play an important role in the orchestration of PIH to IUGR and vice versa. PMID:22918664

  14. Recruitment of Yoruba families from Nigeria for genetic research: experience from a multisite keloid study

    PubMed Central

    2014-01-01

    Background More involvement of sub-Saharan African countries in biomedical studies, specifically in genetic research, is needed to advance individualized medicine that will benefit non-European populations. Missing infrastructure, cultural and religious beliefs as well as lack of understanding of research benefits can pose a challenge to recruitment. Here we describe recruitment efforts for a large genetic study requiring three-generation pedigrees within the Yoruba homelands of Nigeria. The aim of the study was to identify genes responsible for keloids, a wound healing disorder. We also discuss ethical and logistical considerations that we encountered in preparation for this research endeavor. Methods Protocols for this bi-national intercultural study were approved by the Institutional Review Board (IRB) in the US and the ethics committees of the Nigerian institutions for consideration of cultural differences. Principles of community based participatory research were employed throughout the recruitment process. Keloid patients (patient advisors), community leaders, kings/chiefs and medical directors were engaged to assist the research teams with recruitment strategies. Community meetings, church forums, and media outlets (study flyers, radio and TV announcements) were utilized to promote the study in Nigeria. Recruitment of research participants was conducted by trained staff from the local communities. Pedigree structures were re-analyzed on a regular basis as new family members were recruited and recruitment challenges were documented. Results Total recruitment surpassed 4200 study participants over a 7-year period including 79 families with complete three-generation pedigrees. In 9 families more than 20 family members participated, however, in 5 of these families, we encountered issues with pedigree structure as members from different branches presented inconsistent family histories. These issues were due to the traditional open family structure amongst the

  15. Ensuring privacy in the study of pathogen genetics.

    PubMed

    Mehta, Sanjay R; Vinterbo, Staal A; Little, Susan J

    2014-08-01

    Rapid growth in the genetic sequencing of pathogens in recent years has led to the creation of large sequence databases. This aggregated sequence data can be very useful for tracking and predicting epidemics of infectious diseases. However, the balance between the potential public health benefit and the risk to personal privacy for individuals whose genetic data (personal or pathogen) are included in such work has been difficult to delineate, because neither the true benefit nor the actual risk to participants has been adequately defined. Existing approaches to minimise the risk of privacy loss to participants are based on de-identification of data by removal of a predefined set of identifiers. These approaches neither guarantee privacy nor protect the usefulness of the data. We propose a new approach to privacy protection that will quantify the risk to participants, while still maximising the usefulness of the data to researchers. This emerging standard in privacy protection and disclosure control, which is known as differential privacy, uses a process-driven rather than data-centred approach to protecting privacy.

  16. Internet solicitation of research subjects for genetic studies

    SciTech Connect

    Biesecker, L.G.; DeRenzo, E.G.

    1995-11-01

    Communication through electronic messages on the Internet has become a rapid and effective method for exchanging ideas and information in many disciplines. The Human Molecular Genetics network Diagnostics and Clinical Research Section (hum-molgen@nic.surfnet.nl) is now serving this function for the field of human molecular genetics. Our attention was drawn to the power and the pitfalls of this information exchange when we read a solicitation for research subjects by a Canadian medical student. The student was initiating a summer research project on an inherited disorder and requested information to determine the frequency of the disorder and to collect blood samples of affected patients. The student also requested samples of stored blood or DNA of affected persons. On other occasions, the hum-mol-gen service has also been used by clinicians to announce the availability of patients with a particular disorder (or their blood samples) who are interested in participating in research projects. Such uses of the Internet can serve to facilitate communication between researchers and clinicians and enhance clinical research. We believe, however, that some guidelines are necessary to protect human subjects. Investigators in the United States who are subject to U.S. Federal Government human subjects research regulations, or who are attached to an institution conducting such research, should consider some important issues before placing or responding to a request on the Internet. 1 ref.

  17. A behavioral genetic study of the dark triad of personality and moral development.

    PubMed

    Campbell, Jennifer; Schermer, Julie Aitken; Villani, Vanessa C; Nguyen, Brenda; Vickers, Leanne; Vernon, Philip A

    2009-04-01

    The present study is the first behavioral genetic investigation of relationships between the Dark Triad of personality--Machiavellianism, narcissism, and subclinical psychopathy--and moral development. Participants were 154 monozygotic twin pairs and 82 same-sex dizygotic twin pairs. Higher scores on Machiavellianism and psychopathy were positively correlated with low levels of moral development; high psychopathy scores also correlated negatively with high levels of moral development. Individual differences in lower levels of moral development were attributable to genetic and nonshared environmental factors but, very interestingly, individual differences in the highest levels of moral development showed no genetic basis but were entirely attributable to shared and nonshared environmental factors. Finally, correlations between the Dark Triad and moral development variables showed no genetic basis while correlations among the moral development variables were variously attributable to correlated genetic and correlated environmental factors.

  18. The impact of bismuth addition to sequential treatment on Helicobacter pylori eradication: A pilot study.

    PubMed

    Basyigit, Sebahat; Kefeli, Ayse; Sapmaz, Ferdane; Yeniova, Abdullah Ozgür; Asilturk, Zeliha; Hokkaomeroglu, Murat; Uzman, Metin; Nazligul, Yasar

    2015-10-25

    The success of the current anti-Helicobacter pylori (H. pylori) treatment protocols is reported to decrease by years, and research is needed to strengthen the H. pylori eradication treatment. Sequential treatment (ST), one of the treatment modalities for H. pylori eradication, includes amoxicillin 1 gr b.i.d and proton pump inhibitor b.i.d for first 5 days and then includes clarithromycin 500 mg b.i.d, metronidazole 500 mg b.i.d and a proton pump inhibitor b.i.d for remaining 5 days. In this study, we investigated efficacy and tolerability of bismuth addition in to ST. We included patients that underwent upper gastrointestinal endoscopy in which H. pylori infection was diagnosed by histological examination of antral and corporal gastric mucosa biopsy. Participants were randomly administered ST or bismuth containing ST (BST) protocols for the first-line H. pylori eradication therapy. Participants have been tested by urea breath test for eradication success 6 weeks after the completion of treatment. One hundred and fifty patients (93 female, 57 male) were enrolled. There were no significant differences in eradication rates for both intention to treat population (70.2%, 95% confidence interval [CI]: 66.3-74.1% vs. 71.8%, 95% CI: 61.8-81.7%, for ST and BST, respectively, p>0.05) and per protocol population (74.6%, 95% CI: 63.2-85.8% vs. 73.7%, 95% CI: 63.9-83.5% for ST and BST, respectively, p>0.05). Despite the undeniable effect of bismuth, there may be several possible reasons of unsatisfactory eradication success. Drug administration time, coadministration of other drugs, possible H. pylori resistance to bismuth may affect the eradication success. The addition of bismuth subcitrate to ST regimen does not provide significant increase in eradication rates.

  19. Genetic mouse models to study blood–brain barrier development and function

    PubMed Central

    2013-01-01

    The blood–brain barrier (BBB) is a complex physiological structure formed by the blood vessels of the central nervous system (CNS) that tightly regulates the movement of substances between the blood and the neural tissue. Recently, the generation and analysis of different genetic mouse models has allowed for greater understanding of BBB development, how the barrier is regulated during health, and its response to disease. Here we discuss: 1) Genetic mouse models that have been used to study the BBB, 2) Available mouse genetic tools that can aid in the study of the BBB, and 3) Potential tools that if generated could greatly aid in our understanding of the BBB. PMID:23305182

  20. Experimental Study of Disruption of Columnar Grains During Rapid Solidification in Additive Manufacturing

    NASA Astrophysics Data System (ADS)

    Manogharan, Guha; Yelamanchi, Bharat; Aman, Ronald; Mahbooba, Zaynab

    2016-03-01

    Over the years, many studies have been conducted to study and analyze the grain structures of metal alloys during additive manufacturing to improve mechanical properties. In particular, columnar grains are observed predominantly during rapid solidification of molten metal. This leads to lower mechanical properties and requires expensive secondary heat-treatment processes. This study is aimed at disrupting the formation of columnar grain growth during rapid solidification using ultrasonic vibration and analyzes the effects on grain structure and mechanical properties. A gas-metal arc welder mounted on a Rep-Rap-based low-cost metal 3 Dimension printer was used to deposit ER70S-6 mild steel layers on a plate. A contact-type ultrasonic transducer with a control system to vary the frequency and power of the vibration was used. The effects of ultrasonic vibration were determined from the statistical analysis of microstructure and micro-indentation techniques on the deposited layer and heat-affected zone. It was found that both frequency and interaction between frequency and power had significant impact on the refinement of average grain size up to 10.64% and increased the number of grains by approximately 41.78%. Analysis of micro-indentation tests showed that there was an increase of approximately 14.30% in micro-hardness due to the applied frequency during rapid solidification. A pole diagram shows that application of vibration causes randomization of grain orientation. Along with the results from this study, further efforts in modeling and experimentation of multi-directional vibrations would lead to a better understanding of disrupting columnar grains in applications that use mechanical vibrations, such as welding, directed energy deposition, brazing, etc.

  1. Review of the Diabetes Heart Study (DHS) family of studies: a comprehensively examined sample for genetic and epidemiological studies of type 2 diabetes and its complications.

    PubMed

    Bowden, Donald W; Cox, Amanda J; Freedman, Barry I; Hugenschimdt, Christina E; Wagenknecht, Lynne E; Herrington, David; Agarwal, Subhashish; Register, Thomas C; Maldjian, Joseph A; Ng, Maggie C-Y; Hsu, Fang-Chi; Langefeld, Carl D; Williamson, Jeff D; Carr, J Jeffrey

    2010-01-01

    The Diabetes Heart Study (DHS) is a genetic and epidemiological study of 1,443 European American and African American participants from 564 families with multiple cases of type 2 diabetes. Initially, participants were comprehensively examined for measures of subclinical cardiovascular disease (CVD) including computed tomography measurement of vascular calcified plaque, ultrasound imaging of carotid artery wall thickness, and electrocardiographic intervals. Subsequent studies have investigated the relationship between bone mineral density and vascular calcification, measures of adiposity, and biomarkers. Ongoing studies are carrying out an extensive evaluation of cerebrovascular disease using magnetic resonance imaging and cognitive assessment. A second, parallel study, the African American DHS, has expanded the sample of African Americans to investigate marked racial differences in subclinical CVD between European Americans and African Americans. Studies in development will evaluate the impact of social stress during the lifecourse on CVD risk, and the prevalence of gastroparesis in this diabetes enriched sample. In addition, the ongoing high mortality rate in DHS participants provides novel insights into the increased risks for type 2 diabetes affected individuals. A comprehensive genetic analysis of the sample is underway using the genome-wide association study (GWAS) approach. Data from this GWAS survey will complement prior family-based linkage data in the analysis of genetic contributors to the wide range of traits in the sample. To our knowledge the DHS family of studies has created the most comprehensively examined sample of individuals with type 2 diabetes yet available, and represents a unique resource for the study people with type 2 diabetes. The aim of this review is to provide a collective overview of the major results from the DHS family of studies, and relate them to the larger body of biomedical investigations of diabetes and its complications. PMID

  2. A new method for studying population genetics of cyst nematodes based on Pool-Seq and genomewide allele frequency analysis.

    PubMed

    Mimee, Benjamin; Duceppe, Marc-Olivier; Véronneau, Pierre-Yves; Lafond-Lapalme, Joël; Jean, Martine; Belzile, François; Bélair, Guy

    2015-11-01

    Cyst nematodes are important agricultural pests responsible for billions of dollars of losses each year. Plant resistance is the most effective management tool, but it requires a close monitoring of population genetics. Current technologies for pathotyping and genotyping cyst nematodes are time-consuming, expensive and imprecise. In this study, we capitalized on the reproduction mode of cyst nematodes to develop a simple population genetic analysis pipeline based on genotyping-by-sequencing and Pool-Seq. This method yielded thousands of SNPs and allowed us to study the relationships between populations of different origins or pathotypes. Validation of the method on well-characterized populations also demonstrated that it was a powerful and accurate tool for population genetics. The genomewide allele frequencies of 23 populations of golden nematode, from nine countries and representing the five known pathotypes, were compared. A clear separation of the pathotypes and fine genetic relationships between and among global populations were obtained using this method. In addition to being powerful, this tool has proven to be very time- and cost-efficient and could be applied to other cyst nematode species.

  3. The genetic regulatory network centered on Pto-Wuschela and its targets involved in wood formation revealed by association studies.

    PubMed

    Yang, Xiaohui; Wei, Zunzheng; Du, Qingzhang; Chen, Jinhui; Wang, Qingshi; Quan, Mingyang; Song, Yuepeng; Xie, Jianbo; Zhang, Deqiang

    2015-11-09

    Transcription factors (TFs) regulate gene expression and can strongly affect phenotypes. However, few studies have examined TF variants and TF interactions with their targets in plants. Here, we used genetic association in 435 unrelated individuals of Populus tomentosa to explore the variants in Pto-Wuschela and its targets to decipher the genetic regulatory network of Pto-Wuschela. Our bioinformatics and co-expression analysis identified 53 genes with the motif TCACGTGA as putative targets of Pto-Wuschela. Single-marker association analysis showed that Pto-Wuschela was associated with wood properties, which is in agreement with the observation that it has higher expression in stem vascular tissues in Populus. Also, SNPs in the 53 targets were associated with growth or wood properties under additive or dominance effects, suggesting these genes and Pto-Wuschela may act in the same genetic pathways that affect variation in these quantitative traits. Epistasis analysis indicated that 75.5% of these genes directly or indirectly interacted Pto-Wuschela, revealing the coordinated genetic regulatory network formed by Pto-Wuschela and its targets. Thus, our study provides an alternative method for dissection of the interactions between a TF and its targets, which will strength our understanding of the regulatory roles of TFs in complex traits in plants.

  4. The genetic regulatory network centered on Pto-Wuschela and its targets involved in wood formation revealed by association studies

    PubMed Central

    Yang, Xiaohui; Wei, Zunzheng; Du, Qingzhang; Chen, Jinhui; Wang, Qingshi; Quan, Mingyang; Song, Yuepeng; Xie, Jianbo; Zhang, Deqiang

    2015-01-01

    Transcription factors (TFs) regulate gene expression and can strongly affect phenotypes. However, few studies have examined TF variants and TF interactions with their targets in plants. Here, we used genetic association in 435 unrelated individuals of Populus tomentosa to explore the variants in Pto-Wuschela and its targets to decipher the genetic regulatory network of Pto-Wuschela. Our bioinformatics and co-expression analysis identified 53 genes with the motif TCACGTGA as putative targets of Pto-Wuschela. Single-marker association analysis showed that Pto-Wuschela was associated with wood properties, which is in agreement with the observation that it has higher expression in stem vascular tissues in Populus. Also, SNPs in the 53 targets were associated with growth or wood properties under additive or dominance effects, suggesting these genes and Pto-Wuschela may act in the same genetic pathways that affect variation in these quantitative traits. Epistasis analysis indicated that 75.5% of these genes directly or indirectly interacted Pto-Wuschela, revealing the coordinated genetic regulatory network formed by Pto-Wuschela and its targets. Thus, our study provides an alternative method for dissection of the interactions between a TF and its targets, which will strength our understanding of the regulatory roles of TFs in complex traits in plants. PMID:26549216

  5. Development and application of SINE multilocus and quantitative genetic markers to study oilseed rape (Brassica napus L.) crops.

    PubMed

    Allnutt, T R; Roper, K; Henry, C

    2008-01-23

    A genetic marker system based on the S1 Short Interspersed Elements (SINEs) in the important commercial crop, oilseed rape ( Brassica napus L.) has been developed. SINEs provided a successful multilocus, dominant marker system that was capable of clearly delineating winter- and spring-type crop varieties. Sixteen of 20 varieties tested showed unique profiles from the 17 polymorphic SINE markers generated. The 3' or 5' flank region of nine SINE markers were cloned, and DNA was sequenced. In addition, one putative pre-transposition SINE allele was cloned and sequenced. Two SINE flanking sequences were used to design real-time PCR assays. These quantitative SINE assays were applied to study the genetic structure of eight fields of oilseed rape crops. Studied fields were more genetically diverse than expected for the chosen loci (mean H T = 0.23). The spatial distribution of SINE marker frequencies was highly structured in some fields, suggesting locations of volunteer impurities within the crop. In one case, the assay identified a mislabeling of the crop variety. SINE markers were a useful tool for crop genetics, phylogenetics, variety identification, and purity analysis. The use and further application of quantitative, real-time PCR markers are discussed.

  6. Development and application of SINE multilocus and quantitative genetic markers to study oilseed rape (Brassica napus L.) crops.

    PubMed

    Allnutt, T R; Roper, K; Henry, C

    2008-01-23

    A genetic marker system based on the S1 Short Interspersed Elements (SINEs) in the important commercial crop, oilseed rape ( Brassica napus L.) has been developed. SINEs provided a successful multilocus, dominant marker system that was capable of clearly delineating winter- and spring-type crop varieties. Sixteen of 20 varieties tested showed unique profiles from the 17 polymorphic SINE markers generated. The 3' or 5' flank region of nine SINE markers were cloned, and DNA was sequenced. In addition, one putative pre-transposition SINE allele was cloned and sequenced. Two SINE flanking sequences were used to design real-time PCR assays. These quantitative SINE assays were applied to study the genetic structure of eight fields of oilseed rape crops. Studied fields were more genetically diverse than expected for the chosen loci (mean H T = 0.23). The spatial distribution of SINE marker frequencies was highly structured in some fields, suggesting locations of volunteer impurities within the crop. In one case, the assay identified a mislabeling of the crop variety. SINE markers were a useful tool for crop genetics, phylogenetics, variety identification, and purity analysis. The use and further application of quantitative, real-time PCR markers are discussed. PMID:18092752

  7. Evaluating the addition of positive reinforcement for learning a frightening task: a pilot study with horses.

    PubMed

    Heleski, Camie; Bauson, Laura; Bello, Nora

    2008-01-01

    Horse training often relies upon negative reinforcement (NR). This study tested the hypothesis that adding positive reinforcement (PR) to NR would enhance learning in horses (n = 34) being taught to walk over a tarp (novel/typically frightening task). Subjects were Arabians, and the same person handled all of them. This person handled half "traditionally" (NR only)--that is, halter/lead were pulled; when horse stepped forward, pressure was released; process repeated until criterion met (horse crossed the tarp with little/no obvious anxiety). The same person handled the other half traditionally--but with addition of PR < food + verbal praise > (NR + PR). Subjects "failed" the task if they refused to walk onto the tarp after 10 min. Nine horses failed; 6 of 9 failures were from NR only--no significant difference detected (p = .41). The study detected no difference in time to first crossing of the tarp (p = .30) or total time to achieve calmness criterion (p = .67). Overall, adding PR did not significantly enhance learning this task. However, there were practical implications--adding PR made the task safer/less fatiguing for the handler. PMID:18569217

  8. Evaluating the addition of positive reinforcement for learning a frightening task: a pilot study with horses.

    PubMed

    Heleski, Camie; Bauson, Laura; Bello, Nora

    2008-01-01

    Horse training often relies upon negative reinforcement (NR). This study tested the hypothesis that adding positive reinforcement (PR) to NR would enhance learning in horses (n = 34) being taught to walk over a tarp (novel/typically frightening task). Subjects were Arabians, and the same person handled all of them. This person handled half "traditionally" (NR only)--that is, halter/lead were pulled; when horse stepped forward, pressure was released; process repeated until criterion met (horse crossed the tarp with little/no obvious anxiety). The same person handled the other half traditionally--but with addition of PR < food + verbal praise > (NR + PR). Subjects "failed" the task if they refused to walk onto the tarp after 10 min. Nine horses failed; 6 of 9 failures were from NR only--no significant difference detected (p = .41). The study detected no difference in time to first crossing of the tarp (p = .30) or total time to achieve calmness criterion (p = .67). Overall, adding PR did not significantly enhance learning this task. However, there were practical implications--adding PR made the task safer/less fatiguing for the handler.

  9. Synthesis, Characterization, Molecular Modeling, and DNA Interaction Studies of Copper Complex Containing Food Additive Carmoisine Dye.

    PubMed

    Shahabadi, Nahid; Akbari, Alireza; Jamshidbeigi, Mina; Khodarahmi, Reza

    2016-06-01

    A copper complex of carmoisine dye; [Cu(carmoisine)2(H2O)2]; was synthesized and characterized by using physico-chemical and spectroscopic methods. The binding of this complex with calf thymus (ct) DNA was investigated by circular dichroism, absorption studies, emission spectroscopy, and viscosity measurements. UV-vis results confirmed that the Cu complex interacted with DNA to form a ground-state complex and the observed binding constant (2× 10(4) M(-1)) is more in keeping with the groove bindings with DNA. Furthermore, the viscosity measurement result showed that the addition of complex causes no significant change on DNA viscosity and it indicated that the intercalation mode is ruled out. The thermodynamic parameters are calculated by van't Hoff equation, which demonstrated that hydrogen bonds and van der Waals interactions played major roles in the reaction. The results of circular dichroism (CD) suggested that the complex can change the conformation of DNA from B-like form toward A-like conformation. The cytotoxicity studies of the carmoisine dye and its copper complex indicated that both of them had anticancer effects on HT-29 (colon cancer) cell line and they may be new candidates for treatment of the colon cancer.

  10. Density functional theory study of the effects of alloying additions on sulfur adsorption on nickel surfaces

    NASA Astrophysics Data System (ADS)

    Malyi, Oleksandr I.; Chen, Zhong; Kulish, Vadym V.; Bai, Kewu; Wu, Ping

    2013-01-01

    Reactions of hydrogen sulfide (H2S) with Nickel/Ytrria-doped zirconia (Ni/YDZ) anode materials might cause degradation of the performance of solid oxide fuel cells when S containing fuels are used. In this paper, we employ density functional theory to investigate S adsorption on metal (M)-doped and undoped Ni(0 0 1) and Ni(1 1 1) surfaces. Based on the performed calculations, we analyze the effects of 12 alloying additions (Ag, Au, Al, Bi, Cd, Co, Cu, Fe, Sn, Sb, V, and Zn) on the temperature of transition between clean (S atoms do not adsorb on the surfaces) and contaminated (S atoms can adsorb on the surfaces spontaneously) M-doped Ni surfaces for different concentrations of H2S in the fuel. Predicted results are consistent with many experimental studies relevant to S poisoning of both Ni/YDZ and M-doped Ni/YDZ anode materials. This study is important to understand S poisoning phenomena and to develop new S tolerant anode materials.

  11. Synthesis, Characterization, Molecular Modeling, and DNA Interaction Studies of Copper Complex Containing Food Additive Carmoisine Dye.

    PubMed

    Shahabadi, Nahid; Akbari, Alireza; Jamshidbeigi, Mina; Khodarahmi, Reza

    2016-06-01

    A copper complex of carmoisine dye; [Cu(carmoisine)2(H2O)2]; was synthesized and characterized by using physico-chemical and spectroscopic methods. The binding of this complex with calf thymus (ct) DNA was investigated by circular dichroism, absorption studies, emission spectroscopy, and viscosity measurements. UV-vis results confirmed that the Cu complex interacted with DNA to form a ground-state complex and the observed binding constant (2× 10(4) M(-1)) is more in keeping with the groove bindings with DNA. Furthermore, the viscosity measurement result showed that the addition of complex causes no significant change on DNA viscosity and it indicated that the intercalation mode is ruled out. The thermodynamic parameters are calculated by van't Hoff equation, which demonstrated that hydrogen bonds and van der Waals interactions played major roles in the reaction. The results of circular dichroism (CD) suggested that the complex can change the conformation of DNA from B-like form toward A-like conformation. The cytotoxicity studies of the carmoisine dye and its copper complex indicated that both of them had anticancer effects on HT-29 (colon cancer) cell line and they may be new candidates for treatment of the colon cancer. PMID:27152751

  12. Percutaneous Dorsal Instrumentation of Vertebral Burst Fractures: Value of Additional Percutaneous Intravertebral Reposition—Cadaver Study

    PubMed Central

    Krüger, Antonio; Schmuck, Maya; Noriega, David C.; Ruchholtz, Steffen; Baroud, Gamal; Oberkircher, Ludwig

    2015-01-01

    Purpose. The treatment of vertebral burst fractures is still controversial. The aim of the study is to evaluate the purpose of additional percutaneous intravertebral reduction when combined with dorsal instrumentation. Methods. In this biomechanical cadaver study twenty-eight spine segments (T11-L3) were used (male donors, mean age 64.9 ± 6.5 years). Burst fractures of L1 were generated using a standardised protocol. After fracture all spines were allocated to four similar groups and randomised according to surgical techniques (posterior instrumentation; posterior instrumentation + intravertebral reduction device + cement augmentation; posterior instrumentation + intravertebral reduction device without cement; and intravertebral reduction device + cement augmentation). After treatment, 100000 cycles (100–600 N, 3 Hz) were applied using a servohydraulic loading frame. Results. Overall anatomical restoration was better in all groups where the intravertebral reduction device was used (p < 0.05). In particular, it was possible to restore central endplates (p > 0.05). All techniques decreased narrowing of the spinal canal. After loading, clearance could be maintained in all groups fitted with the intravertebral reduction device. Narrowing increased in the group treated with dorsal instrumentation. Conclusions. For height and anatomical restoration, the combination of an intravertebral reduction device with dorsal instrumentation showed significantly better results than sole dorsal instrumentation. PMID:26137481

  13. Genetic Association Studies in Uterine Fibroids: Risk Alleles Presage the Path to Personalized Therapies.

    PubMed

    Gallagher, C Scott; Morton, Cynthia C

    2016-07-01

    Uterine leiomyoma (UL) is the most common tumor of the female reproductive system. Epidemiological analyses, including familial aggregation, twin studies, and racial discrepancies in disease prevalence and morbidity, indicated genetic factors influence risk for developing UL. Genome-wide association studies (GWASs) are a powerful method for identifying genetic variants that are associated with elevated risk for a common, complex disease. To date, three genome-wide scans for UL have been performed: a GWAS in Japanese women, a genome-wide linkage and association study in women of European decent, and an admixture-based analysis in African American women. Results from each of the three genome-wide scans performed have had varying success in identifying unique loci associated with predisposition to developing UL. Here, we address the evidence for a genetic basis for UL risk, discuss genetic association studies and their results, and identify challenges and future directions for UL GWAS analyses. PMID:27513025

  14. A molecular-genetic approach to studying source-sink interactions in Arabidopsis thalian. Final report

    SciTech Connect

    Gibson, S. I.

    2000-06-01

    This is a final report describing the results of the research funded by the DOE Energy Biosciences Program grant entitled ''A Molecular-Genetic Approach to Studying Source-Sink Interactions in Arabidiopsis thaliana''.

  15. Genetic and histological studies on the delayed systemic movement of Tobacco Mosaic Virus in Arabidopsis thaliana

    PubMed Central

    Serrano, Carolina; González-Cruz, Javiera; Jauregui, Francisca; Medina, Consuelo; Mancilla, Pablo; Matus, José Tomás; Arce-Johnson, Patricio

    2008-01-01

    Background Viral infections and their spread throughout a plant require numerous interactions between the host and the virus. While new functions of viral proteins involved in these processes have been revealed, current knowledge of host factors involved in the spread of a viral infection is still insufficient. In Arabidopsis thaliana, different ecotypes present varying susceptibilities to Tobacco mosaic virus strain U1 (TMV-U1). The rate of TMV-U1 systemic movement is delayed in ecotype Col-0 when compared with other 13 ecotypes. We followed viral movement through vascular tissue in Col-0 plants by electronic microscopy studies. In addition, the delay in systemic movement of TMV-U1 was genetically studied. Results TMV-U1 reaches apical leaves only after 18 days post rosette inoculation (dpi) in Col-0, whereas it is detected at 9 dpi in the Uk-4 ecotype. Genetic crosses between Col-0 and Uk-4 ecotypes, followed by analysis of viral movement in F1 and F2 populations, revealed that this delayed movement correlates with a recessive, monogenic and nuclear locus. The use of selected polymorphic markers showed that this locus, denoted DSTM1 (Delayed Systemic Tobamovirus Movement 1), is positioned on the large arm of chromosome II. Electron microscopy studies following the virion's route in stems of Col-0 infected plants showed the presence of curved structures, instead of the typical rigid rods of TMV-U1. This was not observed in the case of TMV-U1 infection in Uk-4, where the observed virions have the typical rigid rod morphology. Conclusion The presence of defectively assembled virions observed by electron microscopy in vascular tissue of Col-0 infected plants correlates with a recessive delayed systemic movement trait of TMV-U1 in this ecotype. PMID:18817581

  16. Assessment of the genetic basis of rosacea by genome-wide association study.

    PubMed

    Chang, Anne Lynn S; Raber, Inbar; Xu, Jin; Li, Rui; Spitale, Robert; Chen, Julia; Kiefer, Amy K; Tian, Chao; Eriksson, Nicholas K; Hinds, David A; Tung, Joyce Y

    2015-06-01

    Rosacea is a common, chronic skin disease that is currently incurable. Although environmental factors influence rosacea, the genetic basis of rosacea is not established. In this genome-wide association study, a discovery group of 22,952 individuals (2,618 rosacea cases and 20,334 controls) was analyzed, leading to identification of two significant single-nucleotide polymorphisms (SNPs) associated with rosacea, one of which replicated in a new group of 29,481 individuals (3,205 rosacea cases and 26,262 controls). The confirmed SNP, rs763035 (P=8.0 × 10(-11) discovery group; P=0.00031 replication group), is intergenic between HLA-DRA and BTNL2. Exploratory immunohistochemical analysis of HLA-DRA and BTNL2 expression in papulopustular rosacea lesions from six individuals, including one with the rs763035 variant, revealed staining in the perifollicular inflammatory infiltrate of rosacea for both proteins. In addition, three HLA alleles, all MHC class II proteins, were significantly associated with rosacea in the discovery group and confirmed in the replication group: HLA-DRB1*03:01 (P=1.0 × 10(-8) discovery group; P=4.4 × 10(-6) replication group), HLA-DQB1*02:01 (P=1.3 × 10(-8) discovery group; P=7.2 × 10(-6) replication group), and HLA-DQA1*05:01 (P=1.4 × 10(-8) discovery group; P=7.6 × 10(-6) replication group). Collectively, the gene variants identified in this study support the concept of a genetic component for rosacea, and provide candidate targets for future studies to better understand and treat rosacea.

  17. Assessment of the genetic basis of rosacea by genome-wide association study.

    PubMed

    Chang, Anne Lynn S; Raber, Inbar; Xu, Jin; Li, Rui; Spitale, Robert; Chen, Julia; Kiefer, Amy K; Tian, Chao; Eriksson, Nicholas K; Hinds, David A; Tung, Joyce Y

    2015-06-01

    Rosacea is a common, chronic skin disease that is currently incurable. Although environmental factors influence rosacea, the genetic basis of rosacea is not established. In this genome-wide association study, a discovery group of 22,952 individuals (2,618 rosacea cases and 20,334 controls) was analyzed, leading to identification of two significant single-nucleotide polymorphisms (SNPs) associated with rosacea, one of which replicated in a new group of 29,481 individuals (3,205 rosacea cases and 26,262 controls). The confirmed SNP, rs763035 (P=8.0 × 10(-11) discovery group; P=0.00031 replication group), is intergenic between HLA-DRA and BTNL2. Exploratory immunohistochemical analysis of HLA-DRA and BTNL2 expression in papulopustular rosacea lesions from six individuals, including one with the rs763035 variant, revealed staining in the perifollicular inflammatory infiltrate of rosacea for both proteins. In addition, three HLA alleles, all MHC class II proteins, were significantly associated with rosacea in the discovery group and confirmed in the replication group: HLA-DRB1*03:01 (P=1.0 × 10(-8) discovery group; P=4.4 × 10(-6) replication group), HLA-DQB1*02:01 (P=1.3 × 10(-8) discovery group; P=7.2 × 10(-6) replication group), and HLA-DQA1*05:01 (P=1.4 × 10(-8) discovery group; P=7.6 × 10(-6) replication group). Collectively, the gene variants identified in this study support the concept of a genetic component for rosacea, and provide candidate targets for future studies to better understand and treat rosacea. PMID:25695682

  18. Genetics of Coronary Artery Disease in Taiwan: A Cardiometabochip Study by the Taichi Consortium

    PubMed Central

    Juang, Jyh-Ming; Guo, Xiuqing; Wang, Tzung-Dau; Kim, Eric T.; Lee, Wen-Jane; Absher, Devin; Chiu, Yen-Feng; Hsu, Chih-Cheng; Chuang, Lee-Ming; Quertermous, Thomas; Hsiung, Chao A.; Rotter, Jerome I.; Sheu, Wayne H.-H.; Chen, Yii-Der Ida; Taylor, Kent D.

    2016-01-01

    By means of a combination of genome-wide and follow-up studies, recent large-scale association studies of populations of European descent have now identified over 46 loci associated with coronary artery disease (CAD). As part of the TAICHI Consortium, we have collected and genotyped 8556 subjects from Taiwan, comprising 5423 controls and 3133 cases with coronary artery disease, for 9087 CAD SNPs using the CardioMetaboChip. We applied penalized logistic regression to ascertain the top SNPs that contribute together to CAD susceptibility in Taiwan. We observed that the 9p21 locus contributes to CAD at the level of genome-wide significance (rs1537372, with the presence of C, the major allele, the effect estimate is -0.216, standard error 0.033, p value 5.8x10-10). In contrast to a previous report, we propose that the 9p21 locus is a single genetic contribution to CAD in Taiwan because: 1) the penalized logistic regression and the follow-up conditional analysis suggested that rs1537372 accounts for all of the CAD association in 9p21, and 2) the high linkage disequilibrium observed for all associated SNPs in 9p21. We also observed evidence for the following loci at a false discovery rate >5%: SH2B3, ADAMTS7, PHACTR1, GGCX, HTRA1, COL4A1, and LARP6-LRRC49. We also took advantage of the fact that penalized methods are an efficient approach to search for gene-by-gene interactions, and observed that two-way interactions between the PHACTR1 and ADAMTS7 loci and between the SH2B3 and COL4A1 loci contribute to CAD risk. Both the similarities and differences between the significance of these loci when compared with significance of loci in studies of populations of European descent underscore the fact that further genetic association of studies in additional populations will provide clues to identify the genetic architecture of CAD across all populations worldwide. PMID:26982883

  19. Developing Exon-Primed Intron-Crossing (EPIC) markers for population genetic studies in three Aedes disease vectors.

    PubMed

    White, Vanessa Linley; Endersby, Nancy Margaret; Chan, Janice; Hoffmann, Ary Anthony; Weeks, Andrew Raymond

    2015-03-01

    Aedes aegypti, Aedes notoscriptus, and Aedes albopictus are important vectors of many arboviruses implicated in human disease such as dengue fever. Genetic markers applied across vector species can provide important information on population structure, gene flow, insecticide resistance, and taxonomy, however, robust microsatellite markers have proven difficult to develop in these species and mosquitoes generally. Here we consider the utility and transferability of 15 Ribosome protein (Rp) Exon-Primed Intron-Crossing (EPIC) markers for population genetic studies in these 3 Aedes species. Rp EPIC markers designed for Ae. aegypti also successfully amplified populations of the sister species, Ae. albopictus, as well as the distantly related species, Ae. notoscriptus. High SNP and good indel diversity in sequenced alleles plus support for amplification of the same regions across populations and species were additional benefits of these markers. These findings point to the general value of EPIC markers in mosquito population studies.

  20. Experimental study of enhanced heat transfer by addition of CuO nanoparticle

    NASA Astrophysics Data System (ADS)

    Jesumathy, Stella; Udayakumar, M.; Suresh, S.

    2012-06-01

    An energy storage system has been designed to study the thermal characteristics of paraffin wax with an embedded nano size copper oxide (CuO) particle. This paper presents studies conducted on phase transition times, heat fraction as well as heat transfer characteristics of paraffin wax as phase change material (PCM) embedded with CuO nanoparticles. 40 nm mean size CuO particles of 2, 5 and 10% by weight were dispersed in PCM for this study. Experiments were performed on a heat exchanger with 1.5-10 l/min of heat transfer fluid (HTF) flow. Time-based variations of the temperature distributions are revealed from the results of observations of melting and solidification curves. The results strongly suggested that the thermal conductivity enhances 6, 6.7 and 7.8% in liquid state and in dynamic viscosity it enhances by 5, 14 and 30% with increasing mass fraction of the CNEPs. The thermal conductivity ratio of the composites can be augmented by a factor up to 1.3. The heat transfer coefficient during solidification increased about 78% for the maximum flow rate. The analysis of experimental results reveals that the addition of copper oxide nanoparticles to the paraffin wax enhances both the conduction and natural convection very effectively in composites and in paraffin wax. The paraffin wax-based composites have great potential for energy storage applications like industrial waste heat recovery, solar thermal applications and solar based dynamic space power generation with optimal fraction of copper oxide nanoparticles.

  1. Increased Risk of Additional Cancers Among Patients with Gastrointestinal Stromal Tumors: A Population-Based Study

    PubMed Central

    Murphy, James D.; Ma, Grace L.; Baumgartner, Joel M.; Madlensky, Lisa; Burgoyne, Adam M.; Tang, Chih-Min; Martinez, Maria Elena; Sicklick, Jason K.

    2015-01-01

    Purpose Most gastrointestinal stromal tumors (GIST) are considered non-hereditary or sporadic. However, single-institution studies suggest that GIST patients develop additional malignancies with increased frequencies. We hypothesized that we could gain greater insight into possible associations between GIST and other malignancies using a national cancer database inquiry. Methods Patients diagnosed with GIST (2001–2011) in the Surveillance, Epidemiology, and End Results database were included. Standardized prevalence ratios (SPRs) and standardized incidence ratios (SIRs) were used to quantify cancer risks incurred by GIST patients before and after GIST diagnoses, respectively, when compared with the general U.S. population. Results Of 6,112 GIST patients, 1,047 (17.1%) had additional cancers. There were significant increases in overall cancer rates: 44% (SPR=1.44) before diagnosis and 66% (SIR=1.66) after GIST diagnoses. Malignancies with significantly increased occurrence both before/after diagnoses included other sarcomas (SPR=5.24/SIR=4.02), neuroendocrine-carcinoid tumors (SPR=3.56/SIR=4.79), non-Hodgkin’s lymphoma (SPR=1.69/SIR=1.76), and colorectal adenocarcinoma (SPR=1.51/SIR=2.16). Esophageal adenocarcinoma (SPR=12.0), bladder adenocarcinoma (SPR=7.51), melanoma (SPR=1.46), and prostate adenocarcinoma (SPR=1.20) were significantly more common only before GIST. Ovarian carcinoma (SIR=8.72), small intestine adenocarcinoma (SIR=5.89), papillary thyroid cancer (SIR=5.16), renal cell carcinoma (SIR=4.46), hepatobiliary adenocarcinomas (SIR=3.10), gastric adenocarcinoma (SIR=2.70), pancreatic adenocarcinoma (SIR=2.03), uterine adenocarcinoma (SIR=1.96), non-small cell lung cancer (SIR=1.74), and transitional cell carcinoma of the bladder (SIR=1.65) were significantly more common only after GIST. Conclusion This is the first population-based study to characterize the associations and temporal relationships between GIST and other cancers, both by site and

  2. 78 FR 68461 - Guidance for Industry: Studies To Evaluate the Utility of Anti-Salmonella Chemical Food Additives...