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Sample records for genetically determined measures

  1. Genetic modification and genetic determinism

    PubMed Central

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

  2. Genetic modification and genetic determinism.

    PubMed

    Resnik, David B; Vorhaus, Daniel B

    2006-06-26

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  3. Measured dose to ovaries and testes from Hodgkin's fields and determination of genetically significant dose

    SciTech Connect

    Niroomand-Rad, A.; Cumberlin, R. )

    1993-03-15

    The purpose of this study was to determine the genetically significant dose from therapeutic radiation exposure with Hodgkin's fields by estimating the doses to ovaries and testes. Phantom measurements were performed to verify estimated doses to ovaries and testes from Hodgkin's fields. Thermoluminescent LiF dosimeters (TLD-100) of 1 x 3 x 3 mm[sup 3] dimensions were embedded in phantoms and exposed to standard mantle and paraaortic fields using Co-60, 4 MV, 6 MV, and 10 MV photon beams. The results show that measured doses to ovaries and testes are about two to five times higher than the corresponding graphically estimated doses for Co-60 and 4 MVX photon beams as depicted in ICRP publication 44. In addition, the measured doses to ovaries and testes are about 30% to 65% lower for 10 MV photon beams than for their corresponding Co-60 photon beams. The genetically significant dose from Hodgkin's treatment (less than 0.01 mSv) adds about 4% to the genetically significant dose contribution to medical procedures and adds less than 1% to the genetically significant dose from all sources. Therefore, the consequence to society is considered to be very small. The consequences for the individual patient are, likewise, small. 28 refs., 3 figs., 5 tabs.

  4. Determination of human skin optical properties from spectrophotometric measurements based on optimization by genetic algorithms.

    PubMed

    Zhang, Rong; Verkruysse, Wim; Choi, Bernard; Viator, John A; Jung, Byungjo; Svaasand, Lars O; Aguilar, Guillermo; Nelson, J Stuart

    2005-01-01

    We present an initial study on applying genetic algorithms (GA) to retrieve human skin optical properties using visual reflectance spectroscopy (VRS). A three-layered skin model consisting of 13 parameters is first used to simulate skin and, through an analytical model based on optical diffusion theory, we study their independent effects on the reflectance spectra. Based on a preliminary analysis, nine skin parameters are chosen to be fitted by GA. The fitting procedure is applied first on simulated reflectance spectra with added white noise, and then on measured spectra from normal and port wine stain (PWS) human skin. A normalized residue of less than 0.005 is achieved for simulated spectra. In the case of measured spectra from human skin, the normalized residue is less than 0.01. Comparisons between applying GA and manual iteration (MI) fitting show that GA performed much better than the MI fitting method and can easily distinguish melanin concentrations for different skin types. Furthermore, the GA approach can lead to a reasonable understanding of the blood volume fraction and other skin properties, provided that the applicability of the diffusion approximation is satisfied.

  5. Determining causes of genetic isolation in a large carnivore (Ursus americanus) population to direct contemporary conservation measures

    PubMed Central

    Obbard, Martyn E.; Harnden, Matthew; McConnell, Sabine; Howe, Eric J.; Burrows, Frank G.; White, Bradley N.; Kyle, Christopher J.

    2017-01-01

    The processes leading to genetic isolation influence a population’s local extinction risk, and should thus be identified before conservation actions are implemented. Natural or human-induced circumstances can result in historical or contemporary barriers to gene flow and/or demographic bottlenecks. Distinguishing between these hypotheses can be achieved by comparing genetic diversity and differentiation in isolated vs. continuous neighboring populations. In Ontario, American black bears (Ursus americanus) are continuously distributed, genetically diverse, and exhibit an isolation-by-distance structuring pattern, except on the Bruce Peninsula (BP). To identify the processes that led to the genetic isolation of BP black bears, we modelled various levels of historical and contemporary migration and population size reductions using forward simulations. We compared simulation results with empirical genetic indices from Ontario black bear populations under different levels of geographic isolation, and conducted additional simulations to determine if translocations could help achieve genetic restoration. From a genetic standpoint, conservation concerns for BP black bears are warranted because our results show that: i) a recent demographic bottleneck associated with recently reduced migration best explains the low genetic diversity on the BP; and ii) under sustained isolation, BP black bears could lose between 70% and 80% of their rare alleles within 100 years. Although restoring migration corridors would be the most effective method to enhance long-term genetic diversity and prevent inbreeding, it is unrealistic to expect connectivity to be re-established. Current levels of genetic diversity could be maintained by successfully translocating 10 bears onto the peninsula every 5 years. Such regular translocations may be more practical than landscape restoration, because areas connecting the peninsula to nearby mainland black bear populations have been irreversibly modified

  6. Determining causes of genetic isolation in a large carnivore (Ursus americanus) population to direct contemporary conservation measures.

    PubMed

    Pelletier, Agnès; Obbard, Martyn E; Harnden, Matthew; McConnell, Sabine; Howe, Eric J; Burrows, Frank G; White, Bradley N; Kyle, Christopher J

    2017-01-01

    The processes leading to genetic isolation influence a population's local extinction risk, and should thus be identified before conservation actions are implemented. Natural or human-induced circumstances can result in historical or contemporary barriers to gene flow and/or demographic bottlenecks. Distinguishing between these hypotheses can be achieved by comparing genetic diversity and differentiation in isolated vs. continuous neighboring populations. In Ontario, American black bears (Ursus americanus) are continuously distributed, genetically diverse, and exhibit an isolation-by-distance structuring pattern, except on the Bruce Peninsula (BP). To identify the processes that led to the genetic isolation of BP black bears, we modelled various levels of historical and contemporary migration and population size reductions using forward simulations. We compared simulation results with empirical genetic indices from Ontario black bear populations under different levels of geographic isolation, and conducted additional simulations to determine if translocations could help achieve genetic restoration. From a genetic standpoint, conservation concerns for BP black bears are warranted because our results show that: i) a recent demographic bottleneck associated with recently reduced migration best explains the low genetic diversity on the BP; and ii) under sustained isolation, BP black bears could lose between 70% and 80% of their rare alleles within 100 years. Although restoring migration corridors would be the most effective method to enhance long-term genetic diversity and prevent inbreeding, it is unrealistic to expect connectivity to be re-established. Current levels of genetic diversity could be maintained by successfully translocating 10 bears onto the peninsula every 5 years. Such regular translocations may be more practical than landscape restoration, because areas connecting the peninsula to nearby mainland black bear populations have been irreversibly modified

  7. Molecular genetics of sex determination.

    PubMed

    Cotinot, Corinne; Pailhoux, Eric; Jaubert, Francis; Fellous, Marc

    2002-08-01

    In humans, the choice between male or female development is genetically determined. Sex determination take place when the bipotential embryonic gonad becomes either testis or ovary. This process is directed by genes that have been discovered by genetic analysis of sex-reversed patients and confirmed by knockout experiments in mice. The testis-determining pathway is better known than the ovary pathway. SRY, a gene located on the Y chromosome, triggers a complex genetic cascade leading to testicular differentiation. In this cascade, two genes play a crucial role in male differentiation, SOX9 and FGF9, which contribute to testicular cord formation. However, only a minority of 46,XY sex-reversed patients can be explained by mutations in known genes such as SRY, SOX9, WTI, and SF1, suggesting that other genes influencing sex determination are yet to be discovered. In females, some rare genes that induce ovarian failure or female-to-male sex reversal have been found through gene-targeted inactivation in mice or positional cloning of mutations in humans and goats. In both sexes, genetic analysis of sex-reversed individuals (XX males, XX and XY hermaphrodites, and XY with complete or partial dysgenesis) remains an approach of choice to isolate new genes involved in sex determination.

  8. Genetic determinants of plasma triglycerides

    PubMed Central

    Johansen, Christopher T.; Kathiresan, Sekar; Hegele, Robert A.

    2011-01-01

    Plasma triglyceride (TG) concentration is reemerging as an important cardiovascular disease risk factor. More complete understanding of the genes and variants that modulate plasma TG should enable development of markers for risk prediction, diagnosis, prognosis, and response to therapies and might help specify new directions for therapeutic interventions. Recent genome-wide association studies (GWAS) have identified both known and novel loci associated with plasma TG concentration. However, genetic variation at these loci explains only ∼10% of overall TG variation within the population. As the GWAS approach may be reaching its limit for discovering genetic determinants of TG, alternative genetic strategies, such as rare variant sequencing studies and evaluation of animal models, may provide complementary information to flesh out knowledge of clinically and biologically important pathways in TG metabolism. Herein, we review genes recently implicated in TG metabolism and describe how some of these genes likely modulate plasma TG concentration. We also discuss lessons regarding plasma TG metabolism learned from various genomic and genetic experimental approaches. Treatment of patients with moderate to severe hypertriglyceridemia with existing therapies is often challenging; thus, gene products and pathways found in recent genetic research studies provide hope for development of more effective clinical strategies. PMID:21041806

  9. Genetic determinants of glucose homeostasis.

    PubMed

    Barker, Adam; Langenberg, Claudia; Wareham, Nicholas J

    2012-04-01

    Type 2 diabetes is a complex metabolic disorder characterised by varying degrees of impairment in insulin secretion and resistance to the action of insulin. Considerable progress has been made recently in understanding the genetic determinants of diabetes. A logical next step is to describe how these variants relate to the underlying pathophysiological processes that lead to diabetes as this may provide insights into pathways to disease. These quantitative traits are, of course, of direct interest in themselves and a growing literature is now emerging on the genetic determinants of insulin secretion and insulin resistance. This review article focuses on describing the complex associations between type 2 diabetes risk variants and quantitative glycaemic traits and the relationship between variants initially discovered in association studies of these traits and risk of type 2 diabetes.

  10. Is health determined by genetic code or zip code? Measuring the health of groups and improving population health.

    PubMed

    Slade-Sawyer, Penelope

    2014-01-01

    Maintaining the optimal health of all North Carolinians is integral to the overall well-being of the state. It is not enough to have policies, initiatives, and reforms created and led by experts in health and health care. To move towards a culture that appreciates and promotes optimal population health, we also need assistance from other arenas. Data continue to suggest that domains such as education, housing, and income may be just as important, if not more important, than determinants that are usually associated with health outcomes. Thus North Carolina's leaders, professionals, and policy makers need to adopt shared responsibility for our population's health by taking a health-in-all-policies stance. Research to expand our understanding of individual and group actions that contribute to health outcomes, collaboration of partners across diverse sectors to implement evidence-based initiatives, and creative thinking and planning for future workforce needs are a few important actions. Together, these efforts can help to shift our long-standing focus on "disease care" to an upstream approach that ultimately reduces health care burdens and improves population health.

  11. How Darwinian reductionism refutes genetic determinism.

    PubMed

    Rosoff, Philip M; Rosenberg, Alex

    2006-03-01

    Genetic determinism labels the morally problematical claim that some socially significant traits, traits we care about, such as sexual orientation, gender roles, violence, alcoholism, mental illness, intelligence, are largely the results of the operation of genes and not much alterable by environment, learning or other human intervention. Genetic determinism does not require that genes literally fix these socially significant traits, but rather that they constrain them within narrow channels beyond human intervention. In this essay we analyze genetic determinism in light of what is now known about the inborn error of metabolism phenylketonuria (PKU), which has for so long been the poster child 'simple' argument in favor of some form of genetic determinism. We demonstrate that this case proves the exact opposite of what it has been proposed to support and provides a strong refutation of genetic determinism in all its guises.

  12. Human genetic determinants of dengue virus susceptibility.

    PubMed

    Coffey, Lark L; Mertens, Eva; Brehin, Anne-Claire; Fernandez-Garcia, Maria Dolores; Amara, Ali; Després, Philippe; Sakuntabhai, Anavaj

    2009-02-01

    Dengue virus (DENV) is an emerging mosquito-borne pathogen that produces significant morbidity worldwide resulting in an estimated 50-100 million infections annually. DENV causes a spectrum of illness ranging from inapparent infection to life-threatening hemorrhagic fever and shock. The varied DENV disease outcome is determined by complex interactions between immunopathologic, viral, and human genetic factors. This review summarizes these interactions with a focus on human genetic determinants of DENV susceptibility, including human leukocyte antigens, blood type, and single nucleotide polymorphisms in immune response genes that have been associated with DENV disease. We also discuss other factors related to DENV outcome including viral genetic determinants, age, ethnicity, and nutritional status as they relate to DENV susceptibility. We emphasize the need for functional genetics studies to complement association-based data and we call for controlled study designs and standard clinical DENV disease definitions that will strengthen conclusions based on human genetic DENV studies.

  13. Genetically Determined Height and Coronary Artery Disease

    PubMed Central

    Nelson, C.P.; Hamby, S.E.; Saleheen, D.; Hopewell, J.C.; Zeng, L.; Assimes, T.L.; Kanoni, S.; Willenborg, C.; Burgess, S.; Amouyel, P.; Anand, S.; Blankenberg, S.; Boehm, B.O.; Clarke, R.J.; Collins, R.; Dedoussis, G.; Farrall, M.; Franks, P.W.; Groop, L.; Hall, A.S.; Hamsten, A.; Hengstenberg, C.; Hovingh, G. Kees; Ingelsson, E.; Kathiresan, S.; Kee, F.; König, I.R.; Kooner, J.; Lehtimäki, T.; März, W.; McPherson, R.; Metspalu, A.; Nieminen, M.S.; O’Donnell, C.J.; Palmer, C.N.A.; Peters, A.; Perola, M.; Reilly, M.P.; Ripatti, S.; Roberts, R.; Salomaa, V.; Shah, S.H.; Schreiber, S.; Siegbahn, A.; Thorsteinsdottir, U.; Veronesi, G.; Wareham, N.; Willer, C.J.; Zalloua, P.A.; Erdmann, J.; Deloukas, P.; Watkins, H.; Schunkert, H.; Danesh, J.; Thompson, J.R.; Samani, N.J.

    2015-01-01

    BACKGROUND The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. CONCLUSIONS There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. PMID:25853659

  14. Genetic and Environmental Determinants of Stress Responding

    PubMed Central

    Clarke, Toni-Kim; Nymberg, Charlotte; Schumann, Gunter

    2012-01-01

    The risk for alcohol dependence throughout development is determined by both genetic and environmental factors. Genetic factors that are thought to modulate this risk act on neurobiological pathways regulating reward, impulsivity, and stress responses. For example, genetic variations in pathways using the brain signaling molecule (i.e., neurotransmitter) dopamine, which likely mediate alcohol’s rewarding effects, and in two hormonal systems involved in the stress response (i.e., the hypothalamic–pituitary–adrenal axis and the corticotropin-releasing factor system) affect alcoholism risk. This liability is modified further by exposure to environmental risk factors, such as environmental stress and alcohol use itself, and the effects of these factors may be enhanced in genetically vulnerable individuals. The transition from alcohol use to dependence is the result of complex interactions of genes, environment, and neurobiology, which fluctuate throughout development. Therefore, the relevant genetic and environmental risk factors may differ during the different stages of alcohol initiation, abuse, and dependence. The complex interaction of these factors is yet to be fully elucidated, and translational studies, ranging from animal studies to research in humans, and well-characterized longitudinal studies are necessary to further understand the development of alcohol dependence. PMID:23584114

  15. Nutritional and Genetic Determinants of Early Puberty

    DTIC Science & Technology

    2006-06-01

    5 weekly sessions of moderate-to-vigorous physical activity and #14 h of weekly screen time (TV, video viewing, computer/ video game use) as...of genetic variants and nutrition in early maturation, obesity patterns and bone density. 7 REFERENCES 1. Henderson BE, Ross RK, Pike MC...physical activity, and energy intake. In a multivariate analysis focusing on the trunk:peripheral fat ratio, this measure of central obesity was

  16. Genetic markers cannot determine Jewish descent

    PubMed Central

    Falk, Raphael

    2015-01-01

    Humans differentiate, classify, and discriminate: social interaction is a basic property of human Darwinian evolution. Presumably inherent differential physical as well as behavioral properties have always been criteria for identifying friend or foe. Yet, biological determinism is a relatively modern term, and scientific racism is, oddly enough, largely a consequence or a product of the Age of Enlightenment and the establishment of the notion of human equality. In recent decades ever-increasing efforts and ingenuity were invested in identifying Biblical Israelite genotypic common denominators by analysing an assortment of phenotypes, like facial patterns, blood types, diseases, DNA-sequences, and more. It becomes overwhelmingly clear that although Jews maintained detectable vertical genetic continuity along generations of socio-religious-cultural relationship, also intensive horizontal genetic relations were maintained both between Jewish communities and with the gentile surrounding. Thus, in spite of considerable consanguinity, there is no Jewish genotype to identify. PMID:25653666

  17. Alphaviruses: Population genetics and determinants of emergence

    PubMed Central

    Weaver, Scott C.; Winegar, Richard; Manger, Ian D.; Forrester, Naomi L.

    2013-01-01

    Alphaviruses are responsible for several medically important emerging diseases and are also significant veterinary pathogens. Due to the aerosol infectivity of some alphaviruses and their ability to cause severe, sometimes fatal neurologic diseases, they are also of biodefense importance. This review discusses the ecology, epidemiology and molecular virology of the alphaviruses, then focuses on three of the most important members of the genus: Venezuelan and eastern equine encephalitis and chikungunya viruses, with emphasis on their genetics and emergence mechanisms, and how current knowledge as well as gaps influence our ability to detect and determine the source of both natural outbreaks and potential use for bioterrorism. This article is one of a series in Antiviral Research on the genetic diversity of emerging viruses. PMID:22522323

  18. Sex determination: where environment and genetics meet.

    PubMed

    Crews, David

    2003-01-01

    In mammals and birds the genetic constitution established at the time of fertilization determines the type of gonad that develops, whereas in all crocodilians and many turtles it is the temperature experienced during the mid-trimester of embryogenesis that initiates gonadal differentiation. Research with the red-eared slider suggests considerable conservation in the genetic cascades that underlie the sex determination process in vertebrates and, further, that the patterns of expression of these genes appear to reflect phylogenetic relationships, with turtles being more similar to mammals than they are to birds and crocodilians. After the determination and differentiation of an individual's gonadal sex, epigenetic forces shape those morphological, physiological, and behavioral traits that characterize each individual's unique sexuality. Research with the leopard gecko thus relates to the fundamental question of what factors determine individual variability, particularly as it relates to sexually dimorphic behaviors. Taken together, this research illustrates how sexuality depends on sex, but sex should not be confused with sexuality. That is, sex is merely a means of categorizing individuals or gonads, whereas sexuality serves as a descriptor of concordant traits each of which is typically sexually dimorphic in its expression.

  19. Weight Stigma Reduction and Genetic Determinism

    PubMed Central

    Hilbert, Anja

    2016-01-01

    One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of—and responsibility for—obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1) develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2) evaluate this intervention in the general population (N = 128) and determine mechanisms of change. The results showed (1) decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2) decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention’s gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity. PMID:27631384

  20. Weight Stigma Reduction and Genetic Determinism.

    PubMed

    Hilbert, Anja

    2016-01-01

    One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of-and responsibility for-obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1) develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2) evaluate this intervention in the general population (N = 128) and determine mechanisms of change. The results showed (1) decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2) decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention's gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity.

  1. Genetic Algorithm for Initial Orbit Determination with Too Short Arc

    NASA Astrophysics Data System (ADS)

    Xin-ran, Li; Xin, Wang

    2017-01-01

    A huge quantity of too-short-arc (TSA) observational data have been obtained in sky surveys of space objects. However, reasonable results for the TSAs can hardly be obtained with the classical methods of initial orbit determination (IOD). In this paper, the IOD is reduced to a two-stage hierarchical optimization problem containing three variables for each stage. Using the genetic algorithm, a new method of the IOD for TSAs is established, through the selections of the optimized variables and the corresponding genetic operators for specific problems. Numerical experiments based on the real measurements show that the method can provide valid initial values for the follow-up work.

  2. On the Measurement of Genetic Interactions

    NASA Astrophysics Data System (ADS)

    de Jong, Edwin; Franke, Lude; Siebes, Arno

    2007-09-01

    Reverse-engineering of genetic interaction networks is one of the primary goals of current bio-informatics research. Accurate knowledge of these networks is of crucial concern for both biological and medical understanding of biological function, and is relevant to the investigation of diseases with genetic origin. In this study, five different measures of genetic interactions are compared with regard to their ability to detect genetic interactions. The results are validated by means of comparison with five databases of known interactions: KEGG, Reactome, BIND, HPRD, and IntAct. A striking finding is that there are substantial differences between the interaction databases with regard to the correspondence with interactions found from gene expression data. These difference overshadow the relatively minor differences between the different interaction measures. These results lead to two conclusions. First, the choice between different interaction measures does not appear do be a crucial factor, given the relatively minor impact of this choice compared to the differences between the results obtained with different interaction databases. Moreover, these findings suggest that gene expression by itself is insufficient as a data source for the detection of genetic interactions. This implies that the identification of other data sources and the integration of multiple data sources are vital issues in improving the quality of bio-informatics approaches to detect genetic interactions.

  3. Optical Constants Determined by Genetic Algorithms

    NASA Astrophysics Data System (ADS)

    Smith, David Y.; Karstens, William; Malghani, Shaheen M.

    2005-03-01

    A recent determination^a of the complex refractive index, n(λ) + i κ(λ), of porous silicon employed a genetic^b algorithm to fit the Fresnel equations to reflectance spectra. The procedure appeared to involve more unknowns than explicit equations available for fitting, an indeterminate problem. However, the index values obtained were reasonable, and predicted the properties of porous-silicon multilayes. We have traced this success to the interpolation formulas used for n and κ in the fitting algorithm. They amount to an implicit optical-constant model with the de facto assumption of an analytic complex index that can be approximated by a cubic polynomial. Our analysis suggests the procedure can be improved by explicitly using a more appropriate model, e.g., one that uses wave number as the expansion variable and requires that n and κ be even and odd functions of λ, respectively. ^a V. Torres-Costa, R. J. Mart'in-Palma, and J. M. Mart'inez-Duart, J. Appl. Phys. 96, 4197 (2004). ^b D. E. Goldberg, Genetic Algorithms in Search, Optimization and Machine Learning (Addison-Wesley, Reading, 1989).

  4. Same genetic components underlie different measures of sweet taste preference.

    PubMed

    Keskitalo, Kaisu; Tuorila, Hely; Spector, Tim D; Cherkas, Lynn F; Knaapila, Antti; Silventoinen, Karri; Perola, Markus

    2007-12-01

    Sweet taste preferences are measured by several often correlated measures. We examined the relative proportions of genetic and environmental effects on sweet taste preference indicators and their mutual correlations. A total of 663 female twins (324 complete pairs, 149 monozygous and 175 dizygous pairs) aged 17-80 y rated the liking and intensity of a 20% (wt/vol) sucrose solution, reported the liking and the use-frequency of 6 sweet foods (sweet desserts, sweets, sweet pastry, ice cream, hard candy, and chocolate), and completed a questionnaire on cravings of sweet foods. The estimated contributions of genetic factors, environmental factors shared by a twin pair, and environmental factors unique to each twin individual to the variance and covariance of the traits were obtained with the use of linear structural equation modeling. Approximately half of the variation in liking for sweet solution and liking and use-frequency of sweet foods (49-53%) was explained by genetic factors, whereas the rest of the variation was due to environmental factors unique to each twin individual. Sweet taste preference-related traits were correlated. Tetravariate modeling showed that the correlation between liking for the sweet solution and liking for sweet foods was due to genetic factors (genetic r = 0.27). Correlations between liking, use-frequency, and craving for sweet foods were due to both genetic and unshared environmental factors. Detailed information on the associations between preference measures is an important intermediate goal in the determination of the genetic components affecting sweet taste preferences.

  5. Genetically determined phenotype covariation networks control bone strength.

    PubMed

    Jepsen, Karl J; Courtland, Hayden-William; Nadeau, Joseph H

    2010-07-01

    To identify genes affecting bone strength, we studied how genetic variants regulate components of a phenotypic covariation network that was previously shown to accurately characterize the compensatory trait interactions involved in functional adaptation during growth. Quantitative trait loci (QTLs) regulating femoral robustness, morphologic compensation, and mineralization (tissue quality) were mapped at three ages during growth using AXB/BXA Recombinant Inbred (RI) mouse strains and adult B6-i(A) Chromosome Substitution Strains (CSS). QTLs for robustness were identified on chromosomes 8, 12, 18, and 19 and confirmed at all three ages, indicating that genetic variants established robustness postnatally without further modification. A QTL for morphologic compensation, which was measured as the relationship between cortical area and body weight, was identified on chromosome 8. This QTL limited the amount of bone formed during growth and thus acted as a setpoint for diaphyseal bone mass. Additional QTLs were identified from the CSS analysis. QTLs for robustness and morphologic compensation regulated bone structure independently (ie, in a nonpleiotropic manner), indicating that each trait may be targeted separately to individualize treatments aiming to improve strength. Multiple regression analyses showed that variation in morphologic compensation and tissue quality, not bone size, determined femoral strength relative to body weight. Thus an individual inheriting slender bones will not necessarily inherit weak bones unless the individual also inherits a gene that impairs compensation. This systems genetic analysis showed that genetically determined phenotype covariation networks control bone strength, suggesting that incorporating functional adaptation into genetic analyses will advance our understanding of the genetic basis of bone strength.

  6. INNER EAR EMBRYOGENESIS: GENETIC AND ENVIRONMENTAL DETERMINANTS

    EPA Science Inventory

    The anatomy and developmental molecular genetics of the inner ear from establishment of the otic placode to formation of the definitive cochlea and vestibular apparatus will be reviewed and the complex 3-D structural changes that shape the developing inner ear will be illustrated...

  7. INNER EAR EMBRYOGENESIS: GENETIC AND ENVIRONMENTAL DETERMINANTS

    EPA Science Inventory

    The anatomy and developmental molecular genetics of the inner ear from establishment of the otic placode to formation of the definitive cochlea and vestibular apparatus will be reviewed and the complex 3-D structural changes that shape the developing inner ear will be illustrated...

  8. Genetic Diseases and Genetic Determinism Models in French Secondary School Biology Textbooks

    ERIC Educational Resources Information Center

    Castera, Jeremy; Bruguiere, Catherine; Clement, Pierre

    2008-01-01

    The presentation of genetic diseases in French secondary school biology textbooks is analysed to determine the major conceptions taught in the field of human genetics. References to genetic diseases, and the processes by which they are explained (monogeny, polygeny, chromosomal anomaly and environmental influence) are studied in recent French…

  9. Genetic Diseases and Genetic Determinism Models in French Secondary School Biology Textbooks

    ERIC Educational Resources Information Center

    Castera, Jeremy; Bruguiere, Catherine; Clement, Pierre

    2008-01-01

    The presentation of genetic diseases in French secondary school biology textbooks is analysed to determine the major conceptions taught in the field of human genetics. References to genetic diseases, and the processes by which they are explained (monogeny, polygeny, chromosomal anomaly and environmental influence) are studied in recent French…

  10. [Elucidation of key genes in sex determination in genetics teaching].

    PubMed

    Li, Meng; He, Zhumei

    2014-06-01

    Sex is an important and complex feature of organisms, which is controlled by the genetic and environmental factors. The genetic factors, i.e., genes, are vital in sex determination. However, not all the related genes play the same roles, and some key genes play a vital role in the sex determination and differentiation. With the development of the modern genetics, a great progress on the key genes has been made in sex determination. In this review, we summarize the mechanism of sex determination and the strategy of how to study the key genes in sex determination. It will help us to understand the mechanism of sex determination better in the teaching of genetics.

  11. Genetic Essentialism: On the Deceptive Determinism of DNA

    PubMed Central

    Dar-Nimrod, Ilan; Heine, Steven J.

    2012-01-01

    This paper introduces the notion of genetic essentialist biases: cognitive biases associated with essentialist thinking that are elicited when people encounter arguments that genes are relevant for a behavior, condition, or social group. Learning about genetic attributions for various human conditions leads to a particular set of thoughts regarding those conditions: they are more likely to be perceived as a) immutable and determined, b) having a specific etiology, c) homogeneous and discrete, and, d) natural, which can lead to the naturalistic fallacy. There are rare cases of “strong genetic explanation” when such responses to genetic attributions may be appropriate, however people tend to over-weigh genetic attributions compared with competing attributions even in cases of “weak genetic explanation,” which are far more common. Research on people’s understanding of race, gender, sexual orientation, criminality, mental illness and obesity is reviewed through a genetic essentialism lens, highlighting attitudinal, cognitive and behavioral changes that stem from consideration of genetic attributions as bases of these categories. Scientists and media portrayals of genetic discoveries are discussed with respect to genetic essentialism, as is the role that genetic essentialism has played (and continues to play) in various public policies, legislation, scientific endeavors, and ideological movements in recent history. Last, moderating factors and interventions to reduce the magnitude of genetic essentialism are discussed that identify promising directions to explore in order to reduce these biases. PMID:21142350

  12. Genetic essentialism: on the deceptive determinism of DNA.

    PubMed

    Dar-Nimrod, Ilan; Heine, Steven J

    2011-09-01

    This article introduces the notion of genetic essentialist biases: cognitive biases associated with essentialist thinking that are elicited when people encounter arguments that genes are relevant for a behavior, condition, or social group. Learning about genetic attributions for various human conditions leads to a particular set of thoughts regarding those conditions: they are more likely to be perceived as (a) immutable and determined, (b) having a specific etiology, (c) homogeneous and discrete, and (d) natural, which can lead to the naturalistic fallacy. There are rare cases of "strong genetic explanation" when such responses to genetic attributions may be appropriate; however, people tend to overweigh genetic attributions compared with competing attributions even in cases of "weak genetic explanation," which are far more common. The authors reviewed research on people's understanding of race, gender, sexual orientation, criminality, mental illness, and obesity through a genetic essentialism lens, highlighting attitudinal, cognitive, and behavioral changes that stem from consideration of genetic attributions as bases of these categories. Scientific and media portrayals of genetic discoveries are discussed with respect to genetic essentialism, as is the role that genetic essentialism has played (and continues to play) in various public policies, legislation, scientific endeavors, and ideological movements in recent history. Last, moderating factors and interventions to reduce the magnitude of genetic essentialism, which identify promising directions to explore in order to reduce these biases, are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  13. The Resurgence of Genetic Determinism: Is It a Distraction?

    ERIC Educational Resources Information Center

    Jackson, Jacquelyne F.

    1998-01-01

    Argues that there is a wealth of little known but rapidly growing evidence that contradicts the assumptions and claims of genetic determinism. Recent research showing the impacts of child maltreatment and environmental pollutants suggest interventions that might alleviate the problems sometimes attributed to genetic deficiencies. (SLD)

  14. A genetic similarity rule determines arthropod community structure.

    PubMed

    Bangert, R K; Turek, R J; Rehill, B; Wimp, G M; Schweitzer, J A; Allan, G J; Bailey, J K; Martinsen, G D; Keim, P; Lindroth, R L; Whitham, T G

    2006-04-01

    We define a genetic similarity rule that predicts how genetic variation in a dominant plant affects the structure of an arthropod community. This rule applies to hybridizing cottonwood species where plant genetic variation determines plant-animal interactions and structures a dependent community of leaf-modifying arthropods. Because the associated arthropod community is expected to respond to important plant traits, we also tested whether plant chemical composition is one potential intermediate link between plant genes and arthropod community composition. Two lines of evidence support our genetic similarity rule. First, in a common garden experiment we found that trees with similar genetic compositions had similar chemical compositions and similar arthropod compositions. Second, in a wild population, we found a similar relationship between genetic similarity in cottonwoods and the dependent arthropod community. Field data demonstrate that the relationship between genes and arthropods was also significant when the hybrids were analysed alone, i.e. the pattern is not dependent upon the inclusion of both parental species. Because plant-animal interactions and natural hybridization are common to diverse plant taxa, we suggest that a genetic similarity rule is potentially applicable, and may be extended, to other systems and ecological processes. For example, plants with similar genetic compositions may exhibit similar litter decomposition rates. A corollary to this genetic similarity rule predicts that in systems with low plant genetic variability, the environment will be a stronger factor structuring the dependent community. Our findings argue that the genetic composition of a dominant plant can structure higher order ecological processes, thus placing community and ecosystem ecology within a genetic and evolutionary framework. A genetic similarity rule also has important conservation implications because the loss of genetic diversity in one species, especially

  15. Genetic and Epigenetic Determinants in Autoinflammatory Diseases

    PubMed Central

    Álvarez-Errico, Damiana; Vento-Tormo, Roser; Ballestar, Esteban

    2017-01-01

    The concept of autoinflammation has evolved over the past 20 years, beginning with the discovery that mutations in the Mediterranean Fever (MEFV) gene were causative of Familial Mediterranean Fever. Currently, autoinflammatory diseases comprise a wide range of disorders with the common features of recurrent fever attacks, prevalence of hyperreactive innate immune cells, and signs of inflammation that can be systemic or organ specific in the absence of pathogenic infection of autoimmunity. Innate immune cells from the myeloid compartment are the main effectors of uncontrolled inflammation that is caused in great extent by the overproduction of inflammatory cytokines such as IL-1β and IL-18. Defects in several signaling pathways that control innate immune defense, particularly the hyperreactivity of one or more inflammasomes, are at the core of pathologic autoinflammatory phenotypes. Although many of the autoinflammatory syndromes are known to be monogenic, some of them are genetically complex and are impacted by environmental factors. Recently, epigenetic dysregulation has surfaced as an additional contributor to pathogenesis. In the present review, we discuss data that are currently available to describe the contribution of epigenetic mechanisms in autoinflammatory diseases. PMID:28382039

  16. Genetic determinants of virulence - Candida parapsilosis.

    PubMed

    Singaravelu, Kumara; Gácser, Attila; Nosanchuk, Joshua D

    2014-01-01

    The global epidemiology of fungal infections is changing. While overall, Candida albicans remains the most common pathogen; several institutions in Europe, Asia and South America have reported the rapid emergence to predominance of Candida parapsilosis. This mini-review examines the impact of gene deletions achieved in C. parapsilosis that have been published to date. The molecular approaches to gene disruption in C. parapsilosis and the molecularly characterized genes to date are reviewed. Similar to C. albicans, factors influencing virulence in C. parapsilosis include adherence, biofilm formation, lipid metabolism, and secretion of hydrolytic enzymes such as lipases, phospholipases and secreted aspartyl proteinases. Development of a targeted gene deletion method has enabled the identification of several unique aspects of C. parapsilosis genes that play a role in host-pathogen interactions - CpLIP1, CpLIP2, SAPP1a, SAPP1b, BCR1, RBT1, CpFAS2, OLE1, FIT-2. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012).

  17. Does the genetic type of collagen determine fibril structure

    SciTech Connect

    Eikenberry, E.; Brodsky, B.; Cassidy, K.

    1980-10-01

    A number of genetic types of collagen, all triple-helical but with significant variations in their amino acid sequences, have been found and the distribution of these genetic types is tissue specific. For example, tendon is composed only of type I collagen, while cartilage contains largely type II collagen. Skin contains a large amount of type I, but has a significant fraction, approx. 15%, of type III. Each of these types can form fibrils, but it is not known whether they form distinctive fibril structures that are important in determining tissue organization. We are using x-ray diffraction to analyze a variety of tissues with different collagen genetic types to compare the fibril structures and thus investigate whether genetic type is an important determinant of this structure.

  18. Genetic Structure and Potential Environmental Determinants of Local Genetic Diversity in Japanese Honeybees (Apis cerana japonica)

    PubMed Central

    Nagamitsu, Teruyoshi; Yasuda, Mika; Saito-Morooka, Fuki; Inoue, Maki N.; Nishiyama, Mio; Goka, Koichi; Sugiura, Shinji; Maeto, Kaoru; Okabe, Kimiko; Taki, Hisatomo

    2016-01-01

    Declines in honeybee populations have been a recent concern. Although causes of the declines remain unclear, environmental factors may be responsible. We focused on the potential environmental determinants of local populations of wild honeybees, Apis cerana japonica, in Japan. This subspecies has little genetic variation in terms of its mitochondrial DNA sequences, and genetic variations at nuclear loci are as yet unknown. We estimated the genetic structure and environmental determinants of local genetic diversity in nuclear microsatellite genotypes of fathers and mothers, inferred from workers collected at 139 sites. The genotypes of fathers and mothers showed weak isolation by distance and negligible genetic structure. The local genetic diversity was high in central Japan, decreasing toward the peripheries, and depended on the climate and land use characteristics of the sites. The local genetic diversity decreased as the annual precipitation increased, and increased as the proportion of urban and paddy field areas increased. Positive effects of natural forest area, which have also been observed in terms of forager abundance in farms, were not detected with respect to the local genetic diversity. The findings suggest that A. cerana japonica forms a single population connected by gene flow in its main distributional range, and that climate and landscape properties potentially affect its local genetic diversity. PMID:27898704

  19. Genetic determinants of depression: Recent findings and future directions

    PubMed Central

    Dunn, Erin C.; Brown, Ruth C.; Dai, Yael; Rosand, Jonathan; Nugent, Nicole R.; Amstadter, Ananda B.; Smoller, Jordan W.

    2014-01-01

    Depression is one of the most prevalent, disabling, and costly mental health conditions in the United States. One promising avenue for preventing depression and informing its clinical treatment lies in uncovering both the genetic and environmental determinants of the disorder as well as their interaction (i.e. gene-environment intervention; GxE). The overarching goal of this review paper is to translate recent findings from studies of genetic association and GxE related to depression, particularly for readers without in-depth knowledge of genetics or genetic methods. This review is organized into three major sections. In the first section, we summarize what is currently known about the genetic determinants of depression, focusing on findings from genome-wide association studies (GWAS). In the second section, we review findings from studies of GxE, which seek to simultaneously examine the role of genes and exposure to specific environments or experiences in the etiology of depression. In the third section, we describe the challenges to genetic discovery in depression and promising strategies for making progress. PMID:25563565

  20. Measuring Financial Gains from Genetically Superior Trees

    Treesearch

    George Dutrow; Clark Row

    1976-01-01

    Planting genetically superior loblolly pines will probably yield high profits.Forest economists have made computer simulations that predict financial gains expected from a tree improvement program under actual field conditions.

  1. Genetics of human body size and shape: pleiotropic and independent genetic determinants of adiposity.

    PubMed

    Livshits, G; Yakovenko, K; Ginsburg, E; Kobyliansky, E

    1998-01-01

    The present study utilized pedigree data from three ethnically different populations of Kirghizstan, Turkmenia and Chuvasha. Principal component analysis was performed on a matrix of genetic correlations between 22 measures of adiposity, including skinfolds, circumferences and indices. Findings are summarized as follows: (1) All three genetic matrices were not positive definite and the first four factors retained even after exclusion RG > or = 1.0, explained from 88% to 97% of the total additive genetic variation in the 22 trials studied. This clearly emphasizes the massive involvement of pleiotropic gene effects in the variability of adiposity traits. (2) Despite the quite natural differences in pairwise correlations between the adiposity traits in the three ethnically different samples under study, factor analysis revealed a common basic pattern of covariability for the adiposity traits. In each of the three samples, four genetic factors were retained, namely, the amount of subcutaneous fat, the total body obesity, the pattern of distribution of subcutaneous fat and the central adiposity distribution. (3) Genetic correlations between the retained four factors were virtually non-existent, suggesting that several independent genetic sources may be governing the variation of adiposity traits. (4) Variance decomposition analysis on the obtained genetic factors leaves no doubt regarding the substantial familial and (most probably genetic) effects on variation of each factor in each studied population. The similarity of results in the three different samples indicates that the findings may be deemed valid and reliable descriptions of the genetic variation and covariation pattern of adiposity traits in the human species.

  2. Genetic determinants of prepubertal and pubertal growth and development.

    PubMed

    Thomis, Martine A; Towne, Bradford

    2006-12-01

    This article surveys the current general understanding of genetic influences on within- and between-population variation in growth and development in the context of establishing an International Growth Standard for Preadolescent and Adolescent Children. Traditional genetic epidemiologic analysis methods are reviewed, and evidence from family studies for genetic effects on different measures of growth and development is then presented. Findings from linkage and association studies seeking to identify specific genomic locations and allelic variants of genes influencing variation in growth and maturation are then summarized. Special mention is made of the need to study the interactions between genes and environments. At present, specific genes and polymorphisms contributing to variation in growth and maturation are only beginning to be identified. Larger genetic epidemiologic studies are needed in different parts of the world to better explore population differences in gene frequencies and gene-environment interactions. As advances continue to be made in molecular and statistical genetic methods, the genetic architecture of complex processes, including those of growth and development, will become better elucidated. For now, it can only be concluded that although the fundamental genetic underpinnings of the growth and development of children worldwide are likely to be essentially the same, there are also likely to be differences between populations in the frequencies of allelic gene variants that influence growth and maturation and in the nature of gene-environment interactions. This does not necessarily preclude an international growth reference, but it does have important implications for the form that such a reference might ultimately take.

  3. Demographic and genetic consequences of disturbed sex determination.

    PubMed

    Wedekind, Claus

    2017-09-19

    During sex determination, genetic and/or environmental factors determine the cascade of processes of gonad development. Many organisms, therefore, have a developmental window in which their sex determination can be sensitive to, for example, unusual temperatures or chemical pollutants. Disturbed environments can distort population sex ratios and may even cause sex reversal in species with genetic sex determination. The resulting genotype-phenotype mismatches can have long-lasting effects on population demography and genetics. I review the theoretical and empirical work in this context and explore in a simple population model the role of the fitness vyy of chromosomally aberrant YY genotypes that are a consequence of environmentally induced feminization. Low vyy is mostly beneficial for population growth. During feminization, low vyy reduces the proportion of genetic males and hence accelerates population growth, especially at low rates of feminization and at high fitness costs of the feminization itself (i.e. when feminization would otherwise not affect population dynamics much). When sex reversal ceases, low vyy mitigates the negative effects of feminization and can even prevent population extinction. Little is known about vyy in natural populations. The available models now need to be parametrized in order to better predict the long-term consequences of disturbed sex determination.This article is part of the themed issue 'Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies'. © 2017 The Author(s).

  4. Genetic determinants of pathogenesis by feline infectious peritonitis virus.

    PubMed

    Brown, Meredith A

    2011-10-15

    Feline infectious peritonitis (FIP) is a fatal, immune-augmented, and progressive viral disease of cats associated with feline coronavirus (FCoV). Viral genetic determinants specifically associated with FIPV pathogenesis have not yet been discovered. Viral gene signatures in the spike, non-structural protein 3c, and membrane of the coronavirus genome have been shown to often correlate with disease manifestation. An "in vivo mutation transition hypothesis" is widely accepted and postulates that de novo virus mutation occurs in vivo giving rise to virulence. The existence of "distinct circulating avirulent and virulent strains" is an alternative hypothesis of viral pathogenesis. It may be possible that viral dynamics from both hypotheses are at play in the occurrence of FIP. Epidemiologic data suggests that the genetic background of the cat contributes to the manifestation of FIP. Further studies exploring both viral and host genetic determinants of disease in FIP offer specific opportunities for the management of this disease.

  5. Intelligence and Race, Gender, Class: The Fallacy of Genetic Determinism.

    ERIC Educational Resources Information Center

    Belkhir, Jean Ait; Duyme, Michael

    1998-01-01

    Biological determinism represents a pseudo-scientific inquiry that is ultimately used to foster a scientific rationale for the maintenance of classism, racism, and sexism in general. Genetic diversity is an inescapable fact, but it is cultures that human brains have created that most severely limit potential. (SLD)

  6. Intelligence and Race, Gender, Class: The Fallacy of Genetic Determinism.

    ERIC Educational Resources Information Center

    Belkhir, Jean Ait; Duyme, Michael

    1998-01-01

    Biological determinism represents a pseudo-scientific inquiry that is ultimately used to foster a scientific rationale for the maintenance of classism, racism, and sexism in general. Genetic diversity is an inescapable fact, but it is cultures that human brains have created that most severely limit potential. (SLD)

  7. Novel PCR assay for determining the genetic sex of mice.

    PubMed

    McFarlane, L; Truong, V; Palmer, J S; Wilhelm, D

    2013-01-01

    A number of studies require the determination of the genetic sex of mouse embryos before sexual differentiation and/or of mutant mice that display partial or complete sex reversal. The majority of current methods for sexing by PCR involve multiplexing of 2 primer pairs. We have developed a novel sexing PCR using a single primer pair that amplifies fragments from the X and the Y chromosome with a clear size difference between the respective amplicons. This assay provides a rapid and reliable method to identify the genetic sex of mice across different mouse strains.

  8. [Genetic determination of fast plasma glucose concentration and correlation with anthropometric indices].

    PubMed

    Jian, Wei-xia; Su, Qing; Luo, Min

    2009-04-01

    To study the genetic determination of fast plasma glucose (FPG) and correlation with its potential correlated traits, anthropometric measures and blood pressure. Two hundred and eighteen Type 2 diabetes mellitus (T2DM) pedigrees composed of 1383 Chinese Han individuals residing in the East and South-East China were analyzed. Univariate variance decomposition analyses were used to estimate the narrow-sense heritability (h(2)) of FPG, anthropometric indices and blood pressure, and bivariate quantitative genetic analyses were used to estimate the genetic and environmental correlations between FPG and anthropometric measures or blood pressure. We found that FPG, blood pressure and all anthropometric indices except for waist to hip ratio were under significant genetic determination, and the h(2) was from 0.28 to 0.43. We did not find significant genetic and environmental correlation between FPG and anthropometric indices and blood pressure. The present study demonstrated that T2DM, obesity and hypertension were controlled by some genetic factors, and FPG shares little common genetic and environmental factors with obesity-related anthropometric indices and blood pressure in our Chinese sample population.

  9. Measurement process error determination and control

    SciTech Connect

    Everhart, J.

    1992-01-01

    Traditional production processes have required repeated inspection activities to assure product quality. A typical production process follows this pattern: production makes product; production inspects product; Quality Control (QC) inspects product to ensure production inspected properly QC then inspects the product on a different gage to ensure the production gage performance; and QC often inspects on a different day to determine environmental effect. All of these costly inspection activities are due to the lack of confidence in the initial production measurement. The Process Measurement Assurance Program (PMAP) is a method of determining and controlling measurement error in design, development, and production. It is a preventive rather than an appraisal method that determines, improves, and controls the error in the measurement process, including measurement equipment, environment, procedure, and personnel. PMAP expands the concept of the Measurement Assurance Program developed in the 1960's by the National Bureau of Standards (NBS), today known as the National Institute of Standards and Technology (NIST). PMAP acts as a bridge in the gap between the Metrology Laboratory and the production environment by introducing standards (or certified parts) into the production process. These certified control standards are then measured as part of the production process. A control system is present to examine the measurement results of the control standards before, during, and after the manufacturing and measuring of the product. The results of the PMAP control charts determine random uncertainty and systematic (bias from the standard) error of the measurement process. The combinations of these uncertainties determine the margin of error of the measurement process. The total measurement process error is determined by combining the margin of error and the uncertainty in the control standard.

  10. Measurement process error determination and control

    SciTech Connect

    Everhart, J.

    1992-11-01

    Traditional production processes have required repeated inspection activities to assure product quality. A typical production process follows this pattern: production makes product; production inspects product; Quality Control (QC) inspects product to ensure production inspected properly QC then inspects the product on a different gage to ensure the production gage performance; and QC often inspects on a different day to determine environmental effect. All of these costly inspection activities are due to the lack of confidence in the initial production measurement. The Process Measurement Assurance Program (PMAP) is a method of determining and controlling measurement error in design, development, and production. It is a preventive rather than an appraisal method that determines, improves, and controls the error in the measurement process, including measurement equipment, environment, procedure, and personnel. PMAP expands the concept of the Measurement Assurance Program developed in the 1960`s by the National Bureau of Standards (NBS), today known as the National Institute of Standards and Technology (NIST). PMAP acts as a bridge in the gap between the Metrology Laboratory and the production environment by introducing standards (or certified parts) into the production process. These certified control standards are then measured as part of the production process. A control system is present to examine the measurement results of the control standards before, during, and after the manufacturing and measuring of the product. The results of the PMAP control charts determine random uncertainty and systematic (bias from the standard) error of the measurement process. The combinations of these uncertainties determine the margin of error of the measurement process. The total measurement process error is determined by combining the margin of error and the uncertainty in the control standard.

  11. Genetic Determinants of P Wave Duration and PR Segment

    PubMed Central

    Verweij, Niek; Leach, Irene Mateo; van den Boogaard, Malou; van Veldhuisen, Dirk J.; Christoffels, Vincent M.; Hillege, Hans L.; van Gilst, Wiek H.; Barnett, Phil; de Boer, Rudolf A.; van der Harst, Pim

    2014-01-01

    Background The PR interval on the electrocardiogram reflects atrial depolarization and AV nodal delay which can be partially differentiated by P wave duration and PR segment, respectively. GWAS have identified a number of genetic loci for PR interval but it remains to be determined whether this is driven by P wave duration, PR segment or both. Methods and Results We replicated 7 of the 9 known PR interval loci in 16,468 individuals of European ancestry. Four loci were unambiguously associated with PR segment while the others were shared for P wave duration and PR segment. Next, we performed a genome-wide analysis on P wave duration and PR segment separately and identified five novel loci. SNPs in KCND3 (P=8.3×10−11) and FADS2 (P=2.7×10−8) were associated with P wave duration, whereas SNPs near IL17D (P=2.3×10−8), in EFHA1 (P=3.3×10−10) and LRCH1 (P=2.1×10−8) were associated with PR segment. Analysis on DNA elements indicated that genome-wide significant SNPs were enriched at genomic regions suggesting active gene transcription in the human right atrium. Quantitative-PCR showed that genes were significantly higher expressed in the right atrium and AV-node compared to left ventricle (P=5.6×10−6). Conclusions Genetic associations of PR interval appear to be mainly driven by genetic determinants of the PR segment. Some of the PR interval associations are strengthened by a directional consistent effect of genetic determinants of P wave duration. Through genome-wide association we also identified genetic variants specifically associated with P wave duration which might be relevant for cardiac biology. PMID:24850809

  12. Genetic determinants of obesity and related vascular diseases.

    PubMed

    Winter, Yaroslav; Sankowski, Roman; Back, Tobias

    2013-01-01

    Obesity is one of the major risk factors of vascular diseases, and its prevalence is increasing worldwide. In the past decade, progress has been made in the understanding of genetic determinants of obesity and obesity-associated diseases. Genome-wide association studies identified a number of genetic variants associated with obesity. In addition to common variants, FTO and MC4R, new loci, such as TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2, and NEGR1 have been detected. In the past years, abdominal obesity has been shown to be a more important vascular risk factor than the body mass index. In the context of vascular risk assessment, identification of genetic polymorphisms associated with accumulation of visceral fat is of special importance. Some polymorphisms associated with abdominal obesity, such as variants of gene encoding microsomal triglyceride transfer protein, have been already discovered. In this chapter, we provide a review of genetic determinants of obesity and discuss their role in obesity-related vascular diseases.

  13. Expectation and futurity: The remarkable success of genetic determinism.

    PubMed

    Esposito, Maurizio

    2017-04-01

    Genetic determinism is nowadays largely questioned and widely criticized. However, if we look at the history of biology in the last one hundred years, we realize that genetic determinism has always been controversial. Why, then, did it acquire such relevance in the past despite facing longstanding criticism? Through the analysis of some of the ambitious expectations of future scientific applications, this article explores the possibility that part of the historical success of genetic determinism lies in the powerful rhetorical strategies that have connected the germinal matter with alluring bio-technological visions. Indeed, in drawing on the recent perspectives of "expectation studies" in science and technology, it will be shown that there has been an interesting historical relationship between reductionist notions of the gene as a hereditary unit, coded information or functional DNA segment, and startling prophecies of what controlling such an entity might achieve. It will also be suggested that the well-known promissory nature of genomics is far older than the emergence of biotechnology in the 1970s. At least from the time of the bio-utopias predicted by J.B.S. Haldane and J. S. Huxley, the gene has often been surrounded by what I call the "rhetoric of futurity": a promissory rhetoric that, despite momentous changes in the life sciences throughout the 20th century, has remained relatively consistent over time.

  14. Genetic regulation of maize flower development and sex determination.

    PubMed

    Li, Qinglin; Liu, Baoshen

    2017-01-01

    The determining process of pistil fate are central to maize sex determination, mainly regulated by a genetic network in which the sex-determining genes SILKLESS 1 , TASSEL SEED 1 , TASSEL SEED 2 and the paramutagenic locus Required to maintain repression 6 play pivotal roles. Maize silks, which emerge from the ear shoot and derived from the pistil, are the functional stigmas of female flowers and play a pivotal role in pollination. Previous studies on sex-related mutants have revealed that sex-determining genes and phytohormones play an important role in the regulation of flower organogenesis. The processes determining pistil fate are central to flower development, where a silk identified gene SILKLESS 1 (SK1) is required to protect pistil primordia from a cell death signal produced by two commonly known genes, TASSEL SEED 1 (TS1) and TASSEL SEED 2 (TS2). In this review, maize flower developmental process is presented together with a focus on important sex-determining mutants and hormonal signaling affecting pistil development. The role of sex-determining genes, microRNAs, phytohormones, and the paramutagenic locus Required to maintain repression 6 (Rmr6), in forming a regulatory network that determines pistil fate, is discussed. Cloning SK1 and clarifying its function were crucial in understanding the regulation network of sex determination. The signaling mechanisms of phytohormones in sex determination are also an important research focus.

  15. Genetics of fat intake in the determination of body mass.

    PubMed

    Chmurzynska, Agata; Mlodzik, Monika A

    2017-03-15

    Body mass and fat intake are multifactorial traits that have genetic and environmental components. The gene with the greatest effect on body mass is FTO (fat mass and obesity-associated), but several studies have shown that the effect of FTO (and of other genes) on body mass can be modified by the intake of nutrients. The so-called gene-environment interactions may also be important for the effectiveness of weight-loss strategies. Food choices, and thus fat intake, depend to some extent on individual preferences. The most important biological component of food preference is taste, and the role of fat sensitivity in fat intake has recently been pointed out. Relatively few studies have analysed the genetic components of fat intake or fatty acid sensitivity in terms of their relation to obesity. It has been proposed that decreased oral fatty acid sensitivity leads to increased fat intake and thus increased body mass. One of the genes that affect fatty acid sensitivity is CD36 (cluster of differentiation 36). However, little is known so far about the genetic component of fat sensing. We performed a literature review to identify the state of knowledge regarding the genetics of fat intake and its relation to body-mass determination, and to identify the priorities for further investigations.

  16. Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria.

    PubMed

    Couce, Alejandro; Rodríguez-Rojas, Alexandro; Blázquez, Jesús

    2016-07-01

    Any pathogen population sufficiently large is expected to harbor spontaneous drug-resistant mutants, often responsible for disease relapse after antibiotic therapy. It is seldom appreciated, however, that while larger populations harbor more mutants, the abundance distribution of these mutants is expected to be markedly uneven. This is because a larger population size allows early mutants to expand for longer, exacerbating their predominance in the final mutant subpopulation. Here, we investigate the extent to which this reduction in evenness can constrain the genetic diversity of spontaneous drug resistance in bacteria. Combining theory and experiments, we show that even small variations in growth rate between resistant mutants and the wild type result in orders-of-magnitude differences in genetic diversity. Indeed, only a slight fitness advantage for the mutant is enough to keep diversity low and independent of population size. These results have important clinical implications. Genetic diversity at antibiotic resistance loci can determine a population's capacity to cope with future challenges (i.e., second-line therapy). We thus revealed an unanticipated way in which the fitness effects of antibiotic resistance can affect the evolvability of pathogens surviving a drug-induced bottleneck. This insight will assist in the fight against multidrug-resistant microbes, as well as contribute to theories aimed at predicting cancer evolution. Copyright © 2016 by the Genetics Society of America.

  17. Measuring genetic knowledge: a brief survey instrument for adolescents and adults.

    PubMed

    Fitzgerald-Butt, S M; Bodine, A; Fry, K M; Ash, J; Zaidi, A N; Garg, V; Gerhardt, C A; McBride, K L

    2016-02-01

    Basic knowledge of genetics is essential for understanding genetic testing and counseling. The lack of a written, English language, validated, published measure has limited our ability to evaluate genetic knowledge of patients and families. Here, we begin the psychometric analysis of a true/false genetic knowledge measure. The 18-item measure was completed by parents of children with congenital heart defects (CHD) (n = 465) and adolescents and young adults with CHD (age: 15-25, n = 196) with a mean total correct score of 12.6 [standard deviation (SD) = 3.5, range: 0-18]. Utilizing exploratory factor analysis, we determined that one to three correlated factors, or abilities, were captured by our measure. Through confirmatory factor analysis, we determined that the two factor model was the best fit. Although it was necessary to remove two items, the remaining items exhibited adequate psychometric properties in a multidimensional item response theory analysis. Scores for each factor were computed, and a sum-score conversion table was derived. We conclude that this genetic knowledge measure discriminates best at low knowledge levels and is therefore well suited to determine a minimum adequate amount of genetic knowledge. However, further reliability testing and validation in diverse research and clinical settings is needed.

  18. Attitude Determination Using Two Vector Measurements

    NASA Technical Reports Server (NTRS)

    Markley, F. Landis

    1998-01-01

    Many spacecraft attitude determination methods use exactly two vector measurements. The two vectors are typically the unit vector to the Sun and the Earth's magnetic field vector for coarse "sun-mag" attitude determination or unit vectors to two stars tracked by two star trackers for fine attitude determination. TRIAD, the earliest published algorithm for determining spacecraft attitude from two vector measurements, has been widely used in both ground-based and onboard attitude determination. Later attitude determination methods have been based on Wahba's optimality criterion for n arbitrarily weighted observations. The solution of Wahba's problem is somewhat difficult in the general case, but there is a simple closed-form solution in the two-observation case. This solution reduces to the TRIAD solution for certain choices of measurement weights. This paper presents and compares these algorithms as well as sub-optimal algorithms proposed by Bar-Itzhack, Harman, and Reynolds. Some new results will be presented, but the paper is primarily a review and tutorial.

  19. Genetic Determinism and the Innate-Acquired Distinction in Medicine

    PubMed Central

    2009-01-01

    This article illustrates in which sense genetic determinism is still part of the contemporary interactionist consensus in medicine. Three dimensions of this consensus are discussed: kinds of causes, a continuum of traits ranging from monogenetic diseases to car accidents, and different kinds of determination due to different norms of reaction. On this basis, this article explicates in which sense the interactionist consensus presupposes the innate–acquired distinction. After a descriptive Part 1, Part 2 reviews why the innate–acquired distinction is under attack in contemporary philosophy of biology. Three arguments are then presented to provide a limited and pragmatic defense of the distinction: an epistemic, a conceptual, and a historical argument. If interpreted in a certain manner, and if the pragmatic goals of prevention and treatment (ideally specifying what medicine and health care is all about) are taken into account, then the innate–acquired distinction can be a useful epistemic tool. It can help, first, to understand that genetic determination does not mean fatalism, and, second, to maintain a system of checks and balances in the continuing nature–nurture debates. PMID:20234831

  20. Genetic Determinism and the Innate-Acquired Distinction in Medicine.

    PubMed

    Kronfeldner, Maria E

    2009-06-01

    This article illustrates in which sense genetic determinism is still part of the contemporary interactionist consensus in medicine. Three dimensions of this consensus are discussed: kinds of causes, a continuum of traits ranging from monogenetic diseases to car accidents, and different kinds of determination due to different norms of reaction. On this basis, this article explicates in which sense the interactionist consensus presupposes the innate-acquired distinction. After a descriptive Part 1, Part 2 reviews why the innate-acquired distinction is under attack in contemporary philosophy of biology. Three arguments are then presented to provide a limited and pragmatic defense of the distinction: an epistemic, a conceptual, and a historical argument. If interpreted in a certain manner, and if the pragmatic goals of prevention and treatment (ideally specifying what medicine and health care is all about) are taken into account, then the innate-acquired distinction can be a useful epistemic tool. It can help, first, to understand that genetic determination does not mean fatalism, and, second, to maintain a system of checks and balances in the continuing nature-nurture debates.

  1. Genetic Determinants of Epigenetic Patterns: Providing Insight into Disease.

    PubMed

    Cazaly, Emma; Charlesworth, Jac; Dickinson, Joanne L; Holloway, Adele F

    2015-03-26

    The field of epigenetics and our understanding of the mechanisms that regulate the establishment, maintenance and heritability of epigenetic patterns continue to grow at a remarkable rate. This information is providing increased understanding of the role of epigenetic changes in disease, insight into the underlying causes of these epigenetic changes and revealing new avenues for therapeutic intervention. Epigenetic modifiers are increasingly being pursued as therapeutic targets in a range of diseases, with a number of agents targeting epigenetic modifications already proving effective in diseases such as cancer. Although it is well established that DNA mutations and aberrant expression of epigenetic modifiers play a key role in disease, attention is now turning to the interplay between genetic and epigenetic factors in complex disease etiology. The role of genetic variability in determining epigenetic profiles, which can then be modified by environmental and stochastic factors, is becoming more apparent. Understanding the interplay between genetic and epigenetic factors is likely to aid in identifying individuals most likely to benefit from epigenetic therapies. This goal is coming closer to realization because of continual advances in laboratory and statistical tools enabling improvements in the integration of genomic, epigenomic and phenotypic data.

  2. Sensitization to cockroach allergen: immune regulation and genetic determinants.

    PubMed

    Gao, Peisong

    2012-01-01

    Asthma is a major public health concern. Cockroach allergen exposure and cockroach allergic sensitization could contribute to the higher prevalence of asthma. However, the underlying immune mechanism and the genetic etiology remain unclear. Recent advances have demonstrated that several receptors (PAR-2, TLRs, CLRs) and their pathways mediate antigen uptake from the environment and induce allergies by signaling T cells to activate an inappropriate immune response. Cockroach-derived protease can disturb airway epithelial integrity via PAR-2 and leads to an increased penetration of cockroach allergen, resulting in activation of innate immune cells (e.g., DCs) via binding to either TLRs or CLRs. The activated DCs can direct cells of the adaptive immune system to facilitate promotion of Th2 cell response and subsequently increase risk of sensitization. Mannose receptor (MR), as a CLR, has been shown to mediate Bla g2 (purified cockroach allergen) uptake by DCs and to determine allergen-induced T cell polarization. Additionally, genetic factors may play an important role in conferring the susceptibility to cockroach sensitization. Several genes have been associated with cockroach sensitization and related phenotypes (HLA-D, TSLP, IL-12A, MBL2). In this review, we have focused on studies on the cockroach allergen induced immunologic responses and genetic basis for cockroach sensitization.

  3. Genetic Determinants of Epigenetic Patterns: Providing Insight into Disease

    PubMed Central

    Cazaly, Emma; Charlesworth, Jac; Dickinson, Joanne L; Holloway, Adele F

    2015-01-01

    The field of epigenetics and our understanding of the mechanisms that regulate the establishment, maintenance and heritability of epigenetic patterns continue to grow at a remarkable rate. This information is providing increased understanding of the role of epigenetic changes in disease, insight into the underlying causes of these epigenetic changes and revealing new avenues for therapeutic intervention. Epigenetic modifiers are increasingly being pursued as therapeutic targets in a range of diseases, with a number of agents targeting epigenetic modifications already proving effective in diseases such as cancer. Although it is well established that DNA mutations and aberrant expression of epigenetic modifiers play a key role in disease, attention is now turning to the interplay between genetic and epigenetic factors in complex disease etiology. The role of genetic variability in determining epigenetic profiles, which can then be modified by environmental and stochastic factors, is becoming more apparent. Understanding the interplay between genetic and epigenetic factors is likely to aid in identifying individuals most likely to benefit from epigenetic therapies. This goal is coming closer to realization because of continual advances in laboratory and statistical tools enabling improvements in the integration of genomic, epigenomic and phenotypic data. PMID:25822796

  4. Sensitization to Cockroach Allergen: Immune Regulation and Genetic Determinants

    PubMed Central

    Gao, Peisong

    2012-01-01

    Asthma is a major public health concern. Cockroach allergen exposure and cockroach allergic sensitization could contribute to the higher prevalence of asthma. However, the underlying immune mechanism and the genetic etiology remain unclear. Recent advances have demonstrated that several receptors (PAR-2, TLRs, CLRs) and their pathways mediate antigen uptake from the environment and induce allergies by signaling T cells to activate an inappropriate immune response. Cockroach-derived protease can disturb airway epithelial integrity via PAR-2 and leads to an increased penetration of cockroach allergen, resulting in activation of innate immune cells (e.g., DCs) via binding to either TLRs or CLRs. The activated DCs can direct cells of the adaptive immune system to facilitate promotion of Th2 cell response and subsequently increase risk of sensitization. Mannose receptor (MR), as a CLR, has been shown to mediate Bla g2 (purified cockroach allergen) uptake by DCs and to determine allergen-induced T cell polarization. Additionally, genetic factors may play an important role in conferring the susceptibility to cockroach sensitization. Several genes have been associated with cockroach sensitization and related phenotypes (HLA-D, TSLP, IL-12A, MBL2). In this review, we have focused on studies on the cockroach allergen induced immunologic responses and genetic basis for cockroach sensitization. PMID:22272212

  5. Historical and ecological determinants of genetic structure in arctic canids.

    PubMed

    Carmichael, L E; Krizan, J; Nagy, J A; Fuglei, E; Dumond, M; Johnson, D; Veitch, A; Berteaux, D; Strobeck, C

    2007-08-01

    Wolves (Canis lupus) and arctic foxes (Alopex lagopus) are the only canid species found throughout the mainland tundra and arctic islands of North America. Contrasting evolutionary histories, and the contemporary ecology of each species, have combined to produce their divergent population genetic characteristics. Arctic foxes are more variable than wolves, and both island and mainland fox populations possess similarly high microsatellite variation. These differences result from larger effective population sizes in arctic foxes, and the fact that, unlike wolves, foxes were not isolated in discrete refugia during the Pleistocene. Despite the large physical distances and distinct ecotypes represented, a single, panmictic population of arctic foxes was found which spans the Svalbard Archipelago and the North American range of the species. This pattern likely reflects both the absence of historical population bottlenecks and current, high levels of gene flow following frequent long-distance foraging movements. In contrast, genetic structure in wolves correlates strongly to transitions in habitat type, and is probably determined by natal habitat-biased dispersal. Nonrandom dispersal may be cued by relative levels of vegetation cover between tundra and forest habitats, but especially by wolf prey specialization on ungulate species of familiar type and behaviour (sedentary or migratory). Results presented here suggest that, through its influence on sea ice, vegetation, prey dynamics and distribution, continued arctic climate change may have effects as dramatic as those of the Pleistocene on the genetic structure of arctic canid species.

  6. Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria

    PubMed Central

    Couce, Alejandro; Rodríguez-Rojas, Alexandro; Blázquez, Jesús

    2016-01-01

    Any pathogen population sufficiently large is expected to harbor spontaneous drug-resistant mutants, often responsible for disease relapse after antibiotic therapy. It is seldom appreciated, however, that while larger populations harbor more mutants, the abundance distribution of these mutants is expected to be markedly uneven. This is because a larger population size allows early mutants to expand for longer, exacerbating their predominance in the final mutant subpopulation. Here, we investigate the extent to which this reduction in evenness can constrain the genetic diversity of spontaneous drug resistance in bacteria. Combining theory and experiments, we show that even small variations in growth rate between resistant mutants and the wild type result in orders-of-magnitude differences in genetic diversity. Indeed, only a slight fitness advantage for the mutant is enough to keep diversity low and independent of population size. These results have important clinical implications. Genetic diversity at antibiotic resistance loci can determine a population’s capacity to cope with future challenges (i.e., second-line therapy). We thus revealed an unanticipated way in which the fitness effects of antibiotic resistance can affect the evolvability of pathogens surviving a drug-induced bottleneck. This insight will assist in the fight against multidrug-resistant microbes, as well as contribute to theories aimed at predicting cancer evolution. PMID:27182949

  7. Procedures for Determining the Equivalence of Measures.

    ERIC Educational Resources Information Center

    Dunivant, Noel

    Eight different methods are reviewed for determining whether two or more tests are equivalent measures. These methods vary in restrictiveness from the Wilks-Votaw test of compound symmetry (which requires that all means, variances, and covariances are equal), to Joreskog's theory of congeneric tests (which requires only that the tests are measures…

  8. Determination of nonlinear genetic architecture using compressed sensing.

    PubMed

    Ho, Chiu Man; Hsu, Stephen D H

    2015-01-01

    One of the fundamental problems of modern genomics is to extract the genetic architecture of a complex trait from a data set of individual genotypes and trait values. Establishing this important connection between genotype and phenotype is complicated by the large number of candidate genes, the potentially large number of causal loci, and the likely presence of some nonlinear interactions between different genes. Compressed Sensing methods obtain solutions to under-constrained systems of linear equations. These methods can be applied to the problem of determining the best model relating genotype to phenotype, and generally deliver better performance than simply regressing the phenotype against each genetic variant, one at a time. We introduce a Compressed Sensing method that can reconstruct nonlinear genetic models (i.e., including epistasis, or gene-gene interactions) from phenotype-genotype (GWAS) data. Our method uses L1-penalized regression applied to nonlinear functions of the sensing matrix. The computational and data resource requirements for our method are similar to those necessary for reconstruction of linear genetic models (or identification of gene-trait associations), assuming a condition of generalized sparsity, which limits the total number of gene-gene interactions. An example of a sparse nonlinear model is one in which a typical locus interacts with several or even many others, but only a small subset of all possible interactions exist. It seems plausible that most genetic architectures fall in this category. We give theoretical arguments suggesting that the method is nearly optimal in performance, and demonstrate its effectiveness on broad classes of nonlinear genetic models using simulated human genomes and the small amount of currently available real data. A phase transition (i.e., dramatic and qualitative change) in the behavior of the algorithm indicates when sufficient data is available for its successful application. Our results indicate

  9. Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

    SciTech Connect

    Kleiman, Norman Jay

    2013-11-30

    The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9

  10. Ecological and genetic determinants of plasmid distribution in Escherichia coli.

    PubMed

    Medaney, Frances; Ellis, Richard J; Raymond, Ben

    2016-11-01

    Bacterial plasmids are important carriers of virulence and antibiotic resistance genes. Nevertheless, little is known of the determinants of plasmid distribution in bacterial populations. Here the factors affecting the diversity and distribution of the large plasmids of Escherichia coli were explored in cattle grazing on semi-natural grassland, a set of populations with low frequencies of antibiotic resistance genes. Critically, the population genetic structure of bacterial hosts was chararacterized. This revealed structured E. coli populations with high diversity between sites and individuals but low diversity within cattle hosts. Plasmid profiles, however, varied considerably within the same E. coli genotype. Both ecological and genetic factors affected plasmid distribution: plasmid profiles were affected by site, E. coli diversity, E. coli genotype and the presence of other large plasmids. Notably 3/26 E. coli serotypes accounted for half the observed plasmid-free isolates indicating that within species variation can substantially affect carriage of the major conjugative plasmids. The observed population structure suggest that most of the opportunities for within species plasmid transfer occur between different individuals of the same genotype and support recent experimental work indicating that plasmid-host coevolution, and epistatic interactions on fitness costs are likely to be important in determining occupancy. © 2016 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

  11. Crystallographic texture determinations from inverse susceptibility measurements

    NASA Astrophysics Data System (ADS)

    Lewis, L. H.; Welch, D. O.

    1997-04-01

    Determination of the quantitative relationship between crystallographic texture and magnetic properties in advanced permanent magnets may be hampered by complex microstructures, which complicate methods that rely on diffraction, or by interparticulate interactions, which adversely affect methods based on magnetic remanence measurements. To this end, new techniques in the determination of texture of bulk permanent magnets are being explored to overcome these inherent experimental difficulties. The analysis of inverse paramagnetic susceptibility measurements constitutes a new method to investigate crystallographic texture. Such measurements also provide Curie temperature data, which are sensitive to chemical changes that may have occurred in the magnetic phase during processing. The mathematical formalism underlying the analysis of inverse susceptibility measurements is outlined, and is used to evaluate magnetic measurements taken from a series of Nd2Fe14B magnets that have been processed by different means, and thus contain different degrees of texture. While this method does provide qualitative information concerning the relative crystallographic alignment of magnet samples, it needs calibration to obtain an explicit value for a texture order parameter.

  12. Genetic relationship between the addiction diagnosis in adults and their childhood measure of addiction liability.

    PubMed

    Vanyukov, Michael; Kim, Kevin; Irons, Daniel; Kirisci, Levent; Neale, Michael; Ridenour, Ty; Hicks, Brian; Tarter, Ralph; Reynolds, Maureen; Kirillova, Galina; McGue, Matt; Iacono, William

    2015-01-01

    Transmissible liability index (TLI), developed employing a high-risk design and item response theory, enables quantification of the latent trait of liability to drug use disorders (DUD) in children. TLI has been shown to have high heritability and predict DUD in young adulthood. This study extends prior research and determines the genetic contribution of DUD liability measured by TLI to adult liability as indexed by DUD diagnosis. The study utilizes data from a twin sample tracked from age 11 to age 25. In addition to confirming TLI's high heritability and predictive validity, it shows that the genetic component of variance in TLI assessed in childhood accounts for over half of the genetic variance in DUD diagnosis and the entire phenotypic relationship between the two liability measures. This validates TLI as an early measure of DUD liability and supports its utility in early-age genetic and other mechanistic studies of DUD.

  13. Repeated measurement sampling in genetic association analysis with genotyping errors.

    PubMed

    Lai, Renzhen; Zhang, Hong; Yang, Yaning

    2007-02-01

    Genotype misclassification occurs frequently in human genetic association studies. When cases and controls are subject to the same misclassification model, Pearson's chi-square test has the correct type I error but may lose power. Most current methods adjusting for genotyping errors assume that the misclassification model is known a priori or can be assessed by a gold standard instrument. But in practical applications, the misclassification probabilities may not be completely known or the gold standard method can be too costly to be available. The repeated measurement design provides an alternative approach for identifying misclassification probabilities. With this design, a proportion of the subjects are measured repeatedly (five or more repeats) for the genotypes when the error model is completely unknown. We investigate the applications of the repeated measurement method in genetic association analysis. Cost-effectiveness study shows that if the phenotyping-to-genotyping cost ratio or the misclassification rates are relatively large, the repeat sampling can gain power over the regular case-control design. We also show that the power gain is not sensitive to the genetic model, genetic relative risk and the population high-risk allele frequency, all of which are typically important ingredients in association studies. An important implication of this result is that whatever the genetic factors are, the repeated measurement method can be applied if the genotyping errors must be accounted for or the phenotyping cost is high.

  14. Genetically Determined Variation in Developmental Physiology of Bivalve Larvae (Crassostrea gigas).

    PubMed

    Francis Pan, T-C; Applebaum, Scott L; Manahan, Donal T

    2015-01-01

    Understanding the complex interactions that regulate growth and form is a central question in developmental physiology. We used experimental crosses of pedigreed lines of the Pacific oyster, Crassostrea gigas, to investigate genetically determined variations in larval growth and nutrient transport. We show that (i) transport rates at 10 and 100 μM glycine scale differentially with size; (ii) size-specific maximum transport capacity (Jmax) is genetically determined; and (iii) Jmax serves as an early predictive index of subsequent growth rate. This relationship between genetically determined Jmax and growth suggests the potential use of transporter genes as biomarkers of growth potential. Analysis of the genome of C. gigas revealed 23 putative amino acid transporter genes. The complexity of gene families that underpin physiological traits has additional precedents in this species and others and warrants caution in the use of gene expression as a biomarker for physiological state. Direct in vivo measurements of physiological processes using species with defined genotypes are required to understand genetically determined variance of nutrient flux and other processes that regulate development and growth.

  15. Genetic and metabolic determinants of human epigenetic variation.

    PubMed

    Haggarty, Paul

    2015-07-01

    Epigenetics has emerged in recent years as one of the most important biological mechanisms linking exposures across the life course to long-term health. This article reviews recent developments in our understanding of the metabolic and genetic determinants of epigenetic variation in human populations. Epigenetic status is influenced by a range of environmental exposures, including diet and nutrition, social status, the early emotional environment, and infertility and its treatment. The period around conception is particularly sensitive to environmental exposures with evidence for effects on epigenetic imprinting within the offspring. Epigenetic status is also influenced by genotype, and genetic variation in methylene tetrahydrofolate reductase, and the DNA methytransferase and ten-eleven translocation methylcytosine dioxygenase proteins has been linked to the epigenetic status, biological function and disease. Epigenetics is at the heart of a series of feedback loops linking the environment to the human genome in a way that allows crosstalk between the genome and the environment it exists within. It offers the potential for modification of adverse epigenetic states resulting from events/exposures at earlier life stages. We need to better understand the nutritional programming of epigenetic states, the persistence of these marks in time and their effect on biological function and health in current and future generations.

  16. Genetic determinants and potential therapeutic targets for pancreatic adenocarcinoma

    PubMed Central

    Reznik, Robert; Hendifar, Andrew E.; Tuli, Richard

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in both men and women in the United States, carrying a 5-year survival rate of approximately 5%, which is the poorest prognosis of any solid tumor type. Given the dismal prognosis associated with PDAC, a more thorough understanding of risk factors and genetic predisposition has important implications not only for cancer prevention, but also for screening techniques and the development of personalized therapies. While screening of the general population is not recommended or practicable with current diagnostic methods, studies are ongoing to evaluate its usefulness in people with at least 5- to 10-fold increased risk of PDAC. In order to help identify high-risk populations who would be most likely to benefit from early detection screening tests for pancreatic cancer, discovery of additional pancreatic cancer susceptibility genes is crucial. Thus, specific gene-based, gene-product, and marker-based testing for the early detection of pancreatic cancer are currently being developed, with the potential for these to be useful as potential therapeutic targets as well. The goal of this review is to provide an overview of the genetic basis for PDAC with a focus on germline and familial determinants. A discussion of potential therapeutic targets and future directions in screening and treatment is also provided. PMID:24624093

  17. Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

    PubMed Central

    Pramstaller, Peter P.; Rudan, Igor; Franklin, Christopher S.; Liebisch, Gerhard; Erdmann, Jeanette; Jonasson, Inger; Zorkoltseva, Irina V.; Pattaro, Cristian; Hayward, Caroline; Isaacs, Aaron; Hengstenberg, Christian; Campbell, Susan; Gnewuch, Carsten; Janssens, A. CecileJ.W.; Kirichenko, Anatoly V.; König, Inke R.; Marroni, Fabio; Polasek, Ozren; Demirkan, Ayse; Kolcic, Ivana; Schwienbacher, Christine; Igl, Wilmar; Biloglav, Zrinka; Witteman, Jacqueline C. M.; Pichler, Irene; Zaboli, Ghazal; Axenovich, Tatiana I.; Peters, Annette; Schreiber, Stefan; Wichmann, H.-Erich; Schunkert, Heribert; Hastie, Nick; Oostra, Ben A.; Wild, Sarah H.; Meitinger, Thomas; Gyllensten, Ulf; van Duijn, Cornelia M.; Wilson, James F.; Wright, Alan; Schmitz, Gerd; Campbell, Harry

    2009-01-01

    Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic β-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08×10−66. The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1–3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10−4 or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be

  18. Determining seabird body condition using nonlethal measures.

    PubMed

    Jacobs, Shoshanah R; Elliott, Kyle; Guigueno, Mélanie F; Gaston, Anthony J; Redman, Paula; Speakman, John R; Weber, Jean-Michel

    2012-01-01

    Energy stores are critical for successful breeding, and longitudinal studies require nonlethal methods to measure energy stores ("body condition"). Nonlethal techniques for measuring energy reserves are seldom verified independently. We compare body mass, size-corrected mass (SCM), plasma lipids, and isotopic dilution with extracted total body lipid content in three seabird species (thick-billed murres Uria lomvia, all four measures; northern fulmars Fulmarus glacialis, three measures; and black-legged kittiwakes Rissa tridactyla, two measures). SCM and body mass were better predictors of total body lipids for the species with high percent lipids (fulmars; R2 = 0.5-0.6) than for the species with low percent lipids (murres and kittiwakes; R2 = 0.2-0.4). The relationship between SCM and percent body lipids, which we argue is often a better measure of condition, was also poor (R2 < 0.2) for species with low lipids. In a literature comparison of 17 bird species, percent lipids was the only predictor of the strength of the relationship between mass and total body lipids; we suggest that SCM be used as an index of energy stores only when lipids exceed 15% of body mass. Across all three species we measured, SCM based on the ordinary least squares regression of mass on the first principal component outperformed other measures. Isotopic dilution was a better predictor of both total body lipids and percent body lipids than were mass, SCM, or plasma lipids in murres. Total body lipids decreased through the breeding season at both sites, while total and neutral plasma lipid concentrations increased at one site but not another, suggesting mobilization of lipid stores for breeding. A literature review showed substantial variation in the reliability of plasma markers, and we recommend isotopic dilution (oxygen-18, plateau) for determination of energy reserves in birds where lipid content is below 15%.

  19. Clock measurements to improve the geopotential determination

    NASA Astrophysics Data System (ADS)

    Lion, Guillaume; Panet, Isabelle; Delva, Pacôme; Wolf, Peter; Bize, Sébastien; Guerlin, Christine

    2017-04-01

    Comparisons between optical clocks with an accuracy and stability approaching the 10-18 in term of relative frequency shift are opening new perspectives for the direct determination of geopotential at a centimeter-level accuracy in geoid height. However, so far detailed quantitative estimates of the possible improvement in geoid determination when adding such clock measurements to existing data are lacking. In this context, the present work aims at evaluating the contribution of this new kind of direct measurements in determining the geopotential at high spatial resolution (10 km). We consider the Massif Central area, marked by smooth, moderate altitude mountains and volcanic plateaus leading to variations of the gravitational field over a range of spatial scales. In such type of region, the scarcity of gravity data is an important limitation in deriving accurate high resolution geopotential models. We summarize our methodology to assess the contribution of clock data in the geopotential recovery, in combination with ground gravity measurements. We sample synthetic gravity and disturbing potential data from a spherical harmonics geopotential model, and a topography model, up to 10 km resolution; we also build a potential control grid. From the synthetic data, we estimate the disturbing potential by least-squares collocation. Finally, we assess the quality of the reconstructed potential by comparing it to that of the control grid. We show that adding only a few clock data reduces the reconstruction bias significantly and improves the standard deviation by a factor 3. We discuss the role of different parameters, such as the effect of the data coverage and data quality on these results, the trade-off between the measurement noise level and the number of data, and the optimization of the clock data network.

  20. B lymphocyte immune response gene phenotype is genetically determined

    SciTech Connect

    Tse, H.Y.; Mond, J.J.; Longo, D.L.

    1982-04-01

    We examined the effects of the developmental milieu on the capacity of B cells to undergo immune response gene-controlled, T cell-dependent polyclonal proliferation. Although I-Aq poly(Glu60 Ala30 Tyr10)n (GAT)-nonresponder T cells developing in a responder environment become phenotypic GAT-responders, I-Aq B cells remain unresponsive to GAT, even after maturation in a GAT-responder animal. Conversely, (B10.A x B10.Q)F1 ((GAT responder x GAT nonresponder)F1) T cells developing in a B10.Q GAT nonresponder host fail to respond to GAT, but F1 B cells from the same F1 leads to parent chimeras make excellent proliferative responses in the presence of GAT and responder T cells. Thus, by this assay, B cell immune response gene function is genetically determined and is not affected by the developmental milieu.

  1. Sarcolemmal phospholipid N-methylation in genetically determined hamster cardiomyopathy

    SciTech Connect

    Okumura, K.; Panagia, V.; Jasmin, G.; Dhalla, N.S.

    1987-02-27

    The heart sarcolemmal phosphatidylethanolamine N-methylation in UM-X7.1 strain of cardiomyopathic hamsters was examined by using 0.055, 10 and 150 microM S-adenosyl-L-(methyl-/sup 3/H) methionine as methyl donor for sites I, II and III, respectively. In comparison with control values, methylation activities at site I was increased in 40, 120 and 250 days old cardiomyopathic hamsters. On the other hand, methylation activities at sites II and III in 120 and 250 days old cardiomyopathic animals were depressed without any change in the 40 days old group. The alterations in N-methylation activities were associated with kinetic changes in apparent Vmax values without any changes in the apparent Km. These results indicate a defect in the phospholipid N-methylation process in heart sarcolemma during the development of genetically determined cardiomyopathy.

  2. Novel genetic algorithm search procedure for LEED surface structure determination.

    PubMed

    Viana, M L; dos Reis, D D; Soares, E A; Van Hove, M A; Moritz, W; de Carvalho, V E

    2014-06-04

    Low Energy Electron Diffraction (LEED) is one of the most powerful experimental techniques for surface structure analysis but until now only a trial-and-error approach has been successful. So far, fitting procedures developed to optimize structural and nonstructural parameters-by minimization of the R-factor-have had a fairly small convergence radius, suitable only for local optimization. However, the identification of the global minimum among the several local minima is essential for complex surface structures. Global optimization methods have been applied to LEED structure determination, but they still require starting from structures that are relatively close to the correct one, in order to find the final structure. For complex systems, the number of trial structures and the resulting computation time increase so rapidly that the task of finding the correct model becomes impractical using the present methodologies. In this work we propose a new search method, based on Genetic Algorithms, which is able to determine the correct structural model starting from completely random structures. This method-called here NGA-LEED for Novel Genetic Algorithm for LEED-utilizes bond lengths and symmetry criteria to select reasonable trial structures before performing LEED calculations. This allows a reduction of the parameter space and, consequently of the calculation time, by several orders of magnitude. A refinement of the parameters by least squares fit of simulated annealing is performed only at some intermediate stages and in the final step. The method was successfully tested for two systems, Ag(1 1 1)(4 × 4)-O and Au(1 1 0)-(1 × 2), both in theory versus theory and in theory versus experiment comparisons. Details of the implementation as well as the results for these two systems are presented.

  3. Node-based measures of connectivity in genetic networks.

    PubMed

    Koen, Erin L; Bowman, Jeff; Wilson, Paul J

    2016-01-01

    At-site environmental conditions can have strong influences on genetic connectivity, and in particular on the immigration and settlement phases of dispersal. However, at-site processes are rarely explored in landscape genetic analyses. Networks can facilitate the study of at-site processes, where network nodes are used to model site-level effects. We used simulated genetic networks to compare and contrast the performance of 7 node-based (as opposed to edge-based) genetic connectivity metrics. We simulated increasing node connectivity by varying migration in two ways: we increased the number of migrants moving between a focal node and a set number of recipient nodes, and we increased the number of recipient nodes receiving a set number of migrants. We found that two metrics in particular, the average edge weight and the average inverse edge weight, varied linearly with simulated connectivity. Conversely, node degree was not a good measure of connectivity. We demonstrated the use of average inverse edge weight to describe the influence of at-site habitat characteristics on genetic connectivity of 653 American martens (Martes americana) in Ontario, Canada. We found that highly connected nodes had high habitat quality for marten (deep snow and high proportions of coniferous and mature forest) and were farther from the range edge. We recommend the use of node-based genetic connectivity metrics, in particular, average edge weight or average inverse edge weight, to model the influences of at-site habitat conditions on the immigration and settlement phases of dispersal.

  4. Measuring Behavior in Genetic Disorders of Mental Retardation

    ERIC Educational Resources Information Center

    Hodapp, Robert M.; Dykens, Elisabeth M.

    2005-01-01

    As researchers have examined the so-called "behavioral phenotypes" of different genetic mental retardation conditions, the measurement of behavior becomes increasingly important. From earlier, more global examinations of noteworthy behaviors or profiles, recent researchers have moved from reliance on a single, all-encompassing questionnaire to…

  5. Genetics of sex determination in the social amoebae.

    PubMed

    Bloomfield, Gareth

    2011-05-01

    The social amoebae possess a sexual cycle that involves transient mutlicellularity: first a zygote attracts surrounding haploid amoebae to form a walled aggregate around it, and then cannibalizes these peripheral cells, eventually forming a dormant single-celled macrocyst. Self-fertile homothallic isolates occur as well as breeding groups of self-infertile heterothallic cells, which commonly have more than two mating types. The mating-type locus of the widely studied model organism Dictyostelium discoideum, which has three mating types, has recently been identified. Two of the three mating types are determined by single putative regulatory genes bearing no mutual similarity, while the third is specified by homologues of both of these genes. This is the first sex-determining locus of an Amoebozoan to be described and, since none of the key regulators show homology to known proteins, may be a first glimpse of a novel mode of regulation used in these organisms. The sexual cycle of dictyostelids has been relatively neglected, but continues to yield much interesting biology as well as having the potential to add to the genetic tools available for the study of these organisms. © 2011 Medical Research Council, UK. Development, Growth & Differentiation © 2011 Japanese Society of Developmental Biologists.

  6. Cellular and network mechanisms of genetically-determined absence seizures

    PubMed Central

    Pinault, Didier; O'Brien, Terence J.

    2005-01-01

    The absence epilepsies are characterized by recurrent episodes of loss of consciousness associated with generalized spike-and-wave discharges, with an abrupt onset and offset, in the thalamocortical system. In the absence of detailed neurophysiological studies in humans, many of the concepts regarding the pathophysiological basis of absence seizures are based on studies in animal models. Each of these models has its particular strengths and limitations, and the validity of findings from these models for the human condition cannot be assumed. Consequently, studies in different models have produced some conflicting findings and conclusions. A long-standing concept, based primarily from studies in vivo in cats and in vitro brain slices, is that these paroxysmal electrical events develop suddenly from sleep-related spindle oscillations. More specifically, it is proposed that the initial mechanisms that underlie absence-related spike-and-wave discharges are located in the thalamus, involving especially the thalamic reticular nucleus. By contrast, more recent studies in well-established, genetic models of absence epilepsy in rats demonstrate that spike-and-wave discharges originate in a cortical focus and develop from a wake-related natural corticothalamic sensorimotor rhythm. In this review we integrate recent findings showing that, in both the thalamus and the neocortex, genetically-determined, absence-related spike-and-wave discharges are the manifestation of hypersynchronized, cellular, rhythmic excitations and inhibitions that result from a combination of complex, intrinsic, synaptic mechanisms. Arguments are put forward supporting the hypothesis that layer VI corticothalamic neurons act as ‘drivers’ in the generation of spike-and-wave discharges in the somatosensory thalamocortical system that result in corticothalamic resonances particularly initially involving the thalamic reticular nucleus. However an important unresolved question is: what are the cellular

  7. Genetic determinants and stroke in children with sickle cell disease.

    PubMed

    Rodrigues, Daniela O W; Ribeiro, Luiz C; Sudário, Lysla C; Teixeira, Maria T B; Martins, Marina L; Pittella, Anuska M O L; Junior, Irtis de O Fernandes

    To verify genetic determinants associated with stroke in children with sickle cell disease (SCD). Prospective cohort with 110 children submitted to neonatal screening by the Neonatal Screening Program, between 1998 and 2007, with SCD diagnosis, followed at a regional reference public service for hemoglobinopathies. The analyzed variables were type of hemoglobinopathy, gender, coexistence with alpha thalassemia (α-thal), haplotypes of the beta globin chain cluster, and stroke. The final analysis was conducted with 66 children with sickle cell anemia (SCA), using the chi-squared test in the program SPSS(®) version 14.0. Among children with SCD, 60% had SCA. The prevalence of coexistence with α-thal was 30.3% and the Bantu haplotype (CAR) was identified in 89.2%. The incidence of stroke was significantly higher in those with SCA (27.3% vs. 2.3%; p=0.001) and males (24.1% vs. 9.6%; p=0.044). The presence of α-thal (p=0.196), the CAR haplotype (p=0.543), and socioeconomic factors were not statistically significant in association with the occurrence of stroke. There is a high incidence of stroke in male children and in children with SCA. Coexistence with α-thal and haplotypes of the beta globin chain cluster did not show any significant association with stroke. The heterogeneity between previously evaluated populations, the non-reproducibility between studies, and the need to identify factors associated with stroke in patients with SCA indicate the necessity of conducting further research to demonstrate the relevance of genetic factors in stroke related to SCD. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  8. The genetic drift inventory: a tool for measuring what advanced undergraduates have mastered about genetic drift.

    PubMed

    Price, Rebecca M; Andrews, Tessa C; McElhinny, Teresa L; Mead, Louise S; Abraham, Joel K; Thanukos, Anna; Perez, Kathryn E

    2014-01-01

    Understanding genetic drift is crucial for a comprehensive understanding of biology, yet it is difficult to learn because it combines the conceptual challenges of both evolution and randomness. To help assess strategies for teaching genetic drift, we have developed and evaluated the Genetic Drift Inventory (GeDI), a concept inventory that measures upper-division students' understanding of this concept. We used an iterative approach that included extensive interviews and field tests involving 1723 students across five different undergraduate campuses. The GeDI consists of 22 agree-disagree statements that assess four key concepts and six misconceptions. Student scores ranged from 4/22 to 22/22. Statements ranged in mean difficulty from 0.29 to 0.80 and in discrimination from 0.09 to 0.46. The internal consistency, as measured with Cronbach's alpha, ranged from 0.58 to 0.88 across five iterations. Test-retest analysis resulted in a coefficient of stability of 0.82. The true-false format means that the GeDI can test how well students grasp key concepts central to understanding genetic drift, while simultaneously testing for the presence of misconceptions that indicate an incomplete understanding of genetic drift. The insights gained from this testing will, over time, allow us to improve instruction about this key component of evolution.

  9. Genetic Determinants of Serum Testosterone Concentrations in Men

    PubMed Central

    Maggio, Marcello; Coviello, Andrea D.; Ferrucci, Luigi; Heier, Margit; Hofman, Albert; Holliday, Kate L.; Jansson, John-Olov; Kähönen, Mika; Karasik, David; Karlsson, Magnus K.; Kiel, Douglas P.; Liu, Yongmei; Ljunggren, Östen; Lorentzon, Mattias; Lyytikäinen, Leo-Pekka; Meitinger, Thomas; Mellström, Dan; Melzer, David; Miljkovic, Iva; Nauck, Matthias; Nilsson, Maria; Penninx, Brenda; Pye, Stephen R.; Vasan, Ramachandran S.; Reincke, Martin; Rivadeneira, Fernando; Tajar, Abdelouahid; Teumer, Alexander; Uitterlinden, André G.; Ulloor, Jagadish; Viikari, Jorma; Völker, Uwe; Völzke, Henry; Wichmann, H. Erich; Wu, Tsung-Sheng; Zhuang, Wei Vivian; Ziv, Elad; Wu, Frederick C. W.; Raitakari, Olli; Eriksson, Anna; Bidlingmaier, Martin; Harris, Tamara B.; Murray, Anna; de Jong, Frank H.; Murabito, Joanne M.; Bhasin, Shalender; Vandenput, Liesbeth; Haring, Robin

    2011-01-01

    Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10−41 and rs6258, p = 2.3×10−22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10−16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation. PMID:21998597

  10. 75 FR 8299 - Draft Environmental Impact Statement; Determination of Regulated Status of Alfalfa Genetically...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-24

    ... and Forage Genetics International alfalfa lines designated as events J101 and J163 as regulated... determination on the status of the Monsanto Company and Forage Genetics International alfalfa lines designated...

  11. An examination of environmental and genetic contributions to the determinants of suicidal behavior among male twins

    PubMed Central

    Smith, April Rose; Ribeiro, Jessica; Mikolajewski, Amy; Taylor, Jeanette; Joiner, Thomas; Iacono, William G.

    2012-01-01

    The purpose of the present study was to examine the relative association of genetic and environmental factors with individual differences in each of the proximal, jointly necessary, and sufficient causes for suicidal behavior, according to the Interpersonal-Psychological Theory of Suicide (IPTS; Joiner, 2005). We examined data on derived scales measuring acquired capability, belongingness, and burdensomeness (the determinants of suicidal behavior, according to theory) from 348 adolescent male twins. Univariate biometrical models were used to estimate the magnitude of additive genetic (A), non-additive genetic (D), shared environmental (C), and nonshared environmental (E) effects associated with the variance in acquired capability, belongingness, and burdensomeness. The best fitting model for the acquired capability allowed for additive genetic and environmental effects, whereas the best fitting model for burdensomeness and belongingness allowed for shared and nonshared environmental effects. The present research extends prior work by specifying the environmental and genetic contributions to the components of the IPTS, and our findings suggest that belongingness and burdensomeness may be more appropriate targets for clinical intervention than acquired capability as these factors may be more malleable or amenable to change. PMID:22417928

  12. Methods for determining the genetic affinity of microorganisms and viruses

    NASA Technical Reports Server (NTRS)

    Fox, George E. (Inventor); Willson, III, Richard C. (Inventor); Zhang, Zhengdong (Inventor)

    2012-01-01

    Selecting which sub-sequences in a database of nucleic acid such as 16S rRNA are highly characteristic of particular groupings of bacteria, microorganisms, fungi, etc. on a substantially phylogenetic tree. Also applicable to viruses comprising viral genomic RNA or DNA. A catalogue of highly characteristic sequences identified by this method is assembled to establish the genetic identity of an unknown organism. The characteristic sequences are used to design nucleic acid hybridization probes that include the characteristic sequence or its complement, or are derived from one or more characteristic sequences. A plurality of these characteristic sequences is used in hybridization to determine the phylogenetic tree position of the organism(s) in a sample. Those target organisms represented in the original sequence database and sufficient characteristic sequences can identify to the species or subspecies level. Oligonucleotide arrays of many probes are especially preferred. A hybridization signal can comprise fluorescence, chemiluminescence, or isotopic labeling, etc.; or sequences in a sample can be detected by direct means, e.g. mass spectrometry. The method's characteristic sequences can also be used to design specific PCR primers. The method uniquely identifies the phylogenetic affinity of an unknown organism without requiring prior knowledge of what is present in the sample. Even if the organism has not been previously encountered, the method still provides useful information about which phylogenetic tree bifurcation nodes encompass the organism.

  13. Genetically determined asynapsis, spermatogenic degeneration, and infertility in men.

    PubMed

    Chaganti, R S; Jhanwar, S C; Ehrenbard, L T; Kourides, I A; Williams, J J

    1980-11-01

    We report a family in which azoospermia and infertility affected two sibs whose parents were first cousins once removed. Meiotic cells of the proband, who had the chromosomal complement of a normal male (46,XY), exhibited asynapsis, defective synaptonemal complex (SC) formation, chiasma failure, and degeneration of prophase spermatocytes with asynapsis. Based on these observations, we suggest that the meiotic abnormalities and infertility in this family comprise a trait with an autosomal recessive mode of inheritance. Review of published cases of infertile men with normal chromosomal complements and disturbed meiosis suggests that genetically determined asynapsis and desynapsis similar to that established in plant and insect species also occur in humans. In humans, asynapsis appears to be inherited as an autosomal recessive. The mode of inheritance of desynapsis is not clear; X-linked recessive or autosomal dominant has been suggested in one family. Studies by us and by others reported in the literature suggest that the mode of action of genes that affect synapsis and cause a reduction in the numbers of visible chiasmata at diakinesis is dissimilar to that of the action of genes that cause defective meiotic recombination, defective repair of induced damage to DNA in somatic cells, and chromosome instability.

  14. Early Determinants of Obesity: Genetic, Epigenetic, and In Utero Influences

    PubMed Central

    Rhee, Kyung E.; Phelan, Suzanne; McCaffery, Jeanne

    2012-01-01

    There is an emerging body of work indicating that genes, epigenetics, and the in utero environment can impact whether or not a child is obese. While certain genes have been identified that increase one's risk for becoming obese, other factors such as excess gestational weight gain, gestational diabetes mellitus, and smoking can also influence this risk. Understanding these influences can help to inform which behaviors and exposures should be targeted if we are to decrease the prevalence of obesity. By helping parents and young children change certain behaviors and exposures during critical time periods, we may be able to alter or modify one's genetic predisposition. However, further research is needed to determine which efforts are effective at decreasing the incidence of obesity and to develop new methods of prevention. In this paper, we will discuss how genes, epigenetics, and in utero influences affect the development of obesity. We will then discuss current efforts to alter these influences and suggest future directions for this work. PMID:22701495

  15. Genetic Determinants of Symptoms on Viral DNA Satellites ▿

    PubMed Central

    Ding, Chenjun; Qing, Ling; Li, Zhenghe; Liu, Yi; Qian, Yajuan; Zhou, Xueping

    2009-01-01

    Begomovirus-DNA-β disease complexes induce different symptom phenotypes in their hosts. To investigate the genetic determinants of the phenotypic differences, Nicotiana spp. and tomato plants were inoculated with infectious clones of Tobacco curly shoot virus (TbCSV)/TbCSV DNA-β (TbCSB) and Tomato yellow leaf curl China virus (TYLCCNV)/TYLCCNV DNA-β (TYLCCNB) pseudorecombinants and showed that TYLCCNB induced characteristic vein-thickening and enation symptoms, while TbCSB only slightly exacerbated the leaf-curling symptoms, regardless of the helper virus being used. The roles of DNA-β-encoded βC1 and a 430-nucleotide fragment containing the A-rich region and the putative βC1 promoter region of the βC1 gene (referred to as AP) in symptom development were further investigated by constructing hybrid satellites in which the βC1 coding region or AP was exchanged between the two satellite molecules. A TYLCCNB hybrid with TbCSB βC1 lost the ability to elicit the vein-thickening and enation phenotypes. TbCSB hybrids containing the TYLCCNB βC1 or AP fragment failed to induce the characteristic vein thickening and enations. A TYLCCNB hybrid having the TbCSB AP fragment produced the enations, but the number of enations was less and their sizes were reduced. Differently from the phloem-specific pattern of the TYLCCNB promoter, a full-length fragment upstream of the TbCSB βC1 gene confers a constitutive β-glucuronidase expression pattern in transgenic tobacco plants. The above results indicate that the DNA-β-encoded βC1 protein is the symptom determinant, but the promoter of the βC1 gene has influence on symptom production. PMID:19542327

  16. Estimation of genetic parameters for wool fiber diameter measures.

    PubMed

    Iman, N Y; Johnson, C L; Russell, W C; Stobart, R H

    1992-04-01

    Genetic and phenotypic correlations and heritability estimates of side, britch, and core diameters; side and britch CV; side and britch diameter difference; and clean fleece weight were investigated using 385 western white-faced ewes produced by 50 sires and maintained at two locations on a selection study. Data were analyzed using analysis of variance procedures, and effects in the final model included breed of sire-selection line combination, sire within breed-selection line, and location. Heritabilities were estimated by paternal half-sib analysis. Sires within breed-selection line represented a significant source of variation for all traits studied. Location had a significant effect on side diameter, side and britch diameter difference, and clean fleece weight. Age of ewe only affected clean fleece weight. Phenotypic and genetic correlations among side, britch, and core diameter measures were high and positive. Phenotypic correlations ranged from .68 to .75 and genetic correlations ranged from .74 to .89. The genetic correlations between side and britch diameter difference and side diameter or core diameter were small (-.16 and .28, respectively). However, there was a stronger genetic correlation between side and britch diameter difference and britch diameter (.55). Heritability of the difference between side and britch diameter was high (.46 +/- .16) and similar to heritability estimates reported for other wool traits. Results of this study indicate that relatively rapid genetic progress through selection for fiber diameter should be possible. In addition, increased uniformity in fiber diameter should be possible through selection for either side and britch diameter difference or side or britch CV.

  17. Young Adults' Belief in Genetic Determinism, and Knowledge and Attitudes towards Modern Genetics and Genomics: The PUGGS Questionnaire.

    PubMed

    Carver, Rebecca Bruu; Castéra, Jérémy; Gericke, Niklas; Evangelista, Neima Alice Menezes; El-Hani, Charbel N

    2017-01-01

    In this paper we present the development and validation a comprehensive questionnaire to assess college students' knowledge about modern genetics and genomics, their belief in genetic determinism, and their attitudes towards applications of modern genetics and genomic-based technologies. Written in everyday language with minimal jargon, the Public Understanding and Attitudes towards Genetics and Genomics (PUGGS) questionnaire is intended for use in research on science education and public understanding of science, as a means to investigate relationships between knowledge, determinism and attitudes about modern genetics, which are to date little understood. We developed a set of core ideas and initial items from reviewing the scientific literature on genetics and previous studies on public and student knowledge and attitudes about genetics. Seventeen international experts from different fields (e.g., genetics, education, philosophy of science) reviewed the initial items and their feedback was used to revise the questionnaire. We validated the questionnaire in two pilot tests with samples of university freshmen students. The final questionnaire contains 45 items, including both multiple choice and Likert scale response formats. Cronbach alpha showed good reliability for each section of the questionnaire. In conclusion, the PUGGS questionnaire is a reliable tool for investigating public understanding and attitudes towards modern genetics and genomic-based technologies.

  18. Young Adults’ Belief in Genetic Determinism, and Knowledge and Attitudes towards Modern Genetics and Genomics: The PUGGS Questionnaire

    PubMed Central

    Carver, Rebecca Bruu; Castéra, Jérémy; Gericke, Niklas; Evangelista, Neima Alice Menezes

    2017-01-01

    In this paper we present the development and validation a comprehensive questionnaire to assess college students’ knowledge about modern genetics and genomics, their belief in genetic determinism, and their attitudes towards applications of modern genetics and genomic-based technologies. Written in everyday language with minimal jargon, the Public Understanding and Attitudes towards Genetics and Genomics (PUGGS) questionnaire is intended for use in research on science education and public understanding of science, as a means to investigate relationships between knowledge, determinism and attitudes about modern genetics, which are to date little understood. We developed a set of core ideas and initial items from reviewing the scientific literature on genetics and previous studies on public and student knowledge and attitudes about genetics. Seventeen international experts from different fields (e.g., genetics, education, philosophy of science) reviewed the initial items and their feedback was used to revise the questionnaire. We validated the questionnaire in two pilot tests with samples of university freshmen students. The final questionnaire contains 45 items, including both multiple choice and Likert scale response formats. Cronbach alpha showed good reliability for each section of the questionnaire. In conclusion, the PUGGS questionnaire is a reliable tool for investigating public understanding and attitudes towards modern genetics and genomic-based technologies. PMID:28114357

  19. Determinants of Public Attitudes to Genetically Modified Salmon

    PubMed Central

    Amin, Latifah; Azad, Md. Abul Kalam; Gausmian, Mohd Hanafy; Zulkifli, Faizah

    2014-01-01

    The objective of this paper is to assess the attitude of Malaysian stakeholders to genetically modified (GM) salmon and to identify the factors that influence their acceptance of GM salmon using a structural equation model. A survey was carried out on 434 representatives from various stakeholder groups in the Klang Valley region of Malaysia. Public attitude towards GM salmon was measured using self-developed questionnaires with seven-point Likert scales. The findings of this study have confirmed that public attitudes towards GM salmon is a complex issue and should be seen as a multi-faceted process. The most important direct predictors for the encouragement of GM salmon are the specific application-linked perceptions about religious acceptability of GM salmon followed by perceived risks and benefits, familiarity, and general promise of modern biotechnology. Encouragement of GM salmon also involves the interplay among other factors such as general concerns of biotechnology, threatening the natural order of things, the need for labeling, the need for patenting, confidence in regulation, and societal values. The research findings can serve as a database that will be useful for understanding the social construct of public attitude towards GM foods in a developing country. PMID:24489695

  20. Determinants of public attitudes to genetically modified salmon.

    PubMed

    Amin, Latifah; Azad, Md Abul Kalam; Gausmian, Mohd Hanafy; Zulkifli, Faizah

    2014-01-01

    The objective of this paper is to assess the attitude of Malaysian stakeholders to genetically modified (GM) salmon and to identify the factors that influence their acceptance of GM salmon using a structural equation model. A survey was carried out on 434 representatives from various stakeholder groups in the Klang Valley region of Malaysia. Public attitude towards GM salmon was measured using self-developed questionnaires with seven-point Likert scales. The findings of this study have confirmed that public attitudes towards GM salmon is a complex issue and should be seen as a multi-faceted process. The most important direct predictors for the encouragement of GM salmon are the specific application-linked perceptions about religious acceptability of GM salmon followed by perceived risks and benefits, familiarity, and general promise of modern biotechnology. Encouragement of GM salmon also involves the interplay among other factors such as general concerns of biotechnology, threatening the natural order of things, the need for labeling, the need for patenting, confidence in regulation, and societal values. The research findings can serve as a database that will be useful for understanding the social construct of public attitude towards GM foods in a developing country.

  1. Genetic Essentialism: On the Deceptive Determinism of DNA

    ERIC Educational Resources Information Center

    Dar-Nimrod, Ilan; Heine, Steven J.

    2011-01-01

    This article introduces the notion of genetic essentialist biases: cognitive biases associated with essentialist thinking that are elicited when people encounter arguments that genes are relevant for a behavior, condition, or social group. Learning about genetic attributions for various human conditions leads to a particular set of thoughts…

  2. Genetic Essentialism: On the Deceptive Determinism of DNA

    ERIC Educational Resources Information Center

    Dar-Nimrod, Ilan; Heine, Steven J.

    2011-01-01

    This article introduces the notion of genetic essentialist biases: cognitive biases associated with essentialist thinking that are elicited when people encounter arguments that genes are relevant for a behavior, condition, or social group. Learning about genetic attributions for various human conditions leads to a particular set of thoughts…

  3. Placebo Responses in Genetically Determined Intellectual Disability: A Meta-Analysis

    PubMed Central

    Curie, Aurore; Yang, Kathy; Kirsch, Irving; Gollub, Randy L.; des Portes, Vincent; Kaptchuk, Ted J.; Jensen, Karin B.

    2015-01-01

    Background Genetically determined Intellectual Disability (ID) is an intractable condition that involves severe impairment of mental abilities such as learning, reasoning and predicting the future. As of today, little is known about the placebo response in patients with ID. Objective To determine if placebo response exists in patients with genetically determined ID. Data sources and Study selection We searched Medline/PubMed, EMBASE, CENTRAL and PsycINFO to find all placebo-controlled double-blind randomized clinical trials (RCTs) in patients with genetically determined ID, published up to April 2013, focusing on core ID symptoms. Data extraction and synthesis Two investigators extracted outcome data independently. Main outcomes and measures Bias-corrected standardized mean difference (Hedge’s g) was computed for each outcome measure, using the Comprehensive Meta-Analysis software. A priori defined patient sub-groups were analyzed using a mixed-effect model. The relationship between pre-defined continuous variable moderators (age, IQ, year of publication and trial duration) and effect size was analyzed using meta-regression Results Twenty-two placebo-controlled double-blind RCTs met the inclusion criteria (n = 721, mean age = 17.1 years, 62% men, mean trial duration = 35 weeks). There was a significant overall placebo response from pre- to post-treatment in patients with ID (g = 0.468, p = 0.002), both for “subjective outcomes” (a third-person’s evaluation of the patient) (g = 0.563, p = 0.022) and “objective outcomes” (direct evaluation of the patient’s abilities) (g = 0.434, p = 0.036). Individuals with higher IQ had higher response to placebo (p = 0.02) and no placebo response was observed in ID patients with comorbid dementia. A significant effect of age (p = 0.02) was found, indicating higher placebo responses in treatment of younger patients. Conclusions and relevance Results suggest that patients with genetically determined ID improve in the

  4. Genetically-encoded probes for measurement of intracellular calcium

    PubMed Central

    Whitaker, Michael

    2012-01-01

    Small, fluorescent, calcium-sensing molecules have been enormously useful in mapping intracellular calcium signals in time and space, as chapters in this volume attest. Despite their widespread adoption and utility, they suffer some disadvantages. Genetically-encoded calcium sensors that can by expressed inside cells by transfection or transgenesis are desirable. The last ten years have been marked by a rapid evolution in the laboratory of genetically encoded calcium sensors two families both figuratively and literally, resulting in11distinct configurations of fluorescent proteins and their attendant calcium sensor modules. Here, I described the design logic and performance of this abundant collection of sensors and describe their use and performance in intro and in vivo. Genetically-encoded calcium sensors have proved valuable in the measurement of calcium concentration in cellular organelles, for the most part in single cells in vitro. Their success as quantitative calcium sensors in tissues in vitro and in vivo is qualified, but they have proved valuable in imaging the pattern of calcium signals within tissues in whole animals. Some branches of the calcium sensor evolutionary tree continue to evolve rapidly and the steady progress in optimising sensor parameters leads to the certain hope that these drawbacks will eventually be overcome by further genetic engineering. PMID:21035686

  5. Determination of genetic relatedness from low-coverage human genome sequences using pedigree simulations.

    PubMed

    Martin, Michael D; Jay, Flora; Castellano, Sergi; Slatkin, Montgomery

    2017-08-01

    We develop and evaluate methods for inferring relatedness among individuals from low-coverage DNA sequences of their genomes, with particular emphasis on sequences obtained from fossil remains. We suggest the major factors complicating the determination of relatedness among ancient individuals are sequencing depth, the number of overlapping sites, the sequencing error rate and the presence of contamination from present-day genetic sources. We develop a theoretical model that facilitates the exploration of these factors and their relative effects, via measurement of pairwise genetic distances, without calling genotypes, and determine the power to infer relatedness under various scenarios of varying sequencing depth, present-day contamination and sequencing error. The model is validated by a simulation study as well as the analysis of aligned sequences from present-day human genomes. We then apply the method to the recently published genome sequences of ancient Europeans, developing a statistical treatment to determine confidence in assigned relatedness that is, in some cases, more precise than previously reported. As the majority of ancient specimens are from animals, this method would be applicable to investigate kinship in nonhuman remains. The developed software grups (Genetic Relatedness Using Pedigree Simulations) is implemented in Python and freely available. © 2017 John Wiley & Sons Ltd.

  6. Genetic determinants of heat resistance in Escherichia coli

    PubMed Central

    Mercer, Ryan G.; Zheng, Jinshui; Garcia-Hernandez, Rigoberto; Ruan, Lifang; Gänzle, Michael G.; McMullen, Lynn M.

    2015-01-01

    Escherichia coli AW1.7 is a heat resistant food isolate and the occurrence of pathogenic strains with comparable heat resistance may pose a risk to food safety. To identify the genetic determinants of heat resistance, 29 strains of E. coli that differed in their of heat resistance were analyzed by comparative genomics. Strains were classified as highly heat resistant strains, exhibiting a D60-value of more than 6 min; moderately heat resistant strains, exhibiting a D60-value of more than 1 min; or as heat sensitive. A ~14 kb genomic island containing 16 predicted open reading frames encoding putative heat shock proteins and proteases was identified only in highly heat resistant strains. The genomic island was termed the locus of heat resistance (LHR). This putative operon is flanked by mobile elements and possesses >99% sequence identity to genomic islands contributing to heat resistance in Cronobacter sakazakii and Klebsiella pneumoniae. An additional 41 LHR sequences with >87% sequence identity were identified in 11 different species of β- and γ-proteobacteria. Cloning of the full length LHR conferred high heat resistance to the heat sensitive E. coli AW1.7ΔpHR1 and DH5α. The presence of the LHR correlates perfectly to heat resistance in several species of Enterobacteriaceae and occurs at a frequency of 2% of all E. coli genomes, including pathogenic strains. This study suggests the LHR has been laterally exchanged among the β- and γ-proteobacteria and is a reliable indicator of high heat resistance in E. coli. PMID:26441869

  7. Spatial and temporal determinants of genetic structure in Gentianella bohemica

    PubMed Central

    Königer, Julia; Rebernig, Carolin A; Brabec, Jiří; Kiehl, Kathrin; Greimler, Josef

    2012-01-01

    The biennial plant Gentianella bohemica is a subendemic of the Bohemian Massif, where it occurs in seminatural grasslands. It has become rare in recent decades as a result of profound changes in land use. Using amplified fragment length polymorphisms (AFLP) fingerprint data, we investigated the genetic structure within and among populations of G. bohemica in Bavaria, the Czech Republic, and the Austrian border region. The aim of our study was (1) to analyze the genetic structure among populations and to discuss these findings in the context of present and historical patterns of connectivity and isolation of populations, (2) to analyze genetic structure among consecutive generations (cohorts of two consecutive years), and (3) to investigate relationships between intrapopulational diversity and effective population size (Ne) as well as plant traits. (1) The German populations were strongly isolated from each other (pairwise FST= 0.29–0.60) and from all other populations (FST= 0.24–0.49). We found a pattern of near panmixis among the latter (FST= 0.15–0.35) with geographical distance explaining only 8% of the genetic variance. These results were congruent with a principal coordinate analysis (PCoA) and analysis using STRUCTURE to identify genetically coherent groups. These findings are in line with the strong physical barrier and historical constraints, resulting in separation of the German populations from the others. (2) We found pronounced genetic differences between consecutive cohorts of the German populations (pairwise FST= 0.23 and 0.31), which can be explained by local population history (land use, disturbance). (3) Genetic diversity within populations (Shannon index, HSh) was significantly correlated with Ne (RS= 0.733) and reflected a loss of diversity due to several demographic bottlenecks. Overall, we found that the genetic structure in G. bohemica is strongly influenced by historical periods of high connectivity and isolation as well as by marked

  8. Determination of genetic status in a closed colony of rhesus monkeys (Macaca mulatta).

    PubMed

    Andrade, Marcia C Ribeiro; Penedo, Maria Cecilia T; Ward, Thea; Silva, Virgilio F; Bertolini, Luciana R; Roberts, Jeffrey A; Leite, Jose Paulo G; Cabello, Pedro H

    2004-07-01

    The long-term management of breeding colonies requires some measure of genetic diversity in the animal population. For the maintenance of breeding colonies of monkeys used for biomedical research, known pedigrees supply precise data to determine the genetic status of colonies. We present data of genetic analyses in an old closed colony of rhesus macaques (Macaca mulatta) that was established in 1932 with 100 animals. For more than 40 years, the animals were kept on an isolated island and, in 1980, single-male breeding groups were established. A total of 333 DNA samples of these animals were typed to 20 microsatellite markers using multiplex PCR in order to verify inbreeding coefficient (alpha) and level of heterozygosity. We found an average heterozygosity of 64% and obtained alpha=-0.03293 (+/-0.00573). Our results indicate that the reproductive strategy used was effective because consanguineous breeding was avoided. A continuous genetic program must be carried out in order to obtain better quality primates for biomedical research.

  9. Genetic diversity in natural populations of Jacaranda decurrens Cham. determined using RAPD and AFLP markers

    PubMed Central

    2010-01-01

    Jacaranda decurrens (Bignoniaceae) is an endemic species of the Cerrado with validated antitumoral activity. The genetic diversity of six populations of J. decurrens located in the State of São Paulo was determined in this study by using molecular markers for randomly amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP). Following optimization of the amplification reaction, 10 selected primers generated 78 reproducible RAPD fragments that were mostly (69.2%) polymorphic. Two hundred and five reproducible AFLP fragments were generated by using four selected primer combinations; 46.3% of these fragments were polymorphic, indicating a considerable level of genetic diversity. Analysis of molecular variance (AMOVA) using these two groups of markers indicated that variability was strongly structured amongst populations. The unweighted pair group method with arithmatic mean (UPGMA) and Pearson's correlation coefficient (RAPD -0.16, p = 0.2082; AFLP 0.37, p = 0.1006) between genetic matrices and geographic distances suggested that the population structure followed an island model in which a single population of infinite size gave rise to the current populations of J. decurrens, independently of their spatial position. The results of this study indicate that RAPD and AFLP markers were similarly efficient in measuring the genetic variability amongst natural populations of J. decurrens. These data may be useful for developing strategies for the preservation of this medicinal species in the Cerrado. PMID:21637428

  10. Genetic diversity in natural populations of Jacaranda decurrens Cham. determined using RAPD and AFLP markers.

    PubMed

    Bertoni, Bianca W; de C Telles, Mariana P; Malosso, Milena G; Torres, Simone C Z; Pereira, José O; Lourenço, Mirian V; de C França, Suzelei; Pereira, Ana M S

    2010-07-01

    Jacaranda decurrens (Bignoniaceae) is an endemic species of the Cerrado with validated antitumoral activity. The genetic diversity of six populations of J. decurrens located in the State of São Paulo was determined in this study by using molecular markers for randomly amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP). Following optimization of the amplification reaction, 10 selected primers generated 78 reproducible RAPD fragments that were mostly (69.2%) polymorphic. Two hundred and five reproducible AFLP fragments were generated by using four selected primer combinations; 46.3% of these fragments were polymorphic, indicating a considerable level of genetic diversity. Analysis of molecular variance (AMOVA) using these two groups of markers indicated that variability was strongly structured amongst populations. The unweighted pair group method with arithmatic mean (UPGMA) and Pearson's correlation coefficient (RAPD -0.16, p = 0.2082; AFLP 0.37, p = 0.1006) between genetic matrices and geographic distances suggested that the population structure followed an island model in which a single population of infinite size gave rise to the current populations of J. decurrens, independently of their spatial position. The results of this study indicate that RAPD and AFLP markers were similarly efficient in measuring the genetic variability amongst natural populations of J. decurrens. These data may be useful for developing strategies for the preservation of this medicinal species in the Cerrado.

  11. Origin and evolution of the dependent lineages in the genetic caste determination system of Pogonomyrmex ants.

    PubMed

    Sirviö, Anu; Pamilo, Pekka; Johnson, Robert A; Page, Robert E; Gadau, Jürgen

    2011-03-01

    Hybridizing harvester ants of the Pogonomyrmex barbatus/rugosus complex have an exceptional genetic caste determination (GCD) mechanism. We combined computer simulations, population genomics, and linkage mapping using >1000 nuclear AFLP markers and a partial mtDNA sequence to explore the genetic architecture and origin of the dependent lineages. Our samples included two pairs of hybridizing lineages, and the mitochondrial and nuclear data showed contradicting affinities between them. Clustering of individual genotypes based on nuclear markers indicated some exceptions to the general GCD system, that is, interlineage hybrid genes as well as some pure-line workers. A genetic linkage map of P. rugosus showed one of the highest recombination rates ever measured in insects (14.0 cM/Mb), supporting the view that social insects are characterized by high recombination rates. The population data had 165 markers in which sibling pairs showed a significant genetic difference depending on the caste. The differences were scattered in the genome; 13 linkage groups had loci with F(ST)>0.9 between the hybridizing lineages J1 and J2.The mapping results and the population data indicate that the dependent lineages have been initially formed through hybridization at different points in time but the role of introgression has been insignificant in their later evolution.

  12. Evidence for a genetic link between bone and vascular measures in African ancestry families.

    PubMed

    Kuipers, Allison L; Miljkovic, Iva; Kammerer, Candace M; Evans, Rhobert W; Bunker, Clareann H; Patrick, Alan L; Wheeler, Victor W; Sutton-Tyrrell, Kim; Zmuda, Joseph M

    2013-08-01

    Bone mineral density (BMD) has been inversely associated with subclinical and clinical cardiovascular disease (CVD) in population studies, but the potential mechanisms underlying this relationship are unclear. To test if there is a genetic basis underlying this association, we determined the phenotypic and genetic correlations between BMD and carotid artery ultrasound measures in families. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were used to measure BMD in 461 individuals with African ancestry belonging to seven large, multigenerational families (mean family size 66; 3414 total relative pairs). Carotid artery ultrasound was used to measure adventitial diameter (AD) and intima-media thickness (IMT). Phenotypic and genetic correlations between BMD and carotid measures were determined using pedigree-based maximum likelihood methods. We adjusted for potential confounding factors, including age, sex, body weight, height, menopausal status, smoking, alcohol intake, walking for exercise, diabetes, hypertension, serum lipid and lipoprotein levels, inflammation markers, and kidney function. We found statistically significant phenotypic (ρ = -0.19) and genetic (ρG  = -0.70) correlations (p < 0.05 for both) between lumbar spine BMD and AD in fully adjusted models. There was also a significant genetic correlation between trabecular BMD at the radius and IMT in fully adjusted models (ρG  = -0.398; p < 0.05). Our findings indicate that the previously observed association between osteoporosis and CVD in population-based studies may be partly mediated by genetic factors and that the pleiotropic effects of these genes may operate independently of traditional risk pathways. Copyright © 2013 American Society for Bone and Mineral Research.

  13. The Genetic Architecture of Hearing Impairment in Mice: Evidence for Frequency-Specific Genetic Determinants.

    PubMed

    Crow, Amanda L; Ohmen, Jeffrey; Wang, Juemei; Lavinsky, Joel; Hartiala, Jaana; Li, Qingzhong; Li, Xin; Salehide, Pezhman; Eskin, Eleazar; Pan, Calvin; Lusis, Aldons J; Allayee, Hooman; Friedman, Rick A

    2015-09-04

    Genome-wide association studies (GWAS) have been successfully applied in humans for the study of many complex phenotypes. However, identification of the genetic determinants of hearing in adults has been hampered, in part, by the relative inability to control for environmental factors that might affect hearing throughout the lifetime, as well as a large degree of phenotypic heterogeneity. These and other factors have limited the number of large-scale studies performed in humans that have identified candidate genes that contribute to the etiology of this complex trait. To address these limitations, we performed a GWAS analysis using a set of inbred mouse strains from the Hybrid Mouse Diversity Panel. Among 99 strains characterized, we observed approximately two-fold to five-fold variation in hearing at six different frequencies, which are differentiated biologically from each other by the location in the cochlea where each frequency is registered. Among all frequencies tested, we identified a total of nine significant loci, several of which contained promising candidate genes for follow-up study. Taken together, our results indicate the existence of both genes that affect global cochlear function, as well as anatomical- and frequency-specific genes, and further demonstrate the complex nature of mammalian hearing variation. Copyright © 2015 Crow et al.

  14. The Genetic Architecture of Hearing Impairment in Mice: Evidence for Frequency-Specific Genetic Determinants

    PubMed Central

    Crow, Amanda L.; Ohmen, Jeffrey; Wang, Juemei; Lavinsky, Joel; Hartiala, Jaana; Li, Qingzhong; Li, Xin; Salehide, Pezhman; Eskin, Eleazar; Pan, Calvin; Lusis, Aldons J.; Allayee, Hooman; Friedman, Rick A.

    2015-01-01

    Genome-wide association studies (GWAS) have been successfully applied in humans for the study of many complex phenotypes. However, identification of the genetic determinants of hearing in adults has been hampered, in part, by the relative inability to control for environmental factors that might affect hearing throughout the lifetime, as well as a large degree of phenotypic heterogeneity. These and other factors have limited the number of large-scale studies performed in humans that have identified candidate genes that contribute to the etiology of this complex trait. To address these limitations, we performed a GWAS analysis using a set of inbred mouse strains from the Hybrid Mouse Diversity Panel. Among 99 strains characterized, we observed approximately two-fold to five-fold variation in hearing at six different frequencies, which are differentiated biologically from each other by the location in the cochlea where each frequency is registered. Among all frequencies tested, we identified a total of nine significant loci, several of which contained promising candidate genes for follow-up study. Taken together, our results indicate the existence of both genes that affect global cochlear function, as well as anatomical- and frequency-specific genes, and further demonstrate the complex nature of mammalian hearing variation. PMID:26342000

  15. Mapping genetic determinants of kidney damage in rat models.

    PubMed

    Schulz, Angela; Kreutz, Reinhold

    2012-07-01

    During the last two decades, significant progress in our understanding of the development of kidney diseases has been achieved by unravelling the mechanisms underlying rare familial forms of human kidney diseases. Due to the genetic heterogeneity in human populations and the complex multifactorial pathogenesis of the disease phenotypes, the dissection of the genetic basis of common chronic kidney diseases (CKD) remains a difficult task. In this regard, several inbred rat models provide valuable complementary tools to uncover the genetic basis of complex renal disease phenotypes that are related to common forms of CKD. In this review, data obtained in nine experimental rat models, including the Buffalo (BUF), Dahl salt-sensitive (SS), Fawn-hooded hypertensive (FHH), Goto-Kakizaki (GK), Lyon hypertensive (LH), Munich Wistar Frömter (MWF), Sabra hypertension-prone (SBH), spontaneously hypertensive rat (SHR) and stroke-prone spontaneously hypertensive rat (SHRSP) inbred strains, that contributed to the genetic dissection of renal disease phenotypes are presented. In this panel of inbred strains, a large number of quantitative trait loci (QTL) linked to albuminuria/proteinuria and other functional or structural kidney abnormalities could be identified by QTL mapping analysis and follow-up studies including consomic and congenic rat lines. The comprehensive exploitation of the genotype-renal phenotype associations that are inherited in this panel of rat strains is suitable for making a significant contribution to the development of an integrated approach to the systems genetics of common CKD.

  16. Genetic Determinants of Pubertal Timing in the General Population

    PubMed Central

    Gajdos, Zofia K.Z.; Henderson, Katherine D.; Hirschhorn, Joel N.

    2010-01-01

    Puberty is an important developmental stage during which reproductive capacity is attained. The timing of puberty varies greatly among healthy individuals in the general population and is influenced by both genetic and environmental factors. Although genetic variation is known to influence the normal spectrum of pubertal timing, the specific genes involved remain largely unknown. Genetic analyses have identified a number of genes responsible for rare disorders of pubertal timing such as hypogonadotropic hypogonadism and Kallmann syndrome. Recently, the first loci with common variation reproducibly associated with population variation in the timing of puberty were identified at 6q21 in or near LIN28B and at 9q31.2. However, these two loci explain only a small fraction of the genetic contribution to population variation in pubertal timing, suggesting the need to continue to consider other loci and other types of variants. Here we provide an update of the genes implicated in disorders of puberty, discuss genes and pathways that may be involved in the timing of normal puberty, and suggest additional avenues of investigation to identify genetic regulators of puberty in the general population. PMID:20144687

  17. Genetic determinants of mate recognition in Brachionus manjavacas (Rotifera).

    PubMed

    Snell, Terry W; Shearer, Tonya L; Smith, Hilary A; Kubanek, Julia; Gribble, Kristin E; Welch, David B Mark

    2009-09-09

    Mate choice is of central importance to most animals, influencing population structure, speciation, and ultimately the survival of a species. Mating behavior of male brachionid rotifers is triggered by the product of a chemosensory gene, a glycoprotein on the body surface of females called the mate recognition pheromone. The mate recognition pheromone has been biochemically characterized, but little was known about the gene(s). We describe the isolation and characterization of the mate recognition pheromone gene through protein purification, N-terminal amino acid sequence determination, identification of the mate recognition pheromone gene from a cDNA library, sequencing, and RNAi knockdown to confirm the functional role of the mate recognition pheromone gene in rotifer mating. A 29 kD protein capable of eliciting rotifer male circling was isolated by high-performance liquid chromatography. Two transcript types containing the N-terminal sequence were identified in a cDNA library; further characterization by screening a genomic library and by polymerase chain reaction revealed two genes belonging to each type. Each gene begins with a signal peptide region followed by nearly perfect repeats of an 87 to 92 codon motif with no codons between repeats and the final motif prematurely terminated by the stop codon. The two Type A genes contain four and seven repeats and the two Type B genes contain three and five repeats, respectively. Only the Type B gene with three repeats encodes a peptide with a molecular weight of 29 kD. Each repeat of the Type B gene products contains three asparagines as potential sites for N-glycosylation; there are no asparagines in the Type A genes. RNAi with Type A double-stranded RNA did not result in less circling than in the phosphate-buffered saline control, but transfection with Type B double-stranded RNA significantly reduced male circling by 17%. The very low divergence between repeat units, even at synonymous positions, suggests that the

  18. Information Measures for Statistical Orbit Determination

    ERIC Educational Resources Information Center

    Mashiku, Alinda K.

    2013-01-01

    The current Situational Space Awareness (SSA) is faced with a huge task of tracking the increasing number of space objects. The tracking of space objects requires frequent and accurate monitoring for orbit maintenance and collision avoidance using methods for statistical orbit determination. Statistical orbit determination enables us to obtain…

  19. Information Measures for Statistical Orbit Determination

    ERIC Educational Resources Information Center

    Mashiku, Alinda K.

    2013-01-01

    The current Situational Space Awareness (SSA) is faced with a huge task of tracking the increasing number of space objects. The tracking of space objects requires frequent and accurate monitoring for orbit maintenance and collision avoidance using methods for statistical orbit determination. Statistical orbit determination enables us to obtain…

  20. Genetic diversity of pomegranate germplasm collection from Spain determined by fruit, seed, leaf and flower characteristics

    PubMed Central

    Melgarejo, Pablo; Legua, Pilar; Garcia-Sanchez, Francisco; Hernández, Francisca

    2016-01-01

    Background. Miguel Hernandez University (Spain) created a germplasm bank of the varieties of pomegranate from different Southeastern Spain localities in order to preserve the crop’s wide genetic diversity. Once this collection was established, the next step was to characterize the phenotype of these varieties to determine the phenotypic variability that existed among all the different pomegranate genotypes, and to understand the degree of polymorphism of the morphometric characteristics among varieties. Methods. Fifty-three pomegranate (Punica granatum L.) accessions were studied in order to determine their degree of polymorphism and to detect similarities in their genotypes. Thirty-one morphometric characteristics were measured in fruits, arils, seeds, leaves and flowers, as well as juice characteristics including content, pH, titratable acidity, total soluble solids and maturity index. ANOVA, principal component analysis, and cluster analysis showed that there was a considerable phenotypic diversity (and presumably genetic). Results. The cluster analysis produced a dendrogram with four main clusters. The dissimilarity level ranged from 1 to 25, indicating that there were varieties that were either very similar or very different from each other, with varieties from the same geographical areas being more closely related. Within each varietal group, different degrees of similarity were found, although there were no accessions that were identical. These results highlight the crop’s great genetic diversity, which can be explained not only by their different geographical origins, but also to the fact that these are native plants that have not come from genetic improvement programs. The geographic origin could be, in the cases where no exchanges of plant material took place, a key criterion for cultivar clustering. Conclusions. As a result of the present study, we can conclude that among all the parameters analyzed, those related to fruit and seed size as well as

  1. Determining the Molecular and Genetic Basis for Diabetes in Navy Bottlenose Dolphins (Tursiops truncatus)

    DTIC Science & Technology

    2015-01-12

    3. DATES COVERED (From Jul 2012-Sep 2013 To) 4. TITLE AND SUBTITLE Determining the molecular and genetic basis for diabetes in Navy bottlenose...thereby reduces hepatic glucose production. 15. SUBJECT TERMS Gluconeogenesis, CREB ZF, Fasting, Diabetes 16. SECURITY CLASSIFICATION OF: a...Number: N000141210617 Award Title: Determining the molecular and genetic basis for diabetes in Navy bottlenose dolphins (Tursiops truncates

  2. Genetic determinants of resistance to gastrointestinal nematodes in ruminants

    USDA-ARS?s Scientific Manuscript database

    Genetic markers for host resistance to gastrointestinal parasites have long been sought by the livestock industry as a way to select more resistant individuals, and alternatively, to help farmers with parasite control because high egg shedders will be removed from the flock and reduce parasite trans...

  3. Genetic Endowment and Environment in the Determination of Behavior.

    ERIC Educational Resources Information Center

    Ehrman, Lee; And Others

    A research workshop was organized to bring together geneticists, psychologists, and other behavioral scientists. The intent was to bring about an interaction of ideas concerned with the genetics of behavior and learning. The emphasis was upon interdisciplinary study among scientists from several fields. Specific issues were isolated in those areas…

  4. Resistance to hepatitis C virus: potential genetic and immunological determinants.

    PubMed

    Mina, Michael M; Luciani, Fabio; Cameron, Barbara; Bull, Rowena A; Beard, Michael R; Booth, David; Lloyd, Andrew R

    2015-04-01

    Studies of individuals who were highly exposed but seronegative (HESN) for HIV infection led to the discovery that homozygosity for the Δ32 deletion mutation in the CCR5 gene prevents viral entry into target cells, and is associated with resistance to infection. Additionally, evidence for protective immunity has been noted in some HESN groups, such as sex workers in The Gambia. Population studies of individuals at high risk for hepatitis C virus infection suggest that an HESN phenotype exists. The body of evidence, which suggests that protective immunity allows clearance of hepatitis C virus without seroconversion is growing. Furthermore, proof-of-principle evidence from in-vitro studies shows that genetic polymorphisms can confer resistance to establishment of infection. This Review discusses the possibility that genetic mutations confer resistance against hepatitis C virus, and also explores evidence for protective immunity, including via genetically programmed variations in host responses. The data generally strengthens the notion that investigations of naturally arising polymorphisms within the hepatitis C virus interactome, and genetic association studies of well characterised HESN individuals, could identify potential targets for vaccine design and inform novel therapies.

  5. Genetic Determinants of Radiographic Knee Osteoarthritis in African Americans.

    PubMed

    Liu, Youfang; Yau, Michelle S; Yerges-Armstrong, Laura M; Duggan, David J; Renner, Jordan B; Hochberg, Marc C; Mitchell, Braxton D; Jackson, Rebecca D; Jordan, Joanne M

    2017-09-15

    The etiology of knee osteoarthritis (OA), the most common form of arthritis, is complex and may differ by race or ethnicity. In recent years, genetic studies have identified many genetic variants associated with OA, but nearly all the studies were conducted in European whites and Asian Americans. Few studies have focused on the genetics of knee OA in African Americans. We performed a genome-wide association study of radiographic knee OA in 1217 African Americans from 2 North American cohort studies: 590 subjects from the Johnston County Osteoarthritis Project and 627 subjects from the Osteoarthritis Initiative. Analyses were conducted in each cohort separately and combined in an inverse variance fixed effects metaanalysis, which were then included in pathway analyses. We additionally tested 12 single-nucleotide polymorphisms robustly associated with OA in European white populations for association in African Americans. We identified a genome-wide significant variant in LINC01006 (minor allele frequency 12%; p = 4.11 × 10(-9)) that is less common in European white populations (minor allele frequency < 3%). Five other independent loci reached suggestive significance (p < 1 × 10(-6)). In pathway analyses, dorsal/ventral neural tube patterning and iron ion transport pathways were significantly associated with knee OA in African Americans (false discovery rate < 0.05). We found no evidence that previously reported OA susceptibility variants in European whites were associated with knee OA in African Americans. These results highlight differences in the genetic architecture of knee OA between African American and European whites. This finding underscores the need to include more diverse populations in OA genetics studies.

  6. The determination of measures of software reliability

    NASA Technical Reports Server (NTRS)

    Maxwell, F. D.; Corn, B. C.

    1978-01-01

    Measurement of software reliability was carried out during the development of data base software for a multi-sensor tracking system. The failure ratio and failure rate were found to be consistent measures. Trend lines could be established from these measurements that provide good visualization of the progress on the job as a whole as well as on individual modules. Over one-half of the observed failures were due to factors associated with the individual run submission rather than with the code proper. Possible application of these findings for line management, project managers, functional management, and regulatory agencies is discussed. Steps for simplifying the measurement process and for use of these data in predicting operational software reliability are outlined.

  7. Nature and Extent of Genetic Diversity of Dengue Viruses Determined by 454 Pyrosequencing

    PubMed Central

    Choudhury, Md Abu; Lott, William B; Banu, Shahera; Cheng, Anthony Youzhi; Teo, Yik-Ying; Ong, Rick Twee-Hee; Aaskov, John

    2015-01-01

    Dengue virus (DENV) populations are characteristically highly diverse. Regular lineage extinction and replacement is an important dynamic DENV feature, and most DENV lineage turnover events are associated with increased incidence of disease. The role of genetic diversity in DENV lineage extinctions is not understood. We investigated the nature and extent of genetic diversity in the envelope (E) gene of DENV serotype 1 representing different lineages histories. A region of the DENV genome spanning the E gene was amplified and sequenced by Roche/454 pyrosequencing. The pyrosequencing results identified distinct sub-populations (haplotypes) for each DENV-1 E gene. A phylogenetic tree was constructed with the consensus DENV-1 E gene nucleotide sequences, and the sequences of each constructed haplotype showed that the haplotypes segregated with the Sanger consensus sequence of the population from which they were drawn. Haplotypes determined through pyrosequencing identified a recombinant DENV genome that could not be identified through Sanger sequencing. Nucleotide level sequence diversities of DENV-1 populations determined from SNP analysis were very low, estimated from 0.009–0.01. There were also no stop codon, frameshift or non-frameshift mutations observed in the E genes of any lineage. No significant correlations between the accumulation of deleterious mutations or increasing genetic diversity and lineage extinction were observed (p>0.5). Although our hypothesis that accumulation of deleterious mutations over time led to the extinction and replacement of DENV lineages was ultimately not supported by the data, our data does highlight the significant technical issues that must be resolved in the way in which population diversity is measured for DENV and other viruses. The results provide an insight into the within-population genetic structure and diversity of DENV-1 populations. PMID:26566128

  8. Genetic determinants of mate recognition in Brachionus manjavacas (Rotifera)

    PubMed Central

    Snell, Terry W; Shearer, Tonya L; Smith, Hilary A; Kubanek, Julia; Gribble, Kristin E; Welch, David B Mark

    2009-01-01

    Background Mate choice is of central importance to most animals, influencing population structure, speciation, and ultimately the survival of a species. Mating behavior of male brachionid rotifers is triggered by the product of a chemosensory gene, a glycoprotein on the body surface of females called the mate recognition pheromone. The mate recognition pheromone has been biochemically characterized, but little was known about the gene(s). We describe the isolation and characterization of the mate recognition pheromone gene through protein purification, N-terminal amino acid sequence determination, identification of the mate recognition pheromone gene from a cDNA library, sequencing, and RNAi knockdown to confirm the functional role of the mate recognition pheromone gene in rotifer mating. Results A 29 kD protein capable of eliciting rotifer male circling was isolated by high-performance liquid chromatography. Two transcript types containing the N-terminal sequence were identified in a cDNA library; further characterization by screening a genomic library and by polymerase chain reaction revealed two genes belonging to each type. Each gene begins with a signal peptide region followed by nearly perfect repeats of an 87 to 92 codon motif with no codons between repeats and the final motif prematurely terminated by the stop codon. The two Type A genes contain four and seven repeats and the two Type B genes contain three and five repeats, respectively. Only the Type B gene with three repeats encodes a peptide with a molecular weight of 29 kD. Each repeat of the Type B gene products contains three asparagines as potential sites for N-glycosylation; there are no asparagines in the Type A genes. RNAi with Type A double-stranded RNA did not result in less circling than in the phosphate-buffered saline control, but transfection with Type B double-stranded RNA significantly reduced male circling by 17%. The very low divergence between repeat units, even at synonymous positions

  9. Genetic and environmental determinants of type II diabetes in Mexico City and San Antonio.

    PubMed

    Stern, M P; Gonzalez, C; Mitchell, B D; Villalpando, E; Haffner, S M; Hazuda, H P

    1992-04-01

    To study genetic and environmental determinants of non-insulin-dependent (type II) diabetes, we compared a random sample of 35- to 64-yr-old Mexican-American men and women living in several low-income barrio neighborhoods of San Antonio to similarly aged Mexicans living in a low-income colonia of Mexico City (Colonia Liberales). A total of 1138 Mexican Americans, representing 64.3% of the original sample, and 646 Mexicans, representing 69.2% of the original sample, participated in the survey. Diabetes was diagnosed using World Health Organization criteria. Genetic susceptibility to type II diabetes was inferred from the percentage of Native American genetic admixture as estimated from skin reflectance measurements. The prevalence of diabetes was 36% higher among San Antonio Mexican Americans than among Mexicans in Mexico City; this difference was highly statistically significant (age- and sex-adjusted prevalence ratio 1.36, P = 0.006). This excess was observed despite the fact that genetic susceptibility, as inferred from the admixture estimates, was similar in the two cities. On the other hand, Mexicans were somewhat leaner as measured by body mass index and skin folds. Mexican women consumed fewer total calories than Mexican-American women, but there was no difference in the caloric intake of men. Mexico City residents ate less fat (18-19% of total calories vs. 31-32% in San Antonio, P less than 0.001), more carbohydrate (64-65 vs. 49%, P less than 0.001), and performed more physical activity than San Antonio Mexican Americans. Mexicans appeared to consume more refined sugar than Mexican Americans.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Determination of the Spatial Distribution in Hydraulic Conductivity Using Genetic Algorithm Optimization

    NASA Astrophysics Data System (ADS)

    Aksoy, A.; Lee, J. H.; Kitanidis, P. K.

    2016-12-01

    Heterogeneity in hydraulic conductivity (K) impacts the transport and fate of contaminants in subsurface as well as design and operation of managed aquifer recharge (MAR) systems. Recently, improvements in computational resources and availability of big data through electrical resistivity tomography (ERT) and remote sensing have provided opportunities to better characterize the subsurface. Yet, there is need to improve prediction and evaluation methods in order to obtain information from field measurements for better field characterization. In this study, genetic algorithm optimization, which has been widely used in optimal aquifer remediation designs, was used to determine the spatial distribution of K. A hypothetical 2 km by 2 km aquifer was considered. A genetic algorithm library, PGAPack, was linked with a fast Fourier transform based random field generator as well as a groundwater flow and contaminant transport simulation model (BIO2D-KE). The objective of the optimization model was to minimize the total squared error between measured and predicted field values. It was assumed measured K values were available through ERT. Performance of genetic algorithm in predicting the distribution of K was tested for different cases. In the first one, it was assumed that observed K values were evaluated using the random field generator only as the forward model. In the second case, as well as K-values obtained through ERT, measured head values were incorporated into evaluation in which BIO2D-KE and random field generator were used as the forward models. Lastly, tracer concentrations were used as additional information in the optimization model. Initial results indicated enhanced performance when random field generator and BIO2D-KE are used in combination in predicting the spatial distribution in K.

  11. Genetic Determinants of Osteoporosis: Common Bases to Cardiovascular Diseases?

    PubMed Central

    Marini, Francesca; Brandi, Maria Luisa

    2010-01-01

    Osteoporosis is the most common and serious age-related skeletal disorder, characterized by a low bone mass and bone microarchitectural deterioration, with a consequent increase in bone fragility and susceptibility to spontaneous fractures, and it represents a major worldwide health care problem with important implications for health care costs, morbidity and mortality. Today is well accepted that osteoporosis is a multifactorial disorder caused by the interaction between environment and genes that singularly exert modest effects on bone mass and other aspects of bone strength and fracture risk. The individuation of genetic factors responsible for osteoporosis predisposition and development is fundamental for the disease prevention and for the setting of novel therapies, before fracture occurrence. In the last decades the interest of the Scientific Community has been concentrated in the understanding the genetic bases of this disease but with controversial and/or inconclusive results. This review tries to summarize data on the most representative osteoporosis candidate genes. Moreover, since recently osteoporosis and cardiovascular diseases have shown to share common physiopathological mechanisms, this review also provides information on the current understanding of osteoporosis and cardiovascular diseases common genetic bases. PMID:20948561

  12. Determination of refractive index, thickness, and the optical losses of thin films from prism-film coupling measurements.

    PubMed

    Cardin, Julien; Leduc, Dominique

    2008-03-01

    We present a method of analysis of prism-film coupler spectroscopy based on the use of transfer matrix and genetic algorithm, which allows the simultaneous determination of refractive index, thickness, and optical losses of the measured layer.

  13. Measuring the Effectiveness of a Genetic Counseling Supervision Training Conference.

    PubMed

    Atzinger, Carrie L; He, Hua; Wusik, Katie

    2016-08-01

    Genetic counselors who receive formal training report increased confidence and competence in their supervisory roles. The effectiveness of specific formal supervision training has not been assessed previously. A day-long GC supervision conference was designed based on published supervision competencies and was attended by 37 genetic counselors. Linear Mixed Model and post-hoc paired t-test was used to compare Psychotherapy Supervisor Development Scale (PSDS) scores among/between individuals pre and post conference. Generalized Estimating Equation (GEE) model and post-hoc McNemar's test was used to determine if the conference had an effect on GC supervision competencies. PSDS scores were significantly increased 1 week (p < 0.001) and 6 months (p < 0.001) following the conference. For three supervision competencies, attendees were more likely to agree they were able to perform them after the conference than before. These effects remained significant 6 months later. For the three remaining competencies, the majority of supervisors agreed they could perform these before the conference; therefore, no change was found. This exploratory study showed this conference increased the perceived confidence and competence of the supervisors who attended and increased their self-reported ability to perform certain supervision competencies. While still preliminary, this supports the idea that a one day conference on supervision has the potential to impact supervisor development.

  14. On Directional Measurement Representation in Orbit Determination

    DTIC Science & Technology

    2016-09-13

    equirectangular projection distorts both distance and direction on a map . One technique is to weight the azimuth residuals by the cosine of the elevation, as in...directional measurements is equivalent to choosing a transformation from location on a sphere to location in a plane which has a long history in map ...The second approach is to preserve area in mapping the celestial sphere to the plane by weighting the azimuth residual by the length of the

  15. Life history determines genetic structure and evolutionary potential of host–parasite interactions

    PubMed Central

    Barrett, Luke G.; Thrall, Peter H.; Burdon, Jeremy J.; Linde, Celeste C.

    2009-01-01

    Measures of population genetic structure and diversity of disease-causing organisms are commonly used to draw inferences regarding their evolutionary history and potential to generate new variation in traits that determine interactions with their hosts. Parasite species exhibit a range of population structures and life-history strategies, including different transmission modes, life-cycle complexity, off-host survival mechanisms and dispersal ability. These are important determinants of the frequency and predictability of interactions with host species. Yet the complex causal relationships between spatial structure, life history and the evolutionary dynamics of parasite populations are not well understood. We demonstrate that a clear picture of the evolutionary potential of parasitic organisms and their demographic and evolutionary histories can only come from understanding the role of life history and spatial structure in influencing population dynamics and epidemiological patterns. PMID:18947899

  16. Accurate measurements of dynamics and reproducibility in small genetic networks

    PubMed Central

    Dubuis, Julien O; Samanta, Reba; Gregor, Thomas

    2013-01-01

    Quantification of gene expression has become a central tool for understanding genetic networks. In many systems, the only viable way to measure protein levels is by immunofluorescence, which is notorious for its limited accuracy. Using the early Drosophila embryo as an example, we show that careful identification and control of experimental error allows for highly accurate gene expression measurements. We generated antibodies in different host species, allowing for simultaneous staining of four Drosophila gap genes in individual embryos. Careful error analysis of hundreds of expression profiles reveals that less than ∼20% of the observed embryo-to-embryo fluctuations stem from experimental error. These measurements make it possible to extract not only very accurate mean gene expression profiles but also their naturally occurring fluctuations of biological origin and corresponding cross-correlations. We use this analysis to extract gap gene profile dynamics with ∼1 min accuracy. The combination of these new measurements and analysis techniques reveals a twofold increase in profile reproducibility owing to a collective network dynamics that relays positional accuracy from the maternal gradients to the pair-rule genes. PMID:23340845

  17. Accurate measurements of dynamics and reproducibility in small genetic networks.

    PubMed

    Dubuis, Julien O; Samanta, Reba; Gregor, Thomas

    2013-01-01

    Quantification of gene expression has become a central tool for understanding genetic networks. In many systems, the only viable way to measure protein levels is by immunofluorescence, which is notorious for its limited accuracy. Using the early Drosophila embryo as an example, we show that careful identification and control of experimental error allows for highly accurate gene expression measurements. We generated antibodies in different host species, allowing for simultaneous staining of four Drosophila gap genes in individual embryos. Careful error analysis of hundreds of expression profiles reveals that less than ∼20% of the observed embryo-to-embryo fluctuations stem from experimental error. These measurements make it possible to extract not only very accurate mean gene expression profiles but also their naturally occurring fluctuations of biological origin and corresponding cross-correlations. We use this analysis to extract gap gene profile dynamics with ∼1 min accuracy. The combination of these new measurements and analysis techniques reveals a twofold increase in profile reproducibility owing to a collective network dynamics that relays positional accuracy from the maternal gradients to the pair-rule genes.

  18. Genetic determinants of blood pressure responses to caffeine drinking.

    PubMed

    Renda, Giulia; Zimarino, Marco; Antonucci, Ivana; Tatasciore, Alfonso; Ruggieri, Benedetta; Bucciarelli, Tonino; Prontera, Tina; Stuppia, Liborio; De Caterina, Raffaele

    2012-01-01

    The widely observed between-subject variability in cardiovascular responses to coffee may have a genetic basis. We evaluated acute blood pressure (BP) responses to caffeine and explored whether they are influenced by candidate gene variants affecting caffeine metabolism (for cytochrome P450 1A2), adenosine metabolism (for adenosine receptor and AMP deaminase), or catecholamine receptors. We recruited 110 healthy male habitual moderate coffee drinkers who refrained from drinking coffee on the day preceding the study. Each subject underwent ambulatory BP monitoring at 6-min intervals for 2 h. Each participant was administered, in a double-blind design, 40 mL of either a decaffeinated coffee preparation plus 3 mg caffeine/kg (caf) or the corresponding vehicle (decaf). The protocol was repeated 24 h later with the alternative preparation. Blood samples were collected for genetic and plasma caffeine and catecholamine evaluations. Compared with decaf, caf was associated with a mean (± SD) significant increase in systolic BP of 4 ± 12 mm Hg and in diastolic BP of 3 ± 10 mm Hg (P < 0.001 for both). Plasma caffeine and adrenaline increased after caf, but not after decaf. Of 11 gene polymorphisms analyzed, a relation was observed between the ADORA2A TT variant and the change in SBP peak and between the ADRA2B I variant and the changes in both SBP mean and peak; mean peak change in SBP; these variants were associated with increased SBP responses to caf. Variability in the acute BP response to coffee may be partly explained by genetic polymorphisms of the adenosine A2A receptors and α(2)-adrenergic receptors. This trial is registered at clinicaltrials.gov as NCT01330680.

  19. Genetic Determinism in the Genetics Curriculum - An Exploratory Study of the Effects of Mendelian and Weldonian Emphases

    NASA Astrophysics Data System (ADS)

    Jamieson, Annie; Radick, Gregory

    2017-07-01

    Twenty-first-century biology rejects genetic determinism, yet an exaggerated view of the power of genes in the making of bodies and minds remains a problem. What accounts for such tenacity? This article reports an exploratory study suggesting that the common reliance on Mendelian examples and concepts at the start of teaching in basic genetics is an eliminable source of support for determinism. Undergraduate students who attended a standard `Mendelian approach' university course in introductory genetics on average showed no change in their determinist views about genes. By contrast, students who attended an alternative course which, inspired by the work of a critic of early Mendelism, W. F. R. Weldon (1860-1906), replaced an emphasis on Mendel's peas with an emphasis on developmental contexts and their role in bringing about phenotypic variability, were less determinist about genes by the end of teaching. Improvements in both the new Weldonian curriculum and the study design are in view for the future.

  20. Genetic influence on blood pressure measured in the office, under laboratory stress and during real life

    PubMed Central

    Wang, Xiaoling; Ding, Xiuhua; Su, Shaoyong; Harshfield, Gregory; Treiber, Frank; Snieder, Harold

    2013-01-01

    To determine to what extent the genetic influences on blood pressure (BP) measured in the office, under psychologically stressful conditions in the laboratory and during real life are different from each other. Office BP, BP during a video game challenge and a social stressor interview, and 24-h ambulatory BP were measured in 238 European American and 186 African American twins. BP values across the two tasks were averaged to represent stress levels. Genetic model fitting showed no ethnic or gender differences for any of the measures. The model fitting resulted in heritability estimates of 63, 75 and 71% for office, stress and 24-h systolic BP (SBP) and 59, 67 and 69% for diastolic BP (DBP), respectively. Up to 81% of the heritability of office SBP and 71% of office DBP were attributed to genes that also influenced stress BP. However, only 45% of the heritability of 24-h SBP and 49% of 24-h DBP were attributed to genes that also influence office BP. Similarly, about 39% of the heritability of 24-h SBP and 42% of 24-h DBP were attributed to genes that also influence stress BP. Substantial overlap exists between genes that influence BP measured in the office, under laboratory stress and during real life. However, significant genetic components specific to each BP measurement also exist. These findings suggest that partly different genes or sets of genes contribute to BP regulation in different conditions. PMID:21068740

  1. Genetic diversity measures of local European beef cattle breeds for conservation purposes

    PubMed Central

    Cañón, Javier; Alexandrino, Paolo; Bessa, Isabel; Carleos, Carlos; Carretero, Yolanda; Dunner, Susana; Ferran, Nuno; Garcia, David; Jordana, Jordi; Laloë, Denis; Pereira, Albano; Sanchez, Armand; Moazami-Goudarzi, Katayoun

    2001-01-01

    This study was undertaken to determine the genetic structure, evolutionary relationships, and the genetic diversity among 18 local cattle breeds from Spain, Portugal, and France using 16 microsatellites. Heterozygosities, estimates of Fst, genetic distances, multivariate and diversity analyses, and assignment tests were performed. Heterozygosities ranged from 0.54 in the Pirenaica breed to 0.72 in the Barrosã breed. Seven percent of the total genetic variability can be attributed to differences among breeds (mean Fst = 0.07; P < 0.01). Five different genetic distances were computed and compared with no correlation found to be significantly different from 0 between distances based on the effective size of the population and those which use the size of the alleles. The Weitzman recursive approach and a multivariate analysis were used to measure the contribution of the breeds diversity. The Weitzman approach suggests that the most important breeds to be preserved are those grouped into two clusters: the cluster formed by the Mirandesa and Alistana breeds and that of the Sayaguesa and Tudanca breeds. The hypothetical extinction of one of those clusters represents a 17% loss of diversity. A correspondence analysis not only distinguished four breed groups but also confirmed results of previous studies classifying the important breeds contributing to diversity. In addition, the variation between breeds was sufficiently high so as to allow individuals to be assigned to their breed of origin with a probability of 99% for simulated samples. PMID:11403750

  2. Genetic determinants of common obesity and their value in prediction.

    PubMed

    Loos, Ruth J F

    2012-04-01

    Genome-wide association studies (GWAS) have revolutionised the discovery of genes for common traits and diseases, including obesity-related traits. In less then four years time, 52 genetic loci were identified to be unequivocally associated with obesity-related traits. This vast success raised hope and expectations that genetic information would become soon an integral part of personalised medicine. However, these loci have only small effects on obesity-susceptibility and explain just a fraction of the total variance. As such, their accuracy to predict obesity is poor and not competitive with the predictive ability of traditional risk factors. Nevertheless, some of these loci are being used in commercially available personal genome tests to estimate individuals' lifetime risk of obesity. While proponents believe that personal genome profiling could have beneficial effects on behaviour, early reports do not support this hypothesis. To conclude, the most valuable contribution of GWAS-identified loci lies in their contribution to elucidating new physiological pathways that underlie obesity-susceptibility.

  3. Genetic determinants of hyaloid and retinal vasculature in zebrafish

    PubMed Central

    Alvarez, Yolanda; Cederlund, Maria L; Cottell, David C; Bill, Brent R; Ekker, Stephen C; Torres-Vazquez, Jesus; Weinstein, Brant M; Hyde, David R; Vihtelic, Thomas S; Kennedy, Breandan N

    2007-01-01

    Background The retinal vasculature is a capillary network of blood vessels that nourishes the inner retina of most mammals. Developmental abnormalities or microvascular complications in the retinal vasculature result in severe human eye diseases that lead to blindness. To exploit the advantages of zebrafish for genetic, developmental and pharmacological studies of retinal vasculature, we characterised the intraocular vasculature in zebrafish. Results We show a detailed morphological and developmental analysis of the retinal blood supply in zebrafish. Similar to the transient hyaloid vasculature in mammalian embryos, vessels are first found attached to the zebrafish lens at 2.5 days post fertilisation. These vessels progressively lose contact with the lens and by 30 days post fertilisation adhere to the inner limiting membrane of the juvenile retina. Ultrastructure analysis shows these vessels to exhibit distinctive hallmarks of mammalian retinal vasculature. For example, smooth muscle actin-expressing pericytes are ensheathed by the basal lamina of the blood vessel, and vesicle vacuolar organelles (VVO), subcellular mediators of vessel-retinal nourishment, are present. Finally, we identify 9 genes with cell membrane, extracellular matrix and unknown identity that are necessary for zebrafish hyaloid and retinal vasculature development. Conclusion Zebrafish have a retinal blood supply with a characteristic developmental and adult morphology. Abnormalities of these intraocular vessels are easily observed, enabling application of genetic and chemical approaches in zebrafish to identify molecular regulators of hyaloid and retinal vasculature in development and disease. PMID:17937808

  4. Strategies for determining kinship in wild populations using genetic data.

    PubMed

    Städele, Veronika; Vigilant, Linda

    2016-09-01

    Knowledge of kin relationships between members of wild animal populations has broad application in ecology and evolution research by allowing the investigation of dispersal dynamics, mating systems, inbreeding avoidance, kin recognition, and kin selection as well as aiding the management of endangered populations. However, the assessment of kinship among members of wild animal populations is difficult in the absence of detailed multigenerational pedigrees. Here, we first review the distinction between genetic relatedness and kinship derived from pedigrees and how this makes the identification of kin using genetic data inherently challenging. We then describe useful approaches to kinship classification, such as parentage analysis and sibship reconstruction, and explain how the combined use of marker systems with biparental and uniparental inheritance, demographic information, likelihood analyses, relatedness coefficients, and estimation of misclassification rates can yield reliable classifications of kinship in groups with complex kin structures. We outline alternative approaches for cases in which explicit knowledge of dyadic kinship is not necessary, but indirect inferences about kinship on a group- or population-wide scale suffice, such as whether more highly related dyads are in closer spatial proximity. Although analysis of highly variable microsatellite loci is still the dominant approach for studies on wild populations, we describe how the long-awaited use of large-scale single-nucleotide polymorphism and sequencing data derived from noninvasive low-quality samples may eventually lead to highly accurate assessments of varying degrees of kinship in wild populations.

  5. Innate immunity and genetic determinants of urinary tract infection susceptibility

    PubMed Central

    Godaly, Gabriela; Ambite, Ines; Svanborg, Catharina

    2015-01-01

    Purpose of review Urinary tract infections (UTIs) are common, dangerous and interesting. Susceptible individuals experience multiple, often clustered episodes, and in a subset of patients, infections progress to acute pyelonephritis (APN), sometimes accompanied by uro-sepsis. Others develop asymptomatic bacteriuria (ABU). Here, we review the molecular basis for these differences, with the intention to distinguish exaggerated host responses that drive disease from attenuated responses that favour protection and to highlight the genetic basis for these extremes, based on knock-out mice and clinical studies. Recent findings The susceptibility to UTI is controlled by specific innate immune signalling and by promoter polymorphisms and transcription factors that modulate the expression of genes controlling these pathways. Gene deletions that disturb innate immune activation either favour asymptomatic bacteriuria or create acute morbidity and disease. Promoter polymorphisms and transcription factor variants affecting those genes are associated with susceptibility in UTI-prone patients. Summary It is time to start using genetics in UTI-prone patients, to improve diagnosis and to assess the risk for chronic sequels such as renal malfunction, hypertension, spontaneous abortions, dialysis and transplantation. Furthermore, the majority of UTI patients do not need follow-up, but for lack of molecular markers, they are unnecessarily investigated. PMID:25539411

  6. Firing up the nature/nurture controversy: bioethics and genetic determinism.

    PubMed

    de Melo-Martín, I

    2005-09-01

    It is argued here that bioethicists might inadvertently be promoting genetic determinism: the idea that genes alone determine human traits and behaviours. Discussions about genetic testing are used to exemplify how they might be doing so. Quite often bioethicists use clinical cases to support particular moral obligations or rights as if these cases were representative of the kind of information we can acquire about human diseases through genetic testing, when they are not. On other occasions, the clinical cases are presented in simplistic ways that portray genetic testing as yielding information more accurate than it actually is. It is concluded that, because of the problematic implications that the ideology of genetic determinism might have for individuals' wellbeing and for our public policies, bioethicists should be careful to present these issues in ways that do not promote questionable ideas about the causal role of genes in human diseases and behaviours.

  7. Trends of the genetic connectedness measures among Nelore beef cattle herds.

    PubMed

    Pegolo, N T; Laloë, D; de Oliveira, H N; Lôbo, R B; Fouilloux, M-N

    2012-02-01

    Validity of comparisons between expected breeding values obtained from best linear unbiased prediction procedures in genetic evaluations is dependent on genetic connectedness among herds. Different cattle breeding programmes have their own particular features that distinguish their database structure and can affect connectedness. Thus, the evolution of these programmes can also alter the connectedness measures. This study analysed the evolution of the genetic connectedness measures among Brazilian Nelore cattle herds from 1999 to 2008, using the French Criterion of Admission to the group of Connected Herds (CACO) method, based on coefficients of determination (CD) of contrasts. Genetic connectedness levels were analysed by using simple and multiple regression analyses on herd descriptors to understand their relationship and their temporal trends from the 1999-2003 to the 2004-2008 period. The results showed a high level of genetic connectedness, with CACO estimates higher than 0.4 for the majority of them. Evaluation of the last 5-year period showed only a small increase in average CACO measures compared with the first 5 years, from 0.77 to 0.80. The percentage of herds with CACO estimates lower than 0.7 decreased from 27.5% in the first period to 16.2% in the last one. The connectedness measures were correlated with percentage of progeny from connecting sires, and the artificial insemination spread among Brazilian herds in recent years. But changes in connectedness levels were shown to be more complex, and their complete explanation cannot consider only herd descriptors. They involve more comprehensive changes in the relationship matrix, which can be only fully expressed by the CD of contrasts.

  8. Genetic Determinism in School Textbooks: A Comparative Study Conducted among Sixteen Countries

    ERIC Educational Resources Information Center

    Castera, Jeremy; Clement, Pierre; Abrougui, Mondher; Nisiforou, Olympia; Valanides, Nicos; Turcinaviciene, Jurga; Sarapuu, Tago; Agorram, Boujemaa; Calado, Florbela; Bogner, Franz; Carvalho, Graca

    2008-01-01

    Genetic concepts have significantly evolved over the last ten years, and are now less connected to innate ideas and reductionism. Unique reference to genetic determinism has been replaced by the interaction between the genes and their environment (epigenetics). Our analyses relate to how current school biology textbooks present this new paradigm…

  9. Determination of Supersymmetric Particle Masses and Attributes with Genetic Divisors

    SciTech Connect

    DAI,YANG; BORISOV,ALEXEY B.; BOYER,KEITH; RHODES,CHARLES K.

    2001-06-01

    Arithmetic conditions relating particle masses can be defined on the basis of (1) the supersymmetric conservation of congruence and (2) the observed characteristics of particle reactions and stabilities. Stated in the form of common divisors, these relations can be interpreted as expressions of genetic elements that represent specific particle characteristics. In order to illustrate this concept, it is shown that the pion triplet ({pi}{sup {+-}}, {pi}{sup 0}) can be associated with the existence of a greatest common divisor d{sub 0{+-}} in a way that can account for both the highly similar physical properties of these particles and the observed {pi}{sup {+-}}/{pi}{sup 0} mass splitting. These results support the conclusion that a corresponding statement holds generally for all particle multiplets. Classification of the respective physical states is achieved by assignment of the common divisors to residue classes in a finite field F{sub P{sub {alpha}}} and the existence of the multiplicative group of units F{sub P{sub {alpha}}} enables the corresponding mass parameters to be associated with a rich subgroup structure. The existence of inverse states in F{sub P{sub {alpha}}} allows relationships connecting particle mass values to be conveniently expressed in a form in which the genetic divisor structure is prominent. An example is given in which the masses of two neutral mesons (K{degree} {r_arrow} {pi}{degree}) are related to the properties of the electron (e), a charged lepton. Physically, since this relationship reflects the cascade decay K{degree} {r_arrow} {pi}{degree} + {pi}{degree}/{pi}{degree} {r_arrow} e{sup +} + e{sup {minus}}, in which a neutral kaon is converted into four charged leptons, it enables the genetic divisor concept, through the intrinsic algebraic structure of the field, to provide a theoretical basis for the conservation of both electric charge and lepton number. It is further shown that the fundamental source of supersymmetry can be expressed

  10. Epilepsy in four genetically determined syndromes of intellectual disability.

    PubMed

    Leung, H T T; Ring, H

    2013-01-01

    Epilepsy occurs with increased frequency in people with an intellectual disability (ID) compared to the rest of the population. A variety of research has in recent years shed light on genetic and biochemical aetiologies of epilepsy and, often in a different literature, on syndromes of ID. The aims of this annotation are to review developments in understanding of the pathophysiology of several ID syndromes in which epilepsy is a frequent co-occurrence and to relate these observations to recent advances in understanding of how these pathophysiological disturbances may lead to epilepsy. The ID syndromes selected for review were fragile X (FXS), Rett (RTT) and Angelman syndromes (AS) and tuberous sclerosis complex (TSC). Epilepsy is a significant aspect of these syndromes and relevant research into the genetic and biochemical pathophysiology of these four ID syndromes may be informative in establishing the association between epilepsy and ID. Employing a structured approach the authors initially searched the PubMed database for large case series describing the characteristics of epilepsy as manifested in these ID syndromes. The criteria for inclusion of the case series in the review were a sample size of greater than 50 and the description of several of the characteristic features of epilepsy, namely prevalence of seizures, age of seizure onset, seizure frequency, seizure semiology, severity and treatment. Following this, studies of the genetic and biochemical pathophysiology of these four ID syndromes were reviewed and the potential relevance of this research in understanding the association with epilepsy highlighted. Findings were considered in a focused manner in terms of effects on excitatory and inhibitory neurotransmitter systems and on glial function. Diverse genetic pathologies underlying several ID syndromes can lead to alterations in the functioning of the glutamatergic and GABAergic neurotransmitter systems. The mechanisms involved include transcriptional

  11. Genetic Determinism of Primary Early-Onset Osteoarthritis.

    PubMed

    Aury-Landas, Juliette; Marcelli, Christian; Leclercq, Sylvain; Boumédiene, Karim; Baugé, Catherine

    2016-01-01

    Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy.

  12. Genetic Distances in Three Ascidian Species determined by PCR Technique

    PubMed Central

    Yoon, Jong-Man

    2016-01-01

    ABSTRACT Seven oligonucleotides primers were shown to generate the shared loci, specific loci, unique shared loci to each species and shared loci by the three species which could be obviously scored. In the present study, 7 oligonucleotides primers produced 401 total loci in the Styela clava (SC) species, 390 in the Halocynthia roretzi (HR) and 434 in the Styela plicata (SP), respectively. Seven oligonucleotides primers generated 275 specific loci in the SC, 341 in the HR and 364 in the SP species, respectively. The oligonucleotides primer BION-23 generated 28 unique loci to each species in the SP species. Especially, the oligonucleotides primer BION-25 produced 7 unique loci to each species, which were identifying each species in the SP species. BION-17 distinguished 21 shared loci by the three ascidian species, major and/or minor fragments of sizes, which were identical in almost all of the samples. Based on the average bandsharing values of all samples, the similarity matrix ranged from 0.519 to 0.774 in the SC species, from 0.261 to 0.683 in the HR species and from 0.346 to 0.730 in the SP species. As regards average bandsharing value (BS) results, individuals from SC species (0.661±0.081) exhibited higher bandsharing values than did individuals from HR species (0.555±0.074) (P<0.05). The dendrogram obtained by the seven oligonucleotides primers indicates three genetic groups. In three ascidian species, the shortest genetic distance (0.071) exhibiting significant molecular difference was also between individual no. 20 and no. 21 within the SP species. PMID:28144642

  13. The Genetic Drift Inventory: A Tool for Measuring What Advanced Undergraduates Have Mastered about Genetic Drift

    ERIC Educational Resources Information Center

    Price, Rebecca M.; Andrews, Tessa C.; McElhinny, Teresa L.; Mead, Louise S.; Abraham, Joel K.; Thanukos, Anna; Perez, Kathryn E.

    2014-01-01

    Understanding genetic drift is crucial for a comprehensive understanding of biology, yet it is difficult to learn because it combines the conceptual challenges of both evolution and randomness. To help assess strategies for teaching genetic drift, we have developed and evaluated the Genetic Drift Inventory (GeDI), a concept inventory that measures…

  14. The Genetic Drift Inventory: A Tool for Measuring What Advanced Undergraduates Have Mastered about Genetic Drift

    ERIC Educational Resources Information Center

    Price, Rebecca M.; Andrews, Tessa C.; McElhinny, Teresa L.; Mead, Louise S.; Abraham, Joel K.; Thanukos, Anna; Perez, Kathryn E.

    2014-01-01

    Understanding genetic drift is crucial for a comprehensive understanding of biology, yet it is difficult to learn because it combines the conceptual challenges of both evolution and randomness. To help assess strategies for teaching genetic drift, we have developed and evaluated the Genetic Drift Inventory (GeDI), a concept inventory that measures…

  15. Frequency of streamflow measurements required to determine forest treatment effects

    Treesearch

    Kenneth G. Reinhart

    1964-01-01

    Most of the stream-discharge records for our experimental watersheds are taken by continuous measurements. But the question arises: are continuous measurements necessary to determine effects of forest treatments? Or could treatment effects be determined by measurement of discharge at intervals, say, once a day or once a week?

  16. Ecological and Genetic Determinants of Pepino Mosaic Virus Emergence

    PubMed Central

    Moreno-Pérez, Manuel G.; Pagán, Israel; Aragón-Caballero, Liliana; Cáceres, Fátima; Fraile, Aurora

    2014-01-01

    ABSTRACT Virus emergence is a complex phenomenon, which generally involves spread to a new host from a wild host, followed by adaptation to the new host. Although viruses account for the largest fraction of emerging crop pathogens, knowledge about their emergence is incomplete. We address here the question of whether Pepino Mosaic Virus (PepMV) emergence as a major tomato pathogen worldwide could have involved spread from wild to cultivated plant species and host adaptation. For this, we surveyed natural populations of wild tomatoes in southern Peru for PepMV infection. PepMV incidence, genetic variation, population structure, and accumulation in various hosts were analyzed. PepMV incidence in wild tomatoes was high, and a strain not yet reported in domestic tomato was characterized. This strain had a wide host range within the Solanaceae, multiplying efficiently in most assayed Solanum species and being adapted to wild tomato hosts. Conversely, PepMV isolates from tomato crops showed evidence of adaptation to domestic tomato, possibly traded against adaptation to wild tomatoes. Phylogenetic reconstructions indicated that the most probable ancestral sequence came from a wild Solanum species. A high incidence of PepMV in wild tomato relatives would favor virus spread to crops and its efficient multiplication in different Solanum species, including tomato, allowing its establishment as an epidemic pathogen. Later, adaptation to tomato, traded off against adaptation to other Solanum species, would isolate tomato populations from those in other hosts. IMPORTANCE Virus emergence is a complex phenomenon involving multiple ecological and genetic factors and is considered to involve three phases: virus encounter with the new host, virus adaptation to the new host, and changes in the epidemiological dynamics. We analyze here if this was the case in the recent emergence of Pepino Mosaic Virus (PepMV) in tomato crops worldwide. We characterized a new strain of PepMV infecting

  17. Genetically Determined Response to Artemisinin Treatment in Western Kenyan Plasmodium falciparum Parasites.

    PubMed

    Chebon, Lorna J; Ngalah, Bidii S; Ingasia, Luicer A; Juma, Dennis W; Muiruri, Peninah; Cheruiyot, Jelagat; Opot, Benjamin; Mbuba, Emmanuel; Imbuga, Mabel; Akala, Hoseah M; Bulimo, Wallace; Andagalu, Ben; Kamau, Edwin

    2016-01-01

    Genetically determined artemisinin resistance in Plasmodium falciparum has been described in Southeast Asia. The relevance of recently described Kelch 13-propeller mutations for artemisinin resistance in Sub-Saharan Africa parasites is still unknown. Southeast Asia parasites have low genetic diversity compared to Sub-Saharan Africa, where parasites are highly genetically diverse. This study attempted to elucidate whether genetics provides a basis for discovering molecular markers in response to artemisinin drug treatment in P. falciparum in Kenya. The genetic diversity of parasites collected pre- and post- introduction of artemisinin combination therapy (ACT) in western Kenya was determined. A panel of 12 microsatellites and 91 single nucleotide polymorphisms (SNPs) distributed across the P. falciparum genome were genotyped. Parasite clearance rates were obtained for the post-ACT parasites. The 12 microsatellites were highly polymorphic with post-ACT parasites being significantly more diverse compared to pre-ACT (p < 0.0001). The median clearance half-life was 2.55 hours for the post-ACT parasites. Based on SNP analysis, 15 of 90 post-ACT parasites were single-clone infections. Analysis revealed 3 SNPs that might have some causal association with parasite clearance rates. Further, genetic analysis using Bayesian tree revealed parasites with similar clearance phenotypes were more closely genetically related. With further studies, SNPs described here and genetically determined response to artemisinin treatment might be useful in tracking artemisinin resistance in Kenya.

  18. Genetically Determined Response to Artemisinin Treatment in Western Kenyan Plasmodium falciparum Parasites

    PubMed Central

    Chebon, Lorna J.; Ngalah, Bidii S.; Ingasia, Luicer A.; Juma, Dennis W.; Muiruri, Peninah; Cheruiyot, Jelagat; Opot, Benjamin; Mbuba, Emmanuel; Imbuga, Mabel; Akala, Hoseah M.; Bulimo, Wallace; Andagalu, Ben; Kamau, Edwin

    2016-01-01

    Genetically determined artemisinin resistance in Plasmodium falciparum has been described in Southeast Asia. The relevance of recently described Kelch 13-propeller mutations for artemisinin resistance in Sub-Saharan Africa parasites is still unknown. Southeast Asia parasites have low genetic diversity compared to Sub-Saharan Africa, where parasites are highly genetically diverse. This study attempted to elucidate whether genetics provides a basis for discovering molecular markers in response to artemisinin drug treatment in P. falciparum in Kenya. The genetic diversity of parasites collected pre- and post- introduction of artemisinin combination therapy (ACT) in western Kenya was determined. A panel of 12 microsatellites and 91 single nucleotide polymorphisms (SNPs) distributed across the P. falciparum genome were genotyped. Parasite clearance rates were obtained for the post-ACT parasites. The 12 microsatellites were highly polymorphic with post-ACT parasites being significantly more diverse compared to pre-ACT (p < 0.0001). The median clearance half-life was 2.55 hours for the post-ACT parasites. Based on SNP analysis, 15 of 90 post-ACT parasites were single-clone infections. Analysis revealed 3 SNPs that might have some causal association with parasite clearance rates. Further, genetic analysis using Bayesian tree revealed parasites with similar clearance phenotypes were more closely genetically related. With further studies, SNPs described here and genetically determined response to artemisinin treatment might be useful in tracking artemisinin resistance in Kenya. PMID:27611315

  19. New thoughts on an old riddle: What determines genetic diversity within and between species?

    PubMed

    Huang, Shi

    2016-07-01

    The question of what determines genetic diversity has long remained unsolved by the modern evolutionary theory (MET). However, it has not deterred researchers from producing interpretations of genetic diversity by using MET. We examine the two observations of genetic diversity made in the 1960s that contributed to the development of MET. The interpretations of these observations by MET are widely known to be inadequate. We review the recent progress of an alternative framework, the maximum genetic diversity (MGD) hypothesis, that uses axioms and natural selection to explain the vast majority of genetic diversity as being at equilibrium that is largely determined by organismal complexity. The MGD hypothesis absorbs the proven virtues of MET and considers its assumptions relevant only to a much more limited scope. This new synthesis has accounted for the overlooked phenomenon of progression towards higher complexity, and more importantly, been instrumental in directing productive research. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Genetic Determinants of the Gut Microbiome in UK Twins.

    PubMed

    Goodrich, Julia K; Davenport, Emily R; Beaumont, Michelle; Jackson, Matthew A; Knight, Rob; Ober, Carole; Spector, Tim D; Bell, Jordana T; Clark, Andrew G; Ley, Ruth E

    2016-05-11

    Studies in mice and humans have revealed intriguing associations between host genetics and the microbiome. Here we report a 16S rRNA-based analysis of the gut microbiome in 1,126 twin pairs, a subset of which was previously reported. Tripling the sample narrowed the confidence intervals around heritability estimates and uncovered additional heritable taxa, some of which are validated in other studies. Repeat sampling of subjects showed heritable taxa to be temporally stable. A candidate gene approach uncovered associations between heritable taxa and genes related to diet, metabolism, and olfaction. We replicate an association between Bifidobacterium and the lactase (LCT) gene locus and identify an association between the host gene ALDH1L1 and the bacteria SHA-98, suggesting a link between formate production and blood pressure. Additional genes detected are involved in barrier defense and self/non-self recognition. Our results indicate that diet-sensing, metabolism, and immune defense are important drivers of human-microbiome co-evolution. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. CTLA-4 as a genetic determinant in autoimmune Addison's disease.

    PubMed

    Wolff, A S B; Mitchell, A L; Cordell, H J; Short, A; Skinningsrud, B; Ollier, W; Badenhoop, K; Meyer, G; Falorni, A; Kampe, O; Undlien, D; Pearce, S H S; Husebye, E S

    2015-09-01

    In common with several other autoimmune diseases, autoimmune Addison's disease (AAD) is thought to be caused by a combination of deleterious susceptibility polymorphisms in several genes, together with undefined environmental factors and stochastic events. To date, the strongest genomic association with AAD has been with alleles at the HLA locus, DR3-DQ2 and DR4. The contribution of other genetic variants has been inconsistent. We have studied the association of 16 single-nucleotide polymorphisms (SNPs) within the CD28-CTLA-4-ICOS genomic locus, in a cohort comprising 691 AAD patients of Norwegian and UK origin with matched controls. We have also performed a meta-analysis including 1002 patients from European countries. The G-allele of SNP rs231775 in CTLA-4 is associated with AAD in Norwegian patients (odds ratio (OR)=1.35 (confidence interval (CI) 1.10-1.66), P=0.004), but not in UK patients. The same allele is associated with AAD in the total European population (OR=1.37 (CI 1.13-1.66), P=0.002). A three-marker haplotype, comprising PROMOTER_1661, rs231726 and rs1896286 was found to be associated with AAD in the Norwegian cohort only (OR 2.43 (CI 1.68-3.51), P=0.00013). This study points to the CTLA-4 gene as a susceptibility locus for the development of AAD, and refines its mapping within the wider genomic locus.

  2. Genetic diversity of bovine Neospora caninum determined by microsatellite markers.

    PubMed

    Salehi, N; Gottstein, B; Haddadzadeh, H R

    2015-10-01

    Neospora caninum is one of the most significant parasitic organisms causing bovine abortion worldwide. Despite the economic impact of this infection, relatively little is known about the genetic diversity of this parasite. In this study, using Nc5 and ITS1 nested PCR, N. caninum has been detected in 12 brain samples of aborted fetuses from 298 seropositive dairy cattle collected from four different regions in Tehran, Iran. These specimen (Nc-Iran) were genotyped in multilocus using 9 different microsatellite markers previously described (MS4, MS5, MS6A, MS6B, MS7, MS8, MS10, MS12 and MS21). Microsatellite amplification was completely feasible in 2 samples, semi-completely in 8 samples, and failed in 2 samples. Within the two completely performed allelic profiles of Nc-Iran strains, unique multilocus profiles were obtained for both and novel allelic patterns were found in the MS8 and MS10 microsatellite markers. The Jaccard's similarity index showed significant difference between these two strains and from other standard isolates derived from GenBank such as Nc-Liv, Nc-SweB1, Nc-GER1, KBA1, and KBA2. All samples originating from the same area showed identical allelic numbers and a correlation between the number of repeats and geographic districts was observed.

  3. Genetic Determinism vs. Phenotypic Plasticity in Protist Morphology.

    PubMed

    Mulot, Matthieu; Marcisz, Katarzyna; Grandgirard, Lara; Lara, Enrique; Kosakyan, Anush; Robroek, Bjorn J M; Lamentowicz, Mariusz; Payne, Richard J; Mitchell, Edward A D

    2017-02-23

    Untangling the relationships between morphology and phylogeny is key to building a reliable taxonomy, but is especially challenging for protists, where the existence of cryptic or pseudocryptic species makes finding relevant discriminant traits difficult. Here we use Hyalosphenia papilio (a testate amoeba) as a model species to investigate the contribution of phylogeny and phenotypic plasticity in its morphology. We study the response of H. papilio morphology (shape and pores number) to environmental variables in (i) a manipulative experiment with controlled conditions (water level), (ii) an observational study of a within-site natural ecological gradient (water level), and (iii) an observational study across 37 European peatlands (climate). We showed that H. papilio morphology is correlated to environmental conditions (climate and water depth) as well as geography, while no relationship between morphology and phylogeny was brought to light. The relative contribution of genetic inheritance and phenotypic plasticity in shaping morphology varies depending on the taxonomic group and the trait under consideration. Thus, our data call for a reassessment of taxonomy based on morphology alone. This clearly calls for a substantial increase in taxonomic research on these globally still under-studied organisms leading to a reassessment of estimates of global microbial eukaryotic diversity.

  4. Genetic Determinants of Type 2 Diabetes in Asians

    PubMed Central

    Qi, Q; Wang, X; Strizich, G; Wang, T

    2016-01-01

    Type 2 diabetes (T2D) has become a major health problem throughout the world and the epidemic is particularly severe in Asian countries. Compared with European populations, Asians tend to develop diabetes at a younger age and at much higher incidence rates given the same amount of weight gain. Genome-wide association studies (GWAS) have identified over 70 loci associated with T2D. Although the majority of GWAS results were conducted in populations of European ancestry, recent GWAS in Asians have made important contributions to the identification of T2D susceptibility loci. These studies not only confirmed T2D susceptibility loci initially identified in European populations, but also identified novel susceptibility loci that provide new insights into the pathophysiology of diseases. In this article, we review GWAS results of T2D conducted in East and South Asians and compare them to those of European populations. Currently identified T2D genetic variants do not appear to explain the phenomenon that Asians are more susceptible to T2D than European populations, suggesting further studies in Asian populations are needed. PMID:27583258

  5. Environmental and Genetic Determinants of Colony Morphology in Yeast

    PubMed Central

    Granek, Joshua A.; Magwene, Paul M.

    2010-01-01

    Nutrient stresses trigger a variety of developmental switches in the budding yeast Saccharomyces cerevisiae. One of the least understood of such responses is the development of complex colony morphology, characterized by intricate, organized, and strain-specific patterns of colony growth and architecture. The genetic bases of this phenotype and the key environmental signals involved in its induction have heretofore remained poorly understood. By surveying multiple strain backgrounds and a large number of growth conditions, we show that limitation for fermentable carbon sources coupled with a rich nitrogen source is the primary trigger for the colony morphology response in budding yeast. Using knockout mutants and transposon-mediated mutagenesis, we demonstrate that two key signaling networks regulating this response are the filamentous growth MAP kinase cascade and the Ras-cAMP-PKA pathway. We further show synergistic epistasis between Rim15, a kinase involved in integration of nutrient signals, and other genes in these pathways. Ploidy, mating-type, and genotype-by-environment interactions also appear to play a role in the controlling colony morphology. Our study highlights the high degree of network reuse in this model eukaryote; yeast use the same core signaling pathways in multiple contexts to integrate information about environmental and physiological states and generate diverse developmental outputs. PMID:20107600

  6. Common genetic determinants of vitamin D insufficiency: the sunlight consortium

    USDA-ARS?s Scientific Manuscript database

    Background: Vitamin D is crucial for maintaining musculoskeletal health. Recently, vitamin D insufficiency has been linked to a number of extraskeletal disorders, including diabetes, cancer, and cardiovascular disease. Determinants of circulating 25-hydroxyvitamin D (25-OH D) include sun exposure an...

  7. Sound Power Determination Using Sound Intensity Measurements: Applications and Extensions

    NASA Astrophysics Data System (ADS)

    Yang, Shaobo

    1995-01-01

    The determination of sound power using sound intensity measurements is one of the most important developments in acoustics since the advent of digital signal processing techniques and FFT (fast Fourier transform) techniques in 1970's. Sound power determination using sound intensity measurements is the only way to precisely determine the sound power of noise sources in operating conditions when other noise sources are operating simultaneously. Sound power determination from sound intensity measurements largely obviates the need for special purpose test facilities, such as an anechoic room or a reverberation room. The determination of sound power from sound intensity measurements has many distinct advantages over the traditional determination of the sound power from sound pressure, and it will soon become the dominant method in the determination of the sound power of noise sources in-situ. Sound intensity measurements have been successfully applied to the determination of the sound power levels of noise sources in laboratory conditions, and of small machinery noise sources. The full scale application of this new technique to industrial machinery noise sources is certainly of importance for practical purposes. This dissertation mainly describes progress made in research on the application of sound intensity measurements for the determination of the sound power of noise sources. Results concerning the sound power determination from sound intensity measurements in the following areas are discussed: sound power determination from sound intensity measurements at low frequency, error analysis of sound intensity estimates at low frequency, and sound power determination from sound intensity measurements in the presence of air flow, sound power determination from sound intensity measurements in the presence of strong background noise and some practical considerations on the application of the sound intensity technique to in-situ sound power determination.

  8. Gestation length in red deer: genetically determined or environmentally controlled?

    PubMed

    Asher, G W

    2007-01-01

    The red deer (Cervus elaphus) of European origin (e.g. subspecies scoticus, hispanicus, hippelaphus) is a medium sized (100-150kg mature hind weight) ruminant that exhibits highly seasonally patterns of autumn conceptions and summer births. Historic data indicate average (+/- s.d.) gestation length of 233-234 (+/- 2-4) days. Recently, however, there has been growing awareness that there is considerably greater variation in gestation length than earlier indicated and that there is a significant element of environmental, and possibly even social, control over the duration of pregnancy in this species. Imposition of variable levels of nutrition over late pregnancy of red deer hinds has been observed to influence fetal growth trajectory and gestation length, with no apparent effect on birth weight. This supports a hypothesis that under conditions of modest feed imbalance, variation in gestation length compensates for variation in fetal growth trajectory to ensure optimisation of birth weight. More recent studies on primiparous (24 month old) red deer hinds have identified surprisingly large variation in gestation length (193-263 days) compared with adult hinds (228-243 days), with earlier conceiving individuals within the primiparous cohort expressing significantly longer gestation than the later conceiving hinds, resulting in a higher level of calving synchrony than expected from known conception dates. This introduces an intriguing hypothesis of social indicative effects on parturition timing to promote within-cohort birth synchrony. Collectively, these data debunk the commonly held notion that gestation length of red deer is genetically fixed within strict limits. A review of the literature points to this as possibly a common phenomenon across a range of non-domesticated ruminant species but this conclusion is not supported by numerous conflicting studies on domestic sheep and cattle.

  9. Determination of an optimal unit pulse response function using real-coded genetic algorithm

    NASA Astrophysics Data System (ADS)

    Jain, Ashu; Srinivasalu, Sanaga; Bhattacharjya, Rajib Kumar

    2005-03-01

    This paper presents the results of employing a real-coded genetic algorithm (GA) to the problem of determining the optimal unit pulse response function (UPRF) using the historical data from watersheds. The existing linear programming (LP) formulation has been modified, and a new problem formulation is proposed. The proposed problem formulation consists of fewer decision variables, only one constraint, and a non-linear objective function. The proposed problem formulation can be used to determine an optimal UPRF of a watershed from a single storm or a composite UPRF from multiple storms. The proposed problem formulation coupled with the solution technique of real-coded GA is tested using the effective rainfall and runoff data derived from two different watersheds and the results are compared with those reported earlier by others using LP methods. The model performance is evaluated using a wide range of standard statistical measures. The results obtained in this study indicate that the real-coded GA can be a suitable alternative to the problem of determining an optimal UPRF from a watershed. The proposed problem formulation when solved using real-coded GA resulted in smoother optimal UPRF without the need of additional constraints. The proposed problem formulation can be particularly useful in determining the optimal composite UPRF from multiple storms in large watersheds having large time bases due to its limited number of decision variables and constraints.

  10. Determining the Genetic Diversity of Lactobacilli from the Oral Cavity

    PubMed Central

    Yang, R.; Argimon, S.; Li, Y.; Zhou, X.; Caufield, P. W.

    2010-01-01

    Summary Several methods for determining the diversity of Lactobacillus spp were evaluated with the purpose of developing a realistic approach for further studies. The patient population was comprised of young children with an oral disease called severe early childhood caries. The ultimate goal of these studies was to ascertain the role of lactobacilli in the caries process. To accomplish that goal, we evaluated several methods and approaches for determining diversity including AP-PCR, chromosomal DNA fingerprinting, denaturing gradient gel electrophoresis, and 16S rRNA gene sequencing. Central to these methods was the gathering and screening of isolates from cultivation medium. Using various estimates of diversity, we addressed the question as to how many isolates represent the overall diversity and how cultivation compares to non-cultivation techniques. Finally, we proposed a working approach for achieving the goals outlined framed by both practical constraints in terms of time, effort and efficacy while yielding a reliable outcome. PMID:20573585

  11. Determining the genetic diversity of lactobacilli from the oral cavity.

    PubMed

    Yang, R; Argimon, S; Li, Y; Gu, H; Zhou, X; Caufield, P W

    2010-08-01

    Several methods for determining the diversity of Lactobacillus spp were evaluated with the purpose of developing a realistic approach for further studies. The patient population was comprised of young children with an oral disease called severe early childhood caries. The ultimate goal of these studies was to ascertain the role of lactobacilli in the caries process. To accomplish that goal, we evaluated several methods and approaches for determining diversity including AP-PCR, chromosomal DNA fingerprinting, denaturing gradient gel electrophoresis, and 16S rRNA gene sequencing. Central to these methods was the gathering and screening of isolates from cultivation medium. Using various estimates of diversity, we addressed the question as to how many isolates represent the overall diversity and how cultivation compares to non-cultivation techniques. Finally, we proposed a working approach for achieving the goals outlined framed by both practical constraints in terms of time, effort and efficacy while yielding a reliable outcome.

  12. Mapping genetic determinants of viral traits with FST and quantitative trait locus (QTL) approaches.

    PubMed

    Doumayrou, Juliette; Thébaud, Gaël; Vuillaume, Florence; Peterschmitt, Michel; Urbino, Cica

    2015-10-01

    The genetic determinism of viral traits can generally be dissected using either forward or reverse genetics because the clonal reproduction of viruses does not require the use of approaches based on laboratory crosses. Nevertheless, we hypothesized that recombinant viruses could be analyzed as sexually reproducing organisms, using either a quantitative trait loci (QTL) approach or a locus-by-locus fixation index (FST). Locus-by-locus FST analysis, and four different regressions and interval mapping algorithms of QTL analysis were applied to a phenotypic and genotypic dataset previously obtained from 47 artificial recombinant genomes generated between two begomovirus species. Both approaches assigned the determinant of within-host accumulation-previously identified using standard virology approaches-to a region including the 5׳ end of the replication-associated protein (Rep) gene and the upstream intergenic region. This study provides a proof of principle that QTL and population genetics tools can be extended to characterize the genetic determinants of viral traits.

  13. Genetic Algorithm for Initial Orbit Determination with Too Short Arc (Continued)

    NASA Astrophysics Data System (ADS)

    Xin-ran, Li; Xin, Wang

    2017-04-01

    When the genetic algorithm is used to solve the problem of too short-arc (TSA) orbit determination, due to the difference of computing process between the genetic algorithm and the classical method, the original method for outlier deletion is no longer applicable. In the genetic algorithm, the robust estimation is realized by introducing different loss functions for the fitness function, then the outlier problem of the TSA orbit determination is solved. Compared with the classical method, the genetic algorithm is greatly simplified by introducing in different loss functions. Through the comparison on the calculations of multiple loss functions, it is found that the least median square (LMS) estimation and least trimmed square (LTS) estimation can greatly improve the robustness of the TSA orbit determination, and have a high breakdown point.

  14. Coordinated Genetic Scaling of the Human Eye: Shared Determination of Axial Eye Length and Corneal Curvature

    PubMed Central

    Guggenheim, Jeremy A.; Zhou, Xin; Evans, David M.; Timpson, Nicholas J.; McMahon, George; Kemp, John P.; St Pourcain, Beate; Northstone, Kate; Ring, Susan M.; Fan, Qiao; Wong, Tien-Yin; Cheng, Ching Yu; Khor, Chiea Chuen; Aung, Tin; Saw, Seang Mei; Williams, Cathy

    2013-01-01

    Purpose. To examine the extent to which the two major determinants of refractive error, corneal curvature and axial length, are scaled relative to one another by shared genetic variants, along with their relationship to the genetic scaling of height. Methods. Corneal curvature, axial length, and height were measured in unrelated 14- to 17-year-old white European participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 1915) and in unrelated 40- to 80-year-old participants of the Singapore Chinese Eye Study (SCES; n = 1642). Univariate and bivariate heritability analyses were performed with methods that avoid confounding by common family environment, using information solely from genome-wide high-density genotypes. Results. In ALSPAC subjects, axial length, corneal curvature, and height had similar lower-bound heritability estimates: axial length, h2 = 0.46 (SE = 0.16, P = 0.002); corneal curvature, h2 = 0.42 (SE = 0.16, P = 0.004); height, h2 = 0.48 (SE = 0.17, P = 0.002). The corresponding estimates in the SCES were 0.79 (SE = 0.18, P < 0.001), 0.35 (SE = 0.20, P = 0.036), and 0.31 (SE = 0.20, P = 0.061), respectively. The genetic correlation between corneal curvature and axial length was 0.69 (SE = 0.17, P = 0.019) for ALSPAC participants and 0.64 (SE = 0.22, P = 0.003) for SCES participants. In the subset of 1478 emmetropic ALSPAC individuals, the genetic correlation was 0.85 (SE = 0.12, P = 0.008). Conclusions. These results imply that coordinated scaling of ocular component dimensions is largely achieved by hundreds to thousands of common genetic variants, each with a small pleiotropic effect. Furthermore, genome-wide association studies (GWAS) for either axial length or corneal curvature are likely to identify variants controlling overall eye size when using discovery cohorts dominated by emmetropes, but trait-specific variants in discovery cohorts dominated by ametropes. PMID:23385790

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

    PubMed

    Monnahan, Patrick J; Kelly, John K

    2015-05-01

    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.

  16. 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

  17. Genetic and physiological determinants of Streptomyces scabies pathogenicity.

    PubMed

    Lerat, Sylvain; Simao-Beaunoir, Anne-Marie; Beaulieu, Carole

    2009-09-01

    SUMMARY Common scab is a severe disease worldwide affecting tap root crops and potato tubers. It is caused by soil-borne filamentous bacteria belonging to the genus Streptomyces. Streptomycetes usually are saprophytic microorganisms, but a few species have acquired the ability to infect underground plant tissues. The predominant causal agent of potato scab worldwide is Streptomyces scabies. The production of phytotoxins called thaxtomins is essential for the virulence of common scab-causing agents. The genes involved in the biosynthetic pathway of thaxtomins and other virulence genes are clustered on a large pathogenicity island. The pathogenicity island can be mobilized and transferred to nonpathogenic relatives, leading to the emergence of new pathogenic streptomycetes. In most pathogenic Streptomyces species, thaxtomin A is the predominant form found. The regulation of thaxtomin A synthesis is complex. Although the plant-derived compound cellobiose is now recognized as the inducer of thaxtomin A synthesis at a genetic level, other molecules (including aromatic amino acids and some secondary metabolites) show inhibitory effects on the production of the toxin. This paper is an overview of common scab with a focus on S. scabies and its virulence mechanisms. Streptomyces scabies (Thaxt.) Lambert and Loria; Kingdom Bacteria; Phylum Actinobacteria; Class Actinomycetes; Order Actinomycetales; Family Streptomycetaceae; genus Streptomyces; species scabies or scabiei. Streptomyces scabies (syn. S. scabiei) has a broad host range comprising tuber vegetables and most tap root crops. Streptomyces scabies causes common scab on potato (Solanum tuberosum), beet (Beta vulgaris), carrot (Daucus carota), parsnip (Pastinaca sativa), radish (Raphanus sativus), rutabaga (Brassica napobrassica) and turnip (Brassica rapa). Disease symptoms: Common scab symptoms appear as randomly distributed shallow, raised or deep-pitted corky lesions. Their size and colour are quite variable, but

  18. In Vivo Measurement of Intramolecular Distances Using Genetically Encoded Reporters

    PubMed Central

    Sandtner, Walter; Bezanilla, Francisco; Correa, Ana M.

    2007-01-01

    The function of membrane proteins occurs in the context of the cell membrane in living cells acting in concert with various cell components such as other proteins, cofactors, etc. The understanding of the function at the molecular level requires structural techniques, but high resolution structural studies are normally obtained in vitro and in artificial membranes or detergent. Ideally the correlation of structure and function should be carried out in the native environment but most of the techniques applicable in vivo lack the high resolution necessary to track conformational changes on a molecular level. Here we report on the successful application of an improved variant of lanthanide-based resonance energy transfer a fluorescent based technique, to Shaker potassium channels expressed in live Xenopus oocytes. Lanthanide-based resonance energy transfer is particularly suitable to measure intramolecular distances with high resolution. The improvements reported in this work are mainly based on the use of two different small genetically encoded tags (the Lanthanide Binding Tag and the hexa-histidine tag), which due to their small size can be encoded at will in many positions of interest without distorting the protein's function. The technique reported here has the additional improvement that the two tags can be placed independently in contrast to previously described techniques that rely on chemical labeling procedures of thiols. PMID:17766346

  19. Genetic determination of telomere size in humans: A twin study of three age groups

    SciTech Connect

    Slagboom, P.E.; Droog, S.; Boomsma, D.I.

    1994-11-01

    Reduction of telomere length has been postulated to be a casual factor in cellular aging. Human telomeres terminate in tandemly arranged repeat arrays consisting of the (TTAGGG) motif. The length of these arrays in cells from human mitotic tissues is inversely related to the age of the donor, indicating telomere reduction with age. In addition to telemore length differences between different age cohorts, considerable variation is present among individuals of the same age. To investigate whether this variation can be ascribed to genetic influences, we have measured the size of terminal restriction fragments (TRFs) in HaeIII-digested genomic DNA from 123 human MZ and DZ twin pairs 2-95 years of age. The average rate of telomere shortening was 31 bp/year, which is similar to that observed by others. Statistical analysis in 115 pairs 2-63 years of age indicates a 78% heritability for mean TRF length in this age cohort. The individual differences in mean TRF length in blood, therefore, seem to a large extent to be genetically determined. 24 refs., 4 figs., 2 tabs.

  20. Genetic Determinants of Parkinson's Disease: Can They Help to Stratify the Patients Based on the Underlying Molecular Defect?

    PubMed Central

    Redenšek, Sara; Trošt, Maja; Dolžan, Vita

    2017-01-01

    Parkinson's disease (PD) is a sporadic progressive neurodegenerative brain disorder with a relatively strong genetic background. We have reviewed the current literature about the genetic factors that could be indicative of pathophysiological pathways of PD and their applications in everyday clinical practice. Information on novel risk genes is coming from several genome-wide association studies (GWASs) and their meta-analyses. GWASs that have been performed so far enabled the identification of 24 loci as PD risk factors. These loci take part in numerous cellular processes that may contribute to PD pathology: protein aggregation, protein, and membrane trafficking, lysosomal autophagy, immune response, synaptic function, endocytosis, inflammation, and metabolic pathways are among the most important ones. The identified single nucleotide polymorphisms are usually located in the non-coding regions and their functionality remains to be determined, although they presumably influence gene expression. It is important to be aware of a very low contribution of a single genetic risk factor to PD development; therefore, novel prognostic indices need to account for the cumulative nature of genetic risk factors. A better understanding of PD pathophysiology and its genetic background will help to elucidate the underlying pathological processes. Such knowledge may help physicians to recognize subjects with the highest risk for the development of PD, and provide an opportunity for the identification of novel potential targets for neuroprotective treatment. Moreover, it may enable stratification of the PD patients according to their genetic fingerprint to properly personalize their treatment as well as supportive measures. PMID:28239348

  1. Genetic determination of male sterility in gynodioecious Silene nutans

    PubMed Central

    Garraud, C; Brachi, B; Dufay, M; Touzet, P; Shykoff, J A

    2011-01-01

    Gynodioecy, the coexistence of female and hermaphrodite plants within a species, is often under nuclear–cytoplasmic sex determination, involving cytoplasmic male sterility (CMS) genes and nuclear restorers. A good knowledge of CMS and restorer polymorphism is essential for understanding the evolution and maintenance of gynodioecy, but reciprocal crossing studies remain scarce. Although mitochondrial diversity has been studied in a few gynodioecious species, the relationship between mitotype diversity and CMS status is poorly known. From a French sample of Silene nutans, a gynodioecious species whose sex determination remains unknown, we chose the four most divergent mitotypes that we had sampled at the cytochrome b gene and tested by reciprocal crosses whether they carry distinct CMS genes. We show that gynodioecy in S. nutans is under nuclear–cytoplasmic control, with at least two different CMSs and up to four restorers with epistatic interactions. Female occurrence and frequency were highly dependent on the mitotype, suggesting that the level of restoration varies greatly among CMSs. Two of the mitotypes, which have broad geographic distributions, represent different CMSs and are very unequally restored. We discuss the dynamics of gynodioecy at the large-scale meta-population level. PMID:20808324

  2. Genetic determinants of telomere length and risk of common cancers: a Mendelian randomization study

    PubMed Central

    Zhang, Chenan; Doherty, Jennifer A.; Burgess, Stephen; Hung, Rayjean J.; Lindström, Sara; Kraft, Peter; Gong, Jian; Amos, Christopher I.; Sellers, Thomas A.; Monteiro, Alvaro N.A.; Chenevix-Trench, Georgia; Bickeböller, Heike; Risch, Angela; Brennan, Paul; Mckay, James D.; Houlston, Richard S.; Landi, Maria Teresa; Timofeeva, Maria N.; Wang, Yufei; Heinrich, Joachim; Kote-Jarai, Zsofia; Eeles, Rosalind A.; Muir, Ken; Wiklund, Fredrik; Grönberg, Henrik; Berndt, Sonja I.; Chanock, Stephen J.; Schumacher, Fredrick; Haiman, Christopher A.; Henderson, Brian E.; Amin Al Olama, Ali; Andrulis, Irene L.; Hopper, John L.; Chang-Claude, Jenny; John, Esther M.; Malone, Kathleen E.; Gammon, Marilie D.; Ursin, Giske; Whittemore, Alice S.; Hunter, David J.; Gruber, Stephen B.; Knight, Julia A.; Hou, Lifang; Le Marchand, Loic; Newcomb, Polly A.; Hudson, Thomas J.; Chan, Andrew T.; Li, Li; Woods, Michael O.; Ahsan, Habibul; Pierce, Brandon L.

    2015-01-01

    Epidemiological studies have reported inconsistent associations between telomere length (TL) and risk for various cancers. These inconsistencies are likely attributable, in part, to biases that arise due to post-diagnostic and post-treatment TL measurement. To avoid such biases, we used a Mendelian randomization approach and estimated associations between nine TL-associated SNPs and risk for five common cancer types (breast, lung, colorectal, ovarian and prostate cancer, including subtypes) using data on 51 725 cases and 62 035 controls. We then used an inverse-variance weighted average of the SNP-specific associations to estimate the association between a genetic score representing long TL and cancer risk. The long TL genetic score was significantly associated with increased risk of lung adenocarcinoma (P = 6.3 × 10−15), even after exclusion of a SNP residing in a known lung cancer susceptibility region (TERT-CLPTM1L) P = 6.6 × 10−6). Under Mendelian randomization assumptions, the association estimate [odds ratio (OR) = 2.78] is interpreted as the OR for lung adenocarcinoma corresponding to a 1000 bp increase in TL. The weighted TL SNP score was not associated with other cancer types or subtypes. Our finding that genetic determinants of long TL increase lung adenocarcinoma risk avoids issues with reverse causality and residual confounding that arise in observational studies of TL and disease risk. Under Mendelian randomization assumptions, our finding suggests that longer TL increases lung adenocarcinoma risk. However, caution regarding this causal interpretation is warranted in light of the potential issue of pleiotropy, and a more general interpretation is that SNPs influencing telomere biology are also implicated in lung adenocarcinoma risk. PMID:26138067

  3. Determination and optimization of spatial samples for distributed measurements.

    SciTech Connect

    Huo, Xiaoming; Tran, Hy D.; Shilling, Katherine Meghan; Kim, Heeyong

    2010-10-01

    There are no accepted standards for determining how many measurements to take during part inspection or where to take them, or for assessing confidence in the evaluation of acceptance based on these measurements. The goal of this work was to develop a standard method for determining the number of measurements, together with the spatial distribution of measurements and the associated risks for false acceptance and false rejection. Two paths have been taken to create a standard method for selecting sampling points. A wavelet-based model has been developed to select measurement points and to determine confidence in the measurement after the points are taken. An adaptive sampling strategy has been studied to determine implementation feasibility on commercial measurement equipment. Results using both real and simulated data are presented for each of the paths.

  4. Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

    PubMed Central

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

    2016-01-01

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

  5. Genetic determinants and cellular constraints in noisy gene expression

    PubMed Central

    Sanchez, Alvaro; Golding, Ido

    2014-01-01

    In individual cells, transcription is a random process obeying single-molecule kinetics. Often, it occurs in a bursty, intermittent manner. The frequency and size of these bursts affect the magnitude of temporal fluctuations in mRNA and protein content within a cell, creating variation or “noise” in gene expression. It is still unclear to what degree transcriptional kinetics are specific to each gene and determined by its promoter sequence. Alternative scenarios have been proposed, where the kinetics of transcription are governed by cellular constraints and follow universal rules across the genome. Evidence from genome-wide noise studies and from systematic perturbations of promoter sequences suggest that both scenarios—namely gene-specific versus genome-wide regulation of transcription kinetics— may be present to different degrees in bacteria, yeast and animal cells. PMID:24311680

  6. Population size and time since island isolation determine genetic diversity loss in insular frog populations.

    PubMed

    Wang, Supen; Zhu, Wei; Gao, Xu; Li, Xianping; Yan, Shaofei; Liu, Xuan; Yang, Ji; Gao, Zengxiang; Li, Yiming

    2014-02-01

    Understanding the factors that contribute to loss of genetic diversity in fragmented populations is crucial for conservation measurements. Land-bridge archipelagoes offer ideal model systems for identifying the long-term effects of these factors on genetic variations in wild populations. In this study, we used nine microsatellite markers to quantify genetic diversity and differentiation of 810 pond frogs (Pelophylax nigromaculatus) from 24 islands of the Zhoushan Archipelago and three sites on nearby mainland China and estimated the effects of the island area, population size, time since island isolation, distance to the mainland and distance to the nearest larger island on reduced genetic diversity of insular populations. The mainland populations displayed higher genetic diversity than insular populations. Genetic differentiations and no obvious gene flow were detected among the frog populations on the islands. Hierarchical partitioning analysis showed that only time since island isolation (square-root-transformed) and population size (log-transformed) significantly contributed to insular genetic diversity. These results suggest that decreased genetic diversity and genetic differentiations among insular populations may have been caused by random genetic drift following isolation by rising sea levels during the Holocene. The results provide strong evidence for a relationship between retained genetic diversity and population size and time since island isolation for pond frogs on the islands, consistent with the prediction of the neutral theory for finite populations. Our study highlights the importance of the size and estimated isolation time of populations in understanding the mechanisms of genetic diversity loss and differentiation in fragmented wild populations. © 2013 John Wiley & Sons Ltd.

  7. Cone photopigment variations in Cebus apella monkeys evidenced by electroretinogram measurements and genetic analysis

    PubMed Central

    Soares, Juliana G.M.; Fiorani, Mario; Araujo, Eduardo A.; Zana, Yossi; Bonci, Daniela M.O.; Neitz, Maureen; Ventura, Dora F.; Gattass, Ricardo

    2011-01-01

    We investigated the color vision pattern in male and female Cebus apella monkeys by means of electroretinogram measurements and genetic analysis. Our objective was to establish a simple, fast and efficient protocol in order to determine the chromatic vision pattern in Cebus monkeys. We found five among ten possible different phenotypes, two trichromats and three dichromats. We also found that Cebus present a new allele with spectral peak near 552 nm, with the amino acid combination SFT at positions 180, 277 and 285 of the opsin gene, in addition to the previously described SYT, AFT and AFA alleles. PMID:19883678

  8. Disentangling genetic and epigenetic determinants of ultrafast adaptation.

    PubMed

    Gjuvsland, Arne B; Zörgö, Enikö; Samy, Jeevan Ka; Stenberg, Simon; Demirsoy, Ibrahim H; Roque, Francisco; Maciaszczyk-Dziubinska, Ewa; Migocka, Magdalena; Alonso-Perez, Elisa; Zackrisson, Martin; Wysocki, Robert; Tamás, Markus J; Jonassen, Inge; Omholt, Stig W; Warringer, Jonas

    2016-12-15

    A major rationale for the advocacy of epigenetically mediated adaptive responses is that they facilitate faster adaptation to environmental challenges. This motivated us to develop a theoretical-experimental framework for disclosing the presence of such adaptation-speeding mechanisms in an experimental evolution setting circumventing the need for pursuing costly mutation-accumulation experiments. To this end, we exposed clonal populations of budding yeast to a whole range of stressors. By growth phenotyping, we found that almost complete adaptation to arsenic emerged after a few mitotic cell divisions without involving any phenotypic plasticity. Causative mutations were identified by deep sequencing of the arsenic-adapted populations and reconstructed for validation. Mutation effects on growth phenotypes, and the associated mutational target sizes were quantified and embedded in data-driven individual-based evolutionary population models. We found that the experimentally observed homogeneity of adaptation speed and heterogeneity of molecular solutions could only be accounted for if the mutation rate had been near estimates of the basal mutation rate. The ultrafast adaptation could be fully explained by extensive positive pleiotropy such that all beneficial mutations dramatically enhanced multiple fitness components in concert. As our approach can be exploited across a range of model organisms exposed to a variety of environmental challenges, it may be used for determining the importance of epigenetic adaptation-speeding mechanisms in general.

  9. Sex determination of Pohnpei Micronesian kingfishers using morphological and molecular genetic techniques

    USGS Publications Warehouse

    Kesler, Dylan C.; Lopes, I.F.; Haig, Susan M.

    2006-01-01

    Conservation-oriented studies of Micronesian Kingfishers (Todiramphus cinnamominus) have been hindered by a lack of basic natural history information, despite the status of the Guam subspecies (T. c. cinnamominus) as one of the most endangered species in the world. We used tissue samples and morphometric measures from museum specimens and wild-captured Pohnpei Micronesian Kingfishers (T. c. reichenbachii) to develop methods for sex determination. We present a modified molecular protocol and a discriminant function that yields the probability that a particular individual is male or female. Our results revealed that females were significantly larger than males, and the discriminant function correctly predicted sex in 73% (30/41) of the individuals. The sex of 86% (18/21) of individuals was correctly assigned when a moderate reliability threshold was set. Sex determination using molecular genetic techniques was more reliable than methods based on morphology. Our results will facilitate recovery efforts for the critically endangered Guam Micronesian Kingfisher and provide a basis for sex determination in the 11 other endangered congeners in the Pacific Basin.

  10. Genetic basis and biotechnological manipulation of sexual dimorphism and sex determination in fish.

    PubMed

    Mei, Jie; Gui, Jian-Fang

    2015-02-01

    Aquaculture has made an enormous contribution to the world food production, especially to the sustainable supply of animal proteins. The utility of diverse reproduction strategies in fish, such as the exploiting use of unisexual gynogenesis, has created a typical case of fish genetic breeding. A number of fish species show substantial sexual dimorphism that is closely linked to multiple economic traits including growth rate and body size, and the efficient development of sex-linked genetic markers and sex control biotechnologies has provided significant approaches to increase the production and value for commercial purposes. Along with the rapid development of genomics and molecular genetic techniques, the genetic basis of sexual dimorphism has been gradually deciphered, and great progress has been made in the mechanisms of fish sex determination and identification of sex-determining genes. This review summarizes the progress to provide some directive and objective thinking for further research in this field.

  11. Comparison of French and Estonian Students' Conceptions in Genetic Determinism of Human Behaviours

    ERIC Educational Resources Information Center

    Castera, Jeremy; Sarapuu, Tago; Clement, Pierre

    2013-01-01

    Innatism is the belief that most of the human personality can be determined by genes. This ideology is dangerous, especially when it claims to be scientific. The present study investigates conceptions of 1060 students from Estonia and France related to genetic determinism of some human behaviours. Factors taken into account included students'…

  12. Comparison of French and Estonian Students' Conceptions in Genetic Determinism of Human Behaviours

    ERIC Educational Resources Information Center

    Castera, Jeremy; Sarapuu, Tago; Clement, Pierre

    2013-01-01

    Innatism is the belief that most of the human personality can be determined by genes. This ideology is dangerous, especially when it claims to be scientific. The present study investigates conceptions of 1060 students from Estonia and France related to genetic determinism of some human behaviours. Factors taken into account included students'…

  13. Genetic determination of exocrine pancreatic function in cystic fibrosis.

    PubMed

    Kristidis, P; Bozon, D; Corey, M; Markiewicz, D; Rommens, J; Tsui, L C; Durie, P

    1992-06-01

    We showed elsewhere that the pancreatic function status of cystic fibrosis (CF) patients could be correlated to mutations in the CF transmembrane conductance regulator (CFTR) gene. Although the majority of CF mutations--including the most common, delta F508--strongly correlated with pancreatic insufficiency (PI), approximately 10% of the mutant alleles may confer pancreatic sufficiency (PS). To extend this observation, genomic DNA of 538 CF patients with well-documented pancreatic function status were analyzed for a series of known mutations in their CFTR genes. Only 20 of the 25 mutations tested were found in this population. They accounted for 84% of the CF chromosomes, with delta F508 being the most frequent (71%), and the other mutations accounted for less than 5% each. A total of 30 different, complete genotypes could be determined in 394 (73%) of the patients. The data showed that each genotype was associated only with PI or only with PS, but not with both. This result is thus consistent with the hypothesis that PI and PS in CF are predisposed by the genotype at the CFTR locus; the PS phenotype occurs in patients who have one or two mild CFTR mutations, such as R117H, R334W, R347P, A455E, and P574H, whereas the PI phenotype occurs in patients with two severe alleles, such as delta F508, delta I507, Q493X, G542X, R553X, W1282X, 621 + 1G----T, 1717-1G----A, 556delA, 3659delC, I148T, G480C, V520F, G551D, and R560T.

  14. Genetic determination of exocrine pancreatic function in cystic fibrosis.

    PubMed Central

    Kristidis, P; Bozon, D; Corey, M; Markiewicz, D; Rommens, J; Tsui, L C; Durie, P

    1992-01-01

    We showed elsewhere that the pancreatic function status of cystic fibrosis (CF) patients could be correlated to mutations in the CF transmembrane conductance regulator (CFTR) gene. Although the majority of CF mutations--including the most common, delta F508--strongly correlated with pancreatic insufficiency (PI), approximately 10% of the mutant alleles may confer pancreatic sufficiency (PS). To extend this observation, genomic DNA of 538 CF patients with well-documented pancreatic function status were analyzed for a series of known mutations in their CFTR genes. Only 20 of the 25 mutations tested were found in this population. They accounted for 84% of the CF chromosomes, with delta F508 being the most frequent (71%), and the other mutations accounted for less than 5% each. A total of 30 different, complete genotypes could be determined in 394 (73%) of the patients. The data showed that each genotype was associated only with PI or only with PS, but not with both. This result is thus consistent with the hypothesis that PI and PS in CF are predisposed by the genotype at the CFTR locus; the PS phenotype occurs in patients who have one or two mild CFTR mutations, such as R117H, R334W, R347P, A455E, and P574H, whereas the PI phenotype occurs in patients with two severe alleles, such as delta F508, delta I507, Q493X, G542X, R553X, W1282X, 621 + 1G----T, 1717-1G----A, 556delA, 3659delC, I148T, G480C, V520F, G551D, and R560T. PMID:1376016

  15. Determinism and Underdetermination in Genetics: Implications for Students' Engagement in Argumentation and Epistemic Practices

    NASA Astrophysics Data System (ADS)

    Jiménez-Aleixandre, María Pilar

    2012-11-01

    In the last two decades science studies and science education research have shifted from an interest in products (of science or of learning), to an interest in processes and practices. The focus of this paper is on students' engagement in epistemic practices (Kelly in Teaching scientific inquiry: Recommendations for research and implementation. Sense Publishers, Rotterdam, pp 99-117, 2008), or on their practical epistemologies (Wickman in Sci Educ 88(3):325-344, 2004). In order to support these practices in genetics classrooms we need to take into account domain-specific features of the epistemology of genetics, in particular issues about determinism and underdetermination. I suggest that certain difficulties may be related to the specific nature of causality in genetics, and in particular to the correspondence between a given set of factors and a range of potential effects, rather than a single one. The paper seeks to bring together recent developments in the epistemology of biology and of genetics, on the one hand, with science education approaches about epistemic practices, on the other. The implications of these perspectives for current challenges in learning genetics are examined, focusing on students' engagement in epistemic practices, as argumentation, understood as using evidence to evaluate knowledge claims. Engaging in argumentation in genetics classrooms is intertwined with practices such as using genetics models to build explanations, or framing genetics issues in their social context. These challenges are illustrated with studies making part of our research program in the USC.

  16. Genetic determinants of haemolysis in sickle cell anaemia.

    PubMed

    Milton, Jacqueline N; Rooks, Helen; Drasar, Emma; McCabe, Elizabeth L; Baldwin, Clinton T; Melista, Efi; Gordeuk, Victor R; Nouraie, Mehdi; Kato, Gregory R; Kato, Gregory J; Minniti, Caterina; Taylor, James; Campbell, Andrew; Luchtman-Jones, Lori; Rana, Sohail; Castro, Oswaldo; Zhang, Yingze; Thein, Swee Lay; Sebastiani, Paola; Gladwin, Mark T; Steinberg, Martin H

    2013-04-01

    Haemolytic anaemia is variable among patients with sickle cell anaemia and can be estimated by reticulocyte count, lactate dehydrogenase, aspartate aminotransferase and bilirubin levels. Using principal component analysis of these measurements we computed a haemolytic score that we used as a subphenotype in a genome-wide association study. We identified in one cohort and replicated in two additional cohorts the association of a single nucleotide polymorphism in NPRL3 (rs7203560; chr16p13·3) (P = 6·04 × 10(-07) ). This association was validated by targeted genotyping in a fourth independent cohort. The HBA1/HBA2 regulatory elements, hypersensitive sites (HS)-33, HS-40 and HS-48 are located in introns of NPRL3. Rs7203560 was in perfect linkage disequilibrium (LD) with rs9926112 (r(2)  = 1) and in strong LD with rs7197554 (r(2)  = 0·75) and rs13336641 (r(2)  = 0·77); the latter is located between HS-33 and HS-40 sites and next to a CTCF binding site. The minor allele for rs7203560 was associated with the -∝(3·7) thalassaemia gene deletion. When adjusting for HbF and ∝ thalassaemia, the association of NPRL3 with the haemolytic score was significant (P = 0·00375) and remained significant when examining only cases without gene deletion∝ thalassaemia (P = 0·02463). Perhaps by independently down-regulating expression of the HBA1/HBA2 genes, variants of the HBA1/HBA2 gene regulatory loci, tagged by rs7203560, reduce haemolysis in sickle cell anaemia.

  17. Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders

    PubMed Central

    Sandholt, Camilla Helene; Grarup, Niels; Jørgensen, Marit Eika; Færgeman, Nils Joakim; Bjerregaard, Peter; Pedersen, Oluf; Moltke, Ida; Hansen, Torben; Albrechtsen, Anders

    2016-01-01

    Fatty acids (FAs) are involved in cellular processes important for normal body function, and perturbation of FA balance has been linked to metabolic disturbances, including type 2 diabetes. An individual’s level of FAs is affected by diet, lifestyle, and genetic variation. We aimed to improve the understanding of the mechanisms and pathways involved in regulation of FA tissue levels, by identifying genetic loci associated with inter-individual differences in erythrocyte membrane FA levels. We assessed the levels of 22 FAs in the phospholipid fraction of erythrocyte membranes from 2,626 Greenlanders in relation to single nucleotide polymorphisms genotyped on the MetaboChip or imputed. We identified six independent association signals. Novel loci were identified on chromosomes 5 and 11 showing strongest association with oleic acid (rs76430747 in ACSL6, beta (SE): -0.386% (0.034), p = 1.8x10-28) and docosahexaenoic acid (rs6035106 in DTD1, 0.137% (0.025), p = 6.4x10-8), respectively. For a missense variant (rs80356779) in CPT1A, we identified a number of novel FA associations, the strongest with 11-eicosenoic acid (0.473% (0.035), p = 2.6x10-38), and for variants in FADS2 (rs174570), LPCAT3 (rs2110073), and CERS4 (rs11881630) we replicated known FA associations. Moreover, we observed metabolic implications of the ACSL6 (rs76430747) and CPT1A (rs80356779) variants, which both were associated with altered HbA1c (0.051% (0.013), p = 5.6x10-6 and -0.034% (0.016), p = 3.1x10-4, respectively). The latter variant was also associated with reduced insulin resistance (HOMA-IR, -0.193 (0.050), p = 3.8x10-6), as well as measures of smaller body size, including weight (-2.676 kg (0.523), p = 2.4x10-7), lean mass (-1.200 kg (0.271), p = 1.7x10-6), height (-0.966 cm (0.230), p = 2.0x10-5), and BMI (-0.638 kg/m2 (0.181), p = 2.8x10-4). In conclusion, we have identified novel genetic determinants of FA composition in phospholipids in erythrocyte membranes, and have shown examples of

  18. Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders.

    PubMed

    Andersen, Mette Korre; Jørsboe, Emil; Sandholt, Camilla Helene; Grarup, Niels; Jørgensen, Marit Eika; Færgeman, Nils Joakim; Bjerregaard, Peter; Pedersen, Oluf; Moltke, Ida; Hansen, Torben; Albrechtsen, Anders

    2016-06-01

    Fatty acids (FAs) are involved in cellular processes important for normal body function, and perturbation of FA balance has been linked to metabolic disturbances, including type 2 diabetes. An individual's level of FAs is affected by diet, lifestyle, and genetic variation. We aimed to improve the understanding of the mechanisms and pathways involved in regulation of FA tissue levels, by identifying genetic loci associated with inter-individual differences in erythrocyte membrane FA levels. We assessed the levels of 22 FAs in the phospholipid fraction of erythrocyte membranes from 2,626 Greenlanders in relation to single nucleotide polymorphisms genotyped on the MetaboChip or imputed. We identified six independent association signals. Novel loci were identified on chromosomes 5 and 11 showing strongest association with oleic acid (rs76430747 in ACSL6, beta (SE): -0.386% (0.034), p = 1.8x10-28) and docosahexaenoic acid (rs6035106 in DTD1, 0.137% (0.025), p = 6.4x10-8), respectively. For a missense variant (rs80356779) in CPT1A, we identified a number of novel FA associations, the strongest with 11-eicosenoic acid (0.473% (0.035), p = 2.6x10-38), and for variants in FADS2 (rs174570), LPCAT3 (rs2110073), and CERS4 (rs11881630) we replicated known FA associations. Moreover, we observed metabolic implications of the ACSL6 (rs76430747) and CPT1A (rs80356779) variants, which both were associated with altered HbA1c (0.051% (0.013), p = 5.6x10-6 and -0.034% (0.016), p = 3.1x10-4, respectively). The latter variant was also associated with reduced insulin resistance (HOMA-IR, -0.193 (0.050), p = 3.8x10-6), as well as measures of smaller body size, including weight (-2.676 kg (0.523), p = 2.4x10-7), lean mass (-1.200 kg (0.271), p = 1.7x10-6), height (-0.966 cm (0.230), p = 2.0x10-5), and BMI (-0.638 kg/m2 (0.181), p = 2.8x10-4). In conclusion, we have identified novel genetic determinants of FA composition in phospholipids in erythrocyte membranes, and have shown examples of

  19. Genetic Determinism of Sensitivity to Corynespora cassiicola Exudates in Rubber Tree (Hevea brasiliensis)

    PubMed Central

    Tran, Dinh Minh; Clément-Demange, André; Déon, Marine; Garcia, Dominique; Le Guen, Vincent; Clément-Vidal, Anne; Soumahoro, Mouman; Masson, Aurélien; Label, Philippe; Le, Mau Tuy; Pujade-Renaud, Valérie

    2016-01-01

    An indirect phenotyping method was developed in order to estimate the susceptibility of rubber tree clonal varieties to Corynespora Leaf Fall (CLF) disease caused by the ascomycete Corynespora cassiicola. This method consists in quantifying the impact of fungal exudates on detached leaves by measuring the induced electrolyte leakage (EL%). The tested exudates were either crude culture filtrates from diverse C. cassiicola isolates or the purified cassiicolin (Cas1), a small secreted effector protein produced by the aggressive isolate CCP. The test was found to be quantitative, with the EL% response proportional to toxin concentration. For eight clones tested with two aggressive isolates, the EL% response to the filtrates positively correlated to the response induced by conidial inoculation. The toxicity test applied to 18 clones using 13 toxinic treatments evidenced an important variability among clones and treatments, with a significant additional clone x treatment interaction effect. A genetic linkage map was built using 306 microsatellite markers, from the F1 population of the PB260 x RRIM600 family. Phenotyping of the population for sensitivity to the purified Cas1 effector and to culture filtrates from seven C. cassiicola isolates revealed a polygenic determinism, with six QTL detected on five chromosomes and percentages of explained phenotypic variance varying from 11 to 17%. Two common QTL were identified for the CCP filtrate and the purified cassiicolin, suggesting that Cas1 may be the main effector of CCP filtrate toxicity. The CCP filtrate clearly contrasted with all other filtrates. The toxicity test based on Electrolyte Leakage Measurement offers the opportunity to assess the sensitivity of rubber genotypes to C. cassiicola exudates or purified effectors for genetic investigations and early selection, without risk of spreading the fungus in plantations. However, the power of this test for predicting field susceptibility of rubber clones to CLF will have

  20. Genetic Determinism of Sensitivity to Corynespora cassiicola Exudates in Rubber Tree (Hevea brasiliensis).

    PubMed

    Tran, Dinh Minh; Clément-Demange, André; Déon, Marine; Garcia, Dominique; Le Guen, Vincent; Clément-Vidal, Anne; Soumahoro, Mouman; Masson, Aurélien; Label, Philippe; Le, Mau Tuy; Pujade-Renaud, Valérie

    2016-01-01

    An indirect phenotyping method was developed in order to estimate the susceptibility of rubber tree clonal varieties to Corynespora Leaf Fall (CLF) disease caused by the ascomycete Corynespora cassiicola. This method consists in quantifying the impact of fungal exudates on detached leaves by measuring the induced electrolyte leakage (EL%). The tested exudates were either crude culture filtrates from diverse C. cassiicola isolates or the purified cassiicolin (Cas1), a small secreted effector protein produced by the aggressive isolate CCP. The test was found to be quantitative, with the EL% response proportional to toxin concentration. For eight clones tested with two aggressive isolates, the EL% response to the filtrates positively correlated to the response induced by conidial inoculation. The toxicity test applied to 18 clones using 13 toxinic treatments evidenced an important variability among clones and treatments, with a significant additional clone x treatment interaction effect. A genetic linkage map was built using 306 microsatellite markers, from the F1 population of the PB260 x RRIM600 family. Phenotyping of the population for sensitivity to the purified Cas1 effector and to culture filtrates from seven C. cassiicola isolates revealed a polygenic determinism, with six QTL detected on five chromosomes and percentages of explained phenotypic variance varying from 11 to 17%. Two common QTL were identified for the CCP filtrate and the purified cassiicolin, suggesting that Cas1 may be the main effector of CCP filtrate toxicity. The CCP filtrate clearly contrasted with all other filtrates. The toxicity test based on Electrolyte Leakage Measurement offers the opportunity to assess the sensitivity of rubber genotypes to C. cassiicola exudates or purified effectors for genetic investigations and early selection, without risk of spreading the fungus in plantations. However, the power of this test for predicting field susceptibility of rubber clones to CLF will have

  1. Heart mass and blood pressure have separate genetic determinants in the New Zealand genetically hypertensive (GH) rat.

    PubMed

    Harris, E L; Phelan, E L; Thompson, C M; Millar, J A; Grigor, M R

    1995-04-01

    To determine associations between cardiovascular parameters and genotype in 205 F2 rats of both sexes and lineages from reciprocal crosses made between rats of the New Zealand genetically hypertensive (GH) and Brown Norway (BN) rat strains. Systolic tail blood pressure, mean arterial blood pressure, pulse rate, heart mass, body mass and relative heart mass were determined for each rat in the age range 17-19 weeks, and DNA polymorphisms were examined for the guanylyl cyclase A (GCA), angiotensin converting enzyme (ACE) and renin (REN) genes. The phenotypic data indicated the presence of genes on the X and Y chromosomes that affected blood pressure. The GH GCA allele, in males only, and the GH ACE allele, in females only, both cosegregated with increased blood pressure. The ACE effect was confined to rats of one lineage only, namely those with GH grandfathers. A cosegregation of the GH REN allele with decreased blood pressure was also detected in females with BN grandfathers. In contrast, the GH REN allele cosegregated with a smaller heart in males only, whereas the GH ACE allele cosegregated with a larger heart both in males and in females. In males this was the consequence of a decrease in body mass with no change in absolute heart mass, whereas in females there were changes in both of these parameters. The results show that cardiac hypertrophy and blood pressure have independent genetic determinants in the GH rat, and indicate the importance of sex in determining the phenotypic expression of genes underlying cardiovascular pathology.

  2. Genetic background, gender, age, body temperature, and arterial blood pH have a major impact on myocardial infarct size in the mouse and need to be carefully measured and/or taken into account: results of a comprehensive analysis of determinants of infarct size in 1,074 mice.

    PubMed

    Guo, Yiru; Flaherty, Michael P; Wu, Wen-Jian; Tan, Wei; Zhu, Xiaoping; Li, Qianhong; Bolli, Roberto

    2012-09-01

    In order to determine whether the myocardial response to ischemia/reperfusion (I/R) injury varies depending on genetic background, gender, age, body temperature, and arterial blood pH, we studied 1,074 mice from 19 strains (including 129S6/SvEvTac (129S6), B6/129P2-Ptgs2(tm1Unc), B6/129SvF(2)/J, B6/129/D2, B6/CBAF1, B6/DBA/1JNcr, BALB/c, BPH2/J, C57BL/6/J (B6/J), C3H/DBA, C3H/FB/FF, C3H/HeJ-Pde6b(rd1), FVB/N/J [FVB/N], FVB/B6, FVB/ICR and Crl:ICR/H [ICR]) and distributed them into 69 groups depending on strain and: (1) two phases of ischemic preconditioning (PC); (2) coronary artery occlusion (O) time; (3) gender; (4) age; (5) blood transfusion; (6) core body temperature; and (7) arterial blood pH. Mice underwent O either without (non-preconditioned [naive]) or with prior cyclic O/reperfusion (R) (PC stimulus) consisting of six 4-min O/4-min R cycles 10 min (early PC, EPC) or 24 h (late PC, LPC) prior to 30 or 45-min O and 24 h R. In B6/J and B6/129/D2 mice, almost the entire risk region was infarcted after a 60-min O. Of the naive mouse hearts, B6/ecSOD(WT) and FVB/N mice had infarct sizes significantly smaller than those of the other mice. All strains except FVB/N benefited from the cardioprotection afforded by the early phase of PC; in contrast, development of LPC was inconsistent amongst groups and was strain-dependent. Female gender (1) was associated with reduced infarct size in ICR mice, (2) determined whether LPC developed in ICR mice, and (3) limited the protection afforded by EPC in 129S6 mice. Importantly, mild hypothermia (1 °C decrease in core temperature) and mild acidosis (0.18 decrease in blood pH) resulted in a striking cardioprotective effect in ICR mice: 67.5 and 43.0 % decrease in infarct size, respectively. Replacing blood losses with crystalloid fluids (instead of blood) during surgery also reduced infarct size. To our knowledge, this is the largest analysis of the determinants of infarct size in mice ever published. The results

  3. Patterns and Mechanisms of Evolutionary Transitions between Genetic Sex-Determining Systems

    PubMed Central

    Sander van Doorn, G.

    2014-01-01

    The diversity and patchy phylogenetic distribution of genetic sex-determining mechanisms observed in some taxa is thought to have arisen by the addition, modification, or replacement of regulators at the upstream end of the sex-determining pathway. Here, I review the various evolutionary forces acting on upstream regulators of sexual development that can cause transitions between sex-determining systems. These include sex-ratio selection and pleiotropic benefits, as well as indirect selection mechanisms involving sex-linked sexually antagonistic loci or recessive deleterious mutations. Most of the current theory concentrates on the population–genetic aspects of sex-determination transitions, using models that do not reflect the developmental mechanisms involved in sex determination. However, the increasing availability of molecular data creates opportunities for the development of mechanistic models that can clarify how selection and developmental architecture interact to direct the evolution of sex-determination genes. PMID:24993578

  4. Genetic determination of fatty acid composition in Spanish Churra sheep milk.

    PubMed

    Sánchez, J P; San Primitivo, F; Barbosa, E; Varona, L; de la Fuente, L F

    2010-01-01

    The objective of this study was to estimate the genetic variation of ovine milk fatty acid (FA) composition. We collected 4,100 milk samples in 14 herds from 976 Churra ewes sired mostly by 15 AI rams and analyzed them by gas-liquid chromatography for milk fatty acid composition. The studied traits were 12 individual FA contents (proportion in relation to the total amount of FA), 3 groups of fatty acids [saturated fatty acids (SFA), monounsaturated FA (MUFA), and polyunsaturated FA (PUFA)], and 2 FA ratios (n-6:n-3 and C18:2 cis-9,trans-11:C18:1 trans-11). In addition, percentages of fat and protein and daily milk yield were studied. For the analysis, repeatability animal models were implemented using Bayesian methods. In an initial step, univariate methods were conducted to test the hypothesis of the traits showing additive genetic determination. Deviance information criterion and Bayes factor were employed as model choice criteria. All the studied SFA showed additive genetic variance, but the estimated heritabilities were low. Among unsaturated FA (UFA), only C18:1 trans-11 and C18:2 cis-9,cis-12 showed additive genetic variation, their estimated heritabilities being [marginal posterior mean (marginal posterior SD)] 0.02(0.01) and 0.11(0.04), respectively. For the FA groups, only PUFA showed significant additive genetic variation. None of the studied ratios of FA showed additive genetic variation. In second multitrait analyses, genetic correlations between individual FA and production traits, and between groups of FA and ratios of FA and production traits, were investigated. Positive genetic correlations were estimated among medium-chain SFA, ranging from 0 to 0.85, but this parameter was close to zero between long-chain SFA (C16:0 and C18:0). Between long- and medium-chain SFA, estimated genetic correlations were negative, around -0.6. Among those UFA showing significant additive genetic variance, genetic correlations were close to zero. The estimated genetic

  5. Privacy and confidentiality measures in genetic testing and counselling: arguing on genetic exceptionalism again?

    PubMed

    Witt, Magdalena M; Witt, Michał P

    2016-11-01

    Medical confidentiality in clinical genetics poses an important question about its scope, which would be in line with professional ethics and simple honesty. It is already known that the maintenance of absolute anonymity, bearing in mind the current progress of genetic techniques, is virtually impossible. On the other hand, our insight into the information contained in the human genome is increasing. This mini-review presents the authors' standpoint regarding this complex and difficult issue.

  6. Genetic Algorithm for Initial Orbit Determination with Too Short Arc (Continued)

    NASA Astrophysics Data System (ADS)

    Li, X. R.; Wang, X.

    2016-03-01

    When using the genetic algorithm to solve the problem of too-short-arc (TSA) determination, due to the difference of computing processes between the genetic algorithm and classical method, the methods for outliers editing are no longer applicable. In the genetic algorithm, the robust estimation is acquired by means of using different loss functions in the fitness function, then the outlier problem of TSAs is solved. Compared with the classical method, the application of loss functions in the genetic algorithm is greatly simplified. Through the comparison of results of different loss functions, it is clear that the methods of least median square and least trimmed square can greatly improve the robustness of TSAs, and have a high breakdown point.

  7. 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 ...

  8. Identification of plant stress-responsive determinants in Arabidopsis by large-scale forward genetic screens.

    PubMed

    Koiwa, Hisashi; Bressan, Ray A; Hasegawa, Paul M

    2006-01-01

    All plants sense and adapt to adverse environmental conditions, however, crop plants exhibit less genetic diversity for abiotic stress tolerance than do wild relatives indicating that a genetic basis exists for stress adaptability. Model plant genetic systems and the plethora of molecular genetic resources that are currently available are greatly enhancing our ability to identify abiotic stress-responsive genetic determinants. Forward genetic screens of T-DNA mutagenized Arabidopsis thaliana populations in the genetic background of ecotypes C24(RD29a-LUC) and Col-0 gl1 sos3-1 were carried out to begin an exhaustive search for such determinants. The C24(RD29a-LUC) screens identified mutants with altered salt/osmotic stress sensitivity or mutants with altered expression of the salt/osmotic/cold/ABA-responsive RD29a gene. Also, mutations that alter the NaCl sensitivity of sos3-1 were screened for potential genetic suppressors or enhancers of salt-stress responses mediated by SOS3. In total, more than 250 000 independent insertion lines were screened and greater than 200 individual mutants that exhibited altered stress/ABA responses were recovered. Although several of these mutants have been reported, most have not yet been studied in detail. Notable examples include novel alleles of SOS1 and mutations to genes encoding the STT3a subunit of the oligosaccharyltransferase, syntaxin, RNA polymerase II CTD phosphatases, transcription factors, ABA biosynthetic enzyme, Na+ transporter HKT1, and SUMO E3 ligase. The stress-specific phenotypes of mutations to genes that are involved in many basic cellular functions provide indication of the wide range of control mechanisms in cellular homeostasis that are involved in stress adaptation.

  9. Determination of the magnetostrictive response of nanoparticles via magnetoelectric measurements.

    PubMed

    Martins, P; Silva, M; Lanceros-Mendez, S

    2015-06-07

    It is successfully demonstrated that nanoparticle's magnetostriction can be accurately determined based on the magnetoelectric effect measured on polymeric composite materials. This represents a novel, simple and versatile method for the determination of particle's magnetostriction at the nano scale and in their dispersed state, which has been, up to now, a difficult and imprecise task.

  10. Environmental and genetic determinants of innovativeness in a natural population of birds

    PubMed Central

    Quinn, John L.; Cole, Ella F.; Reed, Thomas E.

    2016-01-01

    Much of the evidence for the idea that individuals differ in their propensity to innovate and solve new problems has come from studies on captive primates. Increasingly, behavioural ecologists are studying innovativeness in wild populations, and uncovering links with functional behaviour and fitness-related traits. The relative importance of genetic and environmental factors in driving this variation, however, remains unknown. Here, we present the results of the first large-scale study to examine a range of causal factors underlying innovative problem-solving performance (PSP) among 831 great tits (Parus major) temporarily taken into captivity. Analyses show that PSP in this population: (i) was linked to a variety of individual factors, including age, personality and natal origin (immigrant or local-born); (ii) was influenced by natal environment, because individuals had a lower PSP when born in poor-quality habitat, or where local population density was high, leading to cohort effects. Links with many of the individual and environmental factors were present only in some years. In addition, PSP (iii) had little or no measurable heritability, as estimated by a Bayesian animal model; and (iv) was not influenced by maternal effects. Despite previous reports of links between PSP and a range of functional traits in this population, the analyses here suggest that innovativeness had weak if any evolutionary potential. Instead most individual variation was caused by phenotypic plasticity driven by links with other behavioural traits and by environmentally mediated developmental stress. Heritability estimates are population, time and context specific, however, and more studies are needed to determine the generality of these effects. Our results shed light on the causes of innovativeness within populations, and add to the debate on the relative importance of genetic and environmental factors in driving phenotypic variation within populations. PMID:26926275

  11. Environmental and genetic determinants of innovativeness in a natural population of birds.

    PubMed

    Quinn, John L; Cole, Ella F; Reed, Thomas E; Morand-Ferron, Julie

    2016-03-19

    Much of the evidence for the idea that individuals differ in their propensity to innovate and solve new problems has come from studies on captive primates. Increasingly, behavioural ecologists are studying innovativeness in wild populations, and uncovering links with functional behaviour and fitness-related traits. The relative importance of genetic and environmental factors in driving this variation, however, remains unknown. Here, we present the results of the first large-scale study to examine a range of causal factors underlying innovative problem-solving performance (PSP) among 831 great tits (Parus major) temporarily taken into captivity. Analyses show that PSP in this population: (i) was linked to a variety of individual factors, including age, personality and natal origin (immigrant or local-born); (ii) was influenced by natal environment, because individuals had a lower PSP when born in poor-quality habitat, or where local population density was high, leading to cohort effects. Links with many of the individual and environmental factors were present only in some years. In addition, PSP (iii) had little or no measurable heritability, as estimated by a Bayesian animal model; and (iv) was not influenced by maternal effects. Despite previous reports of links between PSP and a range of functional traits in this population, the analyses here suggest that innovativeness had weak if any evolutionary potential. Instead most individual variation was caused by phenotypic plasticity driven by links with other behavioural traits and by environmentally mediated developmental stress. Heritability estimates are population, time and context specific, however, and more studies are needed to determine the generality of these effects. Our results shed light on the causes of innovativeness within populations, and add to the debate on the relative importance of genetic and environmental factors in driving phenotypic variation within populations. © 2016 The Author(s).

  12. Genetic Determinants of Trabecular and Cortical Volumetric Bone Mineral Densities and Bone Microstructure

    PubMed Central

    Kähönen, Mika; Raitakari, Olli; Laaksonen, Marika; Sievänen, Harri; Viikari, Jorma; Lyytikäinen, Leo-Pekka; Mellström, Dan; Karlsson, Magnus; Ljunggren, Östen; Grundberg, Elin; Kemp, John P.; Sayers, Adrian; Nethander, Maria; Evans, David M.; Vandenput, Liesbeth; Tobias, Jon H.; Ohlsson, Claes

    2013-01-01

    Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD), not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD), trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT). Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n = 5,878) followed by replication (n = 1,052) identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p = 3.6×10−14; LOC285735, rs271170, p = 2.7×10−12; OPG, rs7839059, p = 1.2×10−10; and ESR1/C6orf97, rs6909279, p = 1.1×10−9). The trabecular vBMD GWA meta-analysis (n = 2,500) followed by replication (n = 1,022) identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p = 1.9×10−9). High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n = 729). rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60–0.93) and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735) are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose that a genetic

  13. Procedure for Uranium-Molybdenum Density Measurements and Porosity Determination

    SciTech Connect

    Prabhakaran, Ramprashad; Devaraj, Arun; Joshi, Vineet V.; Lavender, Curt A.

    2016-08-13

    The purpose of this document is to provide guidelines for preparing uranium-molybdenum (U-Mo) specimens, performing density measurements, and computing sample porosity. Typical specimens (solids) will be sheared to small rectangular foils, disks, or pieces of metal. A mass balance, solid density determination kit, and a liquid of known density will be used to determine the density of U-Mo specimens using the Archimedes principle. A standard test weight of known density would be used to verify proper operation of the system. By measuring the density of a U-Mo sample, it is possible to determine its porosity.

  14. A new measuring method to determine material spectral emissivity

    NASA Astrophysics Data System (ADS)

    Smetana, W.; Reicher, R.

    1998-05-01

    Emissivity is a measure of how well a real surface can radiate energy as compared with a blackbody. This characteristic radiative number is usually determined by means of optical pyrometry. By contrast an indirect measurement method has been developed which enables the determination of the normal spectral emissivity of various materials at a specific wavelength. A heat flow induced in a test body by the absorbed irradiation of a laser beam may be correlated with the spectral emissivity of its surface. The theory of the measuring principle is discussed and the feasibility of the method evaluated by means of practical experiments utilizing a thermopile built up using a thick film technique.

  15. Teachers' Conceptions about the Genetic Determinism of Human Behaviour: A Survey in 23 Countries

    ERIC Educational Resources Information Center

    Castéra, Jérémy; Clément, Pierre

    2014-01-01

    This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the interviewed…

  16. Teachers' Conceptions About the Genetic Determinism of Human Behaviour: A Survey in 23 Countries

    NASA Astrophysics Data System (ADS)

    Castéra, Jérémy; Clément, Pierre

    2012-07-01

    This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the interviewed teachers' conceptions. This illustrates that innatism is present in two distinct ways: in relation to individuals (e.g. genetic determinism to justify intellectual likeness between individuals such as twins) or in relation to groups of humans (e.g. genetic determinism to justify gender differences or the superiority of some human ethnic groups). A between-factor analysis discriminates between countries, showing very significant differences. There is more innatism among teachers' conceptions in African countries and Lebanon than in European countries, Brazil and Australia. Among the other controlled parameters, only two are significantly independent of the country: the level of training and the level of knowledge of biology. A co-inertia analysis shows a strong correlation between non-citizen attitudes towards and innatist conceptions of genetic determinism regarding human groups. We discuss these findings and their implications for education.

  17. Teachers' Conceptions about the Genetic Determinism of Human Behaviour: A Survey in 23 Countries

    ERIC Educational Resources Information Center

    Castéra, Jérémy; Clément, Pierre

    2014-01-01

    This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the interviewed…

  18. Genetic Ancestry is Associated with Measures of Subclinical Atherosclerosis in African Americans: The Jackson Heart Study

    PubMed Central

    Gebreab, Samson Y; Riestra, Pia; Khan, Rumana J; Xu, Ruihua; Musani, Solomon K; Tekola-Ayele, Fasil; Correa, Adolfo; Wilson, James G; Rotimi, Charles N; Davis, Sharon K

    2015-01-01

    Objective To determine whether genetic ancestry was associated with subclinical atherosclerosis measures after adjustment for traditional CVD risk factors, inflammatory marker, socioeconomic status (SES) and psychosocial factors in a large admixed African American population. Approach and Results Participants were drawn from Jackson Heart Study (JHS). Participant’s percent of European Ancestry (PEA) was estimated based on 1747 genetic markers using HAPMIX. Association of PEA with peripheral arterial disease (PAD) and common carotid intima media thickness (cCIMT) were investigated among 2168 participants and with coronary artery calcification (CAC >0) and abdominal aortic calcification (AAC >0) among 1139 participants. The associations were evaluated using multivariable regression models. Our results showed a 1 standard deviation increase in PEA was associated with a lower PAD prevalence after adjusting for age and gender [Prevalence ratio (PR) = 0. 90 (95% CI: 0.82, 0.99); p=0.036]. Adjustments for traditional CVD risk factors, SES, and psychosocial factors attenuated this association [PR=0.91 (0.82, 1.00); p=0.046]. There was also a non-linear association between PEA and CAC and AAC. The lowest PEA was associated with a lower CAC [PR=0.75 (0.58, 0.96); p=0.022] and a lower AAC [PR=0. 80 (0.67, 0.96); p=0.016] compared to the reference group (10th–90th percentile) after adjusting for traditional CVD risk factors, inflammatory marker, SES and psychosocial factors. However, we found no significant association between PEA and cCIMT. Conclusions Overall, our findings indicate that genetic ancestry was associated with subclinical atherosclerosis, suggesting unmeasured risk factors and/or interactions with genetic factors might contribute to the distribution of subclinical atherosclerosis among African Americans. PMID:25745061

  19. Genetic ancestry is associated with measures of subclinical atherosclerosis in African Americans: the Jackson Heart Study.

    PubMed

    Gebreab, Samson Y; Riestra, Pia; Khan, Rumana J; Xu, Ruihua; Musani, Solomon K; Tekola-Ayele, Fasil; Correa, Adolfo; Wilson, James G; Rotimi, Charles N; Davis, Sharon K

    2015-05-01

    To determine whether genetic ancestry was associated with subclinical atherosclerosis measures after adjustment for traditional cardiovascular disease risk factors, inflammatory marker, socioeconomic status, and psychosocial factors in a large admixed African American population. Participants were drawn from the Jackson Heart Study. Participant's percent of European ancestry (PEA) was estimated based on 1747 genetic markers using HAPMIX. Association of PEA with peripheral arterial disease and common carotid intima-media thickness were investigated among 2168 participants and with coronary artery calcification >0 and abdominal aortic calcification >0 among 1139 participants. The associations were evaluated using multivariable regression models. Our results showed that a 1 SD increase in PEA was associated with a lower peripheral arterial disease prevalence after adjusting for age and sex (prevalence ratio=0.90 [95% CI, 0.82-0.99]; P=0.036). Adjustments for traditional cardiovascular disease risk factors, socioeconomic status, and psychosocial factors attenuated this association (prevalence ratio=0.91 [0.82-1.00]; P=0.046). There was also a nonlinear association between PEA and coronary artery calcification and abdominal aortic calcification. The lowest PEA was associated with a lower coronary artery calcification (prevalence ratio=0.75 [0.58-0.96]; P=0.022) and a lower abdominal aortic calcification [prevalence ratio=0.80 [0.67-0.96]; P=0.016) compared with the reference group (10th-90th percentile) after adjusting for traditional cardiovascular disease risk factors, inflammatory marker, socioeconomic status, and psychosocial factors. However, we found no significant association between PEA and common carotid intima-media thickness. Overall, our findings indicate that genetic ancestry was associated with subclinical atherosclerosis, suggesting unmeasured risk factors and interactions with genetic factors might contribute to the distribution of subclinical

  20. Low-Earth Orbit Determination from Gravity Gradient Measurements

    NASA Astrophysics Data System (ADS)

    Sun, Xiucong; Chen, Pei; Macabiau, Christophe; Han, Chao

    2016-06-01

    An innovative orbit determination method which makes use of gravity gradients for Low-Earth-Orbiting satellites is proposed. The measurement principle of gravity gradiometry is briefly reviewed and the sources of measurement error are analyzed. An adaptive hybrid least squares batch filter based on linearization of the orbital equation and unscented transformation of the measurement equation is developed to estimate the orbital states and the measurement biases. The algorithm is tested with the actual flight data from the European Space Agency's Gravity field and steady-state Ocean Circulation Explorer (GOCE). The orbit determination results are compared with the GPS-derived orbits. The radial and cross-track position errors are on the order of tens of meters, whereas the along-track position error is over one order of magnitude larger. The gravity gradient based orbit determination method is promising for potential use in GPS-denied spacecraft navigation.

  1. Measuring informed choice in population-based reproductive genetic screening: a systematic review

    PubMed Central

    Ames, Alice Grace; Metcalfe, Sylvia Ann; Archibald, Alison Dalton; Duncan, Rony Emily; Emery, Jon

    2015-01-01

    Genetic screening and health-care guidelines recommend that programmes should facilitate informed choice. It is therefore important that accurate measures of informed choice are available to evaluate such programmes. This review synthesises and appraises measures used to evaluate informed choice in population-based genetic screening programmes for reproductive risk. Databases were searched for studies offering genetic screening for the purpose of establishing reproductive risk to an adult population sample, in which aspects of informed choice were measured. Studies were included if, at a minimum, measures of uptake of screening and knowledge were used. Searches identified 1462 citations and 76 studies were reviewed in full text; 34 studies met the inclusion criteria. Over 20 different measures of informed choice were used. Many measures lacked adequate validity and reliability data. This systematic review will inform future evaluation of informed choice in population genetic screening programmes. PMID:24848746

  2. Alteration of Genetic Make-up in Karnal Bunt Pathogen (Tilletia indica) of Wheat in Presence of Host Determinants

    PubMed Central

    Gupta, Atul K.; Seneviratne, J. M.; Bala, Ritu; Jaiswal, J. P.; Kumar, Anil

    2015-01-01

    Alteration of genetic make-up of the isolates and monosporidial strains of Tilletia indica causing Karnal bunt (KB) disease in wheat was analyzed using DNA markers and SDS-PAGE. The generation of new variation with different growth characteristics is not a generalized feature and is not only dependant on the original genetic make up of the base isolate/monosporidial strains but also on interaction with host. Host determinant(s) plays a significant role in the generation of variability and the effect is much pronounced in monosporidial strains with narrow genetic base as compared to broad genetic base. The most plausible explanation of genetic variation in presence of host determinant(s) are the recombination of genetic material from two different mycelial/sporidia through sexual mating as well as through para-sexual means. The morphological and development dependent variability further suggests that the variation in T. indica strains predominantly derived through the genetic rearrangements. PMID:26060428

  3. Towards a measurement instrument for determinants of innovations

    PubMed Central

    Fleuren, Margot A.H.; Paulussen, Theo G.W.M.; Van Dommelen, Paula; Van Buuren, Stef

    2014-01-01

    Objective To develop a short instrument to measure determinants of innovations that may affect its implementation. Design We pooled the original data from eight empirical studies of the implementation of evidence-based innovations. The studies used a list of 60 potentially relevant determinants based on a systematic review of empirical studies and a Delphi study among implementation experts. Each study used similar methods to measure both the implementation of the innovation and determinants. Missing values in the final data set were replaced by plausible values using multiple imputation. We assessed which determinants predicted completeness of use of the innovation (% of recommendations applied). In addition, 22 implementation experts were consulted about the results and about implications for designing a short instrument. Setting Eight innovations introduced in Preventive Child Health Care or schools in the Netherlands. Participants Doctors, nurses, doctor's assistants and teachers; 1977 respondents in total. Results The initial list of 60 determinants could be reduced to 29. Twenty-one determinants were based on the pooled analysis of the eight studies, seven on the theoretical expectations of the experts consulted and one new determinant was added on the basis of the experts' practical experience. Conclusions The instrument is promising and should be further validated. We invite researchers to use and explore the instrument in multiple settings. The instrument describes how each determinant should preferably be measured (questions and response scales). It can be used both before and after the introduction of an innovation to gain an understanding of the critical change objectives. PMID:24951511

  4. Genetic differentiation in Pyrenophora teres populations measured with AFLP markers.

    PubMed

    Serenius, Marjo; Manninen, Outi; Wallwork, Hugh; Williams, Kevin

    2007-02-01

    The genetic structure and occurrence of mating types and forms of Pyrenophora teres, the causal agent of net blotch on barley, was studied among 278 isolates collected from the northern hemisphere and from Australia. Genetic differentiation was high (F(CT) 0.238, P=0.002) between P. teres f. teres (PTT) isolates originating from Northern Europe, North America, Russia and Australia. The P. teres population in Australia was clearly divided into two subgroups (F(CT) 0.793, P<0.001) according to the form identity: PTT and P. teres f. maculata (PTM), with the PTT samples showing a greater degree of differentiation (F(ST) 0.573, P<0.001) among Australian states than the PTM samples (F(CT) 0.219, P<0.001). No differentiation was found among locations within Australian states. Both mating types (MAT1 and MAT2) were equally common (1:1) in several locations in Australia and in Finland. The only exception was Krasnodar, Russia, where only MAT2 was identified. Our results show that the prevalence of sexual reproduction, occurrence of forms of P. teres, and genetic differentiation between geographical regions are highly variable. The paper discusses the various effects and outcomes of population selection in Australia and in the northern barley growing regions.

  5. Determining the effective dimensionality of the genetic variance-covariance matrix.

    PubMed

    Hine, Emma; Blows, Mark W

    2006-06-01

    Determining the dimensionality of G provides an important perspective on the genetic basis of a multivariate suite of traits. Since the introduction of Fisher's geometric model, the number of genetically independent traits underlying a set of functionally related phenotypic traits has been recognized as an important factor influencing the response to selection. Here, we show how the effective dimensionality of G can be established, using a method for the determination of the dimensionality of the effect space from a multivariate general linear model introduced by Amemiya (1985). We compare this approach with two other available methods, factor-analytic modeling and bootstrapping, using a half-sib experiment that estimated G for eight cuticular hydrocarbons of Drosophila serrata. In our example, eight pheromone traits were shown to be adequately represented by only two underlying genetic dimensions by Amemiya's approach and factor-analytic modeling of the covariance structure at the sire level. In contrast, bootstrapping identified four dimensions with significant genetic variance. A simulation study indicated that while the performance of Amemiya's method was more sensitive to power constraints, it performed as well or better than factor-analytic modeling in correctly identifying the original genetic dimensions at moderate to high levels of heritability. The bootstrap approach consistently overestimated the number of dimensions in all cases and performed less well than Amemiya's method at subspace recovery.

  6. Ecology, not the genetics of sex determination, determines who helps in eusocial populations.

    PubMed

    Ross, Laura; Gardner, Andy; Hardy, Nate; West, Stuart A

    2013-12-02

    In eusocial species, the sex ratio of helpers varies from female only, in taxa such as the social Hymenoptera (ants, bees, and wasps) [1], to an unbiased mixture of males and females, as in most termites [2]. Hamilton suggested that this difference owes to the haplodiploid genetics of the Hymenoptera leading to females being relatively more related to their siblings [3]. However, it has been argued that Hamilton's hypothesis does not work [4-9] and that the sex of helpers could instead be explained by variation in the ecological factors that favor eusociality [10]. Here we test these two competing hypotheses, which focus on the possible importance of different terms in Hamilton's rule [2, 11], with a comparative study across all sexual eusocial taxa. We find that the sex ratio of helpers (1) shows no significant correlation with whether species are haplodiploid or diploid and (2) shows a strong correlation with the ecological factor that had favored eusociality. Specifically, when the role of helpers is to defend the nest, both males and females help, whereas when the role of helpers is to provide brood care, then helpers are the sex or sexes that provided parental care ancestrally. More generally, our results confirm the ability of kin selection theory to explain the biology of eusocial species, independently of ploidy, and add support to the idea that haplodiploidy has been more important for shaping conflicts within eusocial societies than for explaining its origins [6, 12-19]. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Genetically encoded FRET-based nanosensor for in vivo measurement of leucine.

    PubMed

    Mohsin, Mohd; Abdin, M Z; Nischal, Lata; Kardam, Hemant; Ahmad, Altaf

    2013-12-15

    Besides fundamental role in protein synthesis, leucine has metabolic roles as energy substrates, precursors for synthesis of other amino acids and as a modulator of muscle protein synthesis via the insulin-signaling pathway. Leucine concentration in cell and tissue is temporally dynamic as the metabolism of leucine is regulated through multiple enzymes and transporters. Assessment of cell-type specific activities of transporters and enzymes by physical fractionation is extremely challenging. Therefore, a method of reporting leucine dynamics at the cellular level is highly desirable. Given this, we developed a series of genetically encoded nanosensors for real-time in vivo measurement of leucine at cellular level. A leucine binding periplasmic binding protein (LivK) of Escherichia coli K12 was flanked with CFP (cyan fluorescent protein) and YFP (yellow fluorescent protein) at N-terminus and C-terminus, respectively. The constructed nanosensors allowed in vitro determination of fluorescence resonance energy transfer (FRET) changes in a concentration-dependent manner. These sensors were found to be specific to leucine, and stable to pH-changes within a physiological range. Genetically encoded sensors can be targeted to a specific cell type, and allow dynamic measurement of leucine concentration in bacterial and yeast cells.

  8. Curve-based multivariate distance matrix regression analysis: application to genetic association analyses involving repeated measures

    PubMed Central

    Salem, Rany M.; O'Connor, Daniel T.

    2010-01-01

    Most, if not all, human phenotypes exhibit a temporal, dosage-dependent, or age effect. Despite this fact, it is rare that data are collected over time or in sequence in relevant studies of the determinants of these phenotypes. The costs and organizational sophistication necessary to collect repeated measurements or longitudinal data for a given phenotype are clearly impediments to this, but greater efforts in this area are needed if insights into human phenotypic expression are to be obtained. Appropriate data analysis methods for genetic association studies involving repeated or longitudinal measures are also needed. We consider the use of longitudinal profiles obtained from fitted functions on repeated data collections from a set of individuals whose similarities are contrasted between sets of individuals with different genotypes to test hypotheses about genetic influences on time-dependent phenotype expression. The proposed approach can accommodate uncertainty of the fitted functions, as well as weighting factors across the time points, and is easily extended to a wide variety of complex analysis settings. We showcase the proposed approach with data from a clinical study investigating human blood vessel response to tyramine. We also compare the proposed approach with standard analytic procedures and investigate its robustness and power via simulation studies. The proposed approach is found to be quite flexible and performs either as well or better than traditional statistical methods. PMID:20423962

  9. Beliefs in genetic determinism and attitudes towards psychiatric genetic research: psychometric scale properties, construct associations, demographic correlates, and cross-cultural comparisons.

    PubMed

    Voracek, Martin; Swami, Viren; Loibl, Lisa Mariella; Furnham, Adrian

    2007-12-01

    Using two new scales, this study examined beliefs in genetic determinism and attitudes towards psychiatric genetic research in student samples from Austria, Malaysia, Romania, and the United Kingdom. For both constructs, effects of culture were detectable, whereas those related to key demographics were either small and inconsistent across samples (political orientation and religiosity) or zero (sex and age). Judged from factorial dimensionality and internal consistency, the psychometric properties of both scales were satisfactory. Belief in genetic determinism had lower prevalence and corresponded only modestly to positive attitudes towards psychiatric genetic research which had higher prevalence. The correlations of both constructs with a preference of inequality among social groups (social dominance orientation) were modest and inconsistent across samples. Both scales appear appropriate for cross-cultural applications, in particular for research into lay theories and public perceptions regarding genetic vs environmental effects on human behavior, mental disorders, and behavioral and psychiatric genetic research related to these.

  10. The Central Role of KNG1 Gene as a Genetic Determinant of Coagulation Pathway-Related Traits: Exploring Metaphenotypes

    PubMed Central

    Massanet, Raimon; Martinez-Perez, Angel; Ziyatdinov, Andrey; Martin-Fernandez, Laura; Souto, Juan Carlos; Perera, Alexandre; Soria, José Manuel

    2016-01-01

    Traditional genetic studies of single traits may be unable to detect the pleiotropic effects involved in complex diseases. To detect the correlation that exists between several phenotypes involved in the same biological process, we introduce an original methodology to analyze sets of correlated phenotypes involved in the coagulation cascade in genome-wide association studies. The methodology consists of a two-stage process. First, we define new phenotypic meta-variables (linear combinations of the original phenotypes), named metaphenotypes, by applying Independent Component Analysis for the multivariate analysis of correlated phenotypes (i.e. the levels of coagulation pathway–related proteins). The resulting metaphenotypes integrate the information regarding the underlying biological process (i.e. thrombus/clot formation). Secondly, we take advantage of a family based Genome Wide Association Study to identify genetic elements influencing these metaphenotypes and consequently thrombosis risk. Our study utilized data from the GAIT Project (Genetic Analysis of Idiopathic Thrombophilia). We obtained 15 metaphenotypes, which showed significant heritabilities, ranging from 0.2 to 0.7. These results indicate the importance of genetic factors in the variability of these traits. We found 4 metaphenotypes that showed significant associations with SNPs. The most relevant were those mapped in a region near the HRG, FETUB and KNG1 genes. Our results are provocative since they show that the KNG1 locus plays a central role as a genetic determinant of the entire coagulation pathway and thrombus/clot formation. Integrating data from multiple correlated measurements through metaphenotypes is a promising approach to elucidate the hidden genetic mechanisms underlying complex diseases. PMID:28005926

  11. The genetic sex-determination system predicts adult sex ratios in tetrapods.

    PubMed

    Pipoly, Ivett; Bókony, Veronika; Kirkpatrick, Mark; Donald, Paul F; Székely, Tamás; Liker, András

    2015-11-05

    The adult sex ratio (ASR) has critical effects on behaviour, ecology and population dynamics, but the causes of variation in ASRs are unclear. Here we assess whether the type of genetic sex determination influences the ASR using data from 344 species in 117 families of tetrapods. We show that taxa with female heterogamety have a significantly more male-biased ASR (proportion of males: 0.55 ± 0.01 (mean ± s.e.m.)) than taxa with male heterogamety (0.43 ± 0.01). The genetic sex-determination system explains 24% of interspecific variation in ASRs in amphibians and 36% in reptiles. We consider several genetic factors that could contribute to this pattern, including meiotic drive and sex-linked deleterious mutations, but further work is needed to quantify their effects. Regardless of the mechanism, the effects of the genetic sex-determination system on the adult sex ratio are likely to have profound effects on the demography and social behaviour of tetrapods.

  12. Determination of the measurement threshold in gamma-ray spectrometry.

    PubMed

    Korun, M; Vodenik, B; Zorko, B

    2017-03-01

    In gamma-ray spectrometry the measurement threshold describes the lover boundary of the interval of peak areas originating in the response of the spectrometer to gamma-rays from the sample measured. In this sense it presents a generalization of the net indication corresponding to the decision threshold, which is the measurement threshold at the quantity value zero for a predetermined probability for making errors of the first kind. Measurement thresholds were determined for peaks appearing in the spectra of radon daughters (214)Pb and (214)Bi by measuring the spectrum 35 times under repeatable conditions. For the calculation of the measurement threshold the probability for detection of the peaks and the mean relative uncertainty of the peak area were used. The relative measurement thresholds, the ratios between the measurement threshold and the mean peak area uncertainty, were determined for 54 peaks where the probability for detection varied between some percent and about 95% and the relative peak area uncertainty between 30% and 80%. The relative measurement thresholds vary considerably from peak to peak, although the nominal value of the sensitivity parameter defining the sensitivity for locating peaks was equal for all peaks. At the value of the sensitivity parameter used, the peak analysis does not locate peaks corresponding to the decision threshold with the probability in excess of 50%. This implies that peaks in the spectrum may not be located, although the true value of the measurand exceeds the decision threshold.

  13. Determining the Differential Emission Measure from EIS, XRT, and AIA

    NASA Technical Reports Server (NTRS)

    Winebarger, Amy R.; Warren, H.P.; Schmelz, J.

    2010-01-01

    This viewgraph presentation determines the Differential Emission Measure (DEM) from the EUV Imaging Spectrometer (EIS), X Ray Telescope (XRT), and Atmospheric Imaging Array (AIA). Common observations with Fe, Si, and Ca EIS lines are shown along with observations with Al-mesh, Ti-poly Al-thick and Be-thick XRT filters. Results from these observations are shown to determine what lines and filters are important to better constrain the hot component.

  14. Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network.

    PubMed

    Aslibekyan, S; An, P; Frazier-Wood, A C; Kabagambe, E K; Irvin, M R; Straka, R J; Tiwari, H K; Tsai, M Y; Hopkins, P N; Borecki, I B; Ordovas, J M; Arnett, D K

    2013-10-01

    Adiponectin is an adipose-secreted protein that has been linked to changes in insulin sensitivity, high-density lipoprotein cholesterol levels, and inflammatory patterns. Although fenofibrate therapy can raise adiponectin levels, treatment response is heterogeneous and heritable, suggesting a role for genetic mediators. This is the first genome-wide association study of fenofibrate effects on circulating adiponectin. Plasma adiponectin was measured in participants of the Genetics of Lipid Lowering Drugs and Diet Network (n = 793) before and after a 3-week daily treatment with 160 mg of fenofibrate. Associations between variants on the Affymetrix Genome-Wide Human SNP Array 6.0 and adiponectin were assessed using mixed linear models, adjusted for age, sex, site, and family. We observed a statistically significant (P = 5 × 10⁻⁸) association between rs2384207 in 12q24, a region previously linked to several metabolic traits, and the fenofibrate-induced change in circulating adiponectin. Additionally, our genome-wide analysis of baseline adiponectin levels replicated the previously reported association with CDH13 and suggested novel associations with markers near the PCK1, ZBP1, TMEM18, and SCUBE1 genes. The findings from the single marker tests were corroborated in gene-based analyses. Biological pathway analyses suggested a borderline significant association between the EGF receptor signaling pathway and baseline adiponectin levels. We present preliminary evidence linking several biologically relevant genetic variants to adiponectin levels at baseline and in response to fenofibrate therapy. Our findings provide support for fine-mapping of the 12q24 region to investigate the shared biological mechanisms underlying levels of circulating adiponectin and susceptibility to metabolic disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Genetic therapy, person-regarding reasons and the determination of identity.

    PubMed

    Elliot, Robert

    1997-04-01

    It has been argued, for example by Ingmar Persson, that genetic therapy performed on a conceptus does not alter the identity of the person that develops from it, even if we are essentially persons. If this claim is true then there can be person-regarding reasons for performing genetic therapy on a conceptus. Here it is argued that such person-regarding reasons obtain only if we are not essentially persons but essentially animals. This conclusion requires the defeat of the origination theory, which says that personal identity is determined by the identity of the foetus from which one originates. It is argued that the origination theory is false in the special case relevant to performing genetic therapy on a conceptus for person-regarding reasons.

  16. System for controllable magnetic measurement with direct field determination

    NASA Astrophysics Data System (ADS)

    Stupakov, O.

    2012-02-01

    This work describes a specially designed setup for magnetic hysteresis and Barkhausen noise measurements. The setup combines two main elements: an improved fast algorithm to control the waveform of magnetic induction and simultaneous direct determination of the magnetic field. The digital feedback algorithm uses only the previous measurement cycle to correct the magnetization voltage without any additional correlation parameter; it usually converges after several tens of cycles. The magnetic field is measured at the sample surface using a vertically mounted array of sensitive Hall sensors. Linear extrapolation of the tangential field profile to the sample surface determines the true waveform of the magnetic field. This unique combination of physically based control for both parameters of the magnetization process provides stable and reliable results, which are independent of a specified experimental configuration. This is illustrated for the industrially attractive measurements of non-oriented electrical steels with a 50 Hz sinusoidal induction waveform.

  17. Genetic and Behavioral Determinants of Hippocampal Volume Recovery During Abstinence from Alcohol

    PubMed Central

    Hoefer, Michael E.; Pennington, David L.; Durazzo, Timothy C.; Mon, Anderson; Abé, Christoph; Truran, Diana; Hutchison, Kent E.; Meyerhoff, Dieter J.

    2014-01-01

    Alcohol-dependent individuals (ALC) have smaller hippocampi and poorer neurocognition than healthy controls. Results from studies on the association between alcohol consumption and hippocampal volume have been mixed, suggesting that comorbid or premorbid factors (i.e., those present prior to the initiation of alcohol dependence) determine hippocampal volume in ALC. We aimed to characterize the effects of select comorbid (i.e., cigarette smoking) and premorbid factors (brain-derived neurotrophic factor [BDNF] genotype [Val66Met rs6265]) on hippocampal volume in an ALC cohort followed longitudinally into extended abstinence. One hundred twenty-one adult ALC in treatment (76 smokers, 45 non-smokers) and 35 non-smoking light-drinking controls underwent quantitative magnetic resonance imaging, BDNF genotyping, and neurocognitive assessments. Representative subgroups were studied at 1 week, 1 month, and at an average of 7 months of abstinence. ALC had smaller hippocampi than healthy controls at all time points. Hippocampal volume at 1 month of abstinence correlated with lower visuospatial function. Smoking status did not influence hippocampal volume or hippocampal volume recovery during abstinence. However, only BDNF Val homozygotes tended to have hippocampal volume increases over 7 months of abstinence, and Val homozygotes had significantly larger hippocampi than Met carriers at 7 months of abstinence. These findings suggest that BDNF genotype, but not smoking status or measures of drinking severity, regulate functionally relevant hippocampal volume recovery in abstinent ALC. Future studies aimed at exploring genetic determinants of brain morphometry in ALC may need to evaluate individuals during extended abstinence after the acute environmental effects of chronic alcohol consumption have waned. PMID:25262572

  18. Genetic and Environmental Determinants of Otitis Media in an Indigenous Filipino Population

    PubMed Central

    Santos-Cortez, Regie Lyn P.; Reyes-Quintos, Ma. Rina T.; Tantoco, Ma. Leah C.; Abbe, Izoduwa; Llanes, Erasmo Gonzalo d.V.; Ajami, Nadim J.; Hutchinson, Diane S.; Petrosino, Joseph F.; Padilla, Carmencita D.; Villarta, Romeo L.; Gloria-Cruz, Teresa Luisa; Chan, Abner L.; Cutiongco-de la Paz, Eva Maria; Chiong, Charlotte M.; Leal, Suzanne M.; Abes, Generoso T.

    2016-01-01

    Objective To identify genetic and environmental risk factors for otitis media in an indigenous Filipino population Study Design Cross-sectional study Setting Indigenous Filipino community Subjects and Methods Clinical history and information on breastfeeding, tobacco smoke exposure and swimming were obtained from community members. Heads of households were interviewed for family history and personal beliefs on ear health. Height and weight were measured. Otoscopic findings were described for presence and character of perforation or discharge. An A2ML1 duplication variant that confers otitis media susceptibility was Sanger-sequenced in all DNA samples. Co-occurrence of middle ear bacteria detected by 16S rRNA gene sequencing was determined according to A2ML1 genotype and social cluster. Results The indigenous Filipino population has a ~50% prevalence of otitis media. Young age was associated with otitis media (4 age strata; p=0.004), however age was non-significant as a bi-stratal or continuous variable. There was no association between otitis media and gender, body mass index, breastfeeding, tobacco exposure or deep swimming. In multivariate analyses, A2ML1 genotype is the strongest predictor of otitis media, with an odds ratio of 3.7 (95%CI: 1.3, 10.8; p=0.005). When otitis media diagnoses were plotted across ages, otitis media was observed within the first year of life and chronic otitis media persisted up to adulthood, particularly in A2ML1 variant carriers. Conclusion Among indigenous Filipinos, A2ML1 genotype is the primary risk factor for otitis media and main determinant of disease progression, although age, the middle ear microbiome and social clusters might modulate the effect of the A2ML1 genotype. PMID:27484237

  19. Genetic and Environmental Determinants of Otitis Media in an Indigenous Filipino Population.

    PubMed

    Santos-Cortez, Regie Lyn P; Reyes-Quintos, Ma Rina T; Tantoco, Ma Leah C; Abbe, Izoduwa; Llanes, Erasmo Gonzalo D V; Ajami, Nadim J; Hutchinson, Diane S; Petrosino, Joseph F; Padilla, Carmencita D; Villarta, Romeo L; Gloria-Cruz, Teresa Luisa; Chan, Abner L; Cutiongco-de la Paz, Eva Maria; Chiong, Charlotte M; Leal, Suzanne M; Abes, Generoso T

    2016-11-01

    To identify genetic and environmental risk factors for otitis media in an indigenous Filipino population. Cross-sectional study. Indigenous Filipino community. Clinical history and information on breastfeeding, tobacco smoke exposure, and swimming were obtained from community members. Heads of households were interviewed for family history and personal beliefs on ear health. Height and weight were measured. Otoscopic findings were described for the presence and character of perforation or discharge. An A2ML1 duplication variant that confers otitis media susceptibility was Sanger sequenced in all DNA samples. Co-occurrence of middle ear bacteria detected by 16S rRNA gene sequencing was determined according to A2ML1 genotype and social cluster. The indigenous Filipino population has a ~50% prevalence of otitis media. Young age was associated with otitis media (4 age strata; P = .004); however, age was nonsignificant as a bistratal or continuous variable. There was no association between otitis media and sex, body mass index, breastfeeding, tobacco exposure, or deep swimming. In multivariate analyses, A2ML1 genotype is the strongest predictor of otitis media, with an odds ratio of 3.7 (95% confidence interval: 1.3-10.8; P = .005). When otitis media diagnoses were plotted across ages, otitis media was observed within the first year of life, and chronic otitis media persisted up to adulthood, particularly in A2ML1-variant carriers. Among indigenous Filipinos, A2ML1 genotype is the primary risk factor for otitis media and main determinant of disease progression, although age, the middle ear microbiome, and social clusters might modulate the effect of the A2ML1 genotype. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  20. Determination of activity of 51Cr on gamma radiation measurements

    NASA Astrophysics Data System (ADS)

    Gorbachev, V. V.; Gavrin, V. N.; Ibragimova, T. V.; Kalikhov, A. V.; Malyshkin, Yu. M.; Shikhin, A. A.

    2017-01-01

    A method of determining the activity of intensive distributed -sources on the measurement of the continuous spectrum of radiation, for example the internal bremsstrahlung, is developed. The recurrent formula for reconstructing of a continuous spectrum, registered in a Ge detector, at distorting it in the detector. The method of precise measurements of the spectrum of 51Cr internal bremsstrahlung using two point sources of low activity is described.

  1. Determining Aerodynamic Loads Based on Optical Deformation Measurements

    NASA Technical Reports Server (NTRS)

    Liu, Tianshu; Barrows, D. A.; Burner, A. W.; Rhew, R. D.

    2001-01-01

    This paper describes a videogrammetric technique for determining aerodynamic loads based on optical elastic deformation measurements. The data reduction methods are developed to extract the normal force and pitching moment from beam deformation data. The axial force is obtained by measuring the axial translational motion of a movable shaft in a spring/bearing device. Proof-of-concept calibration experiments are conducted to assess the accuracy of this optical technique.

  2. Determining Aerodynamic Loads Based on Optical Deformation Measurements

    NASA Technical Reports Server (NTRS)

    Liu, Tianshu; Barrows, D. A.; Burner, A. W.; Rhew, R. D.

    2001-01-01

    This paper describes a videogram metric technique for determining aerodynamic loads based on optical elastic deformation measurements. The data reduction methods are developed to extract the normal force and pitching moment from beam deformation data. The axial force is obtained by measuring the axial translational motion of a movable shaft in a spring/bearing device. Proof-of-concept calibration experiments are conducted to assess the accuracy of this optical technique.

  3. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study.

    PubMed

    Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W

    2016-01-09

    Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with

  4. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

    PubMed Central

    Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W

    2016-01-01

    Summary Background Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for

  5. Conservative Sample Size Determination for Repeated Measures Analysis of Covariance.

    PubMed

    Morgan, Timothy M; Case, L Douglas

    2013-07-05

    In the design of a randomized clinical trial with one pre and multiple post randomized assessments of the outcome variable, one needs to account for the repeated measures in determining the appropriate sample size. Unfortunately, one seldom has a good estimate of the variance of the outcome measure, let alone the correlations among the measurements over time. We show how sample sizes can be calculated by making conservative assumptions regarding the correlations for a variety of covariance structures. The most conservative choice for the correlation depends on the covariance structure and the number of repeated measures. In the absence of good estimates of the correlations, the sample size is often based on a two-sample t-test, making the 'ultra' conservative and unrealistic assumption that there are zero correlations between the baseline and follow-up measures while at the same time assuming there are perfect correlations between the follow-up measures. Compared to the case of taking a single measurement, substantial savings in sample size can be realized by accounting for the repeated measures, even with very conservative assumptions regarding the parameters of the assumed correlation matrix. Assuming compound symmetry, the sample size from the two-sample t-test calculation can be reduced at least 44%, 56%, and 61% for repeated measures analysis of covariance by taking 2, 3, and 4 follow-up measures, respectively. The results offer a rational basis for determining a fairly conservative, yet efficient, sample size for clinical trials with repeated measures and a baseline value.

  6. Genetically Determined Variation in Lysis Time Variance in the Bacteriophage φX174.

    PubMed

    Baker, Christopher W; Miller, Craig R; Thaweethai, Tanayott; Yuan, Jeffrey; Baker, Meghan Hollibaugh; Joyce, Paul; Weinreich, Daniel M

    2016-04-07

    Researchers in evolutionary genetics recently have recognized an exciting opportunity in decomposing beneficial mutations into their proximal, mechanistic determinants. The application of methods and concepts from molecular biology and life history theory to studies of lytic bacteriophages (phages) has allowed them to understand how natural selection sees mutations influencing life history. This work motivated the research presented here, in which we explored whether, under consistent experimental conditions, small differences in the genome of bacteriophage φX174 could lead to altered life history phenotypes among a panel of eight genetically distinct clones. We assessed the clones' phenotypes by applying a novel statistical framework to the results of a serially sampled parallel infection assay, in which we simultaneously inoculated each of a large number of replicate host volumes with ∼1 phage particle. We sequentially plated the volumes over the course of infection and counted the plaques that formed after incubation. These counts served as a proxy for the number of phage particles in a single volume as a function of time. From repeated assays, we inferred significant, genetically determined heterogeneity in lysis time and burst size, including lysis time variance. These findings are interesting in light of the genetic and phenotypic constraints on the single-protein lysis mechanism of φX174. We speculate briefly on the mechanisms underlying our results, and we discuss the potential importance of lysis time variance in viral evolution.

  7. Genetically Determined Variation in Lysis Time Variance in the Bacteriophage φX174

    PubMed Central

    Baker, Christopher W.; Miller, Craig R.; Thaweethai, Tanayott; Yuan, Jeffrey; Baker, Meghan Hollibaugh; Joyce, Paul; Weinreich, Daniel M.

    2016-01-01

    Researchers in evolutionary genetics recently have recognized an exciting opportunity in decomposing beneficial mutations into their proximal, mechanistic determinants. The application of methods and concepts from molecular biology and life history theory to studies of lytic bacteriophages (phages) has allowed them to understand how natural selection sees mutations influencing life history. This work motivated the research presented here, in which we explored whether, under consistent experimental conditions, small differences in the genome of bacteriophage φX174 could lead to altered life history phenotypes among a panel of eight genetically distinct clones. We assessed the clones’ phenotypes by applying a novel statistical framework to the results of a serially sampled parallel infection assay, in which we simultaneously inoculated each of a large number of replicate host volumes with ∼1 phage particle. We sequentially plated the volumes over the course of infection and counted the plaques that formed after incubation. These counts served as a proxy for the number of phage particles in a single volume as a function of time. From repeated assays, we inferred significant, genetically determined heterogeneity in lysis time and burst size, including lysis time variance. These findings are interesting in light of the genetic and phenotypic constraints on the single-protein lysis mechanism of φX174. We speculate briefly on the mechanisms underlying our results, and we discuss the potential importance of lysis time variance in viral evolution. PMID:26921293

  8. Genetic and epigenetic determinants mediate proneness of oncogene breakpoint sites for involvement in TCR translocations.

    PubMed

    Larmonie, N S D; van der Spek, A; Bogers, A J J C; van Dongen, J J M; Langerak, A W

    2014-03-01

    T-cell receptor (TCR) translocations are a genetic hallmark of T-cell acute lymphoblastic leukemia and lead to juxtaposition of oncogene and TCR loci. Oncogene loci become involved in translocations because they are accessible to the V(D)J recombination machinery. Such accessibility is predicted at cryptic recombination signal sequence (cRSS) sites ('Type 1') as well as other sites that are subject to DNA double-strand breaks (DSBs) ('Type 2') during early stages of thymocyte development. As chromatin accessibility markers have not been analyzed in the context of TCR-associated translocations, various genetic and epigenetic determinants of LMO2, TAL1 and TLX1 translocation breakpoint (BP) sites and BP cluster regions (BCRs) were examined in human thymocytes to establish DSB proneness and heterogeneity of BP site involvement in TCR translocations. Our data show that DSBs in BCRs are primarily induced in the presence of a genetic element of sequence vulnerability (cRSSs, transposable elements), whereas breaks at single BP sites lacking such elements are more likely induced by chance or perhaps because of patient-specific genetic vulnerability. Vulnerability to obtain DSBs is increased by features that determine chromatin organization, such as methylation status and nucleosome occupancy, although at different levels at different BP sites.

  9. Beneficence, determinism and justice: an engagement with the argument for the genetic selection of intelligence.

    PubMed

    Birch, Kean

    2005-02-01

    In 2001, Julian Savulescu wrote an article entitled 'Procreative Beneficence: Why We Should Select the Best Children', in which he argued for the genetic selection of intelligence in children. That article contributes to a debate on whether genetic research on intelligence should be undertaken at all and, if so, should intelligence selection be available to potential parents. As such, the question of intelligence selection relates to wider issues concerning the genetic determinism of behavioural traits, i.e. alcoholism. This article is designed as an engagement in the intelligence selection debate using an analysis of Savulescu's arguments to raise a series of problematic issues in relation to the ethics of parental selection of intelligence. These problematic issues relate to wider assumptions that are made in order to put forward intelligence selection as a viable ethical option. Such assumptions are more generic in character, but still relate to Savulescu's article, concerning issues of genetic determinism, private allocation and inequality, and, finally, individual versus aggregate justice. The conclusion focuses on what the implications are for the question of agency, especially if intelligence selection is allowed.

  10. Strain Gage Measurement System to Determine Cryogenic Propellant Tank Level

    NASA Technical Reports Server (NTRS)

    Figueroa, Fernando; St.Cyr, William W.; VanDyke, David; McVay, Greg; Mitchell, Mark; Langford, Lester

    2003-01-01

    Measurement of tank level, particularly for cryogenic propellants, has proven to be a difficult proposition. Current methods based on differential pressure, capacitance sensors, temperature sensors, etc.; do not provide sufficiently accurate or robust measurements, especially at run time. This paper describes a simple, but effective method to determine propellant volume by measuring very small deformations of the structure supporting the tank. Results of a laboratory study to validate the method, and experimental data from a deployed system are presented. A comparison with an existing differential pressure sensor shows that the strain gage system provides a very good quality signal even during pressurization.

  11. Determining H 0 with the Latest H ii Galaxy Measurements

    NASA Astrophysics Data System (ADS)

    Wang, Deng; Meng, Xin-He

    2017-07-01

    We use the latest H ii galaxy measurements to determine the value of H 0 by adopting a combination of model-dependent and model-independent methods. By constraining five cosmological models, we find that the obtained values of H 0 are more consistent with the recent local measurement by Riess et al. at the 1σ confidence level. For the first time, we implement the model-independent Gaussian processes using the H ii galaxy measurements, and confirm the correctness of H 0 values obtained by the model-dependent method at the 1σ confidence level.

  12. Determination of vertical interproximal bone loss topography: correlation between indirect digital radiographic measurement and clinical measurement.

    PubMed

    Esmaeli, Farzad; Shirmohammadi, Adileh; Faramarzie, Masoumeh; Abolfazli, Nader; Rasouli, Hossein; Fallahi, Saied

    2012-06-01

    Diagnosis and accuracy in determining the exact location, extent and configuration of bony defects of the jaw are of utmost importance to determine prognosis, treatment planning and long-term preservation of teeth. If relatively accurate diagnosis can be established by radiography, proper treatment planning prior to treatment procedures will be possible. The aim of the present study was to assess the correlation between indirect digital radiographic measurements and clinical measurements in determining the topography of interproximal bony defects. Twenty interproximal bony defects, preferably in the mandibular and maxillary 5↔5 area were selected and radiographed using the parallel periapical technique. The radiographs were corrected and digitized on a computer using "Linear Measurement" software; then the three parameters of the base of defect (BD), alveolar crest (AC) and cementoenamel junction (CEJ) were determined using a software. Subsequent to radiographic measurements, clinical measurements were carried out meticulously during flap procedures. Then linear measurements were carried out using a periodontal probe to determine the defect depth and its mesiodistal width. Then the amount of correlation between these two measurements was assessed by Pearson's correlation coefficient. The correlation between clinical and radiographic measurements in defect depth determination, in the evaluation of defect angle and in determination of defect width were 88%, 98% and 90%, respectively. Indirect digital radiographic technique can be used to diagnose intra-osseous defects, providing a better opportunity to treat bony defects.

  13. Clinical applications of fetal sex determination in maternal blood in a preimplantation genetic diagnosis centre.

    PubMed

    Tachdjian, Gérard; Frydman, Nelly; Audibert, Franciois; Ray, Pierre; Kerbrat, Violaine; Ernault, Pauline; Frydman, René; Costa, Jean-Marc

    2002-08-01

    Couples with a risk of transmitting X-linked diseases who are included in a preimplantation genetic diagnosis (PGD) programme need early and rapid fetal sex determination in two situations. The first situation is for the control of embryo sexing after PGD and the second situation is for those couples having a spontaneous pregnancy before the start of their PGD cycle. Among invasive techniques, chorionic villus sampling is the earliest procedure for fetal sex determination and molecular analysis of X-linked genetic disorders during the first trimester but it is associated with a risk of fetal loss. Non-invasive procedures such as ultrasound examination allow reliable fetal sex determination only during the second trimester. Reliable fetal sex determination can now be realised by using SRY gene amplification in maternal blood. We report the use of fetal sex determination from maternal serum as a diagnostic tool for the control of embryo sexing (two cases) and to manage spontaneous pregnancies in couples included in a PGD programme for X-linked diseases (five cases). Fetal sex determination using SRY gene amplification in maternal serum were in complete concordance with fetal sex observed by cytogenetic analysis or ultrasound examination and at birth. This novel strategy allowed the PGD results to be controlled precociously and avoided the performance of invasive procedures in four cases of female fetus. This rapid fetal sex determination during the first trimester provides advantages to both clinicians and patients in a PGD centre.

  14. Environmental versus genetic sex determination: a possible factor in dinosaur extinction?

    PubMed

    Miller, David; Summers, Jonathan; Silber, Sherman

    2004-04-01

    This study examined the possibility that genetically based sex-determination mechanisms have evolved to ensure a balanced male/female ratio and that this temperature-independent checkpoint might have been unavailable to long-extinct reptiles, notably the dinosaurs. A review of the literature on molecular and phylogenetic relationships between modes of reproduction and sex determination in extant animals was conducted. Mammals, birds, all snakes and most lizards, amphibians, and some gonochoristic fish use specific sex-determining chromosomes or genes (genetic sex determination, GSD). Some reptiles, however, including all crocodilians studied to date, many turtle and tortoise species, and some lizards, use environmental or temperature-dependent sex determination (TSD). We show that various modes of GSD have evolved many times, independently in different orders. Animals using TSD would be at risk of rapid reproductive failure due to a skewed sex ratio favoring males in response to sustained environmental temperature change and favoring the selection of sex-determining genes. The disadvantage to the evolving male sex-determining chromosome, however, is its decay due to nonrecombination and the subsequent loss of spermatogenesis genes. Global temperature change can skew the sex ratio of TSD animals and might have played a significant role in the demise of long-extinct species, notably the dinosaurs, particularly if the temperature change resulted in a preponderance of males. Current global warming also represents a risk for extant TSD species.

  15. Genetic determinants and epistasis for life history trait differences in the common monkeyflower, Mimulus guttatus.

    PubMed

    Friedman, Jannice

    2014-01-01

    Understanding the genetic basis of complex quantitative traits is a central problem in evolutionary biology, particularly for traits that may lead to adaptations in natural populations. The annual and perennial ecotypes of Mimulus guttatus provide an excellent experimental system for characterizing the genetic components of population divergence. The 2 life history ecotypes coexist throughout the geographic range. Focusing on population differences in life history traits, I examined the strength and direction of pairwise epistatic interactions between 2 target chromosomal regions (DIV1 and DIV2) when singly and cointrogressed into the alternate population's genetic background. I measured a suite of flowering and vegetative traits related to life history divergence in 804 plants from 18 reciprocal near-isogenic lines. I detected pleiotropic main effects for the DIV1 QTL in both genetic backgrounds and weaker main effects of the DIV2 QTL, primarily in the perennial background. Many of the traits showed epistatic interactions between alleles at the DIV1 and DIV2 QTL. Finally, for many traits, the magnitude of effect size was greater in the perennial background. I evaluate these results in the context of their potential role in population divergence in M. guttatus and adaptive evolution in natural populations. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Determination of continuous variable entanglement by purity measurements.

    PubMed

    Adesso, Gerardo; Serafini, Alessio; Illuminati, Fabrizio

    2004-02-27

    We classify the entanglement of two-mode Gaussian states according to their degree of total and partial mixedness. We derive exact bounds that determine maximally and minimally entangled states for fixed global and marginal purities. This characterization allows for an experimentally reliable estimate of continuous variable entanglement based on measurements of purity.

  17. Altimeter measurements for the determination of the Earth's gravity field

    NASA Technical Reports Server (NTRS)

    Tapley, B. D.; Schutz, B. E.; Shum, C. K.

    1986-01-01

    Progress in the following areas is described: refining altimeter and altimeter crossover measurement models for precise orbit determination and for the solution of the earth's gravity field; performing experiments using altimeter data for the improvement of precise satellite ephemerides; and analyzing an optimal relative data weighting algorithm to combine various data types in the solution of the gravity field.

  18. Estimation of genetic parameters for body weights, scrotal circumference, and testicular volume measured at different ages in Nellore cattle.

    PubMed

    Boligon, A A; Silva, J A V; Sesana, R C; Sesana, J C; Junqueira, J B; Albuquerque, L G

    2010-04-01

    Data from 129,575 Nellore cattle born between 1993 and 2006, belonging to the Jacarezinho cattle-raising farm, were used to estimate genetic parameters for scrotal circumference measured at 9 (SC9), 12 (SC12), and 18 (SC18) mo of age and testicular volume measured at the same ages (TV9, TV12, and TV18) and to determine their correlation with weaning weight (WW) and yearling weight (YW), to provide information for the definition of selection criteria in beef cattle. Estimates of (co)variance components were calculated by the REML method applying an animal model in single- and multiple-trait analysis. The following heritability estimates and their respective SE were obtained for WW, YW, SC9, SC12, SC18, TV9, TV12, and TV18: 0.33 +/- 0.02, 0.37 +/- 0.03, 0.29 +/- 0.03, 0.39 +/- 0.04, 0.42 +/- 0.03, 0.19 +/- 0.04, 0.26 +/- 0.05, and 0.39 +/- 0.04, respectively. The genetic correlation between WW and YW was positive and high (0.80 +/- 0.04), indicating that these traits are mainly determined by the same genes. Genetic correlations between the growth traits and scrotal circumference measures were positive and of low to moderate magnitude, ranging from 0.23 +/- 0.04 to 0.38 +/- 0.04. On the other hand, increased genetic associations were estimated between scrotal circumference and testicular volume at different ages (0.61 +/- 0.04 to 0.86 +/- 0.04). Selection for greater scrotal circumference in males should result in greater WW, YW, and testicular volume. In conclusion, in view of the difficulty in measuring testicular volume, there is no need to change the selection criterion from scrotal circumference to testicular volume in genetic breeding programs of Zebu breeds.

  19. [Determination of Virtual Surgery Mass Point Spring Model Parameters Based on Genetic Algorithms].

    PubMed

    Chen, Ying; Hu, Xuyi; Zhu, Qiguang

    2015-12-01

    Mass point-spring model is one of the commonly used models in virtual surgery. However, its model parameters have no clear physical meaning, and it is hard to set the parameter conveniently. We, therefore, proposed a method based on genetic algorithm to determine the mass-spring model parameters. Computer-aided tomography (CAT) data were used to determine the mass value of the particle, and stiffness and damping coefficient were obtained by genetic algorithm. We used the difference between the reference deformation and virtual deformation as the fitness function to get the approximate optimal solution of the model parameters. Experimental results showed that this method could obtain an approximate optimal solution of spring parameters with lower cost, and could accurately reproduce the effect of the actual deformation model as well.

  20. A genetic approach for the identification of exosporium assembly determinants of Bacillus anthracis

    PubMed Central

    Spreng, Krista A.; Thompson, Brian M.; Stewart, George C.

    2013-01-01

    The exosporium is the outermost layer of spores of the zoonotic pathogen Bacillus anthracis. The composition of the exosporium and its functions are only partly understood. Because this outer spore layer is refractive to traditional biochemical analysis, a genetic approach is needed in order to define the proteins which comprise this important spore layer and its assembly pathway. We have created a novel genetic screening system for the identification and isolation of mutants with defects in exosporium assembly during B. anthracis spore maturation. The system is based on the targeting sequence of the BclA exosporium nap layer glycoprotein and a fluorescent reporter. By utilizing this screening system and gene inactivation with Tn916, several novel putative exosporium-associated determinants were identified. A sampling of the mutants obtained was further characterized, confirming their exosporium defect and validating the utility of this screen to identify novel spore determinants in the genome of this pathogen. PMID:23411372

  1. Robust Flight Path Determination for Mars Precision Landing Using Genetic Algorithms

    NASA Technical Reports Server (NTRS)

    Bayard, David S.; Kohen, Hamid

    1997-01-01

    This paper documents the application of genetic algorithms (GAs) to the problem of robust flight path determination for Mars precision landing. The robust flight path problem is defined here as the determination of the flight path which delivers a low-lift open-loop controlled vehicle to its desired final landing location while minimizing the effect of perturbations due to uncertainty in the atmospheric model and entry conditions. The genetic algorithm was capable of finding solutions which reduced the landing error from 111 km RMS radial (open-loop optimal) to 43 km RMS radial (optimized with respect to perturbations) using 200 hours of computation on an Ultra-SPARC workstation. Further reduction in the landing error is possible by going to closed-loop control which can utilize the GA optimized paths as nominal trajectories for linearization.

  2. The quest for genetic determinants of human longevity: challenges and insights

    PubMed Central

    Christensen, Kaare; Johnson, Thomas E.; Vaupel, James W.

    2009-01-01

    Twin studies show that genetic differences account for about a quarter of the variance in adult human lifespan. Common polymorphisms that have a modest effect on lifespan have been identified in one gene, APOE, providing hope that other genetic determinants can be uncovered. However, although variants with substantial beneficial effects have been proposed to exist and several candidates have been put forward, their effects have yet to be confirmed. Human studies of longevity face numerous theoretical and logistical challenges, as the determinants of lifespan are extraordinarily complex. However, large-scale linkage studies of long-lived families, longitudinal candidate-gene association studies and the development of analytical methods provide the potential for future progress. PMID:16708071

  3. Determination of Vertical Interproximal Bone Loss Topography: Correlation Between Indirect Digital Radiographic Measurement and Clinical Measurement

    PubMed Central

    Esmaeli, Farzad; Shirmohammadi, Adileh; Faramarzie, Masoumeh; Abolfazli, Nader; Rasouli, Hossein; Fallahi, Saied

    2012-01-01

    Background Diagnosis and accuracy in determining the exact location, extent and configuration of bony defects of the jaw are of utmost importance to determine prognosis, treatment planning and long-term preservation of teeth. If relatively accurate diagnosis can be established by radiography, proper treatment planning prior to treatment procedures will be possible. Objectives The aim of the present study was to assess the correlation between indirect digital radiographic measurements and clinical measurements in determining the topography of interproximal bony defects. Patients and Methods Twenty interproximal bony defects, preferably in the mandibular and maxillary 5↔5 area were selected and radiographed using the parallel periapical technique. The radiographs were corrected and digitized on a computer using “Linear Measurement” software; then the three parameters of the base of defect (BD), alveolar crest (AC) and cementoenamel junction (CEJ) were determined using a software. Subsequent to radiographic measurements, clinical measurements were carried out meticulously during flap procedures. Then linear measurements were carried out using a periodontal probe to determine the defect depth and its mesiodistal width. Then the amount of correlation between these two measurements was assessed by Pearson's correlation coefficient. Results The correlation between clinical and radiographic measurements in defect depth determination, in the evaluation of defect angle and in determination of defect width were 88%, 98% and 90%, respectively. Conclusions Indirect digital radiographic technique can be used to diagnose intra-osseous defects, providing a better opportunity to treat bony defects. PMID:23329969

  4. The measurement of patient attitudes regarding prenatal and preconception genetic carrier screening and translational behavioral medicine: an integrative review.

    PubMed

    Shiroff, Jennifer J; Gregoski, Mathew J

    2016-08-29

    Measurement of recessive carrier screening attitudes related to conception and pregnancy is necessary to determine current acceptance, and whether behavioral intervention strategies are needed in clinical practice. To evaluate quantitative survey instruments to measure patient attitudes regarding genetic carrier testing prior to conception and pregnancy databases examining patient attitudes regarding genetic screening prior to conception and pregnancy from 2003-2013 were searched yielding 344 articles; eight studies with eight instruments met criteria for inclusion. Data abstraction on theoretical framework, subjects, instrument description, scoring, method of measurement, reliability, validity, feasibility, level of evidence, and outcomes was completed. Reliability information was provided in five studies with an internal consistency of Cronbach's α >0.70. Information pertaining to validity was presented in three studies and included construct validity via factor analysis. Despite limited psychometric information, these questionnaires are self-administered and can be briefly completed, making them a feasible method of evaluation.

  5. The Stability of Genetic Determination from Age 2 to Age 9: A Longitudinal Twin Study.

    ERIC Educational Resources Information Center

    Lytton, Hugh; And Others

    A longitudinal investigation of the social and cognitive development of male twins was conducted when twins were 2.5 years of age, and again when they were 8- to 10-years-old. This study was designed to re-examine the heritability of the traits studied at the earlier age and, thus, to address the question of the stability of genetic determination.…

  6. Reconstructing optical parameters from double-integrating-sphere measurements using a genetic algorithm

    NASA Astrophysics Data System (ADS)

    Böcklin, Christoph; Baumann, Dirk; Stuker, Florian; Klohs, Jan; Rudin, Markus; Fröhlich, Jürg

    2013-02-01

    For the reconstruction of physiological changes in specific tissue layers detected by optical techniques, the exact knowledge of the optical parameters μa, μs and g of different tissue types is of paramount importance. One approach to accurately determine these parameters for biological tissue or phantom material is to use a double-integrating-sphere measurement system. It offers a flexible way to measure various kinds of tissues, liquids and artificial phantom materials. Accurate measurements can be achieved by technical adjustments and calibration of the spheres using commercially available reflection and transmission standards. The determination For the reconstruction of physiological changes in specific tissue layers detected by optical techniques, the exact knowledge of the optical parameters μa, μs and g of different tissue types is of paramount importance. One approach to accurately determine these parameters for biological tissue or phantom material is to use a double-integrating-sphere measurement system. It offers a flexible way to measure various kinds of tissues, liquids and artificial phantom materials. Accurate measurements can be achieved by technical adjustments and calibration of the spheres using commercially available reflection and transmission standards. The determination of the optical parameters of a material is based on two separate steps. Firstly, the reflectance ρs, the total transmittance TsT and the unscattered transmittance TsC of the sample s are measured with the double-integrating-sphere setup. Secondly, the optical parameters μa, μs and g are reconstructed with an inverse search algorithm combined with an appropriate solver for the forward problem (calculating ρs, TsT and TsC from μa, μs and g) has to be applied. In this study a Genetic Algorithm is applied as search heuristic, since it offers the most flexible and general approach without requiring any foreknowledge of the fitness-landscape. Given the challenging

  7. The Sensitivity of Genetic Connectivity Measures to Unsampled and Under-Sampled Sites

    PubMed Central

    Koen, Erin L.; Bowman, Jeff; Garroway, Colin J.; Wilson, Paul J.

    2013-01-01

    Landscape genetic analyses assess the influence of landscape structure on genetic differentiation. It is rarely possible to collect genetic samples from all individuals on the landscape and thus it is important to assess the sensitivity of landscape genetic analyses to the effects of unsampled and under-sampled sites. Network-based measures of genetic distance, such as conditional genetic distance (cGD), might be particularly sensitive to sampling intensity because pairwise estimates are relative to the entire network. We addressed this question by subsampling microsatellite data from two empirical datasets. We found that pairwise estimates of cGD were sensitive to both unsampled and under-sampled sites, and FST, Dest, and deucl were more sensitive to under-sampled than unsampled sites. We found that the rank order of cGD was also sensitive to unsampled and under-sampled sites, but not enough to affect the outcome of Mantel tests for isolation by distance. We simulated isolation by resistance and found that although cGD estimates were sensitive to unsampled sites, by increasing the number of sites sampled the accuracy of conclusions drawn from landscape genetic analyses increased, a feature that is not possible with pairwise estimates of genetic differentiation such as FST, Dest, and deucl. We suggest that users of cGD assess the sensitivity of this measure by subsampling within their own network and use caution when making extrapolations beyond their sampled network. PMID:23409155

  8. Genetic and Environmental Determinants of Plasma Total Homocysteine Levels: Impact of Population-wide Folate Fortification

    PubMed Central

    Nagele, Peter; Meissner, Konrad; Francis, Amber; Födinger, Manuela; Saccone, Nancy L.

    2011-01-01

    Objectives Folate metabolism is an important target for drug therapy. Drug-induced inhibition of folate metabolism often causes an elevation of plasma total homocysteine (tHcy). Plasma tHcy levels are influenced by several non-genetic (e.g., folate intake, age, smoking) as well as genetic factors. Over the last decade, several countries have implemented a nation-wide folate fortification program of all grain products. This investigation sought to determine the impact of folate fortification on the relative contribution of environmental and genetic factors to the variability of plasma tHcy. Methods Two cohorts were compared in this study, one from the U.S. (with folate fortification, n=281), and one from Austria (without folate fortification, n=139). Several environmental factors as well as previously identified gene variants important for tHcy levels (MTHFR C677T, MTHFR A1298C, MTRR A66G) were examined for their ability to predict plasma tHcy in a multiple linear regression model. Results Non-genetic, environmental factors had a comparable influence on plasma tHcy between the two cohorts (R2 ~ 0.19). However, after adjusting for other covariates, the tested gene variants had a substantially smaller impact among patients from the folate fortified cohort (R2= 0.021) compared to the non-folate fortified cohort (R2= 0.095). The MTHFR C677T polymorphism was the single most important genetic factor. Male gender, smoking and folate levels were important predictors for non-folate fortified patients; age for folate fortified. Conclusions Population-wide folate fortification had a significant effect on the variability of plasma tHcy and reduced the influence of genetic factors, most importantly the MTHFR 677TT genotype, and may be an important confounder for a personalized drug therapy. PMID:21597397

  9. Foraging environment determines the genetic architecture and evolutionary potential of trophic morphology in cichlid fishes.

    PubMed

    Parsons, Kevin J; Concannon, Moira; Navon, Dina; Wang, Jason; Ea, Ilene; Groveas, Kiran; Campbell, Calum; Albertson, R Craig

    2016-12-01

    Phenotypic plasticity allows organisms to change their phenotype in response to shifts in the environment. While a central topic in current discussions of evolutionary potential, a comprehensive understanding of the genetic underpinnings of plasticity is lacking in systems undergoing adaptive diversification. Here, we investigate the genetic basis of phenotypic plasticity in a textbook adaptive radiation, Lake Malawi cichlid fishes. Specifically, we crossed two divergent species to generate an F3 hybrid mapping population. At early juvenile stages, hybrid families were split and reared in alternate foraging environments that mimicked benthic/scraping or limnetic/sucking modes of feeding. These alternate treatments produced a variation in morphology that was broadly similar to the major axis of divergence among Malawi cichlids, providing support for the flexible stem theory of adaptive radiation. Next, we found that the genetic architecture of several morphological traits was highly sensitive to the environment. In particular, of 22 significant quantitative trait loci (QTL), only one was shared between the environments. In addition, we identified QTL acting across environments with alternate alleles being differentially sensitive to the environment. Thus, our data suggest that while plasticity is largely determined by loci specific to a given environment, it may also be influenced by loci operating across environments. Finally, our mapping data provide evidence for the evolution of plasticity via genetic assimilation at an important regulatory locus, ptch1. In all, our data address long-standing discussions about the genetic basis and evolution of plasticity. They also underscore the importance of the environment in affecting developmental outcomes, genetic architectures, morphological diversity and evolutionary potential.

  10. New Genetic Element Carrying the Erythromycin Resistance Determinant erm(TR) in Streptococcus pneumoniae▿

    PubMed Central

    Camilli, Romina; Del Grosso, Maria; Iannelli, Francesco; Pantosti, Annalisa

    2008-01-01

    erm(A) subclass erm(TR), a common macrolide resistance determinant in Streptococcus pyogenes but quite rare in Streptococcus pneumoniae, was found in a clinical S. pneumoniae isolate (AP200) from Italy. In this isolate, erm(TR) was found included in a genetic element approximately 56 kb in size that did not appear to be conjugative but could be transferred by transformation. An erm(TR)-containing DNA fragment of approximately 10 kb was sequenced and 12 open reading frames (ORFs) were identified. Upstream of erm(TR), a regulatory protein of the TetR family and the two components of an efflux pump of the ABC type were found. Downstream of erm(TR), there were ORFs homologous to a spectinomycin phosphotransferase, transposases, and a relaxase. Since the genomic sequence of S. pyogenes MGAS10750 carrying erm(TR) became available, comparison between the erm(TR)-containing genetic elements in AP200 and in MGAS10750 was performed. The region flanking erm(TR) in MGAS10750 showed identity with AP200 for 10 ORFs out of 12. PCR mapping using primers designed on the sequence of MGAS10750 confirmed that AP200 carries a genetic element similar to that of MGAS10750. In AP200 the genetic element was inserted inside an ORF homologous to spr0790 of S. pneumoniae R6, coding for a type I restriction modification system. Homologies between the insertion sites in AP200 and MGAS10750 consisted of eight conserved nucleotides, of which three were duplicated, likely representing target site duplication. The structure of the erm(TR)-carrying genetic element shows characteristics of a transposon/prophage remnant chimera. In AP200 this genetic element was designated Tn1806. PMID:18070957

  11. Genetic Covariation Underlying Reading, Language and Related Measures in a Sample Selected for Specific Language Impairment

    PubMed Central

    Logan, Jessica; Petrill, Stephen A.; Flax, Judy; Justice, Laura M.; Hou, Liping; Bassett, Anne S.; Tallal, Paula; Brzustowicz, Linda M.

    2011-01-01

    Specific language impairment is a developmental language disorder characterized by failure to develop language normally in the absence of a specific cause. Previous twin studies have documented the heritability of reading and language measures as well as the genetic correlation between those measures. This paper presents results from an alternative to the classical twin designs by estimating heritability from extended pedigrees. These pedigrees were previously studied as part of series of molecular genetic studies of specific language impairment where the strongest genetic findings were with reading phenotypes rather than language despite selecting pedigrees based on language impairments. To explore the relationship between reading and language in these pedigrees, variance components estimates of heritability of reading and language measures were conducted showing general agreement with the twin literature, as were genetics correlations between reading and language. Phonological short-term memory, phonological awareness and auditory processing were evaluated as candidate mediators of the reading-language genetic correlations. Only phonological awareness showed significant genetic correlations with all reading measures and several language measures while phonological short-term memory and auditory processing did not. PMID:21193955

  12. Genetic sex determination in Astatotilapia calliptera, a prototype species for the Lake Malawi cichlid radiation

    NASA Astrophysics Data System (ADS)

    Peterson, Erin N.; Cline, Maggie E.; Moore, Emily C.; Roberts, Natalie B.; Roberts, Reade B.

    2017-06-01

    East African cichlids display extensive variation in sex determination systems. The species Astatotilapia calliptera is one of the few cichlids that reside both in Lake Malawi and in surrounding waterways. A. calliptera is of interest in evolutionary studies as a putative immediate outgroup species for the Lake Malawi species flock and possibly as a prototype ancestor-like species for the radiation. Here, we use linkage mapping to test association of sex in A. calliptera with loci that have been previously associated with genetic sex determination in East African cichlid species. We identify a male heterogametic XY system segregating at linkage group (LG) 7 in an A. calliptera line that originated from Lake Malawi, at a locus previously shown to act as an XY sex determination system in multiple species of Lake Malawi cichlids. Significant association of genetic markers and sex produce a broad genetic interval of approximately 26 megabases (Mb) using the Nile tilapia genome to orient markers; however, we note that the marker with the strongest association with sex is near a gene that acts as a master sex determiner in other fish species. We demonstrate that alleles of the marker are perfectly associated with sex in Metriaclima mbenjii, a species from the rock-dwelling clade of Lake Malawi. While we do not rule out the possibility of other sex determination loci in A. calliptera, this study provides a foundation for fine mapping of the cichlid sex determination gene on LG7 and evolutionary context regarding the origin and persistence of the LG7 XY across diverse, rapidly evolving lineages.

  13. Determination of iodine to compliment mass spectrometric measurements

    SciTech Connect

    Hohorst, F.A.

    1994-11-01

    The dose of iodine-129 to facility personnel and the general public as a result of past, present, and future activities at DOE sites is of continuing interest, WINCO received about 160 samples annually in a variety of natural matrices, including snow, milk, thyroid tissue, and sagebrush, in which iodine-129 is determined in order to evaluate this dose, Currently, total iodine and the isotopic ratio of iodine-127 to iodine-129 are determined by mass spectrometry. These two measurements determine the concentration of iodine-129 in each sample, These measurements require at least 16 h of mass spectrometer operator time for each sample. A variety of methods are available which concentrate and determine small quantities of iodine. Although useful, these approaches would increase both time and cost. The objective of this effort was to determine total iodine by an alternative method in order to decrease the load on mass spectrometry by 25 to 50%. The preparation of each sample for mass spectrometric analysis involves a common step--collection of iodide on an ion exchange bed. This was the focal point of the effort since the results would be applicable to all samples.

  14. Social determinants of health: a view on theory and measurement.

    PubMed

    De Maio, Fernando; Mazzeo, John; Ritchie, Dannie

    2013-07-01

    The theory and measurement of the social determinants of health featured in a three-part seminar series on Social Determinants of Health, Law and Policy held at the Taubman Center for Public Policy, Brown University in February 2012. The seminar series represents a broader commitment to engage the public, health providers, researchers, and policy makers in dialogue for the purposes of identifying and addressing social determinants of health at community and state levels. This article summarizes and expands upon the first part of the series by defining social determinants of health and exploring methodological debates over their measurement, with a focus on income inequality, racism and discrimination, housing security, and food security. The authors of this article and the members of the seminar series represent the kind of interdisciplinary and applied work necessary for addressing the five key areas of social determinants of health identified in Healthy People 2020: economic stability, education, social and community context, health and health care, and neighborhood and environment.

  15. Ultrasonic attenuation measurements determine onset, degree, and completion of recrystallization

    NASA Technical Reports Server (NTRS)

    Generazio, E. R.

    1988-01-01

    Ultrasonic attenuation was measured for cold worked Nickel 200 samples annealed at increasing temperatures. Localized dislocation density variations, crystalline order and volume percent of recrystallized phase were determined over the anneal temperature range using transmission electron microscopy, X-ray diffraction, and metallurgy. The exponent of the frequency dependence of the attenuation was found to be a key variable relating ultrasonic attenuation to the thermal kinetics of the recrystallization process. Identification of this key variable allows for the ultrasonic determination of onset, degree, and completion of recrystallization.

  16. Determining Mineral Types and Abundances from Reflectance Measurements

    NASA Technical Reports Server (NTRS)

    Smith, M. O.; Adams, J. B.

    1985-01-01

    Mineral types and their abundances were quantitatively determined from laboratory reflectance spectra using principal components analysis (PCA). PCA reduced the measured spectral dimensionality and allowed testing the uniqueness and validity of spectral mixing models. In addition to interpreting absorption bands, in this new approach we interpreted variations in the overall spectral curves in terms of physical processes, namely changes in mixtures of minerals, in particle size and in illumination geometry. Application of this approach to reflectances of planetary surfaces allows interpretation to be extended to quantitative determinations of mineral types and abundances.

  17. Resolving cell composition through simple measurements, genome-scale modeling, and a genetic algorithm.

    PubMed

    Senger, Ryan S; Nazem-Bokaee, Hadi

    2013-01-01

    The biochemical composition of a cell is very complex and dynamic. It varies greatly among different organisms and environmental conditions. Inclusion of proper cell composition data is critical for accurate genome-scale metabolic flux modeling using flux balance analysis (FBA). However, determining cell composition experimentally is currently time-consuming and resource intensive. In this chapter, a method for predicting cell composition using a genome-scale model and "easy to measure" culture data (e.g., glucose uptake rate, and specific growth rate) is presented. The method makes use of a genetic algorithm for nonlinear optimization of a biomass equation (a mathematical description of cell composition). As a case study, the method was used to optimize a biomass equation for Escherichia coli MG1655 under multiple growth environments. The availability of experimentally determined (13)C flux data allowed a direct comparison with FBA predicted fluxes through the TCA cycle. Results showed dramatic improvement upon optimization of the biomass equation. In a second case study, biomass equation optimization was also applied to Clostridium acetobutylicum, an organism with less available biochemical cell composition data in the literature. The method produced a biomass equation highly similar to one determined experimentally for the closely related Gram-positive Bacillus subtilis.

  18. Determination of scattering in intraocular lenses by spectrophotometric measurements.

    PubMed

    Artigas, José M; Felipe, Adelina; Navea, Amparo; García-Domene, M Carmen; Pons, Álvaro; Mataix, Jorge

    2014-12-01

    This study presents a method for measuring scattering in explanted intraocular lenses (IOLs). Currently, determining scattering in IOLs is usually performed by Scheimpflug cameras and the results are expressed in the units used by this apparatus. The method we propose uses a spectrophotometer and this makes it possible to measure the total transmission of the IOL by using an integrating sphere; the direct transmission is determined by the double-beam mode. The difference between these two transmissions gives a value of the scattering in percentage values of light lost. In addition, by obtaining the spectral transmission curve, information about the most scattered wavelengths is also obtained. The IOL power introduces errors when directly measured, particularly with high powers. This problem can be overcome if a tailor-made cuvette is used that shortens the distance between the IOL and the condensing lens of the spectrophotometer when the IOL powers are below 24 diopters. We checked the effectiveness of this method by measuring the scattering of three explanted IOLs from cornea donors. This method, however, does not make it possible to ascertain whether the scattering measured is caused by surface light scattering or internal light scattering.

  19. Structure and Genetic Variability of the Oceanic Whitetip Shark, Carcharhinus longimanus, Determined Using Mitochondrial DNA.

    PubMed

    Camargo, Sâmia M; Coelho, Rui; Chapman, Demian; Howey-Jordan, Lucy; Brooks, Edward J; Fernando, Daniel; Mendes, Natalia J; Hazin, Fabio H V; Oliveira, Claudio; Santos, Miguel N; Foresti, Fausto; Mendonça, Fernando F

    2016-01-01

    Information regarding population structure and genetic connectivity is an important contribution when establishing conservation strategies to manage threatened species. The oceanic whitetip shark, Carcharhinus longimanus, is a highly migratory, large-bodied, pelagic shark listed by the IUCN (International Union for Conservation of Nature) Red List as "vulnerable" throughout its range and "critically endangered" in the western north Atlantic. In 2014, the species was protected globally under Appendix II of CITES (Convention on International Trade in Endangered Species), limiting and regulating trade. This study used partial sequences of mitochondrial DNA (mtDNA) control region to determine the population genetic structure of oceanic whitetip sharks across the Atlantic and Indian Oceans. 724 base pairs were obtained from 215 individuals that identifed nine polymorphic sites and defined 12 distinct haplotypes. Total nucleotide diversity (π) was 0.0013 and haplotype diversity (h) was 0.5953. The Analysis of Molecular Variance (AMOVA) evidenced moderate levels of population structure (ɸST = 0.1039) with restricted gene flow between the western and eastern Atlantic Ocean, and a strong relationship between the latter region and the Indian Ocean. Even though the oceanic whitetip is a highly migratory animal the results presented here show that their genetic variability is slightly below average of other pelagic sharks. Additionally, this study recommends that at least two populations in the Atlantic Ocean should be considered distinct (eastern and western Atlantic) and conservation efforts should be focused in areas with the greatest genetic diversity by environmental managers.

  20. Genetic determinants of cardiometabolic risk: a proposed model for phenotype association and interaction.

    PubMed

    Blackett, Piers R; Sanghera, Dharambir K

    2013-01-01

    This review provides a translational and unifying summary of metabolic syndrome genetics and highlights evidence that genetic studies are starting to unravel and untangle origins of the complex and challenging cluster of disease phenotypes. The associated genes effectively express in the brain, liver, kidney, arterial endothelium, adipocytes, myocytes, and β cells. Progression of syndrome traits has been associated with ectopic lipid accumulation in the arterial wall, visceral adipocytes, myocytes, and liver. Thus, it follows that the genetics of dyslipidemia, obesity, and nonalcoholic fatty liver disease are central in triggering progression of the syndrome to overt expression of disease traits and have become a key focus of interest for early detection and for designing prevention and treatments. To support the "birds' eye view" approach, we provide a road-map depicting commonality and interrelationships between the traits and their genetic and environmental determinants based on known risk factors, metabolic pathways, pharmacologic targets, treatment responses, gene networks, pleiotropy, and association with circadian rhythm. Although only a small portion of the known heritability is accounted for and there is insufficient support for clinical application of gene-based prediction models, there is direction and encouraging progress in a rapidly moving field that is beginning to show clinical relevance.

  1. The genetic architecture of skeletal convergence and sex determination in ninespine sticklebacks

    PubMed Central

    Shapiro, Michael D.; Summers, Brian R.; Balabhadra, Sarita; Aldenhoven, Jaclyn T.; Miller, Ashley L.; Cunningham, Christopher B.; Bell, Michael A.; Kingsley, David M.

    2009-01-01

    SUMMARY The history of life offers plentiful examples of convergent evolution, the independent derivation of similar phenotypes in distinct lineages [1]. Convergent phenotypes among closely related lineages (frequently termed “parallel” evolution) are often assumed to result from changes in similar genes or developmental pathways [2], but the genetic origins of convergence remains poorly understood. Ninespine (Pungitius pungitius) and threespine (Gasterosteus aculeatus) stickleback fish provide many examples of convergent evolution of adaptive phenotypes, both within and between genera. The genetic architecture of several important traits is now known for threespine sticklebacks [3–10]; thus, ninespine sticklebacks thus provide a unique opportunity to critically test whether similar or different chromosome regions control similar phenotypes in these lineages. We have generated the first genome-wide linkage map for the ninespine stickleback and used quantitative trait locus (QTL) mapping to identify chromosome regions controlling several skeletal traits and sex determination. In ninespine sticklebacks, these traits mapped to chromosome regions not previously known to control the corresponding traits in threespine sticklebacks. Therefore, convergent morphological evolution in these related, but independent, vertebrate lineages may have different genetic origins. Comparative genetics in sticklebacks provides an exciting opportunity to study the mechanisms controlling similar phenotypic changes in different groups of animals. PMID:19500990

  2. Structure and Genetic Variability of the Oceanic Whitetip Shark, Carcharhinus longimanus, Determined Using Mitochondrial DNA

    PubMed Central

    Camargo, Sâmia M.; Coelho, Rui; Chapman, Demian; Howey-Jordan, Lucy; Brooks, Edward J.; Fernando, Daniel; Mendes, Natalia J.; Hazin, Fabio H. V.; Oliveira, Claudio; Santos, Miguel N.; Foresti, Fausto; Mendonça, Fernando F.

    2016-01-01

    Information regarding population structure and genetic connectivity is an important contribution when establishing conservation strategies to manage threatened species. The oceanic whitetip shark, Carcharhinus longimanus, is a highly migratory, large-bodied, pelagic shark listed by the IUCN (International Union for Conservation of Nature) Red List as "vulnerable" throughout its range and “critically endangered” in the western north Atlantic. In 2014, the species was protected globally under Appendix II of CITES (Convention on International Trade in Endangered Species), limiting and regulating trade. This study used partial sequences of mitochondrial DNA (mtDNA) control region to determine the population genetic structure of oceanic whitetip sharks across the Atlantic and Indian Oceans. 724 base pairs were obtained from 215 individuals that identifed nine polymorphic sites and defined 12 distinct haplotypes. Total nucleotide diversity (π) was 0.0013 and haplotype diversity (h) was 0.5953. The Analysis of Molecular Variance (AMOVA) evidenced moderate levels of population structure (ɸST = 0.1039) with restricted gene flow between the western and eastern Atlantic Ocean, and a strong relationship between the latter region and the Indian Ocean. Even though the oceanic whitetip is a highly migratory animal the results presented here show that their genetic variability is slightly below average of other pelagic sharks. Additionally, this study recommends that at least two populations in the Atlantic Ocean should be considered distinct (eastern and western Atlantic) and conservation efforts should be focused in areas with the greatest genetic diversity by environmental managers. PMID:27187497

  3. Genetic, nongenetic and epigenetic risk determinants in developmental programming of type 2 diabetes.

    PubMed

    Vaag, Allan; Brøns, Charlotte; Gillberg, Linn; Hansen, Ninna S; Hjort, Line; Arora, Geeti P; Thomas, Nihal; Broholm, Christa; Ribel-Madsen, Rasmus; Grunnet, Louise G

    2014-11-01

    Low birthweight (LBW) individuals and offspring of women with gestational diabetes mellitus (GDM) exhibit increased risk of developing type 2 diabetes (T2D) and associated cardiometabolic traits in adulthood, which for both groups may be mediated by adverse events and developmental changes in fetal life. T2D is a multifactorial disease occurring as a result of complicated interplay between genetic and both prenatal and postnatal nongenetic factors, and it remains unknown to what extent the increased risk of T2D associated with LBW or GDM in the mother may be due to, or confounded by, genetic factors. Indeed, it has been shown that genetic changes influencing risk of diabetes may also be associated with reduced fetal growth as a result of reduced insulin secretion and/or action. Similarly, increased risk of T2D among offspring could be explained by T2D susceptibility genes shared between the mother and her offspring. Epigenetic mechanisms may explain the link between factors operating in fetal life and later risk of developing T2D, but so far convincing evidence is lacking for epigenetic changes as a prime and direct cause of T2D. This review addresses recent literature on the early origins of adult disease hypothesis, with a special emphasis on the role of genetic compared with nongenetic and epigenetic risk determinants and disease mechanisms. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  4. Determination of the Water Content of Snow by Dielectric Measurements

    DTIC Science & Technology

    1992-07-01

    AD- A256 299 R*UIIUIUIIII• 0P Determination of the Water Content of Snow by Dielectric Measurements Paul R. Camp and David R. LaBrecque July 1992 a...kHz to deterrnlne wfether measurements made In this frequency range might prove useful in evaluating the water content of snow. Dielectric heating at...20 kHz proved a very useful means of modifying the water content from 0 to 30% by weight. Six different natural snows were used in these experiments

  5. Infrared measurements of a scramjet exhaust. [to determine combustion efficiency

    NASA Technical Reports Server (NTRS)

    Reed, R. A.; Slack, M. W.

    1980-01-01

    Diagnostic 2 - 5 mm infrared spectra of a hydrogen burning scramjet exhaust were measured with an interferometer spectrometer. Exhaust gas temperatures and water vapor partial pressures were determined from the observed intensity and spectral profile of the H2O 2.7 mm infrared emission band. Overall engine combustion efficiencies were derived by combining these measurements with the known engine operating conditions. Efficiencies fall (70 - 50 percent) as fuel equivalence ratios rise (0.4 - 1.0). Data analysis techniques and sensitivity studies are also presented.

  6. Genome-wide association study identifies genetic determinants of urine PCA3 levels in men.

    PubMed

    Chen, Zhuo; Sun, Jielin; Kim, Seong-Tae; Groskopf, Jack; Feng, Junjie; Isaacs, William B; Rittmaster, Roger S; Condreay, Lynn D; Zheng, Siqun Lilly; Xu, Jianfeng

    2013-04-01

    Prostate cancer gene 3 (PCA3) is a non-coding gene specifically overexpressed in prostate cancer (PCa) that has great potential as a clinical biomarker for predicting prostate biopsy outcome. However, genetic determinants of PCA3 expression level remain unknown. To investigate the association between genetic variants and PCA3 mRNA level, a genome-wide association study was conducted in 1371 men of European descent in the REduction by DUtasteride of prostate Cancer Events trial. First-voided urine specimens containing prostate cells were obtained after digital rectal examination. The PROGENSA PCA3 assay was used to determine PCA3 score in the urinary samples. A linear regression model was used to detect the associations between (single nucleotide polymorphisms) SNPs and PCA3 score under an additive genetic model, adjusting for age and population stratification. Two SNPs, rs10993994 in β-microseminoprotein at 10q11.23 and rs10424878 in kallikrein-related peptidase 2 at 19q13.33, were associated with PCA3 score at genome-wide significance level (P = 1.22 x 10(-9) and 1.06 x 10(-8), respectively). Men carrying the rs10993994 "T" allele or rs10424878 "A" allele had higher PCA3 score compared with men carrying rs10993994 "C" allele or rs10424878 "G" allele (β = 1.25 and 1.24, respectively). This is the first comprehensive search for genetic determinants of PCA3 score. The novel loci identified may provide insight into the molecular mechanisms of PCA3 expression as a potential marker of PCa.

  7. Determination of particle size using measurement of scatter

    NASA Technical Reports Server (NTRS)

    Scott, R. L., Jr.

    1978-01-01

    A literature search was conducted to determine the state of the art particle size measurement by the light scatter technique. This technique may involve diffraction pattern analysis, location of minima and maxima in angular dependence of scattered light, magnitude of intensity verses angle, forward lobe scattered intensity ratio using two small angles, forward scatter in a small cone, and total scatter. Some of the more modern recordings and detection systems are video, holographic, and systems using optical processing.

  8. Determining Confounding Sensitivities In Eddy Current Thin Film Measurements

    SciTech Connect

    Gros, Ethan; Udpa, Lalita; Smith, James A.; Wachs, Katelyn

    2016-07-01

    Determining Confounding Sensitivities In Eddy Current Thin Film Measurements Ethan Gros, Lalita Udpa, Electrical Engineering, Michigan State University, East Lansing MI 48824 James A. Smith, Experiment Analysis, Idaho National Laboratory, Idaho Falls ID 83415 Eddy current (EC) techniques are widely used in industry to measure the thickness of non-conductive films on a metal substrate. This is done using a system whereby a coil carrying a high-frequency alternating current is used to create an alternating magnetic field at the surface of the instrument's probe. When the probe is brought near a conductive surface, the alternating magnetic field will induce ECs in the conductor. The substrate characteristics and the distance of the probe from the substrate (the coating thickness) affect the magnitude of the ECs. The induced currents load the probe coil affecting the terminal impedance of the coil. The measured probe impedance is related to the lift off between coil and conductor as well as conductivity of the test sample. For a known conductivity sample, the probe impedance can be converted into an equivalent film thickness value. The EC measurement can be confounded by a number of measurement parameters. It is the goal of this research to determine which physical properties of the measurement set-up and sample can adversely affect the thickness measurement. The eddy current testing is performed using a commercially available, hand held eddy current probe (ETA3.3H spring loaded eddy probe running at 8 MHz) that comes with a stand to hold the probe. The stand holds the probe and adjusts the probe on the z-axis to help position the probe in the correct area as well as make precise measurements. The signal from the probe is sent to a hand held readout, where the results are recorded directly in terms of liftoff or film thickness. Understanding the effect of certain factors on the measurements of film thickness, will help to evaluate how accurate the ETA3.3H spring loaded

  9. Residual stress determination from a laser-based curvature measurement

    SciTech Connect

    W. D. Swank; R. A. Gavalya; J. K. Wright; R. N. Wright

    2000-05-08

    Thermally sprayed coating characteristics and mechanical properties are in part a result of the residual stress developed during the fabrication process. The total stress state in a coating/substrate is comprised of the quench stress and the coefficient of thermal expansion (CTE) mismatch stress. The quench stress is developed when molten particles impact the substrate and rapidly cool and solidify. The CTE mismatch stress results from a large difference in the thermal expansion coefficients of the coating and substrate material. It comes into effect when the substrate/coating combination cools from the equilibrated deposit temperature to room temperature. This paper describes a laser-based technique for measuring the curvature of a coated substrate and the analysis required to determine residual stress from curvature measurements. Quench stresses were determined by heating the specimen back to the deposit temperature thus removing the CTE mismatch stress. By subtracting the quench stress from the total residual stress at room temperature, the CTE mismatch stress was estimated. Residual stress measurements for thick (>1mm) spinel coatings with a Ni-Al bond coat on 304 stainless steel substrates were made. It was determined that a significant portion of the residual stress results from the quenching stress of the bond coat and that the spinel coating produces a larger CTE mismatch stress than quench stress.

  10. Residual Stress Determination from a Laser-Based Curvature Measurement

    SciTech Connect

    Swank, William David; Gavalya, Rick Allen; Wright, Julie Knibloe; Wright, Richard Neil

    2000-05-01

    Thermally sprayed coating characteristics and mechanical properties are in part a result of the residual stress developed during the fabrication process. The total stress state in a coating/substrate is comprised of the quench stress and the coefficient of thermal expansion (CTE) mismatch stress. The quench stress is developed when molten particles impact the substrate and rapidly cool and solidify. The CTE mismatch stress results from a large difference in the thermal expansion coefficients of the coating and substrate material. It comes into effect when the substrate/coating combination cools from the equilibrated deposit temperature to room temperature. This paper describes a laser-based technique for measuring the curvature of a coated substrate and the analysis required to determine residual stress from curvature measurements. Quench stresses were determined by heating the specimen back to the deposit temperature thus removing the CTE mismatch stress. By subtracting the quench stress from the total residual stress at room temperature, the CTE mismatch stress was estimated. Residual stress measurements for thick (>1mm) spinel coatings with a Ni-Al bond coat on 304 stainless steel substrates were made. It was determined that a significant portion of the residual stress results from the quenching stress of the bond coat and that the spinel coating produces a larger CTE mismatch stress than quench stress.

  11. Genetically Determined Amerindian Ancestry Correlates with Increased Frequency of Risk Alleles for Systemic Lupus Erythematosus

    PubMed Central

    Sanchez, E; Webb, R; Rasmussen, A.; Kelly, J.A; Riba, L.; Kaufman, K.M.; Garcia-de la Torre, I.; Moctezuma, J.F.; Maradiaga-Ceceña, M.A.; Cardiel, M.; Acevedo, E.; Cucho-Venegas, M.; Garcia, M.A.; Gamron, S.; Pons-Estel, B.A.; Vasconcelos, C.; Martin, J.; Tusié-Luna, T.; Harley, J.B.; Richardson, B.; Sawalha, A.H.; Alarcón-Riquelme, M.E.

    2011-01-01

    Objectives To analyze if genetically determined Amerindian ancestry predicts the increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus. Methods Single nucleotide polymorphisms within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo normal healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation of the presence of risk alleles with ancestry was done using linear regression. Results A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, PDCD1, ITGAM, and IRF5 were associated with lupus in a Hispanic-Mestizo cohort enriched for European and Amerindian ancestry. In addition, two SNPs within the MHC region, previously associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression we predict an average increase of 2.34 risk alleles when comparing a lupus patient with 100% Amerindian ancestry to an SLE patient with 0% American Indian Ancestry (p<0.0001). SLE patients with 43% more Amerindian ancestry are predicted to carry one additional risk allele. Conclusion Amerindian ancestry increased the number of risk alleles for lupus. PMID:20848568

  12. Angular measurement for determining muscle tonus in facial paralysis.

    PubMed

    Tessitore, Adriana; Magna, Luis Alberto; Paschoal, Jorge Rizzato

    2010-01-01

    the decrease of facial movements in peripheral facial paralysis and the resulting aesthetical sequels may have important emotional repercussions as a consequence to the functional deficit, and depending on the intensity of the clinical condition. Orofacial rehabilitation has as a purpose to favor the recovery of orofacial movements and to adequate and/or adapt orofacial functions and facial mimic. However, quantifying therapeutic results in an attempt to measure the muscle tonus is a challenge. Generally, the used forms of measurement are general and subjective. to propose the labial commissure angle as an anthropometric marker and to evaluate its reliability as an objective tool to evaluate the modification of the facial muscle tonus after rehabilitation. participants of the study were 20 patients presenting peripheral facial paralysis - level IV. The study was conducted using images from the photographical documentation taken fifteen days to one year post-onset of facial paralysis. The angle was measured by tracings determined by pre-established anthropometric facial points, such as the line between the glabella and the gnation and the crossing with the left and right chelion points determining an angle manually measured with a protractor on the photography. The average Labial Commissure Angle before treatment was of 101.70 and after rehabilitation of 93.80 (standard deviation, SD = 4.3). The statistical analysis indicated a significant difference (p < 0.001). the results obtained suggest that the Labial Commissure Angle allows the objective evaluation of facial muscle tonus modification.

  13. Micromechanical cohesion force measurements to determine cyclopentane hydrate interfacial properties.

    PubMed

    Aman, Zachary M; Joshi, Sanjeev E; Sloan, E Dendy; Sum, Amadeu K; Koh, Carolyn A

    2012-06-15

    Hydrate aggregation and deposition are critical factors in determining where and when hydrates may plug a deepwater flowline. We present the first direct measurement of structure II (cyclopentane) hydrate cohesive forces in the water, liquid hydrocarbon and gas bulk phases. For fully annealed hydrate particles, gas phase cohesive forces were approximately twice that obtained in a liquid hydrocarbon phase, and approximately six times that obtained in the water phase. Direct measurements show that hydrate cohesion force in a water-continuous bulk may be only the product of solid-solid cohesion. When excess water was present on the hydrate surface, gas phase cohesive forces increased by a factor of three, suggesting the importance of the liquid or quasi-liquid layer (QLL) in determining cohesive force. Hydrate-steel adhesion force measurements show that, when the steel surface is coated with hydrophobic wax, forces decrease up to 96%. As the micromechanical force technique is uniquely capable of measuring hydrate-surface forces with variable contact time, the present work contains significant implications for hydrate applications in flow assurance.

  14. Genetic determinism of bone and mineral metabolism in meat-type chickens: A QTL mapping study.

    PubMed

    Mignon-Grasteau, Sandrine; Chantry-Darmon, Céline; Boscher, Marie-Yvonne; Sellier, Nadine; Chabault-Dhuit, Marie; Le Bihan-Duval, Elisabeth; Narcy, Agnès

    2016-12-01

    Skeletal integrity in meat-type chickens is affected by many factors including rapid growth rate, nutrition and genetics. To investigate the genetic basis of bone and mineral metabolism, a QTL detection study was conducted in an intercross between two lines of meat-type chickens divergently selected for their high (D +) or low (D -) digestive efficiency. Tibia size (length, diameter, volume) and ash content were determined at 3 weeks of age as well as phosphorus (P) retention and plasma concentration. Heritability of these traits and their genetic correlations with digestive efficiency were estimated. A QTL mapping study was performed using 3379 SNP markers. Tibia size, weight, ash content and breaking strength were highly heritable (0.42 to 0.61). Relative tibia diameter and volume as well as P retention were strongly and positively genetically correlated with digestive efficiency (0.57 to 0.80). A total of 35 QTL were identified (9 for tibia weight, 13 for tibia size, 5 for bone strength, 5 for bone mineralization, 2 for plasma P concentration and 1 for P retention). Six QTL were genome-wide significant, and 3 QTL for tibia relative volume, weight and ash weight on chromosome 6 were fixed, the positive allele coming from the D-line. For two QTL for ash content on chromosome 18 and relative tibia length on chromosome 26, the confidence intervals were small enough to identify potential candidate genes. These findings support the evidence of multiple genetic loci controlling bone and mineral metabolism. The identification of candidate genes may provide new perspectives in the understanding of bone regulation, even beyond avian species.

  15. Genetic Variation Within Adrenergic Pathways Determines In Vivo Effects of Presynaptic Stimulation in Humans

    PubMed Central

    Fung, Maple M.; Nguyen, Carie; Mehtani, Parag; Salem, Rany M.; Perez, Brandon; Thomas, Brenda; Das, Madhusudan; Schork, Nicholas J.; Mahata, Sushil K.; Ziegler, Michael G.; O’Connor, Daniel T.

    2009-01-01

    Background Catecholamines govern stress blood pressure responses. Catecholaminergic responses may be partially genetic and contribute to the complex heritability of hypertension. Methods and Results To evaluate catecholaminergic responses without systemic counterregulation, we infused graded concentrations of tyramine, an indirect presynaptic norepinephrine releaser, into dorsal hand veins of 49 normotensive men and women of 5 ethnicities. Vascular responses were coupled to common (minor allele frequency >10%) single-nucleotide polymorphisms at adrenergic target loci within presynaptic pathways. Significance was set at P<0.003 after Bonferroni correction. Generalized analysis of molecular variance (GAMOVA) was performed to determine whether genetic admixture contributed to results. Venoconstriction progressed to 47% with increasing concentrations of tyramine (0.129 to 25.8 mmol/L; P<0.001). Family history of hypertension (P<0.001) and female sex (P=0.02) predicted blunted tyramine responses. Two genetic loci significantly predicted vascular response: chromogranin B, which encodes a protein that catalyzes catecholamine vesicle formation (CHGB, exon 4, Glu348Glu; P=0.002), and cytochrome b-561 (CYB561, intron 1, C719G; P<0.001), an electron shuttle for catecholamine synthesis. Stepwise regression suggested important effects for the CHGB locus, with polymorphisms for the vacuolar-ATPase β-subunit (ATP6V1B1, exon 1, Ile30Thr) and flavin-containing monooxygenase-3 (FMO3, exon 3, Lys158Glu, P=0.002). GAMOVA did not show a significant relationship between overall genetic profile and hand-vein constriction (P=0.29), which indicates that population stratification did not contribute to this phenotype. Conclusions Locally infused tyramine produced dose-dependent pressor responses, predicted by family history of hypertension, sex, and genetic variants at loci, particularly CHGB, that encode the biosynthesis, storage, and metabolism of catecholamines. Such variants may

  16. Genetic architecture of sex determination in fish: applications to sex ratio control in aquaculture.

    PubMed

    Martínez, Paulino; Viñas, Ana M; Sánchez, Laura; Díaz, Noelia; Ribas, Laia; Piferrer, Francesc

    2014-01-01

    Controlling the sex ratio is essential in finfish farming. A balanced sex ratio is usually good for broodstock management, since it enables to develop appropriate breeding schemes. However, in some species the production of monosex populations is desirable because the existence of sexual dimorphism, primarily in growth or first time of sexual maturation, but also in color or shape, can render one sex more valuable. The knowledge of the genetic architecture of sex determination (SD) is convenient for controlling sex ratio and for the implementation of breeding programs. Unlike mammals and birds, which show highly conserved master genes that control a conserved genetic network responsible for gonad differentiation (GD), a huge diversity of SD mechanisms has been reported in fish. Despite theory predictions, more than one gene is in many cases involved in fish SD and genetic differences have been observed in the GD network. Environmental factors also play a relevant role and epigenetic mechanisms are becoming increasingly recognized for the establishment and maintenance of the GD pathways. Although major genetic factors are frequently involved in fish SD, these observations strongly suggest that SD in this group resembles a complex trait. Accordingly, the application of quantitative genetics combined with genomic tools is desirable to address its study and in fact, when applied, it has frequently demonstrated a multigene trait interacting with environmental factors in model and cultured fish species. This scenario has notable implications for aquaculture and, depending upon the species, from chromosome manipulation or environmental control techniques up to classical selection or marker assisted selection programs, are being applied. In this review, we selected four relevant species or fish groups to illustrate this diversity and hence the technologies that can be used by the industry for the control of sex ratio: turbot and European sea bass, two reference species of

  17. Genetic architecture of sex determination in fish: applications to sex ratio control in aquaculture

    PubMed Central

    Martínez, Paulino; Viñas, Ana M.; Sánchez, Laura; Díaz, Noelia; Ribas, Laia; Piferrer, Francesc

    2014-01-01

    Controlling the sex ratio is essential in finfish farming. A balanced sex ratio is usually good for broodstock management, since it enables to develop appropriate breeding schemes. However, in some species the production of monosex populations is desirable because the existence of sexual dimorphism, primarily in growth or first time of sexual maturation, but also in color or shape, can render one sex more valuable. The knowledge of the genetic architecture of sex determination (SD) is convenient for controlling sex ratio and for the implementation of breeding programs. Unlike mammals and birds, which show highly conserved master genes that control a conserved genetic network responsible for gonad differentiation (GD), a huge diversity of SD mechanisms has been reported in fish. Despite theory predictions, more than one gene is in many cases involved in fish SD and genetic differences have been observed in the GD network. Environmental factors also play a relevant role and epigenetic mechanisms are becoming increasingly recognized for the establishment and maintenance of the GD pathways. Although major genetic factors are frequently involved in fish SD, these observations strongly suggest that SD in this group resembles a complex trait. Accordingly, the application of quantitative genetics combined with genomic tools is desirable to address its study and in fact, when applied, it has frequently demonstrated a multigene trait interacting with environmental factors in model and cultured fish species. This scenario has notable implications for aquaculture and, depending upon the species, from chromosome manipulation or environmental control techniques up to classical selection or marker assisted selection programs, are being applied. In this review, we selected four relevant species or fish groups to illustrate this diversity and hence the technologies that can be used by the industry for the control of sex ratio: turbot and European sea bass, two reference species of

  18. The Genetic Architecture of Maize (Zea mays L.) Kernel Weight Determination

    PubMed Central

    Prado, Santiago Alvarez; López, César G.; Senior, M. Lynn; Borrás, Lucas

    2014-01-01

    Individual kernel weight is an important trait for maize yield determination. We have identified genomic regions controlling this trait by using the B73xMo17 population; however, the effect of genetic background on control of this complex trait and its physiological components is not yet known. The objective of this study was to understand how genetic background affected our previous results. Two nested stable recombinant inbred line populations (N209xMo17 and R18xMo17) were designed for this purpose. A total of 408 recombinant inbred lines were genotyped and phenotyped at two environments for kernel weight and five other traits related to kernel growth and development. All traits showed very high and significant (P < 0.001) phenotypic variability and medium-to-high heritability (0.60−0.90). When N209xMo17 and R18xMo17 were analyzed separately, a total of 23 environmentally stable quantitative trait loci (QTL) and five epistatic interactions were detected for N209xMo17. For R18xMo17, 59 environmentally stable QTL and 17 epistatic interactions were detected. A joint analysis detected 14 stable QTL regardless of the genetic background. Between 57 and 83% of detected QTL were population specific, denoting medium-to-high genetic background effects. This percentage was dependent on the trait. A meta-analysis including our previous B73xMo17 results identified five relevant genomic regions deserving further characterization. In summary, our grain filling traits were dominated by small additive QTL with several epistatic and few environmental interactions and medium-to-high genetic background effects. This study demonstrates that the number of detected QTL and additive effects for different physiologically related grain filling traits need to be understood relative to the specific germplasm. PMID:25237113

  19. Issues in the measurement of social determinants of health.

    PubMed

    Mooney, Gavin; Fohtung, Nubong G

    2008-01-01

    This article focuses on the measurement of the social determinants of health, and specifically on issues relating to two key variables relevant to the analysis of public health information: poverty and inequality. Although the paper has been written from the perspective of economics, the discipline of the two authors, it is also of relevance to researchers in other disciplines. It is argued that there is a need to ensure that, when considering measurement in this largely neglected area of research, sufficient thought is given to the relationships that are being examined or assessed. We argue further that any attempt at measurement in this area must take into account the historical backdrop and the complex nature of the relationships between these key variables.

  20. Walnut (Juglans spp.) genetic diversity determined by restriction fragment length polymorphisms.

    PubMed

    Fjellstrom, R G; Parfitt, D E

    1994-08-01

    The genetic diversity of 13 Juglans species was characterized using nuclear RFLPs. Allelic frequencies among 41 Juglans populations were determined at 19 RFLP loci by hybridizing single locus probes to walnut DNAs digested with the restriction endonuclease EcoRI or HindIII. A 10-fold difference in species heterozygosity levels was seen among species in different sections of the genus. Differentiation among conspecific populations varied over threefold between species. Genetic differentiation among conspecific east Asian populations was larger than that seen among east Asian species, while the opposite trend was seen for Western Hemisphere species. Taxonomic affinities were also indicated by these results, suggesting that J. cinerea should be included as part of section Cardiocaryon rather than as a unique section, Trachycaryon. Juglans hindsii is classified as a distinct species and not a subspecies of J. californica. Strategies for germplasm preservation and species requiring marked collection efforts are given.

  1. Determining the causes and consequences of nicotine dependence: emerging genetic research methods.

    PubMed

    Ware, Jennifer J; Munafò, Marcus R

    2014-10-01

    Tobacco use remains the leading cause of preventable death worldwide. Establishing the genetic aetiology of tobacco use and dependence is an important first step in understanding the neurobiological mechanisms of tobacco use, and in turn the development of effective treatments. In addition, whilst the effects of tobacco use on a broad range of physical illnesses (e.g. lung cancer, respiratory disease, cardiovascular disease) are now well-established, the causal effects of tobacco use on a number of other outcomes remains to be established. Determining the causes and consequences of tobacco use therefore continues to be both a scientific and a public health priority. Here we review emerging methods in genetic research that allow stronger causal inferences to be drawn from observational data.

  2. Laser tracker error determination using a network measurement

    NASA Astrophysics Data System (ADS)

    Hughes, Ben; Forbes, Alistair; Lewis, Andrew; Sun, Wenjuan; Veal, Dan; Nasr, Karim

    2011-04-01

    We report on a fast, easily implemented method to determine all the geometrical alignment errors of a laser tracker, to high precision. The technique requires no specialist equipment and can be performed in less than an hour. The technique is based on the determination of parameters of a geometric model of the laser tracker, using measurements of a set of fixed target locations, from multiple locations of the tracker. After fitting of the model parameters to the observed data, the model can be used to perform error correction of the raw laser tracker data or to derive correction parameters in the format of the tracker manufacturer's internal error map. In addition to determination of the model parameters, the method also determines the uncertainties and correlations associated with the parameters. We have tested the technique on a commercial laser tracker in the following way. We disabled the tracker's internal error compensation, and used a five-position, fifteen-target network to estimate all the geometric errors of the instrument. Using the error map generated from this network test, the tracker was able to pass a full performance validation test, conducted according to a recognized specification standard (ASME B89.4.19-2006). We conclude that the error correction determined from the network test is as effective as the manufacturer's own error correction methodologies.

  3. Lay responses to health messages about the genetic risk factors for salt sensitivity: do mass media genetic health messages result in genetic determinism?

    PubMed

    Smerecnik, Chris M R

    2010-08-01

    Media coverage of genetics may lead to overestimation of the impact of genetics on disease development. In this study, we presented one student sample and one general public sample from the Netherlands with a general or a genetic health message (HM) about salt sensitivity. After reading the genetic (but not the general) HM, participants reported higher perceived impact of genetic versus lifestyle factors and a higher attributable fraction of genetics on disease development. Nevertheless, participants were able to recognise the balance between lifestyle and genetic risk factors in disease development. They also contextualised and restricted the message's implications to the specific information provided, and did not extrapolate these implications to other diseases. These results illustrate the nuanced understanding the general public may have concerning genetic risk factors.

  4. Effect of a Founder Event on Variation in the Genetic Sex-Determining System of the Fire Ant Solenopsis Invicta

    PubMed Central

    Ross, K. G.; Vargo, E. L.; Keller, L.; Trager, J. C.

    1993-01-01

    Effects of a recent founder event on genetic diversity in wild populations of the fire ant Solenopsis invicta were studied, with particular attention given to the genetic sex-determining system. Diploid males are far more common relative to haploid males in introduced populations than in native populations of fire ants, and queens that produce diploid males account for a significantly larger proportion of the mated queens in introduced than in native populations. Differences between native and introduced populations in attributes of the mating systems (i.e., queen mating frequency or level of inbreeding) can be excluded as factors contributing to these different levels of diploid male production. Thus, we conclude that diploid males have increased in frequency in introduced populations because of a loss of allelic diversity at the sex-determining locus (loci). This loss of sex alleles has generated a substantial increase in the estimated segregational genetic load associated with production of sterile diploid males in introduced populations over the load in native populations. The loss of allelic diversity in the sex-determining system in introduced S. invicta is paralleled by a loss of electrophoretically detectable rare alleles at protein-encoding loci. Such concordance between these different types of markers is predicted because each of the many sex alleles present in the native populations is expected to be rare. Estimates of expected heterozygosity (H(exp)) based on 76 electrophoretic loci do not differ significantly between the native and introduced fire ant populations, illustrating the lack of sensitivity of this measure for detecting many types of bottlenecks. PMID:8293983

  5. Genetic trends for objectively measured and subjectively assessed traits in a Dorper sheep flock.

    PubMed

    Zishiri, Oliver Tendayi; Cloete, Schalk Willem; Olivier, Johannes Jacobus; Dzama, Kennedy

    2013-02-01

    Genetic trends were constructed to monitor the genetic change for subjectively assessed and objectively measured traits using data emanating from complete records from the National Small Stock Improvement Scheme database and performance records accumulated by a single breeder over a period of 24 years. The objectively measured production traits considered were weaning weight, post-weaning weight (PWW), yearling weight, average daily weight gain to weaning (ADGW), average daily weight gain during post-weaning phase (ADGPW) and average daily weight gain up to yearling age. The subjectively assessed traits (scored on a five-point scale) were conformation, fat distribution, size, type and colour. Direct genetic trends for live weight and growth traits (with the exception of ADGPW) were positive. All the objectively measured traits where maternal effects were significant, except PWW, registered small declines in maternal breeding values. The fastest genetic progress was attained by ADGW, which amounted to 0.29 % of the overall phenotypic mean per annum. Conformation and type exhibited positive but slow increments in direct breeding values at an equivalent annual rate amounting to 0.12 and 0.09 % of the overall phenotypic mean, respectively. Size demonstrated a negative genetic trend of -0.14 % of the overall phenotypic mean per annum. Genetic trends for fat distribution and colour were negligible. It was concluded that breeders should focus more on the performance recording of objective traits as they are likely to respond favourably to selection pressure.

  6. Lag time determination in DEC measurements with PTR-MS

    NASA Astrophysics Data System (ADS)

    Taipale, R.; Ruuskanen, T. M.; Rinne, J.

    2010-07-01

    The disjunct eddy covariance (DEC) method has emerged as a popular technique for micrometeorological flux measurements of volatile organic compounds (VOCs). It has usually been combined with proton transfer reaction mass spectrometry (PTR-MS), an online technique for VOC concentration measurements. However, the determination of the lag time between wind and concentration measurements has remained an important challenge. To address this issue, we studied the effect of different lag time methods on DEC fluxes. The analysis was based on both actual DEC measurements with PTR-MS and simulated DEC data derived from high frequency H2O measurements with an infrared gas analyzer. Conventional eddy covariance fluxes of H2O served as a reference in the DEC simulation. The individual flux measurements with PTR-MS were rather sensitive to the lag time methods, but typically this effect averaged out when the median fluxes were considered. The DEC simulation revealed that the maximum covariance method was prone to overestimation of the absolute values of fluxes. The constant lag time methods, one based on a value calculated from the sampling flow and the sampling line dimensions and the other on a typical daytime value, had a tendency to underestimate. The visual assessment method and our new averaging approach utilizing running averaged covariance functions did not yield statistically significant errors and thus fared better than the habitual choice, the maximum covariance method. Given this feature and the potential for automatic flux calculation, we recommend using the averaging approach in DEC measurements with PTR-MS. It also seems well suited to conventional eddy covariance applications when measuring fluxes near the detection limit.

  7. Experimental determination of storage ring optics using orbit response measurements

    NASA Astrophysics Data System (ADS)

    Safranek, J.

    1997-02-01

    The measured response matrix giving the change in orbit at beam position monitors (BPMs) with changes in steering magnet excitation can be used to accurately calibrate the linear optics in an electron storage ring [1-8]. A computer code called LOCO (Linear Optics from Closed Orbits) was developed to analyze the NSLS X-Ray Ring measured response matrix to determine: the gradients in all 56 quadrupole magnets; the calibration of the steering magnets and BPMs; the roll of the quadrupoles, steering magnets, and BPMs about the electron beam direction; the longitudinal magnetic centers of the orbit steering magnets; the horizontal dispersion at the orbit steering magnets; and the transverse mis-alignment of the electron orbit in each of the sextupoles. Random orbit measurement error from the BPMs propagated to give only 0.04% rms error in the determination of individual quadrupole gradients and 0.4 mrad rms error in the determination of individual quadrupole rolls. Small variations of a few parts in a thousand in the quadrupole gradients within an individual family were resolved. The optics derived by LOCO gave accurate predictions of the horizontal dispersion, the beta functions, and the horizontal and vertical emittances, and it gave good qualitative agreement with the measured vertical dispersion. The improved understanding of the X-Ray Ring has enabled us to increase the synchrotron radiation brightness. The LOCO code can also be used to find the quadrupole family gradients that best correct for gradient errors in quadrupoles, in sextupoles, and from synchrotron radiation insertion devices. In this way the design periodicity of a storage ring's optics can be restored. An example of periodicity restoration will be presented for the NSLS VUV Ring. LOCO has also produced useful results when applied to the ALS storage ring [8].

  8. Genetic and pharmacokinetic determinants of response to transdermal nicotine in white, black, and Asian nonsmokers.

    PubMed

    Dempsey, D A; St Helen, G; Jacob, P; Tyndale, R F; Benowitz, N L

    2013-12-01

    The aim of the study was to examine genetic, pharmacokinetic, and demographic factors that influence sensitivity to nicotine in never-smokers. Sixty never-smokers, balanced for gender and race (white, black, and Asian), wore 7-mg nicotine skin patches for up to 8 h. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, encoding the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in nine subjects and was strongly associated with rate of increase and peak concentrations of plasma nicotine. Toxicity and subjective and cardiovascular effects of nicotine were associated with the presence of reduced-function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when they are used for treating medical conditions in nonsmokers, and possibly in vulnerability to developing nicotine dependence.

  9. Precise orbit determination based on raw GPS measurements

    NASA Astrophysics Data System (ADS)

    Zehentner, Norbert; Mayer-Gürr, Torsten

    2016-03-01

    Precise orbit determination is an essential part of the most scientific satellite missions. Highly accurate knowledge of the satellite position is used to geolocate measurements of the onboard sensors. For applications in the field of gravity field research, the position itself can be used as observation. In this context, kinematic orbits of low earth orbiters (LEO) are widely used, because they do not include a priori information about the gravity field. The limiting factor for the achievable accuracy of the gravity field through LEO positions is the orbit accuracy. We make use of raw global positioning system (GPS) observations to estimate the kinematic satellite positions. The method is based on the principles of precise point positioning. Systematic influences are reduced by modeling and correcting for all known error sources. Remaining effects such as the ionospheric influence on the signal propagation are either unknown or not known to a sufficient level of accuracy. These effects are modeled as unknown parameters in the estimation process. The redundancy in the adjustment is reduced; however, an improvement in orbit accuracy leads to a better gravity field estimation. This paper describes our orbit determination approach and its mathematical background. Some examples of real data applications highlight the feasibility of the orbit determination method based on raw GPS measurements. Its suitability for gravity field estimation is presented in a second step.

  10. Determination of uncertainty in spectrophotometric surface color measurement

    NASA Astrophysics Data System (ADS)

    Hanson, Andrew R.; Clarke, Peter J.

    2002-06-01

    This paper reports on work undertaken by nine European laboratories as part of a European Commission funded research project. The project's goal was to improve harmonisation of international colorimetric scales. One objective of the exercise was to devise a means of expressing total uncertainty in color measurement. When measuring color (or indeed any physical quantity), as assessment of the uncertainty of the result is as important as the value itself. This fact, long recognized in physics, is increasingly important to any quality assured organization that relies on measurements. The approach described first determines values of the sources of spectrophotometric uncertainty, and uses a simple model to combine these into total colorimetric uncertainties. The model has been used to determine uncertainties for the follow color data: x,y, T, u', v', L*, a* and b* for the CIE 10° Standard Observer and the CIE Standard Illiminant D65 for three geometries: sepcular included, specular excluded and 0°/45°. The method is used routinely at NPL in its UKAS accredited calibration services.

  11. Determination of the genetic relationships between wild olive (Olea europaea oleaster) varieties grown in the Aegean region.

    PubMed

    Sesli, M; Yeğenoğlu, E D

    2010-05-11

    The RAPD technique was used for determining genetic differences between 12 wild-olive varieties grown in the Aegean provinces of Izmir, Mugla, and Manisa in Turkey. Wild olives obtained from the same provinces were included in the same plot. Twenty of 25 operon primers (OP-I 4, OP-I 14, OP-I 15, OP-I 16, OP-I 17, OP-Q1, OP-Q2, OP-Q3, OP-Q4, OP-Q11, OP-Q12, OP-Q13, OP-Q14, OP-Q15, OP-Q16, OP-Q17, OP-Q18, OP-Q19, OP-Q20, OP-F1, OP-F2, OP-F3, OP-F6, OP-F7, OP-F8) yielded bands. The differences between the varieties were determined based on their genetic similarities, using principal coordinate analysis; genetic distances were determined using neighbor-joining analysis. The varieties wild 7 and wild 12 had the lowest genetic similarity (0.97, Jaccard similarity index); they also had the greatest genetic distance between them (0.3606, Nei's genetic distance). It was concluded that the RAPD technique is adequate for the evaluation of genetic relationships among wild olives. Principal coordinate analysis and neighbor-joining analysis gave results that support the use of this type of analysis to help understand the genetic background of olives and for further genetic studies.

  12. Lag time determination in DEC measurements with PTR-MS

    NASA Astrophysics Data System (ADS)

    Taipale, R.; Ruuskanen, T. M.; Rinne, J.

    2010-02-01

    The disjunct eddy covariance (DEC) method has emerged as a popular technique for micrometeorological flux measurements of volatile organic compounds (VOCs). It has usually been combined with proton transfer reaction mass spectrometry (PTR-MS), an online technique for VOC concentration measurements. However, the determination of the lag time between wind and concentration measurements has remained an important challenge. To address this conundrum, we studied the effect of different lag time methods on DEC fluxes. The analysis was based on both actual DEC measurements with PTR-MS and simulated DEC data derived from high frequency H2O measurements with an infrared gas analyzer. Conventional eddy covariance fluxes of H2O served as a reference in the DEC simulation. The individual flux measurements with PTR-MS were rather sensitive to the lag time methods, but typically this effect averaged out when the median fluxes were considered. The DEC simulation revealed that the maximum covariance method was prone to overestimation of the absolute values of fluxes. The constant lag time methods, one resting on a value calculated from the sampling flow and the sampling line dimensions and the other on a typical daytime value, had a tendency to underestimate. The visual assessment method and our new averaging approach based on running averaged covariance functions did not yield statistically significant errors and thus fared better than the habitual choice, the maximum covariance method. Given this feature and the potential for automatic flux calculation, we recommend using the averaging approach in DEC measurements with PTR-MS.

  13. Lag time determination in DEC measurements with PTR-MS

    NASA Astrophysics Data System (ADS)

    Taipale, Risto; Ruuskanen, Taina M.; Rinne, Janne

    2010-05-01

    The disjunct eddy covariance (DEC) method has emerged as a popular technique for micrometeorological flux measurements of volatile organic compounds (VOCs). It has usually been combined with proton transfer reaction mass spectrometry (PTR-MS), an online technique for VOC concentration measurements. However, the determination of the lag time between wind and concentration measurements has remained an important challenge. To address this conundrum, we studied the effect of different lag time methods on DEC fluxes. The analysis was based on both actual DEC measurements with PTR-MS and simulated DEC data derived from high frequency H2O measurements with an infrared gas analyzer. Conventional eddy covariance fluxes of H2O served as a reference in the DEC simulation. The individual flux measurements with PTR-MS were rather sensitive to the lag time methods, but typically this effect averaged out when the median fluxes were considered. The DEC simulation revealed that the maximum covariance method was prone to overestimation of the absolute values of fluxes. The constant lag time methods, one resting on a value calculated from the sampling flow and the sampling line dimensions and the other on a typical daytime value, had a tendency to underestimate. The visual assessment method and our new averaging approach based on running averaged covariance functions did not yield statistically significant errors and thus fared better than the habitual choice, the maximum covariance method. Given this feature and the potential for automatic flux calculation, we recommend using the averaging approach in DEC measurements with PTR-MS.

  14. Determination of a non-measurable quantity using information from calculations and experimental measurements: application to the damage rate determination

    NASA Astrophysics Data System (ADS)

    Bourganel, Stéphane; Nimal, Jean-Claude

    2017-09-01

    This article presents a method dedicated to the determination of the best value of a required quantity which is estimated by calculation, using information closely related, obtained by measurements and calculations. This best value, called thereafter the "target", is not measurable in most cases. DPA and high energy neutron fluence (typically higher than 1 MeV) involved in vessel surveillance programs, using measurements of dosimeters, are some examples of application of this methodology. This methodology is applied without spectrum adjustment, but the spectrum shape is implicitly taken into account. In this article, an example is presented based on the FLUOLE-2 experimental program, which is developed and conducted by CEA. Neutron information is derived from a set of different kinds of neutron dosimeters. The objective is to estimate the best value of reaction rate values for each kind of dosimeters. All calculations are carried out using TRIPOLI-4 3D pointwise Monte Carlo code, and DARWIN/PEPIN2 depletion code.

  15. Determination of Complex Microcalorimeter Parameters with Impedance Measurements

    NASA Technical Reports Server (NTRS)

    Saab, T.; Bandler, S. R.; Chervenak, J.; Figueroa-Feliciano, E.; Finkbeiner, F.; Iyomoto, N.; Kelley, R.; Kilbourne, C. A.; Lindeman, M. A.; Porter, F. S.; hide

    2005-01-01

    The proper understanding and modeling of a microcalorimeter s response requires the accurate knowledge of a handful of parameters, such as C, G, alpha, . . . . While a few of these, such 8s the normal state resistance and the total thermal conductance to the heat bath (G) are directly determined from the DC IV characteristics, some others, notoriously the heat capacity (C) and alpha, appear in degenerate combinations in most measurable quantities. The case of a complex microcalorimeter, i.e. one in which the absorber s heat capacity is connected by a finite thermal impedance to the sensor, and subsequently by another thermal impedance to the heat bath, results in an added ambiguity in the determination of the individual C's and G's. In general, the dependence of the microcalorimeter s complex impedance on these parameters varies with frequency. This variation allows us to determine the individual parameters by fitting the prediction of the microcalorimeter model to the impedance data. We describe in this paper our efforts at characterizing the Goddard X-ray microcalorimeters. Using the parameters determined with this method we them compare the pulse shape and noise spectra predicted by the microcalorimeter model to data taken with the same devices.

  16. Determination of Complex Microcalorimeter Parameters with Impedance Measurements

    NASA Technical Reports Server (NTRS)

    Saab, T.; Bandler, S. R.; Chervenak, J.; Figueroa-Feliciano, E.; Finkbeiner, F.; Iyomoto, N.; Kelley, R.; Kilbourne, C. A.; Lindeman, M. A.; Porter, F. S.; Sadleir, J.

    2005-01-01

    The proper understanding and modeling of a microcalorimeter s response requires the accurate knowledge of a handful of parameters, such as C, G, alpha, . . . . While a few of these, such 8s the normal state resistance and the total thermal conductance to the heat bath (G) are directly determined from the DC IV characteristics, some others, notoriously the heat capacity (C) and alpha, appear in degenerate combinations in most measurable quantities. The case of a complex microcalorimeter, i.e. one in which the absorber s heat capacity is connected by a finite thermal impedance to the sensor, and subsequently by another thermal impedance to the heat bath, results in an added ambiguity in the determination of the individual C's and G's. In general, the dependence of the microcalorimeter s complex impedance on these parameters varies with frequency. This variation allows us to determine the individual parameters by fitting the prediction of the microcalorimeter model to the impedance data. We describe in this paper our efforts at characterizing the Goddard X-ray microcalorimeters. Using the parameters determined with this method we them compare the pulse shape and noise spectra predicted by the microcalorimeter model to data taken with the same devices.

  17. Determination of Mycotoxin Production of Fusarium Species in Genetically Modified Maize Varieties by Quantitative Flow Immunocytometry

    PubMed Central

    Bánáti, Hajnalka; Darvas, Béla; Fehér-Tóth, Szilvia; Czéh, Árpád; Székács, András

    2017-01-01

    Levels of mycotoxins produced by Fusarium species in genetically modified (GM) and near-isogenic maize, were determined using multi-analyte, microbead-based flow immunocytometry with fluorescence detection, for the parallel quantitative determination of fumonisin B1, deoxynivalenol, zearalenone, T-2, ochratoxin A, and aflatoxin B1. Maize varieties included the genetic events MON 810 and DAS-59122-7, and their isogenic counterparts. Cobs were artificially infested by F. verticillioides and F. proliferatum conidia, and contained F. graminearum and F. sporotrichoides natural infestation. The production of fumonisin B1 and deoxynivalenol was substantially affected in GM maize lines: F. verticillioides, with the addition of F. graminearum and F. sporotrichoides, produced significantly lower levels of fumonisin B1 (~300 mg·kg−1) in DAS-59122-7 than in its isogenic line (~580 mg·kg−1), while F. proliferatum, in addition to F. graminearum and F. sporotrichoides, produced significantly higher levels of deoxynivalenol (~18 mg·kg−1) in MON 810 than in its isogenic line (~5 mg·kg−1). Fusarium verticillioides, with F. graminearum and F. sporotrichoides, produced lower amounts of deoxynivalenol and zearalenone than F. proliferatum, with F. graminearum and F. sporotrichoides. T-2 toxin production remained unchanged when considering the maize variety. The results demonstrate the utility of the Fungi-Plex™ quantitative flow immunocytometry method, applied for the high throughput parallel determination of the target mycotoxins. PMID:28241411

  18. [Useage of genetic markers to determine the impact of radiation on the human body].

    PubMed

    Zedgenidze, A G; Namchevadze, E N; Nikuradze, T D; Zalinian, G G; Parsadanian, G G

    2015-02-01

    The timely determination of the fact of radiation impact on the organism is extremely important for preventive and curative interventions. Despite the fact that so far cytogenetic violations are considered to be the best biomarkers to determine the impact of ionizing radiation on the organism, actual problem is to find the optimal combination of different biomarkers. The aim of the work was investigation of the extended set of biomarkers in distant periods of exposure in people previously assigned to the radiation risk group, as well as the identification of genetic disorders in the process of radiotherapy. The object of the study were 37 residents of districts, where at the beginning of this century radioactive sources were discovered, and 6 oncology patients in the course of radiotherapy. Chromosome disorders, the overall level of DNA cells single-stranded damage by comet-assay method and a method of level detection of buccal micronuclei in were investigated. The results showed heterogeneity of different organism response to irradiation. Determination of absorbed dose, identification of various genetic disorders in individuals exposed to identical doses of radiation, offers the opportunity to judge the individual biological effect and is very important for individual preventive activities.

  19. Determining Relative Importance and Effective Settings for Genetic Algorithm Control Parameters.

    PubMed

    Mills, K L; Filliben, J J; Haines, A L

    2015-01-01

    Setting the control parameters of a genetic algorithm to obtain good results is a long-standing problem. We define an experiment design and analysis method to determine relative importance and effective settings for control parameters of any evolutionary algorithm, and we apply this method to a classic binary-encoded genetic algorithm (GA). Subsequently, as reported elsewhere, we applied the GA, with the control parameter settings determined here, to steer a population of cloud-computing simulators toward behaviors that reveal degraded performance and system collapse. GA-steered simulators could serve as a design tool, empowering system engineers to identify and mitigate low-probability, costly failure scenarios. In the existing GA literature, we uncovered conflicting opinions and evidence regarding key GA control parameters and effective settings to adopt. Consequently, we designed and executed an experiment to determine relative importance and effective settings for seven GA control parameters, when applied across a set of numerical optimization problems drawn from the literature. This paper describes our experiment design, analysis, and results. We found that crossover most significantly influenced GA success, followed by mutation rate and population size and then by rerandomization point and elite selection. Selection method and the precision used within the chromosome to represent numerical values had least influence. Our findings are robust over 60 numerical optimization problems.

  20. [Genetic determinants of pathogenicity of opportunistic enterobacteria isolated from children with acute intestinal infections].

    PubMed

    Anganova, E V; Dukhanina, A V; Savilov, E D

    2012-01-01

    Detection of nucleotide sequences of genes controlling synthesis of pathogenicity factors in clinical strains of opportunistic enterobacteria isolated from children with acute intestinal infections (AII), as well as their association with resistance to antibiotics and the course of the infectious process. 175 clinical strains obtained from children with AII undergoing treatment in Irkutsk state infectious diseases hospital (2007-2010) were studied. Primers to a number of genes detected in Escherichia coli pathogenicity islands, controlling type S and type 1 adhesion; formation of hemolysins; iron-regulatory protein synthesis; capsule formation were used in the study. PCR products analysis was performed by agar gel electrophoresis. Genetic determinants of pathogenicity were detected in bacteria genera Klebsiella, Citrobacter, Enterobacter, Proteus, Kluyvera, Morganella, Pantoea, Serratia. Fragments of hlyA and hlyB genes (hemolysin production) were detected more frequently; less frequently--sfaA, sfaG, fimA (adhesion), as well as irp-2 gene (synthesis of iron-regulatory protein). The largest set of genetic determinants of pathogenicity was noted in clinical strains of Klebsiella spp. Cultures with DNA fragments specific to genes of E. coli pathogenicity clusters were obtained predominately from children aged up to 3 years, had multiple antibiotic resistance and were isolated significantly more frequently in severe forms of AII when compared with strains in which these determinants were not detected. The studies performed showed that clinical strains of opportunistic bacteria isolated from patients with AII have a certain pathogenic potential, as evidenced by the presence of genetic pathogenicity markers in them.

  1. Epistatic genetic determinants of blood pressure and mortality in a salt-sensitive hypertension model.

    PubMed

    Cicila, George T; Morgan, Eric E; Lee, Soon Jin; Farms, Phyllis; Yerga-Woolwine, Shane; Toland, Edward J; Ramdath, Ramona S; Gopalakrishnan, Kathirvel; Bohman, Keith; Nestor-Kalinoski, Andrea L; Khuder, Sadik A; Joe, Bina

    2009-04-01

    Although genetic determinants protecting against the development of elevated blood pressure (BP) are well investigated, less is known regarding their impact on longevity. We concomitantly assessed genomic regions of rat chromosomes 3 and 7 (RNO3 and RNO7) carrying genetic determinants of BP without known epistasis, for their independent and combinatorial effects on BP and the presence of genetic determinants of survival using Dahl salt-sensitive (S) strains carrying congenic segments from Dahl salt-resistant (R) rats. Although congenic and bicongenic S.R strains carried independent BP quantitative trait loci within the RNO3 and RNO7 congenic regions, only the RNO3 allele(s) independently affected survival. The bicongenic S.R strain showed epistasis between R-rat RNO3 and RNO7 alleles for BP under salt-loading conditions, with less-than-additive effects observed on a 2% NaCl diet and greater-than-additive effects observed after prolonged feeding on a 4% NaCl diet. These RNO3 and RNO7 congenic region alleles had more-than-additive effects on survival. Increased survival of bicongenic compared with RNO3 congenic rats was attributable, in part, to maintaining lower BP despite chronic exposure to an increased dietary salt (4% NaCl) intake, with both strains showing delays in reaching highest BP. R-rat RNO3 alleles were also associated with superior systolic function, with the S.R bicongenic strain showing epistasis between R-rat RNO3 and RNO7 alleles leading to compensatory hypertrophy. Whether these alleles affect survival by additional actions within other BP-regulating tissues/organs remains unexplored. This is the first report of simultaneous detection of independent and epistatic loci dictating, in part, longevity in a hypertensive rat strain.

  2. Determination of Inherent Stresses by Measuring Deformations of Drilled Holes

    NASA Technical Reports Server (NTRS)

    Mathar, Josef

    1933-01-01

    Various methods have been proposed for determining the inherent stresses in structural components by disturbing their stress equilibrium through a mechanical device and measuring the resulting deformations. The methods used have disadvantages because they can be used only with specially shaped pieces (those with round or rectangular cross sections), that every form of test piece requires another kind of injury and hence of calculation, and the tested parts are rendered useless. The new test method, which seeks to eliminate these disadvantages, is likewise based on a disturbance of the equilibrium of forces, and indeed by drilling a hole which, however, is so small that the part can be used again. This method serves, among other things, for determining the inherent stresses in castings, welded parts, rolled structural shapes and finished structures.

  3. Determination of particle size distributions from acoustic wave propagation measurements

    SciTech Connect

    Spelt, P.D.; Norato, M.A.; Sangani, A.S.; Tavlarides, L.L.

    1999-05-01

    The wave equations for the interior and exterior of the particles are ensemble averaged and combined with an analysis by Allegra and Hawley [J. Acoust. Soc. Am. {bold 51}, 1545 (1972)] for the interaction of a single particle with the incident wave to determine the phase speed and attenuation of sound waves propagating through dilute slurries. The theory is shown to compare very well with the measured attenuation. The inverse problem, i.e., the problem of determining the particle size distribution given the attenuation as a function of frequency, is examined using regularization techniques that have been successful for bubbly liquids. It is shown that, unlike the bubbly liquids, the success of solving the inverse problem is limited since it depends strongly on the nature of particles and the frequency range used in inverse calculations. {copyright} {ital 1999 American Institute of Physics.}

  4. Intracellular pH-determination by fluorescence measurements.

    PubMed

    Visser, J W; Jongeling, A A; Tanke, H J

    1979-01-01

    A method was developed to determine the intracellular pH (pHi) of individual cells by use of fluorescence measurements. The method is based on the observation that the fluorescence excitation spectrum of fluorescein is pH-dependent. Fluorescence excitation spectra from individual rat bone marrow cells treated with fluorescein diacetate (FDA) were compared with those of fluorescein solutions of known pH values. Cells which were suspended in media of pH between 4.0 and 8.1 with high to normal buffering capacities had pHi values equal to those of the media. Cells suspended in media with low buffering capacities maintained a pH,i of 6.7 +/- 0.2. Preliminary results indicated that the pHi of individual cells may also be determined by using flow cytometry.

  5. Genetic and phenotypic stability of measures of neuroticism over 22 years.

    PubMed

    Wray, Naomi R; Birley, Andrew J; Sullivan, Patrick F; Visscher, Peter M; Martin, Nicholas G

    2007-10-01

    People meeting diagnostic criteria for anxiety or depressive disorders tend to score high on the personality scale of neuroticism. Studying this dimension of personality can therefore give insights into the etiology of important psychiatric disorders. Neuroticism can be assessed easily via self-report questionnaires in large population samples. We have examined the genetic and phenotypic stability of neuroticism, measured up to 4 times over 22 years, on different scales, on a data set of 4,999 families with over 20,000 individuals completing at least 1 neuroticism questionnaire. The neuroticism scales used were the Eysenck Personality Questionnaire revised (EPQ-R), the EPQ-R shortened form, and the NEO 5 factor inventory personality questionnaire. The estimates of heritability of the individual measures ranged from .26 +/- .04 to .36 +/- .03. Genetic, environmental, and phenotypic correlations averaged .91, .42, and .57 respectively. Despite the range in heritabilities, a more parsimonious 'repeatability model' of equal additive genetic variances and genetic correlations of unity could not be rejected. Use of multiple measures increases the effective heritability from .33 for a single measure to .43 for mean score because of the reduction in the estimate of the environmental variance, and this will increase power in genetic linkage or association studies of neuroticism.

  6. Genetic analysis of plasmid determinants for microcin J25 production and immunity.

    PubMed Central

    Solbiati, J O; Ciaccio, M; Farías, R N; Salomón, R A

    1996-01-01

    Microcin J25 (MccJ25) is a small peptide antibiotic produced by an Escherichia coli strain isolated from human feces. The genetic determinants for MccJ25 synthesis and immunity have been cloned from the low-copy-number wild-type plasmid pTUC1OO into the compatible vectors pBR322 and pACYC184. Physical and phenotypical analysis of insertion mutations and complementation tests defined three contiguous genes involved in MccJ25 production which span a region of about 2.2 kb. Immunity to the antibiotic is provided by an additional gene adjacent to the production region. PMID:8655570

  7. Stratospheric thickness determined directly from satellite radiance measurements.

    NASA Technical Reports Server (NTRS)

    Quiroz, R. S.; Gelman, M. E.

    1972-01-01

    Discussion of the use of satellite radiance data for determining the thickness of deep stratospheric layers. Empirical regression equations are shown to provide better estimates of stratospheric thickness than do mean weighted temperatures obtained from the Planck equation. The best regression equations were found for thick layers emitting a substantial portion of the CO2-band infrared radiation measured by satellites. By adding the layer thickness to the observed height field for the lower boundary, it is possible to construct constant-pressure maps at very high altitudes.

  8. Stratospheric thickness determined directly from satellite radiance measurements.

    NASA Technical Reports Server (NTRS)

    Quiroz, R. S.; Gelman, M. E.

    1972-01-01

    Discussion of the use of satellite radiance data for determining the thickness of deep stratospheric layers. Empirical regression equations are shown to provide better estimates of stratospheric thickness than do mean weighted temperatures obtained from the Planck equation. The best regression equations were found for thick layers emitting a substantial portion of the CO2-band infrared radiation measured by satellites. By adding the layer thickness to the observed height field for the lower boundary, it is possible to construct constant-pressure maps at very high altitudes.

  9. Determination of genetic relationships between evergreen azalea cultivars in China using AFLP markers*

    PubMed Central

    Zhou, Hong; Liao, Jin; Xia, Yi-ping; Teng, Yuan-wen

    2013-01-01

    Evergreen azaleas are among the most important ornamental shrubs in China. Today, there are probably over 300 cultivars preserved in different nurseries, but with little information available on the cultivar itself or relationships between cultivars. Amplified fragment length polymorphism (AFLP) markers were employed to determine the genetic relationships between evergreen azalea cultivars in China. One hundred and thirty genotypes collected from gardens and nurseries, including cultivars classified in the groups East, West, Hairy, and Summer, unknown cultivars, and close species, were analyzed using three primer pairs. A total of 408 polymorphic fragments were generated by AFLP reactions with an average of 136 fragments per primer pair. The average values of expected heterozygosity and Shannon’s information index were 0.3395 and 0.5153, respectively. Genetic similarities were generated based on Dice coefficients, used to construct a neighbor joining tree, and bootstrapped for 100 replicates in Treecon V1.3b. Principal coordinate analysis (PCO) was performed based on Dice distances using NTSYS-pc software. The AFLP technique was useful for analyzing genetic diversity in evergreen azaleas. Cluster analysis revealed that cultivars in the West and Summer groups were quite distinct from other groups in the four-group classification system and that the East and Hairy groups should be redefined. PMID:23549847

  10. [Genetic singularity coefficients of common vetch Vicia sativa L. accessions determined with molecular markers].

    PubMed

    Potokina, E K; Aleksandrova, T G

    2008-11-01

    Organization and practical application of ex situ collections require estimation of genetic differences between numerous accessions of local cultivars and field weed forms collected from the same ecological and geographical region and similar in their morphophysiological characteristics. A mathematical algorithm for estimating the degree of genetic singularity of a specimen in the system of local gene pool determined with the help of molecular markers is described. The utility of this algorithm is demonstrated by the example of classification of 677 common vetch accessions from the collection of the Vavilov Institute of Plant Industry from 11 ecological-geographic regions of Russia analyzed using AFLP. The proposed classification of accessions is the result of processing the AFLP data by weighting the marker traits based on their frequency in particular regions. This allowed each accession to be characterized according to the ratio of rare and frequent alleles as a genetic singularity coefficient. The proposed method is appropriate for any types of molecular markers. A practical result of its application is the classification of accessions using a five-point score scale, which can be added to descriptors of certificate databases and used for optimization of the work with collections.

  11. A population genetics perspective on the determinants of intra-tumor heterogeneity.

    PubMed

    Hu, Zheng; Sun, Ruping; Curtis, Christina

    2017-04-01

    Cancer results from the acquisition of somatic alterations in a microevolutionary process that typically occurs over many years, much of which is occult. Understanding the evolutionary dynamics that are operative at different stages of progression in individual tumors might inform the earlier detection, diagnosis, and treatment of cancer. Although these processes cannot be directly observed, the resultant spatiotemporal patterns of genetic variation amongst tumor cells encode their evolutionary histories. Such intra-tumor heterogeneity is pervasive not only at the genomic level, but also at the transcriptomic, phenotypic, and cellular levels. Given the implications for precision medicine, the accurate quantification of heterogeneity within and between tumors has become a major focus of current research. In this review, we provide a population genetics perspective on the determinants of intra-tumor heterogeneity and approaches to quantify genetic diversity. We summarize evidence for different modes of evolution based on recent cancer genome sequencing studies and discuss emerging evolutionary strategies to therapeutically exploit tumor heterogeneity. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Genetic and environmental determinants of the susceptibility of Amerindian derived populations for having hypertriglyceridemia.

    PubMed

    Aguilar-Salinas, Carlos A; Tusie-Luna, Teresa; Pajukanta, Päivi

    2014-07-01

    Here, we discuss potential explanations for the higher prevalence of hypertriglyceridemia in populations with an Amerindian background. Although environmental factors are the triggers, the search for the ethnic related factors that explain the increased susceptibility of the Amerindians is a promising area for research. The study of the genetics of hypertriglyceridemia in Hispanic populations faces several challenges. Ethnicity could be a major confounding variable to prove genetic associations. Despite that, the study of hypertriglyceridemia in Hispanics has resulted in significant contributions. Two GWAS reports have exclusively included Mexican mestizos. Fifty percent of the associations reported in Caucasians could be generalized to the Mexicans, but in many cases the Mexican lead SNP was different than that reported in Europeans. Both reports included new associations with apo B or triglycerides concentrations. The frequency of susceptibility alleles in Mexicans is higher than that found in Europeans for several of the genes with the greatest effect on triglycerides levels. An example is the SNP rs964184 in APOA5. The same trend was observed for ANGPTL3 and TIMD4 variants. In summary, we postulate that the study of the genetic determinants of hypertriglyceridemia in Amerindian populations which have major changes in their lifestyle, may prove to be a great resource to identify new genes and pathways associated with hypertriglyceridemia.

  13. Patients' knowledge of cystic fibrosis: genetic determinism and implications for treatment.

    PubMed

    Chapman, Elizabeth; Bilton, Diana

    2004-10-01

    This paper uses the self-regulation model of illness perceptions (Leventhal et al. , 1984) to consider the implications of different ways of thinking about the causes of illness. The relationship between anxiety/depression and knowledge or denial of illness is also considered. These issues are explored using adherence to treatment in cystic fibrosis (CF) as an example. Twenty-six CF patients took part in semistructured interviews and completed a standardized anxiety and depression scale (HAD, Zigmond and Snaith, 1983). Interview data were analyzed using Interpretative Phenomenological Analysis (Chapman and Smith, 2002). HAD data were analyzed using SPSS. The respondents displayed widely differing levels of knowledge of their condition. Some deterministic comments were also reported. Findings are discussed in relation to the information that physicians might provide to patients and families in the light of increasing knowledge about genetics in society and the genotyping of individuals with genetic conditions specifically. Any important gaps in patient knowledge could usefully be discussed at transition from pediatric to adult care and issues relating to control and genetic determinism discussed with the patients individually.

  14. Genetic and environmental determinants of the susceptibility of Amerindian derived populations for having hypertriglyceridemia

    PubMed Central

    Aguilar-Salinas, Carlos A.; Tusie-Luna, Teresa; Pajukanta, Päivi

    2014-01-01

    Here, we discuss potential explanations for the higher prevalence of hypertriglyceridemia in populations with an Amerindian background. Although environmental factors are the triggers, the search for the ethnic related factors that explains the increased susceptibility of the Amerindians is a promising area for research. The study of the genetics of hypertriglyceridemia in Hispanic populations faces several challenges. Ethnicity could be a major confounding variable to prove genetic associations. Despite that, the study of hypertriglyceridemia in Hispanics has resulted in significant contributions. Two GWAS reports have exclusively included Mexican mestizos. Fifty percent of the associations reported in Caucasians could be generalized to the Mexicans, but in many cases the Mexican lead SNP was different than that reported in Europeans. Both reports included new associations with apo B or triglycerides concentrations. The frequency of susceptibility alleles in Mexicans is higher than that found in Europeans for several of the genes with the greatest effect on triglycerides levels. An example is the SNP rs964184 in APOA5. The same trend was observed for ANGPTL3 and TIMD4 variants. In summary, we postulate that the study of the genetic determinants of hypertriglyceridemia in Amerindian populations which have major changes in their lifestyle, may prove to be a great resource to identify new genes and pathways associated with hypertriglyceridemia. PMID:24768220

  15. Multilevel selection 2: Estimating the genetic parameters determining inheritance and response to selection.

    PubMed

    Bijma, Piter; Muir, William M; Ellen, Esther D; Wolf, Jason B; Van Arendonk, Johan A M

    2007-01-01

    Interactions among individuals are universal, both in animals and in plants and in natural as well as domestic populations. Understanding the consequences of these interactions for the evolution of populations by either natural or artificial selection requires knowledge of the heritable components underlying them. Here we present statistical methodology to estimate the genetic parameters determining response to multilevel selection of traits affected by interactions among individuals in general populations. We apply these methods to obtain estimates of genetic parameters for survival days in a population of layer chickens with high mortality due to pecking behavior. We find that heritable variation is threefold greater than that obtained from classical analyses, meaning that two-thirds of the full heritable variation is hidden to classical analysis due to social interactions. As a consequence, predicted responses to multilevel selection applied to this population are threefold greater than classical predictions. This work, combined with the quantitative genetic theory for response to multilevel selection presented in an accompanying article in this issue, enables the design of selection programs to effectively reduce competitive interactions in livestock and plants and the prediction of the effects of social interactions on evolution in natural populations undergoing multilevel selection.

  16. Unique Regulatory Properties of Mesangial Cells Are Genetically Determined in the Rat

    PubMed Central

    Lai, Ping-Chin; Chiu, Ling-Yin; Srivastava, Prashant; Trento, Cristina; Dazzi, Francesco; Petretto, Enrico; Cook, H. Terence; Behmoaras, Jacques

    2014-01-01

    Mesangial cells are glomerular cells of stromal origin. During immune complex mediated crescentic glomerulonephritis (Crgn), infiltrating and proliferating pro-inflammatory macrophages lead to crescent formation. Here we have hypothesised that mesangial cells, given their mesenchymal stromal origin, show similar immunomodulatory properties as mesenchymal stem cells (MSCs), by regulating macrophage function associated with glomerular crescent formation. We show that rat mesangial cells suppress conA-stimulated splenocyte proliferation in vitro, as previously shown for MSCs. We then investigated mesangial cell-macrophage interaction by using mesangial cells isolated from nephrotoxic nephritis (NTN)-susceptible Wistar Kyoto (WKY) and NTN-resistant Lewis (LEW) rats. We first determined the mesangial cell transcriptome in WKY and LEW rats and showed that this is under marked genetic control. Supernatant transfer results show that WKY mesangial cells shift bone marrow derived macrophage (BMDM) phenotype to M1 or M2 according to the genetic background (WKY or LEW) of the BMDMs. Interestingly, these effects were different when compared to those of MSCs suggesting that mesangial cells can have unique immunomodulatory effects in the kidney. These results demonstrate the importance of the genetic background in the immunosuppressive effects of cells of stromal origin and specifically of mesangial cell-macrophage interactions in the pathophysiology of crescentic glomerulonephritis. PMID:25343449

  17. Ionization Properties of Phospholipids Determined by Zeta Potential Measurements

    PubMed Central

    Sathappa, Murugappan; Alder, Nathan N.

    2016-01-01

    Biological membranes are vital for diverse cellular functions such as maintaining cell and organelle structure, selective permeability, active transport, and signaling. The surface charge of the membrane bilayer plays a critical role in these myriad processes. For most biomembranes, the surface charge of anionic phospholipids contributes to the negative surface charge density within the interfacial region of the bilayer. To quantify surface charge, it is essential to understand the proton dissociation behavior of the titratable headgroups within such lipids. We describe a protocol that uses model membranes for electrokinetic zeta potential measurements coupled with data analysis using Gouy-Chapman-Stern formalism to determine the pKa value of the component lipids. A detailed example is provided for homogeneous bilayers composed of the monoanionic lipid phosphatidylglycerol. This approach can be adapted for the measurement of bilayers with a heterogeneous lipid combination, as well as for lipids with multiple titratable sites in the headgroup (e.g., cardiolipin). PMID:27928550

  18. Determination of Probe Volume Dimensions in Coherent Measurement Techniques

    NASA Technical Reports Server (NTRS)

    Tedder, Sarah A.; Weikl, Markus C.; Seeger, Thomas; Leipertz, Alfred

    2008-01-01

    When investigating combustion phenomena with pump-probe techniques, the spatial resolution is given by the overlapping region of the laser beams and thus defines the probe volume size. The size of this probe volume becomes important when the length scales of interest are on the same order or smaller. In this work, we present a new approach to measure the probe volume in three dimensions (3-D), which can be used to determine the probe volume length, diameter, and shape. The optical arrangement and data evaluation are demonstrated for a dual-pump dual-broadband coherent anti-Stokes Raman scattering (CARS) setup which is used for combustion diagnostics. This new approach offers a simple, quick alternative with more capabilities than formerly used probe volume measurement methods.

  19. Genetic Loci and Novel Discrimination Measures Associated with Blood Pressure Variation in African Americans Living in Tallahassee

    PubMed Central

    Quinlan, Jacklyn; Pearson, Laurel N.; Mitchell, Miaisha M.; Boston, Qasimah; Gravlee, Clarence C.; Mulligan, Connie J.

    2016-01-01

    Sequencing of the human genome and decades of genetic association and linkage studies have dramatically improved our understanding of the etiology of many diseases. However, the multiple causes of complex diseases are still not well understood, in part because genetic and sociocultural risk factors are not typically investigated concurrently. Hypertension is a leading risk factor for cardiovascular disease and afflicts more African Americans than any other racially defined group in the US. Few genetic loci for hypertension have been replicated across populations, which may reflect population-specific differences in genetic variants and/or inattention to relevant sociocultural factors. Discrimination is a salient sociocultural risk factor for poor health and has been associated with hypertension. Here we use a biocultural approach to study blood pressure (BP) variation in African Americans living in Tallahassee, Florida by genotyping over 30,000 single nucleotide polymorphisms (SNPs) and capturing experiences of discrimination using novel measures of unfair treatment of self and others (n = 157). We perform a joint admixture and genetic association analysis for BP that prioritizes regions of the genome with African ancestry. We only report significant SNPs that were confirmed through our simulation analyses, which were performed to determine the false positive rate. We identify eight significant SNPs in five genes that were previously associated with cardiovascular diseases. When we include measures of unfair treatment and test for interactions between SNPs and unfair treatment, we identify a new class of genes involved in multiple phenotypes including psychosocial distress and mood disorders. Our results suggest that inclusion of culturally relevant stress measures, like unfair treatment in African Americans, may reveal new genes and biological pathways relevant to the etiology of hypertension, and may also improve our understanding of the complexity of gene

  20. Genetic determinants of serum vitamin B12 and their relation to body mass index.

    PubMed

    Allin, Kristine H; Friedrich, Nele; Pietzner, Maik; Grarup, Niels; Thuesen, Betina H; Linneberg, Allan; Pisinger, Charlotta; Hansen, Torben; Pedersen, Oluf; Sandholt, Camilla H

    2016-12-19

    Lower serum vitamin B12 levels have been related to adverse metabolic health profiles, including adiposity. We used a Mendelian randomization design to test whether this relation might be causal. We included two Danish population-based studies (ntotal = 9311). Linear regression was used to test for associations between (1) serum vitamin B12 levels and body mass index (BMI), (2) genetic variants and serum vitamin B12 levels, and (3) genetic variants and BMI. The effect of a genetically determined decrease in serum vitamin B12 on BMI was estimated by instrumental variable regression. Decreased serum vitamin B12 associated with increased BMI (P < 1 × 10(-4)). A genetic risk score based on eight vitamin B12 associated variants associated strongly with serum vitamin B12 (P < 2 × 10(-43)), but not with BMI (P = 0.91). Instrumental variable regression showed that a 20% decrease in serum vitamin B12 was associated with a 0.09 kg/m(2) (95% CI 0.05; 0.13) increase in BMI (P = 3 × 10(-5)), whereas a genetically induced 20% decrease in serum vitamin B12 had no effect on BMI [-0.03 (95% CI -0.22; 0.16) kg/m(2)] (P = 0.74). Nevertheless, the strongest serum vitamin B12 variant, FUT2 rs602662, which was excluded from the B12 genetic risk score due to potential pleiotropic effects, showed a per allele effect of 0.15 kg/m(2) (95% CI 0.01; 0.32) on BMI (P = 0.03). This association was accentuated including two German cohorts (ntotal = 5050), with a combined effect of 0.19 kg/m(2) (95% CI 0.08; 0.30) (P = 4 × 10(-4)). We found no support for a causal role of decreased serum vitamin B12 levels in obesity. However, our study suggests that FUT2, through its regulation of the cross-talk between gut microbes and the human host, might explain a part of the observational association between serum vitamin B12 and BMI.

  1. Biological and genetic determinants of atopy are predictors of immediate-type allergy to betalactams, in Spain.

    PubMed

    Cornejo-García, J A; Guéant-Rodriguez, R-M; Torres, M J; Blanca-Lopez, N; Tramoy, D; Romano, A; Blanca, M; Guéant, J-L

    2012-09-01

    Betalactam (BL) immediate-type allergy is influenced by environmental and genetic determinants, as illustrated by differences in worldwide prevalence and ethnicity from a same area and by associations with genes related to atopy. To evaluate the association of atopy with BL allergy. We measured specific Immunoglobulin E (IgE) against prevalent allergens and genetic predictors of atopy, IL13, IL4, IL4RA, IL4, and TNFA, in 340 patients and 340 controls from South of Spain. Total IgE and IgE against mites were at higher concentration in patients. Patients with high total IgE and IgE against prevalent allergens had a slower decrease in BL IgE than nonatopic patients. IL4RA I50V and Q551R were associated with IgE against prevalent allergens and total IgE, respectively, and were also predictors of BL allergy. Interacting determinants of atopy, total IgE, IgE against prevalent allergens, and IL4RA polymorphisms, contribute to the high prevalence of BL allergy in South of Spain. © 2012 John Wiley & Sons A/S.

  2. Step Complexity Measure for Emergency Operating Procedures - Determining Weighting Factors

    SciTech Connect

    Park, Jinkyun; Jung, Wondea; Kim, Jaewhan; Ha, Jaejoo

    2003-09-15

    In complex systems, such as nuclear power plants (NPPs) or airplane control systems, human error has been regarded as the primary cause of many events. Therefore, to ensure system safety, extensive effort has been made to identify the significant factors that can cause human error. According to related studies, written manuals or operating procedures are revealed as one of the important factors, and the understandability is pointed out as one of the major reasons for procedure-related human errors.Many qualitative checklists have been suggested to evaluate emergency operating procedures (EOPs) of NPPs so as to minimize procedure-related human errors. However, since qualitative evaluations using checklists have some drawbacks, a quantitative measure that can quantify the complexity of EOPs is indispensable.From this necessity, Park et al. suggested the step complexity (SC) measure to quantify the complexity of procedural steps included in EOPs. To verify the appropriateness of the SC measure, averaged step performance time data obtained from emergency training records of the loss-of-coolant accident (LOCA) and the excess steam demand event were compared with estimated SC scores. However, although averaged step performance time data and estimated SC scores show meaningful correlation, some important issues such as determining proper weighting factors have to be clarified to ensure the appropriateness of the SC measure. These were not properly dealt with due to a lack of backup data.In this paper, to resolve one of the important issues, emergency training records are additionally collected and analyzed in order to determine proper weighting factors. The total number of collected records is 66, and the training scenarios cover five emergency conditions including the LOCA, the steam generator tube rupture, the loss of all feedwater, the loss of off-site power, and the station blackout. From these records, average step performance time data are retrieved, and new

  3. Determination of measurement uncertainty on coordinate measurement machines by measurement decomposition and utilization of canonical artifacts

    SciTech Connect

    Rasnick, B.; Cox, B.; Sherrill, M.

    1996-08-01

    The requirement for primary-level calibration of complex forms, e.g., gear profiles, has led to development of a method for quantifying the measurement uncertainty on the artifact being calibrated that does not rely on a transfer comparison. This method, developed jointly by National Institute of Standards and Technology (NIST) and Oak Ridge Metrology Center (ORMC) personnel, consists of breaking down the measurement method into simpler components and quantifying these components using generally accepted artifacts with low uncertainties (gage blocks, ring gages, spheres, etc.). Once quantified, these components are added vectorially according to NIST Technical Note 1297, 1994 Edition. Verification of this method can be accomplished by intercomparisons with other methods and laboratories.

  4. Determining confounding sensitivities in eddy current thin film measurements

    NASA Astrophysics Data System (ADS)

    Gros, Ethan; Udpa, Lalita; Smith, James A.; Wachs, Katelyn

    2017-02-01

    Eddy current (EC) techniques are widely used in industry to measure the thickness of non-conductive films on a metal substrate. This is done by using a system whereby a coil carrying a high-frequency alternating current is used to create an alternating magnetic field at the surface of the instrument's probe. When the probe is brought near a conductive surface, the alternating magnetic field will induce ECs in the conductor. The substrate characteristics and the distance of the probe from the substrate (the coating thickness) affect the magnitude of the ECs. The induced currents load the probe coil affecting the terminal impedance of the coil. The measured probe impedance is related to the lift off between coil and conductor as well as conductivity of the test sample. For a known conductivity sample, the probe impedance can be converted into an equivalent film thickness value. The EC measurement can be confounded by a number of measurement parameters. It was the goal of this research to determine which physical properties of the measurement set-up and sample can adversely affect the thickness measurement. The eddy-current testing was performed using a commercially available, hand-held eddy-current probe (ETA3.3H spring-loaded eddy probe running at 8 MHz) that comes with a stand to hold the probe. The stand holds the probe and adjusts the probe on the z-axis to help position the probe in the correct area as well as make precise measurements. The signal from the probe was sent to a hand-held readout, where the results are recorded directly in terms of liftoff or film thickness. Understanding the effect of certain factors on the measurements of film thickness, will help to evaluate how accurate the ETA3.3H spring-loaded eddy probe was at measuring film thickness under varying experimental conditions. This research studied the effects of a number of factors such as i) conductivity, ii) edge effect, iii) surface finish of base material and iv) cable condition.

  5. Genetically determined neuromuscular disorders of some Roma families living in Hungary.

    PubMed

    Aranka, Laszlo; Peter, Mayer; Jeno, Kobor; Katalin, Racz; Gyula, Talosi; Emoke, Endreffy; Agnes, Herczegfalvi; Tibor, Hortobagyi; Laszlo, Tiszlavicz; Edit, Bereg; Marta, Katona; Janos, Szabo; Veronika, Karcagi

    2009-01-30

    The authors discuss the clinical and molecular genetic aspects of genetically determined neuromuscular disorders of some Roma families living in Hungary. Among the autosomal recessively inherited spinal muscular atrophic (SMA) group, 8 Caucasian children had the typical 7-8 exonal deletions of the SMA gene, but only 2 patients belonged to the Roma population. There was no difference in the molecular genetic findings among the Caucasian and the Roma SMA patients. All of them had 7-8 exonal deletions of the SMA gene. We wanted to call attention to the founder mutation of the Roma population in 7 patients suffering from congenital myasthenia (CMS) from 3 Roma families. The 1267G deletion for CMS was detected by molecular genetic method. Clinical onset was pubertal and relatively slow progression of specific and phenotypic features for this founder mutation of acetyl-cholin receptor epsylon gene. In 2 patients (sister and brother) the sarcoglycanopathy 2C type C283Q mutation was proven in one Roma family suffering from limb-girdle muscular dystrophy (LGMD). Two out of the three facioscapular-humeral dystrophy (FSHD) Roma families carried 21.8 kb and 18.5 kb alleles in FSHD A1 gene (D4S139). In one family together with prenatal diagnosis founder mutation in FSHD A1 gene was detected, according to the autosomal dominant (AD) inheritance. In (F2) prenatal diagnosis was carried out, 18.5 kb/18.5 kb homozygosity was proven in the fetus, so the pregnancy was interrupted. In the CMS, LGMD and FSHD Roma patients ancient typical Roma founder mutations were found.

  6. Genetic and environmental determinants of plasma total homocysteine levels: impact of population-wide folate fortification.

    PubMed

    Nagele, Peter; Meissner, Konrad; Francis, Amber; Födinger, Manuela; Saccone, Nancy L

    2011-07-01

    Folate metabolism is an important target for drug therapy. Drug-induced inhibition of folate metabolism often causes an elevation of plasma total homocysteine (tHcy). Plasma tHcy levels are influenced by several nongenetic (e.g. folate intake, age, smoking) as well as genetic factors. Over the last decade, several countries have implemented a nationwide folate fortification program of all grain products. This investigation sought to determine the impact of folate fortification on the relative contribution of environmental and genetic factors to the variability of plasma tHcy. Two cohorts were compared in this study, one from the United States (with folate fortification, n=281) and one from Austria (without folate fortification, n=139). Several environmental factors as well as previously identified gene variants important for tHcy levels (MTHFR C677T, MTHFR A1298C, MTRR A66G) were examined for their ability to predict plasma tHcy in a multiple linear regression model. Nongenetic, environmental factors had a comparable influence on plasma tHcy between the two cohorts (R: approximately 0.19). However, after adjusting for other covariates, the tested gene variants had a substantially smaller impact among patients from the folate-fortified cohort (R=0.021) compared with the nonfolate-fortified cohort (R=0.095). The MTHFR C677T polymorphism was the single most important genetic factor. Male sex, smoking, and folate levels were important predictors for nonfolate-fortified patients; age was for folate-fortified patients. Population wide folate fortification had a significant effect on the variability of plasma tHcy and reduced the influence of genetic factors, most importantly the MTHFR 677TT genotype, and may be an important confounder for a personalized drug therapy.

  7. Genetic determination of the hypothalamic-pituitary-thyroid axis: where do we stand?

    PubMed

    Medici, Marco; Visser, W Edward; Visser, Theo J; Peeters, Robin P

    2015-04-01

    For a long time it has been known that both hypo- and hyperthyroidism are associated with an increased risk of morbidity and mortality. In recent years, it has also become clear that minor variations in thyroid function, including subclinical dysfunction and variation in thyroid function within the reference range, can have important effects on clinical endpoints, such as bone mineral density, depression, metabolic syndrome, and cardiovascular mortality. Serum thyroid parameters show substantial interindividual variability, whereas the intraindividual variability lies within a narrow range. This suggests that every individual has a unique hypothalamus-pituitary-thyroid axis setpoint that is mainly determined by genetic factors, and this heritability has been estimated to be 40-60%. Various mutations in thyroid hormone pathway genes have been identified in persons with thyroid dysfunction or altered thyroid function tests. Because these causes are rare, many candidate gene and linkage studies have been performed over the years to identify more common variants (polymorphisms) associated with thyroid (dys)function, but only a limited number of consistent associations have been found. However, in the past 5 years, advances in genetic research have led to the identification of a large number of new candidate genes. In this review, we provide an overview of the current knowledge about the polygenic basis of thyroid (dys)function. This includes new candidate genes identified by genome-wide approaches, what insights these genes provide into the genetic basis of thyroid (dys)function, and which new techniques will help to further decipher the genetic basis of thyroid (dys)function in the near future.

  8. An Evolving Genetic Architecture Interacts with Hill-Robertson Interference to Determine the Benefit of Sex.

    PubMed

    Whitlock, Alexander O B; Peck, Kayla M; Azevedo, Ricardo B R; Burch, Christina L

    2016-06-01

    Sex is ubiquitous in the natural world, but the nature of its benefits remains controversial. Previous studies have suggested that a major advantage of sex is its ability to eliminate interference between selection on linked mutations, a phenomenon known as Hill-Robertson interference. However, those studies may have missed both important advantages and important disadvantages of sexual reproduction because they did not allow the distributions of mutational effects and interactions (i.e., the genetic architecture) to evolve. Here we investigate how Hill-Robertson interference interacts with an evolving genetic architecture to affect the evolutionary origin and maintenance of sex by simulating evolution in populations of artificial gene networks. We observed a long-term advantage of sex-equilibrium mean fitness of sexual populations exceeded that of asexual populations-that did not depend on population size. We also observed a short-term advantage of sex-sexual modifier mutations readily invaded asexual populations-that increased with population size, as was observed in previous studies. We show that the long- and short-term advantages of sex were both determined by differences between sexual and asexual populations in the evolutionary dynamics of two properties of the genetic architecture: the deleterious mutation rate ([Formula: see text]) and recombination load ([Formula: see text]). These differences resulted from a combination of selection to minimize [Formula: see text] which is experienced only by sexuals, and Hill-Robertson interference experienced primarily by asexuals. In contrast to the previous studies, in which Hill-Robertson interference had only a direct impact on the fitness advantages of sex, the impact of Hill-Robertson interference in our simulations was mediated additionally by an indirect impact on the efficiency with which selection acted to reduce [Formula: see text]. Copyright © 2016 by the Genetics Society of America.

  9. Challenges identifying genetic determinants of pediatric cancers--the childhood leukemia experience.

    PubMed

    Sinnett, Daniel; Labuda, Damian; Krajinovic, Maja

    2006-01-01

    Pediatric cancers affect approximately 1 in every 500 children before the age of 15. Little is known about the etiology of this heterogeneous group of diseases despite the fact they constitute the major cause of death by disease among this population. Because of its relatively high prevalence, most of the work done in pediatric oncogenetics has been focused on leukemias, particularly acute lymphoblastic leukemia (ALL). Although it is now well accepted that genetic variation plays a significant role in determining individual's cancer susceptibility, few studies have explored genetic susceptibility to childhood leukemia with respect to common polymorphisms. The biochemical and genetic mechanisms contributing to cancer susceptibility are numerous and can be grouped into broad categories: (1) cellular growth and differentiation, (2) DNA replication and repair, (3) metabolism of carcinogens (4) apoptosis, (5) oxidative stress response and (6) cell cycle. To evaluate whether candidate genes in these pathways are involved in childhood leukemogenesis, we conducted case-control studies. We showed that leukemogenesis in children may be associated with DNA variants in some of these genes and that the combination of genotypes seems to be more predictive of risk than either of them independently. We also observed that, at least at some loci, the parental genetics might be important in predicting the risk of cancer in this pediatric model of a complex disease. Taken together, these results indicate that the investigation of a single enzyme and/or a single genotype might not be sufficient to explain the etiology of childhood leukemia because of the complexity of the environment and that of the inter-individual variability in cancer susceptibility.

  10. Semantic Referencing - Determining Context Weights for Similarity Measurement

    NASA Astrophysics Data System (ADS)

    Janowicz, Krzysztof; Adams, Benjamin; Raubal, Martin

    Semantic similarity measurement is a key methodology in various domains ranging from cognitive science to geographic information retrieval on the Web. Meaningful notions of similarity, however, cannot be determined without taking additional contextual information into account. One way to make similarity measures context-aware is by introducing weights for specific characteristics. Existing approaches to automatically determine such weights are rather limited or require application specific adjustments. In the past, the possibility to tweak similarity theories until they fit a specific use case has been one of the major criticisms for their evaluation. In this work, we propose a novel approach to semi-automatically adapt similarity theories to the user's needs and hence make them context-aware. Our methodology is inspired by the process of georeferencing images in which known control points between the image and geographic space are used to compute a suitable transformation. We propose to semi-automatically calibrate weights to compute inter-instance and inter-concept similarities by allowing the user to adjust pre-computed similarity rankings. These known control similarities are then used to reference other similarity values.

  11. Determination of the electronics transfer function for current transient measurements

    NASA Astrophysics Data System (ADS)

    Scharf, Christian; Klanner, Robert

    2015-04-01

    We describe a straight-forward method for determining the transfer function of the readout of a sensor for the situation in which the current transient of the sensor can be precisely simulated. The method relies on the convolution theorem of Fourier transforms. The specific example is a planar silicon pad diode. The charge carriers in the sensor are produced by picosecond lasers with light of wavelengths of 675 and 1060 nm. The transfer function is determined from the 1060 nm data with the pad diode biased at 1000 V. It is shown that the simulated sensor response convoluted with this transfer function provides an excellent description of the measured transients for laser light of both wavelengths. The method has been applied successfully for the simulation of current transients of several different silicon pad diodes. It can also be applied for the analysis of transient-current measurements of radiation-damaged solid state sensors, as long as sensors properties, like high-frequency capacitance, are not too different.

  12. Sap flow measurements to determine the transpiration of facade greenings

    NASA Astrophysics Data System (ADS)

    Hölscher, Marie-Therese; Nehls, Thomas; Wessolek, Gerd

    2014-05-01

    Facade greening is expected to make a major contribution to the mitigation of the urban heat-island effect through transpiration cooling, thermal insulation and shading of vertical built structures. However, no studies are available on water demand and the transpiration of urban vertical green. Such knowledge is needed as the plants must be sufficiently watered, otherwise the posited positive effects of vertical green can turn into disadvantages when compared to a white wall. Within the framework of the German Research Group DFG FOR 1736 "Urban Climate and Heat Stress" this study aims to test the practicability of the sap flow technique for transpiration measurements of climbing plants and to obtain potential transpiration rates for the most commonly used species. Using sap flow measurements we determined the transpiration of Fallopia baldschuanica, Parthenocissus tricuspidata and Hedera helix in pot experiments (about 1 m high) during the hot summer period from August 17th to August 30th 2012 under indoor conditions. Sap flow measurements corresponded well to simultaneous weight measurement on a daily base (factor 1.19). Fallopia baldschuanica has the highest daily transpiration rate based on leaf area (1.6 mm d-1) and per base area (5.0 mm d-1). Parthenocissus tricuspidata and Hedera helix show transpiration rates of 3.5 and 0.4 mm d-1 (per base area). Through water shortage, transpiration strongly decreased and leaf temperature measured by infrared thermography increased by 1 K compared to a well watered plant. We transferred the technique to outdoor conditions and will present first results for facade greenings in the inner-city of Berlin for the hottest period in summer 2013.

  13. Determining the Uncertainty of X-Ray Absorption Measurements

    PubMed Central

    Wojcik, Gary S.

    2004-01-01

    X-ray absorption (or more properly, x-ray attenuation) techniques have been applied to study the moisture movement in and moisture content of materials like cement paste, mortar, and wood. An increase in the number of x-ray counts with time at a location in a specimen may indicate a decrease in moisture content. The uncertainty of measurements from an x-ray absorption system, which must be known to properly interpret the data, is often assumed to be the square root of the number of counts, as in a Poisson process. No detailed studies have heretofore been conducted to determine the uncertainty of x-ray absorption measurements or the effect of averaging data on the uncertainty. In this study, the Poisson estimate was found to adequately approximate normalized root mean square errors (a measure of uncertainty) of counts for point measurements and profile measurements of water specimens. The Poisson estimate, however, was not reliable in approximating the magnitude of the uncertainty when averaging data from paste and mortar specimens. Changes in uncertainty from differing averaging procedures were well-approximated by a Poisson process. The normalized root mean square errors decreased when the x-ray source intensity, integration time, collimator size, and number of scanning repetitions increased. Uncertainties in mean paste and mortar count profiles were kept below 2 % by averaging vertical profiles at horizontal spacings of 1 mm or larger with counts per point above 4000. Maximum normalized root mean square errors did not exceed 10 % in any of the tests conducted. PMID:27366627

  14. Variation in salamander tail regeneration is associated with genetic factors that determine tail morphology.

    PubMed

    Voss, Gareth J; Kump, D Kevin; Walker, John A; Voss, S Randal

    2013-01-01

    Very little is known about the factors that cause variation in regenerative potential within and between species. Here, we used a genetic approach to identify heritable genetic factors that explain variation in tail regenerative outgrowth. A hybrid ambystomatid salamander (Ambystoma mexicanum x A. andersoni) was crossed to an A. mexicanum and 217 offspring were induced to undergo metamorphosis and attain terrestrial adult morphology using thyroid hormone. Following metamorphosis, each salamander's tail tip was amputated and allowed to regenerate, and then amputated a second time and allowed to regenerate. Also, DNA was isolated from all individuals and genotypes were determined for 187 molecular markers distributed throughout the genome. The area of tissue that regenerated after the first and second amputations was highly positively correlated across males and females. Males presented wider tails and regenerated more tail tissue during both episodes of regeneration. Approximately 66-68% of the variation in regenerative outgrowth was explained by tail width, while tail length and genetic sex did not explain a significant amount of variation. A small effect QTL was identified as having a sex-independent effect on tail regeneration, but this QTL was only identified for the first episode of regeneration. Several molecular markers significantly affected regenerative outgrowth during both episodes of regeneration, but the effect sizes were small (<4%) and correlated with tail width. The results show that ambysex and minor effect QTL explain variation in adult tail morphology and importantly, tail width. In turn, tail width at the amputation plane largely determines the rate of regenerative outgrowth. Because amputations in this study were made at approximately the same position of the tail, our results resolve an outstanding question in regenerative biology: regenerative outgrowth positively co-varies as a function of tail width at the amputation site.

  15. Variation in Recombination Rate and Its Genetic Determinism in Sheep Populations.

    PubMed

    Petit, Morgane; Astruc, Jean-Michel; Sarry, Julien; Drouilhet, Laurence; Fabre, Stéphane; Moreno, Carole; Servin, Bertrand

    2017-08-09

    Recombination is a complex biological process that results from a cascade of multiple events during meiosis. Understanding the genetic determinism of recombination can help to understand if and how these events are interacting. To tackle this question, we studied the patterns of recombination in sheep, using multiple approaches and datasets. We constructed male recombination maps in a dairy breed from the south of France (the Lacaune breed) at a fine scale by combining meiotic recombination rates from a large pedigree genotyped with a 50K SNP array and historical recombination rates from a sample of unrelated individuals genotyped with a 600K SNP array. This analysis revealed recombination patterns in sheep similar to other mammals but also genome regions that have likely been affected by directional and diversifying selection. We estimated the average recombination rate of Lacaune sheep at 1.5 cM/Mb, identified about 50,000 crossover hotspots on the genome and found a high correlation between historical and meiotic recombination rate estimates. A genome-wide association study revealed two major loci affecting inter-individual variation in recombination rate in Lacaune, including the RNF212 and HEI10 genes and possibly two other loci of smaller effects including the KCNJ15 and FSHR genes. The comparison of these new results to those obtained previously in a distantly related population of domestic sheep (the Soay) revealed that Soay and Lacaune males have a very similar distribution of recombination along the genome. The two datasets were thus combined to create more precise male meiotic recombination maps in Sheep. However, despite their similar recombination maps, Soay and Lacaune males were found to exhibit different heritabilities and QTL effects for inter-individual variation in genome-wide recombination rates. This highlights the robustness of recombination patterns to underlying variation in their genetic determinism. Copyright © 2017, Genetics.

  16. Variation in Salamander Tail Regeneration Is Associated with Genetic Factors That Determine Tail Morphology

    PubMed Central

    Voss, Gareth J.; Kump, D. Kevin; Walker, John A.; Voss, S. Randal

    2013-01-01

    Very little is known about the factors that cause variation in regenerative potential within and between species. Here, we used a genetic approach to identify heritable genetic factors that explain variation in tail regenerative outgrowth. A hybrid ambystomatid salamander (Ambystoma mexicanum x A. andersoni) was crossed to an A. mexicanum and 217 offspring were induced to undergo metamorphosis and attain terrestrial adult morphology using thyroid hormone. Following metamorphosis, each salamander’s tail tip was amputated and allowed to regenerate, and then amputated a second time and allowed to regenerate. Also, DNA was isolated from all individuals and genotypes were determined for 187 molecular markers distributed throughout the genome. The area of tissue that regenerated after the first and second amputations was highly positively correlated across males and females. Males presented wider tails and regenerated more tail tissue during both episodes of regeneration. Approximately 66–68% of the variation in regenerative outgrowth was explained by tail width, while tail length and genetic sex did not explain a significant amount of variation. A small effect QTL was identified as having a sex-independent effect on tail regeneration, but this QTL was only identified for the first episode of regeneration. Several molecular markers significantly affected regenerative outgrowth during both episodes of regeneration, but the effect sizes were small (<4%) and correlated with tail width. The results show that ambysex and minor effect QTL explain variation in adult tail morphology and importantly, tail width. In turn, tail width at the amputation plane largely determines the rate of regenerative outgrowth. Because amputations in this study were made at approximately the same position of the tail, our results resolve an outstanding question in regenerative biology: regenerative outgrowth positively co-varies as a function of tail width at the amputation site. PMID:23843997

  17. Combining Quantitative Genetic Footprinting and Trait Enrichment Analysis to Identify Fitness Determinants of a Bacterial Pathogen

    PubMed Central

    Wiles, Travis J.; Norton, J. Paul; Russell, Colin W.; Dalley, Brian K.; Fischer, Kael F.; Mulvey, Matthew A.

    2013-01-01

    Strains of Extraintestinal Pathogenic Escherichia c oli (ExPEC) exhibit an array of virulence strategies and are a major cause of urinary tract infections, sepsis and meningitis. Efforts to understand ExPEC pathogenesis are challenged by the high degree of genetic and phenotypic variation that exists among isolates. Determining which virulence traits are widespread and which are strain-specific will greatly benefit the design of more effective therapies. Towards this goal, we utilized a quantitative genetic footprinting technique known as transposon insertion sequencing (Tn-seq) in conjunction with comparative pathogenomics to functionally dissect the genetic repertoire of a reference ExPEC isolate. Using Tn-seq and high-throughput zebrafish infection models, we tracked changes in the abundance of ExPEC variants within saturated transposon mutant libraries following selection within distinct host niches. Nine hundred and seventy bacterial genes (18% of the genome) were found to promote pathogen fitness in either a niche-dependent or independent manner. To identify genes with the highest therapeutic and diagnostic potential, a novel Trait Enrichment Analysis (TEA) algorithm was developed to ascertain the phylogenetic distribution of candidate genes. TEA revealed that a significant portion of the 970 genes identified by Tn-seq have homologues more often contained within the genomes of ExPEC and other known pathogens, which, as suggested by the first axiom of molecular Koch's postulates, is considered to be a key feature of true virulence determinants. Three of these Tn-seq-derived pathogen-associated genes—a transcriptional repressor, a putative metalloendopeptidase toxin and a hypothetical DNA binding protein—were deleted and shown to independently affect ExPEC fitness in zebrafish and mouse models of infection. Together, the approaches and observations reported herein provide a resource for future pathogenomics-based research and highlight the diversity of

  18. [Genetic programming used for the measurement of CO concentration based on nondispersive infrared absorption spectroscopy].

    PubMed

    Chen, Jin; Duan, Fa-jie; Tong, Ying; Gao, Qiang

    2011-07-01

    Nondispersive infrared absorption spectroscopy(NDIR) is an important method to measure CO concentration in the air. In the present study, an open-path measurement system and continuous measuring device was developed, and genetic programming was used to establish the calibration model of subjects' light intensity sampling values. Continuous measurements were carried out in 10 different concentration of CO, and 40 sampled data were acquired and analyzed. For validation set, the correlation coefficient was 0.9997. The biggest relative error of validation was 4.00%, and the average relative error was 1.11%. Results show that genetic programming can be a good method for the modeling of gas concentration measurements equipped with NDIR systems.

  19. Biased Random-Key Genetic Algorithms for the Winner Determination Problem in Combinatorial Auctions.

    PubMed

    de Andrade, Carlos Eduardo; Toso, Rodrigo Franco; Resende, Mauricio G C; Miyazawa, Flávio Keidi

    2015-01-01

    In this paper we address the problem of picking a subset of bids in a general combinatorial auction so as to maximize the overall profit using the first-price model. This winner determination problem assumes that a single bidding round is held to determine both the winners and prices to be paid. We introduce six variants of biased random-key genetic algorithms for this problem. Three of them use a novel initialization technique that makes use of solutions of intermediate linear programming relaxations of an exact mixed integer linear programming model as initial chromosomes of the population. An experimental evaluation compares the effectiveness of the proposed algorithms with the standard mixed linear integer programming formulation, a specialized exact algorithm, and the best-performing heuristics proposed for this problem. The proposed algorithms are competitive and offer strong results, mainly for large-scale auctions.

  20. Evidence for genetically influenced caste determination in phylogenetically diverse species of the termite genus Reticulitermes

    PubMed Central

    Kitade, Osamu; Hoshi, Masahiro; Odaira, Shiori; Asano, Akiko; Shimizu, Manami; Hayashi, Yoshinobu; Lo, Nathan

    2011-01-01

    A number of social insect species have recently been shown to have genetically influenced caste determination (GCD), challenging the conventional view that caste determination should be strictly environmental. To date, GCD has been found in phylogenetically isolated species; examples of GCD being present in multiple species of a genus are lacking. Through crossing experiments of neotenic (juvenile) reproductives, we have recently provided the first evidence for a royal versus worker GCD in the termite Reticulitermes speratus. To elucidate whether this system is more widespread, we performed crossing experiments using three additional Reticulitermes species. Offspring caste and sex ratios were found to be highly similar to those found previously in R. speratus, raising the possibility that GCD was present in an ancestral lineage of Reticulitermes, and subsequently maintained throughout several episodes of speciation. PMID:20980291

  1. A comparative analysis of the D-criteria used to determine genetic links of small bodies

    NASA Astrophysics Data System (ADS)

    Sokolova, M. G.; Kondratyeva, E. D.; Nefedyev, Y. A.

    2013-10-01

    In this article the D-criteria, which can be used to determine the genetic relationships of small bodies with their parent bodies in the solar system, are estimated. Drummond (1981), Southworth and Hawkins (1963), Jopek (1993), dynamic (Kalinin and Kulikova, 2007; Holshevnikov and Titov, 2007) D-criteria were analysed. It was found that the Drummond criterion is less sensitive to errors of observations and its upper limit does not exceed 0.2. The Southworth-Hawkins and Jopek D-criteria are more stable and have good convergence. Limiting values, which vary in the range of 0.3-0.6 (except for the Lyrids), were determined on the basis of the analysis of six meteor showers for the Southworth-Hawkins and Jopek criteria.

  2. First Attempt of Orbit Determination of SLR Satellites and Space Debris Using Genetic Algorithms

    NASA Astrophysics Data System (ADS)

    Deleflie, F.; Coulot, D.; Descosta, R.; Fernier, A.; Richard, P.

    2013-08-01

    We present an orbit determination method based on genetic algorithms. Contrary to usual estimation methods mainly based on least-squares methods, these algorithms do not require any a priori knowledge of the initial state vector to be estimated. These algorithms can be applied when a new satellite is launched or for uncatalogued objects that appear in images obtained from robotic telescopes such as the TAROT ones. We show in this paper preliminary results obtained from an SLR satellite, for which tracking data acquired by the ILRS network enable to build accurate orbital arcs at a few centimeter level, which can be used as a reference orbit ; in this case, the basic observations are made up of time series of ranges, obtained from various tracking stations. We show as well the results obtained from the observations acquired by the two TAROT telescopes on the Telecom-2D satellite operated by CNES ; in that case, the observations are made up of time series of azimuths and elevations, seen from the two TAROT telescopes. The method is carried out in several steps: (i) an analytical propagation of the equations of motion, (ii) an estimation kernel based on genetic algorithms, which follows the usual steps of such approaches: initialization and evolution of a selected population, so as to determine the best parameters. Each parameter to be estimated, namely each initial keplerian element, has to be searched among an interval that is preliminary chosen. The algorithm is supposed to converge towards an optimum over a reasonable computational time.

  3. [Analysis of genetic determinants of multidrug and extensively drug-resistant Mycobacterium tuberculosis using oligonucleotide microchip].

    PubMed

    Zimenkov, D V; Kulagina, E V; Antonova, O V; Surzhikov, S A; Bespiatykh, Iu A; Shitikov, E A; Il'ina, E N; Mikhaĭlovich, V M; Zasedatelev, A S; Griadunov, D A

    2014-01-01

    Steadily growing resistance of the tuberculosis causative agent towards a broad spectrum of anti-tuberculosis drugs calls for rapid and reliable methods for identifying the genetic determinants responsible for this resistance. In this study, we present a biochip-based method for simultaneous identification of mutations within rpoB gene associated with rifampin resistance, mutations in katG, inhA, ahpC genes responsible for isoniazid resistance, mutations within the regions of gyrA and gyrB genes leading to fluoroquinolones resistance, and mutations in the rrs gene and the eis promoter region associated with the resistance to kanamycin, capreomycin and amikacin. The oligonucleotide microchip, as the core element of this assay, provides simultaneous identification of 99 mutations in the format "one sample--one PCR--one microchip", and it makes it possible to complete analysis of multi-drug-resistant and extensively drug-resistant tuberculosis within a single day. The tests on 63 Mycobacterium tuberculosis clinical isolates with different resistance profiles using the developed approach allows us to reveal the spectrum of drug-resistance associated mutations, and to estimate the significance of the inclusion of extra genetic loci in the determination of M. tuberculosis drug resistance.

  4. The importance of genetic verification for determination of Atlantic salmon in north Pacific waters

    USGS Publications Warehouse

    Nielsen, J.L.; Williams, I.; Sage, G.K.; Zimmerman, C.E.

    2003-01-01

    Genetic analyses of two unknown but putative Atlantic salmon Salmo salar captured in the Copper River drainage, Alaska, demonstrated the need for validation of morphologically unusual fishes. Mitochondrial DNA sequences (control region and cytochrome b) and data from two nuclear genes [first internal transcribed spacer (ITS-1) sequence and growth hormone (GH1) amplification product] indicated that the fish caught in fresh water on the Martin River was a coho salmon Oncorhynchus kisutch, while the other fish caught in the intertidal zone of the Copper River delta near Grass Island was an Atlantic salmon. Determination of unusual or cryptic fish based on limited physical characteristics and expected seasonal spawning run timing will add to the controversy over farmed Atlantic salmon and their potential effects on native Pacific species. It is clear that determination of all putative collections of Atlantic salmon found in Pacific waters requires validation. Due to uncertainty of fish identification in the field using plastic morphometric characters, it is recommended that genetic analyses be part of the validation process. ?? 2003 The Fisheries Society of the British Isles.

  5. Mutilocus genetic determinants of LDL particle size in coronary artery disease families

    SciTech Connect

    Rotter, J.I.; Bu, X.; Cantor, R.M.

    1996-03-01

    Recent interest in atherosclerosis has focused on the genetic determinants of low-density lipoprotein (LDL) particle size, because of (1) the association of small dense LDL particles with a three-fold increased risk for coronary artery disease (CAD) and (2) the recent report of linkage of the trait to the LDL receptor (chromosome 19). By utilizing nonparametric quantitative sib-pair and relative-pair-analysis methods in CAD families, we tested for linkage of a gene or genes controlling LDL particle sizes with the genetic loci for the major apolipoproteins and enzymes participating in lipoprotein metabolism. We confirmed evidence for linkage to the LDL receptor locus (P = .008). For six candidate gene loci, including apolipoprotein(apo)B, apoAII, apo(a), apoE-CI-CII, lipoprotein lipase, and high-density lipoprotein-binding protein, no evidence for linkage was observed by sib-pair linkage analyses (P values ranged from .24 to .81). However, in addition, we did find tentative evidence for linkage with the apoAI-CIII-AIV locus (chromosome 11) (P = .06) and significant evidence for linkage of the cholesteryl ester transfer protein locus (chromosome 16) (P = .01) and the manganese superoxide dismutase locus (chromosome 6) (P = .001), thus indicating multilocus determination of this atherogenic trait. 73 refs., 3 figs., 4 tabs.

  6. CNS repair and axon regeneration: Using genetic variation to determine mechanisms.

    PubMed

    Tedeschi, Andrea; Omura, Takao; Costigan, Michael

    2017-01-01

    The importance of genetic diversity in biological investigation has been recognized since the pioneering studies of Gregor Johann Mendel and Charles Darwin. Research in this area has been greatly informed recently by the publication of genomes from multiple species. Genes regulate and create every part and process in a living organism, react with the environment to create each living form and morph and mutate to determine the history and future of each species. The regenerative capacity of neurons differs profoundly between animal lineages and within the mammalian central and peripheral nervous systems. Here, we discuss research that suggests that genetic background contributes to the ability of injured axons to regenerate in the mammalian central nervous system (CNS), by controlling the regulation of specific signaling cascades. We detail the methods used to identify these pathways, which include among others Activin signaling and other TGF-β superfamily members. We discuss the potential of altering these pathways in patients with CNS damage and outline strategies to promote regeneration and repair by combinatorial manipulation of neuron-intrinsic and extrinsic determinants.

  7. Genetic Variation Determines PPARγ Function and Antidiabetic Drug Response In Vivo

    PubMed Central

    Soccio, Raymond E.; Chen, Eric R.; Rajapurkar, Satyajit R.; Safabakhsh, Pegah; Marinis, Jill M.; Dispirito, Joanna R.; Emmett, Matthew J.; Briggs, Erika R.; Fang, Bin; Everett, Logan J.; Lim, Hee-Woong; Won, Kyoung-Jae; Steger, David J.; Wu, Ying; Civelek, Mete; Voight, Benjamin F.; Lazar, Mitchell A.

    2015-01-01

    SUMMARY SNPs affecting disease risk often reside in non-coding genomic regions. Here we show that SNPs are highly enriched at mouse strain-selective adipose tissue binding sites for PPARγ, a nuclear receptor for antidiabetic drugs. Many such SNPs alter binding motifs for PPARγ or cooperating factors, and functionally regulate nearby genes whose expression is strain-selective and imbalanced in heterozygous F1 mice. Moreover, genetically-determined binding of PPARγ accounts for mouse strain-specific transcriptional effects of TZD drugs, providing proof-of-concept for personalized medicine related to nuclear receptor genomic occupancy. In human fat, motif-altering SNPs cause differential PPARγ binding, provide a molecular mechanism for some expression quantitative trait loci, and are risk factors for dysmetabolic traits in genome-wide association studies. One PPARγ motif-altering SNP is associated with HDL levels and other metabolic syndrome parameters. Thus, natural genetic variation in PPARγ genomic occupancy determines individual disease risk and drug response. PMID:26140591

  8. Determinants of pulmonary perfusion measured by electrical impedance tomography.

    PubMed

    Smit, Henk J; Vonk Noordegraaf, Anton; Marcus, J Tim; Boonstra, Anco; de Vries, Peter M; Postmus, Pieter E

    2004-06-01

    Electrical impedance tomography (EIT) is a non-invasive imaging technique for detecting blood volume changes that can visualize pulmonary perfusion. The two studies reported here tested the hypothesis that the size of the pulmonary microvascular bed, rather than stroke volume (SV), determines the EIT signal. In the first study, the impedance changes relating to the maximal pulmonary pulsatile blood volume during systole (Delta Z(sys)) were measured in ten healthy subjects, ten patients diagnosed with chronic obstructive pulmonary disease, who were considered to have a reduced pulmonary vascular bed, and ten heart failure patients with an assumed low cardiac output but with a normal lung parenchyma. Mean Delta Z(sys) (SD) in these groups was 261 (34)x10(-5), 196 (39)x10(-5) ( P<0.001) and 233 (61)x10(-5) arbitrary units (AU) (P=NS), respectively. In the second study, including seven healthy volunteers, Delta Z(sys) was measured at rest and during exercise on a recumbent bicycle while SV was measured by means of magnetic resonance imaging. The Delta Z(sys) at rest was 352 (53)x10(-5 ) and 345 (112)x10(-5 )AU during exercise (P=NS), whereas SV increased from 83 (21) to 105 (34) ml (P<0.05). The EIT signal likely reflects the size of the pulmonary microvascular bed, since neither a low cardiac output nor a change in SV of the heart appear to influence EIT.

  9. Determination of spectral irradiances from broadband instrument measurements

    NASA Astrophysics Data System (ADS)

    Diaz, Susana B.; Nelson, Donald W.; Deferrari, Guillermo; Camilion, Carolina

    2002-01-01

    After the discovery of the ozone hole the use of spectral and multiband instruments in UV radiation measurements became more common, but time series for these instruments are still relatively short to determine trends. Nevertheless, systematic measurements of ozone column have been performed since late fifties at several stations and with worldwide coverage since late seventies, and long time series of broadband instruments (Pyranometers, UV and erythemally weighted) are also available at stations all over the world. In this paper we introduce a multi- regressive model that allows inference of spectral or narrowband irradiances from ozone total column and broadband irradiances, in places where a relatively short time series of spectral irradiances is available. To test the model, measurements under all weather, solar zenith angle and ground conditions performed at three of the stations of the NSAF UV Radiation Monitoring Network were used. The model generated very good results over a wide variety of situations. Broadband pyranometer data from the NOAA/CMDL surface radiation budget database for the South Pole Station were used in the model to estimate the daily-integrated narrowband irradiances. A time series of monthly means for the narrowband 303.030-307.692 nm were then computed, dating back to 1978.

  10. Modulation of Protein A Formation in Staphylococcus aureus by Genetic Determinants for Methicillin Resistance

    PubMed Central

    Cohen, Sidney; Sweeney, Helen M.

    1979-01-01

    Many methicillin-resistant (Mecr) strains of Staphylococcus aureus either produce no protein A or secrete it extracellularly (S. Winblad and C. Ericson, Acta Pathol. Microbiol. Scand. Sect. B 81:150–156, 1973). We found that methicillin resistance and protein A production were apparently lost coordinately from the natively Mecr strain A676. Restoration of the genetic determinant for methicillin resistance (mec) by transduction or transformation restored protein A production. In two other Mecr strains, loss of mec was accompanied by marked reduction in protein A formation. Genetic transfer of mec to derivatives of S. aureus 8325 affected protein A formation differently with different mec determinants. Those derived from strain A676 and two other Mecr strains reduced the scanty amount of protein A produced by strain 8325 to even lower or undetectable levels, whereas mec from two more Mecr strains increased its protein A content. This “mec-effect,” i.e., stimulation or inhibition of protein A formation dependent on the combination of host strain and mec determinant, was reduced in methicillin-susceptible (Mecs) mutants produced by ethyl methane sulfonate treatment of Mecr strains. The mec-effect reappeared in spontaneous revertants to methicillin resistance. Phenotypic reduction of methicillin resistance in Mecr strains grown at 44°C was accompanied by reduction of the mec-effect on protein A, but it had no effect on protein A formation in Mecs strains. Two independent mutants of strain 8325 produced large amounts of protein A at rates that were unaffected by growth at 44°C or by the introduction of mec determinants. PMID:533763

  11. Genetically-mediated associations between measures of childhood character and academic achievement.

    PubMed

    Tucker-Drob, Elliot M; Briley, Daniel A; Engelhardt, Laura E; Mann, Frank D; Harden, K Paige

    2016-11-01

    Researchers and the general public have become increasingly intrigued by the roles that systematic tendencies toward thinking, feeling, and behaving might play in academic achievement. Some measures of constructs belonging to this group have been well studied in genetics and psychometrics, while much less is known about measures of other such constructs. The current study focuses on 7 character traits prominently featured in influential intervention-oriented and/or socialization theories of academic achievement: grit, intellectual curiosity, intellectual self-concept, mastery orientation, educational value, intelligence mindset, and test motivation. In a population-based sample of 811 school-aged twins and triplets from the Texas Twin Project, we tested (a) how each measure relates to indices of the Big Five personality traits, (b) how the measures relate to one another, (c) the extent to which each measure is associated with genetic and environmental influences and whether such influences operate through common dimensions of individual differences, and (d) the extent to which genetic and environmental factors mediate the relations between fluid intelligence, character measures, verbal knowledge, and academic achievement. We find moderate relations among the measures that can be captured by a highly heritable common dimension representing a mixture of Openness and Conscientiousness. Moreover, genetically influenced variance in the character measures is associated with multiple measures of verbal knowledge and academic achievement, even after controlling for fluid intelligence. In contrast, environmentally influenced variance in character is largely unrelated to knowledge and achievement outcomes. We propose that character measures popularly used in education may be best conceptualized as indexing facets of personality that are of particular relevance to academic achievement. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  12. Added value measures in education show genetic as well as environmental influence.

    PubMed

    Haworth, Claire M A; Asbury, Kathryn; Dale, Philip S; Plomin, Robert

    2011-02-02

    Does achievement independent of ability or previous attainment provide a purer measure of the added value of school? In a study of 4000 pairs of 12-year-old twins in the UK, we measured achievement with year-long teacher assessments as well as tests. Raw achievement shows moderate heritability (about 50%) and modest shared environmental influences (25%). Unexpectedly, we show that for indices of the added value of school, genetic influences remain moderate (around 50%), and the shared (school) environment is less important (about 12%). The pervasiveness of genetic influence in how and how much children learn is compatible with an active view of learning in which children create their own educational experiences in part on the basis of their genetic propensities.

  13. Phenotypic, genetic, and environmental relationships between self-reported talents and measured intelligence.

    PubMed

    Schermer, Julie Aitken; Johnson, Andrew M; Jang, Kerry L; Vernon, Philip A

    2015-02-01

    The relationship between self-report abilities and measured intelligence was examined at both the phenotypic (zero-order) level as well as at the genetic and environmental levels. Twins and siblings (N = 516) completed a timed intelligence test and a self-report ability questionnaire, which has previously been found to produce 10 factors, including: politics, interpersonal relationships, practical tasks, intellectual pursuits, academic skills, entrepreneur/business, domestic skills, vocal abilities, and creativity. At the phenotypic level, the correlations between the ability factor scores and intelligence ranged from 0.01 to 0.42 (between self-report academic abilities and verbal intelligence). Further analyses found that some of the phenotypic relationships between self-report ability scores and measured intelligence also had significant correlations at the genetic and environmental levels, suggesting that some of the observed relationships may be due to common genetic and/or environmental factors.

  14. Added Value Measures in Education Show Genetic as Well as Environmental Influence

    PubMed Central

    Haworth, Claire M. A.; Asbury, Kathryn; Dale, Philip S.; Plomin, Robert

    2011-01-01

    Does achievement independent of ability or previous attainment provide a purer measure of the added value of school? In a study of 4000 pairs of 12-year-old twins in the UK, we measured achievement with year-long teacher assessments as well as tests. Raw achievement shows moderate heritability (about 50%) and modest shared environmental influences (25%). Unexpectedly, we show that for indices of the added value of school, genetic influences remain moderate (around 50%), and the shared (school) environment is less important (about 12%). The pervasiveness of genetic influence in how and how much children learn is compatible with an active view of learning in which children create their own educational experiences in part on the basis of their genetic propensities. PMID:21311598

  15. Genetic Risk Determinants for Cigarette Smoking Dependence in Mexican Mestizo Families.

    PubMed

    Svyryd, Yevgeniya; Ramírez-Venegas, Alejandra; Sánchez-Hernández, Beatriz; Aguayo-Gómez, Adolfo; Luna-Muñoz, Leonora; Arteaga-Vázquez, Jazmín; Regalado-Pineda, Justino; Mutchinick, Osvaldo M

    2016-05-01

    Tobacco smoking is a leading cause of mortality in developed and developing countries. Despite antitobacco and smoke-free policies, the prevalence of active smokers in Mexican urban populations has remained stable. Mexican smokers differ from Caucasian and other ethnic groups, probably due to sociocultural and genetic background characteristics. This study explored the effect of known genetic variants on smoking behavior in Mexico City residents. Three hundred sixty-four Mexican Mestizo Mexico City residents from 87 families with at least one smoker were assessed for association of 12 gene variants of six candidate genes (CHRNA4, CHRNB2, DRD2, ANKK1, SLC6A3, and CYP2A6) with cigarette consumption, age of initiation and smoking duration. The Family Based Association Test, an extension of the Transmission Disequilibrium Test, was used to perform family-based association analysis. The Family Based Association Test showed statistically significant association between the rs2072658 polymorphism of the CHRNB2 gene and smoking-related phenotypes such as: smoking status (SS), age of onset (AO), years of smoking, and psychological dependence (PD) evaluated by the Glover-Nilsson Smoking Behavior Questionnaire. After Bonferroni correction, only the association with AO remained significant (P = .003). Statistically significant association was also observed for the CYP2A6 rs28399433 T allele with SS (P = .003) and PD (P = .003). Our results indicate effects of the rs2072658 CHRNB2 and rs28399433 CYP2A6 gene variants on AO, SS and PD in Mexican Mestizo smokers. A mild effect of other analyzed gene variants, which may contribute to a putative polygenic predisposition for smoking, is suggested. The understanding of genetic and environmental determinants in the Mexican population is important for other Latin American populations as well, living in their own countries or moving to other ones, particular due to the current migration characteristics and particular genetic background

  16. Genetic determinants of cardiometabolic risk factors in rural families in Brazil.

    PubMed

    Pena, Geórgia G; Martinez-Perez, Angel; Dutra, Míriam Santos; Gazzinelli, Andrea; Corrêa-Oliveira, Rodrigo; Soria, José M; Velasquez-Melendez, Gustavo

    2016-09-10

    The purpose of this study was to estimate the heritability of genetic and environmental correlations between cardiometabolic risk factors in extended pedigrees. The Jequitinhonha Community Family Study Cohort (JCFSC) consists of individuals aged ≥18 years living in rural villages. Family pedigrees were constructed of the cohort. The following data were collected: demographic and socioeconomic status, lifestyle variables, anthropometrics, and lipid traits. The JCFSC consists of 931 individuals distributed into 69 pedigrees with 4,907 members in total. The heritabilities were 0.47 for total cholesterol (TC), 0.44 for triglycerides (TG) and 0.42 for high-density lipoprotein cholesterol (HDLc), 0.49 for metabolic syndrome, approximately 0.60 for anthropometric traits and 0.30 for blood pressure/hypertension. Significant genetic correlations (ρg ) were found mainly between TG and TC (ρg  = 0.58) and hypertension and TG (ρg  = 0.52). Systolic blood pressure (SBP) was correlated with TG (ρg  = 0.39) and HDLc (ρg  = -0.30). Diastolic blood pressures correlated with TG (ρg =0.56) and TC (ρg =0.30). Genetic correlations were also found between anthropometric traits, including: body mass index (BMI) and TG (ρg =0.34), waist circumference (WC) and TG (ρg =0.42), and WC and HDLc (ρg =-0.33). Household effects were found for HDLc (c(2) = 0.19), SBP (c(2)  = 0.14) and Hypertension (c(2) = 0.14). To some phenotypes, including lipids, hypertension, blood pressure, and anthropometric traits, genetic contribution is important in the determination of cardiometabolic risk factors. This study provides a foundation for future studies. These will mainly focus on rare variants that could describe the genetic mechanisms influencing cardiometabolic risk. Am. J. Hum. Biol. 28:619-626, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Psychological determinants of willingness to taste and purchase genetically modified food.

    PubMed

    Townsend, Ellen; Campbell, Scott

    2004-10-01

    Decreasing acceptance of biotechnologies over time has been reported in Europe. Studies claim that attitudes are negative, even hostile, and that people are very worried about genetic engineering in food and medicine. However, such studies are mostly based on surveys and these have significant methodological problems, such as low response rates, which may indicate that only those with strong views respond, thus biasing the sample. Here an alternative method, involving "topic-blind" recruitment of participants and a behavioral measure (food tasting), was used. We show that in a topic-blind sample of 100 individuals, 93% willingly tasted and ate what they believed to be genetically modified (GM) food in an experimental setting, and 48% said they would buy GM food in the future, results that are surprising in the context of other reports about attitudes and intentions toward GM food. Purchasers and nonpurchasers differed in their attitudes toward GM food on key risk-related scales (particularly on a dread-not dread scale--a measure of integral affect--and an ethical-unethical scale). Despite these differences, however, and despite their negative attitude, most nonpurchasers (85.7%) still tasted the GM apple. Incidental affect (state stress and trait worry) was not found to influence risk-related judgments about GM food. Integral affect (dread of GM plants and animals used for food) and concerns about the future risks of GM animals in food were found to be key predictors of willingness to purchase GM food.

  18. Impact of Measurement Error on Testing Genetic Association with Quantitative Traits

    PubMed Central

    Liao, Jiemin; Li, Xiang; Wong, Tien-Yin; Wang, Jie Jin; Khor, Chiea Chuen; Tai, E. Shyong; Aung, Tin; Teo, Yik-Ying; Cheng, Ching-Yu

    2014-01-01

    Measurement error of a phenotypic trait reduces the power to detect genetic associations. We examined the impact of sample size, allele frequency and effect size in presence of measurement error for quantitative traits. The statistical power to detect genetic association with phenotype mean and variability was investigated analytically. The non-centrality parameter for a non-central F distribution was derived and verified using computer simulations. We obtained equivalent formulas for the cost of phenotype measurement error. Effects of differences in measurements were examined in a genome-wide association study (GWAS) of two grading scales for cataract and a replication study of genetic variants influencing blood pressure. The mean absolute difference between the analytic power and simulation power for comparison of phenotypic means and variances was less than 0.005, and the absolute difference did not exceed 0.02. To maintain the same power, a one standard deviation (SD) in measurement error of a standard normal distributed trait required a one-fold increase in sample size for comparison of means, and a three-fold increase in sample size for comparison of variances. GWAS results revealed almost no overlap in the significant SNPs (p<10−5) for the two cataract grading scales while replication results in genetic variants of blood pressure displayed no significant differences between averaged blood pressure measurements and single blood pressure measurements. We have developed a framework for researchers to quantify power in the presence of measurement error, which will be applicable to studies of phenotypes in which the measurement is highly variable. PMID:24475218

  19. Genetic markers that influence feed efficiency phenotypes also affect cattle temperament as measured by flight speed

    USDA-ARS?s Scientific Manuscript database

    The measure of flight speed for cattle has been shown to be a predictive indicator of temperament and has also been associated with feed efficiency phenotypes, thus, genetic markers associated with both traits may assist with the selection of animals with calmer disposition and economic value. Chrom...

  20. Determination of precipitation profiles from airborne passive microwave radiometric measurements

    NASA Technical Reports Server (NTRS)

    Kummerow, Christian; Hakkarinen, Ida M.; Pierce, Harold F.; Weinman, James A.

    1991-01-01

    This study presents the first quantitative retrievals of vertical profiles of precipitation derived from multispectral passive microwave radiometry. Measurements of microwave brightness temperature (Tb) obtained by a NASA high-altitude research aircraft are related to profiles of rainfall rate through a multichannel piecewise-linear statistical regression procedure. Statistics for Tb are obtained from a set of cloud radiative models representing a wide variety of convective, stratiform, and anvil structures. The retrieval scheme itself determines which cloud model best fits the observed meteorological conditions. Retrieved rainfall rate profiles are converted to equivalent radar reflectivity for comparison with observed reflectivities from a ground-based research radar. Results for two case studies, a stratiform rain situation and an intense convective thunderstorm, show that the radiometrically derived profiles capture the major features of the observed vertical structure of hydrometer density.

  1. Determining low-frequency source location from acoustic phase measurements

    NASA Astrophysics Data System (ADS)

    Poole, Travis L.; Frisk, George V.

    2002-11-01

    For low-frequency cw sound sources in shallow water, the time rate-of-change of the measured acoustic phase is well approximated by the time rate-of-change of the source-receiver separation distance. An algorithm for determining a locus of possible source locations based on this idea has been developed. The locus has the general form of a hyperbola, which can be used to provide a bearing estimation at long ranges, and an estimate of source location at short ranges. The algorithm uses only acoustic phase data and receiver geometry as input, and can be used even when the source frequency is slightly unstable and/or imprecisely known. The algorithm has been applied to data from low-frequency experiments (20-300 Hz), both for stable and unstable source frequencies, and shown to perform well. [Work supported by ONR and WHOI Academic Programs Office.

  2. Bayesian source term determination with unknown covariance of measurements

    NASA Astrophysics Data System (ADS)

    Belal, Alkomiet; Tichý, Ondřej; Šmídl, Václav

    2017-04-01

    Determination of a source term of release of a hazardous material into the atmosphere is a very important task for emergency response. We are concerned with the problem of estimation of the source term in the conventional linear inverse problem, y = Mx, where the relationship between the vector of observations y is described using the source-receptor-sensitivity (SRS) matrix M and the unknown source term x. Since the system is typically ill-conditioned, the problem is recast as an optimization problem minR,B(y - Mx)TR-1(y - Mx) + xTB-1x. The first term minimizes the error of the measurements with covariance matrix R, and the second term is a regularization of the source term. There are different types of regularization arising for different choices of matrices R and B, for example, Tikhonov regularization assumes covariance matrix B as the identity matrix multiplied by scalar parameter. In this contribution, we adopt a Bayesian approach to make inference on the unknown source term x as well as unknown R and B. We assume prior on x to be a Gaussian with zero mean and unknown diagonal covariance matrix B. The covariance matrix of the likelihood R is also unknown. We consider two potential choices of the structure of the matrix R. First is the diagonal matrix and the second is a locally correlated structure using information on topology of the measuring network. Since the inference of the model is intractable, iterative variational Bayes algorithm is used for simultaneous estimation of all model parameters. The practical usefulness of our contribution is demonstrated on an application of the resulting algorithm to real data from the European Tracer Experiment (ETEX). This research is supported by EEA/Norwegian Financial Mechanism under project MSMT-28477/2014 Source-Term Determination of Radionuclide Releases by Inverse Atmospheric Dispersion Modelling (STRADI).

  3. A Co-Association Network Analysis of the Genetic Determination of Pig Conformation, Growth and Fatness

    PubMed Central

    Puig-Oliveras, Anna; Ballester, Maria; Corominas, Jordi; Revilla, Manuel; Estellé, Jordi; Fernández, Ana I.; Ramayo-Caldas, Yuliaxis; Folch, Josep M.

    2014-01-01

    Background Several QTLs have been identified for major economically relevant traits in livestock, such as growth and meat quality, revealing the complex genetic architecture of these traits. The use of network approaches considering the interactions of multiple molecules and traits provides useful insights into the molecular underpinnings of complex traits. Here, a network based methodology, named Association Weight Matrix, was applied to study gene interactions and pathways affecting pig conformation, growth and fatness traits. Results The co-association network analysis underpinned three transcription factors, PPARγ, ELF1, and PRDM16 involved in mesoderm tissue differentiation. Fifty-four genes in the network belonged to growth-related ontologies and 46 of them were common with a similar study for growth in cattle supporting our results. The functional analysis uncovered the lipid metabolism and the corticotrophin and gonadotrophin release hormone pathways among the most important pathways influencing these traits. Our results suggest that the genes and pathways here identified are important determining either the total body weight of the animal and the fat content. For instance, a switch in the mesoderm tissue differentiation may determinate the age-related preferred pathways being in the puberty stage those related with the miogenic and osteogenic lineages; on the contrary, in the maturity stage cells may be more prone to the adipocyte fate. Hence, our results demonstrate that an integrative genomic co-association analysis is a powerful approach for identifying new connections and interactions among genes. Conclusions This work provides insights about pathways and key regulators which may be important determining the animal growth, conformation and body proportions and fatness traits. Molecular information concerning genes and pathways here described may be crucial for the improvement of genetic breeding programs applied to pork meat production. PMID:25503799

  4. Prevalence and Potential Genetic Determinants of Sensorineural Deafness in KCNQ1 Homozygosity and Compound Heterozygosity

    PubMed Central

    Giudicessi, John R.; Ackerman, Michael J.

    2013-01-01

    Background Homozygous or compound heterozygous mutations in KCNQ1 cause Jervell and Lange-Nielsen syndrome (JLNS), a rare, autosomal recessive form of long QT syndrome (LQTS) characterized by deafness, marked QT prolongation, and a high risk of sudden death. However, it is not understood why some individuals with mutations on both KCNQ1 alleles present without deafness. Here, we sought to determine the prevalence and genetic determinants of this phenomenon in a large referral population of LQTS patients. Methods and Results Retrospective analysis of all LQTS patients evaluated from July 1998 to April 2012 was used to identify those with ≥1 KCNQ1 mutation. Of the 249 KCNQ1-positive patients identified, 15 patients (6.0%) harbored a rare putative pathogenic mutation on both KCNQ1 alleles. Surprisingly, 11 (73%) of these patients presented without the sensorineural deafness associated with JLNS. The degree of QT interval prolongation and number of breakthrough cardiac events were similar between cases with and without deafness. Interestingly, truncating mutations were more prevalent in JLNS (79%) than non-deaf cases (36%, p<0.001) derived from this study and those in the literature. Conclusions Here, we provide evidence that the “recessive” inheritance of a severe LQT1 phenotype in the absence of an auditory phenotype may represent a more common pattern of LQTS inheritance than previously anticipated and that these cases should be treated as a higher-risk LQTS subset similar to their JLNS counterparts. Furthermore, mutation type may serve as a genetic determinant of deafness, but not cardiac expressivity, in individuals harboring ≥1 KCNQ1 mutation on each allele. PMID:23392653

  5. Method for Determining the Coalbed Methane Content with Determination the Uncertainty of Measurements

    NASA Astrophysics Data System (ADS)

    Szlązak, Nikodem; Korzec, Marek

    2016-06-01

    Methane has a bad influence on safety in underground mines as it is emitted to the air during mining works. Appropriate identification of methane hazard is essential to determining methane hazard prevention methods, ventilation systems and methane drainage systems. Methane hazard is identified while roadways are driven and boreholes are drilled. Coalbed methane content is one of the parameters which is used to assess this threat. This is a requirement according to the Decree of the Minister of Economy dated 28 June 2002 on work safety and hygiene, operation and special firefighting protection in underground mines. For this purpose a new method for determining coalbed methane content in underground coal mines has been developed. This method consists of two stages - collecting samples in a mine and testing the sample in the laboratory. The stage of determining methane content in a coal sample in a laboratory is essential. This article presents the estimation of measurement uncertainty of determining methane content in a coal sample according to this methodology.

  6. Quantitative genetic properties of four measures of deformity in yellowtail kingfish Seriola lalandi Valenciennes, 1833.

    PubMed

    Nguyen, N H; Whatmore, P; Miller, A; Knibb, W

    2016-02-01

    The main aim of this study was to estimate the heritability for four measures of deformity and their genetic associations with growth (body weight and length), carcass (fillet weight and yield) and flesh-quality (fillet fat content) traits in yellowtail kingfish Seriola lalandi. The observed major deformities included lower jaw, nasal erosion, deformed operculum and skinny fish on 480 individuals from 22 families at Clean Seas Tuna Ltd. They were typically recorded as binary traits (presence or absence) and were analysed separately by both threshold generalized models and standard animal mixed models. Consistency of the models was evaluated by calculating simple Pearson correlation of breeding values of full-sib families for jaw deformity. Genetic and phenotypic correlations among traits were estimated using a multitrait linear mixed model in ASReml. Both threshold and linear mixed model analysis showed that there is additive genetic variation in the four measures of deformity, with the estimates of heritability obtained from the former (threshold) models on liability scale ranging from 0.14 to 0.66 (SE 0.32-0.56) and from the latter (linear animal and sire) models on original (observed) scale, 0.01-0.23 (SE 0.03-0.16). When the estimates on the underlying liability were transformed to the observed scale (0, 1), they were generally consistent between threshold and linear mixed models. Phenotypic correlations among deformity traits were weak (close to zero). The genetic correlations among deformity traits were not significantly different from zero. Body weight and fillet carcass showed significant positive genetic correlations with jaw deformity (0.75 and 0.95, respectively). Genetic correlation between body weight and operculum was negative (-0.51, P < 0.05). The genetic correlations' estimates of body and carcass traits with other deformity were not significant due to their relatively high standard errors. Our results showed that there are prospects for genetic

  7. Genetics

    USDA-ARS?s Scientific Manuscript database

    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 ...

  8. Genetics

    USDA-ARS?s Scientific Manuscript database

    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...

  9. Determination of best-fit potential parameters for a reactive force field using a genetic algorithm.

    PubMed

    Pahari, Poonam; Chaturvedi, Shashank

    2012-03-01

    The ReaxFF interatomic potential, used for organic materials, involves more than 600 adjustable parameters, the best-fit values of which must be determined for different materials. A new method of determining the set of best-fit parameters for specific molecules containing carbon, hydrogen, nitrogen and oxygen is presented, based on a parameter reduction technique followed by genetic algorithm (GA) minimization. This work has two novel features. The first is the use of a parameter reduction technique to determine which subset of parameters plays a significant role for the species of interest; this is necessary to reduce the optimization space to manageable levels. The second is the application of the GA technique to a complex potential (ReaxFF) with a very large number of adjustable parameters, which implies a large parameter space for optimization. In this work, GA has been used to optimize the parameter set to determine best-fit parameters that can reproduce molecular properties to within a given accuracy. As a test problem, the use of the algorithm has been demonstrated for nitromethane and its decomposition products.

  10. A conserved genetic pathway determines inflorescence architecture in Arabidopsis and rice.

    PubMed

    Liu, Chang; Teo, Zhi Wei Norman; Bi, Yang; Song, Shiyong; Xi, Wanyan; Yang, Xiaobei; Yin, Zhongchao; Yu, Hao

    2013-03-25

    The spatiotemporal architecture of inflorescences that bear flowers determines plant reproductive success by affecting fruit set and plant interaction with pollinators. The inflorescence architecture that displays great diversity across flowering plants depends on developmental decisions at inflorescence meristems. Here we report a key conserved genetic pathway determining inflorescence architecture in Arabidopsis thaliana and Oryza sativa (rice). In Arabidopsis, four MADS-box genes, SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1, SHORT VEGETATIVE PHASE, AGAMOUS-LIKE 24, and SEPALLATA 4 act redundantly and directly to suppress TERMINAL FLOWER1 (TFL1) in emerging floral meristems. This is indispensable for the well-known function of APETALA1 in specifying floral meristems and is coupled with a conformational change in chromosome looping at the TFL1 locus. Similarly, we demonstrate that the orthologs of these MADS-box genes in rice determine panicle branching by regulating TFL1-like genes. Our findings reveal a conserved regulatory pathway that determines inflorescence architecture in flowering plants. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Evidence for a genetic sex determination in Cnidaria, the Mediterranean red coral (Corallium rubrum)

    PubMed Central

    Haguenauer, A.; Chenesseau, S.; Brener, K. ; Mitta, G.; Toulza, E.; Bonabaud, M.; Rialle, S. ; Aurelle, D.

    2017-01-01

    Sexual reproduction is widespread among eukaryotes, and the sex-determining processes vary greatly among species. While genetic sex determination (GSD) has been intensively described in bilaterian species, no example has yet been recorded among non-bilaterians. However, the quasi-ubiquitous repartition of GSD among multicellular species suggests that similar evolutionary forces can promote this system, and that these forces could occur also in non-bilaterians. Studying sex determination across the range of Metazoan diversity is indeed important to understand better the evolution of this mechanism and its lability. We tested the existence of sex-linked genes in the gonochoric red coral (Corallium rubrum, Cnidaria) using restriction site-associated DNA sequencing. We analysed 27 461 single nucleotide polymorphisms (SNPs) in 354 individuals from 12 populations including 53 that were morphologically sexed. We found a strong association between the allele frequencies of 472 SNPs and the sex of individuals, suggesting an XX/XY sex-determination system. This result was confirmed by the identification of 435 male-specific loci. An independent test confirmed that the amplification of these loci enabled us to identify males with absolute certainty. This is the first demonstration of a GSD system among non-bilaterian species and a new example of its convergence in multicellular eukaryotes. PMID:28405374

  12. Evidence for a genetic sex determination in Cnidaria, the Mediterranean red coral (Corallium rubrum).

    PubMed

    Pratlong, M; Haguenauer, A; Chenesseau, S; Brener, K; Mitta, G; Toulza, E; Bonabaud, M; Rialle, S; Aurelle, D; Pontarotti, P

    2017-03-01

    Sexual reproduction is widespread among eukaryotes, and the sex-determining processes vary greatly among species. While genetic sex determination (GSD) has been intensively described in bilaterian species, no example has yet been recorded among non-bilaterians. However, the quasi-ubiquitous repartition of GSD among multicellular species suggests that similar evolutionary forces can promote this system, and that these forces could occur also in non-bilaterians. Studying sex determination across the range of Metazoan diversity is indeed important to understand better the evolution of this mechanism and its lability. We tested the existence of sex-linked genes in the gonochoric red coral (Corallium rubrum, Cnidaria) using restriction site-associated DNA sequencing. We analysed 27 461 single nucleotide polymorphisms (SNPs) in 354 individuals from 12 populations including 53 that were morphologically sexed. We found a strong association between the allele frequencies of 472 SNPs and the sex of individuals, suggesting an XX/XY sex-determination system. This result was confirmed by the identification of 435 male-specific loci. An independent test confirmed that the amplification of these loci enabled us to identify males with absolute certainty. This is the first demonstration of a GSD system among non-bilaterian species and a new example of its convergence in multicellular eukaryotes.

  13. An Evolving Genetic Architecture Interacts with Hill–Robertson Interference to Determine the Benefit of Sex

    PubMed Central

    Whitlock, Alexander O. B.; Peck, Kayla M.; Azevedo, Ricardo B. R.; Burch, Christina L.

    2016-01-01

    Sex is ubiquitous in the natural world, but the nature of its benefits remains controversial. Previous studies have suggested that a major advantage of sex is its ability to eliminate interference between selection on linked mutations, a phenomenon known as Hill–Robertson interference. However, those studies may have missed both important advantages and important disadvantages of sexual reproduction because they did not allow the distributions of mutational effects and interactions (i.e., the genetic architecture) to evolve. Here we investigate how Hill–Robertson interference interacts with an evolving genetic architecture to affect the evolutionary origin and maintenance of sex by simulating evolution in populations of artificial gene networks. We observed a long-term advantage of sex—equilibrium mean fitness of sexual populations exceeded that of asexual populations—that did not depend on population size. We also observed a short-term advantage of sex—sexual modifier mutations readily invaded asexual populations—that increased with population size, as was observed in previous studies. We show that the long- and short-term advantages of sex were both determined by differences between sexual and asexual populations in the evolutionary dynamics of two properties of the genetic architecture: the deleterious mutation rate (Ud) and recombination load (LR). These differences resulted from a combination of selection to minimize LR, which is experienced only by sexuals, and Hill–Robertson interference experienced primarily by asexuals. In contrast to the previous studies, in which Hill–Robertson interference had only a direct impact on the fitness advantages of sex, the impact of Hill–Robertson interference in our simulations was mediated additionally by an indirect impact on the efficiency with which selection acted to reduce Ud. PMID:27098911

  14. Plant genetics and interspecific competitive interactions determine ectomycorrhizal fungal community responses to climate change.

    PubMed

    Gehring, Catherine; Flores-Rentería, Dulce; Sthultz, Christopher M; Leonard, Tierra M; Flores-Rentería, Lluvia; Whipple, Amy V; Whitham, Thomas G

    2014-03-01

    Although the importance of plant-associated microbes is increasingly recognized, little is known about the biotic and abiotic factors that determine the composition of that microbiome. We examined the influence of plant genetic variation, and two stressors, one biotic and one abiotic, on the ectomycorrhizal (EM) fungal community of a dominant tree species, Pinus edulis. During three periods across 16 years that varied in drought severity, we sampled the EM fungal communities of a wild stand of P. edulis in which genetically based resistance and susceptibility to insect herbivory was linked with drought tolerance and the abundance of competing shrubs. We found that the EM fungal communities of insect-susceptible trees remained relatively constant as climate dried, while those of insect-resistant trees shifted significantly, providing evidence of a genotype by environment interaction. Shrub removal altered the EM fungal communities of insect-resistant trees, but not insect-susceptible trees, also a genotype by environment interaction. The change in the EM fungal community of insect-resistant trees following shrub removal was associated with greater shoot growth, evidence of competitive release. However, shrub removal had a 7-fold greater positive effect on the shoot growth of insect-susceptible trees than insect-resistant trees when shrub density was taken into account. Insect-susceptible trees had higher growth than insect-resistant trees, consistent with the hypothesis that the EM fungi associated with susceptible trees were superior mutualists. These complex, genetic-based interactions among species (tree-shrub-herbivore-fungus) argue that the ultimate impacts of climate change are both ecological and evolutionary.

  15. Genetic Diversity, Rather than Cultivar Type, Determines Relative Grain Cd Accumulation in Hybrid Rice

    PubMed Central

    Sun, Liang; Xu, Xiaxu; Jiang, Youru; Zhu, Qihong; Yang, Fei; Zhou, Jieqiang; Yang, Yuanzhu; Huang, Zhiyuan; Li, Aihong; Chen, Lianghui; Tang, Wenbang; Zhang, Guoyu; Wang, Jiurong; Xiao, Guoying; Huang, Daoyou; Chen, Caiyan

    2016-01-01

    Cadmium (Cd) is a toxic element, and rice is known to be a leading source of dietary Cd for people who consume rice as their main caloric resource. Hybrid rice has dominated rice production in southern China and has been adopted worldwide. The characteristics of high yield heterosis of rice hybrids makes the public think intuitively that the hybrid rice accumulates more Cd in grain than do inbred cultivars. A detailed understanding of the genetic basis of grain Cd accumulation in hybrids and developing Cd-safe rice are one of the top priorities for hybrid rice breeders at present. In this study, we investigated genetic diversity and grain Cd levels in 617 elite rice hybrids collected from the middle and lower Yangtze River Valley in China and 68 inbred cultivars from around the world. We found that there are large variations in grain Cd accumulation in both the hybrids and their inbred counterparts. However, we found grain Cd levels in the rice hybrids to be similar to the levels in indica rice inbreds, suggesting that the hybrids do not accumulate more Cd than do the inbred rice cultivars. Further analysis revealed that the high heritability of Cd accumulation in the grain and the single indica population structure increases the risk of Cd over-accumulation in hybrid rice. The genetic effects of Cd-related QTLs, which have been identified in related Cd-QTL mapping studies, were also determined in the hybrid rice population. Four QTLs were identified as being associated with the variation in grain Cd levels; three of these loci exhibited obvious indica-japonica differentiations. Our study will provide a better understanding of grain Cd accumulations in hybrid rice, and pave the way toward effective breeding for high-yielding, low grain-Cd hybrids in the future. PMID:27708659

  16. Response to enemies in the invasive plant Lythrum salicaria is genetically determined.

    PubMed

    Joshi, Srijana; Tielbörger, Katja

    2012-11-01

    The enemy release hypothesis assumes that invasive plants lose their co-evolved natural enemies during introduction into the new range. This study tested, as proposed by the evolution of increased competitive ability (EICA) hypothesis, whether escape from enemies results in a decrease in defence ability in plants from the invaded range. Two straightforward aspects of the EICA are examined: (1) if invasives have lost their enemies and their defence, they should be more negatively affected by their full natural pre-invasion herbivore spectrum than their native conspecifics; and (2) the genetic basis of evolutionary change in response to enemy release in the invasive range has not been taken sufficiently into account. Lythrum salicaria (purple loosestrife) from several populations in its native (Europe) and invasive range (North America) was exposed to all above-ground herbivores in replicated natural populations in the native range. The experiment was performed both with plants raised from field-collected seeds as well as with offspring of these where maternal effects were removed. Absolute and relative leaf damage was higher for introduced than for native plants. Despite having smaller height growth rate, invasive plants attained a much larger final size than natives irrespective of damage, indicating large tolerance rather than effective defence. Origin effects on response to herbivory and growth were stronger in second-generation plants, suggesting that invasive potential through enemy release has a genetic basis. The findings support two predictions of the EICA hypothesis - a genetically determined difference between native and invasive plants in plant vigour and response to enemies - and point to the importance of experiments that control for maternal effects and include the entire spectrum of native range enemies.

  17. Impact of Mutation Type and Amplicon Characteristics on Genetic Diversity Measures Generated Using a High-Resolution Melting Diversity Assay

    PubMed Central

    Cousins, Matthew M.; Donnell, Deborah; Eshleman, Susan H.

    2013-01-01

    We adapted high-resolution melting (HRM) technology to measure genetic diversity without sequencing. Diversity is measured as a single numeric HRM score. Herein, we determined the impact of mutation types and amplicon characteristics on HRM diversity scores. Plasmids were generated with single-base changes, insertions, and deletions. Different primer sets were used to vary the position of mutations within amplicons. Plasmids and plasmid mixtures were analyzed to determine the impact of mutation type, position, and concentration on HRM scores. The impact of amplicon length and G/C content on HRM scores was also evaluated. Different mutation types affected HRM scores to varying degrees (1-bp deletion < 1-bp change < 3-bp insertion < 9-bp insertion). The impact of mutations on HRM scores was influenced by amplicon length and the position of the mutation within the amplicon. Mutations were detected at concentrations of 5% to 95%, with the greatest impact at 50%. The G/C content altered melting temperature values of amplicons but had no impact on HRM scores. These data are relevant to the design of assays that measure genetic diversity using HRM technology. PMID:23178437

  18. Efficiently determining transform filter coefficients for image processing by applying distributed genetic algorithms

    NASA Astrophysics Data System (ADS)

    Gilligan, Martin; Lamont, Gary B.; Peterson, Michael R.

    2009-05-01

    An important aspect of contemporary military communications in the design of robust image transforms for defense surveillance applications. In particular, efficient yet effective transfer of critical image information is required for decision making. The generic use of wavelets to transform an image is a standard transform approach. However, the resulting bandwidth requirements can be quite high, suggesting that a different bandwidth-limited transform be developed. Thus, our specific use of genetic algorithms (GAs) attempts to replace standard wavelet filter coefficients with an optimized transform filter in order to retain or improve image quality for bandwidth-restricted surveillance applications. To find improved coefficients efficiently, we have developed a software engineered distributed design employing a genetic algorithm (GA) parallel island model on small and large computational clusters with multi-core nodes. The main objective is to determine whether running a distributed GA with multiple islands would either give statistically equivalent results quicker or obtain better results in the same amount of time. In order to compare computational performance with our previous serial results, we evaluate the obtained "optimal" wavelet coefficients on test images from both approaches which results in excellent comparative metric values.

  19. Defining genes using "blueprint" versus "instruction" metaphors: effects for genetic determinism, response efficacy, and perceived control.

    PubMed

    Parrott, Roxanne; Smith, Rachel A

    2014-01-01

    Evidence supports mixed attributions aligned with personal and/or clinical control and gene expression for health in this era of genomic science and health care. We consider variance in these attributions and possible relationships to individual mind sets associated with essentialist beliefs that genes determine health versus threat beliefs that genes increase susceptibility for disease and severity linked to gene-environment interactions. Further, we contribute to theory and empirical research to evaluate the use of metaphors to define genes. Participants (N = 324) read a message that varied the introduction by providing a definition of genes that used either an "instruction" metaphor or a "blueprint" metaphor. The "instruction" metaphor compared to the "blueprint" metaphor promoted stronger threat perceptions, which aligned with both belief in the response efficacy of genetic research for health and perceived behavioral control linked to genes and health. The "blueprint" metaphor compared to the "instruction" metaphor promoted stronger essentialist beliefs, which aligned with more intense positive regard for the efficacy of genetic research and human health. Implications for health communicators include societal effects aligned with stigma and discrimination that such findings portend.

  20. Genetically Determined Chronic Pancreatitis but not Alcoholic Pancreatitis Is a Strong Risk Factor for Pancreatic Cancer.

    PubMed

    Midha, Shallu; Sreenivas, Vishnubhatla; Kabra, Madhulika; Chattopadhyay, Tushar Kanti; Joshi, Yogendra Kumar; Garg, Pramod Kumar

    2016-11-01

    To study if chronic pancreatitis (CP) is a risk factor for pancreatic cancer. Through a cohort and a case-control study design, CP and other important risk factors including smoking, diabetes, alcohol, obesity, and genetic mutations were studied for their association with pancreatic cancer. In the cohort study, 402 patients with CP were included. During 3967.74 person-years of exposure, 5 of the 402 patients (4 idiopathic CP, 1 hereditary CP) developed pancreatic cancer after 16.60 ± 3.51 years of CP. The standardized incidence ratio was 121. In the case-control study, 249 pancreatic cancer patients and 1000 healthy controls were included. Of the 249 patients with pancreatic cancer, 24 had underlying idiopathic CP, and none had alcoholic pancreatitis. SPINK1 gene mutation was present in 16 of 26 patients with idiopathic CP who had pancreatic cancer. Multivariable analysis showed CP (odds ratio [OR], 97.67; 95% confidence interval [CI], 12.69-751.36), diabetes (>4 years duration) (OR, 3.05; 95% CI, 1.79-5.18), smoking (OR, 1.93; 95% CI, 1.38-2.69) as significant risk factors for pancreatic cancer. The population attributable risk was 9.41, 9.06, and 9.50 for diabetes, CP, and smoking, respectively. Genetically determined CP but not alcoholic CP is a strong risk factor for pancreatic cancer.

  1. Genetic determinism of anatomical and hydraulic traits within an apple progeny.

    PubMed

    Lauri, Pierre-Éric; Gorza, Olivier; Cochard, Hervé; Martinez, Sébastien; Celton, Jean-Marc; Ripetti, Véronique; Lartaud, Marc; Bry, Xavier; Trottier, Catherine; Costes, Evelyne

    2011-08-01

    The apple tree is known to have an isohydric behaviour, maintaining rather constant leaf water potential in soil with low water status and/or under high evaporative demand. However, little is known on the xylem water transport from roots to leaves from the two perspectives of efficiency and safety, and on its genetic variability. We analysed 16 traits related to hydraulic efficiency and safety, and anatomical traits in apple stems, and the relationships between them. Most variables were found heritable, and we investigated the determinism underlying their genetic control through a quantitative trait loci (QTL) analysis on 90 genotypes from the same progeny. Principal component analysis (PCA) revealed that all traits related to efficiency, whether hydraulic conductivity, vessel number and area or wood area, were included in the first PC, whereas the second PC included the safety variables, thus confirming the absence of trade-off between these two sets of traits. Our results demonstrated that clustered variables were characterized by common genomic regions. Together with previous results on the same progeny, our study substantiated that hydraulic efficiency traits co-localized with traits identified for tree growth and fruit production.

  2. The geographical and environmental determinants of genetic diversity for four alpine conifers of the European Alps.

    PubMed

    Mosca, E; Eckert, A J; Di Pierro, E A; Rocchini, D; La Porta, Nicola; Belletti, P; Neale, D B

    2012-11-01

    Climate is one of the most important drivers of local adaptation in forest tree species. Standing levels of genetic diversity and structure within and among natural populations of forest trees are determined by the interplay between climatic heterogeneity and the balance between selection and gene flow. To investigate this interplay, single nucleotide polymorphisms (SNPs) were genotyped in 24 to 37 populations from four subalpine conifers, Abies alba Mill., Larix decidua Mill., Pinus cembra L. and Pinus mugo Turra, across their natural ranges in the Italian Alps and Apennines. Patterns of population structure were apparent using a Bayesian clustering program, STRUCTURE, which identified three to five genetic groups per species. Geographical correlates with these patterns, however, were only apparent for P. cembra. Multivariate environmental variables [i.e. principal components (PCs)] were subsequently tested for association with SNPs using a Bayesian generalized linear mixed model. The majority of the SNPs, ranging from six in L. decidua to 18 in P. mugo, were associated with PC1, corresponding to winter precipitation and seasonal minimum temperature. In A. alba, four SNPs were associated with PC2, corresponding to the seasonal minimum temperature. Functional annotation of those genes with the orthologs in Arabidopsis revealed several genes involved in abiotic stress response. This study provides a detailed assessment of population structure and its association with environment and geography in four coniferous species in the Italian mountains.

  3. Correlations between heterozygosity and measures of genetic similarity: implications for understanding mate choice.

    PubMed

    Roberts, S C; Hale, M L; Petrie, M

    2006-03-01

    There is currently considerable interest in testing the effects of genetic compatibility and heterozygosity on animal mate preferences. Evidence for either effect is rapidly accumulating, although results are not always clear-cut. However, correlations between mating preferences and either genetic similarity or heterozygosity are usually tested independently, and the possibility that similarity and heterozygosity may be confounded has rarely been taken into account. Here we show that measures of genetic similarity (allele sharing, relatedness) may be correlated with heterozygosity, using data from 441 human individuals genotyped at major loci in the major histocompatibility complex, and 281 peafowl (Pavo cristatus) individuals genotyped at 13 microsatellite loci. We show that average levels of allele sharing and relatedness are each significantly associated with heterozygosity in both humans and peafowl, that these relationships are influenced by the level of polymorphism, and that these similarity measures may correlate with heterozygosity in qualitatively different ways. We discuss the implications of these inter-relationships for interpretation of mate choice studies. It has recently become apparent that mating preferences for 'good genes' and 'compatible genes' may introduce discordant choice amongst individuals, since the optimal mate for one trait may not be optimal for the other, and our results are consistent with this idea. The inter-relationship between these measures of genetic quality also carries implications for the way in which mate choice studies are designed and interpreted, and generates predictions that can be tested in future research.

  4. Genetic correlation between live body measurements and beef cutability traits in Hanwoo steers

    PubMed Central

    Choy, Yun Ho; Lee, Jae Goo; Mahboob, Alam; Choi, Tae Jeong; Rho, Seung Hee

    2017-01-01

    Objective The growth, carcass and retail cut yield records on 1,428 Hanwoo steers obtained through progeny testing were analyzed in this study, and their heritability and genetic relationships among the traits were estimated using animal models. Methods Two different models were compared in this study. Each model was fitted for different fixed class effects, date of slaughter for carcass traits and batch of progeny test live measurement traits, and a choice of covariates (carcass weight in Model 1 or backfat thickness in Model 2) for carcass traits. Results The differences in body composition among individuals were deemed being unaffected by their age at slaughter, except for carcass weight and backfat thickness. Heritability estimates of body size measurements were 0.21 to 0.36. Heritability estimates of retail cut percentage were high (0.56 from Model 1 and 0.47 from Model 2). And the heritability estimates for loin muscle percentage were 0.36 from Model 1 and 0.42 from Model 2, which were high enough to consider direct selection on carcass cutability traits as effective. The genetic correlations between body size measurements and retail cut ratio (RCR) were close to zero. But, some negative genetic correlations were found with chest girths measured at yearling (Model 1) or at 24 months of age or with chest widths. Loin muscle ratio (LMR) was genetically negatively correlated with body weights or body size measurements, in general in Model 1. These relationships were low close to zero but positive in Model 2. Phenotypic correlation between cutability traits (RCR, LMR) and live body size measurements were moderate and negative in Model 1 while those in Model 2 were all close to zero. Conclusion Therefore, the body weights or linear body measurements at an earlier age may not be the most desirable selection traits for exploitation of correlated responses to improve loin muscle or lean meat yield. PMID:28335095

  5. Fluorescence lifetime measurements of boronate derivatives to determine glucose concentration

    SciTech Connect

    Gable, J H

    2000-06-01

    )-anthracene (MAMA), and N-benzyl-N-methyl-N-methyl anthracene (AB-B). Fluorescence lifetime measurements confirmed the two species of AB, with and without PET. Fluorescence lifetimes were approximately 11 nsec without PET and 3 nsec with PET. The degree of the interaction between the N and the B atoms was also determined by fluorescence lifetime measurements. Electron transfer rates of AB were measured to be on the order of 10{sup 8} sec{sup -1}. Analysis of AB as a glucose sensor shows it has the potential for measuring glucose concentrations in solution with less than 5% error. Two novel glucose sensing molecules, Chloro-oxazone boronate (COB) and Napthyl-imide boronate (NIB), were synthesized. Both molecules have a N{yields}B dative bond similar to AB, but with longer wavelength fluorophores. COB and NIB were found to be unacceptable for use as glucose sensor molecules due to the small changes in average fluorescence lifetime.

  6. Genetic approaches to determine the role of glucocorticoid signaling in osteoblasts.

    PubMed

    Harrison, John R; Woitge, Henning W; Kream, Barbara E

    2002-02-01

    A variety of in vivo and in vitro experimental models have been used to explore the effects of glucococorticoids in bone. Chronically high levels of glucocorticoids typically decrease bone mass in humans and animals and inhibit markers of bone formation in organ and cell cultures. However, under certain experimental conditions, glucocorticoids can stimulate osteoblast differentiation and bone formation in vitro. The relevance of these effects seen in culture models to the role of endogenous glucocorticoids in bone remains unclear. In this article, we briefly review possible pathways for the opposing effects of glucocorticoids on bone formation and propose several genetic loss-of-function mouse models in which disruption of glucocorticoid signaling in cells of the osteoblast lineage would provide a means to determine the role of endogenous glucocorticoids in bone.

  7. Rapid phenotyping of knockout mice to identify genetic determinants of bone strength

    PubMed Central

    Freudenthal, Bernard; Logan, John; Croucher, Peter I

    2016-01-01

    The genetic determinants of osteoporosis remain poorly understood, and there is a large unmet need for new treatments in our ageing society. Thus, new approaches for gene discovery in skeletal disease are required to complement the current genome-wide association studies in human populations. The International Knockout Mouse Consortium (IKMC) and the International Mouse Phenotyping Consortium (IMPC) provide such an opportunity. The IKMC generates knockout mice representing each of the known protein-coding genes in C57BL/6 mice and, as part of the IMPC initiative, the Origins of Bone and Cartilage Disease project identifies mutants with significant outlier skeletal phenotypes. This initiative will add value to data from large human cohorts and provide a new understanding of bone and cartilage pathophysiology, ultimately leading to the identification of novel drug targets for the treatment of skeletal disease. PMID:27535945

  8. Rapid phenotyping of knockout mice to identify genetic determinants of bone strength.

    PubMed

    Freudenthal, Bernard; Logan, John; Croucher, Peter I; Williams, Graham R; Bassett, J H Duncan

    2016-10-01

    The genetic determinants of osteoporosis remain poorly understood, and there is a large unmet need for new treatments in our ageing society. Thus, new approaches for gene discovery in skeletal disease are required to complement the current genome-wide association studies in human populations. The International Knockout Mouse Consortium (IKMC) and the International Mouse Phenotyping Consortium (IMPC) provide such an opportunity. The IKMC generates knockout mice representing each of the known protein-coding genes in C57BL/6 mice and, as part of the IMPC initiative, the Origins of Bone and Cartilage Disease project identifies mutants with significant outlier skeletal phenotypes. This initiative will add value to data from large human cohorts and provide a new understanding of bone and cartilage pathophysiology, ultimately leading to the identification of novel drug targets for the treatment of skeletal disease. © 2016 Society for Endocrinology.

  9. Interpretation of electrophoretograms of seven microsatellite loci to determine the genetic diversity of the Arabian Oryx.

    PubMed

    Arif, I A; Khan, H A; Shobrak, M; Al Homaidan, A A; Al Sadoon, M; Al Farhan, A H; Bahkali, A H

    2010-02-09

    Microsatellite markers are commonly used for examining population structure, especially inbreeding, outbreeding and gene flow. An array of microsatellite loci, preferably with multiallelic presentation, is preferable for ensuring accurate results. However, artifact peaks or stutters in the electrophoretograms significantly hamper the reliable interpretation of genotypes. We interpreted electrophoretograms of seven microsatellite loci to determine the genetic diversity of the Arabian Oryx. All the alleles of different loci exhibited good peak resolutions and hence were clearly identified. Moreover, none of the stutter peaks impaired the recognition or differentiation between homozygote and heterozygote. Our findings suggest that correct identification of alleles in the presence of co-amplified nonspecific fragments is important for reliable interpretation of microsatellite data.

  10. Influence of arginine vasotocin on a genetically determined excessive appetite for water in chickens.

    PubMed

    Raffel, L J; Buss, E G; Glagett, C O

    1976-09-01

    Females from two inbred strains of chickens, one normal and one having hereditary diabetes insipidus, were treated with five levels (2.5, 1.0, 0.5, 0.25, and 0.1 units) of Schwartz-Mann (Grade A, 100 units/mg.) arginine vasotocin via ic. injections at 2-hr. intervals. Paired sibs, one normal and one having diabetes insipidus (di), from an F2 population were used in one experiment to compare responses at the level of 2.5 units. Only di females were used for the remaining four levels of treatment. Water intake was determined every two hours and calculated as a percentage of water (ml.)/body wt. Results show that hereditary diabetes insipidus in chickens is arginine vasotocin-sensitive at the 0.5 unit and higher levels. The genetic defect appears to affect the quantity of antidiuretic hormone produced.

  11. Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes

    PubMed Central

    Lees, John A.; Vehkala, Minna; Välimäki, Niko; Harris, Simon R.; Chewapreecha, Claire; Croucher, Nicholas J.; Marttinen, Pekka; Davies, Mark R.; Steer, Andrew C.; Tong, Steven Y. C.; Honkela, Antti; Parkhill, Julian; Bentley, Stephen D.; Corander, Jukka

    2016-01-01

    Bacterial genomes vary extensively in terms of both gene content and gene sequence. This plasticity hampers the use of traditional SNP-based methods for identifying all genetic associations with phenotypic variation. Here we introduce a computationally scalable and widely applicable statistical method (SEER) for the identification of sequence elements that are significantly enriched in a phenotype of interest. SEER is applicable to tens of thousands of genomes by counting variable-length k-mers using a distributed string-mining algorithm. Robust options are provided for association analysis that also correct for the clonal population structure of bacteria. Using large collections of genomes of the major human pathogens Streptococcus pneumoniae and Streptococcus pyogenes, SEER identifies relevant previously characterized resistance determinants for several antibiotics and discovers potential novel factors related to the invasiveness of S. pyogenes. We thus demonstrate that our method can answer important biologically and medically relevant questions. PMID:27633831

  12. [Experimental analysis of the neurobiological basis of genetically determined alcohol addiction in the progeny].

    PubMed

    Vorob'eva, T M; Geĭko, V V

    1990-01-01

    Experiments on 45 nonlinear albino male rats were made to investigate bioelectrogenesis of the limbic-neocortical parts of the brain, function of the systems of positive and negative reinforcement and emotional behavior of the progeny of long alcoholized animals with successive growth of the extent of alcoholism aggravation. Their different initial characteristics were discovered in intact rats as regards parents' alcoholism and in alcoholism aggravated rats, determining different mechanisms and rates of the development of pathological ethanol addiction. The pathogenic influence of "familial" alcoholism lies in the formation in the progeny of the first and fourth generations of the model of alcohol addiction anticipation, whose pathological integration is realized on the basis of the beforehand prepared model which becomes quantitatively different as a result of genetic anomalies.

  13. A genome scan conducted in a multigenerational pedigree with convergent strabismus supports a complex genetic determinism.

    PubMed

    Georges, Anouk; Cambisano, Nadine; Ahariz, Naïma; Karim, Latifa; Georges, Michel

    2013-01-01

    A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree including all affected individuals were genotyped using a SNP array interrogating > 300,000 common SNPs. We conducted parametric and non-parametric linkage analyses assuming segregation of an autosomal dominant mutation, yet allowing for incomplete penetrance and phenocopies. We detected two chromosome regions with near-suggestive evidence for linkage, respectively on chromosomes 8 and 18. The chromosome 8 linkage implied a penetrance of 0.80 and a rate of phenocopy of 0.11, while the chromosome 18 linkage implied a penetrance of 0.64 and a rate of phenocopy of 0. Our analysis excludes a simple genetic determinism of strabismus in this pedigree.

  14. Treatment factors rather than genetic variation determine metabolic syndrome in childhood cancer survivors.

    PubMed

    van Waas, Marjolein; Neggers, Sebastian J C M M; Uitterlinden, André G; Blijdorp, Karin; van der Geest, Ivana M M; Pieters, Rob; van den Heuvel-Eibrink, Marry M

    2013-02-01

    Genetic variation that regulates insulin resistance, blood pressure and adiposity in the normal population might determine differential vulnerability for metabolic syndrome after treatment for childhood cancer. To evaluate the contribution of candidate single nucleotide polymorphisms (SNPs) relevant for metabolic syndrome in our single centre cohort of adult long-term childhood cancer survivors. In this retrospective study 532 survivors were analysed. Median age at diagnosis was 5.7 years (range 0.0-17.8 years), median follow-up time was 17.9 years (range 5.0-48.8) and median age at follow-up was 25.6 years (range 18.0-50.8). JAZF1 gene rs864745, THADA gene rs7578597, IRS1 gene rs2943641, TFAP2B gene rs987237, MSRA gene rs7826222, ATP2B1 gene rs2681472 and rs2681492 were genotyped. The association of genotypes with total cholesterol levels, blood pressure, body mass index, waist circumference and frequency of diabetes were assessed. Metabolic syndrome was more frequent in cranially (23.3%, P=0.002) and abdominally (23.4%, P=0.009) irradiated survivors as compared with non-irradiated survivors (10.0%). Association of allelic variants in rs2681472 and rs2681492 with hypertension, rs987237 and rs7826222 with waist circumference and rs864745, rs7578597 and rs2943641 with diabetes were not significant. None of the SNPs was associated with the metabolic syndrome. Adjusting for age, sex, follow-up time, cranial irradiation and abdominal irradiation did not change these results. Treatment factors and not genetic variation determine hypertension, waist circumference, diabetes and metabolic syndrome in adult long-term survivors of childhood cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Genetic determinants of anti-malarial acquired immunity in a large multi-centre study.

    PubMed

    Shelton, Jennifer M G; Corran, Patrick; Risley, Paul; Silva, Nilupa; Hubbart, Christina; Jeffreys, Anna; Rowlands, Kate; Craik, Rachel; Cornelius, Victoria; Hensmann, Meike; Molloy, Sile; Sepulveda, Nuno; Clark, Taane G; Band, Gavin; Clarke, Geraldine M; Spencer, Christopher C A; Kerasidou, Angeliki; Campino, Susana; Auburn, Sarah; Tall, Adama; Ly, Alioune Badara; Mercereau-Puijalon, Odile; Sakuntabhai, Anavaj; Djimdé, Abdoulaye; Maiga, Boubacar; Touré, Ousmane; Doumbo, Ogobara K; Dolo, Amagana; Troye-Blomberg, Marita; Mangano, Valentina D; Verra, Frederica; Modiano, David; Bougouma, Edith; Sirima, Sodiomon B; Ibrahim, Muntaser; Hussain, Ayman; Eid, Nahid; Elzein, Abier; Mohammed, Hiba; Elhassan, Ahmed; Elhassan, Ibrahim; Williams, Thomas N; Ndila, Carolyne; Macharia, Alexander; Marsh, Kevin; Manjurano, Alphaxard; Reyburn, Hugh; Lemnge, Martha; Ishengoma, Deus; Carter, Richard; Karunaweera, Nadira; Fernando, Deepika; Dewasurendra, Rajika; Drakeley, Christopher J; Riley, Eleanor M; Kwiatkowski, Dominic P; Rockett, Kirk A

    2015-08-28

    Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of

  16. Active efflux of tetracycline encoded by four genetically different tetracycline resistance determinants in Escherichia coli.

    PubMed Central

    McMurry, L; Petrucci, R E; Levy, S B

    1980-01-01

    Tetracycline resistance encoded by four genetically different determinants residing on plasmids in Escherichia coli was shown to be associated in each case with an energy-dependent decrease in accumulation of the antibiotic in whole cells in which resistance had been induced. The different class determinants examined were those on plasmids RP1 (class A), R222 (class B), R144 (class C), and RA1 (class D). This decrease in accumulation was attributable to an active efflux, because everted (inside-out) membrane vesicles made from tetracycline-induced E. coli cells containing any one of the four plasmids were shown to concentrate tetracycline by an active influx. This active uptake was not seen in inside-out vesicles from sensitive cells or uninduced R222-containing cells. In vesicles from induced R222-containing cells, the efflux appeared to be carrier-mediated with a Km of about 6 microM. These results demonstrate that active export of tetracycline is a common component of the mechanism for tetracycline resistance encoded by different plasmid-borne determinants in bacteria. PMID:7001450

  17. Disentangling genetic vs. environmental causes of sex determination in the common frog, Rana temporaria.

    PubMed

    Matsuba, Chikako; Miura, Ikuo; Merilä, Juha

    2008-01-08

    Understanding of sex ratio dynamics in a given species requires understanding its sex determination system, as well as access for reliable tools for sex identification at different life stages. As in the case of many other amphibians, the common frogs (Rana temporaria) do not have well differentiated sex chromosomes, and an identification of individuals' genetic sex may be complicated by sex reversals. Here, we report results of studies shedding light on the sex determination system and sex ratio variation in this species. A microsatellite locus RtSB03 was found to be sex-linked in four geographically disparate populations, suggesting male heterogamy in common frogs. However, in three other populations examined, no or little evidence for sex-linkage was detected suggesting either ongoing/recent recombination events, and/or frequent sex-reversals. Comparison of inheritance patterns of alleles in RtSB03 and phenotypic sex within sibships revealed a mixed evidence for sex-linkage: all individuals with male phenotype carried a male specific allele in one population, whereas results were more mixed in another population. These results make sense only if we assume that the RtSB03 locus is linked to male sex determination factor in some, but not in all common frog populations, and if phenotypic sex-reversals - for which there is earlier evidence from this species - are frequently occurring.

  18. Disentangling genetic vs. environmental causes of sex determination in the common frog, Rana temporaria

    PubMed Central

    Matsuba, Chikako; Miura, Ikuo; Merilä, Juha

    2008-01-01

    Background Understanding of sex ratio dynamics in a given species requires understanding its sex determination system, as well as access for reliable tools for sex identification at different life stages. As in the case of many other amphibians, the common frogs (Rana temporaria) do not have well differentiated sex chromosomes, and an identification of individuals' genetic sex may be complicated by sex reversals. Here, we report results of studies shedding light on the sex determination system and sex ratio variation in this species. Results A microsatellite locus RtSB03 was found to be sex-linked in four geographically disparate populations, suggesting male heterogamy in common frogs. However, in three other populations examined, no or little evidence for sex-linkage was detected suggesting either ongoing/recent recombination events, and/or frequent sex-reversals. Comparison of inheritance patterns of alleles in RtSB03 and phenotypic sex within sibships revealed a mixed evidence for sex-linkage: all individuals with male phenotype carried a male specific allele in one population, whereas results were more mixed in another population. Conclusion These results make sense only if we assume that the RtSB03 locus is linked to male sex determination factor in some, but not in all common frog populations, and if phenotypic sex-reversals – for which there is earlier evidence from this species – are frequently occurring. PMID:18182101

  19. Float genetic algorithm for determination of particle size distribution and refractive index in polarized LSS

    NASA Astrophysics Data System (ADS)

    Deng, Yong; Hu, Rui; Luo, Qingming; Lu, Qiang

    2005-04-01

    Polarized light scattering spectroscopy (LSS) is sensitive to the cell nuclear morphological changes in the various forms of epithelial dysplasia. Extensive studies illustrate it is a promising in situ technique to detect precancerous and early cancerous changes in the epithelial tissue. To determine the density and size distribution of cell nuclei with spectra, generally, Mie theory-based inverse model is adopted. This model is of multiple parameters, multiple extreme values and nonlinear. The determination of all unknown parameters needs to solve a nonlinear inverse problem. Other than least-square fitting used by previous studies, in this paper, we developed a novel method - float genetic algorithm (FGA) to determine the particle size distribution and refractive index for LSS. Our results showed that, relative errors of three estimated statistical quantities: diameter, standard deviation and refractive index are less than 5% for different additive Gauss noise levels with 70 iteration epochs. The errors gradually decrease with iteration epoch increases. Moreover, comparing with Newton-type iteration method coupled with a Marquardt-Tikhanov regularization scheme, FGA avoids the problems of local extreme value and selection of initial value and regularization parameters, thus obtains the advantages of high precision, stability and robustness.

  20. Using Genetically Encodable Self-Assembling Gd(III) Spin Labels To Make In-Cell Nanometric Distance Measurements.

    PubMed

    Mascali, Florencia C; Ching, H Y Vincent; Rasia, Rodolfo M; Un, Sun; Tabares, Leandro C

    2016-09-05

    Double electron-electron resonance (DEER) can be used to study the structure of a protein in its native cellular environment. Until now, this has required isolation, in vitro labeling, and reintroduction of the protein back into the cells. We describe a completely biosynthetic approach that avoids these steps. It exploits genetically encodable lanthanide-binding tags (LBT) to form self-assembling Gd(III) metal-based spin labels and enables direct in-cell measurements. This approach is demonstrated using a pair of LBTs encoded one at each end of a 3-helix bundle expressed in E. coli grown on Gd(III) -supplemented medium. DEER measurements directly on these cells produced readily detectable time traces from which the distance between the Gd(III) labels could be determined. This work is the first to use biosynthetically produced self-assembling metal-containing spin labels for non-disruptive in-cell structural measurements.

  1. Determination of struvite crystallization mechanisms in urine using turbidity measurement.

    PubMed

    Triger, Aurélien; Pic, Jean-Stéphane; Cabassud, Corinne

    2012-11-15

    Sanitation improvement in developing countries could be achieved through wastewater treatment processes. Nowadays alternative concepts such as urine separate collection are being developed. These processes would be an efficient way to reduce pollution of wastewater while recovering nutrients, especially phosphorus, which are lost in current wastewater treatment methods. The precipitation of struvite (MgNH(4)PO(4)∙6H(2)O) from urine is an efficient process yielding more than 98% phosphorus recovery with very high reaction rates. The work presented here aims to determine the kinetics and mechanisms of struvite precipitation in order to supply data for the design of efficient urine treatment processes. A methodology coupling the resolution of the population balance equation to turbidity measurement was developed, and batch experiments with synthetic and real urine were performed. The main mechanisms of struvite crystallization were identified as crystal growth and nucleation. A satisfactory approximation of the volumetric crystal size distribution was obtained. The study has shown the low influence on the crystallization process of natural organic matter contained in real urine. It has also highlighted the impact of operational parameters. Mixing conditions can create segregation and attrition which influence the nucleation rate, resulting in a change in crystals number, size, and thus final crystal size distribution (CSD). Moreover urine storage conditions can impact urea hydrolysis and lead to spontaneous struvite precipitation in the stock solution also influencing the final CSD. A few limits of the applied methodology and of the proposed modelling, due to these phenomena and to the turbidity measurement, are also discussed.

  2. Determination of the Genetic Diversity of Different Bioluminescent Bacteria by Pulsed-Field Gel Electrophoresis (PFGE)

    PubMed Central

    Ersoy Omeroglu, Esra

    2015-01-01

    Background: There are 4 different genera (i.e. Vibrio, Aliivibrio, Photobacterium, and Shewanella) in the new classification of bioluminescent bacteria. The mechanism of bioluminescence has yet to be fully elucidated. Therefore, the determination of physiological and genetic characteristics of bioluminescent bacteria isolated from different sources is very important. Pulsed-Field Gel Electrophoresis (PFGE) has the highest discriminatory power among the different molecular typing methods for the investigation of the clonal relationships between bacteria. For the PFGE analysis of bioluminescent bacteria, the NotI-HF™ is the method of choice among the restriction enzymes. Objectives: The present study aimed to determine genetic relatedness via PFGE in 41 bioluminescent bacteria (belonging to 10 different species) isolated and identified from various marine sources. Materials and Methods: Different bioluminescent bacteria (i.e. Vibrio gigantis, V. azureus, V. harveyi, V. lentus, V. crassostreae, V. orientalis, Aliivibrio logei, A. fischeri, Shewanella woodyi, and Photobacterium kishitanii) were analyzed by PFGE using the NotI-HF™ restriction enzyme. The whole DNA of the strains embedded into the agarose plugs was digested with enzyme at 37°C for 30 minutes. CHEF-Mapper PFGE system was used for electrophoresis and band profile of the strains for the NotI-HF™ restriction enzyme were analyzed by Bio-Profil-1D++ software (Vilber Lourmat) at 10% homology coefficient. Results: Although all experiments were performed three times, four of forty-one bioluminescent strains (V. gigantis E-16, H-16 and S3W46 strains and A. fischeri E-4 strain) could not be typed by PFGE technique with NotI-HF™ enzyme. While only two strains (V. crassostreae H-12 and H-19 strains) were exhibiting same band pattern profiles (100% genome homology), thirty-six different PFGE band patterns were obtained. Pattern homologies changed between 66% - 92%, 73% - 83% and 49% - 100% for V. gigantis, V

  3. Determination of Ionospheric Total Electron Content Derived from Gnss Measurements

    NASA Astrophysics Data System (ADS)

    Inyurt, S.; Mekik, C.; Yildirim, O.

    2014-12-01

    Global Navigation Satellite System (GNSS) has been used in numerous fields especially related to satellite- based radio navigation system for a long time. Ionosphere, one of the upper atmosphere layers ranges from 60 km to 1500 km, is a dispersive medium and it includes a number of free electrons and ions. The ionization is mainly subject to the sun and its activity. Ionospheric activity depends also on seasonal, diurnal variations and geographical location. Total Electron Content (TEC), which is also called Slant Total Electron Content (STEC), is a parameter that changes according to ionospheric conditions and has highly variable structure. Furthermore, Vertical TEC (VTEC) can be explained as TEC value in the direction of zenith. Thanks to VTEC, TEC values can be modelled. TEC is measured in units of TECU and 1TECU= 1016 electrons/m2. Ionospheric modelling has a great importance for improving the accuracies of positioning and understanding the ionosphere. Thus, various models have been developed to detect TEC value in the last years. Single Layer Model (SLM) which provides determining TEC value and GPS positioning in the ionosphere accurately is one of the most commonly used models. SLM assumes that all free electrons are concentrated in a shell of infinitesimal thickness. In this paper SLM model was used to derive TEC values by means of Bernese 5.0 program developed by the University of Bern, Sweden. In this study, we have used regional ionosphere model to derive TEC value. First of all, GPS data have been collected from 10 stations in Turkey and 13 IGS stations for 7 days from 06.03.2010 to 12.03.2010. Then, Regional Ionosphere Model (RIM) is created with the reference of the GPS data. At the end of the process, the result files are stored as IONEX format. TEC results for those days are obtained with two hours interval. TEC variation related to the research area ranges from nearly 6 TECU to approximately 20 TECU. The obtained results show that TEC values start

  4. Contrasting results from molecular and pedigree-based population diversity measures in captive zebra highlight challenges facing genetic management of zoo populations.

    PubMed

    Ito, Hideyuki; Ogden, Rob; Langenhorst, Tanya; Inoue-Murayama, Miho

    2017-01-01

    Zoo conservation breeding programs manage the retention of population genetic diversity through analysis of pedigree records. The range of demographic and genetic indices determined through pedigree analysis programs allows the conservation of diversity to be monitored relative to the particular founder population for a species. Such approaches are based on a number of well-documented founder assumptions, however without knowledge of actual molecular genetic diversity there is a risk that pedigree-based measures will be misinterpreted and population genetic diversity misunderstood. We examined the genetic diversity of the captive populations of Grevy's zebra, Hartmann's mountain zebra and plains zebra in Japan and the United Kingdom through analysis of mitochondrial DNA sequences. Very low nucleotide variability was observed in Grevy's zebra. The results were evaluated with respect to current and historic diversity in the wild, and indicate that low genetic diversity in the captive population is likely a result of low founder diversity, which in turn suggests relatively low wild genetic diversity prior to recent population declines. Comparison of molecular genetic diversity measures with analogous diversity indices generated from the studbook data for Grevy's zebra and Hartmann's mountain zebra show contrasting patterns, with Grevy's zebra displaying markedly less molecular diversity than mountain zebra, despite studbook analysis indicating that the Grevy's zebra population has substantially more founders, greater effective population size, lower mean kinship, and has suffered less loss of gene diversity. These findings emphasize the need to validate theoretical estimates of genetic diversity in captive breeding programs with empirical molecular genetic data. Zoo Biol. 36:87-94, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Random Genetic Drift Determines the Level of Mutant mtDNA in Human Primary Oocytes

    PubMed Central

    Brown, D. T.; Samuels, D. C.; Michael, E. M.; Turnbull, D. M.; Chinnery, P. F.

    2001-01-01

    We measured the proportion of mutant mtDNA (mutation load) in 82 primary oocytes from a woman who harbored the A3243G mtDNA mutation. The frequency distribution of mutation load indicates that random drift is the principal mechanism that determines the level of mutant mtDNA within individual oocytes. PMID:11133360

  6. 76 FR 8707 - Syngenta Seeds, Inc.; Determination of Nonregulated Status for Corn Genetically Engineered To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ..., ``Introduction of Organisms and Products Altered or Produced Through Genetic Engineering Which Are Plant Pests or... produced through genetic engineering that are plant pests or that there is reason to believe are plant...

  7. 75 FR 1585 - Draft Environmental Impact Statement; Determination of Regulated Status of Alfalfa Genetically...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-12

    ... Through Genetic Engineering Which Are Plant Pests or Which There Is Reason to Believe Are Plant Pests... environment) of organisms and products altered or produced through genetic engineering that are plant pests or...

  8. 77 FR 41350 - Monsanto Co.; Determination of Nonregulated Status of Soybean Genetically Engineered To Produce...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... Through Genetic Engineering Which Are Plant Pests or Which There Is Reason to Believe Are Plant Pests... environment) of organisms and products altered or produced through genetic engineering that are plant pests or...

  9. 78 FR 37201 - Pioneer Hi-Bred International, Inc.; Determination of Nonregulated Status of Maize Genetically...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-20

    ..., ``Introduction of Organisms and Products Altered or Produced Through Genetic Engineering Which Are Plant Pests or... produced through genetic engineering that are plant pests or that there is reason to believe are plant...

  10. 76 FR 63279 - Monsanto Co.; Determination of Nonregulated Status for Soybean Genetically Engineered for Insect...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-12

    ... Through Genetic Engineering Which Are Plant Pests or Which There Is Reason to Believe Are Plant Pests... environment) of organisms and products altered or produced through genetic engineering that are plant pests or...

  11. 75 FR 29969 - Environmental Impact Statement; Determination of Nonregulated Status of Sugar Beet Genetically...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-28

    ... of Organisms and Products Altered or Produced Through Genetic Engineering Which Are Plant Pests or... produced through genetic engineering that are plant pests or that there is reason to believe are plant...

  12. 76 FR 78232 - Monsanto Co.; Determination of Nonregulated Status for Soybean Genetically Engineered To Have a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-16

    ..., ``Introduction of Organisms and Products Altered or Produced Through Genetic Engineering Which Are Plant Pests or... produced through genetic engineering that are plant pests or that there is reason to believe are plant...

  13. DOSE TO CURIE DETERMINATION FOR CONTAINERS WITH MEASURABLE CS-137

    SciTech Connect

    RATHBUN LA; ANDERSON JD; SWAN RJ

    2010-12-03

    The Next Generation Retrieval (NGR) project will retrieve suspect transuranic (TRU) waste containers from Trenches 17 and 27 in the 218-E-12B (12B) burial ground. The trenches were in operation from May 1970 through October 1972. A portion of the retrieved containers that will require shipment to and acceptance at a treatment, storage, and disposal (TSD) facility and the containers will be either remote-handled (RH) and/or contact-handled (CH). The method discussed in this document will be used for the RH and some of the CH containers to determine the radionuclide inventory. Waste disposition (shipment and TSD acceptance) requires that the radioactive content be characterized for each container. Source-term estimates using high resolution, shielded, gamma-ray scan assay techniques cannot be performed on a number of RH and other containers with high dose rates from {sup 137}Cs-{sup 137m}Ba. This document provides the method to quantify the radioactive inventory of fission product gamma emitters within the containers based on the surface dose rate measurements taken in the field with hand-held survey instruments.

  14. Sex impact on the quality of fatty liver and its genetic determinism in mule ducks.

    PubMed

    Marie-Etancelin, C; Retailleau, B; Alinier, A; Vitezica, Z G

    2015-09-01

    Recent changes to French regulations now allow farmers to produce "foie gras" from both male and female mule ducks. The aim of this study was to assess the quality of female fatty liver and to compare, from a phenotypic and genetic point of view, liver quality in males and females. A total of 914 mule ducks (591 males and 323 females), hatched in a single pedigree batch, were reared until 86 d of age and then force-fed for 12 d, before being slaughtered. Carcasses and livers were weighed and liver quality was assessed by grading the extent of liver veining and measuring the liver melting rate, either after sterilization of 60 g of liver or pasteurization of 180 g of liver. Sexual dimorphism was observed in favor of males, with a difference of approximately 10% in carcass and liver weights and up to 54% for the liver melting rate. Moreover, one-third of female livers showed moderate to high veining, whereas this was not the case for male livers. The fatty livers of female mule ducks are, therefore, of poorer quality and could not be transformed into a product with the appellation "100% fatty liver." According to sex and parental line, heritability values ranged from 0.12 ± 0.05 to 0.18 ± 0.07 for fatty liver weight and from 0.09 ± 0.05 to 0.18 ± 0.05 for the 2 melting rate traits. The genetic correlations between the fatty liver weight and both melting rates were high (greater than +0.80) in the Muscovy population, whereas in the Pekin population, the liver weight and melting rates were less strongly correlated (estimates ranging from +0.36 ± 0.30 to +0.45 ± 0.28). Selection for lower liver melting rates without reducing the liver weight would, therefore, be easier to achieve in the Pekin population. Finally, as the 2 melting rate measurements are highly correlated (0.91 and over 0.95 for phenotypic and genetic correlations, respectively), we suggest using the easiest method, that is, sterilization of 60 g of liver.

  15. Genetic and environmental mediation between measures of personality and family environment in twins reared together.

    PubMed

    Kandler, Christian; Riemann, Rainer; Kämpfe, Nicole

    2009-01-01

    In this study we analyzed the etiology of the relationship between personality traits and retrospectively recalled family environment. The data of 226 identical and 168 fraternal twin pairs reared together from the Jena twin study of social attitudes were available. Personality traits were measured using the self- and peer report versions of the German NEO-personality inventory-revised. A German version of Blocks Environmental Questionnaire was applied to measure two broad dimensions of the family environment retrospectively: support and organization. We could replicate earlier findings that retrospective reports of these family environment dimensions were in part genetically influenced. A total of 66% of the genetic variance in support and 24% in organization could be accounted for by heritable variance in self-rated personality. That was replicated by using peer reports of personality, 41% explained genetic variance in support and 17% in organization. Environmental mediations were negligible. This indicates that the relationship between personality and retrospectively recalled family environment is largely genetically mediated.

  16. A genetic strategy to measure circulating Drosophila insulin reveals genes regulating insulin production and secretion.

    PubMed

    Park, Sangbin; Alfa, Ronald W; Topper, Sydni M; Kim, Grace E S; Kockel, Lutz; Kim, Seung K

    2014-08-01

    Insulin is a major regulator of metabolism in metazoans, including the fruit fly Drosophila melanogaster. Genome-wide association studies (GWAS) suggest a genetic basis for reductions of both insulin sensitivity and insulin secretion, phenotypes commonly observed in humans with type 2 diabetes mellitus (T2DM). To identify molecular functions of genes linked to T2DM risk, we developed a genetic tool to measure insulin-like peptide 2 (Ilp2) levels in Drosophila, a model organism with superb experimental genetics. Our system permitted sensitive quantification of circulating Ilp2, including measures of Ilp2 dynamics during fasting and re-feeding, and demonstration of adaptive Ilp2 secretion in response to insulin receptor haploinsufficiency. Tissue specific dissection of this reduced insulin signaling phenotype revealed a critical role for insulin signaling in specific peripheral tissues. Knockdown of the Drosophila orthologues of human T2DM risk genes, including GLIS3 and BCL11A, revealed roles of these Drosophila genes in Ilp2 production or secretion. Discovery of Drosophila mechanisms and regulators controlling in vivo insulin dynamics should accelerate functional dissection of diabetes genetics.

  17. Associations of genetic risk scores based on adult adiposity pathways with childhood growth and adiposity measures.

    PubMed

    Monnereau, Claire; Vogelezang, Suzanne; Kruithof, Claudia J; Jaddoe, Vincent W V; Felix, Janine F

    2016-08-18

    Results from genome-wide association studies (GWAS) identified many loci and biological pathways that influence adult body mass index (BMI). We aimed to identify if biological pathways related to adult BMI also affect infant growth and childhood adiposity measures. We used data from a population-based prospective cohort study among 3,975 children with a mean age of 6 years. Genetic risk scores were constructed based on the 97 SNPs associated with adult BMI previously identified with GWAS and on 28 BMI related biological pathways based on subsets of these 97 SNPs. Outcomes were infant peak weight velocity, BMI at adiposity peak and age at adiposity peak, and childhood BMI, total fat mass percentage, android/gynoid fat ratio, and preperitoneal fat area. Analyses were performed using linear regression models. A higher overall adult BMI risk score was associated with infant BMI at adiposity peak and childhood BMI, total fat mass, android/gynoid fat ratio, and preperitoneal fat area (all p-values < 0.05). Analyses focused on specific biological pathways showed that the membrane proteins genetic risk score was associated with infant peak weight velocity, and the genetic risk scores related to neuronal developmental processes, hypothalamic processes, cyclicAMP, WNT-signaling, membrane proteins, monogenic obesity and/or energy homeostasis, glucose homeostasis, cell cycle, and muscle biology pathways were associated with childhood adiposity measures (all p-values <0.05). None of the pathways were associated with childhood preperitoneal fat area. A genetic risk score based on 97 SNPs related to adult BMI was associated with peak weight velocity during infancy and general and abdominal fat measurements at the age of 6 years. Risk scores based on genetic variants linked to specific biological pathways, including central nervous system and hypothalamic processes, influence body fat development from early life onwards.

  18. Genetic Associations with Performance on a Behavioral Measure of Distress Intolerance

    PubMed Central

    Amstadter, Ananda B.; Daughters, Stacey B.; MacPherson, Laura; Reynolds, Elizabeth K.; Danielson, Carla Kmett; Wang, Frances; Potenza, Marc N.; Gelernter, Joel; Lejuez, C. W.

    2013-01-01

    Both theory and empirical evidence support possible associations between two candidate genetic polymorphisms (SLC6A4 5-HTTLPR l/s and COMT Val158Met – rs4680 variants) and emotion-regulation difficulties. One particular form of emotion-regulation difficulty, distress intolerance, has been measured using a behavioral assessment in youth; data indicate a relationship with poor psychological functioning. No prior study has investigated genetic influences on emotion-regulation difficulties in youth. As part of a larger longitudinal study on adolescent risk behaviors, 218 10-14 year-old youths from the metropolitan Washington, D.C., area completed a measure of distress intolerance, the Behavioral Indicator of Resilience to Distress (BIRD), and provided saliva samples for DNA extraction and genotyping. Results indicate that those with one or two copies of the s allele of the 5-HTTLPR polymorphism were more likely to perform poorly on the task (i.e., choose to quit) than were those homozygous for the l allele. Participants who were Val allele carriers of the COMT Val158Met polymorphism were also more likely to quit the task compared to Met homozygotes. A summative risk allele score was created to combine the two polymorphisms, and each risk allele was associated with a 1.75 fold increased likelihood of quitting the task. Exploratory analyses revealed that emotional abuse moderated the relationship between the 5-HTTLPR and BIRD performance, as well as the genetic risk allele and the BIRD. This is the first investigation of genetic predictors of a behavioral measure of tolerance to distress. Results suggest that distress tolerance is at least partially regulated by specific genetic variants. Implications are discussed. PMID:22024485

  19. 78 FR 13302 - Syngenta Biotechnology, Inc.; Determination of Nonregulated Status of Corn Genetically Engineered...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-27

    ... Products Altered or Produced Through Genetic Engineering Which Are Plant Pests or Which There Is Reason to... movement, or release into the environment) of organisms and products altered or produced through genetic engineering that are plant pests or that there is reason to believe are plant pests. Such genetically...

  20. 76 FR 80869 - Monsanto Co.; Determination of Nonregulated Status of Corn Genetically Engineered for Drought...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-27

    ... Products Altered or Produced Through Genetic Engineering Which Are Plant Pests or Which There Is Reason to... movement, or release into the environment) of organisms and products altered or produced through genetic engineering that are plant pests or that there is reason to believe are plant pests. Such genetically...

  1. 76 FR 5780 - Determination of Regulated Status of Alfalfa Genetically Engineered for Tolerance to the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-02

    ... Products Altered or Produced Through Genetic Engineering Which Are Plant Pests or Which There Is Reason to... movement, or release into the environment) of organisms and products altered or produced through genetic engineering that are plant pests or that there is reason to believe are plant pests. Such genetically...

  2. Environmental and genetic determinants of childhood depression: The roles of DAT1 and the antenatal environment.

    PubMed

    D'Souza, Stephanie; Thompson, John M D; Slykerman, Rebecca; Marlow, Gareth; Wall, Clare; Murphy, Rinki; Ferguson, Lynnette R; Mitchell, Edwin A; Waldie, Karen E

    2016-06-01

    Research on adolescent and adult populations has linked depression to variation in several monoaminergic genes, but genetic association studies on depression in children are limited. Additionally, few studies have investigated whether stressors occurring very early in development moderate the influence of certain genes on depression. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) from monoaminergic genes interacted with measures of early life stress to influence depressive symptoms in children. Participants were members of the Auckland Birthweight Collaborative cohort. Small for gestational age (SGA) and maternal stress during pregnancy were measured at birth and used as indicators of early life stress. At age 11, depressive symptoms were measured using the Centre for Epidemiological Studies Depression Scale for Children (CES-DC) and DNA samples were collected for genotyping. A two-way ANOVA revealed that SGA and a SNP from the dopamine transporter gene DAT1 had an interactive effect on children's depressive symptoms. Specifically, symptoms were greater in children born SGA who are T homozygous for the rs1042098 SNP. These findings suggest that adverse intrauterine environments leading to low birth weight also seem to exacerbate the effects of certain DAT1 variants on depression.

  3. Genetic linkage analysis of longitudinal hypertension phenotypes using three summary measures

    PubMed Central

    Rao, Shaoqi; Li, Lin; Li, Xia; Moser, Kathy L; Guo, Zheng; Shen, Gongqing; Cannata, Ruth; Zirzow, Erich; Topol, Eric J; Wang, Qing

    2003-01-01

    Background Longitudinal data often have multiple (repeated) measures recorded along a time trajectory. For example, the two cohorts from the Framingham Heart Study (GAW13 Problem 1) contain 21 and 5 repeated measures for hypertension phenotypes as well as epidemiological risk factors, respectively. Direct modelling of a large number of serially and biologically correlated traits in the context of linkage analysis can be prohibitively complex. Alternatively, we may consider using univariate transformation for linkage analysis of longitudinal repeated measures. Results We evaluated the utility of three conventional summary measures (mean, slope, and principal components) for genetic linkage analysis of longitudinal phenotypes by analyzing the chromosome 10 data of the Framingham Heart Study. Except for the temporal slope, all of the summary methods and the multivariate analysis identified the previously reported region, marker GATA64A09, for systolic blood pressure or high blood pressure. Further analysis revealed that this region may harbor gene(s) affecting human blood pressure at multiple stages of life. Conclusion We conclude that mean and principal components are feasible alternatives for genetic linkage analysis of longitudinal phenotypes, but the slope might have a separate genetic basis from that of the original longitudinal phenotypes. PMID:14975092

  4. Determination of Slope Safety Factor with Analytical Solution and Searching Critical Slip Surface with Genetic-Traversal Random Method

    PubMed Central

    2014-01-01

    In the current practice, to determine the safety factor of a slope with two-dimensional circular potential failure surface, one of the searching methods for the critical slip surface is Genetic Algorithm (GA), while the method to calculate the slope safety factor is Fellenius' slices method. However GA needs to be validated with more numeric tests, while Fellenius' slices method is just an approximate method like finite element method. This paper proposed a new method to determine the minimum slope safety factor which is the determination of slope safety factor with analytical solution and searching critical slip surface with Genetic-Traversal Random Method. The analytical solution is more accurate than Fellenius' slices method. The Genetic-Traversal Random Method uses random pick to utilize mutation. A computer automatic search program is developed for the Genetic-Traversal Random Method. After comparison with other methods like slope/w software, results indicate that the Genetic-Traversal Random Search Method can give very low safety factor which is about half of the other methods. However the obtained minimum safety factor with Genetic-Traversal Random Search Method is very close to the lower bound solutions of slope safety factor given by the Ansys software. PMID:24782679

  5. The human splicing code reveals new insights into the genetic determinants of disease

    PubMed Central

    Xiong, Hui Y.; Alipanahi, Babak; Lee, Leo J.; Bretschneider, Hannes; Merico, Daniele; Yuen, Ryan K.C.; Hua, Yimin; Gueroussov, Serge; Najafabadi, Hamed S.; Hughes, Timothy R.; Morris, Quaid; Barash, Yoseph; Krainer, Adrian R.; Jojic, Nebojsa; Scherer, Stephen W.; Blencowe, Benjamin J.; Frey, Brendan J.

    2015-01-01

    Introduction Advancing whole-genome precision medicine requires understanding how gene expression is altered by genetic variants, especially those that are outside of protein-coding regions. We developed a computational technique that scores how strongly genetic variants alter RNA splicing, a critical step in gene expression whose disruption contributes to many diseases, including cancers and neurological disorders. A genome-wide analysis reveals tens of thousands of variants that alter splicing and are enriched with a wide range of known diseases. Our results provide insight into the genetic basis of spinal muscular atrophy, hereditary nonpolyposis colorectal cancer and autism spectrum disorder. Methods We used machine learning to derive a computational model that takes as input DNA sequences and applies general rules to predict splicing in human tissues. Given a test variant, our model computes a score that predicts how much the variant disrupts splicing. The model was derived in such a way that it can be used to study diverse diseases and disorders, and to determine the consequences of common, rare, and even spontaneous variants. Results Our technique is able to accurately classify disease-causing variants and provides insights into the role of aberrant splicing in disease. We scored over 650,000 DNA variants and found that disease-causing variants have higher scores than common variants and even those associated with disease in genome-wide association studies. Our model predicts substantial and unexpected aberrant splicing due to variants within introns and exons, including those far from the splice site. For example, among intronic variants that are more than 30 nucleotides away from a splice site, known disease variants alter splicing nine times more often than common variants; among missense exonic disease variants, those that least impact protein function are over five times more likely to alter splicing than other variants. Autism has been associated with

  6. Antimicrobial resistance, virulence determinants and genetic profiles of clinical and nonclinical Enterococcus cecorum from poultry.

    PubMed

    Jackson, C R; Kariyawasam, S; Borst, L B; Frye, J G; Barrett, J B; Hiott, L M; Woodley, T A

    2015-02-01

    Enterococcus cecorum has been implicated as a possible cause of disease in poultry. However, the characteristics that contribute to pathogenesis of Ent. cecorum in poultry have not been defined. In this study, Ent. cecorum from carcass rinsates (n = 75) and diseased broilers and broiler breeders (n = 30) were compared based upon antimicrobial resistance phenotype, the presence of virulence determinants and genetic relatedness using pulsed-field gel electrophoresis (PFGE). Of the 16 antimicrobials tested, Ent. cecorum from carcass rinsates and clinical cases were resistant to ten and six of the antimicrobials, respectively. The majority of Ent. cecorum from carcass rinsates was resistant to lincomycin (54/75; 72%) and tetracycline (46/75; 61.3%) while the highest level of resistance among clinical Ent. cecorum was to tetracycline (22/30; 73.3%) and erythromycin (11/30; 36.7%). Multidrug resistance (resistance to ≥2 antimicrobials) was identified in Ent. cecorum from carcass rinsates (53/75; 70.7%) and diseased poultry (18/30; 60%). Of the virulence determinants tested, efaAfm was present in almost all of the isolates (104/105; 99%). Using PFGE, the majority of clinical isolates clustered together; however, a few clinical isolates grouped with Ent. cecorum from carcass rinsates. These data suggest that distinguishing the two groups of isolates is difficult based upon the characterization criteria used.

  7. Characterization of genetic determinants for R body synthesis and assembly in Caedibacter taeniospiralis 47 and 116.

    PubMed

    Heruth, D P; Pond, F R; Dilts, J A; Quackenbush, R L

    1994-06-01

    Caedibacter taeniospiralis, an obligate bacterial endosymbiont of Paramecium tetraurelia, confers a killing trait upon its host paramecium. Type 51 R bodies (refractile inclusion bodies) are synthesized by these endosymbionts and are required for expression of the killing trait. The nucleotide sequence of the genetic determinants for type 51 R body synthesis and assembly was determined for C. taeniospiralis 47 and 116. Three independently transcribed genes (rebA, rebB, and rebC) were characterized. To date these are the only genes from C. taeniospiralis to be sequenced and characterized. DNA regulatory regions are recognized by Escherichia coli, and codon usage appears similar to that in E. coli. A fourth open reading frame with appropriate regulatory sequences was found within the reb locus, but no evidence was obtained to suggest that this putative gene is expressed in E. coli. The R body-encoding sequences from both strains are identical. Two-dimensional gel electrophoresis of deletion derivatives shows that two polymerization events are involved in R body assembly. One polymerization event requires only RebB and RebC; the other requires all three proteins. Expression of RebC is necessary for the posttranslational modification of RebA and RebB into species with three and two different molecular weights, respectively. In the presence of RebC, each species of RebB with a different molecular weight has six different isoelectric points.

  8. Genetic determinants of HIV-1 infection and progression to AIDS: immune response genes.

    PubMed

    Kaur, G; Mehra, N

    2009-11-01

    Genomic studies involving well-defined multicenter cohorts of HIV-1/AIDS covering multiple populations have led to a greater understanding of the role of host determinants in viral acquisition, disease progression, transmission, and response to anti-retroviral therapy. Similarly, recent knowledge on the virus genetic diversity has helped in elucidating mechanisms leading to the evolution of viral escape mutants and the role played by host immune determinants, in particular the major histocompatibility complex (MHC) associated genes. At least two alleles, HLA-B*27 and B*57, have been identified as 'protective' against HIV-1 while B*35 and B*53 act as susceptibility favoring factors. How human leukocyte antigen (HLA)-mediated selection drives the evolution of HIV-1 and which circulating variants are more likely to evade immune surveillance of the population are now beginning to become clear. Importantly, the rare HLA alleles in a population bear a selective advantage to the host because these can induce immune responses against pre-adapted viruses. It is conceivable that previously established protective HLA associations are shifting with the evolving cytotoxic T lymphocyte (CTL) epitopes and may not remain protective in future. At the same time, this process is unraveling novel sub-dominant epitopes of the virus which could now be incorporated as the dominant target CTL epitopes. An insight into the population-specific correlates of protection is hence necessary for designing future anti-HIV therapeutic and/or prophylactic vaccine formulation(s).

  9. Genetic variants are major determinants of CSF antibody levels in multiple sclerosis.

    PubMed

    Goris, An; Pauwels, Ine; Gustavsen, Marte W; van Son, Brechtje; Hilven, Kelly; Bos, Steffan D; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål; Aarseth, Jan; Myhr, Kjell-Morten; D'Alfonso, Sandra; Barizzone, Nadia; Leone, Maurizio A; Martinelli Boneschi, Filippo; Sorosina, Melissa; Liberatore, Giuseppe; Kockum, Ingrid; Olsson, Tomas; Hillert, Jan; Alfredsson, Lars; Bedri, Sahl Khalid; Hemmer, Bernhard; Buck, Dorothea; Berthele, Achim; Knier, Benjamin; Biberacher, Viola; van Pesch, Vincent; Sindic, Christian; Bang Oturai, Annette; Søndergaard, Helle Bach; Sellebjerg, Finn; Jensen, Poul Erik H; Comabella, Manuel; Montalban, Xavier; Pérez-Boza, Jennifer; Malhotra, Sunny; Lechner-Scott, Jeannette; Broadley, Simon; Slee, Mark; Taylor, Bruce; Kermode, Allan G; Gourraud, Pierre-Antoine; Sawcer, Stephen J; Andreassen, Bettina Kullle; Dubois, Bénédicte; Harbo, Hanne F

    2015-03-01

    as female gender, age at onset and severity. This is the largest study population so far investigated for the genetic influence on antibody levels in the cerebrospinal fluid in multiple sclerosis, including 6950 patients. We confirm that genetic factors underlie these antibody levels and identify both the major histocompatibility complex and immunoglobulin heavy chain region as major determinants. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Genetic variants are major determinants of CSF antibody levels in multiple sclerosis

    PubMed Central

    Pauwels, Ine; Gustavsen, Marte W.; van Son, Brechtje; Hilven, Kelly; Bos, Steffan D.; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål; Aarseth, Jan; Myhr, Kjell-Morten; D’Alfonso, Sandra; Barizzone, Nadia; Leone, Maurizio A.; Martinelli Boneschi, Filippo; Sorosina, Melissa; Liberatore, Giuseppe; Kockum, Ingrid; Olsson, Tomas; Hillert, Jan; Alfredsson, Lars; Bedri, Sahl Khalid; Hemmer, Bernhard; Buck, Dorothea; Berthele, Achim; Knier, Benjamin; Biberacher, Viola; van Pesch, Vincent; Sindic, Christian; Bang Oturai, Annette; Søndergaard, Helle Bach; Sellebjerg, Finn; Jensen, Poul Erik H.; Comabella, Manuel; Montalban, Xavier; Pérez-Boza, Jennifer; Malhotra, Sunny; Lechner-Scott, Jeannette; Broadley, Simon; Slee, Mark; Taylor, Bruce; Kermode, Allan G.; Gourraud, Pierre-Antoine; Sawcer, Stephen J.; Andreassen, Bettina Kullle; Dubois, Bénédicte; Harbo, Hanne F.

    2015-01-01

    as female gender, age at onset and severity. This is the largest study population so far investigated for the genetic influence on antibody levels in the cerebrospinal fluid in multiple sclerosis, including 6950 patients. We confirm that genetic factors underlie these antibody levels and identify both the major histocompatibility complex and immunoglobulin heavy chain region as major determinants. PMID:25616667

  11. Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity

    PubMed Central

    Sorge, Robert E; Trang, Tuan; Dorfman, Ruslan; Smith, Shad B; Beggs, Simon; Ritchie, Jennifer; Austin, Jean-Sebastien; Zaykin, Dmitri V; Meulen, Heather Vander; Costigan, Michael; Herbert, Teri A; Yarkoni-Abitbul, Merav; Tichauer, David; Livneh, Jessica; Gershon, Edith; Zheng, Ming; Tan, Keith; John, Sally L; Slade, Gary D; Jordan, Joanne; Woolf, Clifford J; Peltz, Gary; Maixner, William; Diatchenko, Luda; Seltzer, Ze'ev; Salter, Michael W; Mogil, Jeffrey S

    2012-01-01

    Chronic pain is highly variable between individuals, as is the response to analgesics. Although much of the variability in chronic pain and analgesic response is heritable, an understanding of the genetic determinants underlying this variability is rudimentary1. Here we show that variation within the coding sequence of the gene encoding the P2X7 receptor (P2X7R) affects chronic pain sensitivity in both mice and humans. P2X7Rs, which are members of the family of ionotropic ATP-gated receptors, have two distinct modes of function: they can function through their intrinsic cationic channel or by forming nonselective pores that are permeable to molecules with a mass of up to 900 Da2,3. Using genome-wide linkage analyses, we discovered an association between nerve-injury–induced pain behavior (mechanical allodynia) and the P451L mutation of the mouse P2rx7 gene, such that mice in which P2X7Rs have impaired pore formation as a result of this mutation showed less allodynia than mice with the pore-forming P2rx7 allele. Administration of a peptide corresponding to the P2X7R C-terminal domain, which blocked pore formation but not cation channel activity, selectively reduced nerve injury and inflammatory allodynia only in mice with the pore-forming P2rx7 allele. Moreover, in two independent human chronic pain cohorts, a cohort with pain after mastectomy and a cohort with osteoarthritis, we observed a genetic association between lower pain intensity and the hypofunctional His270 (rs7958311) allele of P2RX7. Our findings suggest that selectively targeting P2X7R pore formation may be a new strategy for individualizing the treatment of chronic pain. PMID:22447075

  12. 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

  13. Genetic determinants of swimming motility in the squid light-organ symbiont Vibrio fischeri

    PubMed Central

    Brennan, Caitlin A; Mandel, Mark J; Gyllborg, Mattias C; Thomasgard, Krista A; Ruby, Edward G

    2013-01-01

    Abstract Bacterial flagellar motility is a complex cellular behavior required for the colonization of the light-emitting organ of the Hawaiian bobtail squid, Euprymna scolopes, by the beneficial bioluminescent symbiont Vibrio fischeri. We characterized the basis of this behavior by performing (i) a forward genetic screen to identify mutants defective in soft-agar motility, as well as (ii) a transcriptional analysis to determine the genes that are expressed downstream of the flagellar master regulator FlrA. Mutants with severe defects in soft-agar motility were identified due to insertions in genes with putative roles in flagellar motility and in genes that were unexpected, including those predicted to encode hypothetical proteins and cell division–related proteins. Analysis of mutants for their ability to enter into a productive symbiosis indicated that flagellar motility mutants are deficient, while chemotaxis mutants are able to colonize a subset of juvenile squid to light-producing levels. Thirty-three genes required for normal motility in soft agar were also downregulated in the absence of FlrA, suggesting they belong to the flagellar regulon of V. fischeri. Mutagenesis of putative paralogs of the flagellar motility genes motA motB, and fliL revealed that motA1 motB1, and both fliL1 and fliL2, but not motA2 and motB2, likely contribute to soft-agar motility. Using these complementary approaches, we have characterized the genetic basis of flagellar motility in V. fischeri and furthered our understanding of the roles of flagellar motility and chemotaxis in colonization of the juvenile squid, including identifying 11 novel mutants unable to enter into a productive light-organ symbiosis. PMID:23907990

  14. Genetic diversity of Streptococcus suis isolates as determined by comparative genome hybridization

    PubMed Central

    2011-01-01

    Background Streptococcus suis is a zoonotic pathogen that causes infections in young piglets. S. suis is a heterogeneous species. Thirty-three different capsular serotypes have been described, that differ in virulence between as well as within serotypes. Results In this study, the correlation between gene content, serotype, phenotype and virulence among 55 S. suis strains was studied using Comparative Genome Hybridization (CGH). Clustering of CGH data divided S. suis isolates into two clusters, A and B. Cluster A isolates could be discriminated from cluster B isolates based on the protein expression of extracellular factor (EF). Cluster A contained serotype 1 and 2 isolates that were correlated with virulence. Cluster B mainly contained serotype 7 and 9 isolates. Genetic similarity was observed between serotype 7 and serotype 2 isolates that do not express muramidase released protein (MRP) and EF (MRP-EF-), suggesting these isolates originated from a common founder. Profiles of 25 putative virulence-associated genes of S. suis were determined among the 55 isolates. Presence of all 25 genes was shown for cluster A isolates, whereas cluster B isolates lacked one or more putative virulence genes. Divergence of S. suis isolates was further studied based on the presence of 39 regions of difference. Conservation of genes was evaluated by the definition of a core genome that contained 78% of all ORFs in P1/7. Conclusions In conclusion, we show that CGH is a valuable method to study distribution of genes or gene clusters among isolates in detail, yielding information on genetic similarity, and virulence traits of S. suis isolates. PMID:21736719

  15. A Differential Fluorescence-Based Genetic Screen Identifies Listeria monocytogenes Determinants Required for Intracellular Replication

    PubMed Central

    Perry, Kyle J.

    2013-01-01

    Listeria monocytogenes is a Gram-positive, facultative intracellular pathogen capable of causing severe invasive disease with high mortality rates in humans. While previous studies have largely elucidated the bacterial and host cell mechanisms necessary for invasion, vacuolar escape, and subsequent cell-to-cell spread, the L. monocytogenes factors required for rapid replication within the restrictive environment of the host cell cytosol are poorly understood. In this report, we describe a differential fluorescence-based genetic screen utilizing fluorescence-activated cell sorting (FACS) and high-throughput microscopy to identify L. monocytogenes mutants defective in optimal intracellular replication. Bacteria harboring deletions within the identified gene menD or pepP were defective for growth in primary murine macrophages and plaque formation in monolayers of L2 fibroblasts, thus validating the ability of the screening method to identify intracellular replication-defective mutants. Genetic complementation of the menD and pepP deletion strains rescued the in vitro intracellular infection defects. Furthermore, the menD deletion strain displayed a general extracellular replication defect that could be complemented by growth under anaerobic conditions, while the intracellular growth defect of this strain could be complemented by the addition of exogenous menaquinone. As prior studies have indicated the importance of aerobic metabolism for L. monocytogenes infection, these findings provide further evidence for the importance of menaquinone and aerobic metabolism for L. monocytogenes pathogenesis. Lastly, both the menD and pepP deletion strains were attenuated during in vivo infection of mice. These findings demonstrate that the differential fluorescence-based screening approach provides a powerful tool for the identification of intracellular replication determinants in multiple bacterial systems. PMID:23687268

  16. Genetic determinants of swimming motility in the squid light-organ symbiont Vibrio fischeri.

    PubMed

    Brennan, Caitlin A; Mandel, Mark J; Gyllborg, Mattias C; Thomasgard, Krista A; Ruby, Edward G

    2013-08-01

    Bacterial flagellar motility is a complex cellular behavior required for the colonization of the light-emitting organ of the Hawaiian bobtail squid, Euprymna scolopes, by the beneficial bioluminescent symbiont Vibrio fischeri. We characterized the basis of this behavior by performing (i) a forward genetic screen to identify mutants defective in soft-agar motility, as well as (ii) a transcriptional analysis to determine the genes that are expressed downstream of the flagellar master regulator FlrA. Mutants with severe defects in soft-agar motility were identified due to insertions in genes with putative roles in flagellar motility and in genes that were unexpected, including those predicted to encode hypothetical proteins and cell division-related proteins. Analysis of mutants for their ability to enter into a productive symbiosis indicated that flagellar motility mutants are deficient, while chemotaxis mutants are able to colonize a subset of juvenile squid to light-producing levels. Thirty-three genes required for normal motility in soft agar were also downregulated in the absence of FlrA, suggesting they belong to the flagellar regulon of V. fischeri. Mutagenesis of putative paralogs of the flagellar motility genes motA, motB, and fliL revealed that motA1, motB1, and both fliL1 and fliL2, but not motA2 and motB2, likely contribute to soft-agar motility. Using these complementary approaches, we have characterized the genetic basis of flagellar motility in V. fischeri and furthered our understanding of the roles of flagellar motility and chemotaxis in colonization of the juvenile squid, including identifying 11 novel mutants unable to enter into a productive light-organ symbiosis. © 2013 The Authors. Microbiology Open published by John Wiley & Sons Ltd.

  17. Genetic determinants of circulating interleukin-1 receptor antagonist levels and their association with glycemic traits.

    PubMed

    Herder, Christian; Nuotio, Marja-Liisa; Shah, Sonia; Blankenberg, Stefan; Brunner, Eric J; Carstensen, Maren; Gieger, Christian; Grallert, Harald; Jula, Antti; Kähönen, Mika; Kettunen, Johannes; Kivimäki, Mika; Koenig, Wolfgang; Kristiansson, Kati; Langenberg, Claudia; Lehtimäki, Terho; Luotola, Kari; Marzi, Carola; Müller, Christian; Peters, Annette; Prokisch, Holger; Raitakari, Olli; Rathmann, Wolfgang; Roden, Michael; Salmi, Marko; Schramm, Katharina; Swerdlow, Daniel; Tabak, Adam G; Thorand, Barbara; Wareham, Nick; Wild, Philipp S; Zeller, Tanja; Hingorani, Aroon D; Witte, Daniel R; Kumari, Meena; Perola, Markus; Salomaa, Veikko

    2014-12-01

    The proinflammatory cytokine interleukin (IL)-1β is implicated in the development of insulin resistance and β-cell dysfunction, whereas higher circulating levels of IL-1 receptor antagonist (IL-1RA), an endogenous inhibitor of IL-1β, has been suggested to improve glycemia and β-cell function in patients with type 2 diabetes. To elucidate the protective role of IL-1RA, this study aimed to identify genetic determinants of circulating IL-1RA concentration and to investigate their associations with immunological and metabolic variables related to cardiometabolic risk. In the analysis of seven discovery and four replication cohort studies, two single nucleotide polymorphisms (SNPs) were independently associated with circulating IL-1RA concentration (rs4251961 at the IL1RN locus [n = 13,955, P = 2.76 × 10(-21)] and rs6759676, closest gene locus IL1F10 [n = 13,994, P = 1.73 × 10(-17)]). The proportion of the variance in IL-1RA explained by both SNPs combined was 2.0%. IL-1RA-raising alleles of both SNPs were associated with lower circulating C-reactive protein concentration. The IL-1RA-raising allele of rs6759676 was also associated with lower fasting insulin levels and lower HOMA insulin resistance. In conclusion, we show that circulating IL-1RA levels are predicted by two independent SNPs at the IL1RN and IL1F10 loci and that genetically raised IL-1RA may be protective against the development of insulin resistance. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  18. Genetically determined heterogeneity of lung disease in a mouse model of airway mucus obstruction.

    PubMed

    Livraghi-Butrico, Alessandra; Grubb, Barbara R; Kelly, Elizabeth J; Wilkinson, Kristen J; Yang, Huifang; Geiser, Marianne; Randell, Scott H; Boucher, Richard C; O'Neal, Wanda K

    2012-04-15

    Mucus clearance is an important airway innate defense mechanism. Airway-targeted overexpression of the epithelial Na(+) channel β-subunit [encoded by sodium channel nonvoltage gated 1, beta subunit (Scnn1b)] in mice [Scnn1b-transgenic (Tg) mice] increases transepithelial Na(+) absorption and dehydrates the airway surface, which produces key features of human obstructive lung diseases, including mucus obstruction, inflammation, and air-space enlargement. Because the first Scnn1b-Tg mice were generated on a mixed background, the impact of genetic background on disease phenotype in Scnn1b-Tg mice is unknown. To explore this issue, congenic Scnn1b-Tg mice strains were generated on C57BL/6N, C3H/HeN, BALB/cJ, and FVB/NJ backgrounds. All strains exhibited a two- to threefold increase in tracheal epithelial Na(+) absorption, and all developed airway mucus obstruction, inflammation, and air-space enlargement. However, there were striking differences in neonatal survival, ranging from 5 to 80% (FVB/NJgenetic context and timing of airway innate immune dysfunction critically determines lung disease phenotype. These mouse strains may be useful to identify key modifier genes and pathways.

  19. The Many Facets of Genetic Literacy: Assessing the Scalability of Multiple Measures for Broad Use in Survey Research

    PubMed Central

    Abrams, Leah R.; McBride, Colleen M.; Hooker, Gillian W.; Cappella, Joseph N.; Koehly, Laura M.

    2015-01-01

    Objectives To determine how three dimensions of genetic literacy (familiarity, skills, and factual knowledge) fit the hierarchy of knowledge outlined in E.M. Rogers’ Diffusion of Innovations to better conceptualize lay understandings of genomics. Methods A consumer panel representing the US adult population (N = 1016) completed an electronic survey in November 2013. Adjusting for education, we used correlations, principle components analysis, Mokken Scale tests, and linear regressions to assess how scores on the three genetic literacy sub-dimensions fit an ordered scale. Results The three scores significantly loaded onto one factor, even when adjusting for education. Analyses revealed moderate strength in scaling (0.416, p<0.001) and a difficulty ordering that matched Rogers’ hierarchy (knowledge more difficult than skills, followed by familiarity). Skills scores partially mediated the association between familiarity and knowledge with a significant indirect effect (0.241, p<0.001). Conclusion We established an ordering in genetic literacy sub-dimensions such that familiarity with terminology precedes skills using information, which in turn precedes factual knowledge. This ordering is important to contextualizing previous findings, guiding measurement in future research, and identifying gaps in the understanding of genomics relevant to the demands of differing applications. PMID:26510161

  20. Genetic determination of tolerance to lethal and sublethal copper concentrations in field populations of Daphnia longispina.

    PubMed

    Lopes, I; Baird, D J; Ribeiro, R

    2004-01-01

    overall increase tolerance of the population at lethal levels was rejected. Changes in life-history patterns were detected, though they were not fully consistent with predictions of life-history theory. Furthermore, these changes in life-history patterns did not involve fitness costs. The fifth hypothesis was rejected since, at sublethal levels of copper, no significant differences were found between the feeding inhibitions of similarly lethal tolerant lineages of the two populations, with only one exception. Therefore, the present study further confirmed the genetic erosion hypothesis and gave further support to the incorporation of genetic diversity measurements into risk assessments.

  1. Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume.

    PubMed

    Giri, Ayush; Edwards, Todd L; Motley, Saundra S; Byerly, Susan H; Fowke, Jay H

    2015-01-01

    Prostate enlargement leading to clinical benign prostatic hyperplasia (BPH) is associated with metabolic dysregulation and obesity. The genetic basis of this association is unclear. Our objective was to evaluate whether single nucleotide polymorphisms (SNPs) previously associated with metabolic disorders are also associated with prostate volume (PV). Participants included 876 men referred for prostate biopsy and found to be prostate cancer free. PV was measured by transrectal ultrasound. Samples were genotyped using the Illumina Cardio-MetaboChip platform. Multivariable adjusted linear regression models were used to evaluate SNPs (additive coding) in relation to natural-log transformed (log) PV. We compared SNP-PV results from biopsy-negative men to 442 men with low-grade prostate cancer with similar levels of obesity and PV. Beta-coefficients from the discovery and replication samples were then aggregated with fixed effects inverse variance weighted meta-analysis. SNP rs11736129 (near the pseudo-gene LOC100131429) was significantly associated with log-PV (beta: 0.16, p-value 1.16x10(-8)) after adjusting for multiple testing. Other noteworthy SNPs that were nominally associated (p-value < 1x10(-4)) with log-PV included rs9583484 (intronic SNP in COL4A2), rs10146527 (intronic SNP in NRXN3), rs9909466 (SNP near RPL32P31), and rs2241606 (synonymous SNP in SLC12A7). We found several SNPs in metabolic loci associated with PV. Further studies are needed to confirm our results and elucidate the mechanism between these genetic loci, PV, and clinical BPH.