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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. Determinants of genetic diversity.

    PubMed

    Ellegren, Hans; Galtier, Nicolas

    2016-07-01

    Genetic polymorphism varies among species and within genomes, and has important implications for the evolution and conservation of species. The determinants of this variation have been poorly understood, but population genomic data from a wide range of organisms now make it possible to delineate the underlying evolutionary processes, notably how variation in the effective population size (Ne) governs genetic diversity. Comparative population genomics is on its way to providing a solution to 'Lewontin's paradox' - the discrepancy between the many orders of magnitude of variation in population size and the much narrower distribution of diversity levels. It seems that linked selection plays an important part both in the overall genetic diversity of a species and in the variation in diversity within the genome. Genetic diversity also seems to be predictable from the life history of a species. PMID:27265362

  3. Disentangling the Genetic Determinants of Human Aging: Biological Age as an Alternative to the Use of Survival Measures

    PubMed Central

    Karasik, David; Demissie, Serkalem; Cupples, L. Adrienne; Kiel, Douglas P.

    2005-01-01

    The choice of a phenotype is critical for the study of a complex genetically regulated process, such as aging. To date, most of the twin and family studies have focused on broad survival measures, primarily age at death or exceptional longevity. However, on the basis of recent studies of twins and families, biological age has also been shown to have a strong genetic component, with heritability estimates ranging from 27% to 57%. The aim of this review is twofold: first, to summarize growing consensus on reliable methods of biological age assessment, and second, to demonstrate validity of this phenotype for research in the genetics of aging in humans. PMID:15972604

  4. Genetic determinants of HDL metabolism.

    PubMed

    Ossoli, A; Gomaraschi, M; Franceschini, G; Calabresi, L

    2014-01-01

    Plasma high density lipoproteins (HDL) comprise a highly heterogeneous family of lipoprotein particles, with subclasses that can be separated and identified according to density, size, surface charge as well as shape and protein composition. There is evidence that these subclasses may differ in their functional properties. The individual plasma HDL cholesterol (HDL-C) level is generally taken as a snapshot of the steady-state concentration of all circulating HDL subclasses together, but this is insufficient to capture the structural and functional variation in HDL particles. HDL are continuously remodeled and metabolized in plasma and interstitial fluids, through the interaction with a large number of factors, including structural proteins, membrane transporters, enzymes, transfer proteins and receptors. Genetic variation in these factors can lead to essential changes in plasma HDL levels, and to remarkable changes in HDL particle density, size, surface charge, shape, and composition in lipids and apolipoproteins. This review discusses the impact of rare mutations and common variants in genes encoding factors involved in HDL remodeling and metabolism on plasma HDL-C levels and particle distribution. The study of the effects of human genetic variation in major players in HDL metabolism provides important clues on how individual factors modulate the formation, maturation, remodeling and catabolism of HDL. PMID:24606513

  5. 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

  6. Host genetic determinants of influenza pathogenicity

    PubMed Central

    Lin, Tsai-Yu; Brass, Abraham L.

    2014-01-01

    Despite effective vaccines, influenza remains a major global health threat due to the morbidity and mortality caused by seasonal epidemics, as well as the 2009 pandemic. Also of profound concern are the rare but potentially catastrophic transmissions of avian influenza to humans, highlighted by a recent H7N9 influenza outbreak. Murine and human studies reveal that the clinical course of influenza is the result of a combination of both host and viral genetic determinants. While viral pathogenicity has long been the subject of intensive efforts, research to elucidate host genetic determinants, particularly human, is now in the ascendant, and the goal of this review is to highlight these recent insights. PMID:23933004

  7. 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

  8. 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

  9. Genetics of sex determination in tilapiine species.

    PubMed

    Cnaani, A; Lee, B-Y; Zilberman, N; Ozouf-Costaz, C; Hulata, G; Ron, M; D'Hont, A; Baroiller, J-F; D'Cotta, H; Penman, D J; Tomasino, E; Coutanceau, J-P; Pepey, E; Shirak, A; Kocher, T D

    2008-01-01

    We identified DNA markers linked to sex determining genes in six closely related species of tilapiine fishes. The mode of sex determination differed among species. In Oreochromis karongae and Tilapia mariae the sex-determining locus is on linkage group (LG) 3 and the female is heterogametic (WZ-ZZ system). In O. niloticus and T. zillii the sex-determining locus is on LG1 and the male is heterogametic (XX-XY system). A more complex pattern was observed in O. aureus and O. mossambicus, in which markers on both LG1 and LG3 were associated with sex. We found evidence for sex-linked lethal effects on LG1, as well as interactions between loci in the two linkage groups. Comparison of genetic and physical maps demonstrated a broad region of recombination suppression harboring the sex-determining locus on LG3. Sex-specific recombination suppression was found in the female heterogametic sex. Sequence analysis showed the accumulation of repetitive elements in this region. Phylogenetic analysis suggests that at least two transitions in the mode of sex determination have occurred in this clade. This variation in sex determination mechanisms among closely related species makes tilapias an excellent model system for studying the evolution of sex chromosomes in vertebrates. PMID:18418034

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

    NASA Astrophysics Data System (ADS)

    Li, X. R.; Wang, X.

    2016-01-01

    The sky surveys of space objects have obtained a huge quantity of too-short-arc (TSA) observation data. However, the classical method of initial orbit determination (IOD) can hardly get reasonable results for the TSAs. 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 selection of optimizing variables as well as the corresponding genetic operator for specific problems. Numerical experiments based on the real measurements show that the method can provide valid initial values for the follow-up work.

  11. Genetic determinants of Sindbis virus neuroinvasiveness.

    PubMed Central

    Dubuisson, J; Lustig, S; Ruggli, N; Akov, Y; Rice, C M

    1997-01-01

    After peripheral inoculation of mice, Sindbis virus replicates in a variety of tissues, leading to viremia. In some cases, the virus can enter the central nervous system (CNS) and cause lethal encephalitis. The outcome of infection is age and virus strain dependent. Recently, two pairs of Sindbis virus variants differing in neurovirulence and neuroinvasiveness were derived by limited serial passaging in mouse brain. Two early passage isolates (SVA and SVB) were neurotropic but did not cause lethal encephalitis. SVB, but not SVA, was neuroinvasive. A second independent pair of isolates (SVN and SVNI), which had undergone more extensive mouse brain passaging, were highly neurotropic and caused lethal encephalitis. Only SVNI could reach the brain after peripheral inoculation. From these isolates, virion RNAs were obtained and used to construct full-length cDNA clones from which infectious RNA transcripts could be recovered. The strains recovered from these clones were shown to retain the appropriate phenotypes in weanling mice. Construction and analysis of recombinant viruses were used to define the genetic loci determining neuroinvasion. For SVB, neuroinvasiveness was determined by a single residue in the E2 glycoprotein (Gln-55). For SVNI, neuroinvasive loci were identified in both the 5' noncoding region (position 8) and the E2 glycoprotein (Met-190). Either of these changes on the SVN background was sufficient to confer a neuroinvasive phenotype, although these recombinants were less virulent. To completely mimic the SVNI phenotype, three SVNI-specific substitutions on the SVN background were required: G at position 8, E2 Met-190, and Lys-260, which by itself had no effect on neuroinvasion. These genetically defined strains should be useful for dissecting the molecular mechanisms leading to Sindbis virus invasion of the CNS. PMID:9060616

  12. Genetic determinants of bone mass in adults. A twin study.

    PubMed Central

    Pocock, N A; Eisman, J A; Hopper, J L; Yeates, M G; Sambrook, P N; Eberl, S

    1987-01-01

    The relative importance of genetic factors in determining bone mass in different parts of the skeleton is poorly understood. Lumbar spine and proximal femur bone mineral density and forearm bone mineral content were measured by photon absorptiometry in 38 monozygotic and 27 dizygotic twin pairs. Bone mineral density was significantly more highly correlated in monozygotic than in dizygotic twins for the spine and proximal femur and in the forearm of premenopausal twin pairs, which is consistent with significant genetic contributions to bone mass at all these sites. The lesser genetic contribution to proximal femur and distal forearm bone mass compared with the spine suggests that environmental factors are of greater importance in the aetiology of osteopenia of the hip and wrist. This is the first demonstration of a genetic contribution to bone mass of the spine and proximal femur in adults and confirms similar findings of the forearm. Furthermore, bivariate analysis suggested that a single gene or set of genes determines bone mass at all sites. PMID:3624485

  13. 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…

  14. Genetic compatibility determines endophyte-grass combinations.

    PubMed

    Saikkonen, Kari; Wäli, Piippa R; Helander, Marjo

    2010-01-01

    Even highly mutually beneficial microbial-plant interactions, such as mycorrhizal- and rhizobial-plant exchanges, involve selfishness, cheating and power-struggles between the partners, which depending on prevailing selective pressures, lead to a continuum of interactions from antagonistic to mutualistic. Using manipulated grass-endophyte combinations in a five year common garden experiment, we show that grass genotypes and genetic mismatches constrain genetic combinations between the vertically (via host seeds) transmitted endophytes and the out-crossing host, thereby reducing infections in established grass populations. Infections were lost in both grass tillers and seedlings in F(1) and F(2) generations, respectively. Experimental plants were collected as seeds from two different environments, i.e., meadows and nearby riverbanks. Endophyte-related benefits to the host included an increased number of inflorescences, but only in meadow plants and not until the last growing season of the experiment. Our results illustrate the importance of genetic host specificity and trans-generational maternal effects on the genetic structure of a host population, which act as destabilizing forces in endophyte-grass symbioses. We propose that (1) genetic mismatches may act as a buffering mechanism against highly competitive endophyte-grass genotype combinations threatening the biodiversity of grassland communities and (2) these mismatches should be acknowledged, particularly in breeding programmes aimed at harnessing systemic and heritable endophytes to improve the agriculturally valuable characteristics of cultivars. PMID:20614034

  15. 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...

  16. 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

  17. Genetic determinants of cutaneous melanoma predisposition.

    PubMed

    Udayakumar, Durga; Mahato, Bisundev; Gabree, Michele; Tsao, Hensin

    2010-09-01

    In the last 2 decades, advances in genomic technologies and molecular biology have accelerated the identification of multiple genetic loci that confer risk for cutaneous melanoma. The risk alleles range from rarely occurring, high-risk variants with a strong familial predisposition to low-risk to moderate-risk variants with modest melanoma association. Although the high-risk alleles are limited to the CDKN2A and CDK4 loci, the authors of recent genome-wide association studies have uncovered a set of variants in pigmentation loci that contribute to low risk. A biological validation of these new findings would provide greater understanding of the disease. In this review we describe some of the important risk loci and their association to risk of developing cutaneous melanoma and also address the current clinical challenges in CDKN2A genetic testing. PMID:21051013

  18. Presence: concept, determinants, and measurement

    NASA Astrophysics Data System (ADS)

    IJsselsteijn, Wijnand A.; de Ridder, Huib; Freeman, Jonathan; Avons, Steve E.

    2000-06-01

    The concept of presence, i.e. the sensation of 'being there' in a mediated environment, has received substantial attention from the virtual reality community, and is becoming increasingly relevant both to broadcasters and display developers. Although research into presence is still at an early stage of development, there is a consensus that presence has multiple determinants. To identify and test which parameters affect presence, a reliable, robust and valid means of measuring presence is required. In this paper, we describe the categories of factors thought to have an impact on presence. Furthermore, we present an overview of various approaches taken to measuring presence, which can be divided into two general categories: subjective measures and objective corroborative measures. Since presence is a subjective experience, the most direct way of assessment is through users' subjective report. This approach has serious limitations however, and should be used judiciously. Objective measures, such as postural, physiological or social responses to media, can be used to corroborate subjective measures, thereby overcoming some of their limitations. At present, the most promising direction for presence measurement is to develop and use an aggregate measure of presence that is comprised of both subjective and objective components, tailored to the specific medium under study.

  19. 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)

  20. Genetic determinants of cutaneous malignant melanoma in Sinclair swine.

    PubMed

    Blangero, J; Tissot, R G; Beattie, C W; Amoss, M S

    1996-03-01

    The role of genetic factors involved in the determination of risk of cutaneous malignant melanoma (CMM) in humans remains unclear owing to genetic heterogeneity and reliance on simplistic models of inheritance. Here, we report a statistical genetic analysis of cutaneous malignant melanoma in Sinclair swine (SSCM), a unique animal model for human CMM. Using complex segregation analysis a two-locus model involving an unknown major locus and a second locus that lies within or close to the swine leukocyte antigen (SLA) complex jointly determine risk of SSCM in pedigreed animals. These loci also influence severity of affection, accounting for approximately 20% of the phenotypic variation in quantitative tumour burden. PMID:8605105

  1. Genetic Determinants of Responses to Selenium Supplementation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In a cohort of healthy adults (106 M, 155 W) in eastern North Dakota, we determined the relationships of five biomarkers of selenium (Se) status (plasma Se, serum selenoprotein P [SePP], plasma glutathione peroxidase [GPX3] activity, buccal cell Se, urine Se) to genotype for four selenoproteins (cyt...

  2. 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

  3. 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)

  4. Tilapia sex determination: Where temperature and genetics meet.

    PubMed

    Baroiller, J F; D'Cotta, H; Bezault, E; Wessels, S; Hoerstgen-Schwark, G

    2009-05-01

    This review deals with the complex sex determining system of Nile tilapia, Oreochromis niloticus, governed by the interactions between a genetic determination and the influence of temperature, shown in both domestic and wild populations. Naturally sex reversed individuals are strongly suggested in two wild populations. This can be due to the masculinising temperatures which some fry encounter during their sex differentiation period when they colonise shallow waters, and/or to the influence of minor genetic factors. Differences regarding a) thermal responsiveness of sex ratios between and within Nile tilapia populations, b) maternal and paternal effects on temperature dependent sex ratios and c) nearly identical results in offspring of repeated matings, demonstrate that thermosensitivity is under genetic control. Selection experiments to increase the thermosensitivity revealed high responses in the high and low sensitive lines. The high-line showed approximately 90% males after 2 generations of selection whereas the weakly sensitive line had 54% males. This is the first evidence that a surplus of males in temperature treated groups can be selected as a quantitative trait. Expression profiles of several genes (Cyp19a, Foxl2, Amh, Sox9a,b) from the gonad and brain were analysed to define temperature action on the sex determining/differentiating cascade in tilapia. The coexistence of GSD and TSD is discussed. PMID:19101647

  5. 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. PMID:26032340

  6. Torus mandibularis: an estimation of the degree of genetic determination.

    PubMed

    Eggen, S

    1989-12-01

    Torus mandibularis has frustrated several attempts to make family patterns of variation fit modifications of Mendelian models. It is suggested that the quasi-continuous model of inheritance provides a rational explanation for the diverging opinions. The model implies an underlying continuous and normally distributed variable, 'liability', with a threshold value beyond which individuals will be affected. Both genetic and environmental factors determine liability, making the system multifactorial. The incidence of variable degrees of torus was examined in two groups of patients with different stresses on the jaws: one group with bruxism and one comparison group. The transformation of incidences to group means and variances of liability was demonstrated. Muscular forces during bruxism were shown to influence liability. The relative importance of environmental and genetic components of variance could, however, not be estimated directly from the entire groups, since both were mixed with regard to the genetic predisposition. To achieve materials with uniform genotypes, all individuals without torus were omitted. The estimate of the genotypic variance (VG) was obtained by subtracting the variance of the bruxism sub-group--the environmental component associated with bruxism (VEB)--from the total phenotypic variance of the comparison sub-group (VP). The estimate of the genetic determination of torus (VG/VP) turned out to be about 30%, whereas approximately 70% of the causes seemed to be attributable to environmental influence in terms of occlusal stress. Gene effects on the morphologic level are usually pleiotropic, and it is suggested that the correlation of torus mandibularis with other clinical variables might make an interesting subject for further investigation. PMID:2609949

  7. Genetic and Environmental Determinants of Bitter Perception and Sweet Preferences

    PubMed Central

    Mennella, Julie A.; Pepino, M. Yanina; Reed, Danielle R.

    2006-01-01

    Objective Flavor is the primary dimension by which young children determine food acceptance. However, children are not merely miniature adults because sensory systems mature postnatally and their responses to certain tastes differ markedly from adults. Among these differences are heightened preferences for sweet-tasting and greater rejection of bitter-tasting foods. The present study tests the hypothesis that genetic variations in the newly discovered TAS2R38 taste gene as well as cultural differences are associated with differences in sensitivity to the bitter taste of propylthiouracil (PROP) and preferences for sucrose and sweet-tasting foods and beverages in children and adults. Design Genomic DNA was extracted from cheek cells of a racially and ethnically diverse sample of 143 children and their mothers. Alleles of the gene TAS2R38 were genotyped. Participants were grouped by the first variant site, denoted A49P, because the allele predicts a change from the amino acid alanine (A) to proline (P) at position 49. Henceforth, individuals who were homozygous for the bitter-insensitive allele are referred to as AA, those who were heterozygous for the bitter-insensitive allele are referred to as AP, and those who were homozygous for the bitter-sensitive allele are referred to as PP. Using identical procedures for children and mothers, PROP sensitivity and sucrose preferences were assessed by using forced-choice procedures that were embedded in the context of games that minimized the impact of language development and were sensitive to the cognitive limitations of pediatric populations. Participants were also asked about their preferences in cereals and beverages, and mothers completed a standardized questionnaire that measured various dimensions of their children’s temperament. Results Genetic variation of the A49P allele influenced bitter perception in children and adults. However, the phenotype-genotype relationship was modified by age such that 64% of

  8. Genetic implanted fuzzy model for water saturation determination

    NASA Astrophysics Data System (ADS)

    Bagheripour, Parisa; Asoodeh, Mojtaba

    2014-04-01

    The portion of rock pore volume occupied with non-hydrocarbon fluids is called water saturation, which plays a significant role in reservoir description and management. Accurate water saturation, directly measured from special core analysis is highly expensive and time consuming. Furthermore, indirect measurements of water saturation from well log interpretation such as empirical correlations or statistical methods do not provide satisfying results. Recent works showed that fuzzy logic is a robust tool for handling geosciences problems which provide more reliable results compared with empirical correlations or statistical methods. This study goes further to improve fuzzy logic for enhancing accuracy of final prediction. It employs hybrid genetic algorithm-pattern search technique instead of widely held subtractive clustering approach for setting up fuzzy rules and for extracting optimal parameters involved in computational structure of fuzzy model. The proposed strategy, called genetic implanted fuzzy model, was used to formulate conventional well log data, including sonic transit time, neutron porosity, formation bulk density, true resistivity, and gamma ray into water saturation, obtained from subtractive clustering approach. Results indicated genetic implanted fuzzy model performed more satisfyingly compared with traditional fuzzy logic model. The propounded model was successfully applied to one of Iranian carbonate reservoir rocks.

  9. 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

  10. 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

  11. 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. PMID:27182949

  12. 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

  13. Genetic and environmental determinants of risk for cholangiocarcinoma in Thailand

    PubMed Central

    Miwa, Masanao; Honjo, Satoshi; You, Gyokukou; Tanaka, Masakazu; Uchida, Kazuhiko; Srivatanakul, Petcharin; Khuhaprema, Thiravud; Loilome, Watcharin; Techasen, Anchalee; Wongkham, Chaisiri; Limpaiboon, Temduang; Yongvanit, Puangrat; Wongkham, Sopit

    2014-01-01

    Cholangiocarcinoma (CCA) is a difficult cancer to diagnose in the early stage and to treat by curative resection. The incidence of CCA in the northeast of Thailand is the highest in the world. To make progress in detecting a high risk group and in the prevention and detection of CCA, we have been analyzing the risk factors for CCA. Although liver fluke infection is known to be a risk factor, there are patients who are not infected with the liver fluke and not all people infected with the liver fluke will suffer from the disease. Therefore, it is of the utmost importance to analyze the risk factors and the mechanism to prevent the disease and also to detect the disease in its early stage to save patients’ lives. Through collaboration among Thai and Japanese researchers, we analyzed the genetic and environmental determinants of risks for CCA. Also, we have been trying to develop methods to detect the disease in a non-invasive way. Without repeating findings reported in various reviews on CCA, we will first discuss the environmental and genetic determinants of the risks for CCA. Second, we will discuss the properties of CCA, including the etiological agents and the mechanism of cholangiocarcinogenesis, and finally, we will discuss future approaches to prevent and cure CCA from the standpoint of evidence-based medicine. We will discuss these points by including the data from our laboratories. We would like to emphasize the importance of the genetic data, especially whole genome approaches, to understand the properties of CCA, to find a high risk population for CCA and to develop effective preventative methods to stop the carcinogenic steps toward CCA in the near future. In addition, it is of the upmost importance to develop a non-invasive, specific and sensitive method to detect CCA in its early stage for the application of modern medical approaches to help patients with CCA. PMID:25401000

  14. Maternal and genetic factors determine early life telomere length

    PubMed Central

    Asghar, Muhammad; Bensch, Staffan; Tarka, Maja; Hansson, Bengt; Hasselquist, Dennis

    2015-01-01

    In a broad range of species—including humans—it has been demonstrated that telomere length declines throughout life and that it may be involved in cell and organismal senescence. This potential link to ageing and thus to fitness has triggered recent interest in understanding how variation in telomere length is inherited and maintained. However, previous studies suffer from two main drawbacks that limit the possibility of understanding the relative importance of genetic, parental and environmental influences on telomere length variation. These studies have been based on (i) telomere lengths measured at different time points in different individuals, despite the fact that telomere length changes over life, and (ii) parent–offspring regression techniques, which do not enable differentiation between genetic and parental components of inheritance. To overcome these drawbacks, in our study of a songbird, the great reed warbler, we have analysed telomere length measured early in life in both parents and offspring and applied statistical models (so-called ‘animal models') that are based on long-term pedigree data. Our results showed a significant heritability of telomere length on the maternal but not on the paternal side, and that the mother's age was positively correlated with their offspring's telomere length. Furthermore, the pedigree-based analyses revealed a significant heritability and an equally large maternal effect. Our study demonstrates strong maternal influence on telomere length and future studies now need to elucidate possible underlying factors, including which types of maternal effects are involved. PMID:25621325

  15. Genetic determinants of dengue type 4 virus neurovirulence for mice.

    PubMed Central

    Kawano, H; Rostapshov, V; Rosen, L; Lai, C J

    1993-01-01

    Mouse-adapted dengue type 4 virus (DEN4) strain H241 is highly neurovirulent for mice, whereas its non-mouse-adapted parent is rarely neurovirulent. The genetic basis for the neurovirulence of the mouse-adapted mutant was studied by comparing intratypic chimeric viruses that contained the three structural protein genes from the parental virus or the neurovirulent mutant in the background sequence of nonneurovirulent DEN4 strain 814669. The chimera that contained the three structural protein genes from mouse neurovirulent DEN4 strain H241 proved to be highly neurovirulent in mice, whereas the chimera that contained the corresponding genes from its non-mouse-adapted parent was not neurovirulent. This finding indicates that most of the genetic loci for the neurovirulence of the DEN4 mutant lie within the structural protein genes. A comparison of the amino acid sequences of the parent and its mouse neurovirulent mutant proteins revealed that there were only five amino acid differences in the structural protein region, and three of these were located in the envelope (E) glycoprotein. Analysis of chimeras which contained one or two of the variant amino acids of the mutant E sequence substituting for the corresponding sequence of the parental virus identified two of these amino acid changes as important determinants of mouse neurovirulence. First, the single substitution of Ile for Thr-155 which ablated one of the two conserved glycosylation sites in parental E yielded a virus that was almost as neurovirulent as the mouse-adapted mutant. Thus, the loss of an E glycosylation site appears to play a role in DEN4 neurovirulence. Second, the substitution of Leu for Phe-401 also yielded a neurovirulent virus, but it was less neurovirulent than the glycosylation mutant. These findings indicate that at least two of the genetic loci responsible for DEN4 mouse neurovirulence map within the structural protein genes. Images PMID:8411360

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

    PubMed

    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 and

  17. 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

  18. 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

  19. 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.

  20. Sphingolipids and Membrane Biology as Determined from Genetic Models

    PubMed Central

    Rao, Raghavendra Pralhada; Acharya, Jairaj K

    2008-01-01

    The importance of sphingolipids in membrane biology was appreciated early in the twentieth century when several human inborn errors of metabolism were linked to defects in sphingolipid degradation. The past two decades have seen an explosion of information linking sphingolipids with cellular processes. Studies have unraveled mechanistic details of the sphingolipid metabolic pathways, and these findings are being exploited in the development of novel therapies, some now in clinical trials. Pioneering work in yeast has laid the foundation for identifying genes encoding the enzymes of the pathways. The advent of the era of genomics and bioinformatics has led to the identification of homologous genes in other species and the subsequent creation of animal knock-out lines for these genes. Discoveries from these efforts have re-kindled interest in the role of sphingolipids in membrane biology. This review highlights some of the recent advances in understanding sphingolipids’ roles in membrane biology as determined from genetic models. PMID:18035569

  1. Orbit determination by genetic algorithm and application to GEO observation

    NASA Astrophysics Data System (ADS)

    Hinagawa, Hideaki; Yamaoka, Hitoshi; Hanada, Toshiya

    2014-02-01

    This paper demonstrates an initial orbit determination method that solves the problem by a genetic algorithm using two well-known solutions for the Lambert's problem: universal variable method and Battin method. This paper also suggests an intuitive error evaluation method in terms of rotational angle and orbit shape by separating orbit elements into two groups. As reference orbit, mean orbit elements (original two-lines elements) and osculating orbit elements considering the J2 effect are adopted and compared. Our proposed orbit determination method has been tested with actual optical observations of a geosynchronous spacecraft. It should be noted that this demonstration of the orbit determination is limited to one test case. This observation was conducted during approximately 70 min on 2013/05/15 UT. Our method was compared with the orbit elements propagated by SGP4 using the TLE of the spacecraft. The result indicates that our proposed method had a slightly better performance on estimating orbit shape than Gauss's methods and Escobal's method by 120 km. In addition, the result of the rotational angle is closer to the osculating orbit elements than the mean orbit elements by 0.02°, which supports that the estimated orbit is valid.

  2. [Genetic analysis of Streptomyces erythreus heteroclones. II. Determination of the distances between genetic loci on the map].

    PubMed

    Pencheva, R; Todorov, T

    1989-01-01

    As a result of recombination experiments between auxotrophic mutants of S. erythreus BTCC2 haploid recombinants and heteroclones were isolated. A genetic map of S. erythreus, including 15 auxotrophic loci was constructed by genetic analysis of the segregants of the heteroclones obtained. The genetic distances between 7 key loci on the map were determined and the entire length of the map of about 105 standard recombination units was calculated. PMID:2624163

  3. Determining the Pathogenicity of Genetic Variants Associated with Cardiac Channelopathies

    PubMed Central

    Campuzano, Oscar; Allegue, Catarina; Fernandez, Anna; Iglesias, Anna; Brugada, Ramon

    2015-01-01

    Advancements in genetic screening have generated massive amounts of data on genetic variation; however, a lack of clear pathogenic stratification has left most variants classified as being of unknown significance. This is a critical limitation for translating genetic data into clinical practice. Genetic screening is currently recommended in the guidelines for diagnosis and treatment of cardiac channelopathies, which are major contributors to sudden cardiac death in young people. We propose to characterize the pathogenicity of genetic variants associated with cardiac channelopathies using a stratified scoring system. The development of this system was considered by using all of the tools currently available to define pathogenicity. The use of this scoring system could help clinicians to understand the limitations of genetic associations with a disease, and help them better define the role that genetics can have in their clinical routine. PMID:25608792

  4. MicroRNA variants as genetic determinants of bone mass.

    PubMed

    Dole, Neha S; Delany, Anne M

    2016-03-01

    Single nucleotide polymorphisms (SNPs) are the most abundant genetic variants that contribute to the heritability of bone mass. MicroRNAs (miRNAs, miRs) are key post-transcriptional regulators that modulate the differentiation and function of skeletal cells by targeting multiple genes in the same or distinct signaling pathways. SNPs in miRNA genes and miRNA binding sites can alter miRNA abundance and mRNA targeting. This review describes the potential impact of miRNA-related SNPs on skeletal phenotype. Although many associations between SNPs and bone mass have been described, this review is limited to gene variants for which a function has been experimentally validated. SNPs in miRNA genes (miR-SNPs) that impair miRNA processing and alter the abundance of mature miRNA are discussed for miR-146a, miR-125a, miR-196a, miR-149 and miR-27a. SNPs in miRNA targeting sites (miR-TS-SNPs) that alter miRNA binding are described for the bone remodeling genes bone morphogenetic protein receptor 1 (Bmpr1), fibroblast growth factor 2 (Fgf2), osteonectin (Sparc) and histone deacetylase 5 (Hdac5). The review highlights two aspects of miRNA-associated SNPs: the mechanism for altering miRNA mediated gene regulation and the potential of miR-associated SNPs to alter osteoblast, osteoclast or chondrocyte differentiation and function. Given the polygenic nature of skeletal diseases like osteoporosis and osteoarthritis, validating the function of additional miRNA-associated SNPs has the potential to enhance our understanding of the genetic determinants of bone mass and predisposition to selected skeletal diseases. PMID:26723575

  5. 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.

  6. Attitude Determination Using Two Vector Measurements

    NASA Technical Reports Server (NTRS)

    Markley, F. Landis

    1999-01-01

    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.

  7. 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. PMID:25917123

  8. 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…

  9. 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.

  10. 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

  11. 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…

  12. 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

  13. 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. PMID:24489695

  14. 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

  15. Genetic determinants of reutericyclin biosynthesis in Lactobacillus reuteri.

    PubMed

    Lin, Xiaoxi B; Lohans, Christopher T; Duar, Rebbeca; Zheng, Jinshui; Vederas, John C; Walter, Jens; Gänzle, Michael

    2015-03-01

    Reutericyclin is a unique antimicrobial tetramic acid produced by some strains of Lactobacillus reuteri. This study aimed to identify the genetic determinants of reutericyclin biosynthesis. Comparisons of the genomes of reutericyclin-producing L. reuteri strains with those of non-reutericyclin-producing strains identified a genomic island of 14 open reading frames (ORFs) including genes coding for a nonribosomal peptide synthetase (NRPS), a polyketide synthase (PKS), homologues of PhlA, PhlB, and PhlC, and putative transport and regulatory proteins. The protein encoded by rtcN is composed of a condensation domain, an adenylation domain likely specific for d-leucine, and a thiolation domain. rtcK codes for a PKS that is composed of a ketosynthase domain, an acyl-carrier protein domain, and a thioesterase domain. The products of rtcA, rtcB, and rtcC are homologous to the diacetylphloroglucinol-biosynthetic proteins PhlABC and may acetylate the tetramic acid moiety produced by RtcN and RtcK, forming reutericyclin. Deletion of rtcN or rtcABC in L. reuteri TMW1.656 abrogated reutericyclin production but did not affect resistance to reutericyclin. Genes coding for transport and regulatory proteins could be deleted only in the reutericyclin-negative L. reuteri strain TMW1.656ΔrtcN, and these deletions eliminated reutericyclin resistance. The genomic analyses suggest that the reutericyclin genomic island was horizontally acquired from an unknown source during a unique event. The combination of PhlABC homologues with both an NRPS and a PKS has also been identified in the lactic acid bacteria Streptococcus mutans and Lactobacillus plantarum, suggesting that the genes in these organisms and those in L. reuteri share an evolutionary origin. PMID:25576609

  16. Genetic Determinants of Reutericyclin Biosynthesis in Lactobacillus reuteri

    PubMed Central

    Lin, Xiaoxi B.; Lohans, Christopher T.; Duar, Rebbeca; Zheng, Jinshui; Vederas, John C.; Walter, Jens

    2015-01-01

    Reutericyclin is a unique antimicrobial tetramic acid produced by some strains of Lactobacillus reuteri. This study aimed to identify the genetic determinants of reutericyclin biosynthesis. Comparisons of the genomes of reutericyclin-producing L. reuteri strains with those of non-reutericyclin-producing strains identified a genomic island of 14 open reading frames (ORFs) including genes coding for a nonribosomal peptide synthetase (NRPS), a polyketide synthase (PKS), homologues of PhlA, PhlB, and PhlC, and putative transport and regulatory proteins. The protein encoded by rtcN is composed of a condensation domain, an adenylation domain likely specific for d-leucine, and a thiolation domain. rtcK codes for a PKS that is composed of a ketosynthase domain, an acyl-carrier protein domain, and a thioesterase domain. The products of rtcA, rtcB, and rtcC are homologous to the diacetylphloroglucinol-biosynthetic proteins PhlABC and may acetylate the tetramic acid moiety produced by RtcN and RtcK, forming reutericyclin. Deletion of rtcN or rtcABC in L. reuteri TMW1.656 abrogated reutericyclin production but did not affect resistance to reutericyclin. Genes coding for transport and regulatory proteins could be deleted only in the reutericyclin-negative L. reuteri strain TMW1.656ΔrtcN, and these deletions eliminated reutericyclin resistance. The genomic analyses suggest that the reutericyclin genomic island was horizontally acquired from an unknown source during a unique event. The combination of PhlABC homologues with both an NRPS and a PKS has also been identified in the lactic acid bacteria Streptococcus mutans and Lactobacillus plantarum, suggesting that the genes in these organisms and those in L. reuteri share an evolutionary origin. PMID:25576609

  17. Genetic Determinants of Thrombin Generation and Their Relation to Venous Thrombosis: Results from the GAIT-2 Project

    PubMed Central

    Martin-Fernandez, Laura; Ziyatdinov, Andrey; Carrasco, Marina; Millon, Juan Antonio; Martinez-Perez, Angel; Vilalta, Noelia; Brunel, Helena; Font, Montserrat; Hamsten, Anders; Souto, Juan Carlos; Soria, José Manuel

    2016-01-01

    Background Venous thromboembolism (VTE) is a common disease where known genetic risk factors explain only a small portion of the genetic variance. Then, the analysis of intermediate phenotypes, such as thrombin generation assay, can be used to identify novel genetic risk factors that contribute to VTE. Objectives To investigate the genetic basis of distinct quantitative phenotypes of thrombin generation and its relationship to the risk of VTE. Patients/Methods Lag time, thrombin peak and endogenous thrombin potential (ETP) were measured in the families of the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT-2) Project. This sample consisted of 935 individuals in 35 extended families selected through a proband with idiopathic thrombophilia. We performed also genome wide association studies (GWAS) with thrombin generation phenotypes. Results The results showed that 67% of the variation in the risk of VTE is attributable to genetic factors. The heritabilities of lag time, thrombin peak and ETP were 49%, 54% and 52%, respectively. More importantly, we demonstrated also the existence of positive genetic correlations between thrombin peak or ETP and the risk of VTE. Moreover, the major genetic determinant of thrombin generation was the F2 gene. However, other suggestive signals were observed. Conclusions The thrombin generation phenotypes are strongly genetically determined. The thrombin peak and ETP are significantly genetically correlated with the risk of VTE. In addition, F2 was identified as a major determinant of thrombin generation. We reported suggestive signals that might increase our knowledge to explain the variability of this important phenotype. Validation and functional studies are required to confirm GWAS results. PMID:26784699

  18. Genetic Determinants of Risk, Severity, and Outcome in Intracerebral Hemorrhage.

    PubMed

    Falcone, Guido J; Rosand, Jonathan

    2016-06-01

    Spontaneous, nontraumatic intracerebral hemorrhage (ICH) is the most severe manifestation of common forms of cerebral small vessel disease. Although ICH represents only 15% of all strokes, it accounts for a large proportion of stroke-related costs and mortality. Preventive and acute treatments remain limited. Because genetic variation contributes substantially to ICH, genomic analyses constitute a powerful tool to identify new biological mechanisms involved in its occurrence. Through translational research efforts, these newly identified mechanisms can become targets for innovative therapeutic interventions. Here, the authors summarize the most recent genetic discoveries for ICH. They also introduce the Platform for Accelerating Genetic Discovery for Cerebrovascular Disease, a newly created resource that aims to create a common workspace for genetic analyses that will bring together 100,000 stroke cases and suitable controls from numerous institutions in several countries. PMID:27214705

  19. 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

  20. Electrochemical noise measurement for determining corrosion rates

    SciTech Connect

    Reichert, D.L.

    1996-12-31

    Electrochemical noise measurements (ENM), linear polarization tests and mass loss measurements were performed in sulfuric acid, acetic acid and other solutions. The ENM data were converted to corrosion rates by calculating the noise resistance, R{sub n} = {sigma}V/{sigma}I where {sigma}V and {sigma}I are the standard deviations of the potential and current. Good correlation among the three methods was obtained for low to moderate corrosion rates, but poor correlation was observed for high rates. ENM has proven valuable for determining corrosion rates in low-conductivity solutions, which are not suitable for linear polarization resistance (LPR) testing, and for measuring very low corrosion rates in which mass loss tests would have required at least 30 days exposure to provide meaningful results.

  1. 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

  2. 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

    2015-11-01

    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

  3. 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

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

    PubMed

    Martinez-Nicolas, Juan J; 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 the

  5. 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

    ...We are advising the public of our determination that a soybean line developed by the Monsanto Co., designated as event MON 87701, which has been genetically engineered for insect resistance, is no longer considered a regulated article under our regulations governing the introduction of certain genetically engineered organisms. Our determination is based on our evaluation of data submitted by......

  6. 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

    ...We are advising the public of our determination that a corn line developed by the Monsanto Co., designated as event MON 87460, which has been genetically engineered for drought tolerance, is no longer considered a regulated article under our regulations governing the introduction of certain genetically engineered organisms. Our determination is based on our evaluation of data submitted by the......

  7. 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

  8. Methods to determine DNA structural alterations and genetic instability

    PubMed Central

    Wang, Guliang; Zhao, Junhua; Vasquez, Karen M.

    2009-01-01

    Chromosomal DNA is a dynamic structure that can adopt a variety of non-canonical (i.e. non-B) conformations. In this regard, at least ten different forms of non-B DNA conformations have been identified, and many of them have been found to be mutagenic, and associated with human disease development. Despite the importance of non-B DNA structures in genetic instability and DNA metabolic processes, mechanisms remain largely undefined. The purpose of this review is to summarize current methodologies that are used to address questions in the field of non-B DNA structure-induced genetic instability. Advantages and disadvantages of each method will be discussed. A focused effort to further elucidate the mechanisms of non-B DNA-induced genetic instability will lead to a better understanding of how these structure-forming sequences contribute to the development of human disease. PMID:19245837

  9. 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

  10. 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…

  11. 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. PMID:26637300

  12. 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

  13. Identifying genetic determinants of autoimmunity and immune dysregulation.

    PubMed

    Lucas, Carrie L; Lenardo, Michael J

    2015-12-01

    Common autoimmune diseases are relatively heterogeneous with both genetic and environmental factors influencing disease susceptibility and progression. As the populations in developed countries age, these chronic diseases will become an increasing burden in human suffering and health care costs. By contrast, rare immune diseases that are severe and develop early in childhood are frequently monogenic and fully penetrant, often with a Mendelian inheritance pattern. Although these may be incompatible with survival or cured by hematopoietic stem cell transplantation, we will argue that they constitute a rich source of genetic insights into immunological diseases. Here, we discuss five examples of well-studied Mendelian disease-causing genes and their known or predicted roles in conferring susceptibility to common, polygenic diseases of autoimmunity. Mendelian disease mutations, as experiments of nature, reveal human loci that are indispensable for immune regulation and, therefore, most promising as therapeutic targets. PMID:26433354

  14. Genetical genomic determinants of alcohol consumption in rats and humans

    PubMed Central

    Tabakoff, Boris; Saba, Laura; Printz, Morton; Flodman, Pam; Hodgkinson, Colin; Goldman, David; Koob, George; Richardson, Heather N; Kechris, Katerina; Bell, Richard L; Hübner, Norbert; Heinig, Matthias; Pravenec, Michal; Mangion, Jonathan; Legault, Lucie; Dongier, Maurice; Conigrave, Katherine M; Whitfield, John B; Saunders, John; Grant, Bridget; Hoffman, Paula L

    2009-01-01

    Background We have used a genetical genomic approach, in conjunction with phenotypic analysis of alcohol consumption, to identify candidate genes that predispose to varying levels of alcohol intake by HXB/BXH recombinant inbred rat strains. In addition, in two populations of humans, we assessed genetic polymorphisms associated with alcohol consumption using a custom genotyping array for 1,350 single nucleotide polymorphisms (SNPs). Our goal was to ascertain whether our approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, could inform interpretation of genetic association studies with human populations. Results In the HXB/BXH recombinant inbred (RI) rats, correlation analysis of brain gene expression levels with alcohol consumption in a two-bottle choice paradigm, and filtering based on behavioral and gene expression quantitative trait locus (QTL) analyses, generated a list of candidate genes. A literature-based, functional analysis of the interactions of the products of these candidate genes defined pathways linked to presynaptic GABA release, activation of dopamine neurons, and postsynaptic GABA receptor trafficking, in brain regions including the hypothalamus, ventral tegmentum and amygdala. The analysis also implicated energy metabolism and caloric intake control as potential influences on alcohol consumption by the recombinant inbred rats. In the human populations, polymorphisms in genes associated with GABA synthesis and GABA receptors, as well as genes related to dopaminergic transmission, were associated with alcohol consumption. Conclusion Our results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption. The results suggest cross-species similarities in pathways that influence predisposition to consume alcohol by rats and humans

  15. 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

  16. 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

  17. 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

  18. PRIOR GENETIC CORRELATIONS AND NON-MEASURED TRAITS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Current international genetic evaluations are based on how related country populations are genetically (across-country genetic correlations). Those correlations may be influenced strongly by prior expectations that were not based on sound scientific principles. Objective methods to predict prior cor...

  19. 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

    ...We are advising the public of our determination that a corn line developed by Syngenta Seeds, Inc., designated as transformation event 3272, which has been genetically engineered to produce a microbial enzyme that facilitates ethanol production, is no longer considered a regulated article under our regulations governing the introduction of certain genetically engineered organisms. Our......

  20. 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…

  1. 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…

  2. [Osteochondrodysplasia determined genetically by a collagen type II gene mutation].

    PubMed

    Czarny-Ratajczak, M; Rogala, P; Wolnik-Brzozowska, D; Latos-Bieleńska, A

    2001-01-01

    Chondrodysplasias are a heterogenous group of skeletal dysplasias, affecting the growing cartilage. The main part of chondrodysplasias is caused by mutations in various types of collagen genes. The current classification within this group of disorder relies on clinical, histological and radiographic features. Type II collagenopathies comprise part of chondrodysplasias, consisting of hereditary disorders caused by defects in the type II collagen. Collagen type II is coded by a large gene--COL2A1. The chromosomal location for the human COL2A1 gene is 12q13.11-q13.12. Defects in collagen type II are caused by point mutations in the COL2A1 gene. Type II collagenopathies form a wide spectrum of clinical severity ranging from lethal achondrogenesis type II, hypochondrogenesis, through severe forms like spondyloepiphyseal dysplasia congenita, spondyloepimetaphyseal dysplasia congenita, Marshall syndrome, to the mild forms--Stickler syndrome and early osteoarthritis. The pathological changes in the patients are observed in the growth plate, nucleus pulposus and vitreous body, where the abnormal collagen type II is distributed. This article presents the genetic background of collagenopathies type II and the results of current molecular studies of the patients. Both the molecular and the clinical studies may promise a better understanding of the relationship between the genotype and the phenotype. We present the patients, who were diagnosed at the Department of Medical Genetics and in the Orthopaedic Department in Poznań. PMID:11481990

  3. Genetic determinants for enhanced glycerol growth of Saccharomyces cerevisiae.

    PubMed

    Swinnen, Steve; Ho, Ping-Wei; Klein, Mathias; Nevoigt, Elke

    2016-07-01

    The yeast Saccharomyces cerevisiae generally shows a low natural capability to utilize glycerol as the sole source of carbon, particularly when synthetic medium is used and complex supplements are omitted. Nevertheless, wild type isolates have been identified that show a moderate growth under these conditions. In the current study we made use of intraspecies diversity to identify targets suitable for reverse metabolic engineering of the non-growing laboratory strain CEN.PK113-1A. A genome-wide genetic mapping experiment using pooled-segregant whole-genome sequence analysis was conducted, and one major and several minor genetic loci were identified responsible for the superior glycerol growth phenotype of the previously selected S. cerevisiae strain CBS 6412-13A. Downscaling of the major locus by fine-mapping and reciprocal hemizygosity analysis allowed the parallel identification of two superior alleles (UBR2CBS 6412-13A and SSK1CBS 6412-13A). These alleles together with the previously identified GUT1CBS 6412-13A allele were used to replace the corresponding alleles in the strain CEN.PK113-1A. In this way, glycerol growth could be established reaching a maximum specific growth rate of 0.08h(-1). Further improvement to a maximum specific growth rate of 0.11h(-1) could be achieved by heterologous expression of the glycerol facilitator FPS1 from Cyberlindnera jadinii. PMID:26971668

  4. 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

  5. Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study.

    PubMed

    Petrovic, Dusan; Pivin, Edward; Ponte, Belen; Dhayat, Nasser; Pruijm, Menno; Ehret, Georg; Ackermann, Daniel; Guessous, Idris; Younes, Sandrine Estoppey; Pechère-Bertschi, Antoinette; Vogt, Bruno; Mohaupt, Markus; Martin, Pierre-Yves; Paccaud, Fred; Burnier, Michel; Bochud, Murielle; Stringhini, Silvia

    2016-05-01

    Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally, we investigate the extent to which AL is genetically determined. We included 803 participants (52% women, mean age 48±16years) from a population and family-based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular, metabolic, lipidic, oxidative, hypothalamus-pituitary-adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status, stress, alcohol intake, smoking, dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99, 95%CI [1.22;13.05]), while the opposite was observed for men (middle vs. high OR=0.48, 95%CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54, 95%CI [1.69;7.4]/OR=1.59, 95%CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5% ±7.9%. Our results suggest that generalized physiological dysregulation, as measured by AL, is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component, which explains approximately 70% of the phenotypic variance. PMID:26881833

  6. 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. PMID:27611315

  7. 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

  8. Toenail iron, genetic determinants of iron status and the risk of glioma

    PubMed Central

    Anic, Gabriella M.; Madden, Melissa H.; Thompson, Reid C.; Nabors, L. Burton; Olson, Jeffrey J.; LaRocca, Renato V.; Browning, James E.; Brockman, John D.; Forsyth, Peter A.; Egan, Kathleen M.

    2013-01-01

    Purpose Iron is essential for oxygen transport and oxidative metabolism; however, elevated iron stores can trigger overproduction of reactive oxygen species and induce DNA damage. Little is known about the association between body iron stores and glioma risk. This study examined associations of iron levels measured in toenails and genetic variants linked to body iron stores with risk of glioma in a clinic-based case-control study. Methods Samples were collected a median of 24 days following glioma diagnosis in the cases (10th-90th percentile range: 10-44 days). Nail iron levels were measured in 300 cases and 300 controls using neutron-activation analysis. A total of 24 genetic variants associated with iron status were genotyped in 622 cases and 628 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for glioma risk according to toenail iron and the examined genotypes. Results No association was observed between toenail iron and glioma risk when restricting to cases with nails collected within ~3 weeks of diagnosis (OR=0.93; 95% CI: 0.46, 1.87 comparing those with high (≥ 14 μg/g) versus low (<6 μg/g) iron levels). In contrast, an inverse association with increasing iron was observed after restricting to cases with a delay of 3 weeks or greater (OR=0.42; 95% CI: 0.19, 0.95) reflecting potentially insidious effects of advancing disease on iron levels among the cases. No associations were observed for any of the examined genetic variants. Conclusion The results do not support a role for body iron stores as a determinant of glioma risk. PMID:23996192

  9. 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. PMID:26835965

  10. Genetic determinants of Tibetan high-altitude adaptation.

    PubMed

    Simonson, Tatum S; McClain, Donald A; Jorde, Lynn B; Prchal, Josef T

    2012-04-01

    Some highland populations have genetic adaptations that enable their successful existence in a hypoxic environment. Tibetans are protected against many of the harmful responses exhibited by non-adapted populations upon exposure to severe hypoxia, including elevated hemoglobin concentration (i.e., polycythemia). Recent studies have highlighted several genes subject to natural selection in native high-altitude Tibetans. Three of these genes, EPAS1, EGLN1 and PPARA, regulate or are regulated by hypoxia inducible factor, a principal controller of erythropoiesis and other organismal functions. Uncovering the molecular basis of hypoxic adaptation should have implications for understanding hematological and other adaptations involved in hypoxia tolerance. Because the hypoxia response involves a variety of cardiovascular, pulmonary and metabolic functions, this knowledge would improve our understanding of disease mechanisms and could ultimately be translated into targeted therapies for oxygen deprivation, cardiopulmonary and cerebral pathologies, and metabolic disorders such as diabetes and obesity. PMID:22068265

  11. Cigarette Experimentation in Mexican Origin Youth: Psychosocial and Genetic Determinants

    PubMed Central

    Wilkinson, Anna V.; Bondy, Melissa L.; Wu, Xifeng; Wang, Jian; Dong, Qiong; D’Amelio, Anthony M.; Prokhorov, Alexander V.; Pu, Xia; Yu, Robert K.; Etzel, Carol J.; Shete, Sanjay; Spitz, Margaret R.

    2011-01-01

    Background Established psychosocial risk factors increase the risk for experimentation among Mexican-origin youth. Now we comprehensively investigate the added contribution of select polymorphisms in candidate genetic pathways associated with sensation seeking, risk taking, and smoking phenotypes to predict experimentation. Methods Participants, (N=1,118 Mexican origin youth) recruited from a large population-based cohort study in Houston, Texas, provided prospective data on cigarette experimentation over three years. Psychosocial data were elicited twice—baseline and final follow-up. Participants were genotyped for 672 functional and tagging variants in the dopamine, serotonin and opioid pathways. Results After adjusting for gender and age, with a Bayesian False Discovery Probability set at 0.8 and prior probability of 0.05, six gene variants were significantly associated with risk of experimentation. After controlling for established risk factors, multivariable analyses revealed that participants with six or more risk alleles were 2.25 (95%CI: 1.62–3.13) times more likely to have experimented since baseline compared to participants with five or fewer. Among committed never smokers (N=872), three genes (OPRM1, SNAP25, HTR1B) were associated with experimentation as were all psychosocial factors. Among susceptible youth (N=246) older age at baseline, living with a smoker, and three different genes (HTR2A, DRD2, SLC6A3) predicted experimentation. Conclusions Our findings, which have implications for development of culturally-specific interventions, need to be validated in other ethnic groups. Impact These results suggest that variations in select genes interact with a cognitive predisposition toward smoking. In susceptible adolescents, the impact of the genetic variants appears to be larger compared to committed never smokers. PMID:22028400

  12. Genetics

    MedlinePlus

    Homozygous; 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 ...

  13. 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 ...

  14. 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. PMID:25988829

  15. 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. PMID:27173935

  16. Genetic determinants of type 1 diabetes: immune response genes.

    PubMed

    Kumar, Neeraj; Kaur, Gurvinder; Mehra, Narinder

    2009-04-01

    Type 1 diabetes (T1D) is a polygenic autoimmune disease. Susceptibility to T1D is strongly linked to a major genetic locus that is the MHC, and several other minor loci including insulin, cytotoxic T-lymphocyte-associated antigen-4, PTPN22 and others that contribute to diabetes risk in an epistatic way. We have observed that there are three sets of DR3-positive autoimmunity-favoring haplotypes in the north-Indian population, including B50-DR3, B58-DR3 and B8-DR3. The classical Caucasian autoimmunity favoring AH8.1 (HLA-A1-B8-DR3) is rare in the Indian population, and has been replaced by a variant AH8.1v, which differs from the Caucasian AH8.1 at several gene loci. Similarly, there are additional HLA-DR3 haplotypes, A26-B8-DR3 (AH8.2), A24-B8-DR3 (AH8.3), A3-B8-DR3 (AH8.4) and A31-B8-DR3 (AH8.5), of which AH8.2 is the most common. The fact that disease-associated DR3-positive haplotypes show heterogeneity in different populations suggests that these might possess certain shared components that are involved in the development of autoimmunity. PMID:20477508

  17. 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.

  18. Genetic network properties of the human cortex based on regional thickness and surface area measures

    PubMed Central

    Docherty, Anna R.; Sawyers, Chelsea K.; Panizzon, Matthew S.; Neale, Michael C.; Eyler, Lisa T.; Fennema-Notestine, Christine; Franz, Carol E.; Chen, Chi-Hua; McEvoy, Linda K.; Verhulst, Brad; Tsuang, Ming T.; Kremen, William S.

    2015-01-01

    We examined network properties of genetic covariance between average cortical thickness (CT) and surface area (SA) within genetically-identified cortical parcellations that we previously derived from human cortical genetic maps using vertex-wise fuzzy clustering analysis with high spatial resolution. There were 24 hierarchical parcellations based on vertex-wise CT and 24 based on vertex-wise SA expansion/contraction; in both cases the 12 parcellations per hemisphere were largely symmetrical. We utilized three techniques—biometrical genetic modeling, cluster analysis, and graph theory—to examine genetic relationships and network properties within and between the 48 parcellation measures. Biometrical modeling indicated significant shared genetic covariance between size of several of the genetic parcellations. Cluster analysis suggested small distinct groupings of genetic covariance; networks highlighted several significant negative and positive genetic correlations between bilateral parcellations. Graph theoretical analysis suggested that small world, but not rich club, network properties may characterize the genetic relationships between these regional size measures. These findings suggest that cortical genetic parcellations exhibit short characteristic path lengths across a broad network of connections. This property may be protective against network failure. In contrast, previous research with structural data has observed strong rich club properties with tightly interconnected hub networks. Future studies of these genetic networks might provide powerful phenotypes for genetic studies of normal and pathological brain development, aging, and function. PMID:26347632

  19. Genetically encoded force sensors for measuring mechanical forces in proteins

    PubMed Central

    Wang, Yuexiu; Sachs, Frederick

    2011-01-01

    There are three sources of free energy for cells: chemical potential, electrical potential and mechanical potential. There is little known about the last one since there have not been simple ways to measure stress in proteins in cells. we have now developed genetically encoded force sensors to assess the stress in fibrous proteins in living cells. These FReT based fluorescence sensors can be read out at video rates and provide real time maps of the stress distribution in cells, tissues and animals. The sensors can be inserted into specific proteins and in general do not disturb the normal function or anatomy. The original sensors used mutant GFPs linked by elastic linkers. These sensors provide a linear output with applied stress but the response is linear in strain. To improve contrast and dynamic range we have now developed a new class of sensors that are smaller making them less invasive, and have much higher intrinsic sensitivity since force modulates the angle between the donor and acceptor much more than the distance between them. Known as cpstFRET, the probe shows improved biocompatibility, wider dynamic range and higher sensitivity. PMID:21966553

  20. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  2. 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.

  3. 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…

  4. Overview of the genetic determinants of primary aldosteronism

    PubMed Central

    Al-Salameh, Abdallah; Cohen, Régis; Desailloud, Rachel

    2014-01-01

    Primary aldosteronism is the most common cause of secondary hypertension. The syndrome accounts for 10% of all cases of hypertension and is primarily caused by bilateral adrenal hyperplasia or aldosterone-producing adenoma. Over the last few years, the use of exome sequencing has significantly improved our understanding of this syndrome. Somatic mutations in the KCNJ5, ATP1A1, ATP2B3 or CACNA1D genes are present in more than half of all cases of aldosterone-producing adenoma (~40%, ~6%, ~1% and ~8%, respectively). Germline gain-of-function mutations in KCNJ5 are now known to cause familial hyperaldosteronism type III, and an additional form of genetic hyperaldosteronism has been reported in patients with germline mutations in CACNA1D. These genes code for channels that control ion homeostasis across the plasma membrane of zona glomerulosa cells. Moreover, all these mutations modulate the same pathway, in which elevated intracellular calcium levels lead to aldosterone hyperproduction and (in some cases) adrenal cell proliferation. From a clinical standpoint, the discovery of these mutations has potential implications for patient management. The mutated channels could be targeted by drugs, in order to control hormonal and overgrowth-related manifestations. Furthermore, some of these mutations are associated with high cell turnover and may be amenable to diagnosis via the sequencing of cell-free (circulating) DNA. However, genotype-phenotype correlations in patients harboring these mutations have yet to be characterized. Despite this recent progress, much remains to be done to elucidate the yet unknown mechanisms underlying sporadic bilateral adrenal hyperplasia. PMID:24817817

  5. Flow Cytometry Enables Multiplexed Measurements of Genetically Encoded Intramolecular FRET Sensors Suitable for Screening.

    PubMed

    Doucette, Jaimee; Zhao, Ziyan; Geyer, Rory J; Barra, Melanie M; Balunas, Marcy J; Zweifach, Adam

    2016-07-01

    Genetically encoded sensors based on intramolecular FRET between CFP and YFP are used extensively in cell biology research. Flow cytometry has been shown to offer a means to measure CFP-YFP FRET; we suspected it would provide a unique way to conduct multiplexed measurements from cells expressing different FRET sensors, which is difficult to do with microscopy, and that this could be used for screening. We confirmed that flow cytometry accurately measures FRET signals using cells transiently transfected with an ERK activity reporter, comparing responses measured with imaging and cytometry. We created polyclonal long-term transfectant lines, each expressing a different intramolecular FRET sensor, and devised a way to bar-code four distinct populations of cells. We demonstrated the feasibility of multiplexed measurements and determined that robust multiplexed measurements can be conducted in plate format. To validate the suitability of the method for screening, we measured responses from a plate of bacterial extracts that in unrelated experiments we had determined contained the protein kinase C (PKC)-activating compound teleocidin A-1. The multiplexed assay correctly identifying the teleocidin A-1-containing well. We propose that multiplexed cytometric FRET measurements will be useful for analyzing cellular function and for screening compound collections. PMID:26908592

  6. 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

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

    PubMed

    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

    2015-09-15

    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

  8. Genetic Determinants of On-Aspirin Platelet Reactivity: Focus on the Influence of PEAR1

    PubMed Central

    Würtz, Morten; Nissen, Peter H.; Grove, Erik Lerkevang; Kristensen, Steen Dalby; Hvas, Anne-Mette

    2014-01-01

    Background Platelet aggregation during aspirin treatment displays considerable inter-individual variability. A genetic etiology likely exists, but it remains unclear to what extent genetic polymorphisms determine platelet aggregation in aspirin-treated individuals. Aim To identify platelet-related single nucleotide polymorphisms (SNPs) influencing platelet aggregation during aspirin treatment. Furthermore, we explored to what extent changes in cyclooxygenase-1 activity and platelet activation may explain such influence. Methods We included 985 Danish patients with stable coronary artery disease treated with aspirin 75 mg/day mono antiplatelet therapy. Patients were genotyped for 16 common SNPs in platelet-related genes using standard PCR-based methods (TaqMan). Platelet aggregation was evaluated by whole blood platelet aggregometry employing Multiplate Analyzer (agonists: arachidonic acid and collagen) and VerifyNow Aspirin. Serum thromboxane B2 was measured to confirm aspirin adherence and was used as a marker of cyclooxygenase-1 activity. Soluble P-selectin was used as marker of platelet activation. Platelet aggregation, cyclooxygenase-1 activity, and platelet activation were compared across genotypes in adjusted analyses. Results The A-allele of the rs12041331 SNP in the platelet endothelial aggregation receptor-1 (PEAR1) gene was associated with reduced platelet aggregation and increased platelet activation, but not with cyclooxygenase-1 activity. Platelet aggregation was unaffected by the other SNPs analyzed. Conclusion A common genetic variant in PEAR1 (rs12041331) reproducibly influenced platelet aggregation in aspirin-treated patients with coronary artery disease. The exact biological mechanism remains elusive, but the effect of this polymorphism may be related to changes in platelet activation. Furthermore, 14 SNPs previously suggested to influence aspirin efficacy were not associated with on-aspirin platelet aggregation. Clinical Trial Registration

  9. 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. PMID:24351057

  10. Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-08-01

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

  12. Genetic Determinants of Tetracycline Resistance in Vibrio harveyi

    PubMed Central

    Teo, Jeanette W. P.; Tan, Theresa M. C.; Poh, Chit Laa

    2002-01-01

    Isolates of Vibrio harveyi, a prawn pathogen, have demonstrated multiple antibiotic resistance to commonly used antimicrobial agents, such as oxytetracycline. In this paper, we describe the cloning and characterization of two tetracycline resistance determinants from V. harveyi strain M3.4L. The first resistance determinant, cloned as a 4,590-bp fragment, was identical to tetA and flanking sequences encoded on transposon Tn10 from Shigella flexneri. The second determinant, cloned as a 3,358-bp fragment in pATJ1, contains two open reading frames, designated tet35 and txr. tet35 encodes a 369-amino-acid protein that was predicted to have nine transmembrane regions. It is a novel protein which has no homology to any other drug resistance protein but has low levels of homology (28%) to Na+/H+ antiporters. Transposon mutagenesis showed that tet35 and txr were required for tetracycline resistance in a heterologous Escherichia coli host. Tetracycline accumulation studies indicate that E. coli carrying tet35 and txr can function as an energy-dependent tetracycline efflux pump but is less efficient than TetA. PMID:11897587

  13. 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. PMID:25563981

  14. Estimating Genetic and Maternal Effects Determining Variation in Immune Function of a Mixed-Mating Snail

    PubMed Central

    Seppälä, Otto; Langeloh, Laura

    2016-01-01

    Evolution of host defenses such as immune function requires heritable genetic variation in them. However, also non-genetic maternal effects can contribute to phenotypic variation, thus being an alternative target for natural selection. We investigated the role of individuals’ genetic background and maternal effects in determining immune defense traits (phenoloxidase and antibacterial activity of hemolymph), as well as in survival and growth, in the simultaneously hermaphroditic snail Lymnaea stagnalis. We utilized the mixed mating system of this species by producing full-sib families in which each parental snail had produced offspring as both a dam and as a sire, and tested whether genetic background (family) and non-genetic maternal effects (dam nested within family) explain trait variation. Immune defense traits and growth were affected solely by individuals’ genetic background. Survival of snails did not show family-level variation. Additionally, some snails were produced through self-fertilization. They showed reduced growth and survival suggesting recessive load or overdominance. Immune defense traits did not respond to inbreeding. Our results suggest that the variation in snail immune function and growth was due to genetic differences. Since immune traits did not respond to inbreeding, this variation is most likely due to additive or epistatic genetic variance. PMID:27551822

  15. Prenatal genetic testing: an investigation of determining factors affecting the decision-making process.

    PubMed

    Pivetti, Monica; Melotti, Giannino

    2013-02-01

    Despite the increase in popularity of prenatal genetic testing, relatively little is known about the role psychological factors play in the decision-making process. In this analogue study, a sample of Italian female university students was used to investigate determining factors that predict the intention of undergoing prenatal genetic testing. Structural Equation Modelling was used to describe the dynamic interplay between knowledge, beliefs, attitudes and health-related behaviour such as prenatal genetic testing. Following the Theory of Reasoned Action, three dimensions predicted the intention to undergo prenatal genetic testing: the need for more scientific information, a positive attitude towards genetic testing, and the inclination to terminate pregnancy after receiving a positive test result. Results showed that less religious women tended to be more in favour of prenatal tests and in undertaking such tests. This preliminary study provides genetic counsellors and policy makers with a clearer picture of their clients' motives and attitudes behind the decision-making process of prenatal genetic testing, contributing to improving both the communication process between counsellors and their clients and the organization of genetic services. PMID:22477148

  16. Estimating Genetic and Maternal Effects Determining Variation in Immune Function of a Mixed-Mating Snail.

    PubMed

    Seppälä, Otto; Langeloh, Laura

    2016-01-01

    Evolution of host defenses such as immune function requires heritable genetic variation in them. However, also non-genetic maternal effects can contribute to phenotypic variation, thus being an alternative target for natural selection. We investigated the role of individuals' genetic background and maternal effects in determining immune defense traits (phenoloxidase and antibacterial activity of hemolymph), as well as in survival and growth, in the simultaneously hermaphroditic snail Lymnaea stagnalis. We utilized the mixed mating system of this species by producing full-sib families in which each parental snail had produced offspring as both a dam and as a sire, and tested whether genetic background (family) and non-genetic maternal effects (dam nested within family) explain trait variation. Immune defense traits and growth were affected solely by individuals' genetic background. Survival of snails did not show family-level variation. Additionally, some snails were produced through self-fertilization. They showed reduced growth and survival suggesting recessive load or overdominance. Immune defense traits did not respond to inbreeding. Our results suggest that the variation in snail immune function and growth was due to genetic differences. Since immune traits did not respond to inbreeding, this variation is most likely due to additive or epistatic genetic variance. PMID:27551822

  17. 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.

  18. 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'…

  19. 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

  20. 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.

  1. [Molecular genetics and determination of time since death - short communication].

    PubMed

    Šaňková, Markéta; Račanská, Michaela

    2016-01-01

    Estimation of time since death, i.e. the post-mortem interval (PMI), is one of the most problematic issues in forensic practice. Accurate determination of the PMI still remains very complicated task even for an experienced forensic pathologist.Physical changes including algor, livor and rigor mortis can be observed already during the first hours after death of an individual. Unfortunately, the estimation of PMI on the basis of these changes is often burdened with a certain degree of inaccuracy, which is caused by the temperature of surrounding environment, constitution of the body, cause of the death, location of the body, drug abuse etc.Accurate PMI estimation requires assessment of such parameters, which change constantly from the moment of death, but independently on ambient factors. According to current research in the field of molecular biology, it appears that a post-mortem degradation of nucleic acids (both DNA and RNA) will correspond to this definition. PMID:27526264

  2. Genetic Determinants of Intrinsic Colistin Tolerance in Acinetobacter baumannii

    PubMed Central

    Hood, M. Indriati; Becker, Kyle W.; Roux, Christelle M.; Dunman, Paul M.

    2013-01-01

    Acinetobacter baumannii is a leading cause of multidrug-resistant infections worldwide. This organism poses a particular challenge due to its ability to acquire resistance to new antibiotics through adaptation or mutation. This study was undertaken to determine the mechanisms governing the adaptability of A. baumannii to the antibiotic colistin. Screening of a transposon mutant library identified over 30 genes involved in inducible colistin resistance in A. baumannii. One of the genes identified was lpsB, which encodes a glycosyltransferase involved in lipopolysaccharide (LPS) synthesis. We demonstrate that loss of LpsB function results in increased sensitivity to both colistin and cationic antimicrobial peptides of the innate immune system. Moreover, LpsB is critical for pathogenesis in a pulmonary model of infection. Taken together, these data define bacterial processes required for intrinsic colistin tolerance in A. baumannii and underscore the importance of outer membrane structure in both antibiotic resistance and the pathogenesis of A. baumannii. PMID:23230287

  3. 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

  4. 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

  5. Genetic determinants of β-thalassemia intermedia in Pakistan.

    PubMed

    Khan, Jabbar; Ahmad, Nafees; Siraj, Sami; Hoti, Naseruddin

    2015-01-01

    This study covers the molecular characterization of clinically diagnosed β-thalassemia intermedia (β-TI) patients in Pakistan. Blood samples of β-TI patients were collected from all four provinces of Pakistan throughout the period of 2011-2013. The study was carried out using allele-specific primers through polymerase chain reaction or sequencing to determine both α- and β-thalassemia (α- and β-thal) mutations, and restriction enzymes for the characterization of β-globin gene arrangements. In a total of 63 patients, the IVS-I-5 (G > C) was the most frequent mutation (33.88%). The codon 30 (G > A) and IVS-II-1 (T > C) mutations were found only in the Punjabi ethnic group, while the codon 30 (G > C) and Hb S (HBB: c.20A > T) mutations were found only in the Pashtoon and Sindhi ethnic groups, respectively. In case of α-globin genotypes, 44 patients were normal (αα/αα), six patients carried the αα/-α(3.7) genotype, 12 patients carried the -α(3.7)/-α(3.7) genotype, while one patient had the αα/ααα(anti 3.7) genotype. We found that haplotype I was the most frequent, mostly associated with the codons 8/9 (+G) mutation, while the Saudi haplotype was found only with Hb S. PMID:25707679

  6. Overcast Clouds Determined By Trmm Measurements

    NASA Technical Reports Server (NTRS)

    Lin, Bing; Minnis, Patrick; Wielicki, Bruce; Hu, Yongxiang; Ho, Shu-Peng

    2000-01-01

    Using the Tropical Rainfall Measuring Mission (TRMM) Visible and Infra-Red Scanner (VIRS) and TRMM Microwave Radiometer (TMI) measurements, this study retrieves cloud optical depth (tau), liquid water path (LWP), and the frequency of co-occurrence of ice and water clouds based on radiative transfer models. Results show that LWP values for warm non-precipitating clouds are approximately 0.06mm and cold clouds have large ice water amount (approximately 0.1mm). The cloud systems with significant amounts of water below ice occur about 10 to approximately 20% of the time.

  7. 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

  8. Genetic determinants of haemolysis in sickle cell anaemia

    PubMed Central

    Milton, Jacqueline N.; Rooks, Helen; Drasar, Emma; McCabe, Elizabeth L.; Baldwin, Clinton T.; Melista, Efi; Gordeuk, Victor R.; Nouraie, Mehdi; Kato, Gregory R.; 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.

    2014-01-01

    Summary 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 (r2 = 1) and in strong LD with rs7197554 (r2 = 0·75) and rs13336641 (r2 = 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 −∝3·7thalassaemia 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. PMID:23406172

  9. [The role of brain serotonin in the expression of genetically determined defensive behavior].

    PubMed

    Popova, N K

    2004-06-01

    The review summarizes the results of long-term studies on the role of the brain mediator serotonin and genetic predisposition to various types of defensive behavior. The involvement of the serotonergic brain system in the mechanisms of genetic control of both active and passive defensive responses has been established using silver foxes, Norway rats of S40 selection for low and high aggressiveness to humans, aggressive mice with genetic knockout of monoaminoxidase A, and S40 rats selected for predisposition to passive defensive response of freezing (catalepsy). The changes in the serotonergic 5-HT1A-brain receptors of rats genetically predisposed to different strategies of defensive behavior were similar. However, the activity of the key enzyme of serotonin biosynthesis and the brain structures, in which serotonin metabolism was altered, significantly differed with regard to the preferred strategy. The conclusion was drawn that the 5-HT1A-receptors and enzymes of serotonin metabolism in the brain are involved in implementing genetic control of defensive behavior. Expression of the 5-HT1A-brain receptors was suggested to determine the levels of fear and anxiety and, consequently, the predisposition to defensive behavior, whereas the preferred strategy of defensive response (active or passive defensive) depends on genetically determined features of serotonin metabolism in the brain structures. PMID:15341267

  10. 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.

  11. Determining camera parameters for round glassware measurements

    NASA Astrophysics Data System (ADS)

    Baldner, F. O.; Costa, P. B.; Gomes, J. F. S.; Filho, D. M. E. S.; Leta, F. R.

    2015-01-01

    Nowadays there are many types of accessible cameras, including digital single lens reflex ones. Although these cameras are not usually employed in machine vision applications, they can be an interesting choice. However, these cameras have many available parameters to be chosen by the user and it may be difficult to select the best of these in order to acquire images with the needed metrological quality. This paper proposes a methodology to select a set of parameters that will supply a machine vision system with the needed quality image, considering the measurement required of a laboratory glassware.

  12. Epigenetic and genetic burden measures are associated with tumor characteristics in invasive breast carcinoma

    PubMed Central

    O'Sullivan, Dylan E.; Johnson, Kevin C.; Skinner, Lucy; Koestler, Devin C.; Christensen, Brock C.

    2016-01-01

    ABSTRACT The development and progression of invasive breast cancer is characterized by alterations to the genome and epigenome. However, the relationship between breast tumor characteristics, disease subtypes, and patient outcomes with the cumulative burden of these molecular alterations are not well characterized. We determined the average departure of tumor DNA methylation from adjacent normal breast DNA methylation using Illumina 450K methylation data from 700 invasive breast tumors and 90 adjacent normal breast tissues in The Cancer Genome Atlas. From this we generated a novel summary measure of altered DNA methylation, the DNA methylation dysregulation index (MDI), and examined the relation of MDI with tumor characteristics and summary measures that quantify cumulative burden of genetic mutation and copy number alterations. Our analysis revealed that MDI was significantly associated with tumor stage (P = 0.017). Across invasive breast tumor subtypes we observed significant differences in genome-wide DNA MDIs (P = 4.9E–09) and in a fraction of the genome with copy number alterations (FGA) (P = 4.6E–03). Results from a linear regression adjusted for subject age, tumor stage, and estimated tumor purity indicated a positive significant association of MDI with both MCB and FGA (P = 0.036 and P < 2.2E–16). A recursively partitioned mixture model of all 3 somatic alteration burden measures resulted in classes of tumors whose epigenetic and genetic burden profile were associated with the PAM50 subtype and mutations in TP53, PIK3CA, and CDH1. Together, our work presents a novel framework for characterizing the epigenetic burden and adds to the understanding of the aggregate impact of epigenetic and genetic alterations in breast cancer. PMID:27070496

  13. 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. PMID:26926275

  14. Genetic determinants of hair and eye colours in the Scottish and Danish populations

    PubMed Central

    2009-01-01

    Background Eye and hair colour is highly variable in the European population, and is largely genetically determined. Both linkage and association studies have previously been used to identify candidate genes underlying this variation. Many of the genes found were previously known as underlying mutant mouse phenotypes or human genetic disease, but others, previously unsuspected as pigmentation genes, have also been discovered. Results We assayed the hair of a population of individuals of Scottish origin using tristimulus colorimetry, in order to produce a quantitative measure of hair colour. Cluster analysis of this data defined two groups, with overlapping borders, which corresponded to visually assessed dark versus red/light hair colour. The Danish population was assigned into categorical hair colour groups. Both cohorts were also assessed for eye colour. DNA from the Scottish group was genotyped at SNPs in 33 candidate genes, using 384 SNPs identified by HapMap as representatives of each gene. Associations found between SNPs and colorimetric hair data and eye colour categories were replicated in a cohort of the Danish population. The Danish population was also genotyped with SNPs in 4 previously described pigmentation genes. We found replicable associations of hair colour with the KITLG and OCA2 genes. MC1R variation correlated, as expected, with the red dimension of colorimetric hair colour in Scots. The Danish analysis excluded those with red hair, and no associations were found with MC1R in this group, emphasising that MC1R regulates the colour rather than the intensity of pigmentation. A previously unreported association with the HPS3 gene was seen in the Scottish population. However, although this replicated in the smaller cohort of the Danish population, no association was seen when the whole study population was analysed. Conclusions We have found novel associations with SNPs in known pigmentation genes and colorimetrically assessed hair colour in a

  15. 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

  16. 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. PMID:18232457

  17. 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.

  18. 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…

  19. 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

    ...This notice advises the public of the Animal and Plant Health Inspection Service's (APHIS) record of decision and determination on the petition regarding the regulated status of alfalfa genetically engineered for tolerance to the herbicide glyphosate based on APHIS' final environmental impact...

  20. Determining the Effective Dimensionality of the Genetic Variance–Covariance Matrix

    PubMed Central

    Hine, Emma; Blows, Mark W.

    2006-01-01

    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. PMID:16547106

  1. Use of RAPD markers to determine the genetic diversity of diploid, wheat genotypes.

    PubMed

    Vierling, R A; Nguyen, H T

    1992-09-01

    The genetic diversity of two diploid wheat species, Triticum monococcum and Triticum urartu (2n=2x=14), was assessed using random primers and the polymerase chain reaction (PCR). Electrophoretic analysis of the amplification products revealed a higher incidence of polymorphism in T. urartu than T. monococcum. Pair-wise comparisons of unique and shared polymorphic amplification products, were used to generate Jaccard's similarity coefficients. These were employed to construct phenograms using an unweighted pair-group method with arithmetical averages (UPGMA). The UPGMA analysis indicated a higher similarity among T. monococcum than T. urartu. Analysis of RAPD data appears to be helpful in determining the genetic relationships among genotypes. PMID:24201483

  2. 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

    2015-11-01

    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. PMID:26444239

  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. Determination of a geocentric coordinate frame for GPS measurements

    NASA Technical Reports Server (NTRS)

    Wu, S. C.; Malla, R. P.

    1988-01-01

    Two strategies for determining the offset from the geocenter for GPS measurements are considered. In the first strategy, VLBI-determined relative positions are used to fix the frame orientation and the absolute scaling, while the geocenter offset is determined from GPS measurements. In the second strategy, the absolute scaling is determined by the adopted gravitational constant of earth and the adjusted periods of GPS orbits, with the latitude being obtained from the time signature of earth rotation in the GPS measurements. The results indicate that geocentric positioning to an accuracy of a few centimeters can be achieved with just one day of precise GPS pseudorange and carrier phase data.

  5. Mapping Determinants of Gene Expression Plasticity by Genetical Genomics in C. elegans

    PubMed Central

    Gutteling, Evert W; Tijsterman, Marcel; Fu, Jingyuan; Riksen, Joost A. G; Hazendonk, Esther; Prins, Pjotr; Plasterk, Ronald H. A; Jansen, Ritsert C; Breitling, Rainer; Kammenga, Jan E

    2006-01-01

    Recent genetical genomics studies have provided intimate views on gene regulatory networks. Gene expression variations between genetically different individuals have been mapped to the causal regulatory regions, termed expression quantitative trait loci. Whether the environment-induced plastic response of gene expression also shows heritable difference has not yet been studied. Here we show that differential expression induced by temperatures of 16 °C and 24 °C has a strong genetic component in Caenorhabditis elegans recombinant inbred strains derived from a cross between strains CB4856 (Hawaii) and N2 (Bristol). No less than 59% of 308 trans-acting genes showed a significant eQTL-by-environment interaction, here termed plasticity quantitative trait loci. In contrast, only 8% of an estimated 188 cis-acting genes showed such interaction. This indicates that heritable differences in plastic responses of gene expression are largely regulated in trans. This regulation is spread over many different regulators. However, for one group of trans-genes we found prominent evidence for a common master regulator: a transband of 66 coregulated genes appeared at 24 °C. Our results suggest widespread genetic variation of differential expression responses to environmental impacts and demonstrate the potential of genetical genomics for mapping the molecular determinants of phenotypic plasticity. PMID:17196041

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

    PubMed

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

    2013-12-01

    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]. PMID:24268409

  7. 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

  8. 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

  9. Host genetics determine susceptibility to avian influenza infection and transmission dynamics.

    PubMed

    Ruiz-Hernandez, Raul; Mwangi, William; Peroval, Marylene; Sadeyen, Jean-Remy; Ascough, Stephanie; Balkissoon, Devanand; Staines, Karen; Boyd, Amy; McCauley, John; Smith, Adrian; Butter, Colin

    2016-01-01

    Host-genetic control of influenza virus infection has been the object of little attention. In this study we determined that two inbred lines of chicken differing in their genetic background , Lines 0 and C-B12, were respectively relatively resistant and susceptible to infection with the low pathogenicity influenza virus A/Turkey/England/647/77 as defined by substantial differences in viral shedding trajectories. Resistant birds, although infected, were unable to transmit virus to contact birds, as ultimately only the presence of a sustained cloacal shedding (and not oropharyngeal shedding) was critical for transmission. Restriction of within-bird transmission of virus occurred in the resistant line, with intra-nares or cloacal infection resulting in only local shedding and failing to transmit fully through the gastro-intestinal-pulmonary tract. Resistance to infection was independent of adaptive immune responses, including the expansion of specific IFNγ secreting cells or production of influenza-specific antibody. Genetic resistance to a novel H9N2 virus was less robust, though significant differences between host genotypes were still clearly evident. The existence of host-genetic determination of the outcome of influenza infection offers tools for the further dissection of this regulation and also for understanding the mechanisms of influenza transmission within and between birds. PMID:27279280

  10. Genetic and Nongenetic Determinants of Cell Growth Variation Assessed by High-Throughput Microscopy

    PubMed Central

    Ziv, Naomi; Siegal, Mark L.; Gresham, David

    2013-01-01

    In microbial populations, growth initiation and proliferation rates are major components of fitness and therefore likely targets of selection. We used a high-throughput microscopy assay, which enables simultaneous analysis of tens of thousands of microcolonies, to determine the sources and extent of growth rate variation in the budding yeast (Saccharomyces cerevisiae) in different glucose environments. We find that cell growth rates are regulated by the extracellular concentration of glucose as proposed by Monod (1949), but that significant heterogeneity in growth rates is observed among genetically identical individuals within an environment. Yeast strains isolated from different geographic locations and habitats differ in their growth rate responses to different glucose concentrations. Inheritance patterns suggest that the genetic determinants of growth rates in different glucose concentrations are distinct. In addition, we identified genotypes that differ in the extent of variation in growth rate within an environment despite nearly identical mean growth rates, providing evidence that alleles controlling phenotypic variability segregate in yeast populations. We find that the time to reinitiation of growth (lag) is negatively correlated with growth rate, yet this relationship is strain-dependent. Between environments, the respirative activity of individual cells negatively correlates with glucose abundance and growth rate, but within an environment respirative activity and growth rate show a positive correlation, which we propose reflects differences in protein expression capacity. Our study quantifies the sources of genetic and nongenetic variation in cell growth rates in different glucose environments with unprecedented precision, facilitating their molecular genetic dissection. PMID:23938868

  11. 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

  12. Host genetics determine susceptibility to avian influenza infection and transmission dynamics

    PubMed Central

    Ruiz-Hernandez, Raul; Mwangi, William; Peroval, Marylene; Sadeyen, Jean-Remy; Ascough, Stephanie; Balkissoon, Devanand; Staines, Karen; Boyd, Amy; McCauley, John; Smith, Adrian; Butter, Colin

    2016-01-01

    Host-genetic control of influenza virus infection has been the object of little attention. In this study we determined that two inbred lines of chicken differing in their genetic background , Lines 0 and C-B12, were respectively relatively resistant and susceptible to infection with the low pathogenicity influenza virus A/Turkey/England/647/77 as defined by substantial differences in viral shedding trajectories. Resistant birds, although infected, were unable to transmit virus to contact birds, as ultimately only the presence of a sustained cloacal shedding (and not oropharyngeal shedding) was critical for transmission. Restriction of within-bird transmission of virus occurred in the resistant line, with intra-nares or cloacal infection resulting in only local shedding and failing to transmit fully through the gastro-intestinal-pulmonary tract. Resistance to infection was independent of adaptive immune responses, including the expansion of specific IFNγ secreting cells or production of influenza-specific antibody. Genetic resistance to a novel H9N2 virus was less robust, though significant differences between host genotypes were still clearly evident. The existence of host-genetic determination of the outcome of influenza infection offers tools for the further dissection of this regulation and also for understanding the mechanisms of influenza transmission within and between birds. PMID:27279280

  13. Genetic parameter estimates for carcass and yearling ultrasound measurements in Brangus cattle.

    PubMed

    Moser, D W; Bertrand, J K; Misztal, I; Kriese, L A; Benyshek, L L

    1998-10-01

    Carcass measurements of 12th-rib fat thickness (CARCFAT), longissimus muscle area (CARCLMA), and weight (CARCWT) on 2,028 Brangus and Brangus-sired fed steers and heifers, as well as yearling weights (YWT) and ultrasound measures of 12th-rib fat thickness (USFAT) and longissimus muscle area (USLMA) on 3,583 Brangus bulls and heifers were analyzed to estimate genetic parameters. Data were analyzed using a six-trait animal model and an average information REML algorithm. The model included fixed effects for contemporary group and breed of dam, covariates for age at slaughter or measurement, and random animal and residual effects. Heritabilities for CARCFAT, CARCLMA, CARCWT, USFAT, USLMA, and YWT were .27+/-.05, .39+/-.05, .59+/-.06, .11+/-.03, .29+/-.04, and .40+/-.04, respectively. Genetic correlations between CARCFAT and USFAT, CARCLMA and USLMA, and CARCWT and YWT were .69+/-.18, .66+/-.14, and .61+/-.11, respectively. The favorable and moderately strong genetic correlations between carcass measurements and similar yearling breeding-animal ultrasound measurements indicate that such measurements of 12th-rib fat and longissimus muscle area are useful in predicting genetic values for carcass leanness and longissimus muscle area. Selection using yearling ultrasound measurements of breeding cattle should result in predictable genetic improvement for carcass characteristics. Inclusion of yearling ultrasound measurements for fat thickness and longissimus muscle area should enhance national cattle evaluation programs. PMID:9814892

  14. 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.

  15. 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.…

  16. Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study.

    PubMed

    Panova-Noeva, Marina; Schulz, Andreas; Hermanns, M Iris; Grossmann, Vera; Pefani, Evgenia; Spronk, Henri M H; Laubert-Reh, Dagmar; Binder, Harald; Beutel, Manfred; Pfeiffer, Norbert; Blankenberg, Stefan; Zeller, Tanja; Münzel, Thomas; Lackner, Karl J; Ten Cate, Hugo; Wild, Philipp S

    2016-01-14

    Mean platelet volume (MPV), a measure of platelet size, is a potential biological marker of platelet function. To date, a comprehensive analysis including known genetic and nongenetic factors that determine MPV is still lacking. MPV has been evaluated in 15 010 individuals from the population-based Gutenberg Health Study. Genetic information was available for 4175 individuals. Our results showed that age (β, 0.0346; 95% confidence interval [CI], 0.0255 to 0.0436), cardiovascular risk factors (CVRFs) such as smoking (β, 0.178; 95% CI, 0.128 to 0.229), hypertension (β, 0.05; 95% CI, 0.00289 to .0981), and high glucose level (β, 0.00179; 95% CI, 0.0006 to 0.00299) were linked with higher MPV in males only. Intake of oral contraceptives (β, 0.150; 95% CI, 0.0649 to 0.236) and menstruation (β, 0.123; 95% CI, 0.0231 to 0.224) were strongly associated with higher MPV in females. Seven single nucleotide polymorphisms (SNPs) for females and 4 SNPs for males were associated with higher MPV. The full model, including age, CVRFs, laboratory parameters, medications, and genetic variation, explained 20.4% of the MPV variance in females and 18.6% in males. The curves of cumulative mortality, stratified for sex, showed worse survival for males only with MPV > 9.96 fL vs MPV ≤ 9.96 fL (P < .0001). This study provides evidence for heterogeneity in the profile of determinants for MPV between sexes. The observed interactions between genetic variability, CVRFs, and MPV and its association with the development of cardiovascular disease or thrombotic risk need to be further investigated. PMID:26518434

  17. Human male sex determination and sexual differentiation: pathways, molecular interactions and genetic disorders.

    PubMed

    Kucinskas, Laimutis; Just, Walter

    2005-01-01

    The complex mechanisms are responsible for male sex determination and differentiation. The steps of formation of the testes are dependent on a series of Y-linked, X-linked and autosomal genes actions and interactions. After formation of testes the gonads secrete hormones, which are essential for the formation of the male genitalia. Hormones are transcription regulators, which function by specific receptors. Ambiguous genitalia are result of disruption of genetic interaction. This review describes the mechanisms, which lead to differentiation of male sex and ways by which the determination and differentiation may be interrupted by naturally occurring mutations, causing different syndromes and diseases. PMID:16160410

  18. Genetic Determinants of Cardio-Metabolic Risk: A Proposed Model for Phenotype Association and Interaction

    PubMed Central

    Blackett, Piers R; Sanghera, Dharambir K

    2012-01-01

    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 non-alcoholic fatty liver (NAFLD) 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, pharmacological 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. PMID:23351585

  19. 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. PMID:25179736

  20. 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. PMID:27187497

  1. 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

  2. The Wilhelmine E. Key 1994 invitational Lecture. Plant genetic diversity and the struggle to measure selection.

    PubMed

    Clegg, M T

    1997-01-01

    The fundamental research program of population genetics has been to seek a quantitative assessment of the role of the various forces of evolution in shaping patterns of genetic variation. This goal has been pursued on both empirical and theoretical fronts. The introduction of biochemical and molecular techniques into population genetics more than 25 years ago revealed vast stores of genetic variation within populations. This level of genetic diversity is difficult to reconcile with balancing selection, and as a consequence, recent thinking has emphasized the role of mutation and genetic random drift as the primary determinants of genetic diversity. The resulting neutral theory of molecular evolution has dominated population genetic thought for more than 20 years. Nonadaptive theories have also emphasized the role of deleterious mutations in driving evolutionary change. New insights into the relative importance of selection and genetic random drift can now be obtained from samples of DNA sequences of genes drawn from within species. The elaboration of coalescence theory, together with the accumulation of data on gene genealogies, permits an integration over relatively long periods of evolutionary time. The ability to integrate over long periods of evolutionary time permits the detection of small selection intensities and it reveals some information about the mode of selection. When the genealogy is consistent with a neutral process, the effective population size can be estimated, as can the age of the coalescent, thus providing new empirical approaches to the estimation of these important parameters. Applications of these approaches in plant population genetics are still in their infancy, but they have already provided new insights into effective population sizes and they are beginning to illustrate how selection for domestication has affected plant genomes. PMID:9048442

  3. 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

  4. 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

  5. Clinical and Genetic Determinants of Cardiomyopathy Risk among Hematopoietic Cell Transplantation Survivors.

    PubMed

    Leger, Kasey J; Cushing-Haugen, Kara; Hansen, John A; Fan, Wenhong; Leisenring, Wendy M; Martin, Paul J; Zhao, Lue Ping; Chow, Eric J

    2016-06-01

    Cardiomyopathy has been recognized as a complication after hematopoietic cell transplantation (HCT). Using a nested case-cohort design, we examined the relationships between demographic, therapeutic, and selected cardiovascular disease risk factors among ≥1-year HCT survivors who developed cardiomyopathy before (n = 43) or after (n = 89) 1 year from HCT as compared to a randomly selected subcohort of survivors without cardiomyopathy (n = 444). Genomic data were available for 79 cases and 267 noncases. Clinical and genetic covariates were examined for association with the risk of early or late cardiomyopathy. Clinical risk factors associated with both early- and late-onset cardiomyopathy included anthracycline exposure ≥250 mg/m(2) and pre-existing hypertension. Among late-onset cardiomyopathy cases, the development of diabetes and ischemic heart disease further increased risk. We replicated several previously reported genetic associations among early-onset cardiomyopathy cases, including rs1786814 in CELF4, rs2232228 in HAS3, and rs17863783 in UGT1A6. None of these markers were associated with risk of late-onset cardiomyopathy. A combination of demographic, treatment, and clinical covariates predicted early-onset cardiomyopathy with reasonable accuracy (area under the curve [AUC], .76; 95% confidence interval [CI], .68 to .83), but prediction of late cardiomyopathy was poor (AUC, .59; 95% CI .53 to .67). The addition of genetic polymorphisms with marginal associations (odds ratios ≥1.3) did not enhance prediction for either early- or late-onset cardiomyopathy. Conventional cardiovascular risk factors influence the risk of both early- and late-onset cardiomyopathy in HCT survivors. Although certain genetic markers may influence the risk of early-onset disease, further work is required to validate previously reported findings and to determine how genetic information should be incorporated into clinically useful risk prediction models. PMID:26968791

  6. 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

  7. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  9. Determining the Causes and Consequences of Nicotine Dependence: Emerging Genetic Research Methods

    PubMed Central

    Ware, Jennifer J.; Munafò, Marcus R.

    2016-01-01

    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. PMID:25135777

  10. Using Neural Networks to Determine Sugeno Measures by Statistics.

    PubMed

    Zhenyuan, Wang; Jia, Wang

    1997-01-01

    To replace the traditional weighted average method, Choquet integrals or Sugeno integrals with respect to fuzzy measures are used to obtain a synthetic evaluation of a given object (or its quality, function, etc. respectively) with multi-attribute. Generally, it is not easy to determine fuzzy measures in real problems due to the subjectivity of human thinking. It is even much more difficult than determining weights in the weighted average method, because of the nonadditivity of fuzzy measures. This paper uses a neural network algorithm to optimize the inverse problem of synthetic evaluation, and thus to determine Sugeno measures by the Choquet integral and statistics of given data. Since the Choquet integral is a generalization of the weighted average method, this technology has a broad applicability in areas of multivariate analysis, decision making, pattern recognition, image and speech processing and expert systems. Copyright 1996 Elsevier Science Ltd. PMID:12662896

  11. 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.

  12. Genetic independence of mouse measures of some aspects of novelty seeking.

    PubMed

    Kliethermes, Christopher L; Crabbe, John C

    2006-03-28

    High novelty seeking is a complex personality attribute correlated with risk for substance abuse. There are many putative mouse models of some aspects of novelty seeking, but little is known of genetic similarities among these models. To assess the genetic coherence of "novelty seeking," we compared the performance of 14 inbred strains of mice in five tests: activity in a novel environment, novel environment preference, head dipping on a hole-board, object preference, and a two-trial version of the spontaneous alternation task. Differences among strains were observed for all tasks, but performance in any given task was generally not predictive of performance in any other. To evaluate similarities among these tasks further, we selectively bred lines of mice for high or low head dipping on the hole-board. Similar to results from the inbred strain experiments, head dipping was not correlated with performance in the other measures but was genetically correlated with differences in locomotor activity. Using two approaches to estimating common genetic influences across tasks, we have found little evidence that these partial models of novelty seeking reflect the influence of common genes or measure a single, unified construct called novelty seeking. Based on the substantial influence of genetic factors, ease of implementation, and relative independence from general locomotion, head dipping on a hole-board is a good task to use in the domain of novelty seeking, but multiple tasks, including others not tested here, would be needed to capture the full genetic range of the behavioral domain. PMID:16551746

  13. 76 FR 63278 - Bayer CropScience LP; Determination of Nonregulated Status for Cotton Genetically Engineered for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-12

    ...We are advising the public of our determination that a genetically engineered cotton developed by Bayer CropScience LP, designated as TwinLinkTM cotton (events T304-40 and GHB119), which has been genetically engineered to be tolerant to the herbicide glufosinate and resistant to several lepidopteran pests, is no longer considered a regulated article under our regulations governing......

  14. 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. PMID:25254350

  15. Utility of genetic determinants of lipids and cardiovascular events in assessing risk.

    PubMed

    Holmes, Michael V; Harrison, Seamus; Talmud, Philippa J; Hingorani, Aroon D; Humphries, Steve E

    2011-04-01

    The prevention of coronary heart disease (CHD) is a major public-health goal, but disease architecture is such that a larger proportion of clinical events occur among the average majority than among the high-risk minority--the prevention paradox. Genetic findings over the past few years have resulted in the reopening of the old debate on whether an individualized or a population-based approach to prevention is preferable. Genetic testing is an attractive tool for CHD risk prediction because it is a low-cost, high-fidelity technology with multiplex capability. Moreover, by contrast with nongenetic markers, genotype is invariant and determined from conception, which eliminates biological variability and makes prediction from early life possible. Mindful of the prevention paradox, this Review examines the potential applications and challenges of using genetic information for predicting CHD, focusing on lipid risk factors and drawing on experience in the evaluation of nongenetic risk factors as screening tests for CHD. Many of the issues we discuss hold true for any late-onset common disease with modifiable risk factors and proven preventative strategies. PMID:21321562

  16. 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

  17. Genetic sex determination, gender identification and pseudohermaphroditism in the knobbed whelk, Busycon carica (Mollusca: Melongenidae).

    PubMed Central

    Avise, John C.; Power, Alan J.; Walker, DeEtte

    2004-01-01

    We report perhaps the first genic-level molecular documentation of a mammalian-like 'X-linked' mode of sex determination in molluscs. From family inheritance data and observed associations between sex-phenotyped adults and genotypes in Busycon carica, we deduce that a polymorphic microsatellite locus (bc2.2) is diploid and usually heterozygous in females, hemizygous in males, and that its alleles are transmitted from mothers to sons and daughters but from fathers to daughters only. We also employ bc2.2 to estimate near-conception sex ratio in whelk embryos, where gender is indeterminable by visual inspection. Statistical corrections are suggested at both family and population levels to accommodate the presence of homozygous bc2.2 females that could otherwise be genetically mistaken for hemizygous males. Knobbed whelks were thought to be sequential hermaphrodites, but our evidence for genetic dioecy supports an earlier hypothesis that whelks are pseudohermaphroditic (falsely appear to switch functional sex when environmental conditions induce changes in sexual phenotype). These findings highlight the distinction between gender in a genetic versus phenotypic sense. PMID:15156923

  18. The role of nutrition and genetics as key determinants of the positive height trend.

    PubMed

    Grasgruber, P; Cacek, J; Kalina, T; Sebera, M

    2014-12-01

    The aim of this study was to identify the most important variables determining current differences in physical stature in Europe and some of its overseas offshoots such as Australia, New Zealand and USA. We collected data on the height of young men from 45 countries and compared them with long-term averages of food consumption from the FAOSTAT database, various development indicators compiled by the World Bank and the CIA World Factbook, and frequencies of several genetic markers. Our analysis demonstrates that the most important factor explaining current differences in stature among nations of European origin is the level of nutrition, especially the ratio between the intake of high-quality proteins from milk products, pork meat and fish, and low-quality proteins from wheat. Possible genetic factors such as the distribution of Y haplogroup I-M170, combined frequencies of Y haplogroups I-M170 and R1b-U106, or the phenotypic distribution of lactose tolerance emerge as comparably important, but the available data are more limited. Moderately significant positive correlations were also found with GDP per capita, health expenditure and partly with the level of urbanization that influences male stature in Western Europe. In contrast, male height correlated inversely with children's mortality and social inequality (Gini index). These results could inspire social and nutritional guidelines that would lead to the optimization of physical growth in children and maximization of the genetic potential, both at the individual and national level. PMID:25190282

  19. Multilevel Selection 2: Estimating the Genetic Parameters Determining Inheritance and Response to Selection

    PubMed Central

    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. PMID:17110493

  20. MEASURES OF EXPOSURE IMPACT GENETIC ASSOCIATION STUDIES: AN EXAMPLE IN VITAMIN K LEVELS AND VKORC1

    PubMed Central

    CRAWFORD, DANA C.; BROWN-GENTRY, KRISTIN; RIEDER, MARK J.

    2014-01-01

    Studies assessing the impact of gene-environment interactions on common human diseases and traits have been relatively few for many reasons. One often acknowledged reason is that it is difficult to accurately measure the environment or exposure. Indeed, most large-scale epidemiologic studies use questionnaires to assess and measure past and current exposure levels. While questionnaires may be cost-effective, the data may or may not accurately represent the exposure compared with more direct measurements (e.g., self-reported current smoking status versus direct measurement for cotinine levels). Much like phenotyping, the choice in how an exposure is measured may impact downstream tests of genetic association and gene-environment interaction studies. As a case study, we performed tests of association between five common VKORC1 SNPs and two different measurements of vitamin K levels, dietary (n=5,725) and serum (n=348), in the Third National Health and Nutrition Examination Studies (NHANES III). We did not replicate previously reported associations between VKORC1 and vitamin K levels using either measure. Furthermore, the suggestive associations and estimated genetic effect sizes identified in this study differed depending on the vitamin K measurement. This case study of VKORC1 and vitamin K levels serves as a cautionary example of the downstream consequences that the type of exposure measurement choices will have on genetic association and possibly gene-environment studies. PMID:25592578

  1. Population differentiation determined from putative neutral and divergent adaptive genetic markers in Eulachon (Thaleichthys pacificus, Osmeridae), an anadromous Pacific smelt.

    PubMed

    Candy, John R; Campbell, Nathan R; Grinnell, Matthew H; Beacham, Terry D; Larson, Wesley A; Narum, Shawn R

    2015-11-01

    Twelve eulachon (Thaleichthys pacificus, Osmeridae) populations ranging from Cook Inlet, Alaska and along the west coast of North America to the Columbia River were examined by restriction-site-associated DNA (RAD) sequencing to elucidate patterns of neutral and adaptive variation in this high geneflow species. A total of 4104 single-nucleotide polymorphisms (SNPs) were discovered across the genome, with 193 putatively adaptive SNPs as determined by F(ST) outlier tests. Estimates of population structure in eulachon with the putatively adaptive SNPs were similar, but provided greater resolution of stocks compared with a putatively neutral panel of 3911 SNPs or previous estimates with 14 microsatellites. A cline of increasing measures of genetic diversity from south to north was found in the adaptive panel, but not in the neutral markers (SNPs or microsatellites). This may indicate divergent selective pressures in differing freshwater and marine environments between regional eulachon populations and that these adaptive diversity patterns not seen with neutral markers could be a consideration when determining genetic boundaries for conservation purposes. Estimates of effective population size (N(e)) were similar with the neutral SNP panel and microsatellites and may be utilized to monitor population status for eulachon where census sizes are difficult to obtain. Greater differentiation with the panel of putatively adaptive SNPs provided higher individual assignment accuracy compared to the neutral panel or microsatellites for stock identification purposes. This study presents the first SNPs that have been developed for eulachon, and analyses with these markers highlighted the importance of integrating genome-wide neutral and adaptive genetic variation for the applications of conservation and management. PMID:25737187

  2. Nature and Nurture: Genetic Contributions to Measures of the Family Environment.

    ERIC Educational Resources Information Center

    Plomin, Robert; And Others

    1994-01-01

    This study of 707 sibling pairs, 10- to 18-years-old, examined parent-child and sibling interactions to determine the effects of genetics on family environment. The sample included identical and fraternal twins and full siblings in nondivorced families, as well as full, half, and unrelated siblings in divorced families. Found significant genetic…

  3. 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. PMID:19248726

  4. T cell genetic background determines default T helper phenotype development in vitro

    PubMed Central

    1995-01-01

    A host's ability to resist certain pathogens such as Leishmania major can depend upon the phenotype of T helper (Th) subset that develops. Different murine genetic backgrounds are known to significantly alter the direction of Th subset development, although the cellular basis of this influence is poorly understood. To examine the basis of this effect we used an in vitro alpha/beta-T cell receptor (TCR) transgenic system for analysis of Th phenotype development. To control for TCR usage, we derived the DO11.10 alpha/beta-TCR transgene in several genetic backgrounds. Our findings suggest that the effects of genetic background on Th phenotype development reside within the T cell, and not the antigen-presenting cell compartment. Transgenic T cells from both the B10.D2 and BALB/c backgrounds showed development toward either the Th1 or Th2 phenotype under the strong directing influence of interleukin (IL) 12 and IL4, respectively. However, when T cells were activated in vitro under neutral conditions in which exogenous cytokines were not added, B10.D2-derived T cells acquired a significantly stronger Th1 phenotype than T cells from the BALB/c background, correspondent with in vivo Th responses to Leishmania in these strains. Importantly, these cytokine differences resulted in distinct functional properties, because B10.D2- but not BALB/c-derived T cells could induce macrophage production of nitric oxide, an important antimicrobial factor. Thus, the genetically determined default Th phenotype development observed in vitro may correspond to in vivo Th subset responses for pathogens such as Leishmania which do not initiate strong Th phenotype-directing signals. PMID:7836924

  5. An investigation of folate-related genetic factors in the determination of birthweight.

    PubMed

    Relton, Caroline L; Pearce, Mark S; Burn, John; Parker, Louise

    2005-09-01

    Recent evidence suggests that maternal folate status in early gestation is a significant determinant of infant birthweight. Folate metabolism is known to be controlled by genetic factors, with a number of polymorphic variations in folate metabolising genes identified, several of which have well-documented functional effects. The current study investigated whether folate-related polymorphic variation, in association with low maternal folate status, influences birthweight. Red blood cell (RBC) folate analysis and genotyping of five polymorphisms in folate-related genes [Methylenetetrahydrofolate reductase (MTHFR) 677C>T; MTHFR 1298A>C; cystathionine-beta-synthase (CbetaS) 844ins68bp; serine hydroxymethyltransferase (SHMT) 1420C>T; reduced folate carrier-1 (RFC-1) 80G>A] were undertaken in mothers and infants from 998 pregnancies. These data were analysed in relation to infant birthweight, adjusted for gender and gestational age (z-score). Low maternal RBC folate status was associated with reduced infant birthweight. None of the genetic variants studied showed an independent association with infant birthweight. However, two genetic variants were shown to have a significant effect on birthweight when found in association with low maternal RBC folate status. When individuals with variant genotypes and mothers with folate in the lowest quintile were compared with wild-type individuals and mothers with folate in the highest quintile, the following differences in mean birthweight (z-score) were observed; maternal MTHFR 677C>T (-0.56 [95% CI -1.00, -0.12]P=0.01) and infant CbetaS 844ins68bp (-0.71 [95% CI -1.97, -0.07]P=0.03). The findings of this study suggest that folate-related genetic polymorphisms do not directly influence infant birthweight. However, when placed on a background of deficient maternal nutritional status, they may detrimentally affect fetal growth. PMID:16115288

  6. 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. PMID:25751422

  7. 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.

  8. An orbit determination from debris impacts on measurement satellites

    NASA Astrophysics Data System (ADS)

    Fujita, Koki; Tasaki, Mitsuhiko; Furumoto, Masahiro; Hanada, Toshiya

    2016-01-01

    This work proposes a method to determine orbital plane of a micron-sized space debris cloud utilizing their impacts on measurement satellites. Given that debris impacts occur on a line of intersection between debris and satellites orbital planes, a couple of debris orbital parameters, right ascension of the ascending node, inclination, and nodal regression rate can be determined by impact times and locations measured from more than two satellites in different earth orbits. This paper proves that unique solution for the debris orbital parameters is obtained from the measurement data, and derives a computational scheme to estimate them. The effectiveness of the proposed scheme is finally demonstrated by a simulation test, in which measurement data are obtained from a numerical simulation considering realistic debris' and satellites' orbits.

  9. 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. PMID:25662420

  10. 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.

  11. The Greenhouse Effect - Determination From Accurate Surface Longwave Radiation Measurements

    NASA Astrophysics Data System (ADS)

    Philipona, R.

    Longwave radiation measurements have been drastically improved in recent years. Uncertainty levels down to s2 Wm-2 are realistic and achieved during long-term ´ longwave irradiance measurements. Longwave downward irradiance measurements together with temperature and humidity measurements at the station are used to sepa- rate clear-sky from cloudy-sky situations. Longwave net radiation separated between clear-sky and all-sky situations allows to determine the longwave cloud radiative forc- ing at the station. For clear-sky situations radiative transfer models demonstrate a lin- ear relation between longwave downward radiation and the greenhouse radiative flux. Clear-sky longwave radiation, temperature and humidity for different atmospheres and different altitudes were modeled with the MODTRAN radiative transfer code and compared to longwave radiation, temperature and humidity measured at 4 radiation stations of the Alpine Surface Radiation Budget (ASRB) network at similar altitude and with corresponding atmospheres. At the 11 ASRB stations the clear-sky green- house effect was determined by using clear-sky longwave downward measurements and MODTRAN model calculations. The all-sky greenhouse effect was determined by adding the longwave cloud radiative forcing to the clear-sky greenhouse radiative flux. The altitude dependence of annual and seasonal mean values of the greenhouse effect will be shown for the altitude range of 400 to 3600 meter a.s.l. in the Alps.

  12. Environmental and genetic determinants of vitamin D insufficiency in 12-month-old infants.

    PubMed

    Suaini, Noor H A; Koplin, Jennifer J; Ellis, Justine A; Peters, Rachel L; Ponsonby, Anne-Louise; Dharmage, Shyamali C; Matheson, Melanie C; Wake, Melissa; Panjari, Mary; Tan, Hern-Tze Tina; Martin, Pamela E; Pezic, Angela; Lowe, Adrian J; Martino, David; Gurrin, Lyle C; Vuillermin, Peter J; Tang, Mimi L K; Allen, Katrina J

    2014-10-01

    We aimed to investigate the relationship between genetic and environmental exposure and vitamin D status at age one, stratified by ethnicity. This study included 563 12-month-old infants in the HealthNuts population-based study. DNA from participants' blood samples was genotyped using Sequenom MassARRAY MALDI-TOF system on 28 single nucleotide polymorphisms (SNPs) in six genes. Using logistic regression, we examined associations between environmental exposure and SNPs in vitamin D pathway and filaggrin genes and vitamin D insufficiency (VDI). VDI, defined as serum 25-hydroxyvitamin D3(25(OH)D3) level ≤50nmol/L, was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Infants were stratified by ethnicity determined by parent's country of birth. Infants formula fed at 12 months were associated with reduced odds of VDI compared to infants with no current formula use at 12 months. This association differed by ethnicity (Pinteraction=0.01). The odds ratio (OR) of VDI was 0.29 for Caucasian infants (95% CI, 0.18-0.47) and 0.04 for Asian infants (95% CI, 0.006-0.23). Maternal vitamin D supplementation during pregnancy and/or breastfeeding were associated with increased odds of infants being VDI (OR, 2.39; 95% CI, 1.11-5.18 and OR, 2.5; 95% CI, 1.20-5.24 respectively). Presence of a minor allele for any GC SNP (rs17467825, rs1155563, rs2282679, rs3755967, rs4588, rs7041) was associated with increased odds of VDI. Caucasian infants homozygous (AA) for rs4588 had an OR of 2.49 of being associated with VDI (95% CI, 1.19-5.18). In a country without routine infant vitamin D supplementation or food chain fortification, formula use is strongly associated with a reduced risk of VDI regardless of ethnicity. There was borderline significance for an association between filaggrin mutations and VDI. However, polymorphisms in vitamin D pathway related genes were associated with increased likelihood of being VDI in infancy. PMID:25174667

  13. 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

  14. Target cell frequency is a genetically determined risk factor in radiation leukaemogenesis.

    PubMed

    Jawad, M; Giotopoulos, G; Cole, C; Plumb, M

    2007-09-01

    Whole body exposure to ionizing radiation increases the risk of radiation-induced acute myeloid leukaemia (r-AML). r-AML is the result of the accumulation of mutations in a single haemopoietic stem cell, so risk is therefore a function of the number of mutations required to transform the stem cell and the mutation rate. There is a genetic component to the risk of AML within the general population, and low penetrance variant alleles encoding DNA repair enzymes have been genetically implicated in therapy-related AML susceptibility. However, what is largely ignored is that target cell number, which defines the number of genomes at risk from DNA damaging agents, is also part of the equation that defines risk. We will review the evidence from genetic studies of inbred mouse models that target cell frequency is a risk factor in radiation leukaemogenesis. Inbred mouse strains that differ in their susceptibility to radiation-induced r-AML and thymic lymphoma (r-TL), spontaneous TL and pristane-induced plasmacytoma (PCT) have been exploited to identify susceptibility loci. The target cell in AML is the haemopoietic stem cell, whereas TLs and PCT arise from more mature lymphoid progenitor cells. Inbred mice also differ significantly in all aspects of haemopoiesis, and these differences have been used to identify quantitative trait loci (QTL) that determine the frequency of specific haemopoietic stem, progenitor or mature blood cells. The co-localization of QTL that determine risk and target cell frequency in all three haemopoietic malignancies is strong evidence that target cell frequency is a risk factor in radiation leukaemogenesis. PMID:17704327

  15. 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.

  16. Sex determination in crayfish: are intersex Cherax quadricarinatus (Decapoda, Parastacidae) genetically females?

    PubMed

    Parnes, S; Khalaila, I; Hulata, G; Sagi, A

    2003-10-01

    In the Australian red-claw crayfish Cherax quadricarinatus (von Martens) (Decapoda, Parastacidae), a gonochoristic species, seven different combinations of intersex individuals (with both male and female genital openings) have been described. However, to date, the genetic basis for this phenomenon has not been investigated. This study was designed to test a simple chromosome-based sex-determination model for C. quadricarinatus that assumes the male to be the homogametic (ZZ) sex. According to our model, intersex individuals that are functionally males are genetically females (WZ). Individual crosses were performed between intersex and female crayfish, with control crosses being performed between normal males and females. The control crosses yielded, in most cases, the expected 1:1 sex ratio in the F1 progeny. Crosses between intersex individuals and females yielded a 1:3 (male:female) sex ratio in most crosses. According to our hypothesis, one-third of the females produced in a cross of a female with an intersex animal should be WW females. The hypothesis was tested by crossing normal males with F1 females, which were progeny of intersex fathers. These crosses yielded almost 100% females, a finding that conforms to the above-suggested sex determination model for C. quadricarinatus and the female WZ genotype of intersex individuals. PMID:14768895

  17. 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.

  18. Genetic Variation Determines PPARγ Function and Anti-diabetic Drug Response In Vivo.

    PubMed

    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

    2015-07-01

    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 anti-diabetic 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

  19. 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.

  20. A genetic determinant of the striatal dopamine response to alcohol in men

    PubMed Central

    Ramchandani, Vijay A.; Umhau, John; Pavon, Francisco J.; Ruiz-Velasco, Victor; Margas, Wojciech; Sun, Hui; Damadzic, Ruslan; Eskay, Robert; Schoor, Michael; Thorsell, Annika; Schwandt, Melanie L.; Sommer, Wolfgang H.; George, David T.; Parsons, Loren H.; Herscovitch, Peter; Hommer, Daniel; Heilig, Markus

    2010-01-01

    Excessive alcohol use, a major cause of morbidity and mortality, is less well understood than other addictive disorders. Dopamine release in ventral striatum is a common element of drug reward, but alcohol has an unusually complex pharmacology, and humans vary greatly in their alcohol responses. This variation is related to genetic susceptibility for alcoholism, which contributes more than half of alcoholism risk. Here, we report that a functional OPRM1 A118G polymorphism is a major determinant of striatal dopamine responses to alcohol. Social drinkers recruited based on OPRM1 genotype were challenged in separate sessions with alcohol and placebo under pharmacokinetically controlled conditions, and examined for striatal dopamine release using positron emission tomography and [11C]-raclopride displacement. A striatal dopamine response to alcohol was restricted to carriers of the minor 118G allele. To directly establish the causal role of OPRM1 A118G variation, we generated two humanized mouse lines, carrying the respective human sequence variant. Brain microdialysis showed a four-fold greater peak dopamine response to an alcohol challenge in h/mOPRM1-118GG than in h/mOPRM1-118AA mice. OPRM1 A118G variation is a genetic determinant of dopamine responses to alcohol, a mechanism by which it likely modulates alcohol reward. PMID:20479755

  1. 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. PMID:25299242

  2. MICROCOSM FOR MEASURING SURVIVAL AND CONJUGATION OF GENETICALLY ENGINEERED BACTERIA IN RHIZOSPHERE ENVIRONMENTS

    EPA Science Inventory

    A microcosm is described to evaluate and measure bacterial conjugation in the rhizosphere of barley and radish with strains of Pseudomonas cepacia. he purpose was to describe a standard method useful for evaluating the propensity of genetically engineered microorganisms (GEMs) to...

  3. Information entropy as a measure of genetic diversity and evolvability in colonization.

    PubMed

    Day, Troy

    2015-05-01

    In recent years, several studies have examined the relationship between genetic diversity and establishment success in colonizing species. Many of these studies have shown that genetic diversity enhances establishment success. There are several hypotheses that might explain this pattern, and here I focus on the possibility that greater genetic diversity results in greater evolvability during colonization. Evaluating the importance of this mechanism first requires that we quantify evolvability. Currently, most measures of evolvability have been developed for quantitative traits whereas many studies of colonization success deal with discrete molecular markers or phenotypes. The purpose of this study is to derive a suitable measure of evolvability for such discrete data. I show that under certain assumptions, Shannon's information entropy of the allelic distribution provides a natural measure of evolvability. This helps to alleviate previous concerns about the interpretation of information entropy for genetic data. I also suggest that information entropy provides a natural generalization to previous measures of evolvability for quantitative traits when the trait distributions are not necessarily multivariate normal. PMID:25604806

  4. Genetic markers that influence feed efficiency phenotypes also affect cattle temperament as measured by flight speed

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. Genetic relationships among temperament score, weight, and backfat measurements in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic parameters for temperament score were estimated from generations five and six of a randomly selected, composite population composed of Duroc, Large White, and two sources of Landrace (n = 1,704). Temperament score (TS), weight (WT), and three backfat measurements (BF1, BF2, and BF3) were rec...

  6. 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

  7. Determination of AFBb using jet charge measurements in Z decays

    NASA Astrophysics Data System (ADS)

    ALEPH Collaboration; Barate, R.; Buskulic, D.; Decamp, D.; Ghez, P.; Goy, C.; Lees, J.-P.; Lucotte, A.; Merle, E.; Minard, M.-N.; Nief, J.-Y.; Pietrzyk, B.; Alemany, R.; Boix, G.; Casado, M. P.; Chmeissani, M.; Crespo, J. M.; Delfino, M.; Fernandez, E.; Fernandez-Bosman, M.; Garrido, Ll.; Graugès, E.; Juste, A.; Martinez, M.; Merino, G.; Miquel, R.; Mir, Ll. M.; Park, I. C.; Pascual, A.; Perlas, J. A.; Riu, I.; Sanchez, F.; Colaleo, A.; Creanza, D.; de Palma, M.; Gelao, G.; Iaselli, G.; Maggi, G.; Maggi, M.; Nuzzo, S.; Ranieri, A.; Raso, G.; Ruggieri, F.; Selvaggi, G.; Silvestris, L.; Tempesta, P.; Tricomi, A.; Zito, G.; Huang, X.; Lin, J.; Ouyang, Q.; Wang, T.; Xie, Y.; Xu, R.; Xue, S.; Zhang, J.; Zhang, L.; Zhao, W.; Abbaneo, D.; Becker, U.; Bright-Thomas, P.; Casper, D.; Cattaneo, M.; Ciulli, V.; Dissertori, G.; Drevermann, H.; Forty, R. W.; Frank, M.; Hagelberg, R.; Hansen, J. B.; Harvey, J.; Janot, P.; Jost, B.; Lehraus, I.; Mato, P.; Minten, A.; Moneta, L.; Pacheco, A.; Pusztaszeri, J.-F.; Ranjard, F.; Rolandi, L.; Rousseau, D.; Schlatter, D.; Schmitt, M.; Schneider, O.; Tejessy, W.; Teubert, F.; Tomalin, I. R.; Wachsmuth, H.; Ajaltouni, Z.; Badaud, F.; Chazelle, G.; Deschamps, O.; Falvard, A.; Ferdi, C.; Gay, P.; Guicheney, C.; Henrard, P.; Jousset, J.; Michel, B.; Monteil, S.; Montret, J.-C.; Pallin, D.; Perret, P.; Podlyski, F.; Proriol, J.; Rosnet, P.; Hansen, J. D.; Hansen, J. R.; Hansen, P. H.; Nilsson, B. S.; Rensch, B.; Wäänänen, A.; Daskalakis, G.; Kyriakis, A.; Markou, C.; Simopoulou, E.; Siotis, I.; Vayaki, A.; Blondel, A.; Bonneaud, G.; Brient, J.-C.; Bourdon, P.; Rougé, A.; Rumpf, M.; Valassi, A.; Verderi, M.; Videau, H.; Focardi, E.; Parrini, G.; Zachariadou, K.; Corden, M.; Georgiopoulos, C.; Jaffe, D. E.; Antonelli, A.; Bencivenni, G.; Bologna, G.; Bossi, F.; Campana, P.; Capon, G.; Cerutti, F.; Chiarella, V.; Felici, G.; Laurelli, P.; Mannocchi, G.; Murtas, F.; Murtas, G. P.; Passalacqua, L.; Pepe-Altarelli, M.; Curtis, L.; Halley, A. W.; Lynch, J. G.; Negus, P.; O'Shea, V.; Raine, C.; Scarr, J. M.; Smith, K.; Teixeira-Dias, P.; Thompson, A. S.; Thomson, E.; Buchmüller, O.; Dhamotharan, S.; Geweniger, C.; Graefe, G.; Hanke, P.; Hansper, G.; Hepp, V.; Kluge, E. E.; Putzer, A.; Sommer, J.; Tittel, K.; Werner, S.; Wunsch, M.; Beuselinck, R.; Binnie, D. M.; Cameron, W.; Dornan, P. J.; Girone, M.; Goodsir, S.; Martin, E. B.; Marinelli, N.; Moutoussi, A.; Nash, J.; Sedgbeer, J. K.; Spagnolo, P.; Williams, M. D.; Ghete, V. M.; Girtler, P.; Kneringer, E.; Kuhn, D.; Rudolph, G.; Betteridge, A. P.; Bowdery, C. K.; Buck, P. G.; Colrain, P.; Crawford, G.; Finch, A. J.; Foster, F.; Hughes, G.; Jones, R. W. L.; Robertson, N. A.; Williams, M. I.; Giehl, I.; Greene, A. M.; Hoffmann, C.; Jakobs, K.; Kleinknecht, K.; Quast, G.; Renk, B.; Rohne, E.; Sander, H.-G.; van Gemmeren, P.; Zeitnitz, C.; Aubert, J. J.; Benchouk, C.; Bonissent, A.; Bujosa, G.; Carr, J.; Coyle, P.; Etienne, F.; Leroy, O.; Motsch, F.; Payre, P.; Talby, M.; Sadouki, A.; Thulasidas, M.; Trabelsi, K.; Aleppo, M.; Antonelli, M.; Ragusa, F.; Berlich, R.; Blum, W.; Büscher, V.; Dietl, H.; Ganis, G.; Kroha, H.; Lütjens, G.; Mannert, C.; Männer, W.; Moser, H.-G.; Schael, S.; Settles, R.; Seywerd, H.; Stenzel, H.; Wiedenmann, W.; Wolf, G.; Boucrot, J.; Callot, O.; Chen, S.; Cordier, A.; Davier, M.; Duflot, L.; Grivaz, J.-F.; Heusse, Ph.; Höcker, A.; Jacholkowska, A.; Kim, D. W.; Le Diberder, F.; Lefrançois, J.; Lutz, A.-M.; Schune, M.-H.; Tournefier, E.; Veillet, J.-J.; Videau, I.; Zerwas, D.; Azzurri, P.; Bagliesi, G.; Batignani, G.; Bettarini, S.; Boccali, T.; Bozzi, C.; Calderini, G.; Carpinelli, M.; Ciocci, M. A.; dell'Orso, R.; Fantechi, R.; Ferrante, I.; Foà, L.; Forti, F.; Giassi, A.; Giorgi, M. A.; Gregorio, A.; Ligabue, F.; Lusiani, A.; Marrocchesi, P. S.; Messineo, A.; Palla, F.; Rizzo, G.; Sanguinetti, G.; Sciabà, A.; Sguazzoni, G.; Tenchini, R.; Tonelli, G.; Vannini, C.; Venturi, A.; Verdini, P. G.; Blair, G. A.; Bryant, L. M.; Chambers, J. T.; Green, M. G.; Medcalf, T.; Perrodo, P.; Strong, J. A.; von Wimmersperg-Toeller, J. H.; Botterill, D. R.; Clifft, R. W.; Edgecock, T. R.; Haywood, S.; Norton, P. R.; Thompson, J. C.; Wright, A. E.; Bloch-Devaux, B.; Colas, P.; Emery, S.; Kozanecki, W.; Lançon, E.; Lemaire, M.-C.; Locci, E.; Perez, P.; Rander, J.; Renardy, J.-F.; Roussarie, A.; Schuller, J.-P.; Schwindling, J.; Trabelsi, A.; Vallage, B.; Black, S. N.; Dann, J. H.; Johnson, R. P.; Kim, H. Y.; Konstantinidis, N.; Litke, A. M.; McNeil, M. A.; Taylor, G.; Booth, C. N.; Brew, C. A. J.; Cartwright, S.; Combley, F.; Kelly, M. S.; Lehto, M.; Reeve, J.; Thompson, L. F.; Affholderbach, K.; Böhrer, A.; Brandt, S.; Cowan, G.; Grupen, C.; Saraiva, P.; Smolik, L.; Stephan, F.; Apollonio, M.; Bosisio, L.; della Marina, R.; Giannini, G.; Gobbo, B.; Musolino, G.; Rothberg, J.; Wasserbaech, S.; Armstrong, S. R.; Charles, E.; Elmer, P.; Ferguson, D. P. S.; Gao, Y.; González, S.; Greening, T. C.; Hayes, O. J.; Hu, H.; Jin, S.; McNamara, P. A., III; Nachtman, J. M.; Nielsen, J.; Orejudos, W.; Pan, Y. B.; Saadi, Y.; Scott, I. J.; Walsh, J.; Wu, Sau Lan; Wu, X.; Zobernig, G.

    1998-04-01

    An improved measurement of the forward-backward asymmetry in decays is presented, based on a sample of 4.1 million hadronic Z decays collected by ALEPH between 1991 and 1995. Data are analysed as a function of polar angle of the event axis and b purity. The event tagging efficiency and mean b-jet hemisphere charge are measured directly from data. From the measured forward-backward jet charge asymmetry, the b quark asymmetry at is determined to be: . In the context of the Standard Model this corresponds to a value of the effective weak mixing angle of .

  8. 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.

  9. Determining aerodynamic conductance of spar chambers from energy balance measurements

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aerodynamic conductance (gA) of SPAR chambers was determined from measurements of energy balance and canopy temperature over a peanut canopy. gA was calculated from the slope of sensible heat flux (H) versus canopy-to-air temperature difference. H and the canopy-to-air temperature were varied by...

  10. Some Recent Secondary Production Measurements for Neutrino Flux Determination

    NASA Astrophysics Data System (ADS)

    Mills, Geoffrey B.

    2011-12-01

    Recent measurements of meson production in proton-nucleus interactions have made possible reliable neutrino flux determinations at modern neutrino experiments. This article discusses preliminary results from the HARP, MIP, and E910 are discussed along with some of their implications for the MINOS, K2K, and MiniBooNE neutrino experiments.

  11. 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. PMID:14995815

  12. 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

  13. 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. PMID:15563302

  14. 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

  15. Measurement network design including traveltime determinations to minimize model prediction uncertainty

    NASA Astrophysics Data System (ADS)

    Janssen, Gijs M. C. M.; Valstar, Johan R.; van der Zee, Sjoerd E. A. T. M.

    2008-02-01

    Traveltime determinations have found increasing application in the characterization of groundwater systems. No algorithms are available, however, to optimally design sampling strategies including this information type. We propose a first-order methodology to include groundwater age or tracer arrival time determinations in measurement network design and apply the methodology in an illustrative example in which the network design is directed at contaminant breakthrough uncertainty minimization. We calculate linearized covariances between potential measurements and the goal variables of which we want to reduce the uncertainty: the groundwater age at the control plane and the breakthrough locations of the contaminant. We assume the traveltime to be lognormally distributed and therefore logtransform the age determinations in compliance with the adopted Bayesian framework. Accordingly, we derive expressions for the linearized covariances between the transformed age determinations and the parameters and states. In our synthetic numerical example, the derived expressions are shown to provide good first-order predictions of the variance of the natural logarithm of groundwater age if the variance of the natural logarithm of the conductivity is less than 3.0. The calculated covariances can be used to predict the posterior breakthrough variance belonging to a candidate network before samples are taken. A Genetic Algorithm is used to efficiently search, among all candidate networks, for a near-optimal one. We show that, in our numerical example, an age estimation network outperforms (in terms of breakthrough uncertainty reduction) equally sized head measurement networks and conductivity measurement networks even if the age estimations are highly uncertain.

  16. 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. PMID:16599932

  17. 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

  18. Genetic determinants of risk factors for cardiovascular disease in a population from rural Brazil.

    PubMed

    Velásquez-Meléndez, Gustavo; Parra, Flavia C; Gazzinelli, Andrea; Williams-Blangero, Sarah; Correa-Oliveira, Rodrigo

    2007-04-01

    We investigate the heritability of and pleiotropic relationships among triglycerides and cholesterol lipoproteins that have long been considered traditional risk factors for cardiovascular disease. Quantitative lipid and lipoprotein phenotypes were determined for a cross-sectional sample of a community in Jequitinhonha valley in northern Minas Gerais state, Brazil. The sample consisted primarily of subsistence farmers. Two hundred sixty-nine individuals (128 males and 141 females), ages 18-88 years, were sampled. Eighty-eight percent (n = 252) of the individuals belonged to a single pedigree, which was highly informative for genetic analysis. Data on anthropometrics, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides were available for each study participant. Extended pedigrees were constructed using the pedigree-based data management software PedSys. Univariate and bivariate variance-components analyses, adjusted by sex and age, were performed using the SOLAR software package. Heritability estimates of lipids and lipoproteins ranged from 29% to 45% (p < 0.008). The highest heritability estimated was for HDL-C (h2 = 44.8%, p < 0.0001), and this was the only trait that exhibited a significant household effect (c2 = 25%). Strong positive genetic correlations were found between triglycerides and very low density lipoprotein (VLDL) (rhog = 0.998) and between total cholesterol and LDL-C (rhog = 0.948). Significant genetic correlations were also found between triglycerides and LDL-C, between total cholesterol and VLDL, and between total cholesterol and LDL-C and VLDL, and finally between LDL and VLDL. There was a significant negative environmental correlation between triglycerides and HDL-C (rhoe = -0.406). PMID:18027813

  19. 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]. PMID:27098911

  20. Genetic and environmental determinants of insect herbivore community structure in a Betula pendula population

    PubMed Central

    Silfver, Tarja

    2014-01-01

    A number of recent studies have shown that intraspecific genetic variation of plants may have a profound effect on the herbivorous communities which depend on them. However less is known about the relative importance of intraspecific variation compared to other ecological factors, for example environmental variation or the effects of herbivore damage. We randomly selected 22 Betula pendula genotypes from a local population (< 0.9 ha), cloned them and planted cloned seedlings on two study sites separated at a regional scale (distance between sites about 30 km) to examine an insect community of 23-27 species on these genotypes. B. pendula genotypes did not differ in their species richness, but the total mean abundance and the structure of the insect herbivore community was significantly affected by the genotype, which could account for up to 27% of the total variation in community structure. B. pendula genotype accounted for two to four times more variation in the arthropod community structure than did environmental (block) variation on a local scale, while on a regional scale, genotypic and environmental (site) variation accounted for 4-14% of the arthropod community structure. The genetic effects were modified by environmental variation on both a local and regional scale over one study year, and locally, the largest part of the variation (38%) could be explained by the genotype × environment (block) interactions. Suppression of insect herbivores during one growing season led to changed arthropod community structure in the following growing season, but this effect was minimal and could explain only 4% of the total variation in insect community structure. Our results suggest that both genetic and environmental factors are important determinants of the community structure of herbivorous insects. Together these mechanisms appear to maintain the high diversity of insects in B. pendula forest ecosystems. PMID:24715977

  1. Genetic and environmental determinants of insect herbivore community structure in a Betula pendula population.

    PubMed

    Silfver, Tarja; Rousi, Matti; Oksanen, Elina; Roininen, Heikki

    2014-01-01

    A number of recent studies have shown that intraspecific genetic variation of plants may have a profound effect on the herbivorous communities which depend on them. However less is known about the relative importance of intraspecific variation compared to other ecological factors, for example environmental variation or the effects of herbivore damage. We randomly selected 22 Betula pendula genotypes from a local population (< 0.9 ha), cloned them and planted cloned seedlings on two study sites separated at a regional scale (distance between sites about 30 km) to examine an insect community of 23-27 species on these genotypes. B. pendula genotypes did not differ in their species richness, but the total mean abundance and the structure of the insect herbivore community was significantly affected by the genotype, which could account for up to 27% of the total variation in community structure. B. pendula genotype accounted for two to four times more variation in the arthropod community structure than did environmental (block) variation on a local scale, while on a regional scale, genotypic and environmental (site) variation accounted for 4-14% of the arthropod community structure. The genetic effects were modified by environmental variation on both a local and regional scale over one study year, and locally, the largest part of the variation (38%) could be explained by the genotype × environment (block) interactions. Suppression of insect herbivores during one growing season led to changed arthropod community structure in the following growing season, but this effect was minimal and could explain only 4% of the total variation in insect community structure. Our results suggest that both genetic and environmental factors are important determinants of the community structure of herbivorous insects. Together these mechanisms appear to maintain the high diversity of insects in B. pendula forest ecosystems. PMID:24715977

  2. Response to enemies in the invasive plant Lythrum salicaria is genetically determined

    PubMed Central

    Joshi, Srijana; Tielbörger, Katja

    2012-01-01

    Background and Aims 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. Methods 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. Key Results 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. Conclusions 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. PMID:22492331

  3. 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.

  4. 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. PMID:23819135

  5. The physicochemical properties of polyurethane membranes determined by swelling measurements

    NASA Astrophysics Data System (ADS)

    Ciobanu, Gabriela; Carja, Gabriela; Apostolescu, Gabriela; Apostolescu, Nicolae

    2009-01-01

    In this work, we have dispersed SAPO-5 zeolite particles in polyurethane matrix for preparation of porous mixed matrix membranes. The goal of work is the determination of the cohesive energy density for unfilled- and zeolite - filled polyurethane membranes. Experimental determination of cohesive energy density values for the prepared membranes is obtained by measuring the swelling coefficients in water and several alcohols (methanol, ethanol, propanol and butanol). The solubility parameters of the membranes are also calculated. For the unfilled membranes the corresponded values of cohesive energy density and solubility parameter increase in comparison to those of the filled membranes. All the tested membranes show a tendency to swell with ethanol.

  6. 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

    2016-09-01

    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. PMID:27496179

  7. Strong genetic influences on measures of behavioral-regulation among inbred rat strains

    PubMed Central

    Richards, Jerry B.; Lloyd, David R.; Kuehlewind, Brandon; Militello, Leah; Paredez, Marita; Solberg -Woods, Leah; Palmer, Abraham A.

    2013-01-01

    A fundamental challenge for any complex nervous system is to regulate behavior in response to environmental challenges. Three measures of behavioral regulation were tested in a panel of 8 inbred rat strains. These measures were; 1) sensation seeking as assessed by locomotor response to novelty and the sensory reinforcing effects of light onset, 2) attention and impulsivity, as measured by a choice reaction time task, and 3) impulsivity as measured by a delay discounting task. Deficient behavioral regulation has been linked to a number of psychopathologies, including ADHD, Schizophrenia, Autism, drug abuse and eating disorders. Eight inbred rat strains (August Copenhagen Irish, Brown Norway, Buffalo, Fischer 344, Wistar Kyoto, Spontaneous Hypertensive Rat, Lewis, Dahl Salt Sensitive) were tested. With n=9 for each strain, we observed robust strain differences for all tasks; heritability was estimated between 0.43 and 0.66. Performance of the 8 inbred rat strains on the choice reaction time task was compared to the performance of out bred Sprague Dawley (n=28) and Heterogeneous strain rats (n=48). The results indicate a strong genetic influence on complex tasks related to behavioral regulation and indicate that some of measures tap common genetically-driven processes. Furthermore, our results establish the potential for future studies aimed at identifying specific alleles that influence variability for these traits. Identification of such alleles could contribute to our understanding of the molecular genetic basis of behavioral regulation, which is of fundamental importance and likely contributes to multiple psychiatric disorders. PMID:23710681

  8. [GENETICALLY DETERMINED DISEASES ASSOCIATED WITH PATHOLOGICAL BRAIN IRON ACCUMULATION AND NEURODEGENERATION].

    PubMed

    Ács, Péter; Molnár, Mária Judit; Klivényi, Péter; Kálmán, Bernadette

    2016-03-30

    The rare, genetically determined group of diseases characterized by pathological accumulation of iron in the central nervous system and progressive, typically movement disorder's symptoms are called NBIA (neurodegeneration with brain iron accumulation). By the rapid development of molecular genetics, it has become apparent that different mutations in numerous genes can lead to pathological cerebral iron accumulation. Simultaneously, it has also been recognized that the age of onset, the symptoms and the prognosis of NBIA disorders are much more diverse than it was previously perceived. To our knowledge, a review article on the most recent clinical data of NBIA has not been published in Hungarian. In the first part of this publication, we survey the general clinical characteristics and the diagnostic algorithm of NBIA diseases and address some considerations for differential diagnostics. In the second part of this review, the particular NBIA disorders are presented in details. The purpose of this article is to provide a clinical overview that may be useful for neurologists, pediatricians and any other medical practitioners interested in this field. PMID:27468605

  9. 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. PMID:23448621

  10. 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.

  11. Determining Maximum Glycolytic Capacity Using Extracellular Flux Measurements

    PubMed Central

    Mookerjee, Shona A.; Nicholls, David G.; Brand, Martin D.

    2016-01-01

    Measurements of glycolytic rate and maximum glycolytic capacity using extracellular flux analysis can give crucial information about cell status and phenotype during normal operation, development of pathology, differentiation, and malignant transformation. They are also of great use when assessing the effects of chemical or drug treatments. Here, we experimentally define maximum glycolytic capacity, demonstrate how it differs from glycolytic rate, and provide a protocol for determining the basal glycolytic rate and maximum glycolytic capacity in cells using extracellular flux measurements. The results illustrate the power of extracellular flux analysis to describe the energetics of adherent cells in culture in a fully quantitative way. PMID:27031845

  12. Determination of time delay between ventricles contraction using impedance measurements

    NASA Astrophysics Data System (ADS)

    Lewandowska, M.; Poliński, A.; Wtorek, J.

    2013-04-01

    The paper presents a novel approach to assessment of ventricular dyssynchrony basing on multichannel electrical impedance measurements. Using a proper placement of electrodes, the sensitivity approach allows estimating time difference between chambers contraction from over determined nonlinear system of equations. The theoretical considerations which include Finite Element Method simulations were verified using measurements on healthy 28 year's old woman. The nonlinear least squares method was applied to obtain a time difference between heart chambers contraction. The obtained value was in a good agreement with theoretical values found in literature.

  13. ‘Stalled' periocular necrotising fasciitis: early effective treatment or host genetic determinants?

    PubMed Central

    Mutamba, A; Verity, D H; Rose, G E

    2013-01-01

    Background Necrotising fasciitis (NF) is a devastating disease with considerable mortality and morbidity, and early aggressive surgical debridement of devitalised necrotic tissues has traditionally been advocated. Methods We describe three patients who were referred from other units several weeks after developing periocular necrotising fasciitis; in all the three, the disease had been managed medically without surgical debridement, with apparent ‘stalling' of the inflammatory process despite persistent necrotic periocular tissue. Results Following ‘elective debridement' of the devitalised tissues and reconstruction with local flaps, all achieved a satisfactory aesthetic result. Discussion The role of host genetic determinants, polarised cytokine responses, and early, effective medical treatment in patients with atypical ‘disease phenotypes' in NF are discussed. PMID:23412558

  14. 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

    2010-01-01

    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. PMID:20198581

  15. A Genome Scan Conducted in a Multigenerational Pedigree with Convergent Strabismus Supports a Complex Genetic Determinism

    PubMed Central

    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. PMID:24376720

  16. Hybrid algorithm for NARX network parameters' determination using differential evolution and genetic algorithm

    NASA Astrophysics Data System (ADS)

    Salami, M. J. E.; Tijani, I. B.; Abdullateef, A. I.; Aibinu, M. A.

    2013-12-01

    A hybrid optimization algorithm using Differential Evolution (DE) and Genetic Algorithm (GA) is proposed in this study to address the problem of network parameters determination associated with the Nonlinear Autoregressive with eXogenous inputs Network (NARX-network). The proposed algorithm involves a two level optimization scheme to search for both optimal network architecture and weights. The DE at the upper level is formulated as combinatorial optimization to search for the network architecture while the associated network weights that minimize the prediction error is provided by the GA at the lower level. The performance of the algorithm is evaluated on identification of a laboratory rotary motion system. The system identification results show the effectiveness of the proposed algorithm for nonparametric model development.

  17. 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.

  18. Genetic associations with performance on a behavioral measure of distress intolerance.

    PubMed

    Amstadter, Ananda B; Daughters, Stacey B; Macpherson, Laura; Reynolds, Elizabeth K; Danielson, Carla Kmett; Wang, Frances; Potenza, Marc N; Gelernter, Joel; Lejuez, C W

    2012-01-01

    Both theory and empirical evidence support possible associations between two candidate genetic polymorphisms (SLC6A4 5-HTTLPR l/s and COMT Val(158)Met--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 Val(158)Met 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. A technique for determining thermal parameters using measured temperatures

    SciTech Connect

    Dincer, I.; Dost, S.

    1995-12-31

    This paper presents a simple but accurate technique for determining thermal parameters during direct cooling of solid objects, in terms of the cooling coefficient, lag factor, thermal diffusivity, and heat transfer coefficient. Solid objects are assumed to be cooled in a fluid medium. In the modeling the objects are approximated to infinite slabs, infinite cylinders or spherical bodies. A one-dimensional unsteady-state heat transfer analysis is carried out under three different conditions: Bi < 0.01, 0.1 < Bi < 100, and Bi > 100. A technique is then developed for determining the thermal parameters during cooling of such objects. The developed technique is illustrated by examples using actual temperature measurements taken from the studies presented previously. Results show that the technique presented here is capable of determining the thermal parameters during such a cooling process accurately.

  20. 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.

  1. 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.

  2. Applications of accurate isentropic exponent determination for fuel gas measurement

    SciTech Connect

    Pack, D.J.; Edwards, T.J.; Fawcett, D.

    1996-07-01

    This paper discusses the determination and application of the isentropic exponent to the various thermodynamic processes found in a high-pressure natural gas transmission system. Increasing demands for more precise measurement of natural gas, coupled with the need for greater efficiency and accountability of transportation and processing operations, had led to the research and development of gas thermodynamic properties including isentropic exponent. The isentropic exponent has many applications, some of which include: the determination of the expansion factor {epsilon}, for calculation of flow using an orifice or venturi-type meter; the volumetric efficiency in a reciprocating compressor; the determination of the compression head for a centrifugal compressor; the engine power required for the given conditions for a gas compressor; the calculation of discharge temperatures for compressors; and the direct measurement of gas density. As can be appreciated, the application of an incorrect value for the isentropic exponent represents an error in the parameter determined. For large volume gas flows, this can translate into a significant cost penalty.

  3. Genetic association between parameters of inmate immunity and measures of mastitis in periparturient Holstein cattle.

    PubMed

    Kelm, S C; Detilleux, J C; Freeman, A E; Kehrli, M E; Dietz, A B; Fox, L K; Butler, J E; Kasckovics, I; Kelley, D H

    1997-08-01

    Relationships between genetic measures of mastitis (somatic cell score, score for clinical mastitis, and scores for IMI with major or minor pathogens) and immunological parameters (physiological and molecular markers) were examined for periparturient Holstein cows. Physiological markers included 11 in vitro immunological assays. Molecular markers included the second exon of the DRB3 locus of the bovine major histocompatibility complex, the IgG2 isotype genotype, and the CD18 genotype (the locus responsible for bovine leukocyte adhesion deficiency). A gene substitution model was used to estimate the additive genetic effects of alleles of the three molecular markers on estimated breeding value (EBV) for mastitis measures. Pearson correlation coefficients between EBV for immunological assays and EBV for mastitis measures were computed. Molecular markers explained up to 40% of the variation in EBV for measures of mastitis. The presence of allele DRB3.2*16 was associated with higher EBV for SCS. Allele DRB3.2*8 was associated with increased EBV for clinical mastitis, as was the IgG2b allele and the normal CD18 allele. Alleles DRB3.2*11, *23, IgG2a, and the recessive allele for bovine leukocyte adhesion deficiency were associated with decreased clinical mastitis. A positive genetic association was found between allele DRB3.2*24 and EBV for IMI by major pathogens and between DRB3.2*3 and IMI by minor pathogens. Several correlations between EBV for immunological assays and EBV for mastitis measures were significantly different from 0. Cows with low EBV for SCS tended to have neutrophils that had greater functional ability at maximal immunosuppression, low serum IgG1, and high numbers of circulating mononuclear cells. Immunological parameters, including physiological and molecular markers, are useful aids to understand the genetics of resistance to mastitis. PMID:9276818

  4. Protocols to determine pollination requirements and optimal pollinators for plant genetic resource regeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Guidelines have been established for the maintenance of plant genetic resource collections, including seed regeneration. When carefully conducted, regeneration is a key tool in germplasm conservation, helping reduce the negative effects of genetic erosion. However, inadequate knowledge of basic p...

  5. Transverse micro-erosion meter measurements; determining minimum sample size

    NASA Astrophysics Data System (ADS)

    Trenhaile, Alan S.; Lakhan, V. Chris

    2011-11-01

    Two transverse micro-erosion meter (TMEM) stations were installed in each of four rock slabs, a slate/shale, basalt, phyllite/schist, and sandstone. One station was sprayed each day with fresh water and the other with a synthetic sea water solution (salt water). To record changes in surface elevation (usually downwearing but with some swelling), 100 measurements (the pilot survey), the maximum for the TMEM used in this study, were made at each station in February 2010, and then at two-monthly intervals until February 2011. The data were normalized using Box-Cox transformations and analyzed to determine the minimum number of measurements needed to obtain station means that fall within a range of confidence limits of the population means, and the means of the pilot survey. The effect on the confidence limits of reducing an already small number of measurements (say 15 or less) is much greater than that of reducing a much larger number of measurements (say more than 50) by the same amount. There was a tendency for the number of measurements, for the same confidence limits, to increase with the rate of downwearing, although it was also dependent on whether the surface was treated with fresh or salt water. About 10 measurements often provided fairly reasonable estimates of rates of surface change but with fairly high percentage confidence intervals in slowly eroding rocks; however, many more measurements were generally needed to derive means within 10% of the population means. The results were tabulated and graphed to provide an indication of the approximate number of measurements required for given confidence limits, and the confidence limits that might be attained for a given number of measurements.

  6. 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. PMID:22484169

  7. 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

  8. 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

  9. 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.

  10. 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. PMID:26440324

  11. Genetic analysis of ultrasound and carcass measurement traits in a regional hanwoo steer population.

    PubMed

    Hwang, Jeong Mi; Cheong, Jae Kyoung; Kim, Sam Su; Jung, Bong Hwan; Koh, Myung Jae; Kim, Hyeong Cheol; Choy, Yun Ho

    2014-04-01

    Ultrasound measurements of backfat thickness (UBF), longissimus muscle area (ULMA) and marbling score (UMS) and carcass measurements of carcass weight (CW), backfat thickness (BF), longissimus muscle area (LMA), and marbling score (MS) on 7,044 Hanwoo steers were analyzed to estimate genetic parameters. Data from Hanwoo steers that were raised, finished in Hoengseong-gun, Gangwon-do (province) and shipped to slaughter houses during the period from October 2010 to April 2013 were evaluated. Ultrasound measurements were taken at approximately three months before slaughter by an experienced operator using a B-mode real-time ultrasound device (HS-2000, FHK Co. Ltd., Tokyo, Japan) with a 3.5 MHz linear probe. Ultrasound scanning was on the left side between 13th rib and the first lumbar vertebrae. All slaughtering processes and carcass evaluations were performed in accordance with the guidelines of beef grading system of Korea. To estimate genetic parameters, multiple trait animal models were applied. Fixed effects included in the models were: the effects of farm, contemporary group effects (year-season at the time of ultrasound scanning in the models for UBF, ULMA, and UMS, and year-season at slaughter in the models for CW, BF, LMA, and MS), the effects of ultrasound technicians as class variables and the effects of the age in days at ultrasound scanning or at slaughtering as linear covariates, respectively for ultrasound and carcass measures. Heritability estimates obtained from our analyses were 0.37 for UBF, 0.13 for ULMA, 0.27 for UMS, 0.44 for CW, 0.33 for BF, 0.36 for LMA and 0.54 MS, respectively. Genetic correlations were strongly positive between corresponding traits of ultrasound and carcass measures. Genetic correlation coefficient between UBF and BF estimate was 0.938, between ULMA and LMA was 0.767 and between UMS and MS was 0.925. These results suggest that ultrasound measurement traits are genetically similar to carcass measurement traits. PMID:25049974

  12. Genetic Analysis of Ultrasound and Carcass Measurement Traits in a Regional Hanwoo Steer Population

    PubMed Central

    Hwang, Jeong Mi; Cheong, Jae Kyoung; Kim, Sam Su; Jung, Bong Hwan; Koh, Myung Jae; Kim, Hyeong Cheol; Choy, Yun Ho

    2014-01-01

    Ultrasound measurements of backfat thickness (UBF), longissimus muscle area (ULMA) and marbling score (UMS) and carcass measurements of carcass weight (CW), backfat thickness (BF), longissimus muscle area (LMA), and marbling score (MS) on 7,044 Hanwoo steers were analyzed to estimate genetic parameters. Data from Hanwoo steers that were raised, finished in Hoengseong-gun, Gangwon-do (province) and shipped to slaughter houses during the period from October 2010 to April 2013 were evaluated. Ultrasound measurements were taken at approximately three months before slaughter by an experienced operator using a B-mode real-time ultrasound device (HS-2000, FHK Co. Ltd., Tokyo, Japan) with a 3.5 MHz linear probe. Ultrasound scanning was on the left side between 13th rib and the first lumbar vertebrae. All slaughtering processes and carcass evaluations were performed in accordance with the guidelines of beef grading system of Korea. To estimate genetic parameters, multiple trait animal models were applied. Fixed effects included in the models were: the effects of farm, contemporary group effects (year-season at the time of ultrasound scanning in the models for UBF, ULMA, and UMS, and year-season at slaughter in the models for CW, BF, LMA, and MS), the effects of ultrasound technicians as class variables and the effects of the age in days at ultrasound scanning or at slaughtering as linear covariates, respectively for ultrasound and carcass measures. Heritability estimates obtained from our analyses were 0.37 for UBF, 0.13 for ULMA, 0.27 for UMS, 0.44 for CW, 0.33 for BF, 0.36 for LMA and 0.54 MS, respectively. Genetic correlations were strongly positive between corresponding traits of ultrasound and carcass measures. Genetic correlation coefficient between UBF and BF estimate was 0.938, between ULMA and LMA was 0.767 and between UMS and MS was 0.925. These results suggest that ultrasound measurement traits are genetically similar to carcass measurement traits. PMID:25049974

  13. 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].

  14. 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. PMID:26991370

  15. 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.

  16. Genetic parameter estimates of yearling live animal ultrasonic measurements in Brangus cattle.

    PubMed

    Stelzleni, A M; Perkins, T L; Brown, A H; Pohlman, F W; Johnson, Z B; Sandelin, B A

    2002-12-01

    The objective of this study was to estimate genetic parameters for real-time ultrasound measurements of longissimus muscle area (LMA), 12th rib backfat thickness (FT), percent intramuscular fat (IMF), and yearling weight (YW) for 1,299 yearling Brangus bulls and heifers. A single ultrasound technician performed all measurements. The number of observations was 1,298, 1,298, 1,215, and 1,170 for LMA, FT, IMF, and YW, respectively. Genetic parameters were estimated for each trait using single- and multiple-trait derivative-free restricted maximal likelihood. Fixed effects were contemporary group (defined as same sex, same age within six months, and same environment), and days of age as a covariate. Correlations were estimated from two-trait models. Heritabilities for LMA, FT, IMF, and YW were 0.31, 0.26, 0.16, and 0.53, respectively. Genetic correlations between LMA and FT, LMA and IMF, LMA and YW, FT and IMF, FT and YW, and IMF and YW were 0.09, 0.25, 0.44, 0.36, 0.42, and 0.31, respectively. Yearling live animal ultrasonic measurements can be used as a selection tool in breeding cattle for the improvement of carcass traits. PMID:12542155

  17. Genetic Mapping of the Antigenic Determinants of Two Polysaccharide K Antigens, K10 and K54, in Escherichia coli

    PubMed Central

    Ørskov, Ida; Nyman, Kate

    1974-01-01

    The genes controlling synthesis of the Escherichia coli acidic polysaccharide capsular antigens K10 and K54 were transferred by conjugation to E. coli strains of other serotypes. The genes concerned with these K antigen determinants showed genetic linkage with the serA locus. We propose to name the K antigen-controlling gene kpsA. The genetic determinants of the two K antigens could also be transferred to enteropathogenic serotypes, even though such strains have never been found in nature with special acidic polysaccharide K antigens. A noncapsulated derivative, K−, of the K10 strain can transfer the genetic determinant of the K antigen, demonstrating the probable existence of another chromosomal locus involved in the production of such acidic polysaccharide K antigens. PMID:4138850

  18. 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

  19. Automatic 3D image registration using voxel similarity measurements based on a genetic algorithm

    NASA Astrophysics Data System (ADS)

    Huang, Wei; Sullivan, John M., Jr.; Kulkarni, Praveen; Murugavel, Murali

    2006-03-01

    An automatic 3D non-rigid body registration system based upon the genetic algorithm (GA) process is presented. The system has been successfully applied to 2D and 3D situations using both rigid-body and affine transformations. Conventional optimization techniques and gradient search strategies generally require a good initial start location. The GA approach avoids the local minima/maxima traps of conventional optimization techniques. Based on the principles of Darwinian natural selection (survival of the fittest), the genetic algorithm has two basic steps: 1. Randomly generate an initial population. 2. Repeated application of the natural selection operation until a termination measure is satisfied. The natural selection process selects individuals based on their fitness to participate in the genetic operations; and it creates new individuals by inheritance from both parents, genetic recombination (crossover) and mutation. Once the termination criteria are satisfied, the optimum is selected from the population. The algorithm was applied on 2D and 3D magnetic resonance images (MRI). It does not require any preprocessing such as threshold, smoothing, segmentation, or definition of base points or edges. To evaluate the performance of the GA registration, the results were compared with results of the Automatic Image Registration technique (AIR) and manual registration which was used as the gold standard. Results showed that our GA implementation was a robust algorithm and gives very close results to the gold standard. A pre-cropping strategy was also discussed as an efficient preprocessing step to enhance the registration accuracy.

  20. Genome-wide genetic investigation of serological measures of common infections.

    PubMed

    Rubicz, Rohina; Yolken, Robert; Drigalenko, Eugene; Carless, Melanie A; Dyer, Thomas D; Kent, Jack; Curran, Joanne E; Johnson, Matthew P; Cole, Shelley A; Fowler, Sharon P; Arya, Rector; Puppala, Sobha; Almasy, Laura; Moses, Eric K; Kraig, Ellen; Duggirala, Ravindranath; Blangero, John; Leach, Charles T; Göring, Harald H H

    2015-11-01

    Populations and individuals differ in susceptibility to infections because of a number of factors, including host genetic variation. We previously demonstrated that differences in antibody titer, which reflect infection history, are significantly heritable. Here we attempt to identify the genetic factors influencing variation in these serological phenotypes. Blood samples from >1300 Mexican Americans were quantified for IgG antibody level against 12 common infections, selected on the basis of their reported role in cardiovascular disease risk: Chlamydia pneumoniae; Helicobacter pylori; Toxoplasma gondii; cytomegalovirus; herpes simplex I virus; herpes simplex II virus; human herpesvirus 6 (HHV6); human herpesvirus 8 (HHV8); varicella zoster virus; hepatitis A virus (HAV); influenza A virus; and influenza B virus. Pathogen-specific quantitative antibody levels were analyzed, as were three measures of pathogen burden. Genome-wide linkage and joint linkage and association analyses were performed using ~1 million SNPs. Significant linkage (lod scores >3.0) was obtained for HHV6 (on chromosome 7), HHV8 (on chromosome 6), and HAV (on chromosome 13). SNP rs4812712 on chromosome 20 was significantly associated with C. pneumoniae (P=5.3 × 10(-8)). However, no genome-wide significant loci were obtained for the other investigated antibodies. We conclude that it is possible to localize host genetic factors influencing some of these antibody traits, but that further larger-scale investigations will be required to elucidate the genetic mechanisms contributing to variation in antibody levels. PMID:25758998

  1. Whole genome sequencing provides insights into the genetic determinants of invasiveness in Salmonella Dublin.

    PubMed

    Mohammed, M; Cormican, M

    2016-08-01

    Salmonella enterica subsp. enterica serovar Dublin (S. Dublin) is one of the non-typhoidal Salmonella (NTS); however, a relatively high proportion of human infections are associated with invasive disease. We applied whole genome sequencing to representative invasive and non-invasive clinical isolates of S. Dublin to determine the genomic variations among them and to investigate the underlying genetic determinants associated with invasiveness in S. Dublin. Although no particular genomic variation was found to differentiate in invasive and non-invasive isolates four virulence factors were detected within the genome of all isolates including two different type VI secretion systems (T6SS) encoded on two Salmonella pathogenicity islands (SPI), including SPI-6 (T6SSSPI-6) and SPI-19 (T6SSSPI-19), an intact lambdoid prophage (Gifsy-2-like prophage) that contributes significantly to the virulence and pathogenesis of Salmonella serotypes in addition to a virulence plasmid. These four virulence factors may all contribute to the potential of S. Dublin to cause invasive disease in humans. PMID:26996313

  2. Genetic and metabolic determinants of nutritional phenotype in an insect-bacterial symbiosis.

    PubMed

    MacDonald, S J; Thomas, G H; Douglas, A E

    2011-05-01

    The pervasive influence of resident microorganisms on the phenotype of their hosts is exemplified by the intracellular bacterium Buchnera aphidicola, which provides its aphid partner with essential amino acids (EAAs). We investigated variation in the dietary requirement for EAAs among four pea aphid (Acyrthosiphon pisum) clones. Buchnera-derived nitrogen contributed to the synthesis of all EAAs for which aphid clones required a dietary supply, and to none of the EAAs for which all four clones had no dietary requirement, suggesting that low total dietary nitrogen may select for reduced synthesis of certain EAAs in some aphid clones. The sequenced Buchnera genomes showed that the EAA nutritional phenotype (i.e. the profile of dietary EAAs required by the aphid) cannot be attributed to sequence variation of Buchnera genes coding EAA biosynthetic enzymes. Metabolic modelling by flux balance analysis demonstrated that EAA output from Buchnera can be determined precisely by the flux of host metabolic precursors to Buchnera. Specifically, the four EAA nutritional phenotypes could be reproduced by metabolic models with unique profiles of host inputs, dominated by variation in supply of aspartate, homocysteine and glutamate. This suggests that the nutritional phenotype of the symbiosis is determined principally by host metabolism and transporter genes that regulate nutrient supply to Buchnera. Intraspecific variation in the nutritional phenotype of symbioses is expected to mediate partitioning of plant resources among aphid genotypes, potentially promoting the genetic subdivision of aphid populations. In this way, microbial symbioses may play an important role in the evolutionary diversification of phytophagous insects. PMID:21392141

  3. 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

  4. Genetic Determinants of Circulating Interleukin-1 Receptor Antagonist Levels and Their Association With Glycemic Traits

    PubMed Central

    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

    2014-01-01

    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. PMID:24969107

  5. 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. PMID:24969107

  6. 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

  7. 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.

  8. 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.

  9. 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.}

  10. Determination of equilibrium free energy from nonequilibrium work measurements

    PubMed Central

    Chen, L. Y.; Bastien, D. A.; Espejel, H. E.

    2010-01-01

    The fluctuation–dissipation theorem (FDT) of Brownian dynamics (BD) is applied to extract the equilibrium free-energy profile from the nonequilibrium, irreversible work measured in single-molecule pulling experiments. Two sets of in silico experiments are performed to explore the free-energy landscape of deca-alanine peptide as a function of its end-to-end distance and to determine the free-energy profile of water permeation through the channels of aquaglyceroporin GlpF. With a small number of pulling paths sampled, the BD-FDT is shown to produce accurate estimates of the free-energy profiles for both systems. PMID:20463999

  11. Determination of RGB Color Coordinates from Spectroscopic Reflectance Measurements

    NASA Astrophysics Data System (ADS)

    Rodriguez, Cesar; Nelson, Cayla; Abdallah, Lina; Zollner, Stefan

    2012-10-01

    A numerical value (RGB coordinate) for a certain color, based on a color model, can be determined from a spectroscopic reflectance measurement. To obtain this measurement, an ellipsometer was used with a wavelength ranging from 380 nm to 780 nm to cover the visible light spectrum. The peaks seen in the reflectance versus wavelength graph represent the color of the sample used. Our paper samples were round and coated with a metallic paint. The data was then analyzed using ASTM Standard E308-99 (adopted in 1999) for ``computing the colors of objects by using the CIE system.'' Once a color is in the CIE color model, it can be transformed into an RGB color model and then compared to the RGB color displayed in many consumer electronics.

  12. 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.

  13. Material Symmetries from Ultrasonic Velocity Measurements: A Genetic Algorithm Based Blind Inversion Method

    SciTech Connect

    Vardhan, J. Vishnu; Balasubramaniam, Krishnan; Krishnamurthy, C. V.

    2007-03-21

    The determination of material symmetries and principle plane orientations of anisotropic plates, whose planes of symmetries are not known apriori, were calculated using a Genetic Algorithm (GA) based blind inversion method. The ultrasonic phase velocity profiles were used as input data to the inversion. The assumption of a general anisotropy was imposed during the start of each blind inversion. The multi-parameter solution space of the Genetic Algorithm was exploited to identify the 'statistically significant' solution sets of elastic moduli in the geometric coordinate system of the plate, by thresholding the coefficients-of-variation (Cv). Using these ''statistically significant'' elastic moduli, the unknown material symmetry and the principle planes (angles between the geometrical coordinates and the material symmetry coordinates) were evaluated using the method proposed by Cowin and Mehrabadi. This procedure was verified using simulated ultrasonic velocity data sets on material with orthotropic symmetry. Experimental validation was also performed on unidirectional Graphite Epoxy [0]7s fiber reinforced composite plate.

  14. Determination of the elastic modulus of snow via acoustic measurements

    NASA Astrophysics Data System (ADS)

    Gerling, Bastian; van Herwijnen, Alec; Löwe, Henning

    2016-04-01

    The elastic modulus of snow is a key quantity from the viewpoint of avalanche research and forecasting, snow engineering or materials science in general. Since it is a fundamental property, many measurements have been reported in the literature. Due to differences in measurement methods, there is a lot of variation in the reported values. Especially values derived via computer tomography (CT) based numerical calculations using finite element methods are not corresponding to the results of other methods. The central issue is that CT based moduli are purely elastic whereas other methods may include viscoelastic deformation. In order to avoid this discrepancy we derived the elastic modulus of snow via wave propagation measurements and compared our results with CT based calculations. We measured the arrival times of acoustic pulses propagating through the snow samples to determine the P-wave velocity and in turn derive the elastic modulus along the direction of wave propagation. We performed a series of laboratory experiments to derive the P-wave modulus of snow in relation to density. The P-wave modulus ranged from 10 to 280 MPa for a snow density between 150 and 370 kg/m³. The moduli derived from the acoustic measurements correlated well with the CT-based values and both exhibited a power law trend over the entire density range. Encouraged by these results we used the acoustic method to investigate the temporal evolution of the elastic modulus. The rate of increase was very close to values mentioned in literature on the sintering rate of snow. Overall, our results are a first but important step towards a new measurement method to attain the elastic properties of snow.

  15. Environmental and Historical Determinants of Patterns of Genetic Differentiation in Wild Soybean (Glycine soja Sieb. et Zucc)

    PubMed Central

    He, Shui-Lian; Wang, Yun-Sheng; Li, De-Zhu; Yi, Ting-Shuang

    2016-01-01

    Wild soybean, the direct progenitor of cultivated soybean, inhabits a wide distribution range across the mainland of East Asia and the Japanese archipelago. A multidisciplinary approach combining analyses of population genetics based on 20 nuclear microsatellites and one plastid locus were applied to reveal the genetic variation of wild soybean, and the contributions of geographical, environmental factors and historic climatic change on its patterns of genetic differentiation. High genetic diversity and significant genetic differentiation were revealed in wild soybean. Wild soybean was inferred to be limited to southern and central China during the Last Glacial Maximum (LGM) and experienced large-scale post-LGM range expansion into northern East Asia. A substantial northward range shift has been predicted to occur by the 2080s. A stronger effect of isolation by environment (IBE) versus isolation by geographical distance (IBD) was found for genetic differentiation in wild soybean, which suggested that environmental factors were responsible for the adaptive eco-geographical differentiation. This study indicated that IBE and historical climatic change together shaped patterns of genetic variation and differentiation of wild soybean. Different conservation measures should be implemented on different populations according to their adaptive potential to future changes in climate and human-induced environmental changes. PMID:26952904

  16. Environmental and Historical Determinants of Patterns of Genetic Differentiation in Wild Soybean (Glycine soja Sieb. et Zucc).

    PubMed

    He, Shui-Lian; Wang, Yun-Sheng; Li, De-Zhu; Yi, Ting-Shuang

    2016-01-01

    Wild soybean, the direct progenitor of cultivated soybean, inhabits a wide distribution range across the mainland of East Asia and the Japanese archipelago. A multidisciplinary approach combining analyses of population genetics based on 20 nuclear microsatellites and one plastid locus were applied to reveal the genetic variation of wild soybean, and the contributions of geographical, environmental factors and historic climatic change on its patterns of genetic differentiation. High genetic diversity and significant genetic differentiation were revealed in wild soybean. Wild soybean was inferred to be limited to southern and central China during the Last Glacial Maximum (LGM) and experienced large-scale post-LGM range expansion into northern East Asia. A substantial northward range shift has been predicted to occur by the 2080s. A stronger effect of isolation by environment (IBE) versus isolation by geographical distance (IBD) was found for genetic differentiation in wild soybean, which suggested that environmental factors were responsible for the adaptive eco-geographical differentiation. This study indicated that IBE and historical climatic change together shaped patterns of genetic variation and differentiation of wild soybean. Different conservation measures should be implemented on different populations according to their adaptive potential to future changes in climate and human-induced environmental changes. PMID:26952904

  17. Evolving Attractive Faces Using Morphing Technology and a Genetic Algorithm: A New Approach to Determining Ideal Facial Aesthetics

    PubMed Central

    Wong, Brian J. F.; Karmi, Koohyar; Devcic, Zlatko; McLaren, Christine E.; Chen, Wen-Pin

    2013-01-01

    Objectives The objectives of this study were to: 1) determine if a genetic algorithm in combination with morphing software can be used to evolve more attractive faces; and 2) evaluate whether this approach can be used as a tool to define or identify the attributes of the ideal attractive face. Study Design Basic research study incorporating focus group evaluations. Methods Digital images were acquired of 250 female volunteers (18–25 y). Randomly selected images were used to produce a parent generation (P) of 30 synthetic faces using morphing software. Then, a focus group of 17 trained volunteers (18–25 y) scored each face on an attractiveness scale ranging from 1 (unattractive) to 10 (attractive). A genetic algorithm was used to select 30 new pairs from the parent generation, and these were morphed using software to produce a new first generation (F1) of faces. The F1 faces were scored by the focus group, and the process was repeated for a total of four iterations of the algorithm. The algorithm mimics natural selection by using the attractiveness score as the selection pressure; the more attractive faces are more likely to morph. All five generations (P-F4) were then scored by three focus groups: a) surgeons (n = 12), b) cosmetology students (n = 44), and c) undergraduate students (n = 44). Morphometric measurements were made of 33 specific features on each of the 150 synthetic faces, and correlated with attractiveness scores using univariate and multivariate analysis. Results The average facial attractiveness scores increased with each generation and were 3.66 (+0.60), 4.59 (±0.73), 5.50 (±0.62), 6.23 (±0.31), and 6.39 (±0.24) for P and F1–F4 generations, respectively. Histograms of attractiveness score distributions show a significant shift in the skew of each curve toward more attractive faces with each generation. Univariate analysis identified nasal width, eyebrow arch height, and lip thickness as being significantly correlated with attractiveness

  18. Determining hypocentral parameters for local earthquakes under ill conditions using genetic algorithm

    NASA Astrophysics Data System (ADS)

    Kim, Woohan; Hahm, In-Kyeong; Kim, Won-Young; Lee, Jung Mo

    2010-10-01

    We demonstrate that GA-MHYPO determines accurate hypocentral parameters for local earthquakes under ill conditions, such as limited number of stations (phase data), large azimuthal gap, and noisy data. The genetic algorithm (GA) in GA-MHYPO searches for the optimal 1-D velocity structure which provides the minimum traveltime differences between observed (true) and calculated P and S arrivals within prescribed ranges. GA-MHYPO is able to determine hypocentral parameters more accurately in many circumstances than conventional methods which rely on an a priori (and possibly incorrect) 1-D velocity model. In our synthetic tests, the accuracy of hypocentral parameters obtained by GA-MHYPO given ill conditions is improved by more than a factor of 20 for error-free data, and by a factor of five for data with errors, compared to that obtained by conventional methods such as HYPOINVERSE. In the case of error-free data, GA-MHYPO yields less than 0.1 km errors in focal depths and hypocenters without strong dependence on azimuthal coverage up to 45°. Errors are less than 1 km for data with errors of a 0.1-s standard deviation. To test the performance using real data, a well-recorded earthquake in the New Madrid seismic zone and earthquakes recorded under ill conditions in the High Himalaya are relocated by GA-MHYPO. The hypocentral parameters determined by GA-MHYPO under both good and ill conditions show similar computational results, which suggest that GA-MHYPO is robust and yields more reliable hypocentral parameters than standard methods under ill conditions for natural earthquakes.

  19. Relationships between four measures of genetic distance and breeding behavior in spring wheat.

    PubMed

    Benin, G; Matei, G; Costa de Oliveira, A; Silva, G O; Hagemann, T R; Lemes da Silva, C; Pagliosa, E S; Beche, E

    2012-01-01

    We estimated the genetic distances among 10 spring wheat genotypes based on pedigree data, morphological traits and AFLP markers, used individually and combined with morphological traits, to find the best predictors of general- and specific-combining abilities among parental genotypes. Ten wheat parents were crossed in a diallel form, disregarding reciprocal hybrids, totaling 45 combinations. The F₁ hybrids, F₂ populations and parents were evaluated in the field in 2007. The experimental plots consisted of 20 plants for F₁ hybrids and 40 plants for parental and F₂ populations. All methods (pedigree data, AFLP markers and morphological traits, used individually and combined) were found to be useful for the assessment of genetic diversity. The significant coefficient correlations ranged from low (0.45) to moderate (0.67) between the distance measures and hybrid performance. There was significant agreement between the distance measures based on AFLP markers vs morphological traits + AFLP markers (r = 0.47) and between pedigree data vs morphological traits + AFLP markers (r = 0.43). The pedigree distance was positively associated with traits 100-kernel weight and grain yield per plant in F₁ (correlations of 0.67 and 0.62, respectively) and F₂ (correlations of 0.62 and 0.59, respectively) generations. These correlation values indicate that the genetic distance, based on pedigree data, could replace diallel crosses for the selection of parents with higher combining ability and with moderate reliability. PMID:22782625

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Determination of measurement uncertainty for the determination of triazines in groundwater from validation data.

    PubMed

    Linsinger, T P; Führer, M; Kandler, W; Schuhmacher, R

    2001-02-01

    Laboratories are increasingly urged to submit full uncertainties of their analytical results rather than only standard deviations. The determination of measurement uncertainties in compliance with the Guide to the Expression of Uncertainty in Measurement (GUM) is demonstrated using the validation approach explicitly endorsed by the recent edition of the EURACHEM guide for the determination of measurement uncertainty. Measurement uncertainty was split into uncertainty of the sample mass, uncertainty of the concentration of the stock standard solution, uncertainty of the calibration and uncertainty connected to within- and between-series precision. Uncertainties of sample mass and of the concentration of the stock standard solution were 0.26 and 1.14% for all analytes, which is negligible compared with the contributions of precision and calibration. Uncertainty of calibration was estimated from the calibration graph. Relative uncertainty of calibration was found to be strongly concentration dependent and to be the main uncertainty contribution below 0.2 microgram L-1. Precision was split into within-series and between-series standard deviation, which dominate the combined standard uncertainty at higher concentrations. The results obtained from these calculations are compared with results for a certified reference material and with the performance in an interlaboratory comparison. It was found that all results agreed within their uncertainty with the target values, showing that the estimated uncertainties are realistic. PMID:11235105

  6. 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. PMID:14985995

  7. Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry

    PubMed Central

    Horowitz, Amir; Strauss-Albee, Dara M.; Leipold, Michael; Kubo, Jessica; Nemat-Gorgani, Neda; Dogan, Ozge C.; Dekker, Cornelia L.; Mackey, Sally; Maecker, Holden; Swan, Gary E.; Davis, Mark M.; Norman, Paul J.; Guethlein, Lisbeth A.; Desai, Manisha; Parham, Peter; Blish, Catherine A.

    2013-01-01

    Natural Killer (NK) cells play critical roles in immune defense and reproduction, yet remain the most poorly understood major lymphocyte population. Because their activation is controlled by a variety of combinatorially expressed activating and inhibitory receptors, NK cell diversity and function are closely linked. To provide an unprecedented understanding of NK cell repertoire diversity, we used mass cytometry to simultaneously analyze 35 parameters, including 28 NK cell receptors, on peripheral blood NK cells from five sets of monozygotic twins and twelve unrelated donors of defined HLA and killer cell immunoglobulin-like receptor (KIR) genotype. This analysis revealed a remarkable degree of NK cell diversity, with an estimated 6,000-30,000 phenotypic populations within an individual and >100,000 phenotypes in this population. Genetics largely determined inhibitory receptor expression, whereas activation receptor expression was heavily environmentally influenced. Therefore, NK cells may maintain self-tolerance through strictly regulated expression of inhibitory receptors, while using adaptable expression patterns of activating and costimulatory receptors to respond to pathogens and tumors. These findings further suggest the possibility that discrete NK cell subpopulations could be harnessed for immunotherapeutic strategies in the settings of infection, reproduction, and transplantation. PMID:24154599

  8. Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization.

    PubMed

    Randles, Michael J; Woolf, Adrian S; Huang, Jennifer L; Byron, Adam; Humphries, Jonathan D; Price, Karen L; Kolatsi-Joannou, Maria; Collinson, Sophie; Denny, Thomas; Knight, David; Mironov, Aleksandr; Starborg, Toby; Korstanje, Ron; Humphries, Martin J; Long, David A; Lennon, Rachel

    2015-12-01

    Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein-protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease. PMID:25896609

  9. Genetic Determinism and Evolutionary Reconstruction of a Host Jump in a Plant Virus.

    PubMed

    Vassilakos, Nikon; Simon, Vincent; Tzima, Aliki; Johansen, Elisabeth; Moury, Benoît

    2016-02-01

    In spite of their widespread occurrence, only few host jumps by plant viruses have been evidenced and the molecular bases of even fewer have been determined. A combination of three independent approaches, 1) experimental evolution followed by reverse genetics analysis, 2) positive selection analysis, and 3) locus-by-locus analysis of molecular variance (AMOVA) allowed reconstructing the Potato virus Y (PVY; genus Potyvirus, family Potyviridae) jump to pepper (Capsicum annuum), probably from other solanaceous plants. Synthetic chimeras between infectious cDNA clones of two PVY isolates with contrasted levels of adaptation to C. annuum showed that the P3 and, to a lower extent, the CI cistron played important roles in infectivity toward C. annuum. The three analytical approaches pinpointed a single nonsynonymous substitution in the P3 and P3N-PIPO cistrons that evolved several times independently and conferred adaptation to C. annuum. In addition to increasing our knowledge of host jumps in plant viruses, this study illustrates also the efficiency of locus-by-locus AMOVA and combined approaches to identify adaptive mutations in the genome of RNA viruses. PMID:26503941

  10. An image segmentation based on a genetic algorithm for determining soil coverage by crop residues.

    PubMed

    Ribeiro, Angela; Ranz, Juan; Burgos-Artizzu, Xavier P; Pajares, Gonzalo; del Arco, Maria J Sanchez; Navarrete, Luis

    2011-01-01

    Determination of the soil coverage by crop residues after ploughing is a fundamental element of Conservation Agriculture. This paper presents the application of genetic algorithms employed during the fine tuning of the segmentation process of a digital image with the aim of automatically quantifying the residue coverage. In other words, the objective is to achieve a segmentation that would permit the discrimination of the texture of the residue so that the output of the segmentation process is a binary image in which residue zones are isolated from the rest. The RGB images used come from a sample of images in which sections of terrain were photographed with a conventional camera positioned in zenith orientation atop a tripod. The images were taken outdoors under uncontrolled lighting conditions. Up to 92% similarity was achieved between the images obtained by the segmentation process proposed in this paper and the templates made by an elaborate manual tracing process. In addition to the proposed segmentation procedure and the fine tuning procedure that was developed, a global quantification of the soil coverage by residues for the sampled area was achieved that differed by only 0.85% from the quantification obtained using template images. Moreover, the proposed method does not depend on the type of residue present in the image. The study was conducted at the experimental farm "El Encín" in Alcalá de Henares (Madrid, Spain). PMID:22163966

  11. Transcription closed and open complex dynamics studies reveal balance between genetic determinants and co-factors

    NASA Astrophysics Data System (ADS)

    Sala, Adrien; Shoaib, Muhammad; Anufrieva, Olga; Mutharasu, Gnanavel; Jahan Hoque, Rawnak; Yli-Harja, Olli; Kandhavelu, Meenakshisundaram

    2015-05-01

    In E. coli, promoter closed and open complexes are key steps in transcription initiation, where magnesium-dependent RNA polymerase catalyzes RNA synthesis. However, the exact mechanism of initiation remains to be fully elucidated. Here, using single mRNA detection and dual reporter studies, we show that increased intracellular magnesium concentration affects Plac initiation complex formation resulting in a highly dynamic process over the cell growth phases. Mg2+ regulates transcription transition, which modulates bimodality of mRNA distribution in the exponential phase. We reveal that Mg2+ regulates the size and frequency of the mRNA burst by changing the open complex duration. Moreover, increasing magnesium concentration leads to higher intrinsic and extrinsic noise in the exponential phase. RNAP-Mg2+ interaction simulation reveals critical movements creating a shorter contact distance between aspartic acid residues and Nucleotide Triphosphate residues and increasing electrostatic charges in the active site. Our findings provide unique biophysical insights into the balanced mechanism of genetic determinants and magnesium ion in transcription initiation regulation during cell growth.

  12. Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease

    PubMed Central

    Miyazaki, Márcia I.; Chiminacio Neto, Nelson; Padeski, Marcela C.; Barros, Ana Cláudia M.

    2016-01-01

    Chagas disease (CD) is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL), a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32). Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003). Furthermore, cardiac patients with genotypes causing MBL deficiency presented less heart damage (P = 0.003, OR = 0.23), compared with cardiac patients having the XA haplotype causing low MBL levels, but fully capable of activating complement (P = 0.005, OR = 7.07). Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031). These findings suggest a protective effect of genetically determined MBL deficiency against the development and progression of chronic CD cardiomyopathy. PMID:26745156

  13. An Image Segmentation Based on a Genetic Algorithm for Determining Soil Coverage by Crop Residues

    PubMed Central

    Ribeiro, Angela; Ranz, Juan; Burgos-Artizzu, Xavier P.; Pajares, Gonzalo; Sanchez del Arco, Maria J.; Navarrete, Luis

    2011-01-01

    Determination of the soil coverage by crop residues after ploughing is a fundamental element of Conservation Agriculture. This paper presents the application of genetic algorithms employed during the fine tuning of the segmentation process of a digital image with the aim of automatically quantifying the residue coverage. In other words, the objective is to achieve a segmentation that would permit the discrimination of the texture of the residue so that the output of the segmentation process is a binary image in which residue zones are isolated from the rest. The RGB images used come from a sample of images in which sections of terrain were photographed with a conventional camera positioned in zenith orientation atop a tripod. The images were taken outdoors under uncontrolled lighting conditions. Up to 92% similarity was achieved between the images obtained by the segmentation process proposed in this paper and the templates made by an elaborate manual tracing process. In addition to the proposed segmentation procedure and the fine tuning procedure that was developed, a global quantification of the soil coverage by residues for the sampled area was achieved that differed by only 0.85% from the quantification obtained using template images. Moreover, the proposed method does not depend on the type of residue present in the image. The study was conducted at the experimental farm “El Encín” in Alcalá de Henares (Madrid, Spain). PMID:22163966

  14. Mutation in the 3'untranslated region of APP as a genetic determinant of cerebral amyloid angiopathy.

    PubMed

    Nicolas, Gaël; Wallon, David; Goupil, Claudia; Richard, Anne-Claire; Pottier, Cyril; Dorval, Véronique; Sarov-Rivière, Mariana; Riant, Florence; Hervé, Dominique; Amouyel, Philippe; Guerchet, Maelenn; Ndamba-Bandzouzi, Bebene; Mbelesso, Pascal; Dartigues, Jean-François; Lambert, Jean-Charles; Preux, Pierre-Marie; Frebourg, Thierry; Campion, Dominique; Hannequin, Didier; Tournier-Lasserve, Elisabeth; Hébert, Sébastien S; Rovelet-Lecrux, Anne

    2016-01-01

    Aβ-related cerebral amyloid angiopathy (CAA) is a major cause of primary non-traumatic brain hemorrhage. In families with an early onset of the disease, CAA can be due to amyloid precursor protein (APP) pathogenic variants or duplications. APP duplications lead to a ~1.5-fold increased APP expression, resulting in Aβ overproduction and deposition in the walls of leptomeningeal vessels. We hypothesized that rare variants in the 3'untranslated region (UTR) of APP might lead to APP overexpression in patients with CAA and no APP pathogenic variant or duplication. We performed direct sequencing of the whole APP 3'UTR in 90 patients with CAA and explored the functional consequences of one previously unreported variant. We identified three sequence variants in four patients, of which a two-base pair deletion (c.*331_*332del) was previously unannotated and absent from 175 controls of same ethnicity. This latter variant was associated with increased APP expression in vivo and in vitro. Bioinformatics and functional assays showed that the APP c.*331_*332del variant affected APP messenger RNA (mRNA) structure and binding of two microRNAs (miR-582-3p and miR-892b), providing a mechanism for the observed effects on APP expression. These results identify APP 3'UTR sequence variants as genetic determinants of Aβ-CAA. PMID:25828868

  15. Conserved genetic determinant of motor organ identity in Medicago truncatula and related legumes

    PubMed Central

    Chen, Jianghua; Moreau, Carol; Liu, Yu; Kawaguchi, Masayoshi; Hofer, Julie; Ellis, Noel; Chen, Rujin

    2012-01-01

    Plants exhibit various kinds of movements that have fascinated scientists and the public for centuries. Physiological studies in plants with the so-called motor organ or pulvinus suggest that cells at opposite sides of the pulvinus mediate leaf or leaflet movements by swelling and shrinking. How motor organ identity is determined is unknown. Using a genetic approach, we isolated a mutant designated elongated petiolule1 (elp1) from Medicago truncatula that fails to fold its leaflets in the dark due to loss of motor organs. Map-based cloning indicated that ELP1 encodes a putative plant-specific LOB domain transcription factor. RNA in situ analysis revealed that ELP1 is expressed in primordial cells that give rise to the motor organ. Ectopic expression of ELP1 resulted in dwarf plants with petioles and rachises reduced in length, and the epidermal cells gained characteristics of motor organ epidermal cells. By identifying ELP1 orthologs from other legume species, namely pea (Pisum sativum) and Lotus japonicus, we show that this motor organ identity is regulated by a conserved molecular mechanism. PMID:22689967

  16. Genetically determined differences in ethanol sensitivity influenced by body temperature during intoxication

    SciTech Connect

    Alkana, R.L.; Finn, D.A.; Bejanian, M.; Crabbe, J.C.

    1988-01-01

    The present study investigated the importance of body temperature during intoxication in mediating differences between five inbred strains of mice (C57BL/6J; BALB/cJ; DBA/2J; A/HeJ; 129/J) in their acute sensitivity to the hypnotic effects of ethanol. Mice exposed to 22/degrees/C after ethanol injection became hypothermic and exhibited statistically significant differences between strains in rectal temperatures at the return of the righting reflex (RORR), duration of loss of the righting reflex (LORR), and blood and brain ethanol concentrations at RORR. Exposure to 34/degrees/C after injection offset ethanol-hypothermia and markedly reduced strain-related differences in rectal temperatures and blood and brain ethanol concentrations at RORR. Brain ethanol concentrations at RORR were significantly lower in C57, BALB, DBA and A/He mice exposed to 34/degrees/C compared to mice exposed to 22/degrees/C during intoxication suggesting that offsetting hypothermia increased ethanol sensitivity in these strains. Taken with previous in vitro studies, these results suggest that genetically determined differences in acute sensitivity to the behavioral effects of ethanol reflect differences in body temperature during intoxication as well as differences in sensitivity to the initial actions of ethanol at the cellular level.

  17. Pyrazinamide resistance determined by liquid culture at low pH better correlates with genetic mutations in MDR tuberculosis isolates.

    PubMed

    Pang, Yu; Wang, Zhongdong; Zheng, Huiwen; Song, Yuanyuan; Wang, Yufeng; Zhao, Yanlin

    2015-12-01

    We detected the pyrazinamide (PZA) susceptibility of Mycobacterium tuberculosis strains in the Bactec MGIT 960 liquid medium with different pH values. Our results demonstrated that PZA resistance determined by liquid culture at pH 5.7 (94.9%) showed better correlation with genetic changes among multidrug-resistant M. tuberculosis isolates (P=0.001). PMID:26506283

  18. 78 FR 25941 - Stine Seed Farm, Inc.; Extension of a Determination of Nonregulated Status of Corn Genetically...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-03

    ...We are advising the public that the Animal and Plant Health Inspection Service is extending to maize line HCEM485, which has been genetically engineered to be resistant to the herbicide glyphosate, our determination of nonregulated status of Roundup Ready[supreg] corn line GA21. Therefore, APHIS no longer considers maize line HCEM485 to be a regulated article under Agency regulations governing......

  19. DETERMINATION OF GENETIC DIVERSITY AND PATERNITY IN THE GRAY-TAILED VOLE (MICROTUS CANICAUDUS) BY RAPD-PCR

    EPA Science Inventory

    Genetic relatedness of gray-tailed voles (Microtus canicaudus) was determined by random amplified polymorphic DNA (RAPD). This work is the first reported use of the RAPD method for pedigree analysis of M. canicaudus and demonstrates the feasibility of RAPD for assessing paternity...

  20. 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... included in the petition. In a notice published in the Federal Register on June 27, 2005 (70 FR...

  1. 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... the Federal Register on June 28, 2011 (76 FR 37771-37772, Docket No. APHIS-2011-0046), APHIS...

  2. 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...' regulations in 7 CFR part 340. In a notice \\1\\ published in the Federal Register on December 27, 2011 (76...

  3. 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... Register on February 27, 2013 (78 FR 13312-13313, Docket No. APHIS-2012-0026), APHIS announced...

  4. Enhancements and justice: problems in determining the requirements of justice in a genetically transformed society.

    PubMed

    Lindsay, Ronald A

    2005-03-01

    There is a concern that genetic engineering will exacerbate existing social divisions and inequalities, especially if only the wealthy can afford genetic enhancements. Accordingly, many argue that justice requires the imposition of constraints on genetic engineering. However, it would be unwise to decide at this time what limits should be imposed in the future. Decision makers currently lack both the theoretical tools and the factual foundation for making sound judgments about the requirements of justice in a genetically transformed society. Moreover, focusing on the uncertain inequities of the future may result in failure to give priority to more pressing inequities of the present. Especially in a country that recently has enacted tax legislation that will widen existing wealth disparities, concern about the distant threat of a genetic aristocracy appears misplaced. PMID:15881599

  5. Determination of alloy content from plume spectral measurements

    NASA Technical Reports Server (NTRS)

    Madzsar, George C.

    1991-01-01

    The mathematical derivation for a method to determine the identities and amounts of alloys present in a flame where numerous alloys may be present is described. This method is applicable if the total number of elemental species from all alloys that may be in the flame is greater than or equal to the total number of alloys. Arranging the atomic spectral line emission equations for the elemental species as a series of simultaneous equations enables solution for identity and amount of the alloy present in the flame. This technique is intended for identification and quantification of alloy content in the plume of a rocket engine. Spectroscopic measurements reveal the atomic species entrained in the plume. Identification of eroding alloys may lead to the identification of the eroding component.

  6. 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.

  7. Identification of Genetic Determinants of the Sexual Dimorphism in CNS Autoimmunity

    PubMed Central

    Bearoff, Frank; Case, Laure K.; Krementsov, Dimitry N.; Wall, Emma H.; Saligrama, Naresha; Blankenhorn, Elizabeth P.; Teuscher, Cory

    2015-01-01

    Multiple sclerosis (MS) is a debilitating chronic inflammatory disease of the nervous system that affects approximately 2.3 million individuals worldwide, with higher prevalence in females, and a strong genetic component. While over 200 MS susceptibility loci have been identified in GWAS, the underlying mechanisms whereby they contribute to disease susceptibility remains ill-defined. Forward genetics approaches using conventional laboratory mouse strains are useful in identifying and functionally dissecting genes controlling disease-relevant phenotypes, but are hindered by the limited genetic diversity represented in such strains. To address this, we have combined the powerful chromosome substitution (consomic) strain approach with the genetic diversity of a wild-derived inbred mouse strain. Using experimental allergic encephalomyelitis (EAE), a mouse model of MS, we evaluated genetic control of disease course among a panel of 26 consomic strains of mice inheriting chromosomes from the wild-derived PWD strain on the C57BL/6J background, which models the genetic diversity seen in human populations. Nineteen linkages on 18 chromosomes were found to harbor loci controlling EAE. Of these 19 linkages, six were male-specific, four were female-specific, and nine were non-sex-specific, consistent with a differential genetic control of disease course between males and females. An MS-GWAS candidate-driven bioinformatic analysis using orthologous genes linked to EAE course identified sex-specific and non-sex-specific gene networks underlying disease pathogenesis. An analysis of sex hormone regulation of genes within these networks identified several key molecules, prominently including the MAP kinase family, known hormone-dependent regulators of sex differences in EAE course. Importantly, our results provide the framework by which consomic mouse strains with overall genome-wide genetic diversity, approximating that seen in humans, can be used as a rapid and powerful tool for

  8. Etiology and measurement of relational aggression: A multi-informant behavior genetic investigation.

    PubMed

    Tackett, Jennifer L; Waldman, Irwin D; Lahey, Benjamin B

    2009-11-01

    Although the study of relational aggression is gaining attention in the literature, little is known about the underlying causes of this behavior and the relative validity of various informants. These issues were addressed in a sample of 1,981 6- to 18-year-old twin pairs (36% female, 34% male, 30% opposite-sex). Relational aggression was assessed via maternal and self-report using a structured interview. Univariate models estimated genetic and environmental influences by informant and examined evidence for gender differences. A psychometric model combined data from both informants to estimate etiologic influences that were both common to the informants and informant specific. In both sexes, the latent variable reflecting the mother's and child's shared perception of the child's relational aggression was substantially influenced by both additive genetic (63%) and shared environmental (37%) influences, although this latent variable accounted for much greater variance in the maternal report (66%) than it did in the youth report (9%). In addition, informant-specific additive genetic and shared environmental influences were found only for the youth report, with all remaining variance in the mother's report attributed to nonshared environmental influences. Results are discussed in the context of measuring relational aggression and the importance of multiple informants. PMID:19899842

  9. Properties of genetically-encoded indicators used for cytosolic and organellar Ca2+ measurements

    PubMed Central

    Park, J. Genevieve; Palmer, Amy E.

    2016-01-01

    For the last 15 years, there has been an explosion in the development of genetically-encoded biosensors that report enzyme activity, chemical transformation, or concentration of ions and molecules in living cells. Now, there are well over 120 biosensors of different cellular targets. As a general design principle, these sensors convert a molecular event, such as the binding of a molecule to a sensing domain or a signal-induced change in protein conformation, into a change in the sensors’ fluorescence properties. In contrast to small-molecule sensors, genetically-encoded sensors are generated as cells, tissues, or organisms translate sensor-encoding nucleic acid sequences, which have been introduced by transgenic technologies. One of the best developed classes of biosensors is that of genetically-encoded Ca2+ indicators (GECIs). Here, we briefly summarize the properties of ratiometric GECIs that permit them to be used to quantify Ca2+ in specific cellular locations, such as the cytosol, nucleus, endoplasmic reticulum, and mitochondria. We also provide two protocols that describe in detail how to carry out such quantitative measurements in cultured mammalian cells. PMID:25561625

  10. Genetic Interactions Found Between Calcium Channel Genes Modulate Amyloid Load Measured by Positron Emission Tomography

    PubMed Central

    Koran, Mary Ellen I.; Hohman, Timothy J.; Thornton-Wells, Tricia A.

    2014-01-01

    Late-onset Alzheimer’s disease (LOAD) is known to have a complex, oligogenic etiology, with considerable genetic heterogeneity. We investigated the influence of genetic interactions between genes in the Alzheimer’s disease (AD) pathway on amyloid-beta (Aβ) deposition as measured by PiB or AV-45 ligand positron emission tomography (PET) to aid in understanding LOAD’s genetic etiology. Subsets of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohorts were used for discovery and for two independent validation analyses. A significant interaction between RYR3 and CACNA1C was confirmed in all three of the independent ADNI datasets. Both genes encode calcium channels expressed in the brain. The results shown here support previous animal studies implicating interactions between these calcium channels in amyloidigenesis and suggest that the pathological cascade of this disease may be modified by interactions in the amyloid-calcium axis. Future work focusing on the mechanisms of such relationships may inform targets for clinical intervention. PMID:24026422

  11. Copy number ratios determined by two digital polymerase chain reaction systems in genetically modified grains

    NASA Astrophysics Data System (ADS)

    Pérez Urquiza, M.; Acatzi Silva, A. I.

    2014-02-01

    Three certified reference materials produced from powdered seeds to measure the copy number ratio sequences of p35S/hmgA in maize containing MON 810 event, p35S/Le1 in soybeans containing GTS 40-3-2 event and DREB1A/acc1 in wheat were produced according to the ISO Guides 34 and 35. In this paper, we report digital polymerase chain reaction (dPCR) protocols, performance parameters and results of copy number ratio content of genetically modified organisms (GMOs) in these materials using two new dPCR systems to detect and quantify molecular deoxyribonucleic acid: the BioMark® (Fluidigm) and the OpenArray® (Life Technologies) systems. These technologies were implemented at the National Institute of Metrology in Mexico (CENAM) and in the Reference Center for GMO Detection from the Ministry of Agriculture (CNRDOGM), respectively. The main advantage of this technique against the more-used quantitative polymerase chain reaction (qPCR) is that it generates an absolute number of target molecules in the sample, without reference to standards or an endogenous control, which is very useful when not much information is available for new developments or there are no standard reference materials in the market as in the wheat case presented, or when it was not possible to test the purity of seeds as in the maize case presented here. Both systems reported enhanced productivity, increased reliability and reduced instrument footprint. In this paper, the performance parameters and uncertainty of measurement obtained with both systems are presented and compared.

  12. 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.

  13. Genetic parameters for androstenone, skatole, indole, and human nose scores as measures of boar taint and their relationship with finishing traits.

    PubMed

    Windig, J J; Mulder, H A; Ten Napel, J; Knol, E F; Mathur, P K; Crump, R E

    2012-07-01

    The purpose of this study was to evaluate measures of boar (Sus scrofa) taint as potential selection criteria to reduce boar taint so that castration of piglets will become unnecessary. Therefore, genetic parameters of boar taint measures and their genetic correlations with finishing traits were estimated. In particular, the usefulness of a human panel assessing boar taint (human nose score) was compared with chemical assessment of boar taint compounds, androstenone, skatole, and indole. Heritability estimates for androstenone, skatole, and indole were 0.54, 0.41, and 0.33, respectively. The heritability for the human nose score using multiple panelists was 0.12, and ranged from 0.12 to 0.19 for individual panelists. Genetic correlations between scores of panelists were generally high up to unity. The genetic correlations between human nose scores and the boar taint compounds ranged from 0.64 to 0.999. The boar taint compounds and human nose scores had low or favorable genetic correlations with finishing traits. Selection index estimates indicated that the effectiveness of a breeding program based on human nose scores can be comparable to a breeding program based on the boar taint compounds themselves. Human nose scores can thus be used as a cheap and fast alternative for the costly determination of boar taint compounds, needed in breeding pigs without boar taint. PMID:22247111

  14. Genetically designed L3 photonic crystal nanocavities with measured quality factor exceeding one million

    SciTech Connect

    Lai, Y.; Badolato, A.; Pirotta, S.; Urbinati, G.; Gerace, D.; Galli, M.; Minkov, M.; Savona, V.

    2014-06-16

    We report on the experimental realization of ultra-high quality factor (Q) designs of the L3-type photonic crystal nanocavity. Based on genetic optimization of the positions of few nearby holes, our design drastically improves the performance of the conventional L3 as experimentally confirmed by direct measurement of Q ≃ 2 × 10{sup 6} in a silicon-based photonic crystal membrane. Our devices rank among the highest Q/V ratios ever reported in photonic crystal cavities, holding great promise for the realization of integrated photonic platforms based on ultra-high-Q resonators.

  15. Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine

    PubMed Central

    Michmerhuizen, Nicole L.; Birkeland, Andrew C.; Bradford, Carol R.; Brenner, J. Chad

    2016-01-01

    While sequencing studies have provided an improved understanding of the genetic landscape of head and neck squamous cell carcinomas (HNSCC), there remains a significant lack of genetic data derived from non-Caucasian cohorts. Additionally, there is wide variation in HNSCC incidence and mortality worldwide both between and within various geographic regions. These epidemiologic differences are in part accounted for by varying exposure to environmental risk factors such as tobacco, alcohol, high risk human papilloma viruses and betel quid. However, inherent genetic factors may also play an important role in this variability. As limited sequencing data is available for many populations, the involvement of unique genetic factors in HNSCC pathogenesis from epidemiologically diverse groups is unknown. Here, we review current knowledge about the epidemiologic, environmental, and genetic variation in HNSCC cohorts globally and discuss future studies necessary to further our understanding of these differences. Long-term, a more complete understanding of the genetic drivers found in diverse HNSCC cohorts may help the development of personalized medicine protocols for patients with rare or complex genetic events. PMID:27551333

  16. Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine.

    PubMed

    Michmerhuizen, Nicole L; Birkeland, Andrew C; Bradford, Carol R; Brenner, J Chad

    2016-05-01

    While sequencing studies have provided an improved understanding of the genetic landscape of head and neck squamous cell carcinomas (HNSCC), there remains a significant lack of genetic data derived from non-Caucasian cohorts. Additionally, there is wide variation in HNSCC incidence and mortality worldwide both between and within various geographic regions. These epidemiologic differences are in part accounted for by varying exposure to environmental risk factors such as tobacco, alcohol, high risk human papilloma viruses and betel quid. However, inherent genetic factors may also play an important role in this variability. As limited sequencing data is available for many populations, the involvement of unique genetic factors in HNSCC pathogenesis from epidemiologically diverse groups is unknown. Here, we review current knowledge about the epidemiologic, environmental, and genetic variation in HNSCC cohorts globally and discuss future studies necessary to further our understanding of these differences. Long-term, a more complete understanding of the genetic drivers found in diverse HNSCC cohorts may help the development of personalized medicine protocols for patients with rare or complex genetic events. PMID:27551333

  17. Genetic Determinants of the Network of Primary Metabolism and Their Relationships to Plant Performance in a Maize Recombinant Inbred Line Population[OPEN

    PubMed Central

    Wen, Weiwei; Li, Kun; Alseekh, Saleh; Omranian, Nooshin; Zhao, Lijun; Zhou, Yang; Xiao, Yingjie; Jin, Min; Yang, Ning; Liu, Haijun; Florian, Alexandra; Li, Wenqiang; Pan, Qingchun; Nikoloski, Zoran; Yan, Jianbing; Fernie, Alisdair R.

    2015-01-01

    Deciphering the influence of genetics on primary metabolism in plants will provide insights useful for genetic improvement and enhance our fundamental understanding of plant growth and development. Although maize (Zea mays) is a major crop for food and feed worldwide, the genetic architecture of its primary metabolism is largely unknown. Here, we use high-density linkage mapping to dissect large-scale metabolic traits measured in three different tissues (leaf at seedling stage, leaf at reproductive stage, and kernel at 15 d after pollination [DAP]) of a maize recombinant inbred line population. We identify 297 quantitative trait loci (QTLs) with moderate (86.2% of the mapped QTL, R2 = 2.4 to 15%) to major effects (13.8% of the mapped QTL, R2 >15%) for 79 primary metabolites across three tissues. Pairwise epistatic interactions between these identified loci are detected for more than 25.9% metabolites explaining 6.6% of the phenotypic variance on average (ranging between 1.7 and 16.6%), which implies that epistasis may play an important role for some metabolites. Key candidate genes are highlighted and mapped to carbohydrate metabolism, the tricarboxylic acid cycle, and several important amino acid biosynthetic and catabolic pathways, with two of them being further validated using candidate gene association and expression profiling analysis. Our results reveal a metabolite-metabolite-agronomic trait network that, together with the genetic determinants of maize primary metabolism identified herein, promotes efficient utilization of metabolites in maize improvement. PMID:26187921

  18. METHODS FOR DETERMINING EXPOSURE TO AND POTENTIAL ECOLOGICAL EFFECTS OF GENE FLOW FROM GENETICALLY MODIFIED CROPS TO COMPATIBLE RELATIVES

    EPA Science Inventory

    SCIENCE QUESTIONS:

    -Does gene flow occur from genetically modified (GM) crop plants to compatible plants?

    -How can it be measured?

    -Are there ecological consequences of GM crop gene flow to plant communities?



    RESEARCH:

    The objectives ...

  19. Genetic determinants of aromatase inhibitor-related arthralgia: the B-ABLE cohort study.

    PubMed

    Garcia-Giralt, Natalia; Rodríguez-Sanz, María; Prieto-Alhambra, Daniel; Servitja, Sonia; Torres-Del Pliego, Elisa; Balcells, Susana; Albanell, Joan; Grinberg, Daniel; Diez-Perez, Adolfo; Tusquets, Ignasi; Nogués, Xavier

    2013-07-01

    A major side effect of aromatase inhibitor (AI) therapy is AI-related arthralgia (AIA), which often leads to therapy discontinuation. We aimed to identify genetic variants associated with AIA and therapy discontinuation in the first year of AI treatment. Our prospective cohort study included 343 postmenopausal women with early breast cancer starting AI therapy. Single nucleotide polymorphisms (SNPs) in candidate genes involved in estrogen and vitamin D signaling were selected. Univariate and multivariate linear/logistic regressions were fitted in order to asses the association between studied SNPs and AIA intensity (visual analogic scale score) at 3 and 12 months of follow-up, worsening pain, and therapy discontinuation. We also tested for a priori-defined interactions by introducing multiplicative terms in the regression equations. SNPs in CYP17A1 and VDR genes appeared significantly associated with AIA (P = 0.003, P = 0.012, respectively). One SNP in CYP27B1 gene was related to therapy discontinuation [P = 0.02; OR 0.29 (0.09-0.99)]. We revealed interactions between CYP27B1 and both CYP17A1 (P = 0.01) and VDR SNPs (P = 0.06). Furthermore, an additive effect on pain intensity was shown for unfavorable alleles, with two points higher mean absolute pain increase and up to 5.3-fold higher risk of worsening pain compared to favorable genotypes. SNPs in CYP17A1, VDR, and CYP27B1 genes predict the risk of AIA. Their determination would be useful to trigger the monitoring strategies in women at risk of therapy discontinuation. PMID:23868189

  20. Genetic Determinants for Pyomelanin Production and Its Protective Effect against Oxidative Stress in Ralstonia solanacearum

    PubMed Central

    Kong, Hyun Gi; Jo, Eun Jeong; Choi, Hye Kyung; Khan, Raees; Lee, Seon-Woo

    2016-01-01

    Ralstonia solanacearum is a soil-borne plant pathogen that infects more than 200 plant species. Its broad host range and long-term survival under different environmental stress conditions suggest that it uses a variety of mechanisms to protect itself against various types of biotic and abiotic stress. R. solanacearum produces a melanin-like brown pigment in the stationary phase when grown in minimal medium containing tyrosine. To gain deeper insight into the genetic determinants involved in melanin production, transposon-inserted mutants of R. solanacearum strain SL341 were screened for strains with defective melanin-producing capability. In addition to one mutant already known to be involved in pyomelanin production (viz., strain SL341D, with disruption of the hydroxphenylpyruvate dioxygenase gene), we identified three other mutants with disruption in the regulatory genes rpoS, hrpG, and oxyR, respectively. Wild-type SL341 produced pyomelanin in minimal medium containing tyrosine whereas the mutant strains did not. Likewise, homogentisate, a major precursor of pyomelanin, was detected in the culture filtrate of the wild-type strain but not in those of the mutant strains. A gene encoding hydroxyphenylpyruvate dioxygenase exhibited a significant high expression in wild type SL341 compared to other mutant strains, suggesting that pyomelanin production is regulated by three different regulatory proteins. However, analysis of the gene encoding homogentisate dioxygenase revealed no significant difference in its relative expression over time in the wild-type SL341 and mutant strains, except for SL341D, at 72 h incubation. The pigmented SL341 strain also exhibited a high tolerance to hydrogen peroxide stress compared with the non-pigmented SL341D strain. Our study suggests that pyomelanin production is controlled by several regulatory factors in R. solanacearum to confer protection under oxidative stress. PMID:27513990

  1. Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer.

    PubMed

    Yuan, Jian-Min; Chan, Kenneth K; Coetzee, Gerhard A; Castelao, J Esteban; Watson, Mary A; Bell, Douglas A; Wang, Renwei; Yu, Mimi C

    2008-07-01

    Genetically determined factors that alter the metabolism of tobacco carcinogens can influence an individual's susceptibility to bladder cancer. The associations between the genotypes of glutathione S-transferase (GST) M1, GSTP1, GSTT1 and N-acetyltransferase (NAT) 1 and the phenotypes of NAT2 and cytochrome P450 (CYP) 1A2 and bladder cancer risk were examined in a case-control study involving 731 bladder cancer patients and 740 control subjects in Los Angeles County, California. Individual null/low-activity genotypes of GSTM1, GSTT1 and GSTP1 were associated with a 19-48% increase in odds ratio (OR) of bladder cancer. The strongest association was noted for GSTM1 [OR for the null genotype = 1.48, 95% confidence interval (CI) = 1.19-1.83]. When the three GST genes were examined together, there was a monotonic, statistically significant association between increasing number of null/low-activity genotypes and risk (P for trend = 0.002). OR (95% CI) for one and two or more null/low-activity GST genotypes was 1.42 (1.12-1.81) and 1.71 (1.25-2.34), respectively, relative to the absence of null/low-activity GST genotype. NAT2 slow acetylation was associated with doubled risk of bladder cancer among individuals with known high exposures to carcinogenic arylamines (OR = 2.03, 95% CI = 1.12-3.69, P = 0.02). The effect of NAT2 slow acetylation was even stronger in the presence of two or more null/low-activity GST genotypes. There were no associations between bladder cancer risk and NAT1 genotype or CYP1A2 phenotype. PMID:18544563

  2. Genetic Determinants for Pyomelanin Production and Its Protective Effect against Oxidative Stress in Ralstonia solanacearum.

    PubMed

    Ahmad, Shabir; Lee, Seung Yeup; Kong, Hyun Gi; Jo, Eun Jeong; Choi, Hye Kyung; Khan, Raees; Lee, Seon-Woo

    2016-01-01

    Ralstonia solanacearum is a soil-borne plant pathogen that infects more than 200 plant species. Its broad host range and long-term survival under different environmental stress conditions suggest that it uses a variety of mechanisms to protect itself against various types of biotic and abiotic stress. R. solanacearum produces a melanin-like brown pigment in the stationary phase when grown in minimal medium containing tyrosine. To gain deeper insight into the genetic determinants involved in melanin production, transposon-inserted mutants of R. solanacearum strain SL341 were screened for strains with defective melanin-producing capability. In addition to one mutant already known to be involved in pyomelanin production (viz., strain SL341D, with disruption of the hydroxphenylpyruvate dioxygenase gene), we identified three other mutants with disruption in the regulatory genes rpoS, hrpG, and oxyR, respectively. Wild-type SL341 produced pyomelanin in minimal medium containing tyrosine whereas the mutant strains did not. Likewise, homogentisate, a major precursor of pyomelanin, was detected in the culture filtrate of the wild-type strain but not in those of the mutant strains. A gene encoding hydroxyphenylpyruvate dioxygenase exhibited a significant high expression in wild type SL341 compared to other mutant strains, suggesting that pyomelanin production is regulated by three different regulatory proteins. However, analysis of the gene encoding homogentisate dioxygenase revealed no significant difference in its relative expression over time in the wild-type SL341 and mutant strains, except for SL341D, at 72 h incubation. The pigmented SL341 strain also exhibited a high tolerance to hydrogen peroxide stress compared with the non-pigmented SL341D strain. Our study suggests that pyomelanin production is controlled by several regulatory factors in R. solanacearum to confer protection under oxidative stress. PMID:27513990

  3. [Root Nodule Bacteria Sinorhizobium meliloti: Tolerance to Salinity and Bacterial Genetic Determinants].

    PubMed

    Roumiantseva, M L; Muntyan, V S

    2015-01-01

    The theoretical and experimental data on salt tolerance of root nodule bacteria Sinorhizobium meliloti (Ensifer meliloti), an alfalfa symbiont, and on genetic determination of this feature are reviewed. Extensive data on the genes affecting adaptation of proteobacteria are provided, as well as on the groups of genes with activity depending on the osmolarity of the medium. Structural and functional polymorphism of the bet genes involved in betaine synthesis and transport in S. meliloti is discussed. The phenotypic and. genotypic polymorphism in 282 environmental rhizobial strains isolated from the centers of alfalfa diversity affected by aridity and salinity is discussed. The isolates from the Aral Sea area and northern Caucasus were shown to possess the betC gene represented by two types of alleles: the dominant A-type allele found in Rm 1021 and the less common divergent E-type allele, which was revealed in regions at the frequencies at the frequencies of 0.35 and 0.48, respectively. In the isolates with the salt-tolerant phenotype, which were isolated from root nodules and subsequently formed less effective symbioses with alfalfa, the frequency of E-type alleles was 2.5 times higher. Analysis of the nucleotide and amino acid sequences of the E-type allele of the betC gene revealed that establishment of this allele in the population was a result of positive selection. It is concluded that diversification of the functionally diverse bet genes occurring in S. meliloti affects the salt tolerance and symbiotic effectivity of rhizobia. PMID:26263687

  4. Genetic Profiling to Determine Risk of Relapse Free Survival in High-risk Localized Prostate Cancer

    PubMed Central

    Barnett, Christine M.; Heinrich, Michael C.; Lim, Jeong; Nelson, Dylan; Beadling, Carol; Warrick, Andrea; Neff, Tanaya; Higano, Celestia S.; Garzotto, Mark; Qian, David; Corless, Christopher L.; Thomas, George V.; Beer, Tomasz M.

    2014-01-01

    Purpose The characterization of actionable mutations in human tumors is a prerequisite for the development of individualized, targeted therapy. We examined the prevalence of potentially therapeutically actionable mutations in patients with high risk clinically localized prostate cancer. Experimental Design 48 samples of formalin fixed paraffin embedded prostatectomy tissue from a neoadjuvant chemotherapy trial were analyzed. DNA extracted from microdissected tumor was analyzed for 643 common solid tumor mutations in 53 genes using mass spectroscopy based sequencing. In addition, PTEN loss and ERG translocations were examined using immunohistochemistry in associated tissue microarrays. Association with relapse during 5 years of follow-up was examined in exploratory analyses of the potential clinical relevance of the genetic alterations. Results Of the 40 tumors evaluable for mutations, 10% had point mutations in potentially actionable cancer genes. Of the 47 tumors evaluable for IHC, 36% had PTEN loss and 40% had ERG rearrangement. Individual mutations were not frequent enough to determine associations with relapse. Using Kaplan-Meier analysis with a log-rank test, the 16 patients who had PTEN loss had a significantly shorter median relapse free survival, 19 vs. 106 months (p = .01). Conclusions This study confirms that point mutations in the most common cancer regulatory genes in prostate cancer are rare. However, the PIK3CA/AKT pathway was mutated in 10% of our samples. While point mutations alone did not have a statistically significant association with relapse, PTEN loss was associated with an increased relapse in high risk prostate cancer treated with chemotherapy followed by surgery. PMID:24352642

  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. Behavioral versus genetic determination of lipoproteins andidentical twins discordant for exercise

    SciTech Connect

    Williams, Paul T.; Blanche, Patricia J.; Krauss, Ronald M.

    2004-06-01

    Lipoprotein and weight differences between vigorously active and sedentary MZ twins are used to: (1) estimate the effects of training while controlling for genotype; (2) estimate genetic concordance in the presence of divergent lifestyles.

  7. Demographic Histories, Isolation and Social Factors as Determinants of the Genetic Structure of Alpine Linguistic Groups

    PubMed Central

    Coia, Valentina; Capocasa, Marco; Anagnostou, Paolo; Pascali, Vincenzo; Scarnicci, Francesca; Boschi, Ilaria; Battaggia, Cinzia; Crivellaro, Federica; Ferri, Gianmarco; Alù, Milena; Brisighelli, Francesca; Busby, George B. J.; Capelli, Cristian; Maixner, Frank; Cipollini, Giovanna; Viazzo, Pier Paolo; Zink, Albert; Destro Bisol, Giovanni

    2013-01-01

    Great European mountain ranges have acted as barriers to gene flow for resident populations since prehistory and have offered a place for the settlement of small, and sometimes culturally diverse, communities. Therefore, the human groups that have settled in these areas are worth exploring as an important potential source of diversity in the genetic structure of European populations. In this study, we present new high resolution data concerning Y chromosomal variation in three distinct Alpine ethno-linguistic groups, Italian, Ladin and German. Combining unpublished and literature data on Y chromosome and mitochondrial variation, we were able to detect different genetic patterns. In fact, within and among population diversity values observed vary across linguistic groups, with German and Italian speakers at the two extremes, and seem to reflect their different demographic histories. Using simulations we inferred that the joint effect of continued genetic isolation and reduced founding group size may explain the apportionment of genetic diversity observed in all groups. Extending the analysis to other continental populations, we observed that the genetic differentiation of Ladins and German speakers from Europeans is comparable or even greater to that observed for well known outliers like Sardinian and Basques. Finally, we found that in south Tyroleans, the social practice of Geschlossener Hof, a hereditary norm which might have favored male dispersal, coincides with a significant intra-group diversity for mtDNA but not for Y chromosome, a genetic pattern which is opposite to those expected among patrilocal populations. Together with previous evidence regarding the possible effects of “local ethnicity” on the genetic structure of German speakers that have settled in the eastern Italian Alps, this finding suggests that taking socio-cultural factors into account together with geographical variables and linguistic diversity may help unveil some yet to be understood

  8. Human usage in the native range may determine future genetic structure of an invasion: insights from Acacia pycnantha

    PubMed Central

    2013-01-01

    Background The influence of introduction history and post-introduction dynamics on genetic diversity and structure has been a major research focus in invasion biology. However, genetic diversity and structure in the invasive range can also be affected by human-mediated processes in the native range prior to species introductions, an aspect often neglected in invasion biology. Here we aim to trace the native provenance of the invasive tree Acacia pycnantha by comparing the genetic diversity and structure between populations in the native Australian range and the invasive range in South Africa. This approach also allowed us to explore how human actions altered genetic structure before and after the introduction of A. pycnantha into South Africa. We hypothesized that extensive movement and replanting in A. pycnantha’s Australian range prior to its introduction to South Africa might result in highly admixed genotypes in the introduced range, comparable genetic diversity in both ranges, and therefore preclude an accurate determination of native provenance(s) of invasive populations. Results In the native range Bayesian assignment tests identified three genetic clusters with substantial admixture and could not clearly differentiate previously identified genetic entities, corroborating admixture as a result of replantings within Australia. Assignment tests that included invasive populations from South Africa indicated similar levels of admixture compared to Australian populations and a lack of genetic structure. Invasive populations of A. pycnantha in South Africa are as genetically diverse as native populations, and could not be assigned to particular native range regions. Conclusions Our results indicate that the genetic structure of A. pycnantha in Australia has been greatly altered through various planting initiatives. Specifically, there is little geographic structure and high levels of admixture. While numerous introduction history scenarios may explain the levels

  9. Determinants of Genetic Structure in a Nonequilibrium Metapopulation of the Plant Silene latifolia

    PubMed Central

    Fields, Peter D.; Taylor, Douglas R.

    2014-01-01

    Population genetic differentiation will be influenced by the demographic history of populations, opportunities for migration among neighboring demes and founder effects associated with repeated extinction and recolonization. In natural populations, these factors are expected to interact with each other and their magnitudes will vary depending on the spatial distribution and age structure of local demes. Although each of these effects has been individually identified as important in structuring genetic variance, their relative magnitude is seldom estimated in nature. We conducted a population genetic analysis in a metapopulation of the angiosperm, Silene latifolia, from which we had more than 20 years of data on the spatial distribution, demographic history, and extinction and colonization of demes. We used hierarchical Bayesian methods to disentangle which features of the populations contributed to among population variation in allele frequencies, including the magnitude and direction of their effects. We show that population age, long-term size and degree of connectivity all combine to affect the distribution of genetic variance; small, recently-founded, isolated populations contributed most to increase FST in the metapopulation. However, the effects of population size and population age are best understood as being modulated through the effects of connectivity to other extant populations, i.e. FST diminishes as populations age, but at a rate that depends how isolated the population is. These spatial and temporal correlates of population structure give insight into how migration, founder effect and within-deme genetic drift have combined to enhance and restrict genetic divergence in a natural metapopulation. PMID:25198341

  10. Genetic diversity in the germplasm of black pepper determined by EST-SSR markers.

    PubMed

    Wu, B D; Fan, R; Hu, L S; Wu, H S; Hao, C Y

    2016-01-01

    This study aimed to assess genetic diversity in the germplasm of black pepper from around the world using SSR markers from EST. In total, 13 markers were selected and successfully amplified the target loci across the black pepper germplasm. All the EST-SSR markers showed high levels of polymorphisms with an average polymorphism information content of 0.93. The genetic similarity coefficients among all accessions ranged from 0.724 to 1.000, with an average of 0.867. These results indicated that black pepper germplasms possess a complex genetic background and high genetic diversity. Based on a cluster analysis, 148 black pepper germplasms were grouped in two major clades: the Neotropics and the Asian tropics. Peperomia pellucida was grouped separately and distantly from all other accessions. These results generally agreed with the genetic and geographic distances. However, the Asian tropics clade did not cluster according to their geographic origins. In addition, compared with the American accessions, the Asian wild accessions and cultivated accessions grouped together, indicating a close genetic relationship. This verified the origin of black pepper. The newly developed EST-SSRs are highly valuable resources for the conservation of black pepper germplasm diversity and for black pepper breeding. PMID:27050963

  11. A new measure for the revised reinforcement sensitivity theory: psychometric criteria and genetic validation

    PubMed Central

    Reuter, Martin; Cooper, Andrew J.; Smillie, Luke D.; Markett, Sebastian; Montag, Christian

    2015-01-01

    Jeffrey Gray's Reinforcement Sensitivity Theory (RST) represents one of the most influential biologically-based personality theories describing individual differences in approach and avoidance tendencies. The most prominent self-report inventory to measure individual differences in approach and avoidance behavior to date is the BIS/BAS scale by Carver and White (1994). As Gray and McNaughton (2000) revised the RST after its initial formulation in the 1970/80s, and given the Carver and White measure is based on the initial conceptualization of RST, there is a growing need for self-report inventories measuring individual differences in the revised behavioral inhibition system (BIS), behavioral activation system (BAS) and the fight, flight, freezing system (FFFS). Therefore, in this paper we present a new questionnaire measuring individual differences in the revised constructs of the BIS, BAS and FFFS in N = 1814 participants (German sample). An English translated version of the new measure is also presented and tested in N = 299 English language participants. A large number of German participants (N = 1090) also filled in the BIS/BAS scales by Carver and White (1994) and the correlations between these measures are presented. Finally, this same subgroup of participants provided buccal swaps for the investigation of the arginine vasopressin receptor 1a (AVPR1a) gene. Here, a functional genetic polymorphism (rs11174811) on the AVPR1a gene was shown to be associated with individual differences in both the revised BIS and classic BIS dimensions. PMID:25852497

  12. When genetic distance matters: Measuring genetic differentiation at microsatellite loci in whole-genome scans of recent and incipient mosquito species

    PubMed Central

    Wang, Rui; Zheng, Liangbiao; Touré, Yeya T.; Dandekar, Thomas; Kafatos, Fotis C.

    2001-01-01

    Genetic distance measurements are an important tool to differentiate field populations of disease vectors such as the mosquito vectors of malaria. Here, we have measured the genetic differentiation between Anopheles arabiensis and Anopheles gambiae, as well as between proposed emerging species of the latter taxon, in whole genome scans by using 23–25 microsatellite loci. In doing so, we have reviewed and evaluated the advantages and disadvantages of standard parameters of genetic distance, FST, RST, (δμ)2, and D. Further, we have introduced new parameters, D′ and DK, which have well defined statistical significance tests and complement the standard parameters to advantage. D′ is a modification of D, whereas DK is a measure of covariance based on Pearson's correlation coefficient. We find that A. gambiae and A. arabiensis are closely related at most autosomal loci but appear to be distantly related on the basis of X-linked chromosomal loci within the chromosomal Xag inversion. The M and S molecular forms of A. gambiae are practically indistinguishable but differ significantly at two microsatellite loci from the proximal region of the X, outside the Xag inversion. At one of these loci, both M and S molecular forms differ significantly from A. arabiensis, but remarkably, at the other locus, A. arabiensis is indistinguishable from the M molecular form of A. gambiae. These data support the recent proposal of genetically differentiated M and S molecular forms of A. gambiae. PMID:11553812

  13. 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. PMID:22975737

  14. 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

  15. Galileo satellites measurement biases and orbit determination : preliminary results

    NASA Astrophysics Data System (ADS)

    Perosanz, Felix; Loyer, Sylvain; Mercier, Flavien; Boulanger, Cyrille; Capdeville, Hugues; Mezerette, Adrien

    2013-04-01

    Thanks to the IGS Multi-GNSS Experiment (M-GEX), signals from new GNSS satellites like Galileo are now available. CNES and IGN joined their efforts to contribute to the densification of this multi-GNSS global network through the REGINA project. However this network includes geodetic receivers from several manufacturers. For this reason we realized a dedicated test campaign to characterize the different receivers available in order to be able to process in a consistent way the data from the MGEX network. The test consisted in zero baseline measurements between receivers. Pseudo range as well as phase and wide-lane biases have been identified between Trimble, Leica, Javad and Septentrio receivers. Then the data from the global M-GEX tracking network have been processed for the Precise Orbit determination (POD) of the Galileo satellite. The strategy followed the one that the CNES-CLS IGS Analysis Center uses to compute hybrid GPS-GLONASS products. Since July 2012, Galileo data are processed and orbit solutions are routinely produced and evaluated. Pseudo-range and phase biases between receiver as well as inter-system biases have been quantified. We also demonstrated that a sub-decimeter 3D-WRMS orbit accuracy of Galileo satellite orbit can be achieved even during the constellation deployment.

  16. Galileo satellites measurement biases and orbit determination: first results

    NASA Astrophysics Data System (ADS)

    Perosanz, F.; Loyer, S.; Mercier, F.; Boulanger, C.; Capdeville, H.; Mezerette, A.

    2012-12-01

    Thanks to the IGS Multi-GNSS Experiment (M-GEX), signals from new GNSS satellites like Galileo are now available. CNES and IGN joined their efforts to contribute to the densification of this multi-GNSS global network through the REGINA project. However this network includes geodetic receivers from several manufacturers. For this reason we realized a dedicated test campaign to characterize the different receivers available in order to be able to process in a consistent way the data from the MGEX network. The test consisted in zero baseline measurements between receivers. Pseudo range as well as phase and wide-lane biases have been identified between Trimble, Leica, Javad and Septentrio receivers. Then the data from the global M-GEX tracking network have been processed for the Precise Orbit determination of the Galileo satellite. The strategy followed the one that the CNES-CLS IGS Analysis Center uses to compute hybrid GPS-GLONASS products. Since July 2012, Galileo data are processed and orbit solutions are routinely produced and evaluated. Pseudo-range and phase biases between receiver as well as inter-system biases have been quantified. We also demonstrated that a decimeter 3D-WRMS orbit accuracy of Galileo satellite orbit can be achieved even during the constellation deployment.

  17. 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.

  18. Environmental and Climatic Determinants of Molecular Diversity and Genetic Population Structure in a Coenagrionid Damselfly

    PubMed Central

    Wellenreuther, Maren; Sánchez-Guillén, Rosa A.; Cordero-Rivera, Adolfo; Svensson, Erik I.; Hansson, Bengt

    2011-01-01

    Identifying environmental factors that structure intraspecific genetic diversity is of interest for both habitat preservation and biodiversity conservation. Recent advances in statistical and geographical genetics make it possible to investigate how environmental factors affect geographic organisation and population structure of molecular genetic diversity within species. Here we present a study on a common and wide ranging insect, the blue tailed damselfly Ischnuraelegans, which has been the target of many ecological and evolutionary studies. We addressed the following questions: (i) Is the population structure affected by longitudinal or latitudinal gradients?; (ii) Do geographic boundaries limit gene flow?; (iii) Does geographic distance affect connectivity and is there a signature of past bottlenecks?; (iv) Is there evidence of a recent range expansion and (vi) what is the effect of geography and climatic factors on population structure? We found low to moderate genetic sub-structuring between populations (mean FST = 0.06, Dest = 0.12), and an effect of longitude, but not latitude, on genetic diversity. No significant effects of geographic boundaries (e.g. water bodies) were found. FST-and Dest-values increased with geographic distance; however, there was no evidence for recent bottlenecks. Finally, we did not detect any molecular signatures of range expansions or an effect of geographic suitability, although local precipitation had a strong effect on genetic differentiation. The population structure of this small insect has probably been shaped by ecological factors that are correlated with longitudinal gradients, geographic distances, and local precipitation. The relatively weak global population structure and high degree of genetic variation within populations suggest that I. elegans has high dispersal ability, which is consistent with this species being an effective and early coloniser of new habitats. PMID:21655216

  19. Quantitative determination of casein genetic variants in goat milk: Application in Girgentana dairy goat breed.

    PubMed

    Montalbano, Maria; Segreto, Roberta; Di Gerlando, Rosalia; Mastrangelo, Salvatore; Sardina, Maria Teresa

    2016-02-01

    The study was conducted to develop a high-performance liquid chromatographic (HPLC) method to quantify casein genetic variants (αs2-, β-, and κ-casein) in milk of homozygous individuals of Girgentana goat breed. For calibration experiments, pure genetic variants were extracted from individual milk samples of animals with known genotypes. The described HPLC approach was precise, accurate and highly suitable for quantification of goat casein genetic variants of homozygous individuals. The amount of each casein per allele was: αs2-casein A = 2.9 ± 0.8 g/L and F = 1.8 ± 0.4 g/L; β-casein C = 3.0 ± 0.8 g/L and C1 = 2.0 ± 0.7 g/L and κ-casein A = 1.6 ± 0.3 g/L and B = 1.1 ± 0.2 g/L. A good correlation was found between the quantities of αs2-casein genetic variants A and F, and β-casein C and C1 with other previously described method. The main important result was obtained for κ-casein because, till now, no data were available on quantification of single genetic variants for this protein. PMID:26304408

  20. Connectivity in grey reef sharks (Carcharhinus amblyrhynchos) determined using empirical and simulated genetic data.

    PubMed

    Momigliano, Paolo; Harcourt, Robert; Robbins, William D; Stow, Adam

    2015-01-01

    Grey reef sharks (Carcharhinus amblyrhynchos) can be one of the numerically dominant high order predators on pristine coral reefs, yet their numbers have declined even in the highly regulated Australian Great Barrier Reef (GBR) Marine Park. Knowledge of both large scale and fine scale genetic connectivity of grey reef sharks is essential for their effective management, but no genetic data are yet available. We investigated grey reef shark genetic structure in the GBR across a 1200 km latitudinal gradient, comparing empirical data with models simulating different levels of migration. The empirical data did not reveal any genetic structuring along the entire latitudinal gradient sampled, suggesting regular widespread dispersal and gene flow of the species throughout most of the GBR. Our simulated datasets indicate that even with substantial migrations (up to 25% of individuals migrating between neighboring reefs) both large scale genetic structure and genotypic spatial autocorrelation at the reef scale were maintained. We suggest that present migration rates therefore exceed this level. These findings have important implications regarding the effectiveness of networks of spatially discontinuous Marine Protected Areas to protect reef sharks. PMID:26314287

  1. Connectivity in grey reef sharks (Carcharhinus amblyrhynchos) determined using empirical and simulated genetic data

    PubMed Central

    Momigliano, Paolo; Harcourt, Robert; Robbins, William D.; Stow, Adam

    2015-01-01

    Grey reef sharks (Carcharhinus amblyrhynchos) can be one of the numerically dominant high order predators on pristine coral reefs, yet their numbers have declined even in the highly regulated Australian Great Barrier Reef (GBR) Marine Park. Knowledge of both large scale and fine scale genetic connectivity of grey reef sharks is essential for their effective management, but no genetic data are yet available. We investigated grey reef shark genetic structure in the GBR across a 1200 km latitudinal gradient, comparing empirical data with models simulating different levels of migration. The empirical data did not reveal any genetic structuring along the entire latitudinal gradient sampled, suggesting regular widespread dispersal and gene flow of the species throughout most of the GBR. Our simulated datasets indicate that even with substantial migrations (up to 25% of individuals migrating between neighboring reefs) both large scale genetic structure and genotypic spatial autocorrelation at the reef scale were maintained. We suggest that present migration rates therefore exceed this level. These findings have important implications regarding the effectiveness of networks of spatially discontinuous Marine Protected Areas to protect reef sharks. PMID:26314287

  2. Genetic variability in four Alouatta species measured by means of nine DNA microsatellite markers: genetic structure and recent bottlenecks.

    PubMed

    Ruiz-Garcia, M; Escobar-Armel, P; Alvarez, D; Mudry, M; Ascunce, M; Gutierrez-Espeleta, G; Shostell, J M

    2007-01-01

    We used microsatellite DNA to study the population genetics of 4 Alouatta species from Central and South America. Our main findings include the following: (1) A. seniculus had the highest level of microsatellite variability while A. caraya and A. palliata had the lowest mean number of alleles per locus and the lowest expected heterozygosity, respectively; (2) the samples of A. seniculus and A. palliata came from different regions and were not in Hardy-Weinberg equilibrium (HWE) which may indicate a Wahlund effect and differentiated gene pools -- in contrast, A. macconnelli and A. caraya were in HWE; (3) the microsatellite genetic heterogeneity of the 4 Alouatta species was similar to the karyotype divergence found among these Alouatta species; the species pair with the lowest level of heterogeneity (genetic differentiation) was A. seniculus/A. caraya, while the Central American species, A. palliata, was highly differentiated from the other 3 South American species; (4) we recommend the establishment of a conservation plan to help protect A. caraya because the Cornuet and Luikart procedure demonstrated a recent bottleneck for this species. PMID:17303937

  3. Quantitative measurement of odor detection thresholds using an air dilution olfactometer, and association with genetic variants in a sample of diverse ancestry

    PubMed Central

    Cook, Gillian R.; Krithika, S; Edwards, Melissa; Kavanagh, Paula

    2014-01-01

    Genetic association studies require a quantitative and reliable method for odor threshold assessment in order to examine the contribution of genetic variants to complex olfactory phenotypes. Our main goal was to assess the feasibility of a portable Scentroid air dilution olfactometer for use in such studies. Using the Scentroid SM110C and the SK5 n-butanol Sensitivity Kit (IDES Canada Inc.), n-butanol odor thresholds were determined for 182 individuals of diverse ancestry (mean age: 20.4 ± 2.5 years; n = 128 female; n = 54 male). Threshold scores from repeat participants were used to calculate a test–retest reliability coefficient, which was statistically significant (r = 0.754, p < 0.001, n = 29), indicating that the Scentroid provides reliable estimates of odor thresholds. In addition, we performed a preliminary genetic analysis evaluating the potential association of n-butanol odor thresholds to six single-nucleotide polymorphisms (SNPs) putatively involved in general olfactory sensitivity (GOS). The results of multiple linear regression analysis revealed no significant association between the SNPs tested and threshold scores. However, our sample size was relatively small, and our study was only powered to identify genetic markers with strong effects on olfactory sensitivity. Overall, we find that the Scentroid provides reliable quantitative measures of odor detection threshold and is well suited for genetic studies of olfactory sensitivity. PMID:25392755

  4. Genetically Determined Dosage of Follicle-Stimulating Hormone (FSH) Affects Male Reproductive Parameters

    PubMed Central

    Grigorova, Marina; Punab, Margus; Ẑilaitienė, Birutė; Erenpreiss, Juris; Ausmees, Kristo; Matuleviĉius, Valentinas; Tsarev, Igor; Jørgensen, Niels

    2011-01-01

    Context: The detailed role of FSH in contributing to male testicular function and fertility has been debated. We have previously identified the association between the T-allele of the FSHB promoter polymorphism (rs10835638; G/T, −211 bp from the mRNA start) and significantly reduced male serum FSH. Objective: In the current study, the T-allele carriers of the FSHB −211 G/T single nucleotide polymorphism represented a natural model for documenting downstream phenotypic consequences of insufficient FSH action. Design and Subjects: We genotyped rs10835638 in the population-based Baltic cohort of young men (n = 1054; GG carriers, n = 796; GT carriers, n = 244; TT carriers, n = 14) recruited by Andrology Centres in Tartu, Estonia; Riga, Latvia; and Kaunas, Lithuania. Marker-trait association testing was performed using linear regression (additive, recessive models) adjusted by age, body mass index, smoking, and recruitment center. Results: Serum hormones directly correlated with the T-allele dosage of rs10835638 included FSH (additive model, P = 1.11 × 10−6; T-allele effect, −0.41 IU/liter), inhibin-B (P = 2.16 × 10−3; T-allele effect, −14.67 pg/ml), and total testosterone (P = 9.30 × 10−3; T-allele effect, −1.46 nmol/liter). Parameters altered only among TT homozygotes were reduced testicular volume (recessive model, P = 1.19 × 10−4; TT genotype effect, −9.47 ml) and increased serum LH (P = 2.25 × 10−2; TT genotype effect, 1.07 IU/liter). The carrier status of rs10835638 alternative genotypes did not affect sperm motility and morphology, calculated free testosterone, serum SHBG, and estradiol concentrations. Conclusion: We showed for the first time that genetically determined low FSH may have wider downstream effects on the male reproductive system, including impaired testes development, altered testicular hormone levels (inhibin-B, total testosterone, LH), and affected male reproductive potential. PMID:21733993

  5. Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential

    PubMed Central

    Kyttälä, Aija; Moraghebi, Roksana; Valensisi, Cristina; Kettunen, Johannes; Andrus, Colin; Pasumarthy, Kalyan Kumar; Nakanishi, Mahito; Nishimura, Ken; Ohtaka, Manami; Weltner, Jere; Van Handel, Ben; Parkkonen, Olavi; Sinisalo, Juha; Jalanko, Anu; Hawkins, R. David; Woods, Niels-Bjarne; Otonkoski, Timo; Trokovic, Ras

    2016-01-01

    Summary Reports on the retention of somatic cell memory in induced pluripotent stem cells (iPSCs) have complicated the selection of the optimal cell type for the generation of iPSC biobanks. To address this issue we compared transcriptomic, epigenetic, and differentiation propensities of genetically matched human iPSCs derived from fibroblasts and blood, two tissues of the most practical relevance for biobanking. Our results show that iPSC lines derived from the same donor are highly similar to each other. However, genetic variation imparts a donor-specific expression and methylation profile in reprogrammed cells that leads to variable functional capacities of iPSC lines. Our results suggest that integration-free, bona fide iPSC lines from fibroblasts and blood can be combined in repositories to form biobanks. Due to the impact of genetic variation on iPSC differentiation, biobanks should contain cells from large numbers of donors. PMID:26777058

  6. [Genetically determined enzyme polymorphism in soy varieties (Glycine max) and in wild soy (Glycine soja)].

    PubMed

    Glazko, V I

    2000-01-01

    Analysis of 22 genetic-biochemical systems (42 loci) in 18 varieties of domestic soybean (G. max) and in 3 population of wild soybean (G. soja) was carried out. The part of polymorphous loci (P), intraspecies genetic differentiation (genetic distances--DN) were higher in domestic plants in comparison with wild ones (P = 45%, 17%: DN = 0.038-0.269, 0.059-0129). The preferable polymorphism of loci, coding the enzymes of glycolysis and Kreb's cycle was revealed in wild species. Domestic soybean had more polymorphous enzyme loci, which did not participate in glucose metabolism in comparison with wild species. The presence of the specific part of the gene pool in ancestor species, which was involved in soybean domestication and forming of varieties was discussed. PMID:10857206

  7. Genetic counseling

    MedlinePlus

    Genetics is the study of heredity, the process of a parent passing certain genes on to their ... certain diseases are also often determined by genes. Genetic counseling is the process where parents can learn ...

  8. Asymmetrical Damage Partitioning in Bacteria: A Model for the Evolution of Stochasticity, Determinism, and Genetic Assimilation

    PubMed Central

    Chao, Lin; Rang, Camilla Ulla; Proenca, Audrey Menegaz; Chao, Jasper Ubirajara

    2016-01-01

    Non-genetic phenotypic variation is common in biological organisms. The variation is potentially beneficial if the environment is changing. If the benefit is large, selection can favor the evolution of genetic assimilation, the process by which the expression of a trait is transferred from environmental to genetic control. Genetic assimilation is an important evolutionary transition, but it is poorly understood because the fitness costs and benefits of variation are often unknown. Here we show that the partitioning of damage by a mother bacterium to its two daughters can evolve through genetic assimilation. Bacterial phenotypes are also highly variable. Because gene-regulating elements can have low copy numbers, the variation is attributed to stochastic sampling. Extant Escherichia coli partition asymmetrically and deterministically more damage to the old daughter, the one receiving the mother’s old pole. By modeling in silico damage partitioning in a population, we show that deterministic asymmetry is advantageous because it increases fitness variance and hence the efficiency of natural selection. However, we find that symmetrical but stochastic partitioning can be similarly beneficial. To examine why bacteria evolved deterministic asymmetry, we modeled the effect of damage anchored to the mother’s old pole. While anchored damage strengthens selection for asymmetry by creating additional fitness variance, it has the opposite effect on symmetry. The difference results because anchored damage reinforces the polarization of partitioning in asymmetric bacteria. In symmetric bacteria, it dilutes the polarization. Thus, stochasticity alone may have protected early bacteria from damage, but deterministic asymmetry has evolved to be equally important in extant bacteria. We estimate that 47% of damage partitioning is deterministic in E. coli. We suggest that the evolution of deterministic asymmetry from stochasticity offers an example of Waddington’s genetic

  9. Asymmetrical Damage Partitioning in Bacteria: A Model for the Evolution of Stochasticity, Determinism, and Genetic Assimilation.

    PubMed

    Chao, Lin; Rang, Camilla Ulla; Proenca, Audrey Menegaz; Chao, Jasper Ubirajara

    2016-01-01

    Non-genetic phenotypic variation is common in biological organisms. The variation is potentially beneficial if the environment is changing. If the benefit is large, selection can favor the evolution of genetic assimilation, the process by which the expression of a trait is transferred from environmental to genetic control. Genetic assimilation is an important evolutionary transition, but it is poorly understood because the fitness costs and benefits of variation are often unknown. Here we show that the partitioning of damage by a mother bacterium to its two daughters can evolve through genetic assimilation. Bacterial phenotypes are also highly variable. Because gene-regulating elements can have low copy numbers, the variation is attributed to stochastic sampling. Extant Escherichia coli partition asymmetrically and deterministically more damage to the old daughter, the one receiving the mother's old pole. By modeling in silico damage partitioning in a population, we show that deterministic asymmetry is advantageous because it increases fitness variance and hence the efficiency of natural selection. However, we find that symmetrical but stochastic partitioning can be similarly beneficial. To examine why bacteria evolved deterministic asymmetry, we modeled the effect of damage anchored to the mother's old pole. While anchored damage strengthens selection for asymmetry by creating additional fitness variance, it has the opposite effect on symmetry. The difference results because anchored damage reinforces the polarization of partitioning in asymmetric bacteria. In symmetric bacteria, it dilutes the polarization. Thus, stochasticity alone may have protected early bacteria from damage, but deterministic asymmetry has evolved to be equally important in extant bacteria. We estimate that 47% of damage partitioning is deterministic in E. coli. We suggest that the evolution of deterministic asymmetry from stochasticity offers an example of Waddington's genetic assimilation

  10. Dispersal ability and habitat requirements determine landscape-level genetic patterns in desert aquatic insects.

    PubMed

    Phillipsen, Ivan C; Kirk, Emily H; Bogan, Michael T; Mims, Meryl C; Olden, Julian D; Lytle, David A

    2015-01-01

    Species occupying the same geographic range can exhibit remarkably different population structures across the landscape, ranging from highly diversified to panmictic. Given limitations on collecting population-level data for large numbers of species, ecologists seek to identify proximate organismal traits-such as dispersal ability, habitat preference and life history-that are strong predictors of realized population structure. We examined how dispersal ability and habitat structure affect the regional balance of gene flow and genetic drift within three aquatic insects that represent the range of dispersal abilities and habitat requirements observed in desert stream insect communities. For each species, we tested for linear relationships between genetic distances and geographic distances using Euclidean and landscape-based metrics of resistance. We found that the moderate-disperser Mesocapnia arizonensis (Plecoptera: Capniidae) has a strong isolation-by-distance pattern, suggesting migration-drift equilibrium. By contrast, population structure in the flightless Abedus herberti (Hemiptera: Belostomatidae) is influenced by genetic drift, while gene flow is the dominant force in the strong-flying Boreonectes aequinoctialis (Coleoptera: Dytiscidae). The best-fitting landscape model for M. arizonensis was based on Euclidean distance. Analyses also identified a strong spatial scale-dependence, where landscape genetic methods only performed well for species that were intermediate in dispersal ability. Our results highlight the fact that when either gene flow or genetic drift dominates in shaping population structure, no detectable relationship between genetic and geographic distances is expected at certain spatial scales. This study provides insight into how gene flow and drift interact at the regional scale for these insects as well as the organisms that share similar habitats and dispersal abilities. PMID:25402260

  11. Genetic parameters for predicted methane production and laser methane detector measurements.

    PubMed

    Pickering, N K; Chagunda, M G G; Banos, G; Mrode, R; McEwan, J C; Wall, E

    2015-01-01

    Enteric ruminant methane is the most important greenhouse gas emitted from the pastoral agricultural systems. Genetic improvement of livestock provides a cumulative and permanent impact on performance, and using high-density SNP panels can increase the speed of improvement for most traits. In this study, a data set of 1,726 dairy cows, collected since 1990, was used to calculate a predicted methane emission (PME) trait from feed and energy intake and requirements based on milk yield, live weight, feed intake, and condition score data. Repeated measurements from laser methane detector (LMD) data were also available from 57 cows. The estimated heritabilities for PME, milk yield, DMI, live weight, condition score, and LMD data were 0.13, 0.25, 0.11, 0.92, 0.38, and 0.05, respectively. There was a high genetic correlation between DMI and PME. No SNP reached the Bonferroni significance threshold for the PME traits. One SNP was within the 3 best SNP for PME at wk 10, 20, 30, and 40. Genomic prediction accuracies between dependent variable and molecular breeding value ranged between 0.26 and 0.30. These results are encouraging; however, more work is required before a PME trait can be implemented in a breeding program. PMID:25403186

  12. Fitting Procedures for Novel Gene-by-Measured Environment Interaction Models in Behavior Genetic Designs

    PubMed Central

    Zheng, Hao; Rathouz, Paul J.

    2015-01-01

    For quantitative behavior genetic (e.g., twin) studies, Purcell proposed a novel model for testing gene-by-measured environment (GxM) interactions while accounting for gene-by-environment correlation. Rathouz et al. expanded this model into a broader class of non-linear biometric models for quantifying and testing such interactions. In this work, we propose a novel factorization of the likelihood for this class of models, and adopt numerical integration techniques to achieve model estimation, especially for those without close-form likelihood. The validity of our procedures is established through numerical simulation studies. The new procedures are illustrated in a twin study analysis of the moderating effect of birth weight on the genetic influences on childhood anxiety. A second example is given in an online appendix. Both the exant GxM models and the new non-linear models critically assume normality of all structural components, which implies continuous, but not normal, manifest response variables. PMID:25732055

  13. Full-Reference Image Quality Assessment with Linear Combination of Genetically Selected Quality Measures

    PubMed Central

    2016-01-01

    Information carried by an image can be distorted due to different image processing steps introduced by different electronic means of storage and communication. Therefore, development of algorithms which can automatically assess a quality of the image in a way that is consistent with human evaluation is important. In this paper, an approach to image quality assessment (IQA) is proposed in which the quality of a given image is evaluated jointly by several IQA approaches. At first, in order to obtain such joint models, an optimisation problem of IQA measures aggregation is defined, where a weighted sum of their outputs, i.e., objective scores, is used as the aggregation operator. Then, the weight of each measure is considered as a decision variable in a problem of minimisation of root mean square error between obtained objective scores and subjective scores. Subjective scores reflect ground-truth and involve evaluation of images by human observers. The optimisation problem is solved using a genetic algorithm, which also selects suitable measures used in aggregation. Obtained multimeasures are evaluated on four largest widely used image benchmarks and compared against state-of-the-art full-reference IQA approaches. Results of comparison reveal that the proposed approach outperforms other competing measures. PMID:27341493

  14. Full-Reference Image Quality Assessment with Linear Combination of Genetically Selected Quality Measures.

    PubMed

    Oszust, Mariusz

    2016-01-01

    Information carried by an image can be distorted due to different image processing steps introduced by different electronic means of storage and communication. Therefore, development of algorithms which can automatically assess a quality of the image in a way that is consistent with human evaluation is important. In this paper, an approach to image quality assessment (IQA) is proposed in which the quality of a given image is evaluated jointly by several IQA approaches. At first, in order to obtain such joint models, an optimisation problem of IQA measures aggregation is defined, where a weighted sum of their outputs, i.e., objective scores, is used as the aggregation operator. Then, the weight of each measure is considered as a decision variable in a problem of minimisation of root mean square error between obtained objective scores and subjective scores. Subjective scores reflect ground-truth and involve evaluation of images by human observers. The optimisation problem is solved using a genetic algorithm, which also selects suitable measures used in aggregation. Obtained multimeasures are evaluated on four largest widely used image benchmarks and compared against state-of-the-art full-reference IQA approaches. Results of comparison reveal that the proposed approach outperforms other competing measures. PMID:27341493

  15. A microsatellite-based genetic linkage map and putative sex-determining genomic regions in Lake Victoria cichlids.

    PubMed

    Kudo, Yu; Nikaido, Masato; Kondo, Azusa; Suzuki, Hikoyu; Yoshida, Kohta; Kikuchi, Kiyoshi; Okada, Norihiro

    2015-04-15

    Cichlid fishes in East Africa have undergone extensive adaptive radiation, which has led to spectacular diversity in their morphology and ecology. To date, genetic linkage maps have been constructed for several tilapias (riverine), Astatotilapia burtoni (Lake Tanganyika), and hybrid lines of Lake Malawi cichlids to facilitate genome-wide comparative analyses. In the present study, we constructed a genetic linkage map of the hybrid line of Lake Victoria cichlids, so that maps of cichlids from all the major areas of East Africa will be available. The genetic linkage map shown here is derived from the F2 progeny of an interspecific cross between Haplochromis chilotes and Haplochromis sauvagei and is based on 184 microsatellite and two single-nucleotide polymorphism (SNP) markers. Most of the microsatellite markers used in the present study were originally designed for other genetic linkage maps, allowing us to directly compare each linkage group (LG) among different cichlid groups. We found 25 LGs, the total length of which was 1133.2cM with an average marker spacing of about 6.09cM. Our subsequent linkage mapping analysis identified two putative sex-determining loci in cichlids. Interestingly, one of these two loci is located on cichlid LG5, on which the female heterogametic ZW locus and several quantitative trait loci (QTLs) related to adaptive evolution have been reported in Lake Malawi cichlids. We also found that V1R1 and V1R2, candidate genes for the fish pheromone receptor, are located very close to the recently detected sex-determining locus on cichlid LG5. The genetic linkage map study presented here may provide a valuable foundation for studying the chromosomal evolution of East African cichlids and the possible role of sex chromosomes in generating their genomic diversity. PMID:25639358

  16. Mouse models for studying genetic influences on factors determining smoking cessation success in humans

    PubMed Central

    Hall, F. Scott; Markou, Athina; Levin, Edward D.; Uhl, George R.

    2014-01-01

    Humans differ in their ability to quit using addictive substances, including nicotine, the major psychoactive ingredient in tobacco. For tobacco smoking, a substantial body of evidence, largely derived from twin studies, indicates that approximately half of these individual differences in ability to quit are heritable [1, 2], genetic influences that likely overlap with those for other addictive substances [3]. Both twin and molecular genetic studies support overlapping influences on nicotine addiction vulnerability and smoking cessation success, although there is little formal analysis of the twin data that supports this important point [2, 3]. None of the current datasets provides clear data concerning which heritable factors might provide robust dimensions around which individuals differ in ability to quit smoking. One approach to this problem is to test mice with genetic variations in genes that contain human variants that alter quit-success. This review considers which features of quit success should be included in a comprehensive approach to elucidating the genetics of quit success, and how those features may be modeled in mice. PMID:22304675

  17. Phylogeography of Pogonomyrmex barbatus and P. rugosus harvester ants with genetic and environmental caste determination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Here we present a phylogeographic study of at least six reproductively isolated lineages of new world harvester ants within the Pogonomyrmex barbatus and P. rugosus species group. The genetic and geographic relationships within this clade are complex: four of the identified lineages are divided into...

  18. Identifying the Environmental Factors That Determine the Genetic Structure of Populations

    PubMed Central

    Foll, Matthieu; Gaggiotti, Oscar

    2006-01-01

    The study of population genetic structure is a fundamental problem in population biology because it helps us obtain a deeper understanding of the evolutionary process. One of the issues most assiduously studied in this context is the assessment of the relative importance of environmental factors (geographic distance, language, temperature, altitude, etc.) on the genetic structure of populations. The most widely used method to address this question is the multivariate Mantel test, a nonparametric method that calculates a correlation coefficient between a dependent matrix of pairwise population genetic distances and one or more independent matrices of environmental differences. Here we present a hierarchical Bayesian method that estimates FST values for each local population and relates them to environmental factors using a generalized linear model. The method is demonstrated by applying it to two data sets, a data set for a population of the argan tree and a human data set comprising 51 populations distributed worldwide. We also carry out a simulation study to investigate the performance of the method and find that it can correctly identify the factors that play a role in the structuring of genetic diversity under a wide range of scenarios. PMID:16951078

  19. Genetic Distances and Variations of Three Clupeid Species Determined by PCR Technique

    PubMed Central

    Choi, Sang-Hoon; Yoon, Jong-Man

    2014-01-01

    In this study, 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 calculated. Euclidean genetic distances within- and between-species were also calculated by complete linkage method with the sustenance of the hierarchical dendevrepogram program Systat version 13. The genomic DNA isolated from herring (Clupea pallasii), Korean anchovy (Coilia nasus) and large-eyed herring (Harengula zunashi), respectively, in the Yellow Sea, were amplified several times by PCR reaction. The hierarchical dendevrepogram shows three chief branches: cluster 1 (PALLASII 01, 02, 03, 04, 06 and 07), cluster 2 (NASUS 08, 09, 10, 11, 12, 13 and 14), and cluster 3 (ZUNASHI 15, 16, 17, 18, 19, 20, 21 and PALLASII 05). In three clupeid species, the shortest genetic distance displaying significant molecular difference was between individual PALLASII no. 03 and PALLASII no. 02 (0.018). Individual no. 06 of PALLASII was most distantly related to NASUS no. 11 (genetic distance = 0.318). Individuals from herring (C. pallasii) species (0.920) exhibited higher bandsharing values than did individuals from Korean anchovy (C. nasus) species (0.872) (P<0.05). As a result, this PCR analysis generated on the genetic data displayed that the herring (C. pallasii) species was widely separated from Korean anchovy (C. nasus) species. Reversely, individuals of Korean anchovy (C. nasus) species were a little closely related to those of large-eyed herring (H. zunashi) species. PMID:25949199

  20. Genetic diversity and phylogenetic relationships among sugarcane and related species determined from microsatellite DNA data

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic diversity and phylogenetic relationships were assessed among 105 clones of commercial sugarcane hybrids and related Saccharum species using 22 microsatellite (SSR) DNA markers. These included 17 sugarcane cultivars from the U.S. mainland, 23 S. officinarum clones, 16 S. robustum clones, 15 ...

  1. Revisiting an Old Riddle: What Determines Genetic Diversity Levels within Species?

    PubMed Central

    Leffler, Ellen M.; Andolfatto, Peter; Przeworski, Molly

    2012-01-01

    Understanding why some species have more genetic diversity than others is central to the study of ecology and evolution, and carries potentially important implications for conservation biology. Yet not only does this question remain unresolved, it has largely fallen into disregard. With the rapid decrease in sequencing costs, we argue that it is time to revive it. PMID:22984349

  2. 78 FR 66891 - Monsanto Co.; Determination of Nonregulated Status of Soybean Genetically Engineered for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... and products altered or produced through genetic engineering that are plant pests or that there is.... In a notice \\2\\ published in the Federal Register on July 13, 2012, (77 FR 41354-41355, Docket No... (77 FR 13258-13260, Docket No. APHIS-2011-0129) a notice describing our public review process...

  3. 75 FR 20560 - Syngenta Biotechnology, Inc.; Determination of Nonregulated Status for Corn Genetically...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-20

    ... and products altered or produced through genetic engineering that are plant pests or that there is... the Federal Register on January 13, 2010 (75 FR 1749-1751, Docket No. APHIS-2009-0072), APHIS... 7 CFR part 340, ``Introduction of Organisms and Products Altered or Produced Through...

  4. 75 FR 32356 - Pioneer Hi-Bred International, Inc.; Determination of Nonregulated Status for Genetically...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-08

    ... and products altered or produced through genetic engineering that are plant pests or that there is...' regulations in 7 CFR part 340. In a notice \\1\\ published in the Federal Register on September 2, 2009 (74 FR... published in the Federal Register on October 26, 2009 (74 FR 54950-54951, Docket No. APHIS-2007-0156),...

  5. 76 FR 37767 - Pioneer Hi-Bred International, Inc.; Determination of Nonregulated Status for Corn Genetically...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ... and products altered or produced through genetic engineering that are plant pests or that there is..., 2011 (76 FR 83-84, Docket No. APHIS-2010-0041), APHIS announced the availability of the Pioneer... regulations in 7 CFR part 340, ``Introduction of Organisms and Products Altered or Produced Through...

  6. 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... Register on July 13, 2012 (77 FR 41366-41367, Docket No. APHIS-2012-0024), APHIS announced the availability... movement, or release into the environment) of organisms and products altered or produced through...

  7. Genetic variability in spotted seatrout (Cynoscion nebulosus), determined with microsatellite DNA markers

    USGS Publications Warehouse

    Ward, R.; Bowers, K.; Hensley, R.; Mobley, B.; Belouski, E.

    2007-01-01

    Variation in the allele frequencies of five microsatellite loci was surveyed in 1256 individual spotted seatrout (Cynoscion nebulosus) obtained from 12 bays and estuaries from Laguna Madre, Texas, to Charlotte Harbor, Florida, to St. John's River on the Florida Atlantic Coast. Texas and Louisiana collection sites were resampled each year for two to four years (1998-2001). Genetic differentiation was observed. Spotted seatrout from Florida waters were strongly differentiated from spotted seatrout collected in Louisiana and Texas. The greatest genetic discontinuity was observed between Tampa Bay and Charlotte Harbor, and Charlotte Harbor seatrout were most similar to Atlantic Coast spotted seatrout. Texas and Louisiana samples were not strongly structured within the northwestern Gulf of Mexico and there was little evidence of temporal differentiation within bays. These findings are contrary to those of earlier analyses with allozymes and mitochondrial DNA (mtDNA) where evidence of spatial differentiation was found for spotted seatrout resident on the Texas coast. The differences in genetic structure observed among these markers may reflect differences in response to selective pressure, or may be due to differences in underlying genetic processes.

  8. 75 FR 8299 - Draft Environmental Impact Statement; Determination of Regulated Status of Alfalfa Genetically...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-24

    ... INFORMATION: On January 12, 2010, we published in the Federal Register (APHIS-2007-0044, 75 FR 1585-1586) a... Agency in the Federal Register on February 5, 2010 (75 FR 6026-6027; Docket No. ER-FRL-8987- 9... Regulated Status of Alfalfa Genetically Engineered for Tolerance to the Herbicide Glyphosate AGENCY:...

  9. Measuring the in situs Kd of a genetically-encoded Ca2+ sensor

    PubMed Central

    Park, J. Genevieve; Palmer, Amy E.

    2016-01-01

    The use of genetically-encoded Ca2+ sensors (GECIs) for long-term monitoring of intracellular Ca2+ has become increasingly common in the last decade. Emission-ratiometric GECIs, such as those in the yellow cameleon family, are capable of making quantitative measurements, meaning that their fluorescence signals can be converted to free Ca2+ concentrations ([Ca2+]free). This conversion is only as accurate as the sensor’s apparent dissociation constant for Ca2+ (Kd’), which depends on temperature, pH, and salt concentration. This protocol describes a method for performing a titration, in living cells (in situ), of cytosolic, nuclear, or mitochondrial sensors. An excellent example of calibration of an ER-targeted sensor is presented elsewhere (Rudolf et al. 2006). PMID:25561615

  10. Determination of Genetic Diversity among Korean Hanwoo Cattle Based on Physical Characteristics

    PubMed Central

    Choi, T. J.; Lee, S. S.; Yoon, D. H.; Kang, H. S.; Kim, C. D.; Hwang, I. H.; Kim, C. Y.; Jin, X.; Yang, C. G.; Seo, K. S.

    2012-01-01

    This study was conducted to establish genetic criteria for phenotypic characteristics of Hanwoo cattle based on allele frequencies and genetic variance analysis using microsatellite markers. Analysis of the genetic diversity among 399 Hanwoo cattle classified according to nose pigmentation and coat color was carried out using 22 microsatellite markers. The results revealed that the INRA035 locus was associated with the highest Fis (0.536). Given that the Fis value for the Hanwoo INRA035 population ranged from 0.533 (white) to 1.000 (white spotted), this finding was consistent with the loci being fixed in Hanwoo cattle. Expected heterozygosities of the Hanwoo groups classified by coat colors and degree of nose pigmentation ranged from 0.689±0.023 (Holstein) to 0.743±0.021 (nose pigmentation level of d). Normal Hanwoo and animals with a mixed white coat showed the closest relationship because the lowest DA value was observed between these groups. However, a pair-wise differentiation test of Fst showed no significant difference among the Hanwoo groups classified by coat color and degree of nose pigmentation (p<0.01). Moreover, results of the neighbor-joining tree based on a DA genetic distance matrix within 399 Hanwoo individuals and principal component analyses confirmed that different groups of cattle with mixed coat color and nose pigmentation formed other specific groups representing Hanwoo genetic and phenotypic characteristics. The results of this study support a relaxation of policies regulating bull selection or animal registration in an effort to minimize financial loss, and could provide basic information that can be used for establishing criteria to classify Hanwoo phenotypes. PMID:25049682

  11. Measuring the Determinants of Relative Economic Performance of Rural Areas

    ERIC Educational Resources Information Center

    Agarwal, Sheela; Rahman, Sanzidur; Errington, Andrew

    2009-01-01

    This paper examines the determinants of economic performance of 149 English rural Local Authority Districts (LADs). A Three Stage Least Square (3SLS) estimation procedure was employed to jointly determine the influence of a wide range of indicators representing economic, human, cultural and environmental capital, as well as less tangible or "soft"…

  12. Determination of uncertainty in parameters extracted from single spectroscopic measurements.

    PubMed

    Sćepanović, Obrad R; Bechtel, Kate L; Haka, Abigail S; Shih, Wei-Chuan; Koo, Tae-Woong; Berger, Andrew J; Feld, Michael S

    2007-01-01

    The ability to quantify uncertainty in information extracted from spectroscopic measurements is important in numerous fields. The traditional approach of repetitive measurements may be impractical or impossible in some measurements scenarios, while chi-squared analysis does not provide insight into the sources of uncertainty. As such, a need exists for analytical expressions for estimating uncertainty and, by extension, minimum detectable concentrations or diagnostic parameters, that can be applied to a single noisy measurement. This work builds on established concepts from estimation theory, such as the Cramer-Rao lower bound on estimator covariance, to present an analytical formula for estimating uncertainty expressed as a simple function of measurement noise, signal strength, and spectral overlap. This formalism can be used to evaluate and improve instrument performance, particularly important for rapid-acquisition biomedical spectroscopy systems. We demonstrate the experimental utility of this expression in assessing concentration uncertainties from spectral measurements of aqueous solutions and diagnostic parameter uncertainties extracted from spectral measurements of human artery tissue. The measured uncertainty, calculated from many independent measurements, is found to be in good agreement with the analytical formula applied to a single spectrum. These results are intended to encourage the widespread use of uncertainty analysis in the biomedical optics community. PMID:18163828

  13. Genetic diversity at neutral and adaptive loci determines individual fitness in a long-lived territorial bird.

    PubMed

    Agudo, Rosa; Carrete, Martina; Alcaide, Miguel; Rico, Ciro; Hiraldo, Fernando; Donázar, José Antonio

    2012-08-22

    There is compelling evidence about the manifest effects of inbreeding depression on individual fitness and populations' risk of extinction. The majority of studies addressing inbreeding depression on wild populations are generally based on indirect measures of inbreeding using neutral markers. However, the study of functional loci, such as genes of the major histocompatibility complex (MHC), is highly recommended. MHC genes constitute an essential component of the immune system of individuals, which is directly related to individual fitness and survival. In this study, we analyse heterozygosity fitness correlations of neutral and adaptive genetic variation (22 microsatellite loci and two loci of the MHC class II, respectively) with the age of recruitment and breeding success of a decimated and geographically isolated population of a long-lived territorial vulture. Our results indicate a negative correlation between neutral genetic diversity and age of recruitment, suggesting that inbreeding may be delaying reproduction. We also found a positive correlation between functional (MHC) genetic diversity and breeding success, together with a specific positive effect of the most frequent pair of cosegregating MHC alleles in the population. Globally, our findings demonstrate that genetic depauperation in small populations has a negative impact on the individual fitness, thus increasing the populations' extinction risk. PMID:22553093

  14. Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies

    PubMed Central

    2014-01-01

    Summary Background The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy). Methods We combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance threshold at p<1·66 × 10−8. Findings We included 8696 cases and 26 157 controls in our analysis. Meta-analysis of the all-epilepsy cohort identified loci at 2q24.3 (p=8·71 × 10−10), implicating SCN1A, and at 4p15.1 (p=5·44 × 10−9), harbouring PCDH7, which encodes a protocadherin molecule not previously implicated in epilepsy. For the cohort of genetic generalised epilepsy, we noted a single signal at 2p16.1 (p=9·99 × 10−9), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy. Interpretation This meta-analysis describes a new locus not previously implicated in epilepsy and provides further evidence about the genetic architecture of these disorders, with the

  15. Multispectral airborne imagery in the field reveals genetic determinisms of morphological and transpiration traits of an apple tree hybrid population in response to water deficit.

    PubMed

    Virlet, Nicolas; Costes, Evelyne; Martinez, Sébastien; Kelner, Jean-Jacques; Regnard, Jean-Luc

    2015-09-01

    Genetic studies of response to water deficit in adult trees are limited by low throughput of the usual phenotyping methods in the field. Here, we aimed at overcoming this bottleneck, applying a new methodology using airborne multispectral imagery and in planta measurements to compare a high number of individuals.An apple tree population, grafted on the same rootstock, was submitted to contrasting summer water regimes over two years. Aerial images acquired in visible, near- and thermal-infrared at three dates each year allowed calculation of vegetation and water stress indices. Tree vigour and fruit production were also assessed. Linear mixed models were built accounting for date and year effects on several variables and including the differential response of genotypes between control and drought conditions.Broad-sense heritability of most variables was high and 18 quantitative trait loci (QTLs) independent of the dates were detected on nine linkage groups of the consensus apple genetic map. For vegetation and stress indices, QTLs were related to the means, the intra-crown heterogeneity, and differences induced by water regimes. Most QTLs explained 15-20% of variance.Airborne multispectral imaging proved relevant to acquire simultaneous information on a whole tree population and to decipher genetic determinisms involved in response to water deficit. PMID:26208644

  16. Multispectral airborne imagery in the field reveals genetic determinisms of morphological and transpiration traits of an apple tree hybrid population in response to water deficit

    PubMed Central

    Virlet, Nicolas; Costes, Evelyne; Martinez, Sébastien; Kelner, Jean-Jacques; Regnard, Jean-Luc

    2015-01-01

    Genetic studies of response to water deficit in adult trees are limited by low throughput of the usual phenotyping methods in the field. Here, we aimed at overcoming this bottleneck, applying a new methodology using airborne multispectral imagery and in planta measurements to compare a high number of individuals. An apple tree population, grafted on the same rootstock, was submitted to contrasting summer water regimes over two years. Aerial images acquired in visible, near- and thermal-infrared at three dates each year allowed calculation of vegetation and water stress indices. Tree vigour and fruit production were also assessed. Linear mixed models were built accounting for date and year effects on several variables and including the differential response of genotypes between control and drought conditions. Broad-sense heritability of most variables was high and 18 quantitative trait loci (QTLs) independent of the dates were detected on nine linkage groups of the consensus apple genetic map. For vegetation and stress indices, QTLs were related to the means, the intra-crown heterogeneity, and differences induced by water regimes. Most QTLs explained 15−20% of variance. Airborne multispectral imaging proved relevant to acquire simultaneous information on a whole tree population and to decipher genetic determinisms involved in response to water deficit. PMID:26208644

  17. Half of the T-cell repertoire combinatorial diversity is genetically determined in humans and humanized mice.

    PubMed

    Pham, Hang-Phuong; Manuel, Manuarii; Petit, Nicolas; Klatzmann, David; Cohen-Kaminsky, Sylvia; Six, Adrien; Marodon, Gilles

    2012-03-01

    In humanized mice, the T-cell repertoire is derived from genetically identical human progenitors in distinct animals. Thus, careful comparison of the T-cell repertoires of humanized mice with those of humans may reveal the contribution of genetic determinism on T-cell repertoire formation. Here, we performed a comprehensive assessment of the distribution of V-J combinations of the human β chain of the T-cell receptor (hTRBV) in NOD.SCID.γc(-/-) (NSG) humanized mice. We observed that numerous V-J combinations were equally distributed in the thymus and in the periphery of humanized mice compared with human references. A global analysis of the data, comparing repertoire perturbation indices in humanized NSG mice and unrelated human PBMCs, reveals that 50% of the hTRBV families significantly overlapped. Using multivariate ranking and bootstrap analyses, we found that 18% of all possible V-J combinations contributed close to 50% of the expressed diversity, with significant over-representation of BV5-J1.1+1.2 and BV6-J1.1+1.2 rearrangements. Finally, comparison of CD3(-) and CD3(+) thymocyte repertoires indicated that the observed V-J combination overlap was already present before TCR-MHC selection in the thymus. Altogether, our results show that half of the T-cell repertoire combinatorial diversity in humans is genetically determined. PMID:22105329

  18. The Roles of Standing Genetic Variation and Evolutionary History in Determining the Evolvability of Anti-Predator Strategies

    PubMed Central

    Dworkin, Ian; Wagner, Aaron P.

    2014-01-01

    Standing genetic variation and the historical environment in which that variation arises (evolutionary history) are both potentially significant determinants of a population's capacity for evolutionary response to a changing environment. Using the open-ended digital evolution software Avida, we evaluated the relative importance of these two factors in influencing evolutionary trajectories in the face of sudden environmental change. We examined how historical exposure to predation pressures, different levels of genetic variation, and combinations of the two, affected the evolvability of anti-predator strategies and competitive abilities in the presence or absence of threats from new, invasive predator populations. We show that while standing genetic variation plays some role in determining evolutionary responses, evolutionary history has the greater influence on a population's capacity to evolve anti-predator traits, i.e. traits effective against novel predators. This adaptability likely reflects the relative ease of repurposing existing, relevant genes and traits, and the broader potential value of the generation and maintenance of adaptively flexible traits in evolving populations. PMID:24955847

  19. Determining Qualtiy Factors of Eggs from Microwave Permittivity Measurements

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dielectric properties of albumen and yolk of eggs were measured at 24 oC over the frequency range from 10 MHz to 1800 MHz to monitor quality changes during a 5-week storage period at 15 oC. Quality factors such as Haugh unit, yolk index, moisture content and egg weight were also measured during the...

  20. Determination of parameters of a nuclear reactor through noise measurements

    DOEpatents

    Cohn, C.E.

    1975-07-15

    A method of measuring parameters of a nuclear reactor by noise measurements is described. Noise signals are developed by the detectors placed in the reactor core. The polarity coincidence between the noise signals is used to develop quantities from which various parameters of the reactor can be calculated. (auth)

  1. Genetic determination of sibship and twin zygosity in a case of an alleged double infant homicide.

    PubMed

    von Wurmb-Schwark, Nicole; Schwark, Thorsten

    2009-04-01

    A 32 year-old woman was hospitalised with severe septic symptoms. The examination of the patient revealed placenta residues in the woman's uterus as cause of the infection. The police was called and investigated her apartment in search of the missing baby. Finally, the bodies of two newborn babies were found in the freezer. According to the mother, the babies were stillborn twins. The autopsy revealed that the smaller, moderately putrefied child was stillborn, while the larger infant showed typical signs of drowning and only slight putrefaction. The placenta was judged by gynaecologists to be that of a single pregnancy. Thus the prosecution suspected that the woman had had two independent pregnancies and ordered an additional genetic analysis. A genetic analysis clearly revealed that the babies were monozygotic twins, supporting the mother's statement of a twin pregnancy. PMID:19269233

  2. The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

    PubMed Central

    Pereyra, Florencia; Jia, Xiaoming; McLaren, Paul J.; Telenti, Amalio; de Bakker, Paul I.W.; Walker, Bruce D.; Jia, Xiaoming; McLaren, Paul J.; Ripke, Stephan; Brumme, Chanson J.; Pulit, Sara L.; Telenti, Amalio; Carrington, Mary; Kadie, Carl M.; Carlson, Jonathan M.; Heckerman, David; de Bakker, Paul I.W.; Pereyra, Florencia; de Bakker, Paul I.W.; Graham, Robert R.; Plenge, Robert M.; Deeks, Steven G.; Walker, Bruce D.; Gianniny, Lauren; Crawford, Gabriel; Sullivan, Jordan; Gonzalez, Elena; Davies, Leela; Camargo, Amy; Moore, Jamie M.; Beattie, Nicole; Gupta, Supriya; Crenshaw, Andrew; Burtt, Noël P.; Guiducci, Candace; Gupta, Namrata; Carrington, Mary; Gao, Xiaojiang; Qi, Ying; Yuki, Yuko; Pereyra, Florencia; Piechocka-Trocha, Alicja; Cutrell, Emily; Rosenberg, Rachel; Moss, Kristin L.; Lemay, Paul; O’Leary, Jessica; Schaefer, Todd; Verma, Pranshu; Toth, Ildiko; Block, Brian; Baker, Brett; Rothchild, Alissa; Lian, Jeffrey; Proudfoot, Jacqueline; Alvino, Donna Marie L.; Vine, Seanna; Addo, Marylyn M.; Allen, Todd M.; Altfeld, Marcus; Henn, Matthew R.; Le Gall, Sylvie; Streeck, Hendrik; Walker, Bruce D.; Haas, David W.; Kuritzkes, Daniel R.; Robbins, Gregory K.; Shafer, Robert W.; Gulick, Roy M.; Shikuma, Cecilia M.; Haubrich, Richard; Riddler, Sharon; Sax, Paul E.; Daar, Eric S.; Ribaudo, Heather J.; Agan, Brian; Agarwal, Shanu; Ahern, Richard L.; Allen, Brady L.; Altidor, Sherly; Altschuler, Eric L.; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Anderson, Val; Andrady, Ushan; Antoniskis, Diana; Bangsberg, David; Barbaro, Daniel; Barrie, William; Bartczak, J.; Barton, Simon; Basden, Patricia; Basgoz, Nesli; Bazner, Suzane; Bellos, Nicholaos C.; Benson, Anne M.; Berger, Judith; Bernard, Nicole F.; Bernard, Annette M.; Birch, Christopher; Bodner, Stanley J.; Bolan, Robert K.; Boudreaux, Emilie T.; Bradley, Meg; Braun, James F.; Brndjar, Jon E.; Brown, Stephen J.; Brown, Katherine; Brown, Sheldon T.; Burack, Jedidiah; Bush, Larry M.; Cafaro, Virginia; Campbell, Omobolaji; Campbell, John; Carlson, Robert H.; Carmichael, J. Kevin; Casey, Kathleen K.; Cavacuiti, Chris; Celestin, Gregory; Chambers, Steven T.; Chez, Nancy; Chirch, Lisa M.; Cimoch, Paul J.; Cohen, Daniel; Cohn, Lillian E.; Conway, Brian; Cooper, David A.; Cornelson, Brian; Cox, David T.; Cristofano, Michael V.; Cuchural, George; Czartoski, Julie L.; Dahman, Joseph M.; Daly, Jennifer S.; Davis, Benjamin T.; Davis, Kristine; Davod, Sheila M.; Deeks, Steven G.; DeJesus, Edwin; Dietz, Craig A.; Dunham, Eleanor; Dunn, Michael E.; Ellerin, Todd B.; Eron, Joseph J.; Fangman, John J.W.; Farel, Claire E.; Ferlazzo, Helen; Fidler, Sarah; Fleenor-Ford, Anita; Frankel, Renee; Freedberg, Kenneth A.; French, Neel K.; Fuchs, Jonathan D.; Fuller, Jon D.; Gaberman, Jonna; Gallant, Joel E.; Gandhi, Rajesh T.; Garcia, Efrain; Garmon, Donald; Gathe, Joseph C.; Gaultier, Cyril R.; Gebre, Wondwoosen; Gilman, Frank D.; Gilson, Ian; Goepfert, Paul A.; Gottlieb, Michael S.; Goulston, Claudia; Groger, Richard K.; Gurley, T. Douglas; Haber, Stuart; Hardwicke, Robin; Hardy, W. David; Harrigan, P. Richard; Hawkins, Trevor N.; Heath, Sonya; Hecht, Frederick M.; Henry, W. Keith; Hladek, Melissa; Hoffman, Robert P.; Horton, James M.; Hsu, Ricky K.; Huhn, Gregory D.; Hunt, Peter; Hupert, Mark J.; Illeman, Mark L.; Jaeger, Hans; Jellinger, Robert M.; John, Mina; Johnson, Jennifer A.; Johnson, Kristin L.; Johnson, Heather; Johnson, Kay; Joly, Jennifer; Jordan, Wilbert C.; Kauffman, Carol A.; Khanlou, Homayoon; Killian, Robert K.; Kim, Arthur Y.; Kim, David D.; Kinder, Clifford A.; Kirchner, Jeffrey T.; Kogelman, Laura; Kojic, Erna Milunka; Korthuis, P. Todd; Kurisu, Wayne; Kwon, Douglas S.; LaMar, Melissa; Lampiris, Harry; Lanzafame, Massimiliano; Lederman, Michael M.; Lee, David M.; Lee, Jean M.L.; Lee, Marah J.; Lee, Edward T.Y.; Lemoine, Janice; Levy, Jay A.; Llibre, Josep M.; Liguori, Michael A.; Little, Susan J.; Liu, Anne Y.; Lopez, Alvaro J.; Loutfy, Mono R.; Loy, Dawn; Mohammed, Debbie Y.; Man, Alan; Mansour, Michael K.; Marconi, Vincent C.; Markowitz, Martin; Marques, Rui; Martin, Jeffrey N.; Martin, Harold L.; Mayer, Kenneth Hugh; McElrath, M. Juliana; McGhee, Theresa A.; McGovern, Barbara H.; McGowan, Katherine; McIntyre, Dawn; Mcleod, Gavin X.; Menezes, Prema; Mesa, Greg; Metroka, Craig E.; Meyer-Olson, Dirk; Miller, Andy O.; Montgomery, Kate; Mounzer, Karam C.; Nagami, Ellen H.; Nagin, Iris; Nahass, Ronald G.; Nelson, Margret O.; Nielsen, Craig; Norene, David L.; O’Connor, David H.; Ojikutu, Bisola O.; Okulicz, Jason; Oladehin, Olakunle O.; Oldfield, Edward C.; Olender, Susan A.; Ostrowski, Mario; Owen, William F.; Pae, Eunice; Parsonnet, Jeffrey; Pavlatos, Andrew M.; Perlmutter, Aaron M.; Pierce, Michael N.; Pincus, Jonathan M.; Pisani, Leandro; Price, Lawrence Jay; Proia, Laurie; Prokesch, Richard C.; Pujet, Heather Calderon; Ramgopal, Moti; Rathod, Almas; Rausch, Michael; Ravishankar, J.; Rhame, Frank S.; Richards, Constance Shamuyarira; Richman, Douglas D.; Robbins, Gregory K.; Rodes, Berta; Rodriguez, Milagros; Rose, Richard C.; Rosenberg, Eric S.; Rosenthal, Daniel; Ross, Polly E.; Rubin, David S.; Rumbaugh, Elease; Saenz, Luis; Salvaggio, Michelle R.; Sanchez, William C.; Sanjana, Veeraf M.; Santiago, Steven; Schmidt, Wolfgang; Schuitemaker, Hanneke; Sestak, Philip M.; Shalit, Peter; Shay, William; Shirvani, Vivian N.; Silebi, Vanessa I.; Sizemore, James M.; Skolnik, Paul R.; Sokol-Anderson, Marcia; Sosman, James M.; Stabile, Paul; Stapleton, Jack T.; Starrett, Sheree; Stein, Francine; Stellbrink, Hans-Jurgen; Sterman, F. Lisa; Stone, Valerie E.; Stone, David R.; Tambussi, Giuseppe; Taplitz, Randy A.; Tedaldi, Ellen M.; Telenti, Amalio; Theisen, William; Torres, Richard; Tosiello, Lorraine; Tremblay, Cecile; Tribble, Marc A.; Trinh, Phuong D.; Tsao, Alice; Ueda, Peggy; Vaccaro, Anthony; Valadas, Emilia; Vanig, Thanes J.; Vecino, Isabel; Vega, Vilma M.; Veikley, Wenoah; Wade, Barbara H.; Walworth, Charles; Wanidworanun, Chingchai; Ward, Douglas J.; Warner, Daniel A.; Weber, Robert D.; Webster, Duncan; Weis, Steve; Wheeler, David A.; White, David J.; Wilkins, Ed; Winston, Alan; Wlodaver, Clifford G.; Wout, Angelique van’t; Wright, David P.; Yang, Otto O.; Yurdin, David L.; Zabukovic, Brandon W.; Zachary, Kimon C.; Zeeman, Beth; Zhao, Meng

    2011-01-01

    Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection. PMID:21051598

  3. Genetic Determinants for Gestational Diabetes Mellitus and Related Metabolic Traits in Mexican Women

    PubMed Central

    Huerta-Chagoya, Alicia; Vázquez-Cárdenas, Paola; Moreno-Macías, Hortensia; Tapia-Maruri, Leonardo; Rodríguez-Guillén, Rosario; López-Vite, Erika; García-Escalante, Guadalupe; Escobedo-Aguirre, Fernando; Parra-Covarrubias, Adalberto; Cordero-Brieño, Roberto; Manzo-Carrillo, Lizette; Zacarías-Castillo, Rogelio; Aguilar-Salinas, Carlos; Tusié-Luna, Teresa

    2015-01-01

    Epidemiological and physiological similarities among Gestational Diabetes Mellitus (GDM) and Type 2 Diabetes (T2D) suggest that both diseases, share a common genetic background. T2D risk variants have been associated to GDM susceptibility. However, the genetic architecture of GDM is not yet completely understood. We analyzed 176 SNPs for 115 loci previously associated to T2D, GDM and body mass index (BMI), as well as a set of 118 Ancestry Informative Markers (AIMs), in 750 pregnant Mexican women. Association with GDM was found for two of the most frequently replicated T2D loci: a TCF7L2 haplotype (CTTC: rs7901695, rs4506565, rs7903146, rs12243326; P=2.16x10-06; OR=2.95) and a KCNQ1 haplotype (TTT: rs2237892, rs163184, rs2237897; P=1.98x10-05; OR=0.55). In addition, we found two loci associated to glycemic traits: CENTD2 (60’ OGTT glycemia: rs1552224, P=0.03727) and MTNR1B (HOMA B: rs1387153, P=0.05358). Remarkably, a major susceptibility SLC16A11 locus for T2D in Mexicans was not shown to play a role in GDM risk. The fact that two of the main T2D associated loci also contribute to the risk of developing GDM in Mexicans, confirm that both diseases share a common genetic background. However, lack of association with a Native American contribution T2D risk haplotype, SLC16A11, suggests that other genetic mechanisms may be in play for GDM. PMID:25973943

  4. Genetic Determinants of Atherosclerosis, Obesity and Energy Balance in Consomic Mice

    PubMed Central

    Spiezio, Sabrina H.; Amon, Lynn M.; McMillen, Timothy S.; Vick, Cynthia M.; Houston, Barbara A.; Caldwell, Mark; Ogimoto, Kayoko; Morton, Gregory J.; Kirk, Elizabeth A.; Schwartz, Michael W.; Nadeau, Joseph H.; LeBoeuf, Renée C.

    2014-01-01

    Metabolic diseases such as obesity and atherosclerosis result from complex interactions between environmental factors and genetic variants. A panel of chromosome substitution strains (CSSs) was developed to characterize genetic and dietary factors contributing to metabolic diseases and other biological traits and biomedical conditions. Our goal here was to identify quantitative trait loci (QTLs) contributing to obesity, energy expenditure and atherosclerosis. Parental strains C57BL/6 and A/J together with a panel of 21 CSSs derived from these progenitors were subjected to chronic feeding of rodent chow and atherosclerotic (females) or diabetogenic (males) test diets, and evaluated for a variety of metabolic phenotypes including several traits unique to this report, namely fat pad weights, energy balance and atherosclerosis. A total of 297 QTLs across 35 traits were discovered, two of which provided significant protection from atherosclerosis, and several dozen QTLs modulated body weight, body composition and circulating lipid levels in females and males. While several QTLs confirmed previous reports, most QTLs were novel. Finally, we applied the CSS quantitative genetic approach to energy balance, and identified three novel QTLs controlling energy expenditure and one QTL modulating food intake. Overall, we identified many new QTLs and phenotyped several novel traits in this mouse model of diet-induced metabolic diseases. PMID:25001233

  5. Genetic determinants of atherosclerosis, obesity, and energy balance in consomic mice.

    PubMed

    Spiezio, Sabrina H; Amon, Lynn M; McMillen, Timothy S; Vick, Cynthia M; Houston, Barbara A; Caldwell, Mark; Ogimoto, Kayoko; Morton, Gregory J; Kirk, Elizabeth A; Schwartz, Michael W; Nadeau, Joseph H; LeBoeuf, Renée C

    2014-12-01

    Metabolic diseases such as obesity and atherosclerosis result from complex interactions between environmental factors and genetic variants. A panel of chromosome substitution strains (CSSs) was developed to characterize genetic and dietary factors contributing to metabolic diseases and other biological traits and biomedical conditions. Our goal here was to identify quantitative trait loci (QTLs) contributing to obesity, energy expenditure, and atherosclerosis. Parental strains C57BL/6 and A/J together with a panel of 21 CSSs derived from these progenitors were subjected to chronic feeding of rodent chow and atherosclerotic (females) or diabetogenic (males) test diets, and evaluated for a variety of metabolic phenotypes including several traits unique to this report, namely fat pad weights, energy balance, and atherosclerosis. A total of 297 QTLs across 35 traits were discovered, two of which provided significant protection from atherosclerosis, and several dozen QTLs modulated body weight, body composition, and circulating lipid levels in females and males. While several QTLs confirmed previous reports, most QTLs were novel. Finally, we applied the CSS quantitative genetic approach to energy balance, and identified three novel QTLs controlling energy expenditure and one QTL modulating food intake. Overall, we identified many new QTLs and phenotyped several novel traits in this mouse model of diet-induced metabolic diseases. PMID:25001233

  6. Farming termites determine the genetic population structure of Termitomyces fungal symbionts.

    PubMed

    Nobre, Tânia; Fernandes, Cecília; Boomsma, Jacobus J; Korb, Judith; Aanen, Duur K

    2011-05-01

    Symbiotic interactions between macrotermitine termites and their fungal symbionts have a moderate degree of specificity. Consistent with horizontal symbiont transmission, host switching has been frequent over evolutionary time so that single termite species can often be associated with several fungal symbionts. However, even in the few termite lineages that secondarily adopted vertical symbiont transmission, the fungal symbionts are not monophyletic. We addressed this paradox by studying differential transmission of fungal symbionts by alate male and female reproductives, and the genetic population structure of Termitomyces fungus gardens across 74 colonies of Macrotermes bellicosus in four west and central African countries. We confirm earlier, more limited, studies showing that the Termitomyces symbionts of M. bellicosus are normally transmitted vertically and clonally by dispersing males. We also document that the symbionts associated with this termite species belong to three main lineages that do not constitute a monophyletic group. The most common lineage occurs over the entire geographical region that we studied, including west, central and southern Africa, where it is also associated with the alternative termite hosts Macrotermes subhyalinus and Macrotermes natalensis. While Termitomyces associated with these alternative hosts are horizontally transmitted and recombine freely, the genetic population structure of the same Termitomyces associated with M. bellicosus is consistent with predominantly clonal reproduction and only occasional recombination. This implies that the genetic population structure of Termitomyces is controlled by the termite host and not by the Termitomyces symbiont. PMID:21410808

  7. Relationship between obesity phenotypes and genetic determinants in a mouse model for juvenile obesity.

    PubMed

    Brockmann, Gudrun A; Schäfer, Nadine; Hesse, Claudia; Heise, Sebastian; Neuschl, Christina; Wagener, Asja; Churchill, Gary A; Li, Renhua

    2013-09-16

    Obesity, a state of imbalance between lean mass and fat mass, is important for the etiology of diseases affected by the interplay of multiple genetic and environmental factors. Although genome-wide association studies have repeatedly associated genes with obesity and body weight, the mechanisms underlying the interaction between the muscle and adipose tissues remain unknown. Using 351 mice (at 10 wk of age) of an intercross population between Berlin Fat Mouse Inbred (BFMI) and C57BL/6NCrl (B6N) mice, we examined the causal relationships between genetic variations and multiple traits: body lean mass and fat mass, adipokines, and bone mineral density. Furthermore, evidence from structural equation modeling suggests causality among these traits. In the BFMI model, juvenile obesity affects lean mass and impairs bone mineral density via adipokines secreted from the white adipose tissues. While previous studies have indicated that lean mass has a causative effect on adiposity, in the Berlin Fat Mouse model that has been selected for juvenile obesity (at 9 wk of age) for >90 generations, however, the causality is switched from fat mass to lean mass. In addition, linkage studies and statistical modeling have indicated that quantitative trait loci on chromosomes 5 and 6 affect both lean mass and fat mass. These lines of evidence indicate that the muscle and adipose tissues interact with one another and the interaction is modulated by genetic variations that are shaped by selections. Experimental examinations are necessary to verify the biological role of the inferred causalities. PMID:23922126

  8. The Pakistan Risk of Myocardial Infarction Study: a resource for the study of genetic, lifestyle and other determinants of myocardial infarction in South Asia

    PubMed Central

    2009-01-01

    The burden of coronary heart disease (CHD) is increasing at a greater rate in South Asia than in any other region globally, but there is little direct evidence about its determinants. The Pakistan Risk of Myocardial Infarction Study (PROMIS) is an epidemiological resource to enable reliable study of genetic, lifestyle and other determinants of CHD in South Asia. By March 2009, PROMIS had recruited over 5,000 cases of first-ever confirmed acute myocardial infarction (MI) and over 5,000 matched controls aged 30–80 years. For each participant, information has been recorded on demographic factors, lifestyle, medical and family history, anthropometry, and a 12-lead electrocardiogram. A range of biological samples has been collected and stored, including DNA, plasma, serum and whole blood. During its next stage, the study aims to expand recruitment to achieve a total of about 20,000 cases and about 20,000 controls, and, in subsets of participants, to enrich the resource by collection of monocytes, establishment of lymphoblastoid cell lines, and by resurveying participants. Measurements in progress include profiling of candidate biochemical factors, assay of 45,000 variants in 2,100 candidate genes, and a genomewide association scan of over 650,000 genetic markers. We have established a large epidemiological resource for CHD in South Asia. In parallel with its further expansion and enrichment, the PROMIS resource will be systematically harvested to help identify and evaluate genetic and other determinants of MI in South Asia. Findings from this study should advance scientific understanding and inform regionally appropriate disease prevention and control strategies. PMID:19404752

  9. Differential plague-transmission dynamics determine Yersinia pestis population genetic structure on local, regional, and global scales

    PubMed Central

    Girard, Jessica M.; Wagner, David M.; Vogler, Amy J.; Keys, Christine; Allender, Christopher J.; Drickamer, Lee C.; Keim, Paul

    2004-01-01

    Plague, the disease caused by the bacterium Yersinia pestis, has greatly impacted human civilization. Y. pestis is a successful global pathogen, with active foci on all continents except Australia and Antarctica. Because the Y. pestis genome is highly monomorphic, previous attempts to characterize the population genetic structure within a single focus have been largely unsuccessful. Here we report that highly mutable marker loci allow determination of Y. pestis population genetic structure and tracking of transmission patterns at two spatial scales within a single focus. In addition, we found that in vitro mutation rates for these loci are similar to those observed in vivo, which allowed us to develop a mutation-rate-based model to examine transmission mechanisms. Our model suggests there are two primary components of plague ecology: a rapid expansion phase for population growth and dispersal followed by a slower persistence phase. This pattern seems consistent across local, regional, and even global scales. PMID:15173603

  10. Phenotypic and genetic variation in leptin as determinants of weight regain

    PubMed Central

    Rudich, A; Meiner, V; Schwarzfuchs, D; Sharon, N; Shpitzen, S; Blüher, M; Stumvoll, M; Thiery, J; Fiedler, GM; Friedlander, Y; Leiterstdorf, E; Shai, I

    2016-01-01

    Aims Over 75% of obese subjects fail to maintain their weight following weight loss interventions. We aimed to identify phenotypic and genetic markers associated with weight maintenance/regain following a dietary intervention. Subjects and methods In the 2-year Dietary Intervention Randomized Controlled Trial, we assessed potential predictors for weight changes during the ‘weight loss phase’ (0–6 months) and the ‘weight maintenance/regain phase’ (7–24 months). Genetic variation between study participants was studied using single-nucleotide polymorphisms in the leptin gene (LEP). Results Mean weight reduction was −5.5% after 6 months, with a mean weight regain of 1.2% of baseline weight during the subsequent 7–24 months. In a multivariate regression model, higher baseline high-molecular-weight adiponectin was the only biomarker predictor of greater success in 0- to 6-month weight loss (β = −0.222, P-value = 0.044). In a multivariate regression model adjusted for 6-month changes in weight and various biomarkers, 6-month plasma leptin reduction exhibited the strongest positive association with 6-month weight loss (β = 0.505, P-value<0.001). Conversely, 6-month plasma leptin reduction independently predicted weight regain during the following 18 months (β = −0.131, P-value<.013). Weight regain was higher among participants who had a greater (top tertiles) 6-month decrease in both weight and leptin (+ 3.4% (95% confidence interval 2.1–4.8)) as compared with those in the lowest combined tertiles (+ 0.2% (95% confidence interval −1.1 to 1.4)); P-value<0.001. Weight regain was further significantly and independently associated with genetic variations in LEP (P = 0.006 for both rs4731426 and rs2071045). Adding genetic data to the phenotypic multivariate model increased its predictive value for weight regain by 34%. Conclusion Although greater reduction in leptin concentrations during the initial phase of a dietary intervention is associated with

  11. The genetic contribution to sex determination and number of sex chromosomes vary among populations of common frogs (Rana temporaria).

    PubMed

    Rodrigues, N; Vuille, Y; Brelsford, A; Merilä, J; Perrin, N

    2016-07-01

    The patterns of sex determination and sex differentiation have been shown to differ among geographic populations of common frogs. Notably, the association between phenotypic sex and linkage group 2 (LG2) has been found to be perfect in a northern Swedish population, but weak and variable among families in a southern one. By analyzing these populations with markers from other linkage groups, we bring two new insights: (1) the variance in phenotypic sex not accounted for by LG2 in the southern population could not be assigned to genetic factors on other linkage groups, suggesting an epigenetic component to sex determination; (2) a second linkage group (LG7) was found to co-segregate with sex and LG2 in the northern population. Given the very short timeframe since post-glacial colonization (in the order of 1000 generations) and its seemingly localized distribution, this neo-sex chromosome system might be the youngest one described so far. It does not result from a fusion, but more likely from a reciprocal translocation between the original Y chromosome (LG2) and an autosome (LG7), causing their co-segregation during male meiosis. By generating a strict linkage between several important genes from the sex-determination cascade (Dmrt1, Amh and Amhr2), this neo-sex chromosome possibly contributes to the 'differentiated sex race' syndrome (strictly genetic sex determination and early gonadal development) that characterizes this northern population. PMID:27071845

  12. Genetic variants of CDH13 determine the susceptibility to chronic obstructive pulmonary disease in a Chinese population

    PubMed Central

    Yuan, Yi-ming; Zhang, Jin-long; Xu, Si-cheng; Ye, Ren-song; Xu, Dan; Zhang, You; Zhang, Yan-Jie; Chen, Yu-long; Liu, Yu-lan; Su, Zhi-guang

    2016-01-01

    Aim: Adiponectin has been implicated in the development of chronic obstructive pulmonary disease (COPD). The CDH13 gene encodes T-cadherin that is an adiponectin receptor, and genetic variants of CDH13 determine blood adiponectin levels. The aim of this study was to investigate the effects of CDH13 variants on COPD susceptibility in a Chinese population. Methods: Ten single-nucleotide polymorphisms (SNP) in CDH13 were screened using the SNaPshot method in 279 COPD patients and 367 control subjects. Association of genotypes or haplotypes constructed from these loci with COPD was analyzed in different genetic models. Results: Among the 10 SNPs tested, rs4783244 and rs12922394 exhibited significant differences in allele or genotype frequencies between COPD patients and control subjects, whereas 8 other SNPs did not. The minor allele T was associated with decreased risk of COPD in the recessive model at rs4783244 (OR=0.42, P=0.023) and in the dominant model at rs12922394 (OR=0.70, P=0.022). The genotype TT at either rs4783244 or rs12922394 was associated with a significantly low level of plasma adiponectin when compared to genotypes GG and CC (P<0.05). Haplotypes GC in block 1 (rs4783244-rs12922394) as well as GTAC and ATGT in block 3 (rs4783266-rs11640522-rs11646849-rs11860282) significantly increased the risk of COPD, whereas haplotypes TT in block 1, TG in block 2 (rs11646011- rs11640875) and ATGC in block 3 were protective against COPD. Conclusion: CDH13 genetic variants determine Chinese individuals' susceptibility to COPD and thus are efficient genetic biomarkers for early detection of COPD. PMID:26806298

  13. DETERMINING UNCERTAINTY IN PHYSICAL PARAMETER MEASUREMENTS BY MONTE CARLO SIMULATION

    EPA Science Inventory

    A statistical approach, often called Monte Carlo Simulation, has been used to examine propagation of error with measurement of several parameters important in predicting environmental transport of chemicals. These parameters are vapor pressure, water solubility, octanol-water par...

  14. Perturbing engine performance measurements to determine optimal engine control settings

    DOEpatents

    Jiang, Li; Lee, Donghoon; Yilmaz, Hakan; Stefanopoulou, Anna

    2014-12-30

    Methods and systems for optimizing a performance of a vehicle engine are provided. The method includes determining an initial value for a first engine control parameter based on one or more detected operating conditions of the vehicle engine, determining a value of an engine performance variable, and artificially perturbing the determined value of the engine performance variable. The initial value for the first engine control parameter is then adjusted based on the perturbed engine performance variable causing the engine performance variable to approach a target engine performance variable. Operation of the vehicle engine is controlled based on the adjusted initial value for the first engine control parameter. These acts are repeated until the engine performance variable approaches the target engine performance variable.

  15. Experimental infrared measurements for hydrocarbon pollutant determination in subterranean waters

    NASA Astrophysics Data System (ADS)

    Lay-Ekuakille, A.; Palamara, I.; Caratelli, D.; Morabito, F. C.

    2013-01-01

    Subterranean waters are often polluted by industrial and anthropic effluents that are drained in subsoil. To prevent and control pollution, legislations of different developed countries require an online monitoring measurement, especially for detecting organic solvents (chlorinated and unchlorinated ones). Online measurements include both real-time and no real-time measurements. In general, it is difficult to implement real-time measurements in stricto sensu for online acquisitions on aqueous effluents since they need to be processed by a modeling. This research presents an experimental measurement system based on infrared (IR) spectroscopy for aqueous effluents containing hydrocarbons and capable of displaying excellent values of pollutant concentrations even in instable conditions; the system is able to detect pollutants either in laminar or turbulent flow. The results show the possibility of avoiding the use of "Pitot tube" that is employed to create a stagnation point in order to convert kinetic energy into potential one. This conversion allows the transformation of a turbulent flow in a laminar flow making easy measurement of pollutants included in an aqueous effluent. Obviously, "Pitot tube" is also used for other fluid effluents. The obtained results have been compared with those produced by means of sophisticated IR instrumentation for laboratory applications.

  16. Genetic and Pharmacokinetic Determinants of Response to Transdermal Nicotine in White, Black and Asian Non-Smokers

    PubMed Central

    Dempsey, Delia A.; St Helen, Gideon; Jacob, Peyton; Tyndale, Rachel F.; Benowitz, Neal L.

    2013-01-01

    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 (Caucasian, Blacks and Asian), wore 7 mg nicotine skin patches for up to 8 hours. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in 9 subjects and was strongly associated with rate of rise and peak concentrations of plasma nicotine. Toxicity, 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 the latter are used for treating medical conditions in non-smokers, and possibly in vulnerability to developing nicotine dependence. PMID:23933970

  17. Investigation of the genetic association between quantitative measures of psychosis and schizophrenia: a polygenic risk score analysis.

    PubMed

    Derks, Eske M; Vorstman, Jacob A S; Ripke, Stephan; Kahn, Rene S; Ophoff, Roel A

    2012-01-01

    The presence of subclinical levels of psychosis in the general population may imply that schizophrenia is the extreme expression of more or less continuously distributed traits in the population. In a previous study, we identified five quantitative measures of schizophrenia (positive, negative, disorganisation, mania, and depression scores). The aim of this study is to examine the association between a direct measure of genetic risk of schizophrenia and the five quantitative measures of psychosis. Estimates of the log of the odds ratios of case/control allelic association tests were obtained from the Psychiatric GWAS Consortium (PGC) (minus our sample) which included genome-wide genotype data of 8,690 schizophrenia cases and 11,831 controls. These data were used to calculate genetic risk scores in 314 schizophrenia cases and 148 controls from the Netherlands for whom genotype data and quantitative symptom scores were available. The genetic risk score of schizophrenia was significantly associated with case-control status (p<0.0001). In the case-control sample, the five psychosis dimensions were found to be significantly associated with genetic risk scores; the correlations ranged between.15 and.27 (all p<.001). However, these correlations were not significant in schizophrenia cases or controls separately. While this study confirms the presence of a genetic risk for schizophrenia as categorical diagnostic trait, we did not find evidence for the genetic risk underlying quantitative schizophrenia symptom dimensions. This does not necessarily imply that a genetic basis is nonexistent, but does suggest that it is distinct from the polygenic risk score for schizophrenia. PMID:22761660

  18. Investigation of the Genetic Association between Quantitative Measures of Psychosis and Schizophrenia: A Polygenic Risk Score Analysis

    PubMed Central

    Ripke, Stephan; Kahn, Rene S.; Ophoff, Roel A.

    2012-01-01

    The presence of subclinical levels of psychosis in the general population may imply that schizophrenia is the extreme expression of more or less continuously distributed traits in the population. In a previous study, we identified five quantitative measures of schizophrenia (positive, negative, disorganisation, mania, and depression scores). The aim of this study is to examine the association between a direct measure of genetic risk of schizophrenia and the five quantitative measures of psychosis. Estimates of the log of the odds ratios of case/control allelic association tests were obtained from the Psychiatric GWAS Consortium (PGC) (minus our sample) which included genome-wide genotype data of 8,690 schizophrenia cases and 11,831 controls. These data were used to calculate genetic risk scores in 314 schizophrenia cases and 148 controls from the Netherlands for whom genotype data and quantitative symptom scores were available. The genetic risk score of schizophrenia was significantly associated with case-control status (p<0.0001). In the case-control sample, the five psychosis dimensions were found to be significantly associated with genetic risk scores; the correlations ranged between.15 and.27 (all p<.001). However, these correlations were not significant in schizophrenia cases or controls separately. While this study confirms the presence of a genetic risk for schizophrenia as categorical diagnostic trait, we did not find evidence for the genetic risk underlying quantitative schizophrenia symptom dimensions. This does not necessarily imply that a genetic basis is nonexistent, but does suggest that it is distinct from the polygenic risk score for schizophrenia. PMID:22761660

  19. The European Prader-Willi Syndrome Clinical Research Database: An Aid in the Investigation of a Rare Genetically Determined Neurodevelopmental Disorder

    ERIC Educational Resources Information Center

    Holland, A.; Whittington, J.; Cohen, O.; Curfs, L.; Delahaye, F.; Dudley, O.; Horsthemke, B.; Lindgren, A. -C.; Nourissier, C.; Sharma, N.; Vogels, A.

    2009-01-01

    Background: Prader-Willi Syndrome (PWS) is a rare genetically determined neurodevelopmental disorder with a complex phenotype that changes with age. The rarity of the syndrome and the need to control for different variables such as genetic sub-type, age and gender limits clinical studies of sufficient size in any one country. A clinical research…

  20. Determination of Thermal Spray Coating Property with Curvature Measurements

    NASA Astrophysics Data System (ADS)

    Dwivedi, Gopal; Nakamura, Toshio; Sampath, Sanjay

    2013-12-01

    Real-time curvature measurement of a coating-substrate system during deposition has facilitated the monitoring of coating stresses and provided additional insights into thermal spray deposition mechanisms. However, the non-equilibrium state of coating formation along with harsh spray booth environment introduces complexity not only in data interpretation but also in the coating properties estimation. In this paper, a new procedure is proposed to estimate the elastic modulus of thermal sprayed ceramic coatings using in situ curvature and temperature measurements. In order to correlate the measurable parameters to coating elastic modulus, a systematic study is conducted to develop a suitable methodology. First, various finite element model analyses are carried out to formulate suitable relations between the measurements and elastic modulus. Subsequently, experiments are conducted to validate the procedure to estimate coating moduli. The results are compared with more accurate measurements obtained from post-deposition characterization technique under low temperature thermal cycles. The comparison suggests that the moduli estimated using the proposed procedure are in good agreements with those obtained from the post-deposition technique. Further, the nonlinear response of coatings are evaluated from the estimated moduli during deposition and cool down, which offer additional information on the characteristics of thermal spray coatings.

  1. Microbial metabolic activity in soil as measured by dehydrogenase determinations

    NASA Technical Reports Server (NTRS)

    Casida, L. E., Jr.

    1977-01-01

    The dehydrogenase technique for measuring the metabolic activity of microorganisms in soil was modified to use a 6-h, 37 C incubation with either glucose or yeast extract as the electron-donating substrate. The rate of formazan production remained constant during this time interval, and cellular multiplication apparently did not occur. The technique was used to follow changes in the overall metabolic activities of microorganisms in soil undergoing incubation with a limiting concentration of added nutrient. The sequence of events was similar to that obtained by using the Warburg respirometer to measure O2 consumption. However, the major peaks of activity occurred earlier with the respirometer. This possibly is due to the lack of atmospheric CO2 during the O2 consumption measurements.

  2. Sonographic measurement versus mapping for determination of residual ridge width.

    PubMed

    Traxler, M; Ulm, C; Solar, P; Lill, W

    1992-03-01

    To achieve long-term success of dental implants, evaluation of the dimensions of the resorbing alveolar process must be accurate because an implant should be surrounded by at least 1 mm of bone. Estimating the thickness of bone is more difficult because the mucosal contour can mask the actual dimension of the residual ridge. With ultrasound, it is possible to analyze and visualize the diameter of maxillary or mandibular residual ridges. Data obtained from ultrasound measurement of residual ridges were compared with the data from ridge mapping with the Wilson bone caliper and the Spoerlein caliper. The ultrasound measurement produced nearly the same data at all measurement points as ridge mapping. Ultrasound also provides exact information about the location of the mental foramen and the maxillary sinus. By using all three methods the initial stage of implant treatment can be planned. PMID:1507101

  3. Can UK fossil fuel emissions be determined by radiocarbon measurements?

    NASA Astrophysics Data System (ADS)

    Wenger, Angelina; O'Doherty, Simon; Rigby, Matthew; Manning, Alistair; Palmer, Paul

    2016-04-01

    The GAUGE project evaluates different methods to estimate UK emissions. However, estimating carbon dioxide emissions as a result of fossil fuel burning is challenging as natural fluxes in and out of the atmosphere are very large. Radiocarbon (14C) measurements offer a way to specifically measure the amount of recently added carbon dioxide from fossil fuel burning. This is possible as, due to their age, all the radiocarbon in fossil fuels has decayed. Hence the amount of recently added CO2 from fossil fuel burning can be measured as a depletion of the 14C content in air. While this method has been successfully applied by several groups on a city or a regional scale, this is the first attempt at using the technique for a national emission estimate. Geographically the UK, being an island, is a good location for such an experiment. But are 14CO2 measurements the ideal solution for estimating fossil fuel emissions as they are heralded to be? Previous studies have shown that 14CO2emissions from the nuclear industry mask the 14C depletion caused by fossil fuel burning and result in an underestimation of the fossil fuel CO2. While this might not be a problem in certain regions around the world, many countries like the UK have a substantial nuclear industry. A correction for this enhancement from the nuclear industry can be applied but are invariably difficult as 14CO2emissions from nuclear power plants have a high temporal variability. We will explain how our sampling strategy was chosen to minimize the influence form the nuclear industry and why this proved to be challenging. In addition we present the results from our ground based measurements to show why trying to estimate national emissions using radiocarbon measurements was overambitious, and how practical the technique is for the UK in general.

  4. Determination of Physical Parameters in Organic Bulk Heterojunction Solar Cells Using a Genetic Algorithm

    NASA Astrophysics Data System (ADS)

    Nishida, Kouhei; Oka, Masaki; Hase, Hiroyuki; Naito, Hiroyoshi

    A method is presented to extract the physical parameters of illuminated organic bulk-heterojunction solar cells based on genetic algorithms and Levenberg-Marquardt method. The solar cell model is the well known single diode equivalent circuit containing four components. The voltage dependence of the photocurrent in the organic solar cells due to electron and hole drift lengths is taken into account. The applicability of the present method is demonstrated by fitting current - voltage characteristics of poly-3-hexylthiophene (P3HT) and [6,6]- phenyl-C61-butyric acid methyl ester (PCBM) bulk-heretojunction solar cells at different light intensities and annealing temperatures.

  5. Markerless Escherichia coli rrn Deletion Strains for Genetic Determination of Ribosomal Binding Sites.

    PubMed

    Quan, Selwyn; Skovgaard, Ole; McLaughlin, Robert E; Buurman, Ed T; Squires, Catherine L

    2015-12-01

    Single-copy rrn strains facilitate genetic ribosomal studies in Escherichia coli. Consecutive markerless deletion of rrn operons resulted in slower growth upon inactivation of the fourth copy, which was reversed by supplying transfer RNA genes encoded in rrn operons in trans. Removal of the sixth, penultimate rrn copy led to a reduced growth rate due to limited rrn gene dosage. Whole-genome sequencing of variants of single-copy rrn strains revealed duplications of large stretches of genomic DNA. The combination of selective pressure, resulting from the decreased growth rate, and the six identical remaining scar sequences, facilitating homologous recombination events, presumably leads to elevated genomic instability. PMID:26438293

  6. Determination of particle size using measurement of scatter

    NASA Technical Reports Server (NTRS)

    Scott, R. L., Jr.

    1976-01-01

    Scatter from glass beads placed on a mirror was measured using a quartz lamp and laser. Data were obtained in the plane containing the normal to the surface and the incident beam. For the quartz lamp the best correlation can be obtained for data measured at a zenith of 55 deg and 180 deg from the incident beam. The best correlation when the laser is used is obtained at about the same position. However, the correlation variables are angular spacing of the minimums of the data versus the size. Whereas, with the quartz lamp the correlation variables are the amount of scattered energy versus size.

  7. Determination of sterilization effectiveness by measuring bacterial growth in a biological indicator through firefly luciferase determination of ATP.

    PubMed

    Webster, J J; Walker, B G; Ford, S R; Leach, F R

    1988-01-01

    A bioluminescence procedure for measurement of microbial ATP allows a rapid determination of the effectiveness of autoclave sterilization. This determination is achieved faster than detection of acid production in a biological indicator via a pH indicator. Bacterial outgrowth from spores on test strips of the biological indicator was detected by measurement of ATP using the firefly luciferase reaction. A measureable increase in ATP was found after 5 hours of incubation of a biological indicator that had been treated under sterilizing conditions that produced 75% sterility of the biological indicator as measured by acid production. This is a marked improvement over the 24-48 hours of incubation currently required. PMID:3213598

  8. Sediment-generated noise (SGN): Laboratory determination of measurement volume

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Passive acoustic technology has the potential to allow continuous measurement of bedload moving through streams by recording Sediment-Generated Noise (SGN) from interactions between coarse bedload particles. The technology is relatively economical and is amenable to automated operation. While the ...

  9. Some measurements for determining strangeness matrix elements in the nucleon

    SciTech Connect

    Henley, E.M.; Pollock, S.J.; Ying, S. ); Frederico, T. , Sao Jose dos Campos, SP . Inst. de Estudos Avancados); Krein, . Inst. de Fisica Teorica); Williams, A.G. )

    1991-01-01

    Some experiments to measure strangeness matrix elements of the proton are proposed. Two of these suggestions are described in some detail, namely electro-production of phi mesons and the difference between neutrino and antineutrino scattering for isospin zero targets such as deuterium.

  10. Some measurements for determining strangeness matrix elements in the nucleon

    SciTech Connect

    Henley, E.M.; Pollock, S.J.; Ying, S.; Frederico, T.; Krein,; Williams, A.G.

    1991-12-31

    Some experiments to measure strangeness matrix elements of the proton are proposed. Two of these suggestions are described in some detail, namely electro-production of phi mesons and the difference between neutrino and antineutrino scattering for isospin zero targets such as deuterium.

  11. Measuring Financial Capability and Its Determinants Using Survey Data

    ERIC Educational Resources Information Center

    Taylor, Mark

    2011-01-01

    Financial capability, or people's ability to manage and take control of their finances, is receiving increasing interest among policy makers as more people find themselves in difficult financial situations during the current economic downturn. We tackle the problem of how to measure financial capability--with a specific focus on making ends meet…

  12. Using reflectance measurements to determine light use efficiency in corn

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examines the ability of narrow band vegetation indexes to detect spectral changes associated with stress and relate them to light use efficiency (LUE) over the course of a day as well as through the growing season. In a corn field in Beltsville, MD, carbon flux measurements were made at a...

  13. 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.

    1987-01-01

    The ability of satellite-borne radar altimeter data to measure the global ocean surface with high precision and dense spatial coverage provides a unique tool for the mapping of the Earth's gravity field and its geoid. The altimeter crossover measurements, created by differencing direct altimeter measurements at the subsatellite points where the orbit ground tracks intersect, have the distinct advantage of eliminating geoid error and other nontemporal or long period oceanographic features. In the 1990's, the joint U.S./French TOPEX/POSEIDON mission and the European Space Agency's ERS-1 mission will carry radar altimeter instruments capable of global ocean mapping with high precision. This investigation aims at the development and application of dynamically consistent direct altimeter and altimeter crossover measurement models to the simultaneous mapping of the Earth's gravity field and its geoid, the ocean tides and the quasi-stationary component of the dynamic sea surface topography. Altimeter data collected by SEASAT, GEOS-3, and GEOSAT are used for the investigation.

  14. Solubility determination as an alternative to migration measurements.

    PubMed

    Bodai, Zsolt; Jakab, Péter Pál; Novák, Márton; Nyiri, Zoltán; Szabó, Bálint Sámuel; Rikker, Tamás; Eke, Zsuzsanna

    2016-03-01

    Solubility values for six UV stabilisers (Cyasorb UV-1164, Tinuvin P, Tinuvin 234, Tinuvin 326, Tinuvin 327 and Tinuvin 1577) and five antioxidants (Irgafos 168, Irganox 1010, Irganox 3114, Irganox 3790 and Irganox 565) were determined in all the liquid food simulants (3% (m/V) acetic acid-water mixture, 10% (V/V), 20% (V/V), 50% (V/V) ethanol-water mixture and vegetable oil) proposed in European Union Regulation No. 10/2011/EC, as well as in fruit juice and cola drink. The applied method was obtained by modification of the method for the determination of water solubility as described in OECD guideline Test No. 105. By using ultrasonication and shorter equilibration time, the time demand of the solubility determinations were decreased notably. Solubility values proved to be lower than the specific migration limits (as specified in 10/2011/EC) at 25°C for almost all target compounds in food simulants A, B, C and D1 as well as in fruit juice and cola drink. The exceptions were Tinuvin P and Irganox 3790 in simulant D1. The solubility in food simulant D2 was higher than 1000 µg ml(-1) for all target compounds. These results show that the solubility of some additives in food simulants can be so low that it makes migration studies for certain additive-food simulant pairs dispensable. PMID:26898268

  15. Genetic determination of nephrogenesis: the Pax/Eya/Six gene network.

    PubMed

    Brodbeck, Stephan; Englert, Christoph

    2004-03-01

    Development of the kidney serves as a paradigm to understand the mechanisms underlying the formation of an organ. The first sign of kidney development is the interaction between two tissues derived from the intermediate mesoderm, the metanephrogenic mesenchyme and the nephric duct. Many of the genes that play a crucial role in early kidney development, such as Pax2, Eya1, Six1, Six2, Sall1, Foxc1, Wt1, and the Hox11 genes, are expressed in the mesenchyme and encode transcription factors that--with few exceptions--are involved in regulation of the Gdnf gene. Moreover, mutations in a number of these genes in humans are associated with kidney diseases. Interestingly, many of the components regulating early kidney development are conserved throughout evolution and are also involved in eye and muscle formation in mammals, as well as in eye development in Drosophila. Genetic and biochemical studies in Drosophila and mice indicate that these genes and their respective products act in a complex network of interdependencies and positive and negative feedback loops. Genetic experiments have allowed us to begin to characterize the complex interactions between the individual components, but it will require additional biochemical and functional experiments to eventually understand the molecular functions of each of the participating proteins. PMID:14673635

  16. Determination of near-optimum use of hospital diagnostic resources using the "GENES" genetic algorithm shell.

    PubMed

    Bickel, A S; Bickel, R W

    1990-01-01

    "GENES", a genetic algorithm shell developed by the authors, was used to optimize allocation of hospital resources for a small set of hypothetical patients. GENES creates a random population of rule sets of the IF..THEN type, which are variable in both the number of rules in each set and in the size of each rule. GENES applies each rule set to a patient data base, ranks the goodness of each set as applied, and uses the mechanisms of population genetics, i.e. mutation, crossover, inversion and survival of the fittest, to create a new, and often improved generation of rule sets. It also allows for the time dependent nature of medical tests, the possibility of injury associated with those tests, and the fact that results may not always be conclusive. Using 10-11 artificially created patients admitted under the diagnosis of possible gall bladder disease, a rule set was obtained which selected a testing strategy from a list of available hospital resources and correctly diagnosed all patients at minimum cost in no more than 3807 generations. PMID:2183963

  17. Evidence of Heterogeneity by Race/Ethnicity in Genetic Determinants of QT Interval

    PubMed Central

    Seyerle, Amanda A.; Young, Alicia M.; Jeff, Janina M.; Melton, Phillip E.; Jorgensen, Neal W.; Lin, Yi; Carty, Cara L.; Deelman, Ewa; Heckbert, Susan R.; Hindorff, Lucia A.; Jackson, Rebecca D.; Martin, Lisa W.; Okin, Peter M; Perez, Marco V.; Psaty, Bruce M.; Soliman, Elsayed Z.; Whitsel, Eric A.; North, Kari E; Laston, Sandra; Kooperberg, Charles; Avery, Christy L.

    2015-01-01

    Background QT-interval (QT) prolongation is an established risk factor for ventricular tachyarrhythmia and sudden cardiac death. Previous genome-wide association studies in populations of the European descent have identified multiple genetic loci that influence QT, but few have examined these loci in ethnically diverse populations. Methods Here, we examine the direction, magnitude, and precision of effect sizes for 21 previously reported SNPs from 12 QT loci, in populations of European (n=16,398), African (n=5,437), American Indian (n=5,032), Hispanic (n=1,143), and Asian (n=932) descent as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. Estimates obtained from linear regression models stratified by race/ethnicity were combined using inverse-variance weighted meta-analysis. Heterogeneity was evaluated using Cochran's Q test. Results Of 21 SNPs, seven showed consistent direction of effect across all five populations, and an additional nine had estimated effects that were consistent across four populations. Despite consistent direction of effect, nine of 16 SNPs had evidence (P < 0.05) of heterogeneity by race/ethnicity. For these 9 SNPs, linkage disequilibrium plots often indicated substantial variation in linkage disequilibrium patterns among the various racial/ethnic groups, as well as possible allelic heterogeneity. Conclusions These results emphasize the importance of analyzing racial/ethnic groups separately in genetic studies. Furthermore, they underscore the possible utility of trans-ethnic studies to pinpoint underlying casual variants influencing heritable traits such as QT. PMID:25166880

  18. The distribution of transgene insertion sites in barley determined by physical and genetic mapping.

    PubMed Central

    Salvo-Garrido, Haroldo; Travella, Silvia; Bilham, Lorelei J; Harwood, Wendy A; Snape, John W

    2004-01-01

    The exact site of transgene insertion into a plant host genome is one feature of the genetic transformation process that cannot, at present, be controlled and is often poorly understood. The site of transgene insertion may have implications for transgene stability and for potential unintended effects of the transgene on plant metabolism. To increase our understanding of transgene insertion sites in barley, a detailed analysis of transgene integration in independently derived transgenic barley lines was carried out. Fluorescence in situ hybridization (FISH) was used to physically map 23 transgene integration sites from 19 independent barley lines. Genetic mapping further confirmed the location of the transgenes in 11 of these lines. Transgene integration sites were present only on five of the seven barley chromosomes. The pattern of transgene integration appeared to be nonrandom and there was evidence of clustering of independent transgene insertion events within the barley genome. In addition, barley genomic regions flanking the transgene insertion site were isolated for seven independent lines. The data from the transgene flanking regions indicated that transgene insertions were preferentially located in gene-rich areas of the genome. These results are discussed in relation to the structure of the barley genome. PMID:15280249

  19. Colorectal adenomatous polyposis syndromes: Genetic determinism, clinical presentation and recommendations for care.

    PubMed

    Buecher, Bruno

    2016-02-01

    Colorectal adenomatous polyposis constitutes a diverse group of disorders with different modes of inheritance. Molecular diagnosis of this condition has become more complex. In fact, somatic mosaicism for APC mutations now appears to be more frequent than previously thought and rare germline alterations of this gene may be implicated in patients tested negative for "classical" APC mutations (point mutations and large genomic rearrangements). Moreover, the knowledge concerning several aspects of the MUTYH-associated polyposis has improved since its first description in 2002 and germline mutations in new genes have recently been implicated in some cases of unexplained adenomatous polyposis. Genetic testing in probands and their relatives should be conducted in the context of pre- and post-test genetic counseling. The recent advent of New Generation Sequencing (NGS) techniques affords the opportunity to rapidly screen patients for a comprehensive panel of colorectal cancer susceptibility genes in a cost-effective fashion. This type of approach will probably replace the classical sequential approach based on clinical presumptive diagnoses in the near future. The risk of colorectal cancer is very high in affected patients in the absence of appropriate care. Clinical management is complex and should be provided in centers with special expertise in these diseases. This review focuses on the various colorectal adenomatous polyposis syndromes with special attention to more innovative and important aspects. PMID:26805944

  20. Families with familial combined hyperlipidemia and families enriched for coronary artery disease share genetic determinants for the atherogenic lipoprotein phenotype

    SciTech Connect

    Allayee, H.; Aouizerat, B.E.; Lusis, A.J.; Cantor, R.M.; Lanning, C.D.; Rotter, J.I.; Dallinga-Thie, G.M.; Krauss, R.M.; Bruin, T.W.A. de

    1998-08-01

    Small, dense LDL particles consistently have been associated with hypertriglyceridemia, premature coronary artery disease (CAD), and familial combined hyperlipidemia (FCH). Previously, the authors have observed linkage of LDL particle size with four separate candidate-gene loci in a study of families enriched for CAD. These loci contain the genes for manganese superoxide dismutase (MnSOD), on chromosome 6q; for apolipoprotein AI-CIII-AIV, on chromosome 11q; for cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl-transferase (LCAT), on chromosome 16q; and for the LDL receptor (LDLR), on chromosome 19p. The authors have now tested whether these loci also contribute to LDL particle size in families ascertained for FCH. The members of 18 families (481 individuals) were typed for genetic markers at the four loci, and linkage to LDL particle size was assessed by nonparametric sib-pair linkage analysis. The presence of small, dense LDL (pattern B) was much more frequent in the FCH probands than in the spouse controls. Evidence for linkage was observed at the MnSOD (P = .02), CETP/LCAT (P = .03), and apolipoprotein AI0CIII0AIV loci (P = .005) but not at the LDLR locus. The authors conclude that there is a genetically based association between FCH and small, dense LDL and that the genetic determinants for LDL particle size are shared, at least in part, among FCH families and the more general population at risk for CAD.

  1. Genetic markers that influence feed efficiency phenotypes also affect cattle temperament as measured by flight speed.

    PubMed

    Lindholm-Perry, A K; Kuehn, L A; Freetly, H C; Snelling, W M

    2015-02-01

    Flight speed is a predictive indicator of cattle temperament and is associated with feed efficiency phenotypes. Genetic markers associated with both traits may assist with selection of calmer animals with improved economic value. A preliminary genome-wide association study determined chromosomal regions on BTA9, and 17 were associated with flight speed. The genes quaking (QKI), glutamate receptor, ionotropic, AMPA 2 (GRIA2) and glycine receptor β (GLRB) were identified in these regions as potential functional candidates. Beef steers (n = 1057) were genotyped with SNPs located within and flanking these genes. One SNP located near QKI and one near GRIA2 were nominally associated with flight speed (P ≤ 0.05) although neither was significant after Bonferroni correction. Several studies have shown a correlation between flight speed and feed intake or gain; therefore, we also analyzed SNPs on BTA6:38-39 Mb known to be associated with average daily gain (ADG) and average daily feed intake (ADFI) for association with flight speed. Several SNPs on BTA6 were associated with flight speed (P ≤ 0.005), and three were significant after Bonferroni correction. These results suggest that the genes tested are unlikely to contribute to flight speed variation for our cattle population, but SNPs on BTA6 associated with ADG and ADFI may influence temperament. Use of these markers to select for economically important feed efficiency phenotypes may produce cattle with more desirable temperaments. PMID:25515066

  2. The Use of Mn(II) Bound to His-tags as Genetically Encodable Spin-Label for Nanometric Distance Determination in Proteins.

    PubMed

    Ching, H Y Vincent; Mascali, Florencia C; Bertrand, Hélène C; Bruch, Eduardo M; Demay-Drouhard, Paul; Rasia, Rodolfo M; Policar, Clotilde; Tabares, Leandro C; Un, Sun

    2016-03-17

    A genetically encodable paramagnetic spin-label capable of self-assembly from naturally available components would offer a means for studying the in-cell structure and interactions of a protein by electron paramagnetic resonance (EPR). Here, we demonstrate pulse electron-electron double resonance (DEER) measurements on spin-labels consisting of Mn(II) ions coordinated to a sequence of histidines, so-called His-tags, that are ubiquitously added by genetic engineering to facilitate protein purification. Although the affinity of His-tags for Mn(II) was low (800 μM), Mn(II)-bound His-tags yielded readily detectable DEER time traces even at concentrations expected in cells. We were able to determine accurately the distance between two His-tag Mn(II) spin-labels at the ends of a rigid helical polyproline peptide of known structure, as well as at the ends of a completely cell-synthesized 3-helix bundle. This approach not only greatly simplifies the labeling procedure but also represents a first step towards using self-assembling metal spin-labels for in-cell distance measurements. PMID:26938795

  3. Associating optical measurements and estimating orbits of geocentric objects with a Genetic Algorithm: performance limitations.

    NASA Astrophysics Data System (ADS)

    Zittersteijn, Michiel; Schildknecht, Thomas; Vananti, Alessandro; Dolado Perez, Juan Carlos; Martinot, Vincent

    2016-07-01

    Currently several thousands of objects are being tracked in the MEO and GEO regions through optical means. With the advent of improved sensors and a heightened interest in the problem of space debris, it is expected that the number of tracked objects will grow by an order of magnitude in the near future. This research aims to provide a method that can treat the correlation and orbit determination problems simultaneously, and is able to efficiently process large data sets with minimal manual intervention. This problem is also known as the Multiple Target Tracking (MTT) problem. The complexity of the MTT problem is defined by its dimension S. Current research tends to focus on the S = 2 MTT problem. The reason for this is that for S = 2 the problem has a P-complexity. However, with S = 2 the decision to associate a set of observations is based on the minimum amount of information, in ambiguous situations (e.g. satellite clusters) this will lead to incorrect associations. The S > 2 MTT problem is an NP-hard combinatorial optimization problem. In previous work an Elitist Genetic Algorithm (EGA) was proposed as a method to approximately solve this problem. It was shown that the EGA is able to find a good approximate solution with a polynomial time complexity. The EGA relies on solving the Lambert problem in order to perform the necessary orbit determinations. This means that the algorithm is restricted to orbits that are described by Keplerian motion. The work presented in this paper focuses on the impact that this restriction has on the algorithm performance.

  4. Determination of soil moisture distribution from impedance and gravimetric measurements

    NASA Technical Reports Server (NTRS)

    Ungar, Stephen G.; Layman, Robert; Campbell, Jeffrey E.; Walsh, John; Mckim, Harlan J.

    1992-01-01

    Daily measurements of the soil dielectric properties at 5 and 10 cm were obtained at five locations throughout the First ISLSCP Field Experiment (FIFE) test site during the 1987 intensive field campaigns (IFCs). An automated vector voltmeter was used to monitor the complex electrical impedance, at 10 MHz, of cylindrical volumes of soil delineated by specially designed soil moisture probes buried at these locations. The objective of this exercise was to test the hypothesis that the soil impedance is sensitive to the moisture content of the soil and that the imaginary part (that is, capacitive reactance) can be used to calculate the volumetric water content of the soil. These measurements were compared with gravimetric samples collected at these locations by the FIFE staff science team.

  5. Determining Transmission Loss from Measured External and Internal Acoustic Environments

    NASA Technical Reports Server (NTRS)

    Scogin, Tyler; Smith, A. M.

    2012-01-01

    An estimate of the internal acoustic environment in each internal cavity of a launch vehicle is needed to ensure survivability of Space Launch System (SLS) avionics. Currently, this is achieved by using the noise reduction database of heritage flight vehicles such as the Space Shuttle and Saturn V for liftoff and ascent flight conditions. Marshall Space Flight Center (MSFC) is conducting a series of transmission loss tests to verify and augment this method. For this test setup, an aluminum orthogrid curved panel representing 1/8th of the circumference of a section of the SLS main structure was mounted in between a reverberation chamber and an anechoic chamber. Transmission loss was measured across the panel using microphones. Data measured during this test will be used to estimate the internal acoustic environments for several of the SLS launch vehicle internal spaces.

  6. Determining biological tissue optical properties via integrating sphere spatial measurements

    DOEpatents

    Baba, Justin S.; Letzen, Brian S.

    2011-01-11

    An optical sample is mounted on a spatial-acquisition apparatus that is placed in or on an enclosure. An incident beam is irradiated on a surface of the sample and the specular reflection is allowed to escape from the enclosure through an opening. The spatial-acquisition apparatus is provided with a light-occluding slider that moves in front of the sample to block portions of diffuse scattering from the sample. As the light-occluding slider moves across the front of the sample, diffuse light scattered into the area of the backside of the light-occluding slider is absorbed by back side surface of the light-occluding slider. By measuring a baseline diffuse reflectance without a light-occluding slider and subtracting measured diffuse reflectance with a light-occluding slider therefrom, diffuse reflectance for the area blocked by the light-occluding slider can be calculated.

  7. Recent advances in the understanding and treatment of anxiety disorders. Resilience: determinants, measurement, and treatment responsiveness.

    PubMed

    Connor, Kathryn M; Zhang, Wei

    2006-10-01

    In human terms, resilience is an ability to cope with stress and varies with context, time, age, gender, and cultural origin. Resilience shifts the focus of psychological investigation onto increasing the positive rather than reducing the negative. Inquiry into resilience has evolved from descriptions of resilient qualities, to discovery of the process to attain resilience, to uncovering the motivation to reintegrate in a resilient manner. Much of the research on resilience has focused on children in settings such as family violence, extreme poverty, war, and natural disasters. A coherent pattern of characteristics associated with successful adaptation has emerged. Salient characteristics include commitment, dynamism, humor in the face of adversity, patience, optimism, faith, and altruism. As such, resilience may represent an important target of treatment in anxiety, depression, and stress reactions. Resilience can be quantified, but available measures need to be validated transculturally. There exist many possible determinants of resilience, including neurobiologic, genetic, temperament, and environmental influences. Resilience is modifiable on individual and cultural levels. Posttraumatic stress disorder is an example of a serious disorder associated with impaired stress coping that can improve with treatment. PMID:17008825

  8. Phylogeography of Pogonomyrmex barbatus and P. rugosus harvester ants with genetic and environmental caste determination

    PubMed Central

    Mott, Brendon M; Gadau, Jürgen; Anderson, Kirk E

    2015-01-01

    We present a phylogeographic study of at least six reproductively isolated lineages of new world harvester ants within the Pogonomyrmex barbatus and P. rugosus species group. The genetic and geographic relationships within this clade are complex: Four of the identified lineages show genetic caste determination (GCD) and are divided into two pairs. Each pair has evolved under a mutualistic system that necessitates sympatry. These paired lineages are dependent upon one another because their GCD requires interlineage matings for the production of F1 hybrid workers, and intralineage matings are required to produce queens. This GCD system maintains genetic isolation among these interdependent lineages, while simultaneously requiring co-expansion and emigration as their distributions have changed over time. It has also been demonstrated that three of these four GCD lineages have undergone historical hybridization, but the narrower sampling range of previous studies has left questions on the hybrid parentage, breadth, and age of these groups. Thus, reconstructing the phylogenetic and geographic history of this group allows us to evaluate past insights and hypotheses and to plan future inquiries in a more complete historical biogeographic context. Using mitochondrial DNA sequences sampled across most of the morphospecies’ ranges in the U.S.A. and Mexico, we conducted a detailed phylogeographic study. Remarkably, our results indicate that one of the GCD lineage pairs has experienced a dramatic range expansion, despite the genetic load and fitness costs of the GCD system. Our analyses also reveal a complex pattern of vicariance and dispersal in Pogonomyrmex harvester ants that is largely concordant with models of late Miocene, Pliocene, and Pleistocene range shifts among various arid-adapted taxa in North America. PMID:26306168

  9. Microburst characteristics determined from 1988-1991 TDWR testbed measurements

    NASA Technical Reports Server (NTRS)

    Biron, Paul J.; Isaminger, Mark A.

    1992-01-01

    This paper presents some recent results germane to airborne windshear system design and certification. We first discuss the data analysis procedure and the associated caveats. The relative frequency, severity, and duration of microburst hazards at the various locations is important for determining the tradeoffs between safety and operational impact of false alerts which are encompassed in detection system thresholds. We then consider radar/lidar design issues such as reflective in microbursts and the vertical structure of outflows. Finally, we provide recent surface thermodynamic data associated with microbursts.

  10. Colored polydimethylsiloxane micropillar arrays for high throughput measurements of forces applied by genetic model organisms.

    PubMed

    Khare, Siddharth M; Awasthi, Anjali; Venkataraman, V; Koushika, Sandhya P

    2015-01-01

    Measuring forces applied by multi-cellular organisms is valuable in investigating biomechanics of their locomotion. Several technologies have been developed to measure such forces, for example, strain gauges, micro-machined sensors, and calibrated cantilevers. We introduce an innovative combination of techniques as a high throughput screening tool to assess forces applied by multiple genetic model organisms. First, we fabricated colored Polydimethylsiloxane (PDMS) micropillars where the color enhances contrast making it easier to detect and track pillar displacement driven by the organism. Second, we developed a semi-automated graphical user interface to analyze the images for pillar displacement, thus reducing the analysis time for each animal to minutes. The addition of color reduced the Young's modulus of PDMS. Therefore, the dye-PDMS composite was characterized using Yeoh's hyperelastic model and the pillars were calibrated using a silicon based force sensor. We used our device to measure forces exerted by wild type and mutant Caenorhabditis elegans moving on an agarose surface. Wild type C. elegans exert an average force of ∼1 μN on an individual pillar and a total average force of ∼7.68 μN. We show that the middle of C. elegans exerts more force than its extremities. We find that C. elegans mutants with defective body wall muscles apply significantly lower force on individual pillars, while mutants defective in sensing externally applied mechanical forces still apply the same average force per pillar compared to wild type animals. Average forces applied per pillar are independent of the length, diameter, or cuticle stiffness of the animal. We also used the device to measure, for the first time, forces applied by Drosophila melanogaster larvae. Peristaltic waves occurred at 0.4 Hz applying an average force of ∼1.58 μN on a single pillar. Our colored microfluidic device along with its displacement tracking software allows us to measure forces

  11. Colored polydimethylsiloxane micropillar arrays for high throughput measurements of forces applied by genetic model organisms

    PubMed Central

    Khare, Siddharth M.; Awasthi, Anjali; Venkataraman, V.; Koushika, Sandhya P.

    2015-01-01

    Measuring forces applied by multi-cellular organisms is valuable in investigating biomechanics of their locomotion. Several technologies have been developed to measure such forces, for example, strain gauges, micro-machined sensors, and calibrated cantilevers. We introduce an innovative combination of techniques as a high throughput screening tool to assess forces applied by multiple genetic model organisms. First, we fabricated colored Polydimethylsiloxane (PDMS) micropillars where the color enhances contrast making it easier to detect and track pillar displacement driven by the organism. Second, we developed a semi-automated graphical user interface to analyze the images for pillar displacement, thus reducing the analysis time for each animal to minutes. The addition of color reduced the Young's modulus of PDMS. Therefore, the dye-PDMS composite was characterized using Yeoh's hyperelastic model and the pillars were calibrated using a silicon based force sensor. We used our device to measure forces exerted by wild type and mutant Caenorhabditis elegans moving on an agarose surface. Wild type C. elegans exert an average force of ∼1 μN on an individual pillar and a total average force of ∼7.68 μN. We show that the middle of C. elegans exerts more force than its extremities. We find that C. elegans mutants with defective body wall muscles apply significantly lower force on individual pillars, while mutants defective in sensing externally applied mechanical forces still apply the same average force per pillar compared to wild type animals. Average forces applied per pillar are independent of the length, diameter, or cuticle stiffness of the animal. We also used the device to measure, for the first time, forces applied by Drosophila melanogaster larvae. Peristaltic waves occurred at 0.4 Hz applying an average force of ∼1.58 μN on a single pillar. Our colored microfluidic device along with its displacement tracking software allows us to measure forces

  12. GENETIC VARIATION MEASURED BY MICROSATELLITES AMONG THREE STRAINS OF DOMESTICATED RAINBOW TROUT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic variation fuels selective change in natural and captive populations. In establishing a broodstock for selective improvement the degree of genetic diversity is an important consideration because it provides an indication of the scope for selective progress. Here three strains of rainbow tro...

  13. Are Endophenotypes Based on Measures of Executive Functions Useful for Molecular Genetic Studies of ADHD?

    ERIC Educational Resources Information Center

    Doyle, Alysa E.; Faraone, Stephen V.; Seidman, Larry J.; Willcutt, Erik G.; Nigg, Joel T.; Waldman, Irwin D.; Pennington, Bruce F.; Peart, Joanne; Biederman, Joseph

    2005-01-01

    Background: Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or…

  14. Measurement and Associations of Pregnancy Risk Factors with Genetic Influences, Postnatal Environmental Influences, and Toddler Behavior

    ERIC Educational Resources Information Center

    Marceau, Kristine; Hajal, Nastassia; Leve, Leslie D.; Reiss, David; Shaw, Daniel S.; Ganiban, Jody M.; Mayes, Linda C.; Neiderhiser, Jenae M.

    2013-01-01

    This study demonstrates the unique contributions of perinatal risk and genetic and environmental influences on child behavior using data from 561 domestic US adoption triads (birth mothers, adopted child, and adoptive parents). Findings show distinct patterns of associations among genetic (birth mother psychopathology), prenatal (six maternal…

  15. Children's History of Speech-Language Difficulties: Genetic Influences and Associations with Reading-Related Measures

    ERIC Educational Resources Information Center

    DeThorne, Laura Segebart; Hart, Sara A.; Petrill, Stephen A.; Deater-Deckard, Kirby; Thompson, Lee Anne; Schatschneider, Chris; Davison, Megan Dunn

    2006-01-01

    Purpose: This study examined (a) the extent of genetic and environmental influences on children's articulation and language difficulties and (b) the phenotypic associations between such difficulties and direct assessments of reading-related skills during early school-age years. Method: Behavioral genetic analyses focused on parent-report data…

  16. Alternative models in genetic analyses of carcass traits measured by ultrasonography in Guzerá cattle: A Bayesian approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to study alternative models for genetic analyses of carcass traits assessed by ultrasonography in Guzerá cattle. Data from 947 measurements (655 animals) of Rib-eye area (REA), rump fat thickness (RFT) and backfat thickness (BFT) were used. Finite polygenic models (FPM), infinitesi...

  17. Engineering genetically encoded nanosensors for real-time in vivo measurements of citrate concentrations.

    PubMed

    Ewald, Jennifer C; Reich, Sabrina; Baumann, Stephan; Frommer, Wolf B; Zamboni, Nicola

    2011-01-01

    Citrate is an intermediate in catabolic as well as biosynthetic pathways and is an important regulatory molecule in the control of glycolysis and lipid metabolism. Mass spectrometric and NMR based metabolomics allow measuring citrate concentrations, but only with limited spatial and temporal resolution. Methods are so far lacking to monitor citrate levels in real-time in-vivo. Here, we present a series of genetically encoded citrate sensors based on Förster resonance energy transfer (FRET). We screened databases for citrate-binding proteins and tested three candidates in vitro. The citrate binding domain of the Klebsiella pneumoniae histidine sensor kinase CitA, inserted between the FRET pair Venus/CFP, yielded a sensor highly specific for citrate. We optimized the peptide linkers to achieve maximal FRET change upon citrate binding. By modifying residues in the citrate binding pocket, we were able to construct seven sensors with different affinities spanning a concentration range of three orders of magnitude without losing specificity. In a first in vivo application we show that E. coli maintains the capacity to take up glucose or acetate within seconds even after long-term starvation. PMID:22164251

  18. Energy yield determination of concentrator solar cells using laboratory measurements

    NASA Astrophysics Data System (ADS)

    Geisz, John F.; García, Iván; McMahon, William E.; Steiner, Myles A.; Ochoa, Mario; France, Ryan M.; Habte, Aron; Friedman, Daniel J.

    2015-09-01

    The annual energy conversion efficiency is calculated for a four junction inverted metamorphic solar cell that has been completely characterized in the laboratory at room temperature using measurements fit to a comprehensive optoelectronic model of the multijunction solar cells. A simple model of the temperature dependence is used predict the performance of the solar cell under varying temperature and spectra characteristic of Golden, CO for an entire year. The annual energy conversion efficiency is calculated by integrating the predicted cell performance over the entire year. The effects of geometric concentration, CPV system thermal characteristics, and luminescent coupling are highlighted.

  19. RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

    PubMed

    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

    To facilitate precision medicine and whole-genome annotation, we developed a machine-learning technique that scores how strongly genetic variants affect RNA splicing, whose alteration contributes to many diseases. Analysis of more than 650,000 intronic and exonic variants revealed widespread patterns of mutation-driven aberrant splicing. Intronic disease mutations that are more than 30 nucleotides from any splice site alter splicing nine times as often as common variants, and missense exonic disease mutations that have the least impact on protein function are five times as likely as others to alter splicing. We detected tens of thousands of disease-causing mutations, including those involved in cancers and spinal muscular atrophy. Examination of intronic and exonic variants found using whole-genome sequencing of individuals with autism revealed misspliced genes with neurodevelopmental phenotypes. Our approach provides evidence for causal variants and should enable new discoveries in precision medicine. PMID:25525159

  20. Genetic determinants of polycystic ovary syndrome: progress and future directions.

    PubMed

    Jones, Michelle R; Goodarzi, Mark O

    2016-07-01

    The field of the genetics of polycystic ovary syndrome (PCOS) has relatively recently moved into the era of genome-wide association studies. This has led to the discovery of 16 robust loci for PCOS. Some loci contain genes with clear roles in reproductive (LHCGR, FSHR, and FSHB) and metabolic (INSR and HMGA2) dysfunction in the syndrome. The next challenge facing the field is the identification of causal variants and genes and the role they play in PCOS pathophysiology. The potential for gene discovery to improve diagnosis and treatment of PCOS is promising, though there is much to be done in the field before the current findings can be translated to the clinic. PMID:27179787

  1. Natural genetic variation for morphological and molecular determinants of plant growth and yield.

    PubMed

    Nunes-Nesi, Adriano; Nascimento, Vitor de Laia; de Oliveira Silva, Franklin Magnum; Zsögön, Agustin; Araújo, Wagner L; Sulpice, Ronan

    2016-05-01

    The rates of increase in yield of the main commercial crops have been steadily falling in many areas worldwide. This generates concerns because there is a growing demand for plant biomass due to the increasing population. Plant yield should thus be improved in the context of climate change and decreasing natural resources. It is a major challenge which could be tackled by improving and/or altering light-use efficiency, CO2 uptake and fixation, primary metabolism, plant architecture and leaf morphology, and developmental plant processes. In this review, we discuss some of the traits which could lead to yield increase, with a focus on how natural genetic variation could be harnessed. Moreover, we provide insights for advancing our understanding of the molecular aspects governing plant growth and yield, and propose future avenues for improvement of crop yield. We also suggest that knowledge accumulated over the last decade in the field of molecular physiology should be integrated into new ideotypes. PMID:27012286

  2. Effect of Antidepressants on Immunological Reactivity in ASC Mice with Genetically Determined Depression-Like State.

    PubMed

    Gevorgyan, M M; Idova, G V; Al'perina, E L; Tikhonova, M A; Kulikov, A V

    2016-06-01

    The effect of chronic treatment with antidepressant drugs fluoxetine (20 mg/kg) and imipramine (25 mg/kg) on the number of antibody-producing cells and the main T cell subpopulations in ASC mice characterized by genetic predisposition to depression-like states was studied at the peak of the SE-induced immune response (5×10(8)). Fluoxetine produced an immunostimulatory effect manifested in an increase in the relative and absolute number of IgM antibody-producing cells in the spleen and index of immunoreactivity (CD4/CD8). Administration of fl uoxetine to parental mouse strains without depression (CBA and AKR) had no effect (CBA) or reduced the immune response. The CD4/CD8 ratio did not increase under these conditions. Imipramine was ineffective in the correction of immune reactions in a depression-like state. PMID:27383160

  3. Major Effects on Teratogen-Induced Facial Clefting in Mice Determined by a Single Genetic Region

    PubMed Central

    Karolyi, J.; Erickson, R. P.; Liu, S.; Killewald, L.

    1990-01-01

    A major correlation has been found between the incidence of glucocorticoid-induced cleft palate and the chromosome 8 segment identified by N-acetyl transferase in mice. The resistant strain became fully susceptible while the susceptible strain became resistant when this chromosomal region, representing <0.7% of the genome, was transferred from one strain to the other by the construction of congenic strains. 6-Aminonicotinamide-induced cleft palate and phenytoin-induced cleft lip with or without cleft palate are also influenced by this genetic region but not as strongly. In both cases the susceptible strain became quite resistant to the teratogen-induced clefting when the N-acetyl transferase region of chromosome 8 was transferred. However, this chromosomal region does not make the resistant strain susceptible to these two teratogens. PMID:2227380

  4. Genetic determinants of cognitive responses to caffeine drinking identified from a double-blind, randomized, controlled trial.

    PubMed

    Renda, Giulia; Committeri, Giorgia; Zimarino, Marco; Di Nicola, Marta; Tatasciore, Alfonso; Ruggieri, Benedetta; Ambrosini, Ettore; Viola, Vanda; Antonucci, Ivana; Stuppia, Liborio; De Caterina, Raffaele

    2015-06-01

    The widely observed between-subject variability in cognitive responses to coffee may have a genetic basis. We evaluated cognitive responses to caffeine throughout three complex cognitive tasks assessing different subdomains of attention, namely Alerting and Orienting (Categorical Search Task) and Executive Control (Stroop Task and Eriksen Flanker Task). We explored whether they are influenced by gene variants affecting adenosine metabolism or catecholamine receptors. We recruited 106 healthy male subjects who were administered, in a double-blind design, 40mL of either a decaffeinated coffee preparation plus 3mg/kg caffeine (caf) or the corresponding vehicle (decaf). The protocol was repeated 24h later with the alternative preparation. Cognitive tasks were performed between 30min and 2h after caf or decaf administration. Each subject underwent ambulatory blood pressure monitoring for 2h. Blood samples were collected for genetic evaluations and for plasma caffeine and catecholamines measures. We found a significant reduction of reaction times in two of the cognitive tasks (Categorical Search Task and Stroop Task) after caf compared with decaf, indicating that caffeine, on average, improved the attention level in the domains under investigation. We also found, however, a great inter-individual variability in the cognitive performance responses to caffeine. In exploring genetic sources for such variability, we found a relation between polymorphisms of adenosine A2A and the caffeine effects on the attentional domains of Orienting and Executive control. In conclusion, variability in the attentional response to coffee may be partly explained by genetic polymorphisms of adenosine and adrenergic receptors. PMID:25819143

  5. Dynamical patterning modules: physico-genetic determinants of morphological development and evolution

    NASA Astrophysics Data System (ADS)

    Newman, Stuart A.; Bhat, Ramray

    2008-03-01

    The shapes and forms of multicellular organisms arise by the generation of new cell states and types and changes in the numbers and rearrangements of the various kinds of cells. While morphogenesis and pattern formation in all animal species are widely recognized to be mediated by the gene products of an evolutionarily conserved 'developmental-genetic toolkit', the link between these molecular players and the physics underlying these processes has been generally ignored. This paper introduces the concept of 'dynamical patterning modules' (DPMs), units consisting of one or more products of the 'toolkit' genes that mobilize physical processes characteristic of chemically and mechanically excitable meso- to macroscopic systems such as cell aggregates: cohesion, viscoelasticity, diffusion, spatiotemporal heterogeneity based on lateral inhibition and multistable and oscillatory dynamics. We suggest that ancient toolkit gene products, most predating the emergence of multicellularity, assumed novel morphogenetic functions due to change in the scale and context inherent to multicellularity. We show that DPMs, acting individually and in concert with each other, constitute a 'pattern language' capable of generating all metazoan body plans and organ forms. The physical dimension of developmental causation implies that multicellular forms during the explosive radiation of animal body plans in the middle Cambrian, approximately 530 million years ago, could have explored an extensive morphospace without concomitant genotypic change or selection for adaptation. The morphologically plastic body plans and organ forms generated by DPMs, and their ontogenetic trajectories, would subsequently have been stabilized and consolidated by natural selection and genetic drift. This perspective also solves the apparent 'molecular homology-analogy paradox', whereby widely divergent modern animal types utilize the same molecular toolkit during development by proposing, in contrast to the Neo

  6. Genetically determined differences in noradrenergic function: The spontaneously hypertensive rat model.

    PubMed

    Sterley, Toni-Lee; Howells, Fleur M; Russell, Vivienne A

    2016-06-15

    While genetic predisposition is a major factor, it is not known how development of attention-deficit/hyperactivity disorder (ADHD) is modulated by early life stress. The spontaneously hypertensive rat (SHR) displays the behavioral characteristics of ADHD (poorly sustained attention, impulsivity, hyperactivity) and is the most widely studied genetic model of ADHD. We have previously shown that SHR have disturbances in the noradrenergic system and that the early life stress of maternal separation failed to produce anxiety-like behavior in SHR, contrary to control Sprague-Dawley and Wistar-Kyoto (WKY) who showed typical anxiety-like behavior in later life. In the present study we investigated the effect of maternal separation on approach behavior (response to a novel object in a familiar environment) in preadolescent SHR and WKY. We also investigated whether maternal separation altered GABAA and NMDA receptor-mediated regulation of norepinephrine release in preadolescent SHR and WKY hippocampus. We found that female SHR, similar to male SHR, exhibited greater exploratory activity than WKY. Maternal separation significantly increased GABAA receptor-mediated inhibition of glutamate-stimulated release of norepinephrine in male and female SHR hippocampus but had no significant effect in WKY. Maternal separation had opposite effects on NMDA receptor-mediated inhibition of norepinephrine release in SHR and WKY hippocampus, as it increased inhibition of both glutamate-stimulated and depolarization-evoked release in SHR hippocampus but not in WKY. The results of the present study show that noradrenergic function is similarly altered by the early life stress of maternal separation in male and female SHR, while GABA- and glutamate-regulation of norepinephrine release remained unaffected by maternal separation in the control, WKY, rat strain. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID:26612520

  7. Multivariate genetic determinants of EEG oscillations in schizophrenia and psychotic bipolar disorder from the BSNIP study

    PubMed Central

    Narayanan, B; Soh, P; Calhoun, V D; Ruaño, G; Kocherla, M; Windemuth, A; Clementz, B A; Tamminga, C A; Sweeney, J A; Keshavan, M S; Pearlson, G D

    2015-01-01

    Schizophrenia (SZ) and psychotic bipolar disorder (PBP) are disabling psychiatric illnesses with complex and unclear etiologies. Electroencephalogram (EEG) oscillatory abnormalities in SZ and PBP probands are heritable and expressed in their relatives, but the neurobiology and genetic factors mediating these abnormalities in the psychosis dimension of either disorder are less explored. We examined the polygenic architecture of eyes-open resting state EEG frequency activity (intrinsic frequency) from 64 channels in 105 SZ, 145 PBP probands and 56 healthy controls (HCs) from the multisite BSNIP (Bipolar-Schizophrenia Network on Intermediate Phenotypes) study. One million single-nucleotide polymorphisms (SNPs) were derived from DNA. We assessed eight data-driven EEG frequency activity derived from group-independent component analysis (ICA) in conjunction with a reduced subset of 10 422 SNPs through novel multivariate association using parallel ICA (para-ICA). Genes contributing to the association were examined collectively using pathway analysis tools. Para-ICA extracted five frequency and nine SNP components, of which theta and delta activities were significantly correlated with two different gene components, comprising genes participating extensively in brain development, neurogenesis and synaptogenesis. Delta and theta abnormality was present in both SZ and PBP, while theta differed between the two disorders. Theta abnormalities were also mediated by gene clusters involved in glutamic acid pathways, cadherin and synaptic contact-based cell adhesion processes. Our data suggest plausible multifactorial genetic networks, including novel and several previously identified (DISC1) candidate risk genes, mediating low frequency delta and theta abnormalities in psychoses. The gene clusters were enriched for biological properties affecting neural circuitry and involved in brain function and/or development. PMID:26101851

  8. Multivariate genetic determinants of EEG oscillations in schizophrenia and psychotic bipolar disorder from the BSNIP study.

    PubMed

    Narayanan, B; Soh, P; Calhoun, V D; Ruaño, G; Kocherla, M; Windemuth, A; Clementz, B A; Tamminga, C A; Sweeney, J A; Keshavan, M S; Pearlson, G D

    2015-01-01

    Schizophrenia (SZ) and psychotic bipolar disorder (PBP) are disabling psychiatric illnesses with complex and unclear etiologies. Electroencephalogram (EEG) oscillatory abnormalities in SZ and PBP probands are heritable and expressed in their relatives, but the neurobiology and genetic factors mediating these abnormalities in the psychosis dimension of either disorder are less explored. We examined the polygenic architecture of eyes-open resting state EEG frequency activity (intrinsic frequency) from 64 channels in 105 SZ, 145 PBP probands and 56 healthy controls (HCs) from the multisite BSNIP (Bipolar-Schizophrenia Network on Intermediate Phenotypes) study. One million single-nucleotide polymorphisms (SNPs) were derived from DNA. We assessed eight data-driven EEG frequency activity derived from group-independent component analysis (ICA) in conjunction with a reduced subset of 10,422 SNPs through novel multivariate association using parallel ICA (para-ICA). Genes contributing to the association were examined collectively using pathway analysis tools. Para-ICA extracted five frequency and nine SNP components, of which theta and delta activities were significantly correlated with two different gene components, comprising genes participating extensively in brain development, neurogenesis and synaptogenesis. Delta and theta abnormality was present in both SZ and PBP, while theta differed between the two disorders. Theta abnormalities were also mediated by gene clusters involved in glutamic acid pathways, cadherin and synaptic contact-based cell adhesion processes. Our data suggest plausible multifactorial genetic networks, including novel and several previously identified (DISC1) candidate risk genes, mediating low frequency delta and theta abnormalities in psychoses. The gene clusters were enriched for biological properties affecting neural circuitry and involved in brain function and/or development. PMID:26101851

  9. Determining index of refraction from polarimetric hyperspectral radiance measurements

    NASA Astrophysics Data System (ADS)

    Martin, Jacob A.; Gross, Kevin C.

    2015-09-01

    Polarimetric hyperspectral imaging (P-HSI) combines two of the most common remote sensing modalities. This work leverages the combination of these techniques to improve material classification. Classifying and identifying materials requires parameters which are invariant to changing viewing conditions, and most often a material's reflectivity or emissivity is used. Measuring these most often requires assumptions be made about the material and atmospheric conditions. Combining both polarimetric and hyperspectral imaging, we propose a method to remotely estimate the index of refraction of a material. In general, this is an underdetermined problem because both the real and imaginary components of index of refraction are unknown at every spectral point. By modeling the spectral variation of the index of refraction using a few parameters, however, the problem can be made overdetermined. A number of different functions can be used to describe this spectral variation, and some are discussed here. Reducing the number of spectral parameters to fit allows us to add parameters which estimate atmospheric downwelling radiance and transmittance. Additionally, the object temperature is added as a fit parameter. The set of these parameters that best replicate the measured data is then found using a bounded Nelder-Mead simplex search algorithm. Other search algorithms are also examined and discussed. Results show that this technique has promise but also some limitations, which are the subject of ongoing work.

  10. Determination of vertical characteristics with different cephalometric measurements

    PubMed Central

    Benedicto, Eduardo de Novaes; Kairalla, Silvana Allegrini; Oliveira, Gustavo Mussi Stefan; Junior, Laerte Ribeiro Menezes; Rosário, Henrique Damian; Paranhos, Luiz Renato

    2016-01-01

    Objective: To analyze a possible correlation between different measures in the definition of vertical facial types. Materials and Methods: This is an analytical observational study about 95 lateral teleradiographs of Caucasian individuals with normal occlusion, of which 54 were male (56.84%) and 41 female (43.16%), aged between 15 years and 2 months old and 21 years and 4 months old. Facial types were divided into dolichofacial, mesofacial, and brachyfacial, according to the standards established by different authors. A relationship between these measurements was verified using total agreement analysis and the Kappa method, with the interpretation suggested by Landis and Koch. Results: Kappa was considered fair for Jarabak X VERT (0.22 and 60%) and slight for Jarabak X SN. GoGn (0.06 and 36.8%). Conclusions: Cephalometric studies often present different interpretations on the description of vertical facial types. In this study, the lowest agreement was between Jarabak and SN.GoGn. Such difference in interpretation may lead to distinct therapeutic approaches and thus different results. PMID:27011750

  11. Kinetic solvent effects on phenolic antioxidants determined by spectrophotometric measurements.

    PubMed

    Foti, M; Ruberto, G

    2001-01-01

    The effects of polar (acetonitrile and tert-butyl alcohol) and apolar (cyclohexane) solvents on the peroxyl-radical-trapping antioxidant activity of some flavonoids, catechol derivatives, hydroquinone, and monophenols have been studied. The inhibition rate constants k(inh) of the antioxidants have been determined by following the increase in absorbance at 234 nm of a dilute solution of linoleic acid at 50 degrees C containing small amounts of antioxidant and radical initiator. Despite the low concentration of linoleic acid, the peroxidation process has been confirmed to be a free radical chain reaction described by the classical kinetic laws for this process. However, in the evaluation of k(inh), a careful analysis of the peroxidation curve, absorbance versus time, must be done because the final oxidation products of phenols may absorb at 234 nm. Phenols with two ortho-hydroxyls are the most active antioxidants, with inhibition rate constants in the range of (3-15) x 10(5) M(-1) x s(-1) (in cyclohexane). Nevertheless, it has been observed that in tert-butyl alcohol (a strong hydrogen bond acceptor) the rate constants dramatically decline to values not detectable by the present kinetic method. In acetonitrile (a weaker hydrogen bond acceptor) instead, the phenols with two ortho-hydroxyls scavenge the peroxyl radicals with rate constants close to those in cyclohexane. From the kinetic solvent effect, the equilibrium constant of the first solvation step of hydroquinone with tert-butyl alcohol has been determined at 50 degrees C, K(1) = 2.5 +/- 0.5 M(-1). PMID:11170597

  12. Genetic and Biochemical Determinants of Serum Concentrations of Monocyte Chemoattractant Protein-1, a Potential Neural Tube Defect Risk Factor

    PubMed Central

    Lu, Zhi-Yong; Morales, Megan; Khartulyari, Stephanie; Mei, Minghua; Murphy, Kristen M.; Stanislawska-Sachadyn, Anna; Summers, Carolyn M.; Huang, Yuehua; Von Feldt, Joan M; Blair, Ian A.; Mitchell, Laura E.; Whitehead, Alexander S.

    2010-01-01

    Background Women with the AA genotype at the (−2518) A>G promoter polymorphism of CCL-2, which encodes the potent pro-inflammatory chemokine monocyte chemoattractant protein 1 (MCP-1), may be at increased risk for having offspring affected by spina bifida. As the A allele at this locus has been associated with decreased transcription of MCP-1 mRNA relative to the G allele, the observed genetic association suggests that the risk of spina bifida may be increased in the offspring of women with low MCP-1 levels. The present study was undertaken to identify potential determinants of MCP-1 levels in women of reproductive age. Methods A small cohort of Caucasian and African-American women of reproductive age was recruited to participate in an exploratory investigation of the determinants of several disease-related, biochemical phenotypes, including MCP-1. Subjects completed a brief questionnaire and provided a fasting blood sample for biochemical and genetic studies. Potential biochemical, genetic and lifestyle factors were assessed for their association with MCP-1 levels using linear regression analyses. Results In this cohort, MCP-1 levels were significantly higher in Caucasians as compared to African-Americans. Further, among women of both races, there was evidence that MCP-1 levels were associated with smoking status, MTHFR 677C>T genotype and red blood cell tetrahydrofolate levels. Conclusions The results of these analyses indicate that, if maternal CCL-2 genotype is related to the risk of spina bifida, this relationship is likely to be more complex than initially hypothesized, perhaps depending upon folate intake, MTHFR 677C>T genotype, the distribution of folate derivatives, and immune/inflammatory activity. PMID:18937353

  13. Balancing genetic uniqueness and genetic variation in determining conservation and translocation strategies: a comprehensive case study of threatened dwarf galaxias, Galaxiella pusilla (Mack) (Pisces: Galaxiidae).

    PubMed

    Coleman, R A; Weeks, A R; Hoffmann, A A

    2013-04-01

    Genetic markers are widely used to define and manage populations of threatened species based on the notion that populations with unique lineages of mtDNA and well-differentiated nuclear marker frequencies should be treated separately. However, a danger of this approach is that genetic uniqueness might be emphasized at the cost of genetic diversity, which is essential for adaptation and is potentially boosted by mixing geographically separate populations. Here, we re-explore the issue of defining management units, focussing on a detailed study of Galaxiella pusilla, a small freshwater fish of national conservation significance in Australia. Using a combination of microsatellite and mitochondrial markers, 51 populations across the species range were surveyed for genetic structure and diversity. We found an inverse relationship between genetic differentiation and genetic diversity, highlighting a long-term risk of deliberate isolation of G. pusilla populations based on protection of unique lineages. Instead, we adopt a method for identifying genetic management units that takes into consideration both uniqueness and genetic variation. This produced a management framework to guide future translocation and re-introduction efforts for G. pusilla, which contrasted to the framework based on a more traditional approach that may overlook important genetic variation in populations. PMID:23432132

  14. Genetic Analyses Reveal Functions for MAP2K3 and MAP2K6 in Mouse Testis Determination.

    PubMed

    Warr, Nick; Siggers, Pam; Carré, Gwenn-Aël; Wells, Sara; Greenfield, Andy

    2016-05-01

    Testis determination in mammals is initiated by expression of SRY in somatic cells of the embryonic gonad. Genetic analyses in the mouse have revealed a requirement for mitogen-activated protein kinase (MAPK) signaling in testis determination: targeted loss of the kinases MAP3K4 and p38 MAPK causes complete XY embryonic gonadal sex reversal. These kinases occupy positions at the top and bottom level, respectively, in the canonical three-tier MAPK-signaling cascade: MAP3K, MAP2K, MAPK. To date, no role in sex determination has been attributed to a MAP2K, although such a function is predicted to exist. Here, we report roles for the kinases MAP2K3 and MAP2K6 in testis determination. C57BL/6J (B6) embryos lacking MAP2K3 exhibited no significant abnormalities of testis development, whilst those lacking MAP2K6 exhibited a minor delay in testis determination. Compound mutants lacking three out of four functional alleles at the two loci also exhibited delayed testis determination and transient ovotestis formation as a consequence, suggestive of partially redundant roles for these kinases in testis determination. Early lethality of double-knockout embryos precludes analysis of sexual development. To reveal their roles in testis determination more clearly, we generated Map2k mutant B6 embryos using a weaker Sry allele (Sry(AKR)). Loss of Map2k3 on this highly sensitized background exacerbates ovotestis development, whilst loss of Map2k6 results in complete XY gonadal sex reversal associated with reduction of Sry expression at 11.25 days postcoitum. Our data suggest that MAP2K6 functions in mouse testis determination, via positive effects on Sry, and also indicate a minor role for MAP2K3. PMID:27009039

  15. Piezoelectric Sensor for Determination of Genetically Modified Soybean Roundup Ready® in Samples not Amplified by PCR

    PubMed Central

    Stobiecka, Magdalena; Cieśla, Jarosław M.; Janowska, Beata; Tudek, Barbara; Radecka, Hanna

    2007-01-01

    The chemically modified piezoelectrodes were utilized to develop relatively cheap and easy to use biosensor for determination of genetically modified Roundup Ready soybean (RR soybean). The biosensor relies on the immobilization onto gold piezoelectrodes of the 21-mer single stranded oligonucleotide (probes) related to 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene, which is an active component of an insert integrated into RR soybean genome. The hybridization reaction between the probe and the target complementary sequence in solution was monitored. The system was optimized using synthetic oligonucleotides, which were applied for EPSPS gene detection in DNA samples extracted from animal feed containing 30% RR soybean amplified by the PCR and nonamplified by PCR. The detection limit for genomic DNA was in the range of 4.7·105 numbers of genom copies contained EPSPS gene in the QCM cell. The properties such as sensitivity and selectivity of piezoelectric senor presented here indicated that it could be applied for the direct determination of genetically modified RR soybean in the samples non-amplified by PCR.

  16. Methods of Temperature and Emission Measure Determination of Coronal Loops

    NASA Astrophysics Data System (ADS)

    Cirtain, J. W.; Schmelz, J. T.; Martens, P. C. H.

    2002-05-01

    Recent observational results from both SOHO-EIT and TRACE indicate that coronal loops are isothermal along their length (axially). These results are obtained from a narrowband filter ratio method that assumes that the plasma is isothermal along the line of sight (radially). However, these temperatures vary greatly from those derived from differential emission measure (DEM) curves produced from spectral lines recorded by SOHO-CDS. The DEM results indicate that the loops are neither axially nor radially isothermal. This discrepancy was investigated by Schmelz et al. (2001). They chose pairs of iron lines from the same CDS data set to mimic the EIT and TRACE loop results. Ratios of different lines gave different temperatures, indicating that the plasma was not radially isothermal. In addition the results indicated that the loop was axially isothermal, even though the DEM analysis of the same data showed this result to be false. Here we have analyzed the EIT data for the CDS loop published by Schmelz et al. (2001). We took the ratios of the 171-to-195 and 195-to-284 filter data, and made temperature maps of the loop. The results indicate that the loop is axially isothermal, but different temperatures were found for each pair of filters. Both ratio techniques force the resultant temperature to lie within the range where the response functions (for filters) or the emissivity functions (for lines) overlap; isothermal loops are therefore a byproduct of the analysis. This conclusion strengthens support for the idea that temperature and emission measure results from filter ratio methods may be misleading or even drastically wrong. This research was funded in part by the NASA/TRACE MODA grant for Montana State University. Solar physics research at the University of Memphis is supported by NASA grant NAG5-9783.

  17. The molecular genetics of sex determination and sex reversal in mammals.

    PubMed

    Quinn, Alexander; Koopman, Peter

    2012-10-01

    The process of sex determination in mammals normally unfolds in three distinct stages: (1) establishment of chromosomal sex at fertilization (XX or XY); (2) commitment to the appropriate pathway of gonadal differentiation with respect to chromosomal sex, through the action (or absence) of the Y chromosome gene SRY; and (3) correct development of secondary sexual characteristics, including internal and external genitalia, in accordance with gonadal sex. At any of these three steps, the process of sex determination can go awry, leading to disorders of sexual development. In this article, we review the typical mechanism and process of mammalian sex determination, with an emphasis on the well-characterized mouse and human models. We also consider aberrant mammalian sex determination, focusing on examples of sex reversal stemming from gene defects. PMID:23044871

  18. Statistical characteristics of atmospheric aerosol as determined from AERONET measurements

    NASA Astrophysics Data System (ADS)

    Yoon, Jongmin; Kokhanovsky, Alexander

    2015-04-01

    Seasonal means and standard deviations of column-integrated aerosol optical properties (e.g. spectral aerosol optical thickness (AOT), single scattering albedo, phase function, Ångström exponent, volume particle size distribution, complex refractive index, absorbing aerosol optical thickness) from several Aerosol Robotic Network (AERONET) sites located in typical aerosol source and background regions are investigated (Holben et al., 1998). The AERONET program is an inclusive network of ground-based sun-photometers that measure atmospheric aerosol optical properties (http://aeronet.gsfc.nasa.gov/). The results can be used for improving the accuracy of satellite-retrieved AOT, assessments of the global aerosol models, studies of atmospheric pollution and aerosol radiative forcing on climate. We have paid a special attention to several AERONET sites that are Mexico_City (Mexico), Alta_Floresta (Brazil), Avignon (France), Solar_Village (Saudi Arabia), and Midway_Island (Pacific) representative for industrial/urban, biomass burning, rural, desert dust and oceanic aerosols, respectively. We have found that the optical and microphysical aerosol properties are highly dependent on the local aerosol emission sources and seasonal meteorological conditions.

  19. The induction of sister chromatid exchanges by environmental pollutants: relationship of SCE to other measures of genetic damage

    SciTech Connect

    Brooks, A.L.; Shimizu, R.W.; Li, A.P.; Benson, J.M.; Dutcher, J.S.

    1984-01-01

    Sister chromatid exchanges (SCEs), induced by environmental pollutants from fossil fuel use, were measured in 2 cell systems, Chinese hamster ovary (CHO) cells and Chinese hamster primary lung cell cultures. The frequency of SCEs induced in these cell systems was related to other measures of genetic damage, namely mutations in CHO cells at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) gene locus and in bacteria (Salmonella mutagenicity test TA-98), produced by the same pollutants. The pollutants were divided into 2 classes: those produced in oxidizing combustion environments--extracts of particles from light-duty diesel cars, spark-ignition cars, and an automotive tunnel; and those produced in reducing environments--extracts from coke oven mains and condensates from a low BTU coal gasifier obtained either before or after cleanup of the process stream. Sister chromatid exchanges were induced by all pollutants without the addition of a rat liver microsomal fraction (S-9 mix), whereas S-9 mix was required to induce a positive response in the CHO/HGPRT assay for all pollutants. The pollutants produced in a reducing environment required metabolic activation by S-9 mix to be mutagenic in the Salmonella mutation assay. The addition of S-9 mix to pollutants produced in an oxidizing environment reduced the response in the Salmonella test. The relative genotoxic potency for each pollutant was determined for all 3 endpoints. The slopes of dose-response curves for each pollutant were plotted for each assay to compare relative potency. When the bacterial mutagenicity test was compared to either mammalian cell assay, SCE or CHO/HGPRT, there was little correlation between relative potencies. However, the data indicated that the responses in the 2 mammalian cell assays, SCE and CHO/HGPRT, showed similar relative responses to the pollutants.

  20. Genetic and Anatomic Determinants of Enzootic Venezuelan Equine Encephalitis Virus Infection of Culex (Melanoconion) taeniopus

    PubMed Central

    Kenney, Joan L.; Adams, A. Paige; Gorchakov, Rodion; Leal, Grace; Weaver, Scott C.

    2012-01-01

    Venezuelan equine encephalitis (VEE) is a re-emerging, mosquito-borne viral disease with the potential to cause fatal encephalitis in both humans and equids. Recently, detection of endemic VEE caused by enzootic strains has escalated in Mexico, Peru, Bolivia, Colombia and Ecuador, emphasizing the importance of understanding the enzootic transmission cycle of the etiologic agent, VEE virus (VEEV). The majority of work examining the viral determinants of vector infection has been performed in the epizootic mosquito vector, Aedes (Ochlerotatus) taeniorhynchus. Based on the fundamental differences between the epizootic and enzootic cycles, we hypothesized that the virus-vector interaction of the enzootic cycle is fundamentally different from that of the epizootic model. We therefore examined the determinants for VEEV IE infection in the enzootic vector, Culex (Melanoconion) taeniopus, and determined the number and susceptibility of midgut epithelial cells initially infected and their distribution compared to the epizootic virus-vector interaction. Using chimeric viruses, we demonstrated that the determinants of infection for the enzootic vector are different than those observed for the epizootic vector. Similarly, we showed that, unlike A. taeniorhynchus infection with subtype IC VEEV, C. taeniopus does not have a limited subpopulation of midgut cells susceptible to subtype IE VEEV. These findings support the hypothesis that the enzootic VEEV relationship with C. taeniopus differs from the epizootic virus-vector interaction in that the determinants appear to be found in both the nonstructural and structural regions, and initial midgut infection is not limited to a small population of susceptible cells. PMID:22509419

  1. Ontogeny and phylogeny of femoro-tibial characters in humans and hominid fossils: functional influence and genetic determinism.

    PubMed

    Tardieu, C

    1999-11-01

    prominence of the lateral lip of the trochlea arises before any use, and thus appears to be genetically determined. However, the postnatal development of this joint shows that this feature is also modified epigenetically by use. It is argued that the hominid femoro-patellar joint would have been reshaped following the process of genetic assimilation (Waddington [1942] Nature 3811:563-565). The prominence of the lateral lip of the femoral trochlea was probably selected following a two-staged process-first epigenetic, then genetic. Far from being a Lamarckian explanation, this concept applies precisely to adaptive characters that are induced by an external stimulus during a single lifetime and are replaced through natural selection by genetically based equivalent characters. The nature of the structures involved in the studied features is shown to be an important parameter determining their mode of development and selection. PMID:10516567

  2. Phenotype Similarity Regression for Identifying the Genetic Determinants of Rare Diseases

    PubMed Central

    Greene, Daniel; Richardson, Sylvia; Turro, Ernest

    2016-01-01

    Rare genetic disorders, which can now be studied systematically with affordable genome sequencing, are often caused by high-penetrance rare variants. Such disorders are often heterogeneous and characterized by abnormalities spanning multiple organ systems ascertained with variable clinical precision. Existing methods for identifying genes with variants responsible for rare diseases summarize phenotypes with unstructured binary or quantitative variables. The Human Phenotype Ontology (HPO) allows composite phenotypes to be represented systematically but association methods accounting for the ontological relationship between HPO terms do not exist. We present a Bayesian method to model the association between an HPO-coded patient phenotype and genotype. Our method estimates the probability of an association together with an HPO-coded phenotype characteristic of the disease. We thus formalize a clinical approach to phenotyping that is lacking in standard regression techniques for rare disease research. We demonstrate the power of our method by uncovering a number of true associations in a large collection of genome-sequenced and HPO-coded cases with rare diseases. PMID:26924528

  3. Genetically determined variation in stress responsiveness in rainbow trout: behavior and neurobiology.

    PubMed

    Schjolden, Joachim; Winberg, Svante

    2007-01-01

    It is becoming increasingly recognized that the diversity in stressors, their intensity, predictability and the context in which they are experienced, will result in behavioral and physiological responses just as diverse. In addition, stress responses are characterized by individual variations where the physiological and behavioral reactions are associated in such a manner that distinct stress coping styles encompassing suites of correlated traits can be identified. These are often referred to as proactive and reactive stress coping styles. Proactive coping is characterized by more aggression, higher general activity and higher sympathetic activation, whereas reactive coping is characterized by immobility, lack of initiative and a higher parasympathetic/hypothalamic activation. Stable coping styles appear to coexist within populations, and these strategies appear to be largely innate. Moreover, the physiological and behavioral traits of coping styles appear to be heritable. These stress coping styles have proven to play a major role in competitive ability and subsequent social position in different species of vertebrates. However, there are also studies showing that social position can affect parameters encompassing the stress coping style of individuals. In this regard it is important, but not always easy, to distinguish between causes and effects of behavioral and physiological responses to stressors. The question raised is to what extent and rigidness stress coping styles are guided by genetic factors. PMID:17914254

  4. Genetic diversity and phylogeny of toxic cyanobacteria determined by DNA polymorphisms within the phycocyanin locus.

    PubMed Central

    Neilan, B A; Jacobs, D; Goodman, A E

    1995-01-01

    Cyanobacteria are a highly diverse group in relation to form, function, and habitat. Current cyanobacterial systematics relies on the observation of minor and plastic morphological characters. Accurate and reliable delineation of toxic and bloom-forming strains of cyanobacteria has not been possible by traditional methods. We have designed general primers to the phycocyanin operon (cpc gene) and developed a PCR which allows the amplification of a region of this gene, including a variable intergenic spacer sequence. Because of the specificity of this PCR for cyanobacterial isolates, the assay is appropriate for the rapid and reliable identification of strains in freshwater samples. Successive restriction endonuclease digestion of this amplification product, with a total of nine enzymes, yielded many identifying DNA profiles specific to the various taxonomic levels of cyanobacteria. The restriction enzyme profiles for MspI, RsaI, and TaqI were conserved for strains within each of the eight genera (40 strains) studied and clearly discriminated among these genera. Intrageneric delineation of strains was revealed by the enzymes AluI, CfoI, and HaeIII for members of the genus Microcystis, while strains of genus Anabaena were differentiated by the digestion patterns provided by AluI, CfoI, and ScrFI. Phenetic and cladistic analyses of the data were used to infer the genetic relatedness and evolution of toxic and bloom-forming cyanobacteria. PMID:8526499

  5. Genetic determination of the cellular basis of the ghrelin-dependent bone remodeling

    PubMed Central

    Ma, Chengshan; Fukuda, Toru; Ochi, Hiroki; Sunamura, Satoko; Xu, Cheng; Xu, Ren; Okawa, Atsushi; Takeda, Shu

    2015-01-01

    Objective Bone mass is maintained through a balance of bone formation and resorption. This homeostatic balance is regulated by various systems involving humoral and local factors. The discovery that the anorexigenic hormone leptin regulates bone mass via neuronal pathways revealed that neurons and neuropeptides are intimately involved in bone homeostasis. Ghrelin is a stomach-derived orexigenic hormone that counteracts leptin's action. However, the physiological role of ghrelin in bone homeostasis remains unknown. In this study, through the global knockout of ghrelin receptor (Ghsr) followed by tissue-specific re-expression, we addressed the molecular basis of the action of ghrelin in bone remodeling in vivo. Methods We performed molecular, genetic and cell biological analyses of Ghsr-null mice and Ghsr-null mice with tissue specific Ghsr restoration. Furthermore, we evaluated the molecular mechanism of ghrelin by molecular and cell-based assays. Results Ghsr-null mice showed a low bone mass phenotype with poor bone formation. Restoring the expression of Ghsr specifically in osteoblasts, and not in osteoclasts or the central nervous system, ameliorated bone abnormalities in Ghsr-null mice. Cell-based assays revealed ghrelin induced the phosphorylation of CREB and the expression of Runx2, which in turn accelerated osteoblast differentiation. Conclusions Our data show that ghrelin regulates bone remodeling through Ghsr in osteoblasts by modulating the CREB and Runx2 pathways. PMID:25737953

  6. Mycobacterium leprae–host-cell interactions and genetic determinants in leprosy: an overview

    PubMed Central

    Pinheiro, Roberta Olmo; de Souza Salles, Jorgenilce; Sarno, Euzenir Nunes; Sampaio, Elizabeth Pereira

    2011-01-01

    Leprosy, also known as Hansen’s disease, is a chronic infectious disease caused by Mycobacterium leprae in which susceptibility to the mycobacteria and its clinical manifestations are attributed to the host immune response. Even though leprosy prevalence has decreased dramatically, the high number of new cases indicates active transmission. Owing to its singular features, M. leprae infection is an attractive model for investigating the regulation of human immune responses to pathogen-induced disease. Leprosy is one of the most common causes of nontraumatic peripheral neuropathy worldwide. The proportion of patients with disabilities is affected by the type of leprosy and delay in diagnosis. This article briefly reviews the clinical features as well as the immunopathological mechanisms related to the establishment of the different polar forms of leprosy, the mechanisms related to M. leprae–host cell interactions and prophylaxis and diagnosis of this complex disease. Host genetic factors are summarized and the impact of the development of interventions that prevent, reverse or limit leprosy-related nerve impairments are discussed. PMID:21366421

  7. Phenotype Similarity Regression for Identifying the Genetic Determinants of Rare Diseases.

    PubMed

    Greene, Daniel; Richardson, Sylvia; Turro, Ernest

    2016-03-01

    Rare genetic disorders, which can now be studied systematically with affordable genome sequencing, are often caused by high-penetrance rare variants. Such disorders are often heterogeneous and characterized by abnormalities spanning multiple organ systems ascertained with variable clinical precision. Existing methods for identifying genes with variants responsible for rare diseases summarize phenotypes with unstructured binary or quantitative variables. The Human Phenotype Ontology (HPO) allows composite phenotypes to be represented systematically but association methods accounting for the ontological relationship between HPO terms do not exist. We present a Bayesian method to model the association between an HPO-coded patient phenotype and genotype. Our method estimates the probability of an association together with an HPO-coded phenotype characteristic of the disease. We thus formalize a clinical approach to phenotyping that is lacking in standard regression techniques for rare disease research. We demonstrate the power of our method by uncovering a number of true associations in a large collection of genome-sequenced and HPO-coded cases with rare diseases. PMID:26924528

  8. A Transposon Screen Identifies Genetic Determinants of Vibrio cholerae Resistance to High-Molecular-Weight Antibiotics.

    PubMed

    Dörr, Tobias; Delgado, Fernanda; Umans, Benjamin D; Gerding, Matthew A; Davis, Brigid M; Waldor, Matthew K

    2016-08-01

    Gram-negative bacteria are notoriously resistant to a variety of high-molecular-weight antibiotics due to the limited permeability of their outer membrane (OM). The basis of OM barrier function and the genetic factors required for its maintenance remain incompletely understood. Here, we employed transposon insertion sequencing to identify genes required for Vibrio cholerae resistance to vancomycin and bacitracin, antibiotics that are thought to be too large to efficiently penetrate the OM. The screen yielded several genes whose protein products are predicted to participate in processes important for OM barrier functions and for biofilm formation. In addition, we identified a novel factor, designated vigA (for vancomycin inhibits growth), that has not previously been characterized or linked to outer membrane function. The vigA open reading frame (ORF) codes for an inner membrane protein, and in its absence, cells became highly sensitive to glycopeptide antibiotics (vancomycin and ramoplanin) and bacitracin but not to other large antibiotics or detergents. In contrast to wild-type (WT) cells, the vigA mutant was stained with fluorescent vancomycin. These observations suggest that VigA specifically prevents the periplasmic accumulation of certain large antibiotics without exerting a general role in the maintenance of OM integrity. We also observed marked interspecies variability in the susceptibilities of Gram-negative pathogens to glycopeptides and bacitracin. Collectively, our findings suggest that the OM barrier is not absolute but rather depends on specific OM-antibiotic interactions. PMID:27216069

  9. Genetic variation, multiple paternity, and measures of reproductive success in the critically endangered hawksbill turtle (Eretmochelys imbricata).

    PubMed

    González-Garza, Blanca Idalia; Stow, Adam; Sánchez-Teyer, Lorenzo Felipe; Zapata-Pérez, Omar

    2015-12-01

    The Yucatán Peninsula in Mexico contains some of the largest breeding groups of the globally distributed and critically endangered hawksbill turtle (Eretmochelys imbricata). An improved understanding of the breeding system of this species and how its genetic variation is structured among nesting areas is required before the threats to its survival can be properly evaluated. Here, we genotype 1195 hatchlings and 41 nesting females at 12 microsatellite loci to assess levels of multiple paternity, genetic variation and whether individual levels of homozygosity are associated with reproductive success. Of the 50 clutches analyzed, only 6% have multiple paternity. The distribution of pairwise relatedness among nesting localities (rookeries) was not random with elevated within-rookery relatedness, and declining relatedness with geographic distance indicating some natal philopatry. Although there was no strong evidence that particular rookeries had lost allelic variation via drift, younger turtles had significantly lower levels of genetic variation than older turtles, suggesting some loss of genetic variation. At present there is no indication that levels of genetic variation are associated with measures of reproductive success such as clutch size, hatching success, and frequency of infertile eggs. PMID:26811751

  10. Direct determination of fluorescent whitening agents by absorption measurement in situ on thin layer chromatograms.

    PubMed

    Theidel, H

    1975-01-01

    The measuring technique for the chromatogram spectrophotometer (Zeiss) to determine the reflectance curves, the analysis according to the Kubelka-Munck function, and the basic outlines of the quantitative determination of stilbene fluorescent whitening agents (FWAs) are explained. PMID:1064527

  11. The modern budget of atmospheric methane determined from measurements (Invited)

    NASA Astrophysics Data System (ADS)

    Dlugokencky, E. J.; Nisbet, E. G.; Kirschke, S.; Bergamaschi, P. M.; Houweling, S.

    2013-12-01

    Reducing radiative forcing by atmospheric CH4 is often considered a means to slow the rate of increase in climate forcing by long-lived greenhouse gases, because there are cost-effective ways to reduce its anthropogenic emissions. For this to be effective, we have to be sure that increased emissions from natural sources responding to climate change do not cancel reductions in anthropogenic emissions. Much of what we know about the global CH4 budget is based on nearly 3 decades of high-precision, well-calibrated atmospheric observations of its spatial and temporal distribution. The observations indicate a decreasing growth rate of atmospheric CH4 from 1984 to 1998, stabilization in the CH4 burden from 1999 to 2006, and increasing CH4 at a near-constant rate since 2007. Superimposed on this long-term behavior is significant interannual variability in growth rate. What can these observations tell us about emissions? At the global scale, total emissions of CH4 are well constrained by measurements of CH4 atmospheric abundance and rate of increase with an estimate of its lifetime (~9 yr). Assuming that the lifetime has remained constant, annual emissions from 1984 through 2012 have averaged 548 Tg CH4, but emissions from 2007-2012 are 14 Tg CH4 yr-1 greater than the long-term average. While total global emissions are known reasonably well, quantification of emissions from individual sources remains difficult, in part because sources are spread over enormous areas, and emission factors vary over relatively small spatial scales and change over time. A common approach to estimating CH4 emissions from specific sources is to assimilate the spatial and temporal variations of observed CH4 abundance in a chemical transport model. Robust conclusions of these studies are that most of the interannual variability in CH4 growth rate is caused by temperature- and precipitation-driven changes in wetland emissions, with smaller contributions from its major loss process (atmospheric

  12. Profiles of Material Properties in Induction-Hardened Steel Determined through Inversion of Resonant Acoustic Measurements

    SciTech Connect

    Johnson, W.L.; Kim, S.A.; Norton, S.J.

    2005-04-09

    Electromagnetic-acoustic measurements of resonant frequencies of induction-hardened steel shafts were used in an inverse calculation to determine parameters of the radial variations in the shear constant and density, including the effects of material variations and residual stress. Parameters determined for the profile of the shear constant were consistent with independent measurements on cut specimens and estimates of the acoustoelastic contribution. The profiles determined for material variations were close to those of the measured hardness.

  13. Genetic polymorphisms as determinants for disease preventive effects of vitamin E

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polymorphisms in genes involved in vitamin E uptake, distribution, metabolism and molecular action may be important determinants for the protective effects of vitamin E supplementation. The haptoglobin 2-2 polymorphism is associated with increased production of oxygen free radicals and the consequen...

  14. A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity

    PubMed Central

    Heijink, Anne Margriet; Blomen, Vincent A.; Bisteau, Xavier; Degener, Fabian; Matsushita, Felipe Yu; Foijer, Floris; van Vugt, Marcel A. T. M.

    2015-01-01

    The Wee1 cell cycle checkpoint kinase prevents premature mitotic entry by inhibiting cyclin-dependent kinases. Chemical inhibitors of Wee1 are currently being tested clinically as targeted anticancer drugs. Wee1 inhibition is thought to be preferentially cytotoxic in p53-defective cancer cells. However, TP53 mutant cancers do not respond consistently to Wee1 inhibitor treatment, indicating the existence of genetic determinants of Wee1 inhibitor sensitivity other than TP53 status. To optimally facilitate patient selection for Wee1 inhibition and uncover potential resistance mechanisms, identification of these currently unknown genes is necessary. The aim of this study was therefore to identify gene mutations that determine Wee1 inhibitor sensitivity. We performed a genome-wide unbiased functional genetic screen in TP53 mutant near-haploid KBM-7 cells using gene-trap insertional mutagenesis. Insertion site mapping of cells that survived long-term Wee1 inhibition revealed enrichment of G1/S regulatory genes, including SKP2, CUL1, and CDK2. Stable depletion of SKP2, CUL1, or CDK2 or chemical Cdk2 inhibition rescued the γ-H2AX induction and abrogation of G2 phase as induced by Wee1 inhibition in breast and ovarian cancer cell lines. Remarkably, live cell imaging showed that depletion of SKP2, CUL1, or CDK2 did not rescue the Wee1 inhibition-induced karyokinesis and cytokinesis defects. These data indicate that the activity of the DNA replication machinery, beyond TP53 mutation status, determines Wee1 inhibitor sensitivity, and could serve as a selection criterion for Wee1-inhibitor eligible patients. Conversely, loss of the identified S-phase genes could serve as a mechanism of acquired resistance, which goes along with development of severe genomic instability. PMID:26598692

  15. Host Genetic Determinants of T Cell Responses to the MRKAd5 HIV-1 gag/pol/nef Vaccine in the Step Trial

    PubMed Central

    Fellay, Jacques; Frahm, Nicole; Shianna, Kevin V.; Cirulli, Elizabeth T.; Casimiro, Danilo R.; Robertson, Michael N.; Haynes, Barton F.; Geraghty, Daniel E.; McElrath, M. Juliana

    2011-01-01

    Understanding how human genetic variation impacts individual response to immunogens is fundamental for rational vaccine development. To explore host mechanisms involved in cellular immune responses to the MRKAd5 human immunodeficiency virus type 1 (HIV-1) gag/pol/nef vaccine tested in the Step trial, we performed a genome-wide association study of determinants of HIV-specific T cell responses, measured by interferon γ enzyme-linked immunospot assays. No human genetic variant reached genome-wide significance, but polymorphisms located in the major histocompatibility complex (MHC) region showed the strongest association with response to the HIV-1 Gag protein: HLA-B alleles known to be associated with differences in HIV-1 control were responsible for these associations. The implication of the same HLA alleles in vaccine-induced cellular immunity and in natural immune control is of relevance for vaccine design. Furthermore, our results demonstrate the importance of considering the host immunogenetic background in the analysis of immune responses to T cell vaccines. PMID:21278214

  16. Genetically Determined Susceptibility to Tuberculosis in Mice Causally Involves Accelerated and Enhanced Recruitment of Granulocytes

    PubMed Central

    Keller, Christine; Hoffmann, Reinhard; Lang, Roland; Brandau, Sven; Hermann, Corinna; Ehlers, Stefan

    2006-01-01

    Classical twin studies and recent linkage analyses of African populations have revealed a potential involvement of host genetic factors in susceptibility or resistance to Mycobacterium tuberculosis infection. In order to identify the candidate genes involved and test their causal implication, we capitalized on the mouse model of tuberculosis, since inbred mouse strains also differ substantially in their susceptibility to infection. Two susceptible and two resistant mouse strains were aerogenically infected with 1,000 CFU of M. tuberculosis, and the regulation of gene expression was examined by Affymetrix GeneChip U74A array with total lung RNA 2 and 4 weeks postinfection. Four weeks after infection, 96 genes, many of which are involved in inflammatory cell recruitment and activation, were regulated in common. One hundred seven genes were differentially regulated in susceptible mouse strains, whereas 43 genes were differentially expressed only in resistant mice. Data mining revealed a bias towards the expression of genes involved in granulocyte pathophysiology in susceptible mice, such as an upregulation of those for the neutrophil chemoattractant LIX (CXCL5), interleukin 17 receptor, phosphoinositide kinase 3 delta, or gamma interferon-inducible protein 10. Following M. tuberculosis challenge in both airways or peritoneum, granulocytes were recruited significantly faster and at higher numbers in susceptible than in resistant mice. When granulocytes were efficiently depleted by either of two regimens at the onset of infection, only susceptible mice survived aerosol challenge with M. tuberculosis significantly longer than control mice. We conclude that initially enhanced recruitment of granulocytes contributes to susceptibility to tuberculosis. PMID:16790804

  17. The genetic tumor background is an important determinant for heterogeneous MYCN-amplified neuroblastoma.

    PubMed

    Bogen, Dominik; Brunner, Clemens; Walder, Diana; Ziegler, Andrea; Abbasi, Reza; Ladenstein, Ruth L; Noguera, Rosa; Martinsson, Tommy; Amann, Gabriele; Schilling, Freimut H; Ussowicz, Marek; Benesch, Martin; Ambros, Peter F; Ambros, Inge M

    2016-07-01

    Amplification of MYCN is the signature genetic aberration of 20-25% of neuroblastoma and a stratifying marker associated with aggressive tumor behavior. The detection of heterogeneous MYCN amplification (hetMNA) poses a diagnostic dilemma due to the uncertainty of its relevance to tumor behavior. Here, we aimed to shed light on the genomic background which permits hetMNA in neuroblastoma and tied the occurrence to other stratifying markers and disease outcome. We performed SNP analysis using Affymetrix Cytoscan HD arrays on 63 samples including constitutional DNA, tumor, bone marrow and relapse samples of 26 patients with confirmed hetMNA by MYCN-FISH. Tumors of patients ≤18m were mostly aneuploid with numeric chromosomal aberrations (NCAs), presented a prominent MNA subclone and carried none or a few segmental chromosomal aberrations (SCAs). In older patients, tumors were mostly di- or tetraploid, contained a lower number of MNA cells and displayed a multitude of SCAs including concomitant 11q deletions. These patients often suffered disease progression, tumor dissemination and relapse. Restricted to aneuploid tumors, we detected chromosomes with uniparental di- or trisomy (UPD/UPT) in almost every sample. UPD11 was exclusive to tumors of younger patients whereas older patients featured UPD14. In this study, the MNA subclone appears to be constraint by the tumor environment and thus less relevant for tumor behavior in aggressive tumors with a high genomic instability and many segmental aberrations. A more benign tumor background and lower tumor stage may favor an outgrowth of the MNA clone but tumors generally responded better to treatment. PMID:26910568

  18. What determines the acceptability of genetically modified food that can improve human nutrition?

    SciTech Connect

    Purchase, Iain F.H. . E-mail: ifhp@chadzombe.u-net.com

    2005-09-01

    It has been predicted that by 2025 there will be an annual shortfall of cereals for feeding the human population of 68.5 million tonnes. One possible solution is the use of genetically modified (GM) crops, which are already grown extensively (59 million ha of GM crops were planted in 2002) in the USA, South America, Africa and China. Nevertheless, there is considerable disagreement about the advisability of using such crops, particularly in Europe. Obviously, the safety of the food derived from the GM crops is a primary consideration. Safety assessment relies on establishing that the food is substantially equivalent to its non-GM counterpart and specific testing for allergenicity of proteins and toxicity of metabolites and the whole food. There appears to be international agreement on the principles of safety assessment. Safety to the environment is equally important, but will not be covered in this presentation. The public's perception of the risk of new technology is critical to its acceptance. Perception of risk, in turn, depends on the credibility of the source of the information and trust in the regulatory process. In many countries, the public appears to have lost its trust in the scientists and government dealing with GM food, making the acceptability of GM crops uncertain. Of equal importance are the socio-economic factors that impinge on the viability of GM produce. These include intellectual property protection, trade liberalisation (through subsidy and tariff barriers in developed countries) and the intensity of bio safety regulations. The socio-economic interests of developed and developing countries may diverge and may even be contradictory in any one country. Acceptance of GM crops will thus depend on detailed issues surrounding particular crops and economies.

  19. What determines the acceptability of genetically modified food that can improve human nutrition?

    PubMed

    Purchase, Iain F H

    2005-09-01

    It has been predicted that by 2025 there will be an annual shortfall of cereals for feeding the human population of 68.5 million tones. One possible solution is the use of genetically modified (GM) crops, which are already grown extensively (59 million ha of GM crops were planted in 2002) in the USA, South America, Africa and China. Nevertheless, there is considerable disagreement about the advisability of using such crops, particularly in Europe. Obviously, the safety of the food derived from the GM crops is a primary consideration. Safety assessment relies on establishing that the food is substantially equivalent to its non-GM counterpart and specific testing for allergenicity of proteins and toxicity of metabolites and the whole food. There appears to be international agreement on the principles of safety assessment. Safety to the environment is equally important, but will not be covered in this presentation. The public's perception of the risk of new technology is critical to its acceptance. Perception of risk, in turn, depends on the credibility of the source of the information and trust in the regulatory process. In many countries, the public appears to have lost its trust in the scientists and government dealing with GM food, making the acceptability of GM crops uncertain. Of equal importance are the socio-economic factors that impinge on the viability of GM produce. These include intellectual property protection, trade liberalization (through subsidy and tariff barriers in developed countries) and the intensity of bio safety regulations. The socio-economic interests of developed and developing countries may diverge and may even be contradictory in any one country. Acceptance of GM crops will thus depend on detailed issues surrounding particular crops and economies. PMID:15982686

  20. The genetic tumor background is an important determinant for heterogeneous MYCN‐amplified neuroblastoma

    PubMed Central

    Bogen, Dominik; Brunner, Clemens; Walder, Diana; Ziegler, Andrea; Abbasi, Reza; Ladenstein, Ruth L.; Noguera, Rosa; Martinsson, Tommy; Amann, Gabriele; Schilling, Freimut H.; Ussowicz, Marek; Benesch, Martin

    2016-01-01

    Amplification of MYCN is the signature genetic aberration of 20–25% of neuroblastoma and a stratifying marker associated with aggressive tumor behavior. The detection of heterogeneous MYCN amplification (hetMNA) poses a diagnostic dilemma due to the uncertainty of its relevance to tumor behavior. Here, we aimed to shed light on the genomic background which permits hetMNA in neuroblastoma and tied the occurrence to other stratifying markers and disease outcome. We performed SNP analysis using Affymetrix Cytoscan HD arrays on 63 samples including constitutional DNA, tumor, bone marrow and relapse samples of 26 patients with confirmed hetMNA by MYCN‐FISH. Tumors of patients ≤18m were mostly aneuploid with numeric chromosomal aberrations (NCAs), presented a prominent MNA subclone and carried none or a few segmental chromosomal aberrations (SCAs). In older patients, tumors were mostly di‐ or tetraploid, contained a lower number of MNA cells and displayed a multitude of SCAs including concomitant 11q deletions. These patients often suffered disease progression, tumor dissemination and relapse. Restricted to aneuploid tumors, we detected chromosomes with uniparental di‐ or trisomy (UPD/UPT) in almost every sample. UPD11 was exclusive to tumors of younger patients whereas older patients featured UPD14. In this study, the MNA subclone appears to be constraint by the tumor environment and thus less relevant for tumor behavior in aggressive tumors with a high genomic instability and many segmental aberrations. A more benign tumor background and lower tumor stage may favor an outgrowth of the MNA clone but tumors generally responded better to treatment. PMID:26910568

  1. Virulence determinants, drug resistance and mobile genetic elements of Laribacter hongkongensis: a genome-wide analysis

    PubMed Central

    2011-01-01

    Background Laribacter hongkongensis is associated with community-acquired gastroenteritis and traveler's diarrhea. In this study, we performed an in-depth annotation of the genes in its genome related to the various steps in the infective process, drug resistance and mobile genetic elements. Results For acid and bile resistance, L. hongkongensis possessed a urease gene cassette, two arc gene clusters and bile salt efflux systems. For intestinal colonization, it possessed a putative adhesin of the autotransporter family homologous to those of diffusely adherent Escherichia coli (E. coli) and enterotoxigenic E. coli. To evade from host defense, it possessed superoxide dismutase and catalases. For lipopolysaccharide biosynthesis, it possessed the same set of genes that encode enzymes for synthesizing lipid A, two Kdo units and heptose units as E. coli, but different genes for its symmetrical acylation pattern, and nine genes for polysaccharide side chains biosynthesis. It contained a number of CDSs that encode putative cell surface acting (RTX toxin and hemolysins) and intracellular cytotoxins (patatin-like proteins) and enzymes for invasion (outer membrane phospholipase A). It contained a broad variety of antibiotic resistance-related genes, including genes related to β-lactam (n = 10) and multidrug efflux (n = 54). It also contained eight prophages, 17 other phage-related CDSs and 26 CDSs for transposases. Conclusions The L. hongkongensis genome possessed genes for acid and bile resistance, intestinal mucosa colonization, evasion of host defense and cytotoxicity and invasion. A broad variety of antibiotic resistance or multidrug resistance genes, a high number of prophages, other phage-related CDSs and CDSs for transposases, were also identified. PMID:21711902

  2. Genetically determined ancestry is more informative than self-reported race in HIV-infected and -exposed children.

    PubMed

    Spector, Stephen A; Brummel, Sean S; Nievergelt, Caroline M; Maihofer, Adam X; Singh, Kumud K; Purswani, Murli U; Williams, Paige L; Hazra, Rohan; Van Dyke, Russell; Seage, George R

    2016-09-01

    The Pediatric HIV/AIDS Cohort Study (PHACS), the largest ongoing longitudinal study of perinatal HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) children in the United States, comprises the Surveillance Monitoring of Antiretroviral Therapy [ART] Toxicities (SMARTT) Study in PHEU children and the Adolescent Master Protocol (AMP) that includes PHIV and PHEU children ≥7 years. Although race/ethnicity is often used to assess health outcomes, this approach remains controversial and may fail to accurately reflect the backgrounds of ancestry-diverse populations as represented in the PHACS participants.In this study, we compared genetically determined ancestry (GDA) and self-reported race/ethnicity (SRR) in the PHACS cohort. GDA was estimated using a highly discriminative panel of 41 single nucleotide polymorphisms and compared to SRR. Because SRR was similar between the PHIV and PHEU, and between the AMP and SMARTT cohorts, data for all unique 1958 participants were combined.According to SRR, 63% of study participants identified as Black/African-American, 27% White, and 34% Hispanic. Using the highest percentage of ancestry/ethnicity to identify GDA, 9.5% of subjects were placed in the incorrect superpopulation based on SRR. When ≥50% or ≥75% GDA of a given superpopulation was required, 12% and 25%, respectively, of subjects were placed in the incorrect superpopulation based on SRR, and the percent of subjects classified as multiracial increased. Of 126 participants with unidentified SRR, 71% were genetically identified as Eurasian.GDA provides a more robust assessment of race/ethnicity when compared to self-report, and study participants with unidentified SRR could be assigned GDA using genetic markers. In addition, identification of continental ancestry removes the taxonomic identification of race as a variable when identifying risk for clinical outcomes. PMID:27603370

  3. Genetic determinants of folate and vitamin B12 metabolism: a common pathway in neural tube defect and Down syndrome?

    PubMed

    Guéant, Jean-Louis; Guéant-Rodriguez, Rosa-Maria; Anello, Guido; Bosco, Paolo; Brunaud, Laurent; Romano, Corrado; Ferri, Rafaele; Romano, Antonino; Candito, Mirande; Namour, Bernard

    2003-11-01

    One-carbon metabolism is under the influence of folate, vitamin B12 and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR 677 C --> T and 1298 A --> C), of methionine synthase (MTR 2756 C --> G), methionine synthase reductase (MTRR 66 A --> G) and transcobalamin (TCN 776 C --> G). The pathogenesis of neural tube defect (NTD) may be related to this metabolism. The influence of the MTHFR 677 C --> T polymorphism reported in The Netherlands and Ireland can be questioned in southern Italy, France and Great Britain. MTRR, combined with a low level of vitamin B12, increases the risk of NTD and of having a child with NTD in Canada, while TCN 776 GG and MTRR 66 GG mutated genotypes associated with the MTHFR 677 CC wild-type are predictors of NTD cases in Sicily. Down syndrome (DS) is due to a failure of normal chromosomal segregation during meiosis, possibly related to one-carbon metabolism. MTHFR 677 C --> T and MTRR 66 A --> G polymorphisms are associated with a greater risk of having a child with DS in North America, Ireland and The Netherlands. In contrast, MTHFR 677 C --> T has no influence on DS risk in France and Sicily, while homocysteine and MTR 2756 AG/GG genotypes are predictors of DS risk in Sicily. In conclusion, NTD and DS are influenced by the same genetic determinants of one-carbon metabolism. The distinct data produced in different geographical areas may be explained by differences in the nutritional environment and genetic characteristics of the populations. PMID:14656028

  4. Genetic Determinants for Enzymatic Digestion of Lignocellulosic Biomass Are Independent of Those for Lignin Abundance in a Maize Recombinant Inbred Population1[W][OPEN

    PubMed Central

    Penning, Bryan W.; Sykes, Robert W.; Babcock, Nicholas C.; Dugard, Christopher K.; Held, Michael A.; Klimek, John F.; Shreve, Jacob T.; Fowler, Matthew; Ziebell, Angela; Davis, Mark F.; Decker, Stephen R.; Turner, Geoffrey B.; Mosier, Nathan S.; Springer, Nathan M.; Thimmapuram, Jyothi; Weil, Clifford F.; McCann, Maureen C.; Carpita, Nicholas C.

    2014-01-01

    Biotechnological approaches to reduce or modify lignin in biomass crops are predicated on the assumption that it is the principal determinant of the recalcitrance of biomass to enzymatic digestion for biofuels production. We defined quantitative trait loci (QTL) in the Intermated B73 × Mo17 recombinant inbred maize (Zea mays) population using pyrolysis molecular-beam mass spectrometry to establish stem lignin content and an enzymatic hydrolysis assay to measure glucose and xylose yield. Among five multiyear QTL for lignin abundance, two for 4-vinylphenol abundance, and four for glucose and/or xylose yield, not a single QTL for aromatic abundance and sugar yield was shared. A genome-wide association study for lignin abundance and sugar yield of the 282-member maize association panel provided candidate genes in the 11 QTL of the B73 and Mo17 parents but showed that many other alleles impacting these traits exist among this broader pool of maize genetic diversity. B73 and Mo17 genotypes exhibited large differences in gene expression in developing stem tissues independent of allelic variation. Combining these complementary genetic approaches provides a narrowed list of candidate genes. A cluster of SCARECROW-LIKE9 and SCARECROW-LIKE14 transcription factor genes provides exceptionally strong candidate genes emerging from the genome-wide association study. In addition to these and genes associated with cell wall metabolism, candidates include several other transcription factors associated with vascularization and fiber formation and components of cellular signaling pathways. These results provide new insights and strategies beyond the modification of lignin to enhance yields of biofuels from genetically modified biomass. PMID:24972714

  5. Genetic Determinants for Enzymatic Digestion of Lignocellulosic Biomass Are Independent of Those for Lignin Abundance in a Maize Recombinant Inbred Population

    DOE PAGESBeta

    Penning, Bryan W.; Sykes, Robert W.; Babcock, Nicholas C.; Dugard, Christopher K.; Held, Michael A.; Klimek, John F.; Shreve, Jacob T.; Fowler, Matthew; Ziebell, Angela; Davis, Mark F.; et al

    2014-06-27

    Biotechnological approaches to reduce or modify lignin in biomass crops are predicated on the assumption that it is the principal determinant of the recalcitrance of biomass to enzymatic digestion for biofuels production. We defined quantitative trait loci (QTL) in the Intermated B73 x 3 Mo17 recombinant inbred maize (Zea mays) population using pyrolysis molecular-beam mass spectrometry to establish stem lignin content and an enzymatic hydrolysis assay to measure glucose and xylose yield. Among five multiyear QTL for lignin abundance, two for 4-vinylphenol abundance, and four for glucose and/or xylose yield, not a single QTL for aromatic abundance and sugar yieldmore » was shared. A genome-wide association study for lignin abundance and sugar yield of the 282- member maize association panel provided candidate genes in the 11 QTL of the B73 and Mo17 parents but showed that many other alleles impacting these traits exist among this broader pool of maize genetic diversity. B73 and Mo17 genotypes exhibited large differences in gene expression in developing stem tissues independent of allelic variation. Combining these complementary genetic approaches provides a narrowed list of candidate genes. A cluster of SCARECROW-LIKE9 and SCARECROW-LIKE14 transcription factor genes provides exceptionally strong candidate genes emerging from the genome-wide association study. In addition to these and genes associated with cell wall metabolism, candidates include several other transcription factors associated with vascularization and fiber formation and components of cellular signaling pathways. Finally, these results provide new insights and strategies beyond the modification of lignin to enhance yields of biofuels from genetically modified biomass.« less

  6. Genetic Determinants for Enzymatic Digestion of Lignocellulosic Biomass Are Independent of Those for Lignin Abundance in a Maize Recombinant Inbred Population.

    PubMed

    Penning, Bryan W; Sykes, Robert W; Babcock, Nicholas C; Dugard, Christopher K; Held, Michael A; Klimek, John F; Shreve, Jacob T; Fowler, Matthew; Ziebell, Angela; Davis, Mark F; Decker, Stephen R; Turner, Geoffrey B; Mosier, Nathan S; Springer, Nathan M; Thimmapuram, Jyothi; Weil, Clifford F; McCann, Maureen C; Carpita, Nicholas C

    2014-06-27

    Biotechnological approaches to reduce or modify lignin in biomass crops are predicated on the assumption that it is the principal determinant of the recalcitrance of biomass to enzymatic digestion for biofuels production. We defined quantitative trait loci (QTL) in the Intermated B73 × Mo17 recombinant inbred maize (Zea mays) population using pyrolysis molecular-beam mass spectrometry to establish stem lignin content and an enzymatic hydrolysis assay to measure glucose and xylose yield. Among five multiyear QTL for lignin abundance, two for 4-vinylphenol abundance, and four for glucose and/or xylose yield, not a single QTL for aromatic abundance and sugar yield was shared. A genome-wide association study for lignin abundance and sugar yield of the 282-member maize association panel provided candidate genes in the 11 QTL of the B73 and Mo17 parents but showed that many other alleles impacting these traits exist among this broader pool of maize genetic diversity. B73 and Mo17 genotypes exhibited large differences in gene expression in developing stem tissues independent of allelic variation. Combining these complementary genetic approaches provides a narrowed list of candidate genes. A cluster of SCARECROW-LIKE9 and SCARECROW-LIKE14 transcription factor genes provides exceptionally strong candidate genes emerging from the genome-wide association study. In addition to these and genes associated with cell wall metabolism, candidates include several other transcription factors associated with vascularization and fiber formation and components of cellular signaling pathways. These results provide new insights and strategies beyond the modification of lignin to enhance yields of biofuels from genetically modified biomass. PMID:24972714

  7. Genetic Determinants for Enzymatic Digestion of Lignocellulosic Biomass Are Independent of Those for Lignin Abundance in a Maize Recombinant Inbred Population

    SciTech Connect

    Penning, Bryan W.; Sykes, Robert W.; Babcock, Nicholas C.; Dugard, Christopher K.; Held, Michael A.; Klimek, John F.; Shreve, Jacob T.; Fowler, Matthew; Ziebell, Angela; Davis, Mark F.; Decker, Stephen R.; Turner, Geoffrey B.; Mosier, Nathan S.; Springer, Nathan M.; Thimmapuram, Jyothi; Weil, Clifford F.; McCann, Maureen C.; Carpita, Nicholas C.

    2014-06-27

    Biotechnological approaches to reduce or modify lignin in biomass crops are predicated on the assumption that it is the principal determinant of the recalcitrance of biomass to enzymatic digestion for biofuels production. We defined quantitative trait loci (QTL) in the Intermated B73 x 3 Mo17 recombinant inbred maize (Zea mays) population using pyrolysis molecular-beam mass spectrometry to establish stem lignin content and an enzymatic hydrolysis assay to measure glucose and xylose yield. Among five multiyear QTL for lignin abundance, two for 4-vinylphenol abundance, and four for glucose and/or xylose yield, not a single QTL for aromatic abundance and sugar yield was shared. A genome-wide association study for lignin abundance and sugar yield of the 282- member maize association panel provided candidate genes in the 11 QTL of the B73 and Mo17 parents but showed that many other alleles impacting these traits exist among this broader pool of maize genetic diversity. B73 and Mo17 genotypes exhibited large differences in gene expression in developing stem tissues independent of allelic variation. Combining these complementary genetic approaches provides a narrowed list of candidate genes. A cluster of SCARECROW-LIKE9 and SCARECROW-LIKE14 transcription factor genes provides exceptionally strong candidate genes emerging from the genome-wide association study. In addition to these and genes associated with cell wall metabolism, candidates include several other transcription factors associated with vascularization and fiber formation and components of cellular signaling pathways. Finally, these results provide new insights and strategies beyond the modification of lignin to enhance yields of biofuels from genetically modified biomass.