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Sample records for genetic evidence links

  1. Genetic evidence linking lung cancer and COPD: a new perspective

    Directory of Open Access Journals (Sweden)

    Crapo JD

    2011-07-01

    Full Text Available Robert P Young1,4, Raewyn J Hopkins1, Gregory D Gamble1, Carol Etzel2, Randa El-Zein2, James D Crapo31Department of Medicine and School of Biological Sciences, University of Auckland, Auckland, New Zealand; 2Department of Epidemiology, UT MD Anderson Cancer Center, Houston, TX, USA; 3National Jewish Health, Denver, CO, USA; 4Synergenz Biosciences Ltd, Auckland, New ZealandAbstract: Epidemiological studies indicate that tobacco smoke exposure accounts for nearly 90% of cases of chronic obstructive pulmonary disease (COPD and lung cancer. However, genetic factors may explain why 10%–30% of smokers develop these complications. This perspective reviews the evidence suggesting that COPD is closely linked to susceptibility to lung cancer and outlines the potential relevance of this observation. Epidemiological studies show that COPD is the single most important risk factor for lung cancer among smokers and predates lung cancer in up to 80% of cases. Genome-wide association studies of lung cancer, lung function, and COPD have identified a number of overlapping “susceptibility” loci. With stringent phenotyping, it has recently been shown that several of these overlapping loci are independently associated with both COPD and lung cancer. These loci implicate genes underlying pulmonary inflammation and apoptotic processes mediated by the bronchial epithelium, and link COPD with lung cancer at a molecular genetic level. It is currently possible to derive risk models for lung cancer that incorporate lung cancer-specific genetic variants, recently identified “COPD-related” genetic variants, and clinical variables. Early studies suggest that single nucleotide polymorphism-based risk stratification of smokers might help better target novel prevention and early diagnostic strategies in lung cancer.Keywords: lung cancer, chronic obstructive pulmonary disease, association study, single nucleotide polymorphism, risk model

  2. Physiologic and genetic evidence links hemopexin to triglycerides in mice and humans.

    Science.gov (United States)

    Lawson, H A; Zayed, M; Wayhart, J P; Fabbrini, E; Love-Gregory, L; Klein, S; Semenkovich, C F

    2017-04-01

    Elevated triglycerides predict insulin resistance and vascular disease in obesity, but how the inert triglyceride molecule is related to development of metabolic disease is unknown. To pursue novel potential mediators of triglyceride-associated metabolic disease, we used a forward genetics approach involving inbred mice and translated our findings to human subjects. Hemopexin (HPX) was identified as a differentially expressed gene within a quantitative trait locus associated with serum triglycerides in an F 16 advanced intercross between the LG/J and SM/J strains of mice. Hpx expression was evaluated in both the reproductive fat pads and livers of mice representing three strains, LG/J (n=25), SM/J (n=27) and C57Bl/6J (n=19), on high- and low-fat diets. The effect of altered Hpx expression on adipogenesis was studied in 3T3-L1 cells. Circulating HPX protein along with HPX expression were characterized in subcutaneous white adipose tissue samples obtained from a cohort of metabolically abnormal (n=18) and of metabolically normal (n=24) obese human subjects. We further examined the relationship between HPX and triglycerides in human atherosclerotic plaques (n=18). HPX expression in mouse adipose tissue, but not in liver, was regulated by dietary fat regardless of genetic background. HPX increased in concert with adipogenesis in 3T3-L1 cells, and disruption of its expression impaired adipocyte differentiation. RNAseq data from the adipose tissue of obese humans showed differential expression of HPX based on metabolic disease status (Ptriglycerides in these subjects (r=0.33; P=0.03). HPX was also found in an unbiased proteomic screen of human atherosclerotic plaques and shown to display differential abundance based on the extent of disease and triglyceride content (Ptriglycerides and provide a framework for understanding mechanisms underlying lipid metabolism and metabolic disease.

  3. The genetic link between the Azores Archipelago and the Southern Azores Seamount Chain (SASC): The elemental, isotopic and chronological evidences

    Science.gov (United States)

    Ribeiro, Luisa Pinto; Martins, Sofia; Hildenbrand, Anthony; Madureira, Pedro; Mata, João

    2017-12-01

    New geochemical, isotopic (Sr-Nd-Hf-Pb) and K-Ar data, are presented here on samples from the Southern Azores Seamount Chain (SASC) located south of the Azores Plateau. The SASC also includes the Great Meteor, Small Meteor and Closs seamounts, morphologically connected by a saddle at - 4100 m deep. We conclude that the SASC are characterized by a narrow isotopic variability that falls within the Azores isotopic field. Although each seamount has its own isotopic signature, their mantle source must comprise four local mantle end-members, three of which are common to the Azores, e.g. Plato isotopic signature results from the mixing between HIMU and N-MORB while Great Meteor signature results from this mix with the Azores Common Component (AzCC). A fourth end-member with high 208Pb/204Pb and decoupled Th/U ratios (Δ8/4 up to 59.2) is identified on Great Meteor northern flank. New K-Ar ages on Plato (33.4 ± 0.5 Ma) and Small Hyeres (31.6 ± 0.4 Ma) show nearly coeval volcanism, which is contemporaneous with the E-MORBs erupted at the MAR, drilled on oceanic crust with 30-34 Ma (DSDP82). This study endorses the genetic link between the Azores Archipelago and the SASC to the long-term activity of the Azores plume and the large-scale ridge-hotspot interaction, contributing to better constrain the temporal-spatial evolution of this region of the North Atlantic.

  4. Negative self-referential processing is associated with genetic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR): Evidence from two independent studies.

    Science.gov (United States)

    Dainer-Best, Justin; Disner, Seth G; McGeary, John E; Hamilton, Bethany J; Beevers, Christopher G

    2018-01-01

    The current research examined whether carriers of the short 5-HTTLPR allele (in SLC6A4), who have been shown to selectively attend to negative information, exhibit a bias towards negative self-referent processing. The self-referent encoding task (SRET) was used to measure self-referential processing of positive and negative adjectives. Ratcliff's diffusion model isolated and extracted decision-making components from SRET responses and reaction times. Across the initial (N = 183) and replication (N = 137) studies, results indicated that short 5-HTTLPR allele carriers more easily categorized negative adjectives as self-referential (i.e., higher drift rate). Further, drift rate was associated with recall of negative self-referential stimuli. Findings across both studies provide further evidence that genetic variation may contribute to the etiology of negatively biased processing of self-referent information. Large scale studies examining the genetic contributions to negative self-referent processing may be warranted.

  5. Hypothetical link between infertility and genetically modified food.

    Science.gov (United States)

    Gao, Mingxia; Li, Bin; Yuan, Wenzhen; Zhao, Lihui; Zhang, Xuehong

    2014-01-01

    It is speculated that genetically modified food (GMF)/genetically modified organism (GMO) is responsible for infertility development. The risk linked with a wide use of GMFs/GMOs offers the basic elements for social criticism. However, to date, it has not been justified whether the bad effects are directly resulted from products of genetic modifications or trans-genesis process. Extensive experience with the risk assessment of whole foods has been applied recently on the safety and nutritional testing of GMFs/GMOs. Investigations have tested the safety of GMFs including sub-acute, chronic, reproductive, multi-generation and carcinogenicity studies. We extrapolated the potential risks associated with GMFs/GMOs on reproduction, and analyzed the multi-aspect linked between infertility and GMFs/GMOs. It could be conjectured that GMFs/GMOs could be potential hazard on reproduction, linking to the development of infertility through influencing the endocrine metabolism, endometriosis. However, little evidence shows the impaction on embryo or reproductive related tumor due to the limited literatures, and needs further research. The article presents some related patents on GMFs/GMOs, and some methods for tracking GMOs.

  6. Genetics Home Reference: X-linked acrogigantism

    Science.gov (United States)

    ... that is caused by pituitary gland abnormalities (pituitary gigantism). Related Information What information about a genetic condition can statistics provide? Why are some genetic conditions more common ...

  7. Linking unfounded beliefs to genetic dopamine availability

    Science.gov (United States)

    Schmack, Katharina; Rössler, Hannes; Sekutowicz, Maria; Brandl, Eva J.; Müller, Daniel J.; Petrovic, Predrag; Sterzer, Philipp

    2015-01-01

    Unfounded convictions involving beliefs in the paranormal, grandiosity ideas or suspicious thoughts are endorsed at varying degrees among the general population. Here, we investigated the neurobiopsychological basis of the observed inter-individual variability in the propensity toward unfounded beliefs. One hundred two healthy individuals were genotyped for four polymorphisms in the COMT gene (rs6269, rs4633, rs4818, and rs4680, also known as val158met) that define common functional haplotypes with substantial impact on synaptic dopamine degradation, completed a questionnaire measuring unfounded beliefs, and took part in a behavioral experiment assessing perceptual inference. We found that greater dopamine availability was associated with a stronger propensity toward unfounded beliefs, and that this effect was statistically mediated by an enhanced influence of expectations on perceptual inference. Our results indicate that genetic differences in dopaminergic neurotransmission account for inter-individual differences in perceptual inference linked to the formation and maintenance of unfounded beliefs. Thus, dopamine might be critically involved in the processes underlying one's interpretation of the relationship between the self and the world. PMID:26483654

  8. Linking unfounded beliefs to genetic dopamine availability

    Directory of Open Access Journals (Sweden)

    Katharina eSchmack

    2015-09-01

    Full Text Available Unfounded convictions involving beliefs in the paranormal, grandiosity ideas or suspicious thoughts are endorsed at varying degrees among the general population. Here, we investigated the neurobiopsychological basis of the observed inter-individual variability in the propensity towards unfounded beliefs. 109 healthy individuals were genotyped for four polymorphisms in the COMT gene (rs6269, rs4633, rs4818 and rs4680, also known as val158met that define common functional haplotypes with substantial impact on synaptic dopamine degradation, completed a questionnaire measuring unfounded beliefs, and took part in a behavioural experiment assessing perceptual inference. We found that greater dopamine availability was associated with a stronger propensity towards unfounded beliefs, and that this effect was mediated by an enhanced influence of expectations on perceptual inference. Our results indicate that genetic differences in dopaminergic neurotransmission account for inter-individual differences in perceptual inference linked to the formation and maintenance of unfounded beliefs. Thus, dopamine might be critically involved in the processes underlying one's interpretation of the relationship between the self and the world.

  9. Genetics Home Reference: X-linked adrenoleukodystrophy

    Science.gov (United States)

    ... PubMed Wanders RJ, Waterham HR. Peroxisomal disorders I: biochemistry and genetics of peroxisome biogenesis disorders. Clin Genet. ... not be used as a substitute for professional medical care or advice. Users with questions about a ...

  10. The importance of link evidence in Wikipedia

    NARCIS (Netherlands)

    Kamps, J.; Koolen, M.

    2008-01-01

    Wikipedia is one of the most popular information sources on the Web. The free encyclopedia is densely linked. The link structure in Wikipedia differs from the Web at large: internal links in Wikipedia are typically based on words naturally occurring in a page, and link to another semantically

  11. Genetics Home Reference: X-linked thrombocytopenia

    Science.gov (United States)

    ... Benson EM. Identification of WASP mutations in 10 Australian families with Wiskott-Aldrich syndrome and X-linked ... API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & Players U.S. Department of ...

  12. Genetics Home Reference: X-linked severe combined immunodeficiency

    Science.gov (United States)

    ... Severe Combined Immunodeficiency National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases Educational Resources (6 links) Boston Children's Hospital Genetic Science Learning Center, University of Utah Great Ormond ...

  13. AMD genetics in India: The missing links

    Directory of Open Access Journals (Sweden)

    Akshay eAnand

    2016-05-01

    Full Text Available Age related macular degeneration is a disease condition which occurs in aged peoples. There are various changes occurs at the cellular, molecular and physiological levels with age (Kaushal et al, 2013; Samiec et al 1988. Drusen deposition between RPE and Bruch’s membrane is one of the key features in AMD patients (Mullins RF et al, 2000; Hagemana et al, 2001 as Aβ/tau aggregates in AD patients. The primary goal of this review is to discuss whether the various candidate genes and associated biomarkers, that are supposed to play an independent role in progression of AMD, exert deleterious effect on phenotype, alone or in combination, in Indian AMD patients from the same ethnic group. A statistical model for probable interaction between genes could also be derived from such analysis. We can use multiple modalities to identify and enrol AMD patients based on established clinical criteria and examine the risk factors to determine if these genes are associated with risk factors, biomarkers or disease by Mendelian randomization. Similarly, there are large numbers of single nucleotide polymorphisms (SNPs identified in human population. Even non-synonymous SNPs (nsSNPs are believed to induce deleterious effects on the functionality of various proteins. The study of such snSNPs could provide a better genetic insight for diverse phenotypes of AMD patients, predicting significant risk factors for the disease. Therefore, the prediction of biological effect of nsSNPs in the candidate genes is highly solicited.Therefore, genotyping and levels of protein expression of various genes would provide bigger canvas in genetic complexity of AMD pathology which should be evaluated by valid statistical and bioinformatics’ tools. Longitudinal follow up of Indian AMD patients to evaluate the temporal effect of SNPs and biomarkers on progression of disease could also provide unique strategy in the field.

  14. Strengthening health systems through linking research evidence to ...

    African Journals Online (AJOL)

    informed policies. Accordingly, a critical way of addressing these challenges facing health systems in the region is through the linking of health research findings to policy. Keywords: Evidence; Sub-Saharan Africa; Health Policy; Health Systems ...

  15. Optimal design of link systems using successive zooming genetic algorithm

    Science.gov (United States)

    Kwon, Young-Doo; Sohn, Chang-hyun; Kwon, Soon-Bum; Lim, Jae-gyoo

    2009-07-01

    Link-systems have been around for a long time and are still used to control motion in diverse applications such as automobiles, robots and industrial machinery. This study presents a procedure involving the use of a genetic algorithm for the optimal design of single four-bar link systems and a double four-bar link system used in diesel engine. We adopted the Successive Zooming Genetic Algorithm (SZGA), which has one of the most rapid convergence rates among global search algorithms. The results are verified by experiment and the Recurdyn dynamic motion analysis package. During the optimal design of single four-bar link systems, we found in the case of identical input/output (IO) angles that the initial and final configurations show certain symmetry. For the double link system, we introduced weighting factors for the multi-objective functions, which minimize the difference between output angles, providing balanced engine performance, as well as the difference between final output angle and the desired magnitudes of final output angle. We adopted a graphical method to select a proper ratio between the weighting factors.

  16. Zika Virus Infection and Microcephaly: Evidence for a Causal Link

    Directory of Open Access Journals (Sweden)

    Jin-Na Wang

    2016-10-01

    Full Text Available Zika virus (ZIKV is a flavivirus related to the Dengue, yellow fever and West Nile viruses. Since the explosive outbreaks of ZIKV in Latin America in 2015, a sudden increase in the number of microcephaly cases has been observed in infants of women who were pregnant when they contracted the virus. The severity of this condition raises grave concerns, and extensive studies on the possible link between ZIKV infection and microcephaly have been conducted. There is substantial evidence suggesting that there is a causal link between ZIKV and microcephaly, however, future studies are warranted to solidify this association. To summarize the most recent evidence on this issue and provide perspectives for future studies, we reviewed the literature to identify existing evidence of the causal link between ZIKV infection and microcephaly within research related to the epidemics, laboratory diagnosis, and possible mechanisms.

  17. Zika Virus Infection and Microcephaly: Evidence for a Causal Link.

    Science.gov (United States)

    Wang, Jin-Na; Ling, Feng

    2016-10-20

    Zika virus (ZIKV) is a flavivirus related to the Dengue, yellow fever and West Nile viruses. Since the explosive outbreaks of ZIKV in Latin America in 2015, a sudden increase in the number of microcephaly cases has been observed in infants of women who were pregnant when they contracted the virus. The severity of this condition raises grave concerns, and extensive studies on the possible link between ZIKV infection and microcephaly have been conducted. There is substantial evidence suggesting that there is a causal link between ZIKV and microcephaly, however, future studies are warranted to solidify this association. To summarize the most recent evidence on this issue and provide perspectives for future studies, we reviewed the literature to identify existing evidence of the causal link between ZIKV infection and microcephaly within research related to the epidemics, laboratory diagnosis, and possible mechanisms.

  18. Intelligent DNA-based molecular diagnostics using linked genetic markers

    Energy Technology Data Exchange (ETDEWEB)

    Pathak, D.K.; Perlin, M.W.; Hoffman, E.P.

    1994-12-31

    This paper describes a knowledge-based system for molecular diagnostics, and its application to fully automated diagnosis of X-linked genetic disorders. Molecular diagnostic information is used in clinical practice for determining genetic risks, such as carrier determination and prenatal diagnosis. Initially, blood samples are obtained from related individuals, and PCR amplification is performed. Linkage-based molecular diagnosis then entails three data analysis steps. First, for every individual, the alleles (i.e., DNA composition) are determined at specified chromosomal locations. Second, the flow of genetic material among the individuals is established. Third, the probability that a given individual is either a carrier of the disease or affected by the disease is determined. The current practice is to perform each of these three steps manually, which is costly, time consuming, labor-intensive, and error-prone. As such, the knowledge-intensive data analysis and interpretation supersede the actual experimentation effort as the major bottleneck in molecular diagnostics. By examining the human problem solving for the task, we have designed and implemented a prototype knowledge-based system capable of fully automating linkage-based molecular diagnostics in X-linked genetic disorders, including Duchenne Muscular Dystrophy (DMD). Our system uses knowledge-based interpretation of gel electrophoresis images to determine individual DNA marker labels, a constraint satisfaction search for consistent genetic flow among individuals, and a blackboard-style problem solver for risk assessment. We describe the system`s successful diagnosis of DMD carrier and affected individuals from raw clinical data.

  19. Impact of Behavioral Genetic Evidence on the Adjudication of Criminal Behavior

    OpenAIRE

    Appelbaum, Paul S.; Scurich, Nicholas

    2014-01-01

    Recent advances in behavioral genetics suggest a modest relationship among certain gene variants, early childhood experiences, and criminal behavior. Although scientific research examining this link is still at an early stage, genetic data are already being introduced in criminal trials. However, the extent to which such evidence is likely to affect jurors’ decisions has not previously been explored. In the present study, a representative sample of the U.S. population (n=250) received a vigne...

  20. From the genome to the phenome and back: linking genes with human brain function and structure using genetically informed neuroimaging

    DEFF Research Database (Denmark)

    Siebner, H R; Callicott, J H; Sommer, T

    2009-01-01

    In recent years, an array of brain mapping techniques has been successfully employed to link individual differences in circuit function or structure in the living human brain with individual variations in the human genome. Several proof-of-principle studies provided converging evidence that brain...... imaging can establish important links between genes and behaviour. The overarching goal is to use genetically informed brain imaging to pinpoint neurobiological mechanisms that contribute to behavioural intermediate phenotypes or disease states. This special issue on "Linking Genes to Brain Function...... in Health and Disease" provides an overview over how the "imaging genetics" approach is currently applied in the various fields of systems neuroscience to reveal the genetic underpinnings of complex behaviours and brain diseases. While the rapidly emerging field of imaging genetics holds great promise...

  1. Impact of behavioral genetic evidence on the adjudication of criminal behavior.

    Science.gov (United States)

    Appelbaum, Paul S; Scurich, Nicholas

    2014-01-01

    Recent advances in behavioral genetics suggest a modest relationship among certain gene variants, early childhood experiences, and criminal behavior. Although scientific research examining this link is still at an early stage, genetic data are already being introduced in criminal trials. However, the extent to which such evidence is likely to affect jurors' decisions has not been explored. In the present study, a representative sample of the U.S. population (n = 250) received a vignette describing an apparently impulsive homicide, accompanied by one of four explanations of the defendant's impulsivity: childhood abuse, genetic predisposition, childhood abuse and genetic predisposition, or simple impulsive behavior. The participants were asked to identify the crime that the defendant had committed and to select an appropriate sentence range. Evidence of genetic predisposition did not affect the crime of which the defendant was convicted or the sentence. However, participants who received the abuse or genetic + abuse explanation imposed longer prison sentences. Paradoxically, the genetic and genetic + abuse conditions engendered the greatest fear of the defendant. These findings should allay concerns that genetic evidence in criminal adjudications will be overly persuasive to jurors, but should raise questions about the impact of genetic attributions on perceptions of dangerousness.

  2. Effects of Behavioral Genetic Evidence on Perceptions of Criminal Responsibility and Appropriate Punishment

    Science.gov (United States)

    Appelbaum, Paul S.; Scurich, Nicholas; Raad, Raymond

    2015-01-01

    Demonstrations of a link between genetic variants and criminal behavior have stimulated increasing use of genetic evidence to reduce perceptions of defendants’ responsibility for criminal behavior and to mitigate punishment. However, because only limited data exist regarding the impact of such evidence on decision makers and the public at large, we recruited a representative sample of the U.S. adult population (n=960) for a web-based survey. Participants were presented with descriptions of three legal cases and were asked to: determine the length of incarceration for a convicted murderer; adjudicate an insanity defense; and decide whether a defendant should receive the death penalty. A fully crossed, between-participants, factorial design was used, varying the type of evidence (none, genetic, neuroimaging, both), heinousness of the crime, and past criminal record, with sentence or verdict as the primary outcome. Also assessed were participants’ apprehension of the defendant, belief in free will, political ideology, and genetic knowledge. Across all three cases, genetic evidence had no significant effects on outcomes. Neuroimaging data showed an inconsistent effect in one of the two cases in which it was introduced. In contrast, heinousness of the offense and past criminal record were strongly related to participants’ decisions. Moreover, participants’ beliefs about the controllability of criminal behavior and political orientations were significantly associated with their choices. Our findings suggest that neither hopes that genetic evidence will modify judgments of culpability and punishment nor fears about the impact of genetic evidence on decision makers are likely to come to fruition. PMID:26240516

  3. Effects of Behavioral Genetic Evidence on Perceptions of Criminal Responsibility and Appropriate Punishment.

    Science.gov (United States)

    Appelbaum, Paul S; Scurich, Nicholas; Raad, Raymond

    2015-05-01

    Demonstrations of a link between genetic variants and criminal behavior have stimulated increasing use of genetic evidence to reduce perceptions of defendants' responsibility for criminal behavior and to mitigate punishment. However, because only limited data exist regarding the impact of such evidence on decision makers and the public at large, we recruited a representative sample of the U.S. adult population (n=960) for a web-based survey. Participants were presented with descriptions of three legal cases and were asked to: determine the length of incarceration for a convicted murderer; adjudicate an insanity defense; and decide whether a defendant should receive the death penalty. A fully crossed, between-participants, factorial design was used, varying the type of evidence (none, genetic, neuroimaging, both), heinousness of the crime, and past criminal record, with sentence or verdict as the primary outcome. Also assessed were participants' apprehension of the defendant, belief in free will, political ideology, and genetic knowledge. Across all three cases, genetic evidence had no significant effects on outcomes. Neuroimaging data showed an inconsistent effect in one of the two cases in which it was introduced. In contrast, heinousness of the offense and past criminal record were strongly related to participants' decisions. Moreover, participants' beliefs about the controllability of criminal behavior and political orientations were significantly associated with their choices. Our findings suggest that neither hopes that genetic evidence will modify judgments of culpability and punishment nor fears about the impact of genetic evidence on decision makers are likely to come to fruition.

  4. Genetic Variation Linked to Lung Cancer Survival in White Smokers | Center for Cancer Research

    Science.gov (United States)

    CCR investigators have discovered evidence that links lung cancer survival with genetic variations (called single nucleotide polymorphisms) in the MBL2 gene, a key player in innate immunity. The variations in the gene, which codes for a protein called the mannose-binding lectin, occur in its promoter region, where the RNA polymerase molecule binds to start transcription, and in the first exon that is responsible for the correct structure of MBL. The findings appear in the September 19, 2007, issue of the Journal of the National Cancer Institute.

  5. Linking genetic variants of the mineralocorticoid receptor and negative memory bias: Interaction with prior life adversity

    NARCIS (Netherlands)

    Vogel, S.; Gerritsen, L.; Oostrom, I.I.H. van; Arias Vasquez, A.; Rijpkema, M.J.P.; Joels, M.; Franke, B.; Tendolkar, I.; Fernandez, G.S.E.

    2014-01-01

    Substantial research has been conducted investigating the association between life adversity and genetic vulnerability for depression, but clear mechanistic links are rarely identified and investigation often focused on single genetic variants. Complex phenotypes like depression, however, are likely

  6. Genetic determination of human facial morphology: links between cleft-lips and normal variation.

    Science.gov (United States)

    Boehringer, Stefan; van der Lijn, Fedde; Liu, Fan; Günther, Manuel; Sinigerova, Stella; Nowak, Stefanie; Ludwig, Kerstin U; Herberz, Ruth; Klein, Stefan; Hofman, Albert; Uitterlinden, Andre G; Niessen, Wiro J; Breteler, Monique M B; van der Lugt, Aad; Würtz, Rolf P; Nöthen, Markus M; Horsthemke, Bernhard; Wieczorek, Dagmar; Mangold, Elisabeth; Kayser, Manfred

    2011-11-01

    Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and other previous studies showed distinctly differing facial distance measurements when comparing unaffected relatives of NSCL/P patients with normal controls. Here, we test the hypothesis that genetic loci involved in NSCL/P also influence normal variation in facial morphology. We tested 11 SNPs from 10 genomic regions previously showing replicated evidence of association with NSCL/P for association with normal variation of nose width and bizygomatic distance in two cohorts from Germany (N=529) and the Netherlands (N=2497). The two most significant associations found were between nose width and SNP rs1258763 near the GREM1 gene in the German cohort (P=6 × 10(-4)), and between bizygomatic distance and SNP rs987525 at 8q24.21 near the CCDC26 gene (P=0.017) in the Dutch sample. A genetic prediction model explained 2% of phenotype variation in nose width in the German and 0.5% of bizygomatic distance variation in the Dutch cohort. Although preliminary, our data provide a first link between genetic loci involved in a pathological facial trait such as NSCL/P and variation of normal facial morphology. Moreover, we present a first approach for understanding the genetic basis of human facial appearance, a highly intriguing trait with implications on clinical practice, clinical genetics, forensic intelligence, social interactions and personal identity.

  7. Genetics Home Reference: X-linked creatine deficiency

    Science.gov (United States)

    ... Health Conditions X-linked creatine deficiency X-linked creatine deficiency Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description X-linked creatine deficiency is an inherited disorder that primarily affects ...

  8. Genetics Home Reference: X-linked sideroblastic anemia

    Science.gov (United States)

    ... Conditions X-linked sideroblastic anemia X-linked sideroblastic anemia Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description X-linked sideroblastic anemia is an inherited disorder that prevents developing red ...

  9. Genetics Home Reference: X-linked sideroblastic anemia and ataxia

    Science.gov (United States)

    ... linked sideroblastic anemia and ataxia X-linked sideroblastic anemia and ataxia Printable PDF Open All Close All ... the expand/collapse boxes. Description X-linked sideroblastic anemia and ataxia is a rare condition characterized by ...

  10. Evidence linking coronal mass ejections with interplanetary magnetic clouds

    International Nuclear Information System (INIS)

    Wilson, R.M.; Hildner, E.

    1983-12-01

    Using proxy data for the occurrence of those mass ejections from the solar corona which are directed earthward, we investigate the association between the post-1970 interplanetary magnetic clouds of Klein and Burlaga and coronal mass ejections. The evidence linking magnetic clouds following shocks with coronal mass ejections is striking. Six of nine clouds observed at Earth were preceded an appropriate time earlier by meter-wave type II radio bursts indicative of coronal shock waves and coronal mass ejections occurring near central meridian. During the selected periods when no clouds were detected near Earth, the only type II bursts reported were associated with solar activity near the limbs. Where the proxy solar data to be sought are not so clearly suggested, that is, for clouds preceding interaction regions and clouds within cold magnetic enhancements, the evidence linking the clouds and coronal mass ejections is not as clear proxy data usually suggest many candidate mass-ejection events for each cloud. Overall, the data are consistent with and support the hypothesis suggested by Klein and Burlaga that magnetic clouds observed with spacecraft at 1 AU are manifestations of solar coronal mass ejection transients

  11. X-Linked Dystonia Parkinsonism: Clinical Phenotype, Genetics and Therapeutics

    Directory of Open Access Journals (Sweden)

    Raymond L. Rosales

    2010-10-01

    Full Text Available The clinical phenotype of X-Linked Dystonia Parkinsonism (XDP is typically one that involves a Filipino adult male whose ancestry is mostly traced in the Philippine island of Panay. Dystonia usually starts focally in the lower limbs or oromandibular regions, then spreads to become generalized eventually. Parkinsonism sets in later into the disease and usually in combination with dystonia. /DYT3/ and /TAF1/ are the two genes associated with XDP. An SVA retrotransposon insertion in an intron of /TAF1/ may reduce neuron-specific expression of the /TAF1/ isoform in the caudate nucleus, and subsequently interfere with the transcription of many neuronal genes. Polypharmacy with oral benzodiazepines, anticholinergic agents and muscle relaxants leaves much to be desired in terms of efficacy. The medications to date that may appear beneficial, especially in disabling dystonias, are zolpidem, muscle afferent block with lidocaine-ethanol and botulinum toxin type A. Despite the few cases undergoing deep brain stimulation, this functional surgery has shown the greatest promise in XDP. An illustrative case of XDP in a family depicts the variable course of illness, including a bout of “status dystonicus,” challenges in therapy, reckoning with the social impact of the disease, and eventual patient demise. Indeed, there remains some gaps in understanding some phenomenological, genetic and treatment aspects of XDP, the areas upon which future research directions may be worthwhile.

  12. Current Evidence and Insights about Genetics in Thoracic Aorta Disease

    Science.gov (United States)

    Muneretto, Claudio

    2013-01-01

    Thoracic aortic aneurysms have been historically considered to be caused by etiologic factors similar to those implied in abdominal aortic aneurysms. However, during the past decade, there has been increasing evidence that almost 20% of thoracic aortic aneurysms may be associated with a genetic disease, often within a syndromic or familial disorder. Moreover, the presence of congenital anomalies, such as bicuspid aortic valve, may have a unique common genetic underlying cause. Finally, also sporadic forms have been found to be potentially associated with genetic disorders, as highlighted by the analysis of rare variants and expression of specific microRNAs. We therefore sought to perform a comprehensive review of the role of genetic causes in the development of thoracic aortic aneurysms, by analyzing in detail the current evidence of genetic alterations in syndromes such as Marfan, Loeys-Dietz, and Ehler-Danlos, familial or sporadic forms, or forms associated with bicuspid aortic valve. PMID:24453931

  13. Marine proxy evidence linking decadal North Pacific and Atlantic climate

    Energy Technology Data Exchange (ETDEWEB)

    Hetzinger, S. [University of Toronto Mississauga, CPS-Department, Mississauga, ON (Canada); Leibniz Institute of Marine Sciences, IFM-GEOMAR, Kiel (Germany); Halfar, J. [University of Toronto Mississauga, CPS-Department, Mississauga, ON (Canada); Mecking, J.V.; Keenlyside, N.S. [Leibniz Institute of Marine Sciences, IFM-GEOMAR, Kiel (Germany); University of Bergen, Geophysical Institute and Bjerknes Centre for Climate Research, Bergen (Norway); Kronz, A. [University of Goettingen, Geowissenschaftliches Zentrum, Goettingen (Germany); Steneck, R.S. [University of Maine, Darling Marine Center, Walpole, ME (United States); Adey, W.H. [Smithsonian Institution, Department of Botany, Washington, DC (United States); Lebednik, P.A. [ARCADIS U.S. Inc., Walnut Creek, CA (United States)

    2012-09-15

    Decadal- to multidecadal variability in the extra-tropical North Pacific is evident in 20th century instrumental records and has significant impacts on Northern Hemisphere climate and marine ecosystems. Several studies have discussed a potential linkage between North Pacific and Atlantic climate on various time scales. On decadal time scales no relationship could be confirmed, potentially due to sparse instrumental observations before 1950. Proxy data are limited and no multi-centennial high-resolution marine geochemical proxy records are available from the subarctic North Pacific. Here we present an annually-resolved record (1818-1967) of Mg/Ca variations from a North Pacific/Bering Sea coralline alga that extends our knowledge in this region beyond available data. It shows for the first time a statistically significant link between decadal fluctuations in sea-level pressure in the North Pacific and North Atlantic. The record is a lagged proxy for decadal-scale variations of the Aleutian Low. It is significantly related to regional sea surface temperature and the North Atlantic Oscillation (NAO) index in late boreal winter on these time scales. Our data show that on decadal time scales a weaker Aleutian Low precedes a negative NAO by several years. This atmospheric link can explain the coherence of decadal North Pacific and Atlantic Multidecadal Variability, as suggested by earlier studies using climate models and limited instrumental data. (orig.)

  14. Genetics Home Reference: X-linked intellectual disability, Siderius type

    Science.gov (United States)

    ... Cleft Lip and Palate MalaCards: x-linked intellectual disability, siderius type March of Dimes: Cleft Lip and Cleft Palate Merck Manual Consumer Version: Intellectual Disability Orphanet: X-linked intellectual disability, Siderius type Patient ...

  15. Genetic association in chronic periodontitis through dermatoglyphics: An unsolved link?

    Directory of Open Access Journals (Sweden)

    Sowmya Astekar

    2017-01-01

    Full Text Available Introduction: Because dermatoglyphic features are strongly affected by genetic and environmental factors, using it as supportive evidence in the diagnosis of hereditary disorders becomes a reality. Offspring of patients suffering from chronic periodontitis have a high prevalence rate of periodontal breakdown, suggesting strong familial influence. Aims: The present study intends to evaluate and compare the dermatoglyphic patterns in controls and periodontally compromised patients. Settings and Design: A hospital based cross-sectional study was conducted, including a total of 60 individuals, divided into study and control groups of 30 each. The study group included clinically diagnosed periodontitis patients.Materials and Methods: The digital prints were collected using biometric scanner and palmer prints using digital flatbed scanner. Care was taken to ensure that full prints of ridges were obtained. The periodontal status of all 60 participants was assessed clinically for attachment level and pocket depth. Later, Russell's periodontal index was also calculated. Statistical Analysis: The data obtained was subjected to statistical analysis using chi square and Student's t-test. Results: Among the finger ridge patterns, whorl pattern was found to be the most common in the study group whereas loop pattern was the most common in the control group. Mean total finger ridge count in the study group (165.69 ± 25.30 was significantly higher (P = 0.001 than the control group (125.4 ± 16.38. Mean dat angle was significantly higher (P = 0.039 in the study group (60.60 ± 2.76 than the control group (59.20 ± 2.62. Conclusion: Dermatoglyphics may serve as an early predictor in identifying high risk group individuals of developing diseases like periodontitis.

  16. Genetics Home Reference: X-linked spondyloepiphyseal dysplasia tarda

    Science.gov (United States)

    ... Educational Resources (6 links) Cincinnati Children's Hospital: Coxa Vera Disease InfoSearch: Spondyloepiphyseal dysplasia tarda X-linked Johns ... Free article on PubMed Central Savarirayan R, Thompson E, Gécz J. Spondyloepiphyseal dysplasia tarda (SEDL, MIM #313400). ...

  17. Linking Essential Tremor to the Cerebellum: Clinical Evidence.

    Science.gov (United States)

    Benito-León, Julián; Labiano-Fontcuberta, Andrés

    2016-06-01

    Essential tremor (ET) might be a family of diseases unified by the presence of kinetic tremor, but also showing etiological, pathological, and clinical heterogeneity. In this review, we will describe the most significant clinical evidence, which suggests that ET is linked to the cerebellum. Data for this review were identified by searching PUBMED (January 1966 to May 2015) crossing the terms "essential tremor" (ET) and "cerebellum," which yielded 201 entries, 11 of which included the term "cerebellum" in the article title. This was supplemented by articles in the author's files that pertained to this topic. The wide spectrum of clinical features of ET that suggest that it originates as a cerebellar or cerebellar outflow problem include the presence of intentional tremor, gait and balance abnormalities, subtle features of dysarthria, and oculomotor abnormalities, as well as deficits in eye-hand coordination, motor learning deficits, incoordination during spiral drawing task, abnormalities in motor timing and visual reaction time, impairment of social abilities, improvement in tremor after cerebellar stroke, efficacy of deep brain stimulation (which blocks cerebellar outflow), and cognitive dysfunction. It is unlikely, however, that cerebellar dysfunction, per se, fully explains ET-associated dementia, because the cognitive deficits that have been described in patients with cerebellar lesions are generally mild. Overall, a variety of clinical findings suggest that in at least a sizable proportion of patients with ET, there is an underlying abnormality of the cerebellum and/or its pathways.

  18. Genetics Home Reference: X-linked cardiac valvular dysplasia

    Science.gov (United States)

    ... my area? Other Names for This Condition congenital valvular heart disease CVD1 filamin-A-associated myxomatous mitral valve disease ... Valves (image) Encyclopedia: Mitral Valve Prolapse Health Topic: Heart Valve Diseases Health Topic: Mitral Valve Prolapse Genetic and Rare ...

  19. Review: domestic animal forensic genetics - biological evidence, genetic markers, analytical approaches and challenges.

    Science.gov (United States)

    Kanthaswamy, S

    2015-10-01

    This review highlights the importance of domestic animal genetic evidence sources, genetic testing, markers and analytical approaches as well as the challenges this field is facing in view of the de facto 'gold standard' human DNA identification. Because of the genetic similarity between humans and domestic animals, genetic analysis of domestic animal hair, saliva, urine, blood and other biological material has generated vital investigative leads that have been admitted into a variety of court proceedings, including criminal and civil litigation. Information on validated short tandem repeat, single nucleotide polymorphism and mitochondrial DNA markers and public access to genetic databases for forensic DNA analysis is becoming readily available. Although the fundamental aspects of animal forensic genetic testing may be reliable and acceptable, animal forensic testing still lacks the standardized testing protocols that human genetic profiling requires, probably because of the absence of monetary support from government agencies and the difficulty in promoting cooperation among competing laboratories. Moreover, there is a lack in consensus about how to best present the results and expert opinion to comply with court standards and bear judicial scrutiny. This has been the single most persistent challenge ever since the earliest use of domestic animal forensic genetic testing in a criminal case in the mid-1990s. Crime laboratory accreditation ensures that genetic test results have the courts' confidence. Because accreditation requires significant commitments of effort, time and resources, the vast majority of animal forensic genetic laboratories are not accredited nor are their analysts certified forensic examiners. The relevance of domestic animal forensic genetics in the criminal justice system is undeniable. However, further improvements are needed in a wide range of supporting resources, including standardized quality assurance and control protocols for sample

  20. Evidence for nonallelic genetic heterogeneity in autosomal recessive retinitis pigmentosa

    NARCIS (Netherlands)

    Bleeker-Wagemakers, L. M.; Gal, A.; Kumar-Singh, R.; van den Born, L. I.; Li, Y.; Schwinger, E.; Sandkuijl, L. A.; Bergen, A. A.; Kenna, P.; Humphries, P.

    1992-01-01

    Recent evidence suggesting the involvement of mutant rhodopsin proteins in the pathogenesis of autosomal recessive retinitis pigmentosa has prompted us to investigate whether this form of the disease shows non-allelic genetic heterogeneity, as has previously been shown to be the case in autosomal

  1. Genetic and biochemical evidences reveal novel insights into the ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 41; Issue 4. Genetic and biochemical evidences reveal novel insights into the mechanism underlying Saccharomyces cerevisiae Sae2-mediated abrogation of DNA replication stress. INDRAJEET GHODKE K MUNIYAPPA. ARTICLE Volume 41 Issue 4 December 2016 pp ...

  2. Genetics Home Reference: X-linked dilated cardiomyopathy

    Science.gov (United States)

    ... The other conditions in the spectrum, Duchenne and Becker muscular dystrophy , are characterized by progressive weakness and wasting of ... linked dilated cardiomyopathy is sometimes classified as subclinical Becker muscular dystrophy. Related Information What does it mean if a ...

  3. Genetics Home Reference: X-linked congenital stationary night blindness

    Science.gov (United States)

    ... collapse boxes. Description X-linked congenital stationary night blindness is a disorder of the retina , which is the specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing ...

  4. Genetics Home Reference: X-linked juvenile retinoschisis

    Science.gov (United States)

    ... in a decrease in or complete loss of functional retinoschisin, which disrupts the maintenance and organization of ... sides of the retina, resulting in impaired peripheral vision. Some individuals with X-linked juvenile retinoschisis do ...

  5. Levels of Evidence: Cancer Genetics Studies (PDQ®)—Health Professional Version

    Science.gov (United States)

    Levels of Evidence for Cancer Genetics Studies addresses the process and challenges of developing evidence-based summaries. Get information about how to weigh the strength of the evidence from cancer genetics studies in this summary for clinicians.

  6. Linking Essential Tremor to the Cerebellum: Neuropathological Evidence.

    Science.gov (United States)

    Louis, Elan D

    2016-06-01

    A fundamental question about essential tremor (ET) is whether its associated pathological changes and disease mechanisms are linkable to a specific brain region. To that end, recent tissue-based studies have made significant strides in elucidating changes in the ET brain. Emerging from these studies is increasing neuropathological evidence linking ET to the cerebellum. These studies have systematically identified a broad range of structural, degenerative changes in the ET cerebellum, spanning across all Purkinje cell compartments. These include the dendritic compartment (where there is an increase in number of Purkinje cell dendritic swellings, a pruning of the dendritic arbor, and a reduction in spine density), the cell body (where, aside from reductions in Purkinje cell linear density in some studies, there is an increase in the number of heterotopic Purkinje cell soma), and the axonal compartment (where a plethora of changes in axonal morphology have been observed, including an increase in the number of thickened axonal profiles, torpedoes, axonal recurrent collaterals, axonal branching, and terminal axonal sprouting). Additional changes, possibly due to secondary remodeling, have been observed in neighboring neuronal populations. These include a hypertrophy of basket cell axonal processes and changes in the distribution of climbing fiber-Purkinje cell synapses. These changes all distinguish ET from normal control brains. Initial studies further indicate that the profile (i.e., constellation) of these changes may separate ET from other diseases of the cerebellum, thereby serving as a disease signature. With the discovery of these changes, a new model of ET has arisen, which posits that it may be a neurodegenerative disorder centered in the cerebellar cortex. These newly emerging neuropathological studies pave the way for anatomically focused, hypothesis-driven, molecular mechanistic studies of disease pathogenesis.

  7. Genetic Evidence for Modifying Oceanic Boundaries Relative to Fiji.

    Science.gov (United States)

    Shipley, Gerhard P; Taylor, Diana A; N'Yeurt, Antoine D R; Tyagi, Anand; Tiwari, Geetanjali; Redd, Alan J

    2016-07-01

    We present the most comprehensive genetic characterization to date of five Fijian island populations: Viti Levu, Vanua Levu, Kadavu, the Lau Islands, and Rotuma, including nonrecombinant Y (NRY) chromosome and mitochondrial DNA (mtDNA) haplotypes and haplogroups. As a whole, Fijians are genetically intermediate between Melanesians and Polynesians, but the individual Fijian island populations exhibit significant genetic structure reflecting different settlement experiences in which the Rotumans and the Lau Islanders were more influenced by Polynesians, and the other Fijian island populations were more influenced by Melanesians. In particular, Rotuman and Lau Islander NRY chromosomal and mtDNA haplogroup frequencies and Rotuman mtDNA hypervariable segment 1 region haplotypes more closely resemble those of Polynesians, while genetic markers of the other populations more closely resemble those of the Near Oceanic Melanesians. Our findings provide genetic evidence supportive of modifying regional boundaries relative to Fiji, as has been suggested by others based on a variety of nongenetic evidence. Specifically, for the traditional Melanesia/Polynesia/Micronesia scheme, our findings support moving the Melanesia-Polynesia boundary to include Rotuma and the Lau Islands in Polynesia. For the newer Near/Remote Oceania scheme, our findings support keeping Rotuma and the Lau Islands in Remote Oceania and locating the other Fijian island populations in an intermediate or "Central Oceania" region to better reflect the great diversity of Oceania.

  8. Missing Links in Genes to Traits: Toward Teaching for an Integrated Framework of Genetics

    Science.gov (United States)

    Pavlova, Iglika V.; Kreher, Scott A.

    2013-01-01

    Genetics, one of the most influential fields, underlies all of biology and produces discoveries that are in the news daily. However, many students leave introductory biology and genetics courses lacking a coherent framework of knowledge to use in their daily lives. We identify substantial "missing links" in the teaching of foundational…

  9. Genetics of Schizophrenia: Historical Insights and Prevailing Evidence.

    Science.gov (United States)

    van de Leemput, J; Hess, J L; Glatt, S J; Tsuang, M T

    2016-01-01

    Schizophrenia's (SZ's) heritability and familial transmission have been known for several decades; however, despite the clear evidence for a genetic component, it has been very difficult to pinpoint specific causative genes. Even so genetic studies have taught us a lot, even in the pregenomic era, about the molecular underpinnings and disease-relevant pathways. Recurring themes emerged revealing the involvement of neurodevelopmental processes, glutamate regulation, and immune system differential activation in SZ etiology. The recent emergence of epigenetic studies aimed at shedding light on the biological mechanisms underlying SZ has provided another layer of information in the investigation of gene and environment interactions. However, this epigenetic insight also brings forth another layer of complexity to the (epi)genomic landscape such as interactions between genetic variants, epigenetic marks-including cross-talk between DNA methylation and histone modification processes-, gene expression regulation, and environmental influences. In this review, we seek to synthesize perspectives, including limitations and obstacles yet to overcome, from genetic and epigenetic literature on SZ through a qualitative review of risk factors and prevailing hypotheses. Encouraged by the findings of both genetic and epigenetic studies to date, as well as the continued development of new technologies to collect and interpret large-scale studies, we are left with a positive outlook for the future of elucidating the molecular genetic mechanisms underlying SZ and other complex neuropsychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. X linked neonatal centronuclear/myotubular myopathy: evidence for linkage to Xq28 DNA marker loci.

    Science.gov (United States)

    Thomas, N S; Williams, H; Cole, G; Roberts, K; Clarke, A; Liechti-Gallati, S; Braga, S; Gerber, A; Meier, C; Moser, H

    1990-05-01

    We have studied the inheritance of several polymorphic Xq27/28 DNA marker loci in two three generation families with the X linked neonatal lethal form of centronuclear/myotubular myopathy (XL MTM). We found complete linkage of XLMTM to all four informative Xq28 markers analysed, with GCP/RCP (Z = 3.876, theta = 0.00), with DXS15 (Z = 3.737, theta = 0.00), with DXS52 (Z = 2.709, theta = 0.00), and with F8C (Z = 1.020, theta = 0.00). In the absence of any observable recombination, we are unable to sublocalise the XLMTM locus further within the Xq28 region. This evidence for an Xq28 localisation may allow us to carry out useful genetic counselling within such families.

  11. Genetics Home Reference: X-linked lymphoproliferative disease

    Science.gov (United States)

    ... my area? Other Names for This Condition Duncan disease Epstein-Barr virus-induced lymphoproliferative disease in males familial fatal ... the proapoptotic SAP function in X-linked lymphoproliferative disease aggravates Epstein-Barr virus (EBV) induced mononucleosis and promotes lymphoma development. ...

  12. Developmental imaging genetics: linking dopamine function to adolescent behavior.

    Science.gov (United States)

    Padmanabhan, Aarthi; Luna, Beatriz

    2014-08-01

    Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to non-invasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Genetic moderation of multiple pathways linking early cumulative socioeconomic adversity and young adults' cardiometabolic disease risk.

    Science.gov (United States)

    Wickrama, Kandauda A S; Lee, Tae Kyoung; O'Neal, Catherine Walker

    2018-02-01

    Recent research suggests that psychosocial resources and life stressors are mediating pathways explaining socioeconomic variation in young adults' health risks. However, less research has examined both these pathways simultaneously and their genetic moderation. A nationally representative sample of 11,030 respondents with prospective data collected over 13 years from the National Study of Adolescent to Adult Health was examined. First, the association between early cumulative socioeconomic adversity and young adults' (ages 25-34) cardiometabolic disease risk, as measured by 10 biomarkers, through psychosocial resources (educational attainment) and life stressors (accelerated transition to adulthood) was examined. Second, moderation of these pathways by the serotonin transporter linked polymorphic region gene (5-HTTLPR) was examined. There was evidence for the association between early socioeconomic adversity and young adults' cardiometabolic disease risk directly and indirectly through educational attainment and accelerated transitions. These direct and mediating pathways were amplified by the 5-HTTLPR polymorphism. These findings elucidate how early adversity can have an enduring influence on young adults' cardiometabolic disease risk directly and indirectly through psychosocial resources and life stressors and their genetic moderation. This information suggests that effective intervention and prevention programs should focus on early adversity, youth educational attainment, and their transition to young adulthood.

  14. The Genetic Link between Parkinson's Disease and the Kynurenine Pathway Is Still Missing.

    Science.gov (United States)

    Török, Nóra; Török, Rita; Szolnoki, Zoltán; Somogyvári, Ferenc; Klivényi, Péter; Vécsei, László

    2015-01-01

    Background. There is substantial evidence that the kynurenine pathway (KP) plays a role in the normal physiology of the brain and is involved in the pathology of neurodegenerative disorders such as Huntington's disease and Parkinson's disease (PD). Objective. We set out to investigate the potential roles in PD of single nucleotide polymorphisms (SNPs) from one of the key enzymes of the KP, kynurenine 3-monooxygenase (KMO). Methods. 105 unrelated, clinically definitive PD patients and 131 healthy controls were enrolled to investigate the possible effects of the different alleles of KMO. Fluorescently labeled TaqMan probes were used for allele discrimination. Results. None of the four investigated SNPs proved to be associated with PD or influenced the age at onset of the disease. Conclusions. The genetic link between the KP and PD is still missing. The investigated SNPs presumably do not appear to influence the function of KMO and probably do not contain binding sites for regulatory proteins of relevance in PD. This is the first study to assess the genetic background behind the biochemical alterations of the kynurenine pathway in PD, directing the attention to this previously unexamined field.

  15. The Genetic Link between Parkinson’s Disease and the Kynurenine Pathway Is Still Missing

    Directory of Open Access Journals (Sweden)

    Nóra Török

    2015-01-01

    Full Text Available Background. There is substantial evidence that the kynurenine pathway (KP plays a role in the normal physiology of the brain and is involved in the pathology of neurodegenerative disorders such as Huntington’s disease and Parkinson’s disease (PD. Objective. We set out to investigate the potential roles in PD of single nucleotide polymorphisms (SNPs from one of the key enzymes of the KP, kynurenine 3-monooxygenase (KMO. Methods. 105 unrelated, clinically definitive PD patients and 131 healthy controls were enrolled to investigate the possible effects of the different alleles of KMO. Fluorescently labeled TaqMan probes were used for allele discrimination. Results. None of the four investigated SNPs proved to be associated with PD or influenced the age at onset of the disease. Conclusions. The genetic link between the KP and PD is still missing. The investigated SNPs presumably do not appear to influence the function of KMO and probably do not contain binding sites for regulatory proteins of relevance in PD. This is the first study to assess the genetic background behind the biochemical alterations of the kynurenine pathway in PD, directing the attention to this previously unexamined field.

  16. X linked exudative vitreoretinopathy: clinical features and genetic linkage analysis.

    Science.gov (United States)

    Fullwood, P; Jones, J; Bundey, S; Dudgeon, J; Fielder, A R; Kilpatrick, M W

    1993-03-01

    A four generation family in which familial exudative vitreoretinopathy is inherited as an X linked condition is described. Essentially the condition is one of abnormal vascularisation and signs at birth are those of a retinopathy superficially resembling retinopathy of prematurity, retinal folds, or, in advanced cases, enophthalmos or even phthisis. Prognosis depends on the progression of the retinal changes. The family members, including seven affected males and five obligate carrier females, have been types for 20 DNA markers, and linkage analysis suggests a gene locus either at Xq21.3 or at Xp11. As the latter region includes the locus for the gene for Norrie disease, it is possible that this and X linked vitreoretinopathy are allelic. We can further speculate that the differences in severity of the clinical manifestations are dependent only upon the timing of the insult.

  17. Genetic evidence for patrilocal mating behavior among Neandertal groups

    DEFF Research Database (Denmark)

    Lalueza-Fox, Carles; Rosas, Antonio; Estalrrich, Almudena

    2011-01-01

    The remains of 12 Neandertal individuals have been found at the El Sidrón site (Asturias, Spain), consisting of six adults, three adolescents, two juveniles, and one infant. Archaeological, paleontological, and geological evidence indicates that these individuals represent all or part of a contem...... of the three adult females carried different mtDNA lineages. These findings provide evidence to indicate that Neandertal groups not only were small and characterized by low genetic diversity but also were likely to have practiced patrilocal mating behavior....

  18. Towards a systemic paradigm in carcinogenesis: linking epigenetics and genetics.

    Science.gov (United States)

    Burgio, Ernesto; Migliore, Lucia

    2015-04-01

    For at least 30 years cancer has been defined as a genetic disease and explained by the so-called somatic mutation theory (SMT), which has dominated the carcinogenesis field. Criticism of the SMT has recently greatly increased, although still not enough to force all SMT supporters to recognize its limits. Various researchers point out that cancer appears to be a complex process concerning a whole tissue; and that genomic mutations, although variably deleterious and unpredictably important in determining the establishment of the neoplastic phenotype, are not the primary origin for a malignant neoplasia. We attempt to describe the inadequacies of the SMT and demonstrate that epigenetics is a more logical cause of carcinogenesis. Many previous models of carcinogenesis fall into two classes: (i) in which some biological changes inside cells alone lead to malignancy; and (ii) requiring changes in stroma/extracellular matrix. We try to make clear that in the (ii) model genomic instability is induced by persistent signals coming from the microenvironment, provoking epigenetic and genetic modifications in tissue stem cells that can lead to cancer. In this perspective, stochastic mutations of DNA are a critical by-product rather then the primary cause of cancer. Indirect support for such model of carcinogenesis comes from the in vitro and vivo experiments showing apparent 'reversion' of cancer phenotypes obtained via physiological factors of cellular differentiation (cytokines and other signaling molecules) or drugs, even if the key mutations are not 'reversed'.

  19. Spontaneous chromosome aberrations in cancer cells. Evidence of existence of hidden genetic lesions in genetic structures

    International Nuclear Information System (INIS)

    Poryadkova-Luchnik, N.A.; Kuz'mina, E.G.

    1996-01-01

    Chromosome aberrations spontaneously observed in cancer cells were quantitively studied under the effect of non-mutagenic (suboptimal temperature, low content of propilgallate and caffeine) and mutagenic (ionizing radiation) factors. Human larynx cancer cells during several years or gamma-irradiation were used to carry out experiments. The experiments linked with cloning of the initial population and investigation into chromosome aberrations in 22 clones demonstrated persuasively the occurrence of latent genetic lesions in cancer cells

  20. Genetic evidence for a Paleolithic human population expansion in Africa

    Science.gov (United States)

    Reich, David E.; Goldstein, David B.

    1998-01-01

    Human populations have undergone dramatic expansions in size, but other than the growth associated with agriculture, the dates and magnitudes of those expansions have never been resolved. Here, we introduce two new statistical tests for population expansion, which use variation at a number of unlinked genetic markers to study the demographic histories of natural populations. By analyzing genetic variation in various aboriginal populations from throughout the world, we show highly significant evidence for a major human population expansion in Africa, but no evidence of expansion outside of Africa. The inferred African expansion is estimated to have occurred between 49,000 and 640,000 years ago, certainly before the Neolithic expansions, and probably before the splitting of African and non-African populations. In showing a significant difference between African and non-African populations, our analysis supports the unique role of Africa in human evolutionary history, as has been suggested by most other genetic work. In addition, the missing signal in non-African populations may be the result of a population bottleneck associated with the emergence of these populations from Africa, as postulated in the “Out of Africa” model of modern human origins. PMID:9653150

  1. The genetic links between the big five personality traits and general interest domains.

    Science.gov (United States)

    Kandler, Christian; Bleidorn, Wiebke; Riemann, Rainer; Angleitner, Alois; Spinath, Frank M

    2011-12-01

    This is the first genetically informative study in which multiple informants were used to quantify the genetic and environmental sources of individual differences in general interests as well as the phenotypic and genetic links between general interests and Big Five personality traits. Self-reports and two peer ratings from 844 individuals, including 225 monozygotic and 113 dizygotic complete twin pairs, were collected. Multiple-rater scores (composites) revealed that the averaged levels of genetic and environmental effects on seven broad interest domains were similar to those on personality traits. Multivariate analyses showed that about 35% of the genetic and 9% of the environmental variance in interests were explained by personality domains, in particular by Openness. The findings suggest that interests cannot easily be considered as a byproduct of the interactions between personality genotypes and the environmental influences but rather as an internal regulation of behavior with an own genetic basis.

  2. Find the weakest link. A comparison between demographic, genetic and demo-genetic metapopulation extinction times

    Directory of Open Access Journals (Sweden)

    Robert Alexandre

    2011-09-01

    Full Text Available Abstract Background While the ultimate causes of most species extinctions are environmental, environmental constraints have various secondary consequences on evolutionary and ecological processes. The roles of demographic, genetic mechanisms and their interactions in limiting the viabilities of species or populations have stirred much debate and remain difficult to evaluate in the absence of demography-genetics conceptual and technical framework. Here, I computed projected times to metapopulation extinction using (1 a model focusing on the effects of species properties, habitat quality, quantity and temporal variability on the time to demographic extinction; (2 a genetic model focusing on the dynamics of the drift and inbreeding loads under the same species and habitat constraints; (3 a demo-genetic model accounting for demographic-genetic processes and feedbacks. Results Results indicate that a given population may have a high demographic, but low genetic viability or vice versa; and whether genetic or demographic aspects will be the most limiting to overall viability depends on the constraints faced by the species (e.g., reduction of habitat quantity or quality. As a consequence, depending on metapopulation or species characteristics, incorporating genetic considerations to demographically-based viability assessments may either moderately or severely reduce the persistence time. On the other hand, purely genetically-based estimates of species viability may either underestimate (by neglecting demo-genetic interactions or overestimate (by neglecting the demographic resilience true viability. Conclusion Unbiased assessments of the viabilities of species may only be obtained by identifying and considering the most limiting processes (i.e., demography or genetics, or, preferentially, by integrating them.

  3. New Evidence Links Stellar Remains to Oldest Recorded Supernova

    Science.gov (United States)

    2006-09-01

    Recent observations have uncovered evidence that helps to confirm the identification of the remains of one of the earliest stellar explosions recorded by humans. The new study shows that the supernova remnant RCW 86 is much younger than previously thought. As such, the formation of the remnant appears to coincide with a supernova observed by Chinese astronomers in 185 A.D. The study used data from NASA's Chandra X-ray Observatory and the European Space Agency's XMM-Newton Observatory, "There have been previous suggestions that RCW 86 is the remains of the supernova from 185 A.D.," said Jacco Vink of University of Utrecht, the Netherlands, and lead author of the study. "These new X-ray data greatly strengthen the case." When a massive star runs out of fuel, it collapses on itself, creating a supernova that can outshine an entire galaxy. The intense explosion hurls the outer layers of the star into space and produces powerful shock waves. The remains of the star and the material it encounters are heated to millions of degrees and can emit intense X-ray radiation for thousands of years. Animation of a Massive Star Explosion Animation of a Massive Star Explosion In their stellar forensic work, Vink and colleagues studied the debris in RCW 86 to estimate when its progenitor star originally exploded. They calculated how quickly the shocked, or energized, shell is moving in RCW 86, by studying one part of the remnant. They combined this expansion velocity with the size of the remnant and a basic understanding of how supernovas expand to estimate the age of RCW 86. "Our new calculations tell us the remnant is about 2,000 years old," said Aya Bamba, a coauthor from the Institute of Physical and Chemical Research (RIKEN), Japan. "Previously astronomers had estimated an age of 10,000 years." The younger age for RCW 86 may explain an astronomical event observed almost 2000 years ago. In 185 AD, Chinese astronomers (and possibly the Romans) recorded the appearance of a new

  4. Mythology and evidence-based oncology: An indivisible link.

    Science.gov (United States)

    Rathod, Shrinivas; Agarwal, Jai Prakash; Munshi, Anusheel

    2016-01-01

    Religion has an important role in the birth of medicine and shares a long history. Contradiction has separated spirituality and medicine. For so many years, the spiritual dimension of medicine was seen as unnecessary and inappropriate. However times are changing again and since the last few decades, recent literature and various ongoing studies have focused on unmet spiritual needs of physician and patient. This article focuses on the rejuvenating link between medicine and spirituality.

  5. Linking Essential Tremor to the Cerebellum: Neurochemical Evidence.

    Science.gov (United States)

    Marin-Lahoz, Juan; Gironell, Alexandre

    2016-06-01

    The pathophysiology and the exact anatomy of essential tremor (ET) is not well known. One of the pillars that support the cerebellum as the main anatomical locus in ET is neurochemistry. This review examines the link between neurochemical abnormalities found in ET and cerebellum. The review is based on published data about neurochemical abnormalities described in ET both in human and in animal studies. We try to link those findings with cerebellum. γ-aminobutyric acid (GABA) is the main neurotransmitter involved in the pathophysiology of ET. There are several studies about GABA that clearly points to a main role of the cerebellum. There are few data about other neurochemical abnormalities in ET. These include studies with noradrenaline, glutamate, adenosine, proteins, and T-type calcium channels. One single study reveals high levels of noradrenaline in the cerebellar cortex. Another study about serotonin neurotransmitter results negative for cerebellum involvement. Finally, studies on T-type calcium channels yield positive results linking the rhythmicity of ET and cerebellum. Neurochemistry supports the cerebellum as the main anatomical locus in ET. The main neurotransmitter involved is GABA, and the GABA hypothesis remains the most robust pathophysiological theory of ET to date. However, this hypothesis does not rule out other mechanisms and may be seen as the main scaffold to support findings in other systems. We clearly need to perform more studies about neurochemistry in ET to better understand the relations among the diverse systems implied in ET. This is mandatory to develop more effective pharmacological therapies.

  6. Evidence for a genetic etiology of early-onset delinquency.

    Science.gov (United States)

    Taylor, J; Iacono, W G; McGue, M

    2000-11-01

    Age at onset of antisocial behavior discriminates persistent and transitory offenders. The authors proposed that early-onset delinquency has an underlying genetic influence that manifests in problems related to inhibition, whereas late-onset delinquency is more environmentally mediated. To test these notions, they selected 36 early starters, 86 late starters, and 25 nondelinquent controls from a large sample of 11-year-old twins and compared them on several measures related to inhibition and a peer group measure. As expected, early starters had more psychological, behavioral, and emotional problems related to inhibition than late starters and controls. A longitudinal analysis indicated an increase an antisocial behavior among peers of late starters shortly before their delinquency onset. Family history data and a twin analysis provided evidence of greater genetic influence on early-onset than late-onset delinquency.

  7. INFORMATION TECHNOLOGY AND ROMANIAN HIGHER EDUCATION - EVIDENCE ON LINKED DYNAMIC

    Directory of Open Access Journals (Sweden)

    Bogdan Nichifor

    2014-07-01

    Full Text Available The link between education, in general, and information technologies is one that does not necessarily have to be demonstrated. But it is interesting to see the specific link that is established between these two components of modern society. In recent years, part-time education forms tend to occupy an increasingly important position in the Romanian higher education from the perspective of the total number of students opting for distance learning or traditional part-time learning. This development occurred amid expansion of information technology - more and more households have Internet access and frequency of its use is increasing from year to year – in the context in which forms of part – time learning require the use of this means of information and communication. On this background more and more people over 25 years become interested in further developing their studies, including employed persons opting for further studies, increasing the share of students over 25 years in total students and the share of employed population over 25 years with higher education in total in respective age group.

  8. Linking Essential Tremor to the Cerebellum: Physiological Evidence.

    Science.gov (United States)

    Filip, Pavel; Lungu, Ovidiu V; Manto, Mario-Ubaldo; Bareš, Martin

    2016-12-01

    Essential tremor (ET), clinically characterized by postural and kinetic tremors, predominantly in the upper extremities, originates from pathological activity in the dynamic oscillatory network comprising the majority of nodes in the central motor network. Evidence indicates dysfunction in the thalamus, the olivocerebellar loops, and intermittent cortical engagement. Pathology of the cerebellum, a structure with architecture intrinsically predisposed to oscillatory activity, has also been implicated in ET as shown by clinical, neuroimaging, and pathological studies. Despite electrophysiological studies assessing cerebellar impairment in ET being scarce, their impact is tangible, as summarized in this review. The electromyography-magnetoencephalography combination provided the first direct evidence of pathological alteration in cortico-subcortical communication, with a significant emphasis on the cerebellum. Furthermore, complex electromyography studies showed disruptions in the timing of agonist and antagonist muscle activation, a process generally attributed to the cerebellum. Evidence pointing to cerebellar engagement in ET has also been found in electrooculography measurements, cerebellar repetitive transcranial magnetic stimulation studies, and, indirectly, in complex analyses of the activity of the ventral intermediate thalamic nucleus (an area primarily receiving inputs from the cerebellum), which is also used in the advanced treatment of ET. In summary, further progress in therapy will require comprehensive electrophysiological and physiological analyses to elucidate the precise mechanisms leading to disease symptoms. The cerebellum, as a major node of this dynamic oscillatory network, requires further study to aid this endeavor.

  9. Linking Essential Tremor to the Cerebellum-Neuroimaging Evidence.

    Science.gov (United States)

    Cerasa, Antonio; Quattrone, Aldo

    2016-06-01

    Essential tremor (ET) is the most common pathological tremor disorder in the world, and post-mortem evidence has shown that the cerebellum is the most consistent area of pathology in ET. In the last few years, advanced neuroimaging has tried to confirm this evidence. The aim of the present review is to discuss to what extent the evidence provided by this field of study may be generalised. We performed a systematic literature search combining the terms ET with the following keywords: MRI, VBM, MRS, DTI, fMRI, PET and SPECT. We summarised and discussed each study and placed the results in the context of existing knowledge regarding the cerebellar involvement in ET. A total of 51 neuroimaging studies met our search criteria, roughly divided into 19 structural and 32 functional studies. Despite clinical and methodological differences, both functional and structural imaging studies showed similar findings but without defining a clear topography of neurodegeneration. Indeed, the vast majority of studies found functional and structural abnormalities in several parts of the anterior and posterior cerebellar lobules, but it remains to be established to what degree these neural changes contribute to clinical symptoms of ET. Currently, advanced neuroimaging has confirmed the involvement of the cerebellum in pathophysiological processes of ET, although a high variability in results persists. For this reason, the translation of this knowledge into daily clinical practice is again partially limited, although new advanced multivariate neuroimaging approaches (machine-learning) are proving interesting changes of perspective.

  10. Observational Evidence Linking Interstellar UV Absorption to PAH Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Blasberger, Avi; Behar, Ehud; Perets, Hagai B. [Department of Physics, Technion (Israel); Brosch, Noah [The Wise Observatory and School of Physics and Astronomy, Tel Aviv University (Israel); Tielens, Alexander G. G. M. [Leiden Observatory, Leiden University (Netherlands)

    2017-02-20

    The 2175 Å UV extinction feature was discovered in the mid-1960s, yet its physical origin remains poorly understood. One suggestion is absorption by polycyclic aromatic hydrocarbon (PAH) molecules, which is supported by theoretical molecular structure computations and by laboratory experiments. PAHs are positively detected by their 3.3, 6.2, 7.7, 8.6, 11.3, and 12.7 μ m IR emission bands, which are specified by their modes of vibration. A definitive empirical link between the 2175 Å UV extinction and the IR PAH emission bands, however, is still missing. We present a new sample of hot stars that have both 2175 Å absorption and IR PAH emission. We find significant shifts of the central wavelength of the UV absorption feature, up to 2350 Å, but predominantly in stars that also have IR PAH emission. These UV shifts depend on stellar temperature in a fashion that is similar to the shifts of the 6.2 and 7.7 μ m IR PAH bands, that is, the features are increasingly more redshifted as the stellar temperature decreases, but only below ∼15 kK. Above 15 kK both UV and IR features retain their nominal values. Moreover, we find a suggestive correlation between the UV and IR shifts. We hypothesize that these similar dependences of both the UV and IR features on stellar temperature hint at a common origin of the two in PAH molecules and may establish the missing link between the UV and IR observations. We further suggest that the shifts depend on molecular size, and that the critical temperature of ∼15 kK above which no shifts are observed is related to the onset of UV-driven hot-star winds and their associated shocks.

  11. Observational Evidence Linking Interstellar UV Absorption to PAH Molecules

    International Nuclear Information System (INIS)

    Blasberger, Avi; Behar, Ehud; Perets, Hagai B.; Brosch, Noah; Tielens, Alexander G. G. M.

    2017-01-01

    The 2175 Å UV extinction feature was discovered in the mid-1960s, yet its physical origin remains poorly understood. One suggestion is absorption by polycyclic aromatic hydrocarbon (PAH) molecules, which is supported by theoretical molecular structure computations and by laboratory experiments. PAHs are positively detected by their 3.3, 6.2, 7.7, 8.6, 11.3, and 12.7 μ m IR emission bands, which are specified by their modes of vibration. A definitive empirical link between the 2175 Å UV extinction and the IR PAH emission bands, however, is still missing. We present a new sample of hot stars that have both 2175 Å absorption and IR PAH emission. We find significant shifts of the central wavelength of the UV absorption feature, up to 2350 Å, but predominantly in stars that also have IR PAH emission. These UV shifts depend on stellar temperature in a fashion that is similar to the shifts of the 6.2 and 7.7 μ m IR PAH bands, that is, the features are increasingly more redshifted as the stellar temperature decreases, but only below ∼15 kK. Above 15 kK both UV and IR features retain their nominal values. Moreover, we find a suggestive correlation between the UV and IR shifts. We hypothesize that these similar dependences of both the UV and IR features on stellar temperature hint at a common origin of the two in PAH molecules and may establish the missing link between the UV and IR observations. We further suggest that the shifts depend on molecular size, and that the critical temperature of ∼15 kK above which no shifts are observed is related to the onset of UV-driven hot-star winds and their associated shocks.

  12. The Epidemiologic Evidence Linking Autoimmune Diseases and Psychosis

    DEFF Research Database (Denmark)

    Benros, Michael E; Eaton, William W; Mortensen, Preben B

    2014-01-01

    diseases involve multiple organs and general dysfunction of the immune system, which could affect the brain and induce psychiatric symptoms. Most studies have been cross-sectional, observing an increased prevalence of a broad number of autoimmune diseases in people with psychotic disorders. Furthermore......, there is some evidence of associations of psychosis with a family history of autoimmune disorders and vice versa. Additionally, several autoimmune diseases, individually and in aggregate, have been identified as raising the risk for psychotic disorders in longitudinal studies. The associations have been...

  13. Preliminary evidence for genetic overlap between body mass index and striatal reward response.

    Science.gov (United States)

    Lancaster, T M; Ihssen, I; Brindley, L M; Linden, D E

    2018-01-10

    The reward-processing network is implicated in the aetiology of obesity. Several lines of evidence suggest obesity-linked genetic risk loci (such as DRD2 and FTO) may influence individual variation in body mass index (BMI) through neuropsychological processes reflected in alterations in activation of the striatum during reward processing. However, no study has tested the broader hypotheses that (a) the relationship between BMI and reward-related brain activation (measured through the blood oxygenation-dependent (BOLD) signal) may be observed in a large population study and (b) the overall genetic architecture of these phenotypes overlap, an assumption critical for the progression of imaging genetic studies in obesity research. Using data from the Human Connectome Project (N = 1055 healthy, young individuals: average BMI = 26.4), we first establish a phenotypic relationship between BMI and ventral striatal (VS) BOLD during the processing of rewarding (monetary) stimuli (β = 0.44, P = 0.013), accounting for potential confounds. BMI and VS BOLD were both significantly influenced by additive genetic factors (H2r = 0.57; 0.12, respectively). Further decomposition of this variance suggested that the relationship was driven by shared genetic (ρ g  = 0.47, P = 0.011), but not environmental (ρ E  = -0.07, P = 0.29) factors. To validate the assumption of genetic pleiotropy between BMI and VS BOLD, we further show that polygenic risk for higher BMI is also associated with increased VS BOLD response to appetitive stimuli (calorically high food images), in an independent sample (N = 81; P FWE-ROI  < 0.005). Together, these observations suggest that the genetic factors link risk to obesity to alterations within key nodes of the brain's reward circuity. These observations provide a basis for future work exploring the mechanistic role of genetic loci that confer risk for obesity using the imaging genetics approach.

  14. Depression and cardiovascular disease: Epidemiological evidence on their linking mechanisms.

    Science.gov (United States)

    Penninx, Brenda W J H

    2017-03-01

    Depression's burden of disease goes beyond functioning and quality of life and extends to somatic health. Results from longitudinal cohort studies converge in illustrating that major depressive disorder (MDD) subsequently increases the risk of cardiovascular morbidity and mortality with about 80%. The impact of MDD on cardiovascular health may be partly explained by mediating mechanisms such as unhealthy lifestyle (smoking, excessive alcohol use, physical inactivity, unhealthy diet, therapy non-compliance) and unfavorable pathophysiological disturbances (autonomic, HPA-axis, metabolic and immuno-inflammatory dysregulations). A summary of the literature findings as well as relevant results from the large-scale Netherlands Study of Depression and Anxiety (N=2981) are presented. Persons with MDD have significantly worse lifestyles as well as more pathophysiological disturbances as compared to healthy controls. Some of these differences seem to be specific for (typical versus 'atypical', or antidepressant treated versus drug-naive) subgroups of MDD patients. Alternative explanations are also present, namely undetected confounding, iatrogenic effects or 'third factors' such as genetics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. New genetic loci link adipose and insulin biology to body fat distribution

    NARCIS (Netherlands)

    D. Shungin (Dmitry); T.W. Winkler (Thomas W.); D.C. Croteau-Chonka (Damien); T. Ferreira (Teresa); A. Locke (Adam); R. Mägi (Reedik); R.J. Strawbridge (Rona); T.H. Pers (Tune); K. Fischer (Krista); A.E. Justice (Anne); T. Workalemahu (Tsegaselassie); J.M.W. Wu (Joseph M. W.); M.L. Buchkovich (Martin); N.L. Heard-Costa (Nancy); T.S. Roman (Tamara S.); A. Drong (Alexander); C. Song (Ci); S. Gustafsson (Stefan); F.R. Day (Felix); T. Esko (Tõnu); M. Fall (Magnus); Z. Kutalik (Zolta'n); J. Luan; J.C. Randall (Joshua); A. Scherag (Andre); S. Vedantam (Sailaja); A.R. Wood (Andrew); J. Chen (Jin); R.S.N. Fehrmann (Rudolf); J. Karjalainen (Juha); B. Kahali (Bratati); C.-T. Liu (Ching-Ti); E.M. Schmidt (Ellen); D. Absher (Devin); N. Amin (Najaf); M. Beekman (Marian); J.L. Bragg-Gresham (Jennifer L.); S. Buyske (Steven); A. Demirkan (Ayşe); G.B. Ehret (Georg); M.F. Feitosa (Mary Furlan); A. Goel (Anuj); A.U. Jackson (Anne); T. Johnson (Toby); M.E. Kleber (Marcus); K. Kristiansson (Kati); M. Mangino (Massimo); I.M. Leach (Irene Mateo); M.C. Medina-Gomez (Carolina); C. Palmer (Cameron); D. Pasko (Dorota); S. Pechlivanis (Sonali); M.J. Peters (Marjolein); I. Prokopenko (Inga); A. Stanca'kova' (Alena); Y.J. Sung (Yun Ju); T. Tanaka (Toshiko); A. Teumer (Alexander); J.V. van Vliet-Ostaptchouk (Jana); L. Yengo (Loic); W. Zhang (Weihua); E. Albrecht (Eva); J. Ärnlöv (Johan); G.M. Arscott (Gillian M.); S. Bandinelli (Stefania); A. Barrett (Angela); C. Bellis (Claire); A.J. Bennett (Amanda); C. Berne (Christian); M. Blüher (Matthias); S. Böhringer (Stefan); F. Bonnet (Fabrice); Y. Böttcher (Yvonne); M. Bruinenberg (M.); D.B. Carba (Delia B.); I.H. Caspersen (Ida H.); R. Clarke (Robert); E.W. Daw (E. Warwick); J. Deelen (Joris); E. Deelman (Ewa); G. Delgado; A.S.F. Doney (Alex); N. Eklund (Niina); M.R. Erdos (Michael); K. Estrada Gil (Karol); E. Eury (Elodie); N. Friedrich (Nele); M. Garcia (Melissa); V. Giedraitis (Vilmantas); B. Gigante (Bruna); A. Go (Attie); A. Golay (Alain); H. Grallert (Harald); T.B. Grammer (Tanja); J. Gräsler (Jürgen); J. Grewal (Jagvir); C.J. Groves (Christopher); T. Haller (Toomas); G. Hallmans (Göran); C.A. Hartman (Catharina); M. Hassinen (Maija); C. Hayward (Caroline); K. Heikkilä (Kauko); K.H. Herzig; Q. Helmer (Quinta); H.L. Hillege (Hans); O.L. Holmen (Oddgeir); S.C. Hunt (Steven); A. Isaacs (Aaron); T. Ittermann (Till); A.L. James (Alan); I. Johansson (Inger); T. Juliusdottir (Thorhildur); I.-P. Kalafati (Ioanna-Panagiota); L. Kinnunen (Leena); W. Koenig (Wolfgang); I.K. Kooner (Ishminder K.); W. Kratzer (Wolfgang); C. Lamina (Claudia); K. Leander (Karin); N.R. Lee (Nanette R.); P. Lichtner (Peter); L. Lind (Lars); J. Lindström (Jaana); S. Lobbens (Stéphane); M. Lorentzon (Mattias); F. MacH (François); P.K. Magnusson (Patrik); A. Mahajan (Anubha); W.L. McArdle (Wendy); C. Menni (Cristina); S. Merger (Sigrun); E. Mihailov (Evelin); L. Milani (Lili); R. Mills (Rebecca); A. Moayyeri (Alireza); K.L. Monda (Keri); S.P. Mooijaart (Simon); T.W. Mühleisen (Thomas); A. Mulas (Antonella); G. Müller (Gabriele); M. Müller-Nurasyid (Martina); R. Nagaraja (Ramaiah); M.A. Nalls (Michael); N. Narisu (Narisu); N. Glorioso (Nicola); I.M. Nolte (Ilja M.); M. Olden (Matthias); N.W. Rayner (Nigel William); F. Renström (Frida); J.S. Ried (Janina); N.R. Robertson (Neil R.); L.M. Rose (Lynda); S. Sanna (Serena); H. Scharnagl (Hubert); S. Scholtens (Salome); B. Sennblad (Bengt); T. Seufferlein (Thomas); C.M. Sitlani (Colleen); G.D. Smith; K. Stirrups (Kathy); H.M. Stringham (Heather); J. Sundstrom (Johan); M. Swertz (Morris); A.J. Swift (Amy); A.C. Syvanen; B. Tayo (Bamidele); B. Thorand (Barbara); G. Thorleifsson (Gudmar); A. Tomaschitz (Andreas); C. Troffa (Chiara); F.V.A. van Oort (Floor); N. Verweij (Niek); J.M. Vonk (Judith); L. Waite (Lindsay); R. Wennauer (Roman); T. Wilsgaard (Tom); M.K. Wojczynski (Mary ); A. Wong (Andrew); Q. Zhang (Qunyuan); J.H. Zhao (Jing Hua); E.P. Brennan (Eoin P.); M. Choi (Murim); P. Eriksson (Per); L. Folkersen (Lasse); A. Franco-Cereceda (Anders); A.G. Gharavi (Ali G.); A.K. Hedman (Asa); M.-F. Hivert (Marie-France); J. Huang (Jinyan); S. Kanoni (Stavroula); F. Karpe (Fredrik); S. Keildson (Sarah); K. Kiryluk (Krzysztof); L. Liang (Liming); R.P. Lifton (Richard); B. Ma (Baoshan); A.J. McKnight (Amy J.); R. McPherson (Ruth); A. Metspalu (Andres); J.L. Min (Josine L.); M.F. Moffatt (Miriam); G.W. Montgomery (Grant); J. Murabito (Joanne); G. Nicholson (Ggeorge); A.S. Dimas (Antigone); C. Olsson (Christian); J.R.B. Perry (John); E. Reinmaa (Eva); R.M. Salem (Rany); N. Sandholm (Niina); E.E. Schadt (Eric); R.A. Scott (Robert); L. Stolk (Lisette); E.E. Vallejo (Edgar E.); H.J. Westra (Harm-Jan); K.T. Zondervan (Krina); P. Amouyel (Philippe); D. Arveiler (Dominique); S.J.L. Bakker (Stephan); J.P. Beilby (John); R.N. Bergman (Richard); J. Blangero (John); M.J. Brown (Morris); M. Burnier (Michel); H. Campbell (Harry); A. Chakravarti (Aravinda); P.S. Chines (Peter); S. Claudi-Boehm (Simone); F.S. Collins (Francis); D.C. Crawford (Dana); J. Danesh (John); U. de Faire (Ulf); E.J.C. de Geus (Eco); M. Dörr (Marcus); R. Erbel (Raimund); K. Hagen (Knut); M. Farrall (Martin); E. Ferrannini (Ele); J. Ferrieres (Jean); N.G. Forouhi (Nita); T. Forrester (Terrence); O.H. Franco (Oscar); R.T. Gansevoort (Ron); C. Gieger (Christian); V. Gudnason (Vilmundur); C.A. Haiman (Christopher); T.B. Harris (Tamara); A.T. Hattersley (Andrew); M. Heliovaara (Markku); A.A. Hicks (Andrew); A. Hingorani (Aroon); W. Hoffmann (Wolfgang); A. Hofman (Albert); G. Homuth (Georg); S.E. Humphries (Steve); E. Hypponen (Elina); T. Illig (Thomas); M.-R. Jarvelin (Marjo-Riitta); B. Johansen (Berit); P. Jousilahti (Pekka); A. Jula (Antti); J. Kaprio (Jaakko); F. Kee (F.); S. Keinanen-Kiukaanniemi (Sirkka); J.S. Kooner (Jaspal S.); C. Kooperberg (Charles); P. Kovacs (Peter); A. Kraja (Aldi); M. Kumari (Meena); K. Kuulasmaa (Kari); J. Kuusisto (Johanna); T.A. Lakka (Timo); C. Langenberg (Claudia); L. Le Marchand (Loic); T. Lehtimäki (Terho); V. Lyssenko (Valeriya); S. Männistö (Satu); A. Marette (Andre'); T.C. Matise (Tara C.); C.A. McKenzie (Colin A.); B. McKnight (Barbara); A.W. Musk (Arthur); S. Möhlenkamp (Stefan); A.D. Morris (Andrew); M. Nelis (Mari); C. Ohlsson (Claes); A.J. Oldehinkel (Albertine); K.K. Ong (Ken K.); C. Palmer (Cameron); B.W.J.H. Penninx (Brenda); A. Peters (Annette); P.P. Pramstaller (Peter Paul); O. Raitakari (Olli); T. Rankinen (Tuomo); D.C. Rao (Dabeeru C.); T.K. Rice (Treva K.); P.M. Ridker (Paul); M.D. Ritchie (Marylyn D.); I. Rudan (Igor); V. Salomaa (Veikko); N.J. Samani (Nilesh); J. Saramies (Jouko); M.A. Sarzynski (Mark A.); P.E.H. Schwarz (Peter E. H.); A.R. Shuldiner (Alan); J.A. Staessen (Jan); V. Steinthorsdottir (Valgerdur); R.P. Stolk (Ronald); K. Strauch (Konstantin); A. Tönjes (Anke); A. Tremblay (Angelo); E. Tremoli (Elena); M.-C. Vohl (Marie-Claude); U. Völker (Uwe); P. Vollenweider (Peter); J.F. Wilson (James F); J.C.M. Witteman (Jacqueline); L.S. Adair (Linda); M. Bochud (Murielle); B.O. Boehm (Bernhard); S.R. Bornstein (Stefan R.); C. Bouchard (Claude); S. Cauchi (Ste'phane); M. Caulfield (Mark); J.C. Chambers (John C.); D.I. Chasman (Daniel); R.S. Cooper (Richard S.); G.V. Dedoussis (George); L. Ferrucci (Luigi); P. Froguel (Philippe); H.J. Grabe (Hans Jörgen); A. Hamsten (Anders); J. Hui (Jennie); K. Hveem (Kristian); K.-H. Jöckel (Karl-Heinz); M. Kivimaki (Mika); D. Kuh (Diana); M. Laakso (Markku); Y. Liu (YongMei); W. März (Winfried); P. Munroe (Patricia); I. Njølstad (Inger); B.A. Oostra (Ben); C.N.A. Palmer (Colin); N.L. Pedersen (Nancy L.); M. Perola (Markus); L. Perusse (Louis); U. Peters (Ulrike); C. Power (Christopher); T. Quertermous (Thomas); R. Rauramaa (Rainer); F. Rivadeneira Ramirez (Fernando); T. Saaristo (Timo); D. Saleheen; J. Sinisalo (Juha); P.E. Slagboom (Eline); H. Snieder (Harold); T.D. Spector (Timothy); U. Thorsteinsdottir (Unnur); M. Stumvoll (Michael); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); M. Uusitupa (Matti); P. van der Harst (Pim); G. Veronesi (Giovanni); M. Walker (Mark); N.J. Wareham (Nick); H. Watkins (Hugh); H.E. Wichmann (Heinz Erich); G.R. Abecasis (Gonçalo); T.L. Assimes (Themistocles); S.I. Berndt (Sonja); M. Boehnke (Michael); I.B. Borecki (Ingrid); P. Deloukas (Panagiotis); L. Franke (Lude); T.M. Frayling (Timothy); L. Groop (Leif); D. Hunter (David); R.C. Kaplan (Robert); J.R. O´Connell; L. Qi (Lu); D. Schlessinger (David); D.P. Strachan (David); J-A. Zwart (John-Anker); C.M. van Duijn (Cornelia); C.J. Willer (Cristen); P.M. Visscher (Peter); J. Yang (Joanna); J.N. Hirschhorn (Joel N.); M.C. Zillikens (Carola); M.I. McCarthy (Mark); E.K. Speliotes (Elizabeth); K.E. North (Kari); C.S. Fox (Caroline S.); I.E. Barroso (Inês); P.W. Franks (Paul); D. Anderson (Denise); E. Ingelsson (Erik); I.M. Heid (Iris); R.J.F. Loos (Ruth); L.A. Cupples (Adrienne); A.P. Morris (Andrew); C.M. Lindgren (Cecilia); K.L. Mohlke (Karen)

    2015-01-01

    textabstractBody fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct

  16. New genetic loci link adipose and insulin biology to body fat distribution

    NARCIS (Netherlands)

    Shungin, Dmitry; Winkler, Thomas W.; Croteau-Chonka, Damien C.; Ferreira, Teresa; Locke, Adam E.; Mägi, Reedik; Strawbridge, Rona J.; Pers, Tune H.; Fischer, Krista; Justice, Anne E.; Workalemahu, Tsegaselassie; Wu, Joseph M. W.; Buchkovich, Martin L.; Heard-Costa, Nancy L.; Roman, Tamara S.; Drong, Alexander W.; Song, Ci; Gustafsson, Stefan; Day, Felix R.; Esko, Tonu; Fall, Tove; Kutalik, Zoltán; Luan, Jian'an; Randall, Joshua C.; Scherag, André; Vedantam, Sailaja; Wood, Andrew R.; Chen, Jin; Fehrmann, Rudolf; Karjalainen, Juha; Kahali, Bratati; Liu, Ching-Ti; Schmidt, Ellen M.; Absher, Devin; Amin, Najaf; Anderson, Denise; Beekman, Marian; Bragg-Gresham, Jennifer L.; Buyske, Steven; Demirkan, Ayse; Ehret, Georg B.; Feitosa, Mary F.; Goel, Anuj; Jackson, Anne U.; Johnson, Toby; Kleber, Marcus E.; Kristiansson, Kati; Mangino, Massimo; Mateo Leach, Irene; Medina-Gomez, Carolina; Palmer, Cameron D.; Pasko, Dorota; Pechlivanis, Sonali; Peters, Marjolein J.; Prokopenko, Inga; Stančáková, Alena; Ju Sung, Yun; Tanaka, Toshiko; Teumer, Alexander; van Vliet-Ostaptchouk, Jana V.; Yengo, Loïc; Zhang, Weihua; Albrecht, Eva; Ärnlöv, Johan; Arscott, Gillian M.; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J.; Berne, Christian; Blüher, Matthias; Böhringer, Stefan; Bonnet, Fabrice; Böttcher, Yvonne; Bruinenberg, Marcel; Carba, Delia B.; Caspersen, Ida H.; Clarke, Robert; Daw, E. Warwick; Deelen, Joris; Deelman, Ewa; Delgado, Graciela; Doney, Alex S. F.; Eklund, Niina; Erdos, Michael R.; Estrada, Karol; Eury, Elodie; Friedrich, Nele; Garcia, Melissa E.; Giedraitis, Vilmantas; Gigante, Bruna; Go, Alan S.; Golay, Alain; Grallert, Harald; Grammer, Tanja B.; Gräßler, Jürgen; Grewal, Jagvir; Groves, Christopher J.; Haller, Toomas; Hallmans, Goran; Hartman, Catharina A.; Hassinen, Maija; Hayward, Caroline; Heikkilä, Kauko; Herzig, Karl-Heinz; Helmer, Quinta; Hillege, Hans L.; Holmen, Oddgeir; Hunt, Steven C.; Isaacs, Aaron; Ittermann, Till; James, Alan L.; Johansson, Ingegerd; Juliusdottir, Thorhildur; Kalafati, Ioanna-Panagiota; Kinnunen, Leena; Koenig, Wolfgang; Kooner, Ishminder K.; Kratzer, Wolfgang; Lamina, Claudia; Leander, Karin; Lee, Nanette R.; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Mach, François; Magnusson, Patrik K. E.; Mahajan, Anubha; McArdle, Wendy L.; Menni, Cristina; Merger, Sigrun; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Moayyeri, Alireza; Monda, Keri L.; Mooijaart, Simon P.; Mühleisen, Thomas W.; Mulas, Antonella; Müller, Gabriele; Müller-Nurasyid, Martina; Nagaraja, Ramaiah; Nalls, Michael A.; Narisu, Narisu; Glorioso, Nicola; Nolte, Ilja M.; Olden, Matthias; Rayner, Nigel W.; Renstrom, Frida; Ried, Janina S.; Robertson, Neil R.; Rose, Lynda M.; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Sennblad, Bengt; Seufferlein, Thomas; Sitlani, Colleen M.; Vernon Smith, Albert; Stirrups, Kathleen; Stringham, Heather M.; Sundström, Johan; Swertz, Morris A.; Swift, Amy J.; Syvänen, Ann-Christine; Tayo, Bamidele O.; Thorand, Barbara; Thorleifsson, Gudmar; Tomaschitz, Andreas; Troffa, Chiara; van Oort, Floor V. A.; Verweij, Niek; Vonk, Judith M.; Waite, Lindsay L.; Wennauer, Roman; Wilsgaard, Tom; Wojczynski, Mary K.; Wong, Andrew; Zhang, Qunyuan; Hua Zhao, Jing; Brennan, Eoin P.; Choi, Murim; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Gharavi, Ali G.; Hedman, Åsa K.; Hivert, Marie-France; Huang, Jinyan; Kanoni, Stavroula; Karpe, Fredrik; Keildson, Sarah; Kiryluk, Krzysztof; Liang, Liming; Lifton, Richard P.; Ma, Baoshan; McKnight, Amy J.; McPherson, Ruth; Metspalu, Andres; Min, Josine L.; Moffatt, Miriam F.; Montgomery, Grant W.; Murabito, Joanne M.; Nicholson, George; Nyholt, Dale R.; Olsson, Christian; Perry, John R. B.; Reinmaa, Eva; Salem, Rany M.; Sandholm, Niina; Schadt, Eric E.; Scott, Robert A.; Stolk, Lisette; Vallejo, Edgar E.; Westra, Harm-Jan; Zondervan, Krina T.; Amouyel, Philippe; Arveiler, Dominique; Bakker, Stephan J. L.; Beilby, John; Bergman, Richard N.; Blangero, John; Brown, Morris J.; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chines, Peter S.; Claudi-Boehm, Simone; Collins, Francis S.; Crawford, Dana C.; Danesh, John; de Faire, Ulf; de Geus, Eco J. C.; Dörr, Marcus; Erbel, Raimund; Eriksson, Johan G.; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Forouhi, Nita G.; Forrester, Terrence; Franco, Oscar H.; Gansevoort, Ron T.; Gieger, Christian; Gudnason, Vilmundur; Haiman, Christopher A.; Harris, Tamara B.; Hattersley, Andrew T.; Heliövaara, Markku; Hicks, Andrew A.; Hingorani, Aroon D.; Hoffmann, Wolfgang; Hofman, Albert; Homuth, Georg; Humphries, Steve E.; Hyppönen, Elina; Illig, Thomas; Jarvelin, Marjo-Riitta; Johansen, Berit; Jousilahti, Pekka; Jula, Antti M.; Kaprio, Jaakko; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M.; Kooner, Jaspal S.; Kooperberg, Charles; Kovacs, Peter; Kraja, Aldi T.; Kumari, Meena; Kuulasmaa, Kari; Kuusisto, Johanna; Lakka, Timo A.; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lyssenko, Valeriya; Männistö, Satu; Marette, André; Matise, Tara C.; McKenzie, Colin A.; McKnight, Barbara; Musk, Arthur W.; Möhlenkamp, Stefan; Morris, Andrew D.; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J.; Ong, Ken K.; Palmer, Lyle J.; Penninx, Brenda W.; Peters, Annette; Pramstaller, Peter P.; Raitakari, Olli T.; Rankinen, Tuomo; Rao, D. C.; Rice, Treva K.; Ridker, Paul M.; Ritchie, Marylyn D.; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J.; Saramies, Jouko; Sarzynski, Mark A.; Schwarz, Peter E. H.; Shuldiner, Alan R.; Staessen, Jan A.; Steinthorsdottir, Valgerdur; Stolk, Ronald P.; Strauch, Konstantin; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Vohl, Marie-Claude; Völker, Uwe; Vollenweider, Peter; Wilson, James F.; Witteman, Jacqueline C.; Adair, Linda S.; Bochud, Murielle; Boehm, Bernhard O.; Bornstein, Stefan R.; Bouchard, Claude; Cauchi, Stéphane; Caulfield, Mark J.; Chambers, John C.; Chasman, Daniel I.; Cooper, Richard S.; Dedoussis, George; Ferrucci, Luigi; Froguel, Philippe; Grabe, Hans-Jörgen; Hamsten, Anders; Hui, Jennie; Hveem, Kristian; Jöckel, Karl-Heinz; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; März, Winfried; Munroe, Patricia B.; Njølstad, Inger; Oostra, Ben A.; Palmer, Colin N. A.; Pedersen, Nancy L.; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Rivadeneira, Fernando; Saaristo, Timo E.; Saleheen, Danish; Sinisalo, Juha; Slagboom, P. Eline; Snieder, Harold; Spector, Tim D.; Thorsteinsdottir, Unnur; Stumvoll, Michael; Tuomilehto, Jaakko; Uitterlinden, André G.; Uusitupa, Matti; van der Harst, Pim; Veronesi, Giovanni; Walker, Mark; Wareham, Nicholas J.; Watkins, Hugh; Wichmann, H.-Erich; Abecasis, Goncalo R.; Assimes, Themistocles L.; Berndt, Sonja I.; Boehnke, Michael; Borecki, Ingrid B.; Deloukas, Panos; Franke, Lude; Frayling, Timothy M.; Groop, Leif C.; Hunter, David J.; Kaplan, Robert C.; O'Connell, Jeffrey R.; Qi, Lu; Schlessinger, David; Strachan, David P.; Stefansson, Kari; van Duijn, Cornelia M.; Willer, Cristen J.; Visscher, Peter M.; Yang, Jian; Hirschhorn, Joel N.; Zillikens, M. Carola; McCarthy, Mark I.; Speliotes, Elizabeth K.; North, Kari E.; Fox, Caroline S.; Barroso, Inês; Franks, Paul W.; Ingelsson, Erik; Heid, Iris M.; Loos, Ruth J. F.; Cupples, L. Adrienne; Morris, Andrew P.; Lindgren, Cecilia M.; Mohlke, Karen L.; Dastani, Zari; Timpson, Nicholas; Yuan, Xin; Henneman, Peter; Kizer, Jorge R.; Lyytikainen, Leo-Pekka; Fuchsberger, Christian; Small, Kerrin; Coassin, Stefan; Lohman, Kurt; Pankow, James S.; Uh, Hae-Won; Wu, Ying; Bidulescu, Aurelian; Rasmussen-Torvik, Laura J.; Greenwood, Celia M. T.; Ladouceur, Martin; Grimsby, Jonna; Manning, Alisa K.; Kooner, Jaspal; Mooser, Vincent E.; Kapur, Karen A.; Chambers, John; Frants, Rune; Willemsvan-vanDijk, Ko; Willems, Sara M.; Winkler, Thomas; Psaty, Bruce M.; Tracy, Russell P.; Brody, Jennifer; Chen, Ida; Viikari, Jorma; Kähönen, Mika; Evans, David M.; St Pourcain, Beate; Sattar, Naveed; Wood, Andy; Carlson, Olga D.; Egan, Josephine M.; van Heemst, Diana; Kedenko, Lyudmyla; Nuotio, Marja-Liisa; Loo, Britt-Marie; Harris, Tamara; Garcia, Melissa; Kanaya, Alka; Haun, Margot; Klopp, Norman; Wichmann, H. Erich; Katsareli, Efi; Couper, David J.; Duncan, Bruce B.; Kloppenburg, Margreet; Borja, Judith B.; Wilson, James G.; Musani, Solomon; Guo, Xiuqing; Semple, Robert; Teslovich, Tanya M.; Allison, Matthew A.; Redline, Susan; Buxbaum, Sarah G.; Meulenbelt, Ingrid; Ballantyne, Christie M.; Dedoussis, George V.; Hu, Frank B.; Paulweber, Bernhard; Spector, Timothy D.; Jula, Antti; Raitakari, Olli; Florez, Jose C.; Smith, George Davey; Siscovick, David S.; Kronenberg, Florian; van Duijn, Cornelia; Waterworth, Dawn M.; Meigs, James B.; Dupuis, Josee; Richards, John Brent; Willenborg, Christina; Thompson, John R.; Erdmann, Jeanette; Goldstein, Benjamin A.; König, Inke R.; Cazier, Jean-Baptiste; Johansson, Åsa; Hall, Alistair S.; Lee, Jong-Young; Esko, Tõnu; Grundberg, Elin; Havulinna, Aki S.; Ho, Weang K.; Hopewell, Jemma C.; Eriksson, Niclas; Lundmark, Per; Lyytikäinen, Leo-Pekka; Rafelt, Suzanne; Tikkanen, Emmi; van Zuydam, Natalie; Voight, Benjamin F.; Ziegler, Andreas; Altshuler, David; Balmforth, Anthony J.; Braund, Peter S.; Burgdorf, Christof; Cox, David; Dimitriou, Maria; Do, Ron; El Mokhtari, NourEddine; Fontanillas, Pierre; Groop, Leif; Hager, Jörg; Hallmans, Göran; Han, Bok-Ghee; Hunt, Sarah E.; Kang, Hyun M.; Kessler, Thorsten; Knowles, Joshua W.; Kolovou, Genovefa; Langford, Cordelia; Lokki, Marja-Liisa; Lundmark, Anders; Meisinger, Christa; Melander, Olle; Maouche, Seraya; Nikus, Kjell; Peden, John F.; Rayner, N. William; Rasheed, Asif; Rosinger, Silke; Rubin, Diana; Rumpf, Moritz P.; Schäfer, Arne; Sivananthan, Mohan; Stewart, Alexandre F. R.; Tan, Sian-Tsung; Thorgeirsson, Gudmundur; van der Schoot, C. Ellen; Wagner, Peter J.; Wells, George A.; Wild, Philipp S.; Yang, Tsun-Po; Basart, Hanneke; Boerwinkle, Eric; Brambilla, Paolo; Cambien, Francois; Cupples, Adrienne L.; Dehghan, Abbas; Diemert, Patrick; Epstein, Stephen E.; Evans, Alun; Ferrario, Marco M.; Gauguier, Dominique; Goodall, Alison H.; Gudnason, Villi; Hazen, Stanley L.; Holm, Hilma; Iribarren, Carlos; Jang, Yangsoo; Kim, Hyo-Soo; Laaksonen, Reijo; Lee, Ji-Young; Ouwehand, Willem H.; Parish, Sarah; Park, Jeong E.; Rader, Daniel J.; Schadt, Eric; Shah, Svati H.; Stark, Klaus; Trégouët, David-Alexandre; Virtamo, Jarmo; Wallentin, Lars; Wareham, Nicholas; Zimmermann, Martina E.; Nieminen, Markku S.; Hengstenberg, Christian; Sandhu, Manjinder S.; Pastinen, Tomi; Hovingh, G. Kees; Zalloua, Pierre A.; Siegbahn, Agneta; Schreiber, Stefan; Ripatti, Samuli; Blankenberg, Stefan S.; O'Donnell, Christopher; Reilly, Muredach P.; Collins, Rory; Kathiresan, Sekar; Roberts, Robert; Schunkert, Heribert; Pattaro, Cristian; Köttgen, Anna; Garnaas, Maija; Böger, Carsten A.; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; O'Seaghdha, Conall M.; Glazer, Nicole; Smith, Albert V.; Struchalin, Maksim; Li, Guo; Johnson, Andrew D.; Gierman, Hinco J.; Feitosa, Mary; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Cornelis, Marilyn C.; Chouraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; de Andrade, Mariza; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Döring, Angela; Wichmann, H. -Erich; Kolcic, Ivana; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Endlich, Karlhans; Ernst, Florian; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völzke, Henry; Uitterlinden, Andre G.; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Ruggiero, Daniela; Bergmann, Sven; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Giulianini, Franco; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Sala, Cinzia; Metzger, Marie; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K.; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Toniolo, Daniela; Coresh, Josef; Schmidt, Reinhold; Borecki, Ingrid; Kardia, Sharon L. R.; Curhan, Gary C.; Gyllensten, Ulf; Franke, Andre; Rettig, Rainer; Witteman, Jacqueline C. M.; Ridker, Paul; Parsa, Afshin; Goessling, Wolfram; Kao, W. H. Linda; de Boer, Ian H.; Glazer, Nicole L.; Peralta, Carmen A.; Zhao, Jing Hua; Akylbekova, Ermeg; Kramer, Holly; Arking, Dan E.; Franceschini, Nora; Egan, Josephine; Hernandez, Dena; Reilly, Muredach; Townsend, Raymond R.; Lumley, Thomas; Kestenbaum, Bryan; Haritunians, Talin; Waeber, Gerard; Mooser, Vincent; Waterworth, Dawn; Lu, Xiaoning; Leak, Tennille S.; Aasarød, Knut; Skorpen, Frank; Baumert, Jens; Devuyst, Olivier; Mychaleckyj, Josyf C.; Hastie, Nicholas D.; Curhan, Gary; Hallan, Stein; Navis, Gerjan; Shlipak, Michael G.; Bull, Shelley B.; Paterson, Andrew D.; Rotter, Jerome I.; Beckmann, Jacques S.; Dreisbach, Albert W.; Kao, W. H. L.; Styrkarsdottir, Unnur; Evangelou, Evangelos; Hsu, Yi-Hsiang; Duncan, Emma L.; Ntzani, Evangelia E.; Oei, Ling; Albagha, Omar M. E.; Kemp, John P.; Koller, Daniel L.; Minster, Ryan L.; Vandenput, Liesbeth; Willner, Dana; Xiao, Su-Mei; Yerges-Armstrong, Laura M.; Zheng, Hou-Feng; Alonso, Nerea; Eriksson, Joel; Kammerer, Candace M.; Kaptoge, Stephen K.; Leo, Paul J.; Wilson, Scott G.; Aalto, Ville; Alen, Markku; Aragaki, Aaron K.; Center, Jacqueline R.; Dailiana, Zoe; Duggan, David J.; Garcia-Giralt, Natàlia; Giroux, Sylvie; Hocking, Lynne J.; Husted, Lise Bjerre; Jameson, Karen A.; Khusainova, Rita; Kim, Ghi Su; Koromila, Theodora; Kruk, Marcin; Laaksonen, Marika; LaCroix, Andrea Z.; Lee, Seung Hun; Leung, Ping C.; Lewis, Joshua R.; Masi, Laura; Mencej-Bedrac, Simona; Nguyen, Tuan V.; Nogues, Xavier; Patel, Millan S.; Prezelj, Janez; Scollen, Serena; Siggeirsdottir, Kristin; Svensson, Olle; Trummer, Olivia; van Schoor, Natasja M.; Woo, Jean; Zhu, Kun; Balcells, Susana; Brandi, Maria Luisa; Cheng, Sulin; Christiansen, Claus; Cooper, Cyrus; Frost, Morten; Goltzman, David; González-Macías, Jesús; Karlsson, Magnus; Khusnutdinova, Elza; Koh, Jung-Min; Kollia, Panagoula; Langdahl, Bente Lomholt; Leslie, William D.; Lips, Paul; Ljunggren, Östen; Lorenc, Roman S.; Marc, Janja; Mellström, Dan; Obermayer-Pietsch, Barbara; Olmos, José M.; Pettersson-Kymmer, Ulrika; Reid, David M.; Riancho, José A.; Rousseau, François; Tang, Nelson L. S.; Urreizti, Roser; van Hul, Wim; Zarrabeitia, María T.; Castano-Betancourt, Martha; Herrera, Lizbeth; Ingvarsson, Thorvaldur; Johannsdottir, Hrefna; Kwan, Tony; Li, Rui; Luben, Robert; Medina-Gómez, Carolina; Palsson, Stefan Th; Reppe, Sjur; Sigurdsson, Gunnar; van Meurs, Joyce B. J.; Verlaan, Dominique; Williams, Frances M. K.; Zhou, Yanhua; Gautvik, Kaare M.; Raychaudhuri, Soumya; Cauley, Jane A.; Clark, Graeme R.; Cummings, Steven R.; Danoy, Patrick; Dennison, Elaine M.; Eastell, Richard; Eisman, John A.; Jackson, Rebecca D.; Jones, Graeme; Khaw, Kay-Tee; McCloskey, Eugene; Nandakumar, Kannabiran; Nicholson, Geoffrey C.; Peacock, Munro; Pols, Huibert A. P.; Prince, Richard L.; Reid, Ian R.; Robbins, John; Sambrook, Philip N.; Sham, Pak Chung; Tylavsky, Frances A.; Wareham, Nick J.; Econs, Michael J.; Kung, Annie Wai Chee; Reeve, Jonathan; Streeten, Elizabeth A.; Karasik, David; Richards, J. Brent; Brown, Matthew A.; Ralston, Stuart H.; Ioannidis, John P. A.; Kiel, Douglas P.; McKnight, Amy Jayne; Forsblom, Carol; Isakova, Tamara; McKay, Gareth J.; Williams, Winfred W.; Sadlier, Denise M.; Mäkinen, Ville-Petteri; Swan, Elizabeth J.; Palmer, Cameron; Boright, Andrew P.; Ahlqvist, Emma; Deshmukh, Harshal A.; Keller, Benjamin J.; Huang, Huateng; Ahola, Aila; Fagerholm, Emma; Gordin, Daniel; Harjutsalo, Valma; He, Bing; Heikkilä, Outi; Hietala, Kustaa; Kytö, Janne; Lahermo, Päivi; Lehto, Markku; Österholm, Anne-May; Parkkonen, Maija; Pitkäniemi, Janne; Rosengård-Bärlund, Milla; Saraheimo, Markku; Sarti, Cinzia; Söderlund, Jenny; Soro-Paavonen, Aino; Syreeni, Anna; Thorn, Lena M.; Tikkanen, Heikki; Tolonen, Nina; Tryggvason, Karl; Wadén, Johan; Gill, Geoffrey V.; Prior, Sarah; Guiducci, Candace; Mirel, Daniel B.; Taylor, Andrew; Hosseini, Mohsen; Parving, Hans-Henrik; Rossing, Peter; Tarnow, Lise; Ladenvall, Claes; Alhenc-Gelas, François; Lefebvre, Pierre; Rigalleau, Vincent; Roussel, Ronan; Tregouet, David-Alexandre; Maestroni, Anna; Maestroni, Silvia; Falhammar, Henrik; Gu, Tianwei; Möllsten, Anna; Cimponeriu, Dan; Mihai, Ioana; Mota, Maria; Mota, Eugen; Serafinceanu, Cristian; Stavarachi, Monica; Hanson, Robert L.; Nelson, Robert G.; Kretzler, Matthias; Colhoun, Helen M.; Panduru, Nicolae Mircea; Gu, Harvest F.; Brismar, Kerstin; Zerbini, Gianpaolo; Hadjadj, Samy; Marre, Michel; Lajer, Maria; Waggott, Daryl; Savage, David A.; Bain, Stephen C.; Martin, Finian; Godson, Catherine; Groop, Per-Henrik; Maxwell, Alexander P.; Sengupta, Sebanti; Peloso, Gina M.; Ganna, Andrea; Mora, Samia; Chang, Hsing-Yi; Demirkan, Ayşe; den Hertog, Heleen M.; Donnelly, Louise A.; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Kaakinen, Marika; Kettunen, Johannes; Li, Xiaohui; Montasser, May E.; Petersen, Ann-Kristin; Saxena, Richa; Service, Susan K.; Shah, Sonia; Sidore, Carlo; Surakka, Ida; van den Herik, Evita G.; Volcik, Kelly A.; Asiki, Gershim; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L.; Burnett, Mary S.; Cesana, Giancarlo; Elliott, Paul; Eyjolfsson, Gudmundur Ingi; Goodarzi, Mark O.; Gravito, Martha L.; Hartikainen, Anna-Liisa; Hung, Yi-Jen; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J. P.; Kim, Eric; Komulainen, Pirjo; Lin, Shih-Yi; Müller, Gabrielle; Nieminen, Tuomo V. M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Ruokonen, Aimo; Samani, Nilesh; Seeley, Janet; Silander, Kaisa; Tiret, Laurence; van Pelt, L. Joost; Wainwright, Nicholas; Wijmenga, Cisca; Willemsen, Gonneke; Young, Elizabeth H.; Bennett, Franklyn; Boomsma, Dorret I.; Bovet, Pascal; Chen, Yii-Der Ida; Feranil, Alan B.; Freimer, Nelson B.; Hingorani, Aroon; Hsiung, Chao Agnes; Järvelin, Marjo-Riitta; Kesäniemi, Antero; Koudstaal, Peter J.; Krauss, Ronald M.; Kyvik, Kirsten O.; Martin, Nicholas G.; Meneton, Pierre; Moilanen, Leena; Price, Jackie F.; Sanghera, Dharambir K.; Sheu, Wayne H.-H.; Whitfield, John B.; Wolffenbuttel, Bruce H. R.; Ordovas, Jose M.; Rich, Stephen S.; Abecasis, Gonçalo R.; Abecasis, Gonçalo; Caulfield, Mark; Chasman, Dan; Ehret, Georg; Johnson, Andrew; Johnson, Louise; Larson, Martin; Levy, Daniel; Munroe, Patricia; Newton-Cheh, Christopher; O'Reilly, Paul; Palmas, Walter; Psaty, Bruce; Rice, Kenneth; Smith, Albert; Snider, Harold; Tobin, Martin; Verwoert, Germaine; Rice, Kenneth M.; Tobin, Martin D.; Verwoert, Germaine C.; Pihur, Vasyl; O'Reilly, Paul F.; Launer, Lenore; Aulchenko, Yurii; Heath, Simon; Sõber, Siim; Arora, Pankaj; Zhang, Feng; Lucas, Gavin; Milaneschi, Yuri; Parker, Alex N.; Fava, Cristiano; Fox, Ervin R.; Go, Min Jin; Kao, Wen Hong Linda; Sjögren, Marketa; Vinay, D. G.; Alexander, Myriam; Tabara, Yasuharu; Shaw-Hawkins, Sue; Whincup, Peter H.; Shi, Gang; Tayo, Bamidele; Seielstad, Mark; Sim, Xueling; Nguyen, Khanh-Dung Hoang; Matullo, Giuseppe; Gaunt, Tom R.; Onland-Moret, N. Charlotte; Cooper, Matthew N.; Platou, Carl G. P.; Org, Elin; Hardy, Rebecca; Dahgam, Santosh; Palmen, Jutta; Kuznetsova, Tatiana; Uiterwaal, Cuno S. P. M.; Adeyemo, Adebowale; Ludwig, Barbara; Tomaszewski, Maciej; Tzoulaki, Ioanna; Palmer, Nicholette D.; Chang, Yen-Pei C.; Steinle, Nanette I.; Grobbee, Diederick E.; Kardia, Sharon L.; Morrison, Alanna C.; Najjar, Samer; Hadley, David; Connell, John M.; Day, Ian N. M.; Lawlor, Debbie A.; Beilby, John P.; Lawrence, Robert W.; Ongen, Halit; Li, Yali; Young, J. H.; Bis, Joshua C.; Bolton, Judith A. Hoffman; Chaturvedi, Nish; Islam, Muhammad; Jafar, Tazeen H.; Kulkarni, Smita R.; Grässler, Jürgen; Howard, Philip; Guarrera, Simonetta; Ricceri, Fulvio; Emilsson, Valur; Plump, Andrew; Weder, Alan B.; Sun, Yan V.; Scott, Laura J.; Peltonen, Leena; Vartiainen, Erkki; Brand, Stefan-Martin; Wang, Thomas J.; Burton, Paul R.; Artigas, Maria Soler; Dong, Yanbin; Wang, Xiaoling; Zhu, Haidong; Lohman, Kurt K.; Rudock, Megan E.; Heckbert, Susan R.; Smith, Nicholas L.; Wiggins, Kerri L.; Doumatey, Ayo; Shriner, Daniel; Veldre, Gudrun; Viigimaa, Margus; Kinra, Sanjay; Prabhakaran, Dorairajan; Tripathy, Vikal; Langefeld, Carl D.; Rosengren, Annika; Thelle, Dag S.; Corsi, Anna Maria; Singleton, Andrew; Hilton, Gina; Salako, Tunde; Iwai, Naoharu; Kita, Yoshikuni; Ogihara, Toshio; Ohkubo, Takayoshi; Okamura, Tomonori; Ueshima, Hirotsugu; Umemura, Satoshi; Eyheramendy, Susana; Meitinger, Thomas; Cho, Yoon Shin; Kim, Hyung-Lae; Scott, James; Sehmi, Joban S.; Hedblad, Bo; Nilsson, Peter; Stanèáková, Alena; Raffel, Leslie J.; Yao, Jie; O'Donnell, Chris; Schwartz, Stephen M.; Ikram, M. Arfan; Longstreth, W. T.; Mosley, Thomas H.; Seshadri, Sudha; Shrine, Nick R. G.; Wain, Louise V.; Morken, Mario A.; Laitinen, Jaana; Zitting, Paavo; Cooper, Jackie A.; van Gilst, Wiek H.; Janipalli, Charles S.; Mani, K. Radha; Yajnik, Chittaranjan S.; Mattace-Raso, Francesco U. S.; Lakatta, Edward G.; Orru, Marco; Scuteri, Angelo; Ala-Korpela, Mika; Kangas, Antti J.; Soininen, Pasi; Tukiainen, Taru; Würtz, Peter; Ong, Rick Twee-Hee; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Zelenika, Diana; Zhai, Guangju; Meschia, James F.; Sharma, Pankaj; Terzic, Janos; Kumar, M. J. Kranthi; Denniff, Matthew; Zukowska-Szczechowska, Ewa; Wagenknecht, Lynne E.; Fowkes, F. Gerald R.; Charchar, Fadi J.; Rotimi, Charles; Bots, Michiel L.; Brand, Eva; Talmud, Philippa J.; Nyberg, Fredrik; Laan, Maris; van der Schouw, Yvonne T.; Casas, Juan P.; Vineis, Paolo; Ganesh, Santhi K.; Wong, Tien Y.; Tai, E. Shyong; Rao, Dabeeru C.; Morris, Richard W.; Dominiczak, Anna F.; Marmot, Michael G.; Miki, Tetsuro; Chandak, Giriraj R.; Zhu, Xiaofeng; Gyllensten, Ulf B.; Elosua, Roberto; Soranzo, Nicole; Sijbrands, Eric J. G.; Uda, Manuela; Vasan, Ramachandran S.; Larson, Martin G.; Anderson, Carl A.; Gordon, Scott D.; Guo, Qun; Henders, Anjali K.; Lambert, Ann; Lee, Sang Hong; Kraft, Peter; Kennedy, Stephen H.; Macgregor, Stuart; Missmer, Stacey A.; Painter, Jodie N.; Roseman, Fenella; Treloar, Susan A.; Wallace, Leanne; Alizadeh, Behrooz Z.; de Boer, Rudolf A.; Boezen, H. Marike; van der Klauw, Melanie M.; Ormel, Johan; Postma, Dirkje S.; Rosmalen, Judith G. M.; Slaets, Joris P.; Lagou, Vasiliki; Welch, Ryan P.; Wheeler, Eleanor; Rehnberg, Emil; Lecoeur, Cecile; Johnson, Paul C. D.; Hottenga, Jouke-Jan; Salo, Perttu; Timpson, Nicholas J.; Bielak, Lawrence F.; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Esko, Tönu; Chen, Han; Robertson, Neil; Rybin, Denis; Kang, Hyun Min; Song, Kijoung; An, Ping; Marullo, Letizia; Jansen, Hanneke; Edkins, Sarah; Varga, Tibor V.; Oksa, Heikki; Antonella, Mulas; Kong, Augustine; Herder, Christian; Antti, Jula; Miljkovic, Iva; Atalay, Mustafa; Kiess, Wieland; Smit, Johannes H.; Campbell, Susan; Fowkes, Gerard R.; Rathmann, Wolfgang; Maerz, Winfried; Province, Michael A.; Watanabe, Richard M.; Toenjes, Anke; Peyser, Patricia A.; Körner, Antje; Dupuis, Josée; Cucca, Francesco; Balkau, Beverley; Bouatia-Naji, Nabila; Ahmadi, Kourosh R.; Ainali, Chrysanthi; Bataille, Veronique; Bell, Jordana T.; Buil, Alfonso; Dermitzakis, Emmanouil T.; Dimas, Antigone S.; Durbin, Richard; Glass, Daniel; Hassanali, Neelam; Ingle, Catherine; Knowles, David; Krestyaninova, Maria; Lowe, Christopher E.; Meduri, Eshwar; di Meglio, Paola; Montgomery, Stephen B.; Nestle, Frank O.; Nica, Alexandra C.; Nisbet, James; O'Rahilly, Stephen; Parts, Leopold; Potter, Simon; Sekowska, Magdalena; Shin, So-Youn; Small, Kerrin S.; Surdulescu, Gabriela; Travers, Mary E.; Tsaprouni, Loukia; Tsoka, Sophia; Wilk, Alicja; Matise, Tara; Buyske, Steve; Higashio, Julia; Williams, Rasheeda; Nato, Andrew; Ambite, Jose Luis; Manolio, Teri; Hindorff, Lucia; Heiss, Gerardo; Taylor, Kira; Avery, Christy; Graff, Misa; Lin, Danyu; Quibrera, Miguel; Cochran, Barbara; Kao, Linda; Umans, Jason; Cole, Shelley; MacCluer, Jean; Person, Sharina; Pankow, James; Gross, Myron; Fornage, Myriam; Durda, Peter; Jenny, Nancy; Patsy, Bruce; Arnold, Alice; Buzkova, Petra; Crawford, Dana; Haines, Jonathan; Murdock, Deborah; Glenn, Kim; Brown-Gentry, Kristin; Thornton-Wells, Tricia; Dumitrescu, Logan; Jeff, Janina; Bush, William S.; Mitchell, Sabrina L.; Goodloe, Robert; Wilson, Sarah; Boston, Jonathan; Malinowski, Jennifer; Restrepo, Nicole; Oetjens, Matthew; Fowke, Jay; Zheng, Wei; Spencer, Kylee; Ritchie, Marylyn; Pendergrass, Sarah; Le Marchand, Loïc; Wilkens, Lynne; Park, Lani; Tiirikainen, Maarit; Kolonel, Laurence; Lim, Unhee; Cheng, Iona; Wang, Hansong; Shohet, Ralph; Haiman, Christopher; Stram, Daniel; Henderson, Brian; Monroe, Kristine; Schumacher, Fredrick; Anderson, Garnet; Carlson, Chris; Prentice, Ross; LaCroix, Andrea; Wu, Chunyuan; Carty, Cara; Gong, Jian; Rosse, Stephanie; Young, Alicia; Haessler, Jeff; Kocarnik, Jonathan; Lin, Yi; Jackson, Rebecca; Duggan, David; Kuller, Lew; He, Chunyan; Sulem, Patrick; Barbalic, Maja; Broer, Linda; Byrne, Enda M.; Gudbjartsson, Daniel F.; McArdle, Patick F.; Porcu, Eleonora; van Wingerden, Sophie; Zhuang, Wei V.; Lauc, Lovorka Barac; Broekmans, Frank J.; Burri, Andrea; Chanock, Stephen J.; Chen, Constance; Corre, Tanguy; Coviello, Andrea D.; D'Adamo, Pio; Davies, Gail; Deary, Ian J.; Dedoussis, George V. Z.; Deloukas, Panagiotis; Ebrahim, Shah; Fauser, Bart C. J. M.; Ferreli, Liana; Folsom, Aaron R.; Hall, Per; Hankinson, Susan E.; Hass, Merli; Heath, Andrew C.; Janssens, A. Cecile J. W.; Keyzer, Jules; Lahti, Jari; Lai, Sandra; Laisk, Triin; Laven, Joop S. E.; Liu, Jianjun; Lopez, Lorna M.; Louwers, Yvonne V.; Marongiu, Mara; Klaric, Irena Martinovic; Masciullo, Corrado; Medland, Sarah E.; Melzer, David; Newman, Anne B.; Paré, Guillaume; Peeters, Petra H. M.; Plump, Andrew S.; Pop, Victor J. M.; Räikkönen, Katri; Salumets, Andres; Smith, Jennifer A.; Stacey, Simon N.; Starr, John M.; Stathopoulou, Maria G.; Tenesa, Albert; Tryggvadottir, Laufey; Tsui, Kim; van Dam, Rob M.; van Gils, Carla H.; van Nierop, Peter; Vink, Jacqueline M.; Voorhuis, Marlies; Waeber, Gérard; Wallaschofski, Henri; Widen, Elisabeth; Wijnands-van Gent, Colette J. M.; Zgaga, Lina; Zygmunt, Marek; Arnold, Alice M.; Buring, Julie E.; Crisponi, Laura; Demerath, Ellen W.; Murray, Anna; Visser, Jenny A.; Lunetta, Kathryn L.; Elks, Cathy E.; Cousminer, Diana L.; Feenstra, Bjarke; Lin, Peng; McArdle, Patrick F.; van Wingerden, Sophie W.; Smith, Erin N.; Ulivi, Shelia; Warrington, Nicole M.; Alavere, Helen; Barroso, Ines; Berenson, Gerald S.; Blackburn, Hannah; Busonero, Fabio; Chen, Wei; Couper, David; Easton, Douglas F.; Eriksson, Johan; Foroud, Tatiana; Geller, Frank; Hernandez, Dena G.; Kilpeläinen, Tuomas O.; Li, Shengxu; Melbye, Mads; Murray, Jeffrey C.; Murray, Sarah S.; Ness, Andrew R.; Northstone, Kate; Pennell, Craig E.; Pharoah, Paul; Rafnar, Thorunn; Rice, John P.; Ring, Susan M.; Schork, Nicholas J.; Segrè, Ayellet V.; Sovio, Ulla; Srinivasan, Sathanur R.; Tammesoo, Mar-Liis; Tyrer, Jonathon; van Meurs, Joyve B. J.; Weedon, Michael N.; Young, Lauren; Zhuang, Wei Vivian; Bierut, Laura J.; Boyd, Heather A.

    2015-01-01

    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide

  17. Genetic and Environmental Links between Natural Language Use and Cognitive Ability in Toddlers

    Science.gov (United States)

    Canfield, Caitlin F.; Edelson, Lisa R.; Saudino, Kimberly J.

    2017-01-01

    Although the phenotypic correlation between language and nonverbal cognitive ability is well-documented, studies examining the etiology of the covariance between these abilities are scant, particularly in very young children. The goal of this study was to address this gap in the literature by examining the genetic and environmental links between…

  18. New genetic loci link adipose and insulin biology to body fat distribution

    DEFF Research Database (Denmark)

    Shungin, Dmitry; Winkler, Thomas W; Croteau-Chonka, Damien C.

    2015-01-01

    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome...

  19. The link between infertility and poverty: evidence from Bangladesh.

    Science.gov (United States)

    Nahar, Papreen

    2012-03-01

    The link between high fertility and poverty is well established. However, this paper shows how infertility may also generate poverty among childless families in Bangladesh. An ethnographic study was conducted, involving various qualitative research methods that revealed economic consequences to be one of the crucial sequelae of childlessness in Bangladesh. This paper details how the poverty/fertility relationship is dependent on social and institutional characteristics, including patriarchal values, education, urban-rural location and health services. Empirical data show that childlessness generates poverty in various ways, including the deprivation of children's earnings, decline in women's mobility, demoralisation of men to earn an income, marriage devaluation by the husband, disbursements for treatment and denial of microcredit (very small loans to those in poverty, which support them to become self-employed to generate income). The current study shows that the infertility/poverty relationship is mostly contingent upon class and gender. It is therefore the rural poor childless women who are most badly affected economically in Bangladesh rather than the urban middle class childless women. In other words, this study reveal that along with gender, class plays a dominant role in terms of the economic consequences of childlessness in Bangladesh. It sheds light on a different and unusual aspect of poverty and aims to contribute to the gender discussion of livelihood and poverty.

  20. Narcissism predicts impulsive buying: phenotypic and genetic evidence

    Science.gov (United States)

    Cai, Huajian; Shi, Yuanyuan; Fang, Xiang; Luo, Yu L. L.

    2015-01-01

    Impulsive buying makes billions of dollars for retail businesses every year, particularly in an era of thriving e-commerce. Narcissism, characterized by impulsivity and materialism, may serve as a potential antecedent to impulsive buying. To test this hypothesis, two studies examined the relationship between narcissism and impulsive buying. In Study 1, we surveyed an online sample and found that while adaptive narcissism was not correlated with impulsive buying, maladaptive narcissism was significantly predictive of the impulsive buying tendency. By investigating 304 twin pairs, Study 2 showed that global narcissism and its two components, adaptive and maladaptive narcissism, as well as the impulsive buying tendency were heritable. The study found, moreover, that the connections between global narcissism and impulsive buying, and between maladaptive narcissism and impulsive buying were genetically based. These findings not only establish a link between narcissism and impulsive buying but also help to identify the origins of the link. The present studies deepen our understanding of narcissism, impulsive buying, and their interrelationship. PMID:26217251

  1. Narcissism predicts impulsive buying: phenotypic and genetic evidence.

    Science.gov (United States)

    Cai, Huajian; Shi, Yuanyuan; Fang, Xiang; Luo, Yu L L

    2015-01-01

    Impulsive buying makes billions of dollars for retail businesses every year, particularly in an era of thriving e-commerce. Narcissism, characterized by impulsivity and materialism, may serve as a potential antecedent to impulsive buying. To test this hypothesis, two studies examined the relationship between narcissism and impulsive buying. In Study 1, we surveyed an online sample and found that while adaptive narcissism was not correlated with impulsive buying, maladaptive narcissism was significantly predictive of the impulsive buying tendency. By investigating 304 twin pairs, Study 2 showed that global narcissism and its two components, adaptive and maladaptive narcissism, as well as the impulsive buying tendency were heritable. The study found, moreover, that the connections between global narcissism and impulsive buying, and between maladaptive narcissism and impulsive buying were genetically based. These findings not only establish a link between narcissism and impulsive buying but also help to identify the origins of the link. The present studies deepen our understanding of narcissism, impulsive buying, and their interrelationship.

  2. Narcissism predicts impulsive buying: phenotypic and genetic evidence

    Directory of Open Access Journals (Sweden)

    Huajian eCai

    2015-07-01

    Full Text Available Impulsive buying makes billions of dollars for retail businesses every year, particularly in an era of thriving e-commerce. Narcissism, characterized by impulsivity and materialism, may serve as a potential antecedent to impulsive buying. To test this hypothesis, two studies examined the relationship between narcissism and impulsive buying. In study 1, we surveyed narcissism and the impulsive buying tendency among an online sample and found that while adaptive narcissism was not correlated with impulsive buying, maladaptive narcissism was significantly predictive of the impulsive buying tendency. By investigating narcissism and the impulsive buying tendency in 304 twin pairs, study 2 showed that global narcissism and its two components, adaptive and maladaptive narcissism, as well as the impulsive buying tendency were heritable. The study found, moreover, that the connections between global narcissism and impulsive buying, and between maladaptive narcissism and impulsive buying were genetically based. These findings not only establish a link between narcissism and impulsive buying but also help to identify the origins of the link. The present studies deepen our understanding of narcissism, impulsive buying, and their interrelationship.

  3. Gathering Empirical Evidence Concerning Links between Computer Aided Design (CAD) and Creativity

    Science.gov (United States)

    Musta'amal, Aede Hatib; Norman, Eddie; Hodgson, Tony

    2009-01-01

    Discussion is often reported concerning potential links between computer-aided designing and creativity, but there is a lack of systematic enquiry to gather empirical evidence concerning such links. This paper reports an indication of findings from other research studies carried out in contexts beyond general education that have sought evidence…

  4. Retinoblastoma and the Genetic Theory of Cancer: An Old Paradigm Trying to Survive to the Evidence

    International Nuclear Information System (INIS)

    Mastrangelo, D.; Lore, C.; Hadjistilianou, T.; De Francesco, S.

    2009-01-01

    Retinoblastoma (Rb) is considered to represent the prototype of cancer linked to the sequential loss or inactivation of both alleles of a so-called “tumor suppressor gene”, the Rb1 gene. The pathogenetic mechanism behind this tumor was first hypothesized by Knudson in 1971 and further confirmed by others who identified the Rb1 gene whose loss or inactivation was claimed to be responsible for the disease. However, after about four decades of continuous research in the field of molecular biology, the evidence behind the role of the Rb1 gene in Rb appears to be seriously flawed in the light of epidemiological, biological, and clinical evidences. This editorial summarizes the inconsistencies on this subject. Nevertheless, the molecular biology establishment still adheres to the biased view of the genetic origin of Rb and other cancers, and hardly any alternative explanations are taken into account.

  5. Preimplantation genetic diagnosis of X-linked diseases examined by indirect linkage analysis.

    Science.gov (United States)

    Borgulova, I; Putzova, M; Soldatova, I; Krautova, L; Pecnova, L; Mika, J; Kren, R; Potuznikova, P; Stejskal, D

    2015-01-01

    Many centers of assisted reproduction in the Czech Republic offer preimplantation genetic diagnosis with fluorescent in situ hybridization (FISH) to couples requiring preimplantation genetic diagnosis (PGD) of X-linked diseases. However, this process results in discarding all male embryos and is not able to distinguish a carrier or healthy female embryo in X-linked recessive disorders. The main aim of this study was to summarize a six-year period of PGD of X-linked monogenic diseases using indirect linkage analysis. We wanted to accentuate the advantage indirect analysis of PGD using multiple displacement amplification (MDA) followed by short tandem repeat (STR) analysis. We present forty-six PGD cycles, including pre-case haplotyping (PGH) panel, for fifteen X-linked diseases. Embryo transfer was made thirty-eight times and gravidity was confirmed in thirteen female probands with a success rate of pregnancy calculated at 42 %. PGD procedure using MDA amplification followed by STR analysis provides help in identifying genetic defects within embryos prior to implantation. The reliability of the method was also supported by high pregnancy rate compared to other publications, which commonly achieved a 30-35 % success rate (Tab. 2, Fig. 1, Ref. 33).

  6. Consequences of population topology for studying gene flow using link-based landscape genetic methods.

    Science.gov (United States)

    van Strien, Maarten J

    2017-07-01

    Many landscape genetic studies aim to determine the effect of landscape on gene flow between populations. These studies frequently employ link-based methods that relate pairwise measures of historical gene flow to measures of the landscape and the geographical distance between populations. However, apart from landscape and distance, there is a third important factor that can influence historical gene flow, that is, population topology (i.e., the arrangement of populations throughout a landscape). As the population topology is determined in part by the landscape configuration, I argue that it should play a more prominent role in landscape genetics. Making use of existing literature and theoretical examples, I discuss how population topology can influence results in landscape genetic studies and how it can be taken into account to improve the accuracy of these results. In support of my arguments, I have performed a literature review of landscape genetic studies published during the first half of 2015 as well as several computer simulations of gene flow between populations. First, I argue why one should carefully consider which population pairs should be included in link-based analyses. Second, I discuss several ways in which the population topology can be incorporated in response and explanatory variables. Third, I outline why it is important to sample populations in such a way that a good representation of the population topology is obtained. Fourth, I discuss how statistical testing for link-based approaches could be influenced by the population topology. I conclude the article with six recommendations geared toward better incorporating population topology in link-based landscape genetic studies.

  7. Genetic evidence for hybrid trait speciation in heliconius butterflies.

    Directory of Open Access Journals (Sweden)

    Camilo Salazar

    2010-04-01

    Full Text Available Homoploid hybrid speciation is the formation of a new hybrid species without change in chromosome number. So far, there has been a lack of direct molecular evidence for hybridization generating novel traits directly involved in animal speciation. Heliconius butterflies exhibit bright aposematic color patterns that also act as cues in assortative mating. Heliconius heurippa has been proposed as a hybrid species, and its color pattern can be recreated by introgression of the H. m. melpomene red band into the genetic background of the yellow banded H. cydno cordula. This hybrid color pattern is also involved in mate choice and leads to reproductive isolation between H. heurippa and its close relatives. Here, we provide molecular evidence for adaptive introgression by sequencing genes across the Heliconius red band locus and comparing them to unlinked wing patterning genes in H. melpomene, H. cydno, and H. heurippa. 670 SNPs distributed among 29 unlinked coding genes (25,847bp showed H. heurippa was related to H. c. cordula or the three species were intermixed. In contrast, among 344 SNPs distributed among 13 genes in the red band region (18,629bp, most showed H. heurippa related with H. c. cordula, but a block of around 6,5kb located in the 3' of a putative kinesin gene grouped H. heurippa with H. m. melpomene, supporting the hybrid introgression hypothesis. Genealogical reconstruction showed that this introgression occurred after divergence of the parental species, perhaps around 0.43Mya. Expression of the kinesin gene is spatially restricted to the distal region of the forewing, suggesting a mechanism for pattern regulation. This gene therefore constitutes the first molecular evidence for adaptive introgression during hybrid speciation and is the first clear candidate for a Heliconius wing patterning locus.

  8. Highly specific detection of genetic modification events using an enzyme-linked probe hybridization chip.

    Science.gov (United States)

    Zhang, M Z; Zhang, X F; Chen, X M; Chen, X; Wu, S; Xu, L L

    2015-08-10

    The enzyme-linked probe hybridization chip utilizes a method based on ligase-hybridizing probe chip technology, with the principle of using thio-primers for protection against enzyme digestion, and using lambda DNA exonuclease to cut multiple PCR products obtained from the sample being tested into single-strand chains for hybridization. The 5'-end amino-labeled probe was fixed onto the aldehyde chip, and hybridized with the single-stranded PCR product, followed by addition of a fluorescent-modified probe that was then enzymatically linked with the adjacent, substrate-bound probe in order to achieve highly specific, parallel, and high-throughput detection. Specificity and sensitivity testing demonstrated that enzyme-linked probe hybridization technology could be applied to the specific detection of eight genetic modification events at the same time, with a sensitivity reaching 0.1% and the achievement of accurate, efficient, and stable results.

  9. Evidence for genetic association of RORB with bipolar disorder

    Directory of Open Access Journals (Sweden)

    Mick Eric

    2009-11-01

    Full Text Available Abstract Background Bipolar disorder, particularly in children, is characterized by rapid cycling and switching, making circadian clock genes plausible molecular underpinnings for bipolar disorder. We previously reported work establishing mice lacking the clock gene D-box binding protein (DBP as a stress-reactive genetic animal model of bipolar disorder. Microarray studies revealed that expression of two closely related clock genes, RAR-related orphan receptors alpha (RORA and beta (RORB, was altered in these mice. These retinoid-related receptors are involved in a number of pathways including neurogenesis, stress response, and modulation of circadian rhythms. Here we report association studies between bipolar disorder and single-nucleotide polymorphisms (SNPs in RORA and RORB. Methods We genotyped 355 RORA and RORB SNPs in a pediatric cohort consisting of a family-based sample of 153 trios and an independent, non-overlapping case-control sample of 152 cases and 140 controls. Bipolar disorder in children and adolescents is characterized by increased stress reactivity and frequent episodes of shorter duration; thus our cohort provides a potentially enriched sample for identifying genes involved in cycling and switching. Results We report that four intronic RORB SNPs showed positive associations with the pediatric bipolar phenotype that survived Bonferroni correction for multiple comparisons in the case-control sample. Three RORB haplotype blocks implicating an additional 11 SNPs were also associated with the disease in the case-control sample. However, these significant associations were not replicated in the sample of trios. There was no evidence for association between pediatric bipolar disorder and any RORA SNPs or haplotype blocks after multiple-test correction. In addition, we found no strong evidence for association between the age-at-onset of bipolar disorder with any RORA or RORB SNPs. Conclusion Our findings suggest that clock genes in

  10. Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

    Directory of Open Access Journals (Sweden)

    Salvatore De Rosa

    2018-01-01

    Full Text Available Type 2 diabetes mellitus (DM is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD, which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose

  11. The genetics of music accomplishment: evidence for gene-environment correlation and interaction.

    Science.gov (United States)

    Hambrick, David Z; Tucker-Drob, Elliot M

    2015-02-01

    Theories of skilled performance that emphasize training history, such as K. Anders Ericsson and colleagues' deliberate-practice theory, have received a great deal of recent attention in both the scientific literature and the popular press. Twin studies, however, have demonstrated evidence for moderate-to-strong genetic influences on skilled performance. Focusing on musical accomplishment in a sample of over 800 pairs of twins, we found evidence for gene-environment correlation, in the form of a genetic effect on music practice. However, only about one quarter of the genetic effect on music accomplishment was explained by this genetic effect on music practice, suggesting that genetically influenced factors other than practice contribute to individual differences in music accomplishment. We also found evidence for gene-environment interaction, such that genetic effects on music accomplishment were most pronounced among those engaging in music practice, suggesting that genetic potentials for skilled performance are most fully expressed and fostered by practice.

  12. Cumulative t-link threshold models for the genetic analysis of calving ease scores

    Directory of Open Access Journals (Sweden)

    Tempelman Robert J

    2003-09-01

    Full Text Available Abstract In this study, a hierarchical threshold mixed model based on a cumulative t-link specification for the analysis of ordinal data or more, specifically, calving ease scores, was developed. The validation of this model and the Markov chain Monte Carlo (MCMC algorithm was carried out on simulated data from normally and t4 (i.e. a t-distribution with four degrees of freedom distributed populations using the deviance information criterion (DIC and a pseudo Bayes factor (PBF measure to validate recently proposed model choice criteria. The simulation study indicated that although inference on the degrees of freedom parameter is possible, MCMC mixing was problematic. Nevertheless, the DIC and PBF were validated to be satisfactory measures of model fit to data. A sire and maternal grandsire cumulative t-link model was applied to a calving ease dataset from 8847 Italian Piemontese first parity dams. The cumulative t-link model was shown to lead to posterior means of direct and maternal heritabilities (0.40 ± 0.06, 0.11 ± 0.04 and a direct maternal genetic correlation (-0.58 ± 0.15 that were not different from the corresponding posterior means of the heritabilities (0.42 ± 0.07, 0.14 ± 0.04 and the genetic correlation (-0.55 ± 0.14 inferred under the conventional cumulative probit link threshold model. Furthermore, the correlation (> 0.99 between posterior means of sire progeny merit from the two models suggested no meaningful rerankings. Nevertheless, the cumulative t-link model was decisively chosen as the better fitting model for this calving ease data using DIC and PBF.

  13. First evidence of intraclonal genetic exchange in trypanosomatids using two Leishmania infantum fluorescent transgenic clones.

    Directory of Open Access Journals (Sweden)

    Estefanía Calvo-Álvarez

    2014-09-01

    Full Text Available The mode of reproduction in Leishmania spp has been argued to be essentially clonal. However, recent data (genetic analysis of populations and co-infections in sand flies have proposed the existence of a non-obligate sexual cycle in the extracellular stage of the parasite within the sand fly vector. In this article we propose the existence of intraclonal genetic exchange in the natural vector of Leishmania infantum.We have developed transgenic L. infantum lines expressing drug resistance markers linked to green and red fluorescent reporters. We hypothesized whether those cells with identical genotype can recognize each other and mate. Both types of markers were successfully exchanged within the sand fly midgut of the natural vector Phlebotomus perniciosus when individuals from these species were fed with a mixture of parental clones. Using the yellow phenotype and drug resistance markers, we provide evidence for genetic exchange in L. infantum. The hybrid progeny appeared to be triploid based on DNA content analysis. The hybrid clone analyzed was stable throughout the complete parasite life cycle. The progress of infections by the hybrid clone in BALB/c mice caused a reduction in parasite loads in both spleen and liver, and provided weight values similar to those obtained with uninfected mice. Spleen arginase activity was also significantly reduced relative to parental strains.A L. infantum hybrid lineage was obtained from intraclonal genetic exchange within the midgut of the natural vector, suggesting the ability of this parasite to recognize the same genotype and mate. The yellow hybrid progeny is stable throughout the whole parasite life cycle but with a slower virulence, which correlates well with the lower arginase activity detected both in vitro and in vivo infections.

  14. The Impact of Educational Mismatch on Firm Productivity: Evidence from Linked Panel Data

    Science.gov (United States)

    Kampelmann, Stephan; Rycx, Francois

    2012-01-01

    We provide first evidence regarding the direct impact of educational mismatch on firm productivity. To do so, we rely on representative linked employer-employee panel data for Belgium covering the period 1999-2006. Controlling for simultaneity issues, time-invariant unobserved workplace characteristics, cohort effects and dynamics in the…

  15. [Hypothetical link between endometriosis and xenobiotics-associated genetically modified food].

    Science.gov (United States)

    Aris, A; Paris, K

    2010-12-01

    Endometriosis is an oestrogen-dependent inflammatory disease affecting 10 % of reproductive-aged women. Often accompanied by chronic pelvic pain and infertility, endometriosis rigorously interferes with women's quality of life. Although the pathophysiology of endometriosis remains unclear, a growing body of evidence points to the implication of environmental toxicants. Over the last decade, an increase in the incidence of endometriosis has been reported and coincides with the introduction of genetically modified foods in our diet. Even though assessments of genetically modified food risk have not indicated any hazard on human health, xenobiotics-associated genetically modified food, such as pesticides residues and xenoproteins, could be harmful in the long-term. The "low-dose hypothesis", accumulation and biotransformation of pesticides-associated genetically modified food and the multiplied toxicity of pesticides-formulation adjuvants support this hypothesis. This review summarizes toxic effects (in vitro and on animal models) of some xenobiotics-associated genetically modified food, such as glyphosate and Cry1Ab protein, and extrapolates on their potential role in the pathophysiology of endometriosis. Their roles as immune toxicants, pro-oxidants, endocrine disruptors and epigenetic modulators are discussed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  16. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability.

    Science.gov (United States)

    Colotta, Francesco; Allavena, Paola; Sica, Antonio; Garlanda, Cecilia; Mantovani, Alberto

    2009-07-01

    Inflammatory conditions in selected organs increase the risk of cancer. An inflammatory component is present also in the microenvironment of tumors that are not epidemiologically related to inflammation. Recent studies have begun to unravel molecular pathways linking inflammation and cancer. In the tumor microenvironment, smoldering inflammation contributes to proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, reduced response to hormones and chemotherapeutic agents. Recent data suggest that an additional mechanism involved in cancer-related inflammation (CRI) is induction of genetic instability by inflammatory mediators, leading to accumulation of random genetic alterations in cancer cells. In a seminal contribution, Hanahan and Weinberg [(2000) Cell, 100, 57-70] identified the six hallmarks of cancer. We surmise that CRI represents the seventh hallmark.

  17. Linking movement behavior and fine-scale genetic structure to model landscape connectivity for bobcats (Lynx rufus)

    Science.gov (United States)

    Dawn M. Reding; Samuel A. Cushman; Todd E. Gosselink; William R. Clark

    2013-01-01

    Spatial heterogeneity can constrain the movement of individuals and consequently genes across a landscape, influencing demographic and genetic processes. In this study, we linked information on landscape composition, movement behavior, and genetic differentiation to gain a mechanistic understanding of how spatial heterogeneity may influence movement and gene flow of...

  18. Evidence that pairing with genetically similar mates is maladaptive in a monogamous bird

    Science.gov (United States)

    Mulard, Hervé; Danchin, E.; Talbot, S.L.; Ramey, A.M.; Hatch, Shyla A.; White, J.F.; Helfenstein, F.; Wagner, R.H.

    2009-01-01

    Background. Evidence of multiple genetic criteria of mate choice is accumulating in numerous taxa. In many species, females have been shown to pair with genetically dissimilar mates or with extra-pair partners that are more genetically compatible than their social mates, thereby increasing their offsprings' heterozygosity which often correlates with offspring fitness. While most studies have focused on genetically promiscuous species, few studies have addressed genetically monogamous species, in which mate choice tends to be mutual. Results. Here, we used microsatellite markers to assess individual global heterozygosity and genetic similarity of pairs in a socially and genetically monogamous seabird, the black-legged kittiwake Rissa tridactyla. We found that pairs were more genetically dissimilar than expected by chance. We also identified fitness costs of breeding with genetically similar partners: (i) genetic similarity of pairs was negatively correlated with the number of chicks hatched, and (ii) offspring heterozygosity was positively correlated with growth rate and survival. Conclusion. These findings provide evidence that breeders in a genetically monogamous species may avoid the fitness costs of reproducing with a genetically similar mate. In such species that lack the opportunity to obtain extra-pair fertilizations, mate choice may therefore be under high selective pressure. ?? 2009 Mulard et al; licensee BioMed Central Ltd.

  19. Evidence that pairing with genetically similar mates is maladaptive in a monogamous bird

    Directory of Open Access Journals (Sweden)

    Ramey Andrew M

    2009-06-01

    Full Text Available Abstract Background Evidence of multiple genetic criteria of mate choice is accumulating in numerous taxa. In many species, females have been shown to pair with genetically dissimilar mates or with extra-pair partners that are more genetically compatible than their social mates, thereby increasing their offsprings' heterozygosity which often correlates with offspring fitness. While most studies have focused on genetically promiscuous species, few studies have addressed genetically monogamous species, in which mate choice tends to be mutual. Results Here, we used microsatellite markers to assess individual global heterozygosity and genetic similarity of pairs in a socially and genetically monogamous seabird, the black-legged kittiwake Rissa tridactyla. We found that pairs were more genetically dissimilar than expected by chance. We also identified fitness costs of breeding with genetically similar partners: (i genetic similarity of pairs was negatively correlated with the number of chicks hatched, and (ii offspring heterozygosity was positively correlated with growth rate and survival. Conclusion These findings provide evidence that breeders in a genetically monogamous species may avoid the fitness costs of reproducing with a genetically similar mate. In such species that lack the opportunity to obtain extra-pair fertilizations, mate choice may therefore be under high selective pressure.

  20. Genetic Testing Confirmed the Early Diagnosis of X-Linked Hypophosphatemic Rickets in a 7-Month-Old Infant

    Directory of Open Access Journals (Sweden)

    Kok Siong Poon BSc

    2015-08-01

    Full Text Available Loss-of-function mutations in the p hosphate regulating gene with h omologies to e ndopeptidases on the X -chromosome ( PHEX have been causally associated with X-linked hypophosphatemic rickets (XLHR. The early diagnosis of XLHR in infants is challenging when it is based solely on clinical features and biochemical findings. We report a 7-month-old boy with a family history of hypophosphatemic rickets., who demonstrated early clinical evidence of rickets, although serial biochemical findings could not definitively confirm rickets. A sequencing assay targeting the PHEX gene was first performed on the mother’s DNA to screen for mutations in the 5′UTR, 22 coding exons, and the exon-intron junctions. Targeted mutation analysis and mRNA studies were subsequently performed on the boys’ DNA to investigate the pathogenicity of the identified mutation. Genetic screening of the PHEX gene revealed a novel mutation, c.1080-2A>C, at the splice acceptor site in intron 9. The detection of an aberrant mRNA transcript with skipped (loss of exon 10 establishes its pathogenicity and confirms the diagnosis of XLHR in this infant. Genetic testing of the PHEX gene resulted in early diagnosis of XLHR, thus enabling initiation of therapy and prevention of progressive rachitic changes in the infant.

  1. Linking social and pathogen transmission networks using microbial genetics in giraffe (Giraffa camelopardalis).

    Science.gov (United States)

    VanderWaal, Kimberly L; Atwill, Edward R; Isbell, Lynne A; McCowan, Brenda

    2014-03-01

    Although network analysis has drawn considerable attention as a promising tool for disease ecology, empirical research has been hindered by limitations in detecting the occurrence of pathogen transmission (who transmitted to whom) within social networks. Using a novel approach, we utilize the genetics of a diverse microbe, Escherichia coli, to infer where direct or indirect transmission has occurred and use these data to construct transmission networks for a wild giraffe population (Giraffe camelopardalis). Individuals were considered to be a part of the same transmission chain and were interlinked in the transmission network if they shared genetic subtypes of E. coli. By using microbial genetics to quantify who transmits to whom independently from the behavioural data on who is in contact with whom, we were able to directly investigate how the structure of contact networks influences the structure of the transmission network. To distinguish between the effects of social and environmental contact on transmission dynamics, the transmission network was compared with two separate contact networks defined from the behavioural data: a social network based on association patterns, and a spatial network based on patterns of home-range overlap among individuals. We found that links in the transmission network were more likely to occur between individuals that were strongly linked in the social network. Furthermore, individuals that had more numerous connections or that occupied 'bottleneck' positions in the social network tended to occupy similar positions in the transmission network. No similar correlations were observed between the spatial and transmission networks. This indicates that an individual's social network position is predictive of transmission network position, which has implications for identifying individuals that function as super-spreaders or transmission bottlenecks in the population. These results emphasize the importance of association patterns in

  2. Genetic link between family socioeconomic status and children's educational achievement estimated from genome-wide SNPs.

    Science.gov (United States)

    Krapohl, E; Plomin, R

    2016-03-01

    One of the best predictors of children's educational achievement is their family's socioeconomic status (SES), but the degree to which this association is genetically mediated remains unclear. For 3000 UK-representative unrelated children we found that genome-wide single-nucleotide polymorphisms could explain a third of the variance of scores on an age-16 UK national examination of educational achievement and half of the correlation between their scores and family SES. Moreover, genome-wide polygenic scores based on a previously published genome-wide association meta-analysis of total number of years in education accounted for ~3.0% variance in educational achievement and ~2.5% in family SES. This study provides the first molecular evidence for substantial genetic influence on differences in children's educational achievement and its association with family SES.

  3. Genetic Variance in Homophobia: Evidence from Self- and Peer Reports.

    Science.gov (United States)

    Zapko-Willmes, Alexandra; Kandler, Christian

    2018-01-01

    The present twin study combined self- and peer assessments of twins' general homophobia targeting gay men in order to replicate previous behavior genetic findings across different rater perspectives and to disentangle self-rater-specific variance from common variance in self- and peer-reported homophobia (i.e., rater-consistent variance). We hypothesized rater-consistent variance in homophobia to be attributable to genetic and nonshared environmental effects, and self-rater-specific variance to be partially accounted for by genetic influences. A sample of 869 twins and 1329 peer raters completed a seven item scale containing cognitive, affective, and discriminatory homophobic tendencies. After correction for age and sex differences, we found most of the genetic contributions (62%) and significant nonshared environmental contributions (16%) to individual differences in self-reports on homophobia to be also reflected in peer-reported homophobia. A significant genetic component, however, was self-report-specific (38%), suggesting that self-assessments alone produce inflated heritability estimates to some degree. Different explanations are discussed.

  4. Assessing the evidence for shared genetic risks across psychiatric disorders and traits.

    Science.gov (United States)

    Martin, Joanna; Taylor, Mark J; Lichtenstein, Paul

    2017-12-04

    Genetic influences play a significant role in risk for psychiatric disorders, prompting numerous endeavors to further understand their underlying genetic architecture. In this paper, we summarize and review evidence from traditional twin studies and more recent genome-wide molecular genetic analyses regarding two important issues that have proven particularly informative for psychiatric genetic research. First, emerging results are beginning to suggest that genetic risk factors for some (but not all) clinically diagnosed psychiatric disorders or extreme manifestations of psychiatric traits in the population share genetic risks with quantitative variation in milder traits of the same disorder throughout the general population. Second, there is now evidence for substantial sharing of genetic risks across different psychiatric disorders. This extends to the level of characteristic traits throughout the population, with which some clinical disorders also share genetic risks. In this review, we summarize and evaluate the evidence for these two issues, for a range of psychiatric disorders. We then critically appraise putative interpretations regarding the potential meaning of genetic correlation across psychiatric phenotypes. We highlight several new methods and studies which are already using these insights into the genetic architecture of psychiatric disorders to gain additional understanding regarding the underlying biology of these disorders. We conclude by outlining opportunities for future research in this area.

  5. Identification of genetic markers linked to anthracnose resistance in sorghum using association analysis.

    Science.gov (United States)

    Upadhyaya, Hari D; Wang, Yi-Hong; Sharma, Rajan; Sharma, Shivali

    2013-06-01

    Anthracnose in sorghum caused by Colletotrichum sublineolum is one of the most destructive diseases affecting sorghum production under warm and humid conditions. Markers and genes linked to resistance to the disease are important for plant breeding. Using 14,739 SNP markers, we have mapped eight loci linked to resistance in sorghum through association analysis of a sorghum mini-core collection consisting of 242 diverse accessions evaluated for anthracnose resistance for 2 years in the field. The mini-core was representative of the International Crops Research Institute for the Semi-Arid Tropics' world-wide sorghum landrace collection. Eight marker loci were associated with anthracnose resistance in both years. Except locus 8, disease resistance-related genes were found in all loci based on their physical distance from linked SNP markers. These include two NB-ARC class of R genes on chromosome 10 that were partially homologous to the rice blast resistance gene Pib, two hypersensitive response-related genes: autophagy-related protein 3 on chromosome 1 and 4 harpin-induced 1 (Hin1) homologs on chromosome 8, a RAV transcription factor that is also part of R gene pathway, an oxysterol-binding protein that functions in the non-specific host resistance, and homologs of menthone:neomenthol reductase (MNR) that catalyzes a menthone reduction to produce the antimicrobial neomenthol. These genes and markers may be developed into molecular tools for genetic improvement of anthracnose resistance in sorghum.

  6. Drought-adaptation potential in Fagus sylvatica: linking moisture availability with genetic diversity and dendrochronology.

    Directory of Open Access Journals (Sweden)

    Andrea R Pluess

    Full Text Available BACKGROUND: Microevolution is essential for species persistence especially under anticipated climate change scenarios. Species distribution projection models suggested that the dominant tree species of lowland forests in Switzerland, European beech (Fagus sylvatica L., might disappear from most areas due to expected longer dry periods. However, if genotypes at the moisture boundary of the species climatic envelope are adapted to lower moisture availability, they can serve as seed source for the continuation of beech forests under changing climates. METHODOLOGY/PRINCIPAL FINDINGS: With an AFLP genome scan approach, we studied neutral and potentially adaptive genetic variation in Fagus sylvatica in three regions containing a dry and a mesic site each (n(ind. = 241, n(markers = 517. We linked this dataset with dendrochronological growth measures and local moisture availabilities based on precipitation and soil characteristics. Genetic diversity decreased slightly at dry sites. Overall genetic differentiation was low (F(st = 0.028 and Bayesian cluster analysis grouped all populations together suggesting high (historical gene flow. The Bayesian outlier analyses indicated 13 markers with three markers differing between all dry and mesic sites and the others between the contrasting sites within individual regions. A total of 41 markers, including seven outlier loci, changed their frequency with local moisture availability. Tree height and median basal growth increments were reduced at dry sites, but marker presence/absence was not related to dendrochronological characteristics. CONCLUSION AND THEIR SIGNIFICANCE: The outlier alleles and the makers with changing frequencies in relation to moisture availability indicate microevolutionary processes occurring within short geographic distances. The general genetic similarity among sites suggests that 'preadaptive' genes can easily spread across the landscape. Yet, due to the long live span of

  7. Drought-adaptation potential in Fagus sylvatica: linking moisture availability with genetic diversity and dendrochronology.

    Science.gov (United States)

    Pluess, Andrea R; Weber, Pascale

    2012-01-01

    Microevolution is essential for species persistence especially under anticipated climate change scenarios. Species distribution projection models suggested that the dominant tree species of lowland forests in Switzerland, European beech (Fagus sylvatica L.), might disappear from most areas due to expected longer dry periods. However, if genotypes at the moisture boundary of the species climatic envelope are adapted to lower moisture availability, they can serve as seed source for the continuation of beech forests under changing climates. With an AFLP genome scan approach, we studied neutral and potentially adaptive genetic variation in Fagus sylvatica in three regions containing a dry and a mesic site each (n(ind.) = 241, n(markers) = 517). We linked this dataset with dendrochronological growth measures and local moisture availabilities based on precipitation and soil characteristics. Genetic diversity decreased slightly at dry sites. Overall genetic differentiation was low (F(st) = 0.028) and Bayesian cluster analysis grouped all populations together suggesting high (historical) gene flow. The Bayesian outlier analyses indicated 13 markers with three markers differing between all dry and mesic sites and the others between the contrasting sites within individual regions. A total of 41 markers, including seven outlier loci, changed their frequency with local moisture availability. Tree height and median basal growth increments were reduced at dry sites, but marker presence/absence was not related to dendrochronological characteristics. CONCLUSION AND THEIR SIGNIFICANCE: The outlier alleles and the makers with changing frequencies in relation to moisture availability indicate microevolutionary processes occurring within short geographic distances. The general genetic similarity among sites suggests that 'preadaptive' genes can easily spread across the landscape. Yet, due to the long live span of trees, fostering saplings originating from dry sites and

  8. Genetic relationships and epidemiological links between wild type 1 poliovirus isolates in Pakistan and Afghanistan.

    Science.gov (United States)

    Angez, Mehar; Shaukat, Shahzad; Alam, Muhammad M; Sharif, Salmaan; Khurshid, Adnan; Zaidi, Syed Sohail Zahoor

    2012-02-22

    Efforts have been made to eliminate wild poliovirus transmission since 1988 when the World Health Organization began its global eradication campaign. Since then, the incidence of polio has decreased significantly. However, serotype 1 and serotype 3 still circulate endemically in Pakistan and Afghanistan. Both countries constitute a single epidemiologic block representing one of the three remaining major global reservoirs of poliovirus transmission. In this study we used genetic sequence data to investigate transmission links among viruses from diverse locations during 2005-2007. In order to find the origins and routes of wild type 1 poliovirus circulation, polioviruses were isolated from faecal samples of Acute Flaccid Paralysis (AFP) patients. We used viral cultures, two intratypic differentiation methods PCR, ELISA to characterize as vaccine or wild type 1 and nucleic acid sequencing of entire VP1 region of poliovirus genome to determine the genetic relatedness. One hundred eleven wild type 1 poliovirus isolates were subjected to nucleotide sequencing for genetic variation study. Considering the 15% divergence of the sequences from Sabin 1, Phylogenetic analysis by MEGA software revealed that active inter and intra country transmission of many genetically distinct strains of wild poliovirus type 1 belonged to genotype SOAS which is indigenous in this region. By grouping wild type 1 polioviruses according to nucleotide sequence homology, three distinct clusters A, B and C were obtained with multiple chains of transmission together with some silent circulations represented by orphan lineages. Our results emphasize that there was a persistent transmission of wild type 1 polioviruses in Pakistan and Afghanistan during 2005-2007. The epidemiologic information provided by the sequence data can contribute to the formulation of better strategies for poliomyelitis control to those critical areas, associated with high risk population groups which include migrants

  9. Genetic evidence for monogamy in the dwarf seahorse, Hippocampus zosterae.

    Science.gov (United States)

    Rose, Emily; Small, Clayton M; Saucedo, Hector A; Harper, Cristin; Jones, Adam G

    2014-01-01

    Syngnathid fishes (pipefishes, seahorses, and seadragons) exhibit a wide array of mating systems ranging from monogamy with long-term pair bonds to more promiscuous mating systems, such as polyandry and polygynandry. Some seahorses, including the dwarf seahorse Hippocampus zosterae, have been found to be socially monogamous. Although several seahorse species have also been shown to be genetically monogamous, parentage analysis has not yet been applied to the dwarf seahorse. We developed 8 novel microsatellites for the dwarf seahorse to conduct genetic parentage analysis to confirm that this species is indeed monogamous. Using 4 selected loci and a total of 16 pregnant male seahorses, with 8 collected in Florida and 8 sampled in Texas, we genotyped all of the offspring within each male's brood to determine the maternal contributions to each brood. We found a maximum of 4 alleles per locus segregating within each pregnant male's brood, a pattern consistent with each brood having exactly 1 mother and 1 father. These results support previous laboratory-based behavioral studies and indicate that the dwarf seahorse, H. zosterae, is genetically monogamous. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Population genetic structure in a Robertsonian race of house mice: evidence from microsatellite polymorphism

    NARCIS (Netherlands)

    Dallas, J.F.; Bonhomme, F.; Boursot, P.; Britton-Davidian, J.; Bauchau, V.

    1998-01-01

    Genetic evidence was assessed for inbreeding and population subdivision in a Robertsonian fusion (Rb) race of the western European form of house mouse, Mus musculus domesticus, in central Belgium. Inbreeding, and the factors responsible for subdivision (genetic drift and extinction-recolonization)

  11. Nutrigenetics: links between genetic background and response to Mediterranean-type diets.

    Science.gov (United States)

    Lairon, Denis; Defoort, Catherine; Martin, Jean-Charles; Amiot-Carlin, Marie-Jo; Gastaldi, Marguerite; Planells, Richard

    2009-09-01

    It has been substantiated that the onset of most major diseases (CVD, diabetes, obesity, cancers, etc.) is modulated by the interaction between genetic traits (susceptibility) and environmental factors, especially diet. We aim to report more specific observations relating the effects of Mediterranean-type diets on cardiovascular risk factors and the genetic background of subjects. In the first part, general concepts about nutrigenetics are briefly presented. Human genome has, overall, only marginally changed since its origin but it is thought that minor changes (polymorphisms) of common genes that occurred during evolution are now widespread in human populations, and can alter metabolic pathways and response to diets. In the second part, we report the data obtained during the Medi-RIVAGE intervention study performed in the South-East of France. Data obtained in 169 subjects at moderate cardiovascular risk after a 3-month dietary intervention indicate that some of the twenty-three single nucleotide polymorphisms (SNP) studied exhibit interactions with diets regarding changes of particular parameters after 3-month regimens. Detailed examples are presented, such as interactions between SNP in genes coding for microsomial transfer protein (MTTP) or intestinal fatty acid binding protein (FABP2) and triglyceride, LDL-cholesterol or Framigham score lowering in responses to Mediterranean-type diets. The data provided add further evidence of the interaction between particular SNP and metabolic responses to diets. Finally, improvement in dietary recommendations by taking into account known genetic variability has been discussed.

  12. Review: fetal programming of polycystic ovary syndrome by androgen excess: evidence from experimental, clinical, and genetic association studies.

    Science.gov (United States)

    Xita, Nectaria; Tsatsoulis, Agathocles

    2006-05-01

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder of premenopausal women, characterized by hyperandrogenism, polycystic ovaries, and chronic anovulation along with insulin resistance and abdominal obesity as frequent metabolic traits. Although PCOS manifests clinically during adolescence, emerging data suggest that the natural history of PCOS may originate in intrauterine life. Evidence from experimental, clinical, and genetic research supporting the hypothesis for the fetal origins of PCOS has been analyzed. Female primates, exposed in utero to androgen excess, exhibit the phenotypic features of PCOS during adult life. Clinical observations also support a potential fetal origin of PCOS. Women with fetal androgen excess disorders, including congenital 21-hydroxylase deficiency and congenital adrenal virilizing tumors, develop features characteristic of PCOS during adulthood despite the normalization of androgen excess after birth. The potential mechanisms of fetal androgen excess leading to a PCOS phenotype in humans are not clearly understood. However, maternal and/or fetal hyperandrogenism can provide a plausible mechanism for fetal programing of PCOS, and this, in part, may be genetically determined. Thus, genetic association studies have indicated that common polymorphic variants of genes determining androgen activity or genes that influence the availability of androgens to target tissues are associated with PCOS and increased androgen levels. These genomic variants may provide the genetic link to prenatal androgenization in human PCOS. Prenatal androgenization of the female fetus induced by genetic and environmental factors, or the interaction of both, may program differentiating target tissues toward the development of PCOS phenotype in adult life.

  13. Genetic Evidence for Recent Population Mixture in India

    OpenAIRE

    Moorjani, Priya; Thangaraj, Kumarasamy; Patterson, Nick; Lipson, Mark; Loh, Po-Ru; Govindaraj, Periyasamy; Berger, Bonnie; Reich, David; Singh, Lalji

    2013-01-01

    Most Indian groups descend from a mixture of two genetically divergent populations: Ancestral North Indians (ANI) related to Central Asians, Middle Easterners, Caucasians, and Europeans; and Ancestral South Indians (ASI) not closely related to groups outside the subcontinent. The date of mixture is unknown but has implications for understanding Indian history. We report genome-wide data from 73 groups from the Indian subcontinent and analyze linkage disequilibrium to estimate ANI-ASI mixture ...

  14. Genetic evidence of subaortic stenosis in the Newfoundland dog.

    Science.gov (United States)

    Reist-Marti, S B; Dolf, G; Leeb, T; Kottmann, S; Kietzmann, S; Butenhoff, K; Rieder, S

    2012-06-09

    Subaortic stenosis (SAS) is a cardiac disorder with a narrowing of the descending aorta below the left ventricular outflow tract of the heart. It occurs in several species and breeds. The Newfoundland is one of the dog breeds where it is more common and usually leads to death at early adulthood. It is still discussed to which extent SAS has a genetic background and what its mode of inheritance could be. Extensive pedigree data comprising more than 230,000 Newfoundland dogs from the European and North American population reaching back to the 19th century including 6023 dogs with a SAS diagnosis were analysed for genetic factors influencing SAS affection. The incidence and prevalence of SAS in the analysed Newfoundland population sample were much higher than those reported in previous studies on smaller population samples. Assuming that some SAS-affected dogs remained undiscovered or were not reported, these figures may even be underestimated. SAS-affected Newfoundland dogs were more often inbred and closer related to each other than unaffected dogs, which is an indicator for a genetic background of SAS. The sex had no significant impact on SAS affectedness, pointing at an autosomal inheritance. The only simple mode of inheritance that fitted the data well was autosomal codominant with lethal homozygosity and a penetrance of 1/3 in the heterozygotes.

  15. Linking clinical quality indicators to research evidence - a case study in asthma management for children.

    Science.gov (United States)

    Choong, Miew Keen; Tsafnat, Guy; Hibbert, Peter; Runciman, William B; Coiera, Enrico

    2017-07-21

    Clinical quality indicators are used to monitor the performance of healthcare services and should wherever possible be based on research evidence. Little is known however about the extent to which indicators in common use are based on research. The objective of this study is to measure the extent to which clinical quality indicators used in asthma management in children with outcome measurements can be linked to results in randomised controlled clinical trial (RCT) reports. This work is part of a broader research program to trial methods that improve the efficiency and accuracy of indicator development. National-level indicators for asthma management in children were extracted from the National Quality Measures Clearinghouse database and the National Institute for Health and Care Excellence quality standards by two independent appraisers. Outcome measures were extracted from all published English language RCT reports for asthma management in children below the age of 12 published between 2005 and 2014. The two sets were then linked by manually mapping both to a common set of Unified Medical Language System (UMLS) concepts. The analysis identified 39 indicators and 562 full text RCTs dealing with asthma management in children. About 95% (37/39) of the indicators could be linked to RCT outcome measures. It is possible to identify relevant RCT reports for the majority of indicators used to assess the quality of asthma management in childhood. The methods reported here could be automated to more generally support assessment of candidate indicators against the research evidence.

  16. Behavioral and Genetic Evidence for GIRK Channels in the CNS: Role in Physiology, Pathophysiology, and Drug Addiction.

    Science.gov (United States)

    Mayfield, Jody; Blednov, Yuri A; Harris, R Adron

    2015-01-01

    G protein-coupled inwardly rectifying potassium (GIRK) channels are widely expressed throughout the brain and mediate the inhibitory effects of many neurotransmitters. As a result, these channels are important for normal CNS function and have also been implicated in Down syndrome, Parkinson's disease, psychiatric disorders, epilepsy, and drug addiction. Knockout mouse models have provided extensive insight into the significance of GIRK channels under these conditions. This review examines the behavioral and genetic evidence from animal models and genetic association studies in humans linking GIRK channels with CNS disorders. We further explore the possibility that subunit-selective modulators and other advanced research tools will be instrumental in establishing the role of individual GIRK subunits in drug addiction and other relevant CNS diseases and in potentially advancing treatment options for these disorders. © 2015 Elsevier Inc. All rights reserved.

  17. Non-syndromic posterior lenticonus a cause of childhood cataract: evidence for X-linked inheritance.

    Science.gov (United States)

    Russell-Eggitt, I M

    2000-12-01

    When an X-linked pedigree of posterior lenticonus with cataract was identified further evidence for X-linked inheritance of this condition was sought. Forty-three cases of posterior lenticonus were identified from a database of 354 children with cataract. Two children with the X-linked syndromes of Lowe and Nance-Horan and 3 children with Fanconi syndrome have been excluded from further analysis. None of the children was deaf. None of the non-syndromic cases had microcornea. There were 38 cases of non-syndromic posterior lenticonus (approximately 11%). There were 15 children from 13 pedigrees and 23 apparently sporadic cases. Of the 106 cases on the database with unilateral cataract 15 had posterior lenticonus (approximately 14%). Eleven of 13 pedigrees were compatible with X-linked inheritance or autosomal dominant inheritance with variable expression. However, in 2 pedigrees there was father to son transmission. Posterior lenticonus is a common cause of unilateral infantile cataract, but is thought to be a rare cause of bilateral cataracts. This study suggests that posterior lenticonus is responsible for a significant proportion of childhood cataracts (approximately 14% of unilateral and approximately 9% of bilateral cases). Posterior lenticonus is generally thought to occur as a sporadic condition. This study demonstrates that there is a family history of early-onset cataract in a significant number of bilateral cases (approximately 58%).

  18. Extensive genetic diversity, unique population structure and evidence of genetic exchange in the sexually transmitted parasite Trichomonas vaginalis.

    Directory of Open Access Journals (Sweden)

    Melissa D Conrad

    Full Text Available Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection world-wide. Despite its prevalence, little is known about the genetic diversity and population structure of this haploid parasite due to the lack of appropriate tools. The development of a panel of microsatellite makers and SNPs from mining the parasite's genome sequence has paved the way to a global analysis of the genetic structure of the pathogen and association with clinical phenotypes.Here we utilize a panel of T. vaginalis-specific genetic markers to genotype 235 isolates from Mexico, Chile, India, Australia, Papua New Guinea, Italy, Africa and the United States, including 19 clinical isolates recently collected from 270 women attending New York City sexually transmitted disease clinics. Using population genetic analysis, we show that T. vaginalis is a genetically diverse parasite with a unique population structure consisting of two types present in equal proportions world-wide. Parasites belonging to the two types (type 1 and type 2 differ significantly in the rate at which they harbor the T. vaginalis virus, a dsRNA virus implicated in parasite pathogenesis, and in their sensitivity to the widely-used drug, metronidazole. We also uncover evidence of genetic exchange, indicating a sexual life-cycle of the parasite despite an absence of morphologically-distinct sexual stages.Our study represents the first robust and comprehensive evaluation of global T. vaginalis genetic diversity and population structure. Our identification of a unique two-type structure, and the clinically relevant phenotypes associated with them, provides a new dimension for understanding T. vaginalis pathogenesis. In addition, our demonstration of the possibility of genetic exchange in the parasite has important implications for genetic research and control of the disease.

  19. Extensive genetic diversity, unique population structure and evidence of genetic exchange in the sexually transmitted parasite Trichomonas vaginalis.

    Science.gov (United States)

    Conrad, Melissa D; Gorman, Andrew W; Schillinger, Julia A; Fiori, Pier Luigi; Arroyo, Rossana; Malla, Nancy; Dubey, Mohan Lal; Gonzalez, Jorge; Blank, Susan; Secor, William E; Carlton, Jane M

    2012-01-01

    Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection world-wide. Despite its prevalence, little is known about the genetic diversity and population structure of this haploid parasite due to the lack of appropriate tools. The development of a panel of microsatellite makers and SNPs from mining the parasite's genome sequence has paved the way to a global analysis of the genetic structure of the pathogen and association with clinical phenotypes. Here we utilize a panel of T. vaginalis-specific genetic markers to genotype 235 isolates from Mexico, Chile, India, Australia, Papua New Guinea, Italy, Africa and the United States, including 19 clinical isolates recently collected from 270 women attending New York City sexually transmitted disease clinics. Using population genetic analysis, we show that T. vaginalis is a genetically diverse parasite with a unique population structure consisting of two types present in equal proportions world-wide. Parasites belonging to the two types (type 1 and type 2) differ significantly in the rate at which they harbor the T. vaginalis virus, a dsRNA virus implicated in parasite pathogenesis, and in their sensitivity to the widely-used drug, metronidazole. We also uncover evidence of genetic exchange, indicating a sexual life-cycle of the parasite despite an absence of morphologically-distinct sexual stages. Our study represents the first robust and comprehensive evaluation of global T. vaginalis genetic diversity and population structure. Our identification of a unique two-type structure, and the clinically relevant phenotypes associated with them, provides a new dimension for understanding T. vaginalis pathogenesis. In addition, our demonstration of the possibility of genetic exchange in the parasite has important implications for genetic research and control of the disease.

  20. Asset management using genetic algorithm: Evidence from Tehran Stock Exchange

    Directory of Open Access Journals (Sweden)

    Abbas Sarijaloo

    2014-02-01

    Full Text Available This paper presents an empirical investigation to study the effect of market management using Markowitz theorem. The study uses the information of 50 best performers on Tehran Stock Exchange over the period 2006-2009 and, using Markowitz theorem, the efficient asset allocation are determined and the result are analyzed. The proposed model of this paper has been solved using genetic algorithm. The results indicate that Tehran Stock Exchange has managed to perform much better than average world market in most years of studies especially on year 2009. The results of our investigation have also indicated that one could reach outstanding results using GA and forming efficient portfolio.

  1. The genetic basis of individual differences in reward processing and the link to addictive behavior and social cognition.

    Science.gov (United States)

    Yacubian, J; Büchel, C

    2009-11-24

    Dopaminergic neurotransmission is widely recognized to be critical to the neurobiology of reward, motivation and addiction. Interestingly, social interactions and related behavior also activate the same neuronal system. Consequently, genetic variations of dopamine neurotransmission are thought influence reward processing that in turn may affect distinctive social behavior and susceptibility to addiction. This review focuses on advances made to date in an effort to link genetic individual variations and reward processing as a possible basis for addictive behaviors.

  2. Youth Excel: towards a pan-Canadian platform linking evidence and action for prevention.

    Science.gov (United States)

    Riley, Barbara L; Manske, Steve; Cameron, Roy

    2011-05-15

    Population-level intervention is required to prevent cancer and other chronic diseases. It also promotes health for those living with established risk factors and illness. In this article, the authors describe a vision and approach for continuously improving population-level programs and policies within and beyond the health sector. The vision and approach are anchored in contemporary thinking about what is required to link evidence and action in the field of population and public health. The authors believe that, as a cancer prevention and control community, organizations and practitioners must be able to use the best available evidence to inform action and continually generate evidence that improves prevention policies and programs on an ongoing basis. These imperatives require leaders in policy, practice, and research fields to work together to jointly plan, conduct, and act on relevant evidence. The Propel Center and colleagues are implementing this approach in Youth Excel-a pan-Canadian initiative that brings together national and provincial organizations from health and education sectors and capitalizes on a history of collaboration. The objective of Youth Excel is to build sustainable capacity for knowledge development and exchange that can guide and redirect prevention efforts in a rapidly evolving social environment. This goal is to contribute to creating health-promoting environments and to accelerate progress in preventing cancer and other diseases among youth and young adults and in the wider population. Although prevention is the aim, health-promoting environments also can support health gains for individuals of all ages and with established illness. In addition, the approach Youth Excel is taking to link evidence and action may be applicable to early intervention and treatment components of cancer control. © 2011 American Cancer Society

  3. Genetic evidence of multiple loci in dystocia - difficult labour

    Directory of Open Access Journals (Sweden)

    Westgren Magnus

    2010-06-01

    Full Text Available Abstract Background Dystocia, difficult labour, is a common but also complex problem during childbirth. It can be attributed to either weak contractions of the uterus, a large infant, reduced capacity of the pelvis or combinations of these. Previous studies have indicated that there is a genetic component in the susceptibility of experiencing dystocia. The purpose of this study was to identify susceptibility genes in dystocia. Methods A total of 104 women in 47 families were included where at least two sisters had undergone caesarean section at a gestational length of 286 days or more at their first delivery. Study of medical records and a telephone interview was performed to identify subjects with dystocia. Whole-genome scanning using Affymetrix genotyping-arrays and non-parametric linkage (NPL analysis was made in 39 women exhibiting the phenotype of dystocia from 19 families. In 68 women re-sequencing was performed of candidate genes showing suggestive linkage: oxytocin (OXT on chromosome 20 and oxytocin-receptor (OXTR on chromosome 3. Results We found a trend towards linkage with suggestive NPL-score (3.15 on chromosome 12p12. Suggestive linkage peaks were observed on chromosomes 3, 4, 6, 10, 20. Re-sequencing of OXT and OXTR did not reveal any causal variants. Conclusions Dystocia is likely to have a genetic component with variations in multiple genes affecting the patient outcome. We found 6 loci that could be re-evaluated in larger patient cohorts.

  4. Genetic evidence of multiple loci in dystocia - difficult labour

    Science.gov (United States)

    2010-01-01

    Background Dystocia, difficult labour, is a common but also complex problem during childbirth. It can be attributed to either weak contractions of the uterus, a large infant, reduced capacity of the pelvis or combinations of these. Previous studies have indicated that there is a genetic component in the susceptibility of experiencing dystocia. The purpose of this study was to identify susceptibility genes in dystocia. Methods A total of 104 women in 47 families were included where at least two sisters had undergone caesarean section at a gestational length of 286 days or more at their first delivery. Study of medical records and a telephone interview was performed to identify subjects with dystocia. Whole-genome scanning using Affymetrix genotyping-arrays and non-parametric linkage (NPL) analysis was made in 39 women exhibiting the phenotype of dystocia from 19 families. In 68 women re-sequencing was performed of candidate genes showing suggestive linkage: oxytocin (OXT) on chromosome 20 and oxytocin-receptor (OXTR) on chromosome 3. Results We found a trend towards linkage with suggestive NPL-score (3.15) on chromosome 12p12. Suggestive linkage peaks were observed on chromosomes 3, 4, 6, 10, 20. Re-sequencing of OXT and OXTR did not reveal any causal variants. Conclusions Dystocia is likely to have a genetic component with variations in multiple genes affecting the patient outcome. We found 6 loci that could be re-evaluated in larger patient cohorts. PMID:20587075

  5. Genetic localization and phenotypic expression of X-linked cataract (Xcat) in Mus musculus.

    Science.gov (United States)

    Favor, J; Pretsch, W

    1990-01-01

    Linkage data relative to the markers tabby and glucose-6-phosphate dehydrogenase are presented to locate X-linked cataract (Xcat) in the distal portion of the mouse X-chromosome between jimpy and hypophosphatemia. The human X-linked cataract-dental syndrome, Nance-Horan Syndrome, also maps closely to human hypophosphatemia and would suggest homology between mouse Xcat and human Nance-Horan Syndrome genes. In hemizygous males and homozygous females penetrance is complete with only slight variation in the degree of expression. Phenotypic expression in Xcat heterozygous females ranges from totally clear to totally opaque lenses. The phenotypic expression between the two lenses of a heterozygous individual could also vary between totally clear and totally opaque lenses. However, a correlation in the degree of expression between the eyes of an individual was observed. A variegated pattern of lens opacity was evident in female heterozygotes. Based on these observations, the site of gene action for the Xcat locus is suggested to be endogenous to the lens cells and the precursor cell population of the lens is concluded to be small. The identification of an X-linked cataract locus is an important contribution to the estimate of the number of mutable loci resulting in cataract, an estimate required so that dominant cataract mutagenesis results may be expressed on a per locus basis. The Xcat mutation may be a useful marker for a distal region of the mouse X-chromosome which is relatively sparsely marked and the X-linked cataract mutation may be employed in gene expression and lens development studies.

  6. Genetic relationships and epidemiological links between wild type 1 poliovirus isolates in Pakistan and Afghanistan

    Directory of Open Access Journals (Sweden)

    Angez Mehar

    2012-02-01

    Full Text Available Abstract Background/Aim Efforts have been made to eliminate wild poliovirus transmission since 1988 when the World Health Organization began its global eradication campaign. Since then, the incidence of polio has decreased significantly. However, serotype 1 and serotype 3 still circulate endemically in Pakistan and Afghanistan. Both countries constitute a single epidemiologic block representing one of the three remaining major global reservoirs of poliovirus transmission. In this study we used genetic sequence data to investigate transmission links among viruses from diverse locations during 2005-2007. Methods In order to find the origins and routes of wild type 1 poliovirus circulation, polioviruses were isolated from faecal samples of Acute Flaccid Paralysis (AFP patients. We used viral cultures, two intratypic differentiation methods PCR, ELISA to characterize as vaccine or wild type 1 and nucleic acid sequencing of entire VP1 region of poliovirus genome to determine the genetic relatedness. Results One hundred eleven wild type 1 poliovirus isolates were subjected to nucleotide sequencing for genetic variation study. Considering the 15% divergence of the sequences from Sabin 1, Phylogenetic analysis by MEGA software revealed that active inter and intra country transmission of many genetically distinct strains of wild poliovirus type 1 belonged to genotype SOAS which is indigenous in this region. By grouping wild type 1 polioviruses according to nucleotide sequence homology, three distinct clusters A, B and C were obtained with multiple chains of transmission together with some silent circulations represented by orphan lineages. Conclusion Our results emphasize that there was a persistent transmission of wild type1 polioviruses in Pakistan and Afghanistan during 2005-2007. The epidemiologic information provided by the sequence data can contribute to the formulation of better strategies for poliomyelitis control to those critical areas

  7. Loss of Function Studies in Mice and Genetic Association Link Receptor Protein Tyrosine Phosphatase a to Schizophrenia

    DEFF Research Database (Denmark)

    Takahashi, Nagahide; Nielsen, Karin Sandager; Aleksic, Branko

    2011-01-01

    Solid evidence links schizophrenia (SZ) susceptibility to neurodevelopmental processes involving tyrosine phosphorylation-mediated signaling. Mouse studies implicate the Ptpra gene, encoding protein tyrosine phosphatase RPTPa, in the control of radial neuronal migration, cortical cytoarchitecture...

  8. Firms’ wage policies: New evidence from linked employer-employee data

    OpenAIRE

    Suleman, F.; Lagoa, S.; Suleman, A.; Pereira, M.L.

    2013-01-01

    The research on wage policies has been triggered by the interest in identifying whether labour market or institutional forces shape the wage settings inside firms. This paper draws on linked employer-employee data and uses a fuzzy c-means clustering analysis to identify typical wage policies of medium and large firms in Portugal. Empirical evidence suggests that firms are segmented into four clusters that can be labelled according to wage rules as “Regulated”, “Asymmetric”, “Hierarchical” and...

  9. Novel canine circovirus strains from Thailand: Evidence for genetic recombination.

    Science.gov (United States)

    Piewbang, Chutchai; Jo, Wendy K; Puff, Christina; van der Vries, Erhard; Kesdangsakonwut, Sawang; Rungsipipat, Anudep; Kruppa, Jochen; Jung, Klaus; Baumgärtner, Wolfgang; Techangamsuwan, Somporn; Ludlow, Martin; Osterhaus, Albert D M E

    2018-05-14

    Canine circoviruses (CanineCV's), belonging to the genus Circovirus of the Circoviridae family, were detected by next generation sequencing in samples from Thai dogs with respiratory symptoms. Genetic characterization and phylogenetic analysis of nearly complete CanineCV genomes suggested that natural recombination had occurred among different lineages of CanineCV's. Similarity plot and bootscaning analyses indicated that American and Chinese viruses had served as major and minor parental viruses, respectively. Positions of recombination breakpoints were estimated using maximum-likelihood frameworks with statistical significant testing. The putative recombination event was located in the Replicase gene, intersecting with open reading frame-3. Analysis of nucleotide changes confirmed the origin of the recombination event. This is the first description of naturally occurring recombinant CanineCV's that have resulted in the circulation of newly emerging CanineCV lineages.

  10. Aggressive Behavior between Siblings and the Development of Externalizing Problems: Evidence from a Genetically Sensitive Study

    Science.gov (United States)

    Natsuaki, Misaki N.; Ge, Xiaojia; Reiss, David; Neiderhiser, Jenae M.

    2009-01-01

    This study investigated the prospective links between sibling aggression and the development of externalizing problems using a multilevel modeling approach with a genetically sensitive design. The sample consisted of 780 adolescents (390 sibling pairs) who participated in 2 waves of the Nonshared Environment in Adolescent Development project.…

  11. MyGeneFriends: A Social Network Linking Genes, Genetic Diseases, and Researchers.

    Science.gov (United States)

    Allot, Alexis; Chennen, Kirsley; Nevers, Yannis; Poidevin, Laetitia; Kress, Arnaud; Ripp, Raymond; Thompson, Julie Dawn; Poch, Olivier; Lecompte, Odile

    2017-06-16

    The constant and massive increase of biological data offers unprecedented opportunities to decipher the function and evolution of genes and their roles in human diseases. However, the multiplicity of sources and flow of data mean that efficient access to useful information and knowledge production has become a major challenge. This challenge can be addressed by taking inspiration from Web 2.0 and particularly social networks, which are at the forefront of big data exploration and human-data interaction. MyGeneFriends is a Web platform inspired by social networks, devoted to genetic disease analysis, and organized around three types of proactive agents: genes, humans, and genetic diseases. The aim of this study was to improve exploration and exploitation of biological, postgenomic era big data. MyGeneFriends leverages conventions popularized by top social networks (Facebook, LinkedIn, etc), such as networks of friends, profile pages, friendship recommendations, affinity scores, news feeds, content recommendation, and data visualization. MyGeneFriends provides simple and intuitive interactions with data through evaluation and visualization of connections (friendships) between genes, humans, and diseases. The platform suggests new friends and publications and allows agents to follow the activity of their friends. It dynamically personalizes information depending on the user's specific interests and provides an efficient way to share information with collaborators. Furthermore, the user's behavior itself generates new information that constitutes an added value integrated in the network, which can be used to discover new connections between biological agents. We have developed MyGeneFriends, a Web platform leveraging conventions from popular social networks to redefine the relationship between humans and biological big data and improve human processing of biomedical data. MyGeneFriends is available at lbgi.fr/mygenefriends. ©Alexis Allot, Kirsley Chennen, Yannis

  12. Genetic evidence on the origins of Indian caste populations.

    Science.gov (United States)

    Bamshad, M; Kivisild, T; Watkins, W S; Dixon, M E; Ricker, C E; Rao, B B; Naidu, J M; Prasad, B V; Reddy, P G; Rasanayagam, A; Papiha, S S; Villems, R; Redd, A J; Hammer, M F; Nguyen, S V; Carroll, M L; Batzer, M A; Jorde, L B

    2001-06-01

    The origins and affinities of the approximately 1 billion people living on the subcontinent of India have long been contested. This is owing, in part, to the many different waves of immigrants that have influenced the genetic structure of India. In the most recent of these waves, Indo-European-speaking people from West Eurasia entered India from the Northwest and diffused throughout the subcontinent. They purportedly admixed with or displaced indigenous Dravidic-speaking populations. Subsequently they may have established the Hindu caste system and placed themselves primarily in castes of higher rank. To explore the impact of West Eurasians on contemporary Indian caste populations, we compared mtDNA (400 bp of hypervariable region 1 and 14 restriction site polymorphisms) and Y-chromosome (20 biallelic polymorphisms and 5 short tandem repeats) variation in approximately 265 males from eight castes of different rank to approximately 750 Africans, Asians, Europeans, and other Indians. For maternally inherited mtDNA, each caste is most similar to Asians. However, 20%-30% of Indian mtDNA haplotypes belong to West Eurasian haplogroups, and the frequency of these haplotypes is proportional to caste rank, the highest frequency of West Eurasian haplotypes being found in the upper castes. In contrast, for paternally inherited Y-chromosome variation each caste is more similar to Europeans than to Asians. Moreover, the affinity to Europeans is proportionate to caste rank, the upper castes being most similar to Europeans, particularly East Europeans. These findings are consistent with greater West Eurasian male admixture with castes of higher rank. Nevertheless, the mitochondrial genome and the Y chromosome each represents only a single haploid locus and is more susceptible to large stochastic variation, bottlenecks, and selective sweeps. Thus, to increase the power of our analysis, we assayed 40 independent, biparentally inherited autosomal loci (1 LINE-1 and 39 Alu elements

  13. Diversification and the rate of molecular evolution: no evidence of a link in mammals

    Directory of Open Access Journals (Sweden)

    Bromham Lindell

    2011-10-01

    Full Text Available Abstract Background Recent research has indicated a positive association between rates of molecular evolution and diversification in a number of taxa. However debate continues concerning the universality and cause of this relationship. Here, we present the first systematic investigation of this relationship within the mammals. We use phylogenetically independent sister-pair comparisons to test for a relationship between substitution rates and clade size at a number of taxonomic levels. Total, non-synonymous and synonymous substitution rates were estimated from mitochondrial and nuclear DNA sequences. Results We found no evidence for an association between clade size and substitution rates in mammals, for either the nuclear or the mitochondrial sequences. We found significant associations between body size and substitution rates, as previously reported. Conclusions Our results present a contrast to previous research, which has reported significant positive associations between substitution rates and diversification for birds, angiosperms and reptiles. There are three possible reasons for the differences between the observed results in mammals versus other clades. First, there may be no link between substitution rates and diversification in mammals. Second, this link may exist, but may be much weaker in mammals than in other clades. Third, the link between substitution rates and diversification may exist in mammals, but may be confounded by other variables.

  14. Diversification and the rate of molecular evolution: no evidence of a link in mammals.

    Science.gov (United States)

    Goldie, Xavier; Lanfear, Robert; Bromham, Lindell

    2011-10-04

    Recent research has indicated a positive association between rates of molecular evolution and diversification in a number of taxa. However debate continues concerning the universality and cause of this relationship. Here, we present the first systematic investigation of this relationship within the mammals. We use phylogenetically independent sister-pair comparisons to test for a relationship between substitution rates and clade size at a number of taxonomic levels. Total, non-synonymous and synonymous substitution rates were estimated from mitochondrial and nuclear DNA sequences. We found no evidence for an association between clade size and substitution rates in mammals, for either the nuclear or the mitochondrial sequences. We found significant associations between body size and substitution rates, as previously reported. Our results present a contrast to previous research, which has reported significant positive associations between substitution rates and diversification for birds, angiosperms and reptiles. There are three possible reasons for the differences between the observed results in mammals versus other clades. First, there may be no link between substitution rates and diversification in mammals. Second, this link may exist, but may be much weaker in mammals than in other clades. Third, the link between substitution rates and diversification may exist in mammals, but may be confounded by other variables.

  15. Evidence of genetic susceptibility to infectious mononucleosis: a twin study.

    Science.gov (United States)

    Hwang, A E; Hamilton, A S; Cockburn, M G; Ambinder, R; Zadnick, J; Brown, E E; Mack, T M; Cozen, W

    2012-11-01

    Infectious mononucleosis is a clinical manifestation of primary Epstein-Barr virus infection. It is unknown whether genetic factors contribute to risk. To assess heritability, we compared disease concordance in monozygotic to dizygotic twin pairs from the population-based California Twin Program and assessed the risk to initially unaffected co-twins. One member of 611 and both members of 58 twin pairs reported a history of infectious mononucleosis. Pairwise concordance in monozygotic and dizygotic pairs was respectively 12·1% [standard error (s.e.)=1·9%] and 6·1% (s.e.=1·2%). The relative risk (hazard ratio) of monozygotic compared to dizygotic unaffected co-twins of cases was 1·9 [95% confidence interval (CI) 1·1-3·4, P=0·03], over the follow-up period. When the analysis was restricted to same-sex twin pairs, that estimate was 2·5 (95% CI 1·2-5·3, P=0·02). The results are compatible with a heritable contribution to the risk of infectious mononucleosis.

  16. Iridoschisis: high frequency ultrasound imaging. Evidence for a genetic defect?

    Science.gov (United States)

    Danias, J; Aslanides, I M; Eichenbaum, J W; Silverman, R H; Reinstein, D Z; Coleman, D J

    1996-01-01

    AIMS: To elucidate changes in the anatomy of the anterior chamber associated with iridoschisis, a rare form of iris atrophy, and their potential contribution to angle closure glaucoma. METHODS: Both eyes of a 71-year-old woman with bilateral iridoschisis and fibrous dysplasia and her asymptomatic 50-year-old daughter were scanned with a very high frequency (50 MHz) ultrasound system. RESULTS: The symptomatic patient exhibited diffuse changes in the iris stoma with an intact posterior iris pigmented layer in both eyes. These changes were clinically compatible with the lack of iris transillumination defects. Additionally, iris bowing with a resultant narrowing of the angle occurred. The asymptomatic daughter showed discrete, but less severe iris stromal changes. CONCLUSION: This is the first detailed study of high frequency ultrasonic imaging of the iris in iridoschisis. The observed structural changes suggest angle narrowing by forward bowing of the anterior iris stroma may be a mechanism of IOP elevation in this condition. The ultrasonic detection of iris changes in the asymptomatic daughter of the symptomatic patient and the association of iridoschisis with fibrous dysplasia suggest a possible genetic component in the pathogenesis of this condition. Images PMID:9059271

  17. Carrier detection in X-linked retinitis pigmentosa by multipoint DNA analysis. Problems due to genetic heterogeneity

    NARCIS (Netherlands)

    Bergen, A. A.; Platje, E. J.; Craig, I.; Bakker, E.; Bleeker-Wagemakers, E. M.; van Ommen, G. J.

    1991-01-01

    DNA diagnosis of X-linked retinitis pigmentosa (XLRP) is hampered by its genetic heterogeneity, while a clinical subdivision is almost impossible to make. So far, diagnostic services have been offered only to those families in which linkage to one RP locus (RP2 or RP3) has been clearly established.

  18. Genetics Home Reference: alpha thalassemia X-linked intellectual disability syndrome

    Science.gov (United States)

    ... Alpha thalassemia X-linked intellectual disability syndrome Alpha thalassemia X-linked intellectual disability syndrome Printable PDF Open ... to view the expand/collapse boxes. Description Alpha thalassemia X-linked intellectual disability syndrome is an inherited ...

  19. Delusional disorder: molecular genetic evidence for dopamine psychosis.

    Science.gov (United States)

    Morimoto, Kiyoshi; Miyatake, Ryosuke; Nakamura, Mitsuo; Watanabe, Takemi; Hirao, Toru; Suwaki, Hiroshi

    2002-06-01

    Since delusional disorder is characterized by mono-symptomatic paranoid symptoms, it can be a good clinical model for investigating the dopaminergic mechanism responsible for paranoid symptoms. We examined neuroleptic responses, plasma homovanillic acid (pHVA) and genes of the dopamine receptor (DR) and its synthesizing enzyme (tyrosine hydroxylase: TH) in patients with delusional disorder and compared them with those of schizophrenic patients and healthy controls. (1) A relatively small dose of haloperidol was more effective for delusional disorder than for schizophrenia. (2) The pretreatment level of pHVA was higher in patients with persecution-type, but not in those with jealousy-type delusional disorder, compared with age- and sex-matched controls. This increased pHVA level was decreased eight weeks after successful haloperidol treatment. (3) The genotype frequency of the DRD2 gene Ser311Cys was significantly higher in patients with persecution-type delusional disorder (21%), compared with schizophrenic patients (6%) or controls (6%). (4) Patients homozygous for the DRD3 gene Ser9Ser had higher pretreatment levels of pHVA than those heterozygous for Ser9Gly. (v) A significant positive correlation was found between the polymorphic (TCAT)(n) repeat in the first intron of the TH gene and pretreatment levels of pHVA in delusional disorder. We suggest that delusional disorder, especially the persecution-type, includes a "dopamine psychosis," and that polymorphism of the DRD2, DRD3 and/or TH gene is part of the genetic basis underlying the hyperdopaminergic state that produces paranoid symptoms. Further studies on a large sample size are required.

  20. An Efficient Stepwise Statistical Test to Identify Multiple Linked Human Genetic Variants Associated with Specific Phenotypic Traits.

    Directory of Open Access Journals (Sweden)

    Iksoo Huh

    Full Text Available Recent advances in genotyping methodologies have allowed genome-wide association studies (GWAS to accurately identify genetic variants that associate with common or pathological complex traits. Although most GWAS have focused on associations with single genetic variants, joint identification of multiple genetic variants, and how they interact, is essential for understanding the genetic architecture of complex phenotypic traits. Here, we propose an efficient stepwise method based on the Cochran-Mantel-Haenszel test (for stratified categorical data to identify causal joint multiple genetic variants in GWAS. This method combines the CMH statistic with a stepwise procedure to detect multiple genetic variants associated with specific categorical traits, using a series of associated I × J contingency tables and a null hypothesis of no phenotype association. Through a new stratification scheme based on the sum of minor allele count criteria, we make the method more feasible for GWAS data having sample sizes of several thousands. We also examine the properties of the proposed stepwise method via simulation studies, and show that the stepwise CMH test performs better than other existing methods (e.g., logistic regression and detection of associations by Markov blanket for identifying multiple genetic variants. Finally, we apply the proposed approach to two genomic sequencing datasets to detect linked genetic variants associated with bipolar disorder and obesity, respectively.

  1. Genetic structure of populations of whale sharks among ocean basins and evidence for their historic rise and recent decline

    KAUST Repository

    Vignaud, Thomas M.; Maynard, Jeffrey Allen; Leblois, Raphaë l; Meekan, Mark G.; Vá zquez-Juá rez, Ricardo; Ramí rez-Mací as, Dení ; Pierce, Simon J.; Rowat, David; Berumen, Michael L.; Beeravolu, Champak R.; Baksay, Sandra; Planes, Serge

    2014-01-01

    This study presents genetic evidence that whale sharks, Rhincodon typus, are comprised of at least two populations that rarely mix and is the first to document a population expansion. Relatively high genetic structure is found when comparing sharks

  2. Evidence of two genetic clusters of manatees with low genetic diversity in Mexico and implications for their conservation

    Science.gov (United States)

    Nourisson, C.; Morales-Vela, B.; Padilla-Saldivar, J.; Tucker, K.P.; Clark, A.; Olivera-Gomez, L. D.; Bonde, R.; McGuire, P.

    2011-01-01

    The Antillean manatee (Trichechus manatus manatus) occupies the tropical coastal waters of the Greater Antilles and Caribbean, extending from Mexico along Central and South America to Brazil. Historically, manatees were abundant in Mexico, but hunting during the pre-Columbian period, the Spanish colonization and throughout the history of Mexico, has resulted in the significantly reduced population occupying Mexico today. The genetic structure, using microsatellites, shows the presence of two populations in Mexico: the Gulf of Mexico (GMx) and Chetumal Bay (ChB) on the Caribbean coast, with a zone of admixture in between. Both populations show low genetic diversity (GMx: NA=2.69; HE=0.41 and ChB: NA=3.0; HE=0.46). The lower genetic diversity found in the GMx, the largest manatee population in Mexico, is probably due to a combination of a founder effect, as this is the northern range of the sub-species of T. m. manatus, and a bottleneck event. The greater genetic diversity observed along the Caribbean coast, which also has the smallest estimated number of individuals, is possibly due to manatees that come from the GMx and Belize. There is evidence to support limited or unidirectional gene flow between these two important areas. The analyses presented here also suggest minimal evidence of a handful of individual migrants possibly between Florida and Mexico. To address management issues we suggest considering two distinct genetic populations in Mexico, one along the Caribbean coast and one in the riverine systems connected to the GMx. ?? 2011 Springer Science+Business Media B.V.

  3. Evidence of two genetic clusters of manatees with low genetic diversity in Mexico and implications for their conservation.

    Science.gov (United States)

    Nourisson, Coralie; Morales-Vela, Benjamín; Padilla-Saldívar, Janneth; Tucker, Kimberly Pause; Clark, Annmarie; Olivera-Gómez, Leon David; Bonde, Robert; McGuire, Peter

    2011-07-01

    The Antillean manatee (Trichechus manatus manatus) occupies the tropical coastal waters of the Greater Antilles and Caribbean, extending from Mexico along Central and South America to Brazil. Historically, manatees were abundant in Mexico, but hunting during the pre-Columbian period, the Spanish colonization and throughout the history of Mexico, has resulted in the significantly reduced population occupying Mexico today. The genetic structure, using microsatellites, shows the presence of two populations in Mexico: the Gulf of Mexico (GMx) and Chetumal Bay (ChB) on the Caribbean coast, with a zone of admixture in between. Both populations show low genetic diversity (GMx: N(A) = 2.69; H(E) = 0.41 and ChB: N(A) = 3.0; H(E) = 0.46). The lower genetic diversity found in the GMx, the largest manatee population in Mexico, is probably due to a combination of a founder effect, as this is the northern range of the sub-species of T. m. manatus, and a bottleneck event. The greater genetic diversity observed along the Caribbean coast, which also has the smallest estimated number of individuals, is possibly due to manatees that come from the GMx and Belize. There is evidence to support limited or unidirectional gene flow between these two important areas. The analyses presented here also suggest minimal evidence of a handful of individual migrants possibly between Florida and Mexico. To address management issues we suggest considering two distinct genetic populations in Mexico, one along the Caribbean coast and one in the riverine systems connected to the GMx.

  4. Evidence of two genetic clusters of manatees with low genetic diversity in Mexico and implications for their conservation

    Science.gov (United States)

    Nourisson, Coralie; Morales-Vela, Benjamin; Padilla-Saldivar, Janneth; Tucker, Kimberly Pause; Clark, Ann Marie; Olivera-Gomez, Leon David; Bonde, Robert; McGuire, Peter

    2011-01-01

    The Antillean manatee (Trichechus manatus manatus) occupies the tropical coastal waters of the Greater Antilles and Caribbean, extending from Mexico along Central and South America to Brazil. Historically, manatees were abundant in Mexico, but hunting during the pre-Columbian period, the Spanish colonization and throughout the history of Mexico, has resulted in the significantly reduced population occupying Mexico today. The genetic structure, using microsatellites, shows the presence of two populations in Mexico: the Gulf of Mexico (GMx) and Chetumal Bay (ChB) on the Caribbean coast, with a zone of admixture in between. Both populations show low genetic diversity (GMx: NA = 2.69; HE = 0.41 and ChB: NA = 3.0; HE = 0.46). The lower genetic diversity found in the GMx, the largest manatee population in Mexico, is probably due to a combination of a founder effect, as this is the northern range of the sub-species of T. m. manatus, and a bottleneck event. The greater genetic diversity observed along the Caribbean coast, which also has the smallest estimated number of individuals, is possibly due to manatees that come from the GMx and Belize. There is evidence to support limited or unidirectional gene flow between these two important areas. The analyses presented here also suggest minimal evidence of a handful of individual migrants possibly between Florida and Mexico. To address management issues we suggest considering two distinct genetic populations in Mexico, one along the Caribbean coast and one in the riverine systems connected to the GMx.

  5. Interpreting genetics in the context of eating disorders: evidence of disease, not diversity.

    Science.gov (United States)

    Easter, Michele

    2014-07-01

    How is genetic involvement interpreted for disorders whose medicalisation is contested? Framing psychiatric and behavioural disorders in terms of genetics is expected to make them seem more medical. Yet a genetic aetiology can also be used to frame behaviour as acceptable human variation, rather than a medical problem (for example, sexual orientation). I analyse responses to the idea that there is a genetic component in anorexia and bulimia nervosa (AN or BN) via semi-structured interviews with a sample of 50 women diagnosed with an eating disorder (25 had recovered). All but three volunteered that genetics would medicalise AN or BN by (i) making eating disorders seem more like 'real diseases'; implying that these disorders need (ii) professional treatment or (iii) a biologically based treatment. The results also indicate there are several counter-logics by which genetic framing could support non-medical definitions of AN or BN. I argue that genetic framing reduces perceived individual responsibility, which can support definitions of behaviour as either a reflection of disease (which entails intervention) or a reflection of normal human diversity (which does not). In the context of public scepticism as to the 'reality' of AN or BN, genetic involvement was taken as evidence of disease in ongoing negotiations about the medical and moral status of people with eating disorders. © 2013 The Author. Sociology of Health & Illness © 2013 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd.

  6. A complex genetic basis to X-linked hybrid male sterility between two species of house mice.

    Science.gov (United States)

    Good, Jeffrey M; Dean, Matthew D; Nachman, Michael W

    2008-08-01

    The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome.

  7. Infertility etiologies are genetically and clinically linked with other diseases in single meta-diseases.

    Science.gov (United States)

    Tarín, Juan J; García-Pérez, Miguel A; Hamatani, Toshio; Cano, Antonio

    2015-04-15

    linked with other diseases in single meta-diseases. This finding opens new insights for clinicians and reproductive biologists to treat infertility problems using a phenomic approach instead of considering infertility as an isolated and exclusive disease of the reproductive system/hypothalamic-pituitary-gonadal axis. In agreement with a previous validation analysis of the utility of DiseaseConnect web server, the present study does not show a univocal correspondence between common gene expression and clinical comorbid relationship. Further work is needed to untangle the potential genetic, epigenetic and phenotypic relationships that may be present among different infertility etiologies, morbid conditions and physical/cognitive traits.

  8. Linking energy efficiency and innovation practices: Empirical evidence from the foundry sector

    International Nuclear Information System (INIS)

    Cagno, Enrico; Ramirez-Portilla, Andres; Trianni, Andrea

    2015-01-01

    The Europe 2020 strategy currently promotes energy efficiency and innovation through disconnected targets focusing on either energy or R&D. Similar policies indicate that in practice, these two concepts are usually perceived as mutually exclusive. Furthermore, evidence in the literature regarding the relationship between R&D and energy efficiency is still highly limited. This exploratory study aims to address this gap by investigating the link between innovation practices and energy efficiency through a multiple case study of 30 foundries in Northern Italy. We analysed the firms' innovativeness, measured by internal R&D and Open Innovation practices (inbound and outbound), and energy efficiency, measured by specific energy consumption, level of adoption of energy-efficient technologies and barriers to energy efficiency. The results seem to show that those foundries complementing internal R&D with inbound practices have a higher level of energy efficiency, a higher level of adoption of available technologies, and a lower perception of barriers to efficiency improvements. This finding suggests that diversifying innovation practices could lead to better performance with respect to all three indicators of energy efficiency analysed. This study contributes to understanding how more innovative firms can be more energy efficient, providing interesting highlights for managers and policymakers. -- Highlights: •The relation between innovation practices and energy efficiency is articulated. •The link between innovation practices and energy efficiency is tested for foundries. •Energy efficiency is measured with three different indicators. •Analyses of the relations between these indicators support the link with innovation. •Concurrent adoption of internal R&D and inbound practices leads to higher efficiency

  9. Understanding the cognitive and genetic underpinnings of procrastination: Evidence for shared genetic influences with goal management and executive function abilities.

    Science.gov (United States)

    Gustavson, Daniel E; Miyake, Akira; Hewitt, John K; Friedman, Naomi P

    2015-12-01

    Previous research has suggested that individual differences in procrastination are tied to everyday goal-management abilities, but little research has been conducted on specific cognitive abilities that may underlie tendencies for procrastination, such as executive functions (EFs). In this study, we used behavioral genetics methodology to investigate 2 hypotheses about the relationships between procrastination and EF ability: (a) that procrastination is negatively correlated with general EF ability, and (b) that this relationship is due to the genetic components of procrastination that are most related to other everyday goal-management abilities. The results confirmed both of these hypotheses. Procrastination was related to worse general EF ability at both the phenotypic and genetic levels, and this relationship was due to the component of procrastination shared with self-report measures of everyday goal-management failures. These results were observed even after controlling for potential self-report biases stemming from the urge to respond in a socially desirable manner. Together, these findings provide strong evidence for growing theories of procrastination emphasizing the importance of goal-related cognitive abilities and further highlight important genetic influences that underlie procrastination. (c) 2015 APA, all rights reserved).

  10. Energy Link Optimization in a Wireless Power Transfer Grid under Energy Autonomy Based on the Improved Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Zhihao Zhao

    2016-08-01

    Full Text Available In this paper, an optimization method is proposed for the energy link in a wireless power transfer grid, which is a regional smart microgrid comprised of distributed devices equipped with wireless power transfer technology in a certain area. The relevant optimization model of the energy link is established by considering the wireless power transfer characteristics and the grid characteristics brought in by the device repeaters. Then, a concentration adaptive genetic algorithm (CAGA is proposed to optimize the energy link. The algorithm avoided the unification trend by introducing the concentration mechanism and a new crossover method named forward order crossover, as well as the adaptive parameter mechanism, which are utilized together to keep the diversity of the optimization solution groups. The results show that CAGA is feasible and competitive for the energy link optimization in different situations. This proposed algorithm performs better than its counterparts in the global convergence ability and the algorithm robustness.

  11. Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence.

    LENUS (Irish Health Repository)

    Murphy, S

    2012-02-01

    BACKGROUND: Cognitive impairment and dementia has been reported in autosomal dominant hereditary spastic paraparesis (HSP) linked to the SPG4 locus. There has only been one postmortem examination described; not all accept that progressive cognitive decline is a feature of this disorder. OBJECTIVE: A family with SPG4-HSP known to have a deletion of exon 17 in the spastin gene (SPG4delEx17) was cognitively assessed over a 7-year period. The index family member died and a postmortem examination was performed. METHODS: Thirteen family members older than 40 years were clinically and cognitively assessed using the Cambridge Cognitive Assessment over a 7-year period. The presence of SPG4delEx17 was assessed; a neuropathologic examination of the brain of the index family member was performed. RESULTS: Cognitive decline occurred in 6 of the 13 family members and in all 4 older than 60 years. Two genetic deletions were identified: SPG4delEx17 in 12 of the 13 family members and a deletion of SPG6 (SPG6del) in 5. Eight individuals had the SPG4delEx17 deletion only; 4 had evidence of progressive cognitive impairment. Four family members had both SPG4delEx17 and SPG6del; 2 of these had cognitive impairment. One family member with the SPG6del alone had neither HSP nor cognitive impairment. The index case with both deletions died with dementia; the brain showed widespread ubiquitin positivity within the neocortex and white matter. CONCLUSION: Cognitive decline and dementia is a feature of SPG4-HSP due to a deletion of exon 17 of the spastin gene.

  12. Evidence from mammalian studies on genetic effects of low level irradiation

    International Nuclear Information System (INIS)

    Searle, A.G.

    1989-01-01

    The major components of genetic damage and associated human risks are discussed, together with the experimental evidence on induction rates of chromosome anomalies in mice, and monkeys male and female germ cells, using low and high LET low level irradiation. (UK)

  13. Tourette's Disorder: Genetic Update, Neurological Correlates, and Evidence-Based Interventions

    Science.gov (United States)

    Phelps, LeAdelle

    2008-01-01

    This article provides an update of the search for genetic markers related to Tourette's Disorder. The probable neurophysiology of the disorder is reviewed. Frequently prescribed medications are related to the probable biological bases of the disorder. Behavioral interventions and assessment tools are examined. It is concluded that evidence based…

  14. Genetic evidence of hybridization between Onothera wolfii (Wolf's evening primrose) and O. glaziovana, a garden escape

    Science.gov (United States)

    Jennifer DeWoody; Leonel Arguello; David Imper; Robert D. Westfall; Valerie D. Hipkins

    2008-01-01

    Isozyme analysis of the rare Oenothera wolfii (Wolf's evening primrose) and the garden escape, O. glazioviana, indicates that hybridization between these species may be more widespread than morphological evidence indicates. Although both species contained low amounts of genetic variation, unique alleles were identified in...

  15. Genetics Ustilago violacea. XXXIII. Genetic evidence for insertional mutations in the magenta locus

    International Nuclear Information System (INIS)

    Garber, E.D.; Ruddat, M.

    1996-01-01

    Three spontaneous mutants (m-1, m-2, and m-31) with a new sporidial colony color (magenta, m) were found in the stable pink 1.A1 a-1 and 2.A2 a-2 laboratory strains. The m-1 and white (w) mutations were very closely linked (<0.1 cM); the m locus was assumed to be distal from the w locus and in the same chromosome arm. The color mutations formed a map of very closely linked (<1 cM), centromere-linked loci: orange (o)-pumpkin (p)-yellow (y)-centr-wA-wB-m. Crosses between the m-1 and m-2 mutants, between the m-2 mutant and laboratory strains with a different color, and between the m-2 mutant and strains from the herbarium/field collections gave nonsectored and sectored teliospore colonies with a nonparental color. All of the teliospores colonies from cross AV13 involving strains 1.C417* y and 2.C413 p had a nonparental color or different nonparental colors, including magenta. The UV-irradiation of m-1, m-2, and m-31 sporidia gave mostly pink (+) colonies, ranging from 9% to 48%. Occasional nonsectored w and p colonies as well as one bisectored m/+ and one w/+ colony were found. Approximately 103 m-1 sporidia were UV-irradiated, and the following colonies with a nonparental color were found: w (one), p (three), o (one), +f (one), ms (supermagenta) (one), and m/+ (one). Crosses involving the m-2 mutant and the +f, ms, p, w, and y mutants indicated that the +f and ms mutants resulted from an insertional mutation and the others from a genic mutation. Sites of element insertion were (1) most likely in the pericentric regions to give the pink phenotype, (2) less likely in the y and p loci in the same chromosome arm and in the complex w locus, and (3) least likely in the o locus in one arm and m locus in the other arm. These observations were explained by proposing the transcentric transposition of a cryptic or a transactive element in the homologous chromosome with the color mutations during meiosis and to the UV-induced transposition of an element in sporidia

  16. Genetic diversity of the NE Atlantic sea urchin Strongylocentrotus droebachiensis unveils chaotic genetic patchiness possibly linked to local selective pressure.

    Science.gov (United States)

    Norderhaug, K M; Anglès d'Auriac, M B; Fagerli, C W; Gundersen, H; Christie, H; Dahl, K; Hobæk, A

    We compared the genetic differentiation in the green sea urchin Strongylocentrotus droebachiensis from discrete populations on the NE Atlantic coast. By using eight recently developed microsatellite markers, genetic structure was compared between populations from the Danish Strait in the south to the Barents Sea in the north (56-79°N). Urchins are spread by pelagic larvae and may be transported long distances by northwards-going ocean currents. Two main superimposed patterns were identified. The first showed a subtle but significant genetic differentiation from the southernmost to the northernmost of the studied populations and could be explained by an isolation by distance model. The second pattern included two coastal populations in mid-Norway (65°N), NH and NS, as well as the northernmost population of continental Norway (71°N) FV. They showed a high degree of differentiation from all other populations. The explanation to the second pattern is most likely chaotic genetic patchiness caused by introgression from another species, S. pallidus, into S. droebachiensis resulting from selective pressure. Ongoing sea urchin collapse and kelp forests recovery are observed in the area of NH, NS and FV populations. High gene flow between populations spanning more than 22° in latitude suggests a high risk of new grazing events to occur rapidly in the future if conditions for sea urchins are favourable. On the other hand, the possibility of hybridization in association with collapsing populations may be used as an early warning indicator for monitoring purposes.

  17. No evidence for a genetic blueprint: The case of the "complex" mammalian photoreceptor

    Directory of Open Access Journals (Sweden)

    G Kumaramanickavel

    2015-01-01

    Full Text Available Despite the intensity of the search for genes causing inherited retinal degenerations over the past 3 decades, of the approximately 200 disease genes identified to date, all appear to be ordinary housekeeping genes specifying proteins playing basic structural and functional roles in the mature photoreceptor cells. No genes or genetic elements have been identified which can be construed as having a specific morphogenic role, directing the development of the cytoarchitecture of any particular retinal cell. The evidence suggests that the cytoarchitecture of the retinal photoreceptors, although enormously complex, arises from the self-organization of the cells constituents without any regulation or direction from an external genetic blueprint.

  18. Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women

    DEFF Research Database (Denmark)

    Mehta, Divya; Tropf, Felix C; Gratten, Jacob

    2016-01-01

    IMPORTANCE: A recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due......), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014. CONCLUSIONS AND RELEVANCE: This study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported...

  19. Linking the planktonic and benthic habitat: genetic structure of the marine diatom Skeletonema marinoi.

    Science.gov (United States)

    Godhe, Anna; Härnström, Karolina

    2010-10-01

    Dormant life stages are important strategies for many aquatic organisms. The formation of resting stages will provide a refuge from unfavourable conditions in the water column, and their successive accumulation in the benthos will constitute a genetic reservoir for future planktonic populations. We have determined the genetic structure of a common bloom-forming diatom, Skeletonema marinoi, in the sediment and the plankton during spring, summer and autumn two subsequent years (2007-2009) in Gullmar Fjord on the Swedish west coast. Eight polymorphic microsatellite loci were used to assess the level of genetic differentiation and the respective gene diversity of the two different habitats. We also determined the degree of genetic differentiation between the seed banks inside the fjord and the open sea. The results indicate that Gullmar Fjord has one dominant endogenous population of S. marinoi, which is genetically differentiated from the open sea population. The fjord population is encountered in the plankton and in the sediment. Shifts from the dominant population can happen, and in our study, two genetically differentiated plankton populations, displaying reduced genetic diversity, occurred in September 2007 and 2008. Based on our results, we suggest that sill fjords maintain local long-lived and well-adapted protist populations, which continuously shift between the planktonic and benthic habitats. Intermittently, short-lived and mainly asexually reproducing populations can replace the dominant population in the water column, without influencing the genetic structure of the benthic seed bank. © 2010 Blackwell Publishing Ltd.

  20. A review of the evidence linking child stunting to economic outcomes

    Science.gov (United States)

    McGovern, Mark E; Krishna, Aditi; Aguayo, Victor M; Subramanian, SV

    2017-01-01

    Abstract Background To understand the full impact of stunting in childhood it is important to consider the long-run effects of undernutrition on the outcomes of adults who were affected in early life. Focusing on the costs of stunting provides a means of evaluating the economic case for investing in childhood nutrition. Methods We review the literature on the association between stunting and undernutrition in childhood and economic outcomes in adulthood. At the national level, we also evaluate the evidence linking stunting to economic growth. Throughout, we consider randomized controlled trials (RCTs), quasi-experimental approaches and observational studies. Results Long-run evaluations of two randomized nutrition interventions indicate substantial returns to the programmes (a 25% and 46% increase in wages for those affected as children, respectively). Cost-benefit analyses of nutrition interventions using calibrated return estimates report a median return of 17.9:1 per child. Assessing the wage premium associated with adult height, we find that a 1-cm increase in stature is associated with a 4% increase in wages for men and a 6% increase in wages for women in our preferred set of studies which attempt to address unobserved confounding and measurement error. In contrast, the evidence on the association between economic growth and stunting is mixed. Conclusions Countries with high rates of stunting, such as those in South Asia and sub-Saharan Africa, should scale up policies and programmes aiming to reduce child undernutrition as cost-beneficial investments that expand the economic opportunities of their children, better allowing them and their countries to reach their full potential. However, economic growth as a policy will only be effective at reducing the prevalence of stunting when increases in national income are directed at improving the diets of children, addressing gender inequalities and strengthening the status of women, improving sanitation and reducing

  1. A review of the evidence linking child stunting to economic outcomes.

    Science.gov (United States)

    McGovern, Mark E; Krishna, Aditi; Aguayo, Victor M; Subramanian, S V

    2017-08-01

    To understand the full impact of stunting in childhood it is important to consider the long-run effects of undernutrition on the outcomes of adults who were affected in early life. Focusing on the costs of stunting provides a means of evaluating the economic case for investing in childhood nutrition. We review the literature on the association between stunting and undernutrition in childhood and economic outcomes in adulthood. At the national level, we also evaluate the evidence linking stunting to economic growth. Throughout, we consider randomized controlled trials (RCTs), quasi-experimental approaches and observational studies. Long-run evaluations of two randomized nutrition interventions indicate substantial returns to the programmes (a 25% and 46% increase in wages for those affected as children, respectively). Cost-benefit analyses of nutrition interventions using calibrated return estimates report a median return of 17.9:1 per child. Assessing the wage premium associated with adult height, we find that a 1-cm increase in stature is associated with a 4% increase in wages for men and a 6% increase in wages for women in our preferred set of studies which attempt to address unobserved confounding and measurement error. In contrast, the evidence on the association between economic growth and stunting is mixed. Countries with high rates of stunting, such as those in South Asia and sub-Saharan Africa, should scale up policies and programmes aiming to reduce child undernutrition as cost-beneficial investments that expand the economic opportunities of their children, better allowing them and their countries to reach their full potential. However, economic growth as a policy will only be effective at reducing the prevalence of stunting when increases in national income are directed at improving the diets of children, addressing gender inequalities and strengthening the status of women, improving sanitation and reducing poverty and inequities. © The Author 2017

  2. 4-aminobutyrate aminotransferase (ABAT: genetic and pharmacological evidence for an involvement in gastro esophageal reflux disease.

    Directory of Open Access Journals (Sweden)

    Johan Jirholt

    Full Text Available Gastro-esophageal reflux disease (GERD is partly caused by genetic factors. The underlying susceptibility genes are currently unknown, with the exception of COL3A1. We used three independent GERD patient cohorts to identify GERD susceptibility genes. Thirty-six families, demonstrating dominant transmission of GERD were subjected to whole genome microsatellite genotyping and linkage analysis. Five linked regions were identified. Two families shared a linked region (LOD 3.9 and 2.0 on chromosome 16. We used two additional independent GERD patient cohorts, one consisting of 219 trios (affected child with parents and the other an adult GERD case control cohort consisting of 256 cases and 485 controls, to validate individual genes in the linked region through association analysis. Sixty six single nucleotide polymorphism (SNP markers distributed over the nine genes present in the linked region were genotyped in the independent GERD trio cohort. Transmission disequilibrium test analysis followed by multiple testing adjustments revealed a significant genetic association for one SNP located in an intron of the gene 4-aminobutyrate aminotransferase (ABAT (P(adj = 0.027. This association did not replicate in the adult case-control cohort, possibly due to the differences in ethnicity between the cohorts. Finally, using the selective ABAT inhibitor vigabatrin (γ-vinyl GABA in a dog study, we were able to show a reduction of transient lower esophageal sphincter relaxations (TLESRs by 57.3 ± 11.4 % (p = 0.007 and the reflux events from 3.1 ± 0.4 to 0.8 ± 0.4 (p = 0.007. Our results demonstrate the direct involvement of ABAT in pathways affecting lower esophageal sphincter (LES control and identifies ABAT as a genetic risk factor for GERD.

  3. 4-aminobutyrate aminotransferase (ABAT): genetic and pharmacological evidence for an involvement in gastro esophageal reflux disease.

    Science.gov (United States)

    Jirholt, Johan; Asling, Bengt; Hammond, Paul; Davidson, Geoffrey; Knutsson, Mikael; Walentinsson, Anna; Jensen, Jörgen M; Lehmann, Anders; Agreus, Lars; Lagerström-Fermer, Maria

    2011-04-28

    Gastro-esophageal reflux disease (GERD) is partly caused by genetic factors. The underlying susceptibility genes are currently unknown, with the exception of COL3A1. We used three independent GERD patient cohorts to identify GERD susceptibility genes. Thirty-six families, demonstrating dominant transmission of GERD were subjected to whole genome microsatellite genotyping and linkage analysis. Five linked regions were identified. Two families shared a linked region (LOD 3.9 and 2.0) on chromosome 16. We used two additional independent GERD patient cohorts, one consisting of 219 trios (affected child with parents) and the other an adult GERD case control cohort consisting of 256 cases and 485 controls, to validate individual genes in the linked region through association analysis. Sixty six single nucleotide polymorphism (SNP) markers distributed over the nine genes present in the linked region were genotyped in the independent GERD trio cohort. Transmission disequilibrium test analysis followed by multiple testing adjustments revealed a significant genetic association for one SNP located in an intron of the gene 4-aminobutyrate aminotransferase (ABAT) (P(adj) = 0.027). This association did not replicate in the adult case-control cohort, possibly due to the differences in ethnicity between the cohorts. Finally, using the selective ABAT inhibitor vigabatrin (γ-vinyl GABA) in a dog study, we were able to show a reduction of transient lower esophageal sphincter relaxations (TLESRs) by 57.3 ± 11.4 % (p = 0.007) and the reflux events from 3.1 ± 0.4 to 0.8 ± 0.4 (p = 0.007). Our results demonstrate the direct involvement of ABAT in pathways affecting lower esophageal sphincter (LES) control and identifies ABAT as a genetic risk factor for GERD.

  4. Behavioural and Psychiatric Phenotypes in Men and Boys with X-Linked Ichthyosis: Evidence from a Worldwide Online Survey.

    Directory of Open Access Journals (Sweden)

    Sohini Chatterjee

    Full Text Available X-linked ichthyosis (XLI is a rare dermatological condition arising from deficiency for the enzyme steroid sulfatase (STS. Preliminary evidence in boys with XLI, and animal model studies, suggests that individuals lacking STS are at increased risk of developmental disorders and associated traits. However, the behavioural profile of children with XLI is poorly-characterised, and the behavioural profile of adults with XLI has not yet been documented at all.Using an online survey, advertised worldwide, we collected detailed self- or parent-reported information on behaviour in adult (n = 58 and younger (≤18yrs, n = 24 males with XLI for comparison to data from their non-affected brothers, and age/gender-matched previously-published normative data. The survey comprised demographic and background information (including any prior clinical diagnoses and validated questionnaires assaying phenotypes of particular interest (Adult ADHD Self-Report Scale v1.1, Barrett Impulsiveness Scale-11, adult and adolescent Autism Quotient, Kessler Psychological Distress Scales, and Disruptive Behaviour Disorder Rating Scale.Individuals with XLI generally exhibited normal sensory function. Boys with XLI were at increased risk of developmental disorder, whilst adults with the condition were at increased risk of both developmental and mood disorders. Both adult and younger XLI groups scored significantly more highly than male general population norms on measures of inattention, impulsivity, autism-related traits, psychological distress and disruptive behavioural traits.These findings indicate that both adult and younger males with XLI exhibit personality profiles that are distinct from those of males within the general population, and suggest that individuals with XLI may be at heightened risk of psychopathology. The data are consistent with the notion that STS is important in neurodevelopment and ongoing brain function, and with previous work suggesting high rates of

  5. "Gum bug, leave my heart alone!"--epidemiologic and mechanistic evidence linking periodontal infections and atherosclerosis.

    Science.gov (United States)

    Kebschull, M; Demmer, R T; Papapanou, P N

    2010-09-01

    Evidence from epidemiologic studies suggests that periodontal infections are independently associated with subclinical and clinical atherosclerotic vascular disease. Although the strength of the reported associations is modest, the consistency of the data across diverse populations and a variety of exposure and outcome variables suggests that the findings are not spurious or attributable only to the effects of confounders. Analysis of limited data from interventional studies suggests that periodontal treatment generally results in favorable effects on subclinical markers of atherosclerosis, although such analysis also indicates considerable heterogeneity in responses. Experimental mechanistic in vitro and in vivo studies have established the plausibility of a link between periodontal infections and atherogenesis, and have identified biological pathways by which these effects may be mediated. However, the utilized models are mostly mono-infections of host cells by a limited number of 'model' periodontal pathogens, and therefore may not adequately portray human periodontitis as a polymicrobial, biofilm-mediated disease. Future research must identify in vivo pathways in humans that may (i) lead to periodontitis-induced atherogenesis, or (ii) result in treatment-induced reduction of atherosclerosis risk. Data from these studies will be essential for determining whether periodontal interventions have a role in the primary or secondary prevention of atherosclerosis.

  6. Novel mitochondrial extensions provide evidence for a link between microtubule-directed movement and mitochondrial fission

    International Nuclear Information System (INIS)

    Bowes, Timothy; Gupta, Radhey S.

    2008-01-01

    Mitochondrial dynamics play an important role in a large number of cellular processes. Previously, we reported that treatment of mammalian cells with the cysteine-alkylators, N-ethylmaleimide and ethacrynic acid, induced rapid mitochondrial fusion forming a large reticulum approximately 30 min after treatment. Here, we further investigated this phenomenon using a number of techniques including live-cell confocal microscopy. In live cells, drug-induced fusion coincided with a cessation of fast mitochondrial movement which was dependent on microtubules. During this loss of movement, thin mitochondrial tubules extending from mitochondria were also observed, which we refer to as 'mitochondrial extensions'. The formation of these mitochondrial extensions, which were not observed in untreated cells, depended on microtubules and was abolished by pretreatment with nocodazole. In this study, we provide evidence that these extensions result from of a block in mitochondrial fission combined with continued application of motile force by microtubule-dependent motor complexes. Our observations strongly suggest the existence of a link between microtubule-based mitochondrial trafficking and mitochondrial fission

  7. Common species link global ecosystems to climate change: dynamical evidence in the planktonic fossil record.

    Science.gov (United States)

    Hannisdal, Bjarte; Haaga, Kristian Agasøster; Reitan, Trond; Diego, David; Liow, Lee Hsiang

    2017-07-12

    Common species shape the world around us, and changes in their commonness signify large-scale shifts in ecosystem structure and function. However, our understanding of long-term ecosystem response to environmental forcing in the deep past is centred on species richness, neglecting the disproportional impact of common species. Here, we use common and widespread species of planktonic foraminifera in deep-sea sediments to track changes in observed global occupancy (proportion of sampled sites at which a species is present and observed) through the turbulent climatic history of the last 65 Myr. Our approach is sensitive to relative changes in global abundance of the species set and robust to factors that bias richness estimators. Using three independent methods for detecting causality, we show that the observed global occupancy of planktonic foraminifera has been dynamically coupled to past oceanographic changes captured in deep-ocean temperature reconstructions. The causal inference does not imply a direct mechanism, but is consistent with an indirect, time-delayed causal linkage. Given the strong quantitative evidence that a dynamical coupling exists, we hypothesize that mixotrophy (symbiont hosting) may be an ecological factor linking the global abundance of planktonic foraminifera to long-term climate changes via the relative extent of oligotrophic oceans. © 2017 The Authors.

  8. A review of the evidence linking adult attachment theory and chronic pain: presenting a conceptual model.

    Science.gov (United States)

    Meredith, Pamela; Ownsworth, Tamara; Strong, Jenny

    2008-03-01

    It is now well established that pain is a multidimensional phenomenon, affected by a gamut of psychosocial and biological variables. According to diathesis-stress models of chronic pain, some individuals are more vulnerable to developing disability following acute pain because they possess particular psychosocial vulnerabilities which interact with physical pathology to impact negatively upon outcome. Attachment theory, a theory of social and personality development, has been proposed as a comprehensive developmental model of pain, implicating individual adult attachment pattern in the ontogenesis and maintenance of chronic pain. The present paper reviews and critically appraises studies which link adult attachment theory with chronic pain. Together, these papers offer support for the role of insecure attachment as a diathesis (or vulnerability) for problematic adjustment to pain. The Attachment-Diathesis Model of Chronic Pain developed from this body of literature, combines adult attachment theory with the diathesis-stress approach to chronic pain. The evidence presented in this review, and the associated model, advances our understanding of the developmental origins of chronic pain conditions, with potential application in guiding early pain intervention and prevention efforts, as well as tailoring interventions to suit specific patient needs.

  9. Autosomal STRs provide genetic evidence for the hypothesis that Tai people originate from southern China.

    Directory of Open Access Journals (Sweden)

    Hao Sun

    Full Text Available Tai people are widely distributed in Thailand, Laos and southwestern China and are a large population of Southeast Asia. Although most anthropologists and historians agree that modern Tai people are from southwestern China and northern Thailand, the place from which they historically migrated remains controversial. Three popular hypotheses have been proposed: northern origin hypothesis, southern origin hypothesis or an indigenous origin. We compared the genetic relationships between the Tai in China and their "siblings" to test different hypotheses by analyzing 10 autosomal microsatellites. The genetic data of 916 samples from 19 populations were analyzed in this survey. The autosomal STR data from 15 of the 19 populations came from our previous study (Lin et al., 2010. 194 samples from four additional populations were genotyped in this study: Han (Yunnan, Dai (Dehong, Dai (Yuxi and Mongolian. The results of genetic distance comparisons, genetic structure analyses and admixture analyses all indicate that populations from northern origin hypothesis have large genetic distances and are clearly differentiated from the Tai. The simulation-based ABC analysis also indicates this. The posterior probability of the northern origin hypothesis is just 0.04 [95%CI: (0.01-0.06]. Conversely, genetic relationships were very close between the Tai and populations from southern origin or an indigenous origin hypothesis. Simulation-based ABC analyses were also used to distinguish the southern origin hypothesis from the indigenous origin hypothesis. The results indicate that the posterior probability of the southern origin hypothesis [0.640, 95%CI: (0.524-0.757] is greater than that of the indigenous origin hypothesis [0.324, 95%CI: (0.211-0.438]. Therefore, we propose that the genetic evidence does not support the hypothesis of northern origin. Our genetic data indicate that the southern origin hypothesis has higher probability than the other two hypotheses

  10. Genetic structure and evidence of putative Darwinian diversifying selection in the Potato yellow vein virus (PYVV

    Directory of Open Access Journals (Sweden)

    Giovanni Chaves-Bedoya

    2013-08-01

    Full Text Available The population structure and genetic variation of Potato yellow vein virus (PYVV were estimated by analysis of the nucleotide and deduced amino acid sequence of the coat protein of 69 isolates, reported in GenBank, from Solanum tuberosum (ST and Solanum phureja (SP hosts from different regions; predominantly Cundinamarca, Antioquia and Nariño, located in central and southwestern Colombia. Bioinformatics analysis revealed that despite the wide geographic distribution of different hosts and different collecting years, PYVV maintains a genetic similarity between 97.1 to 100.0%, indicating high spatial and temporal genetic stability of the major coat protein. No recombination events were found, but evidence was seen for the first time that this protein could be undergoing Darwinian diversifying selection

  11. Evidence for Absolute Moral Opposition to Genetically Modified Food in the United States.

    Science.gov (United States)

    Scott, Sydney E; Inbar, Yoel; Rozin, Paul

    2016-05-01

    Public opposition to genetic modification (GM) technology in the food domain is widespread (Frewer et al., 2013). In a survey of U.S. residents representative of the population on gender, age, and income, 64% opposed GM, and 71% of GM opponents (45% of the entire sample) were "absolutely" opposed-that is, they agreed that GM should be prohibited no matter the risks and benefits. "Absolutist" opponents were more disgust sensitive in general and more disgusted by the consumption of genetically modified food than were non-absolutist opponents or supporters. Furthermore, disgust predicted support for legal restrictions on genetically modified foods, even after controlling for explicit risk-benefit assessments. This research suggests that many opponents are evidence insensitive and will not be influenced by arguments about risks and benefits. © The Author(s) 2016.

  12. Gene × Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models

    Directory of Open Access Journals (Sweden)

    Paula Moran

    2016-01-01

    Full Text Available The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia.

  13. Gene × Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models.

    Science.gov (United States)

    Moran, Paula; Stokes, Jennifer; Marr, Julia; Bock, Gavin; Desbonnet, Lieve; Waddington, John; O'Tuathaigh, Colm

    2016-01-01

    The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia.

  14. Gene × Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models

    Science.gov (United States)

    Marr, Julia; Bock, Gavin; Desbonnet, Lieve; Waddington, John

    2016-01-01

    The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia. PMID:27725886

  15. Not the time or the place: the missing spatio-temporal link in publicly available genetic data.

    Science.gov (United States)

    Pope, Lisa C; Liggins, Libby; Keyse, Jude; Carvalho, Silvia B; Riginos, Cynthia

    2015-08-01

    Genetic data are being generated at unprecedented rates. Policies of many journals, institutions and funding bodies aim to ensure that these data are publicly archived so that published results are reproducible. Additionally, publicly archived data can be 'repurposed' to address new questions in the future. In 2011, along with other leading journals in ecology and evolution, Molecular Ecology implemented mandatory public data archiving (the Joint Data Archiving Policy). To evaluate the effect of this policy, we assessed the genetic, spatial and temporal data archived for 419 data sets from 289 articles in Molecular Ecology from 2009 to 2013. We then determined whether archived data could be used to reproduce analyses as presented in the manuscript. We found that the journal's mandatory archiving policy has had a substantial positive impact, increasing genetic data archiving from 49 (pre-2011) to 98% (2011-present). However, 31% of publicly archived genetic data sets could not be recreated based on information supplied in either the manuscript or public archives, with incomplete data or inconsistent codes linking genetic data and metadata as the primary reasons. While the majority of articles did provide some geographic information, 40% did not provide this information as geographic coordinates. Furthermore, a large proportion of articles did not contain any information regarding date of sampling (40%). Although the inclusion of spatio-temporal data does require an increase in effort, we argue that the enduring value of publicly accessible genetic data to the molecular ecology field is greatly compromised when such metadata are not archived alongside genetic data. © 2015 John Wiley & Sons Ltd.

  16. Defining the genetic connection linking amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD).

    Science.gov (United States)

    Lattante, Serena; Ciura, Sorana; Rouleau, Guy A; Kabashi, Edor

    2015-05-01

    Several genetic causes have been recently described for neurological diseases, increasing our knowledge of the common pathological mechanisms involved in these disorders. Mutation analysis has shown common causative factors for two major neurodegenerative disorders, ALS and FTD. Shared pathological and genetic markers as well as common neurological signs between these diseases have given rise to the notion of an ALS/FTD spectrum. This overlap among genetic factors causing ALS/FTD and the coincidence of mutated alleles (including causative, risk and modifier variants) have given rise to the notion of an oligogenic model of disease. In this review we summarize major advances in the elucidation of novel genetic factors in these diseases which have led to a better understanding of the common pathogenic factors leading to neurodegeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Genetic studies and a search for molecular markers that are linked ...

    African Journals Online (AJOL)

    SERVER

    Instead, linkage analysis resulted in the construction of a molecular marker linkage map consisting of 45 ..... This limits the application of this marker type, particularly in ... primer design when one uses RAPDs. .... Concepts of Genetics. Fourth.

  18. Evidence for genetic differentiation at the microgeographic scale in Phlebotomus papatasi populations from Sudan

    Directory of Open Access Journals (Sweden)

    Khalid Noteila M

    2012-11-01

    Full Text Available Abstract Background Cutaneous Leishmaniasis (CL is endemic in Sudan. It is caused by Leishmania major parasites and transmitted by Phlebotomus papatasi sandflies. Recently, uncommon clinical manifestations of CL have been reported. Moreover, L. donovani parasites that cause Visceral Leishmaniasis (VL have been isolated from CL lesions of some patients who contracted the disease in Khartoum State, Central Sudan with no history of travelling to VL endemic sites on south-eastern Sudan. Because different clinical manifestations and the parasite behaviour could be related to genetic differentiation, or even sub-structuring within sandfly vector populations, a population genetic study was conducted on P. papatasi populations collected from different localities in Khartoum State known for their uncommon CL cases and characterized by contrasting environmental conditions. Methods A set of seven microsatellite loci was used to investigate the population structure of P. papatasi samples collected from different localities in Khartoum State, Central Sudan. Populations from Kassala State, Eastern Sudan and Egypt were also included in the analyses as outgroups. The level of genetic diversity and genetic differentiation among natural populations of P. papatasi was determined using FST statistics and Bayesian assignments. Results Genetic analyses revealed significant genetic differentiation (FST between the Sudanese and the Egyptian populations. Within the Sudanese P. papatasi populations, one population from Gerif West, Khartoum State, exhibited significant genetic differentiation from all other populations including those collected as near as 22 km. Conclusion The significant genetic differentiation of Gerif West P. papatasi population from other Sudanese populations may have important implication for the epidemiology of leishmaniasis in Khartoum State and needs to be further investigated. Primarily, it could be linked to the unique location of Gerif West

  19. Genetic evidence of population structuring in the neotropical freshwater fish Brycon hilarii (Valenciennes, 1850

    Directory of Open Access Journals (Sweden)

    A Sanches

    Full Text Available Brycon hilarii is a migratory fish widely distributed throughout the Paraguay River Basin. It is appreciated in sport fishing and for its superior meat quality. It is also the main species for tourist attraction in the Bonito region (State of Mato Grosso do Sul, Brazil. Considering the lack of information on the genetic structure of the fish of this species, the aim of the present study was to detect the genetic variability of Brycon hilarii through RAPD markers. A total of eighty specimens collected in different seasons at four sites of the Miranda River sub-basin (Paraguay River Basin, Brazil were used for analysis. The results of genetic similarity, Shannon diversity, and AMOVA revealed differences between the sampling sites. Through AMOVA, differences between populations were more evident among the animals collected during the non-reproductive season, corresponding to a time of less movement of these fish. A population structuring model in which B. hilarii appears organized into genetically differentiated reproductive units that coexist and co-migrate through the studied system was suggested, contrasting the currently accepted idea that freshwater migratory fish form large panmictic populations in a determined hydrographic system. Despite the lack of a complete picture regarding the distribution of B. hilarii in the studied region, this initial idea on its population genetic structure could be an important contribution to providing aid for management and conservation programs of these fish.

  20. The evidence base regarding the experiences of and attitudes to preimplantation genetic diagnosis in prospective parents.

    Science.gov (United States)

    Cunningham, Jenny; Goldsmith, Lesley; Skirton, Heather

    2015-02-01

    Preimplantation genetic diagnosis was developed as an alternative to prenatal diagnosis for couples with a family history of genetic disease. After in vitro fertilization, the embryos can be analysed to ensure that only healthy embryos are transferred to the uterus. Past studies have suggested that couples who wish to avoid having a child with an inherited genetic condition look favourably on preimplantation genetic diagnosis as it prevents the need for termination of pregnancy following prenatal diagnosis of an affected fetus. However, it is important to understand the experiences of couples who have used or consider using this technique. To ascertain the current evidence base on this topic, we conducted a mixed methods systematic review. Four databases were searched for relevant peer-reviewed papers published between 2000 and 2013. Of 453 papers, nine satisfied the inclusion criteria and were assessed for quality. Results of nine papers were analysed and synthesised using a narrative approach. Three main themes emerged: (1) motivating factors; (2) emotional labour; (3) choices and uncertainty. The review has identified an emotional and difficult journey for couples pursuing preimplantation genetic diagnosis. While use of the technique gives hope to families who wish to prevent transmission of a genetic disease this is not without hard decision-making and periods of uncertainty. Lack of information was perceived as a barrier to access this reproductive option. Recommendations include: training and education in genetics for midwives who are the first point of contact for pregnant women; clinics to use a decision-making tool to emphasise the uncertainty involved in PGD and improved communication and psychological support to couples. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Evidence for shared genetic risk between ADHD symptoms and reduced mathematics ability: a twin study.

    Science.gov (United States)

    Greven, Corina U; Kovas, Yulia; Willcutt, Erik G; Petrill, Stephen A; Plomin, Robert

    2014-01-01

    Attention-deficit/hyperactivity disorder (ADHD) symptoms and mathematics ability are associated, but little is known about the genetic and environmental influences underlying this association. Data came from more than 6,000 twelve-year-old twin pairs from the UK population-representative Twins Early Development Study. Parents rated each twin's behaviour using a DSM-IV-based 18-item questionnaire of inattentive and hyperactive-impulsive ADHD symptoms. Mathematics tests based on the UK National Curriculum were completed by each twin. The twins also completed standardised tests of reading and general cognitive ability. Multivariate twin model fitting was applied. Inattentive and hyperactive-impulsive ADHD symptoms were highly heritable (67% and 73% respectively). Mathematics ability was moderately heritable (46%). Mathematics ability and inattentiveness showed a significantly greater phenotypic correlation (r(p) = -.26) and genetic correlation (r(A) = -.41) than mathematics ability and hyperactivity-impulsivity (r(p) = -.18; r(A) = -.22). The genetic correlation between inattentiveness and mathematics ability was largely independent from hyperactivity-impulsivity, and was only partially accounted for by genetic influences related to reading and general cognitive ability. Results revealed the novel finding that mathematics ability shows significantly stronger phenotypic and genetic associations with inattentiveness than with hyperactivity-impulsivity. Genetic associations between inattentiveness and mathematics ability could only partially be accounted for by hyperactivity-impulsivity, reading and general cognitive ability. Results suggest that mathematics ability is associated with ADHD symptoms largely because it shares genetic risk factors with inattentiveness, and provide further evidence for considering inattentiveness and hyperactivity-impulsivity separately. DNA markers for ADHD symptoms (especially inattentiveness) may also be candidate risk factors for

  2. Harbor porpoise Phocoena phocoena strandings on the Dutch coast: No genetic structure, but evidence of inbreeding

    Science.gov (United States)

    van der Plas-Duivesteijn, Suzanne J.; Smit, Femmie J. L.; van Alphen, Jacques J. M.; Kraaijeveld, Ken

    2015-03-01

    Conservation management in the North Sea is often motivated by the population size of marine mammals, like harbor porpoises Phocoena phocoena. In the Dutch part of the North Sea, sighting and stranding data are used to estimate population sizes, but these data give little insight into genetic structuring of the population. In this study we investigated genetic structure among animals stranded at different locations and times of year. We also tested whether there is a link between stranding and necropsy data, and genetic diversity. We made use of both mitochondrial (mtDNA) and microsatellite DNA analysis of samples from dead stranded porpoises along the Dutch coast during 2007. mtDNA analysis showed 6 variable positions in the control region, defining 3 different haplotypes. mtDNA haplotypes were not randomly distributed along the Dutch coastline. However, microsatellite analysis showed that these mtDNA haplotypes did not represent separate groups on a nuclear level. Furthermore, microsatellite analysis revealed no genotypic differences between seasons, locations or genders. The results of this study indicate that the Dutch population is panmictic. In contrast, heterozygosity levels were low, indicating some level of inbreeding in this population. However, this was not corroborated by other indices of inbreeding. This research provided insight into genetic structuring of stranded porpoises in 2007, but data from multiple years should be included to be able to help estimate population sizes.

  3. Is rumination after bereavement linked with loss avoidance? Evidence from eye-tracking.

    Directory of Open Access Journals (Sweden)

    Maarten C Eisma

    Full Text Available Rumination is a risk factor in adjustment to bereavement. It is associated with and predicts psychopathology after loss. Yet, the function of rumination in bereavement remains unclear. In the past, researchers often assumed rumination to be a maladaptive confrontation process. However, based on cognitive avoidance theories of worry in generalised anxiety disorder (GAD and rumination after post-traumatic stress disorder (PTSD, others have suggested that rumination may serve to avoid painful aspects of the loss, thereby contributing to complicated grief. To examine if rumination is linked with loss avoidance, an eye-tracking study was conducted with 54 bereaved individuals (27 high and 27 low ruminators. On 24 trials, participants looked for 10 seconds at a picture of the deceased and a picture of a stranger, randomly combined with negative, neutral or loss-related words. High ruminators were expected to show initial vigilance followed by subsequent disengagement for loss stimuli (i.e., picture deceased with a loss word in the first 1500 ms. Additionally, we expected high ruminators to avoid these loss stimuli and to show attentional preference for non-loss-related negative stimuli (i.e., picture stranger with a negative word on longer exposure durations (1500-10000 ms. Contrary to expectations, we found no evidence for an effect of rumination on vigilance and disengagement of loss stimuli in the first 1500 ms. However, in the 1500-10000 ms interval, high ruminators showed shorter gaze times for loss stimuli and longer gaze times for negative (and neutral non-loss-related stimuli, even when controlling for depression and complicated grief symptom levels. Effects of rumination on average fixation times mirrored these findings. This suggests that rumination and loss avoidance are closely associated. A potential clinical implication is that rumination and grief complications after bereavement may be reduced through the use of exposure and acceptance

  4. Eco-Health Linkages: evidence base and socio-economic considerations for linking ecosystem goods and services to human health

    Science.gov (United States)

    Ecosystem goods and services (EGS) are thought to play a role in protecting human health, but the empirical evidence directly linking EGS to human health outcomes is limited, and our ability to detect Eco-Health linkages is confounded by socio-economic factors. These limitations ...

  5. Meta-Ethnography and Systematic Reviews--Linked to the Evidence Movement and Caught in a Dilemma

    Science.gov (United States)

    Borgnakke, Karen

    2017-01-01

    Meta-ethnography and systematic review of qualitative research are needed but also challenged by the link to the evidence movement's models and PISA-traditions for measuring learning effects. For reflections on the perspective for meta-ethnography it means to reconstruct the methodological argument almost divided in a "Before and After…

  6. Linking individual migratory behaviour of Atlantic salmon to their genetic origin

    DEFF Research Database (Denmark)

    Jepsen, Niels; Eg Nielsen, Einar; Deacon, M.

    2005-01-01

    (Salmo salar) in a Danish lowland river. The river has a small population of native salmon, but salmon juveniles from Irish, Scottish and Swedish populations have been stocked and return as adults. A total of 39 salmon were caught by electrofishing and tagged by surgical implantation. A tissue sample......Many stocks of fish consist of mixtures of individuals originating from different populations. This is particularly true for many salmon and trout stocks, where fish of different genetic background are being found in the same rivers and/or lakes due to stocking activities or straying caused...... by increased aquaculture activities. The interpretation of results from studies of survival and behaviour of fish from such “mixed stocks” require information of the genetic background of individual fish. We used genetic analysis combined with radiotelemetry to study upstream migration of Atlantic salmon...

  7. A UV-Induced Genetic Network Links the RSC Complex to Nucleotide Excision Repair and Shows Dose-Dependent Rewiring

    Directory of Open Access Journals (Sweden)

    Rohith Srivas

    2013-12-01

    Full Text Available Efficient repair of UV-induced DNA damage requires the precise coordination of nucleotide excision repair (NER with numerous other biological processes. To map this crosstalk, we generated a differential genetic interaction map centered on quantitative growth measurements of >45,000 double mutants before and after different doses of UV radiation. Integration of genetic data with physical interaction networks identified a global map of 89 UV-induced functional interactions among 62 protein complexes, including a number of links between the RSC complex and several NER factors. We show that RSC is recruited to both silenced and transcribed loci following UV damage where it facilitates efficient repair by promoting nucleosome remodeling. Finally, a comparison of the response to high versus low levels of UV shows that the degree of genetic rewiring correlates with dose of UV and reveals a network of dose-specific interactions. This study makes available a large resource of UV-induced interactions, and it illustrates a methodology for identifying dose-dependent interactions based on quantitative shifts in genetic networks.

  8. Matrilineal Heritage in Southern Iberia Reveals Deep Genetic Links between Continents.

    Science.gov (United States)

    Hernández, Candela L; Calderón, Rosario

    2017-03-01

    Within the Mediterranean Basin, the Iberian Peninsula has been a focus of attraction for several cultures and civilizations from its prehistory and history, making it a target territory for studying human migration patterns and peopling processes using a wide and heterogeneous spectrum of genomic markers. While its Cantabrian fringe represents the most regularly analysed area in terms of its mitochondrial diversity, the absence of monographic surveys on the maternal genetic composition of southern Iberians (i.e., Andalusians) is striking. In this work, we present a comprehensive view of various aspects of the human maternal heritage of the autochthonous Andalusian population regarding specific mitochondrial haplogroups considered key candidates to determine the genetic relationship between Europe and Africa. Data reveal that southern Iberian populations do not have genetically homogeneous mitochondrial DNA profiles, and their observed genetic affinity with north-western African populations represents strong signals of old, sustained and bidirectional human movements between the northern and southern shores of the western Mediterranean. Thorough analyses of African mtDNA haplogroups have shown that the most relevant African contribution within Iberian Peninsula could be explained as a consequence of prehistoric events. The subsequent historic episodes helped to strengthen the ties between both shores. In southern Iberia, mitochondrial and other genetic markers show that the Strait of Gibraltar together with its surrounding maritime areas should be considered a bridge between continents. More broadly, the Mediterranean Sea has acted as a transport surface, that is, as a permeable barrier to human migrations from prehistoric and historic times. In conclusion, this research contributes to our knowledge of processes that have shaped the recent human genetic history in the Mediterranean and, more specifically, of the population dynamics that the inhabitants of southern

  9. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

    DEFF Research Database (Denmark)

    Horikoshi, Momoko; Yaghootkar, Hanieh; Mook-Kanamori, Dennis O

    2013-01-01

    -wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between...... diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome......Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2...

  10. Neighborhood alcohol outlet density and genetic influences on alcohol use: evidence for gene-environment interaction.

    Science.gov (United States)

    Slutske, Wendy S; Deutsch, Arielle R; Piasecki, Thomas M

    2018-05-07

    Genetic influences on alcohol involvement are likely to vary as a function of the 'alcohol environment,' given that exposure to alcohol is a necessary precondition for genetic risk to be expressed. However, few gene-environment interaction studies of alcohol involvement have focused on characteristics of the community-level alcohol environment. The goal of this study was to examine whether living in a community with more alcohol outlets would facilitate the expression of the genetic propensity to drink in a genetically-informed national survey of United States young adults. The participants were 2434 18-26-year-old twin, full-, and half-sibling pairs from Wave III of the National Longitudinal Study of Adolescent to Adult Health. Participants completed in-home interviews in which alcohol use was assessed. Alcohol outlet densities were extracted from state-level liquor license databases aggregated at the census tract level to derive the density of outlets. There was evidence that the estimates of genetic and environmental influences on alcohol use varied as a function of the density of alcohol outlets in the community. For example, the heritability of the frequency of alcohol use for those residing in a neighborhood with ten or more outlets was 74% (95% confidence limits = 55-94%), compared with 16% (95% confidence limits = 0-34%) for those in a neighborhood with zero outlets. This moderating effect of alcohol outlet density was not explained by the state of residence, population density, or neighborhood sociodemographic characteristics. The results suggest that living in a neighborhood with many alcohol outlets may be especially high-risk for those individuals who are genetically predisposed to frequently drink.

  11. Comparative population genetics of two invading ticks: Evidence of the ecological mechanisms underlying tick range expansions.

    Science.gov (United States)

    Nadolny, Robyn; Gaff, Holly; Carlsson, Jens; Gauthier, David

    2015-10-01

    Two species of ixodid tick, Ixodes affinis Neumann and Amblyomma maculatum Koch, are simultaneously expanding their ranges throughout the mid-Atlantic region of the US. Although we have some understanding of the ecology and life history of these species, the ecological mechanisms governing where and how new populations establish and persist are unclear. To assess population connectivity and ancestry, we sequenced a fragment of the 16S mitochondrial rRNA gene from a representative sample of individuals of both species from populations throughout the eastern US. We found that despite overlapping host preferences throughout ontogeny, each species exhibited very different genetic and geographic patterns of population establishment and connectivity. I. affinis was of two distinct mitochondrial clades, with a clear geographic break separating northern and southern populations. Both I. affinis populations showed evidence of recent expansion, although the southern population was more genetically diverse, indicating a longer history of establishment. A. maculatum exhibited diverse haplotypes that showed no significant relationship with geographic patterns and little apparent connectivity between sites. Heteroplasmy was also observed in the 16S mitochondrial rRNA gene in 3.5% of A. maculatum individuals. Genetic evidence suggests that these species rely on different key life stages to successfully disperse into novel environments, and that host vagility, habitat stability and habitat connectivity all play critical roles in the establishment of new tick populations. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Three Molecular Markers Show No Evidence of Population Genetic Structure in the Gouldian Finch (Erythrura gouldiae.

    Directory of Open Access Journals (Sweden)

    Peri E Bolton

    Full Text Available Assessment of genetic diversity and connectivity between regions can inform conservation managers about risk of inbreeding, potential for adaptation and where population boundaries lie. The Gouldian finch (Erythrura gouldiae is a threatened species in northern Australia, occupying the savannah woodlands of the biogeographically complex monsoon tropics. We present the most comprehensive population genetic analysis of diversity and structure the Gouldian finch using 16 microsatellite markers, mitochondrial control region and 3,389 SNPs from genotyping-by-sequencing. Mitochondrial diversity is compared across three related, co-distributed finches with different conservation threat-statuses. There was no evidence of genetic differentiation across the western part of the range in any of the molecular markers, and haplotype diversity but not richness was lower than a common co-distributed species. Individuals within the panmictic population in the west may be highly dispersive within this wide area, and we urge caution when interpreting anecdotal observations of changes to the distribution and/or flock sizes of Gouldian finch populations as evidence of overall changes to the population size of this species.

  13. Evidence suggesting a genetic contribution to kidney stone in northeastern Thai population.

    Science.gov (United States)

    Sritippayawan, Suchai; Borvornpadungkitti, Sombat; Paemanee, Atchara; Predanon, Chagkrapan; Susaengrat, Wattanachai; Chuawattana, Duangporn; Sawasdee, Nunghathai; Nakjang, Sirintra; Pongtepaditep, Suttikarn; Nettuwakul, Choochai; Rungroj, Nanyawan; Vasuvattakul, Somkiat; Malasit, Prida; Yenchitsomanus, Pa-thai

    2009-06-01

    Genetic factor may play a role in the pathogenesis of kidney stone that is found in the northeastern (NE) Thai population. Herein, we report initial evidence suggesting genetic contribution to the disease in this population. We examined 1,034 subjects including 135 patients with kidney stone, 551 family members, and 348 villagers by radiography of kidney-ureter-bladder (KUB) and other methods, and also analyzed stones removed by surgical operations. One hundred and sixteen of 551 family members (21.05%) and 23 of the 348 villagers (6.61%) were affected with kidney stone. The relative risk (lambda(R)) of the disease among family members was 3.18. Calcium stones (whewellite, dahllite, and weddellite) were observed in about 88% of stones analyzed. Our data indicate familial aggregation of kidney stone in this population supporting that genetic factor should play some role in its pathogenesis. Genetic and genomic studies will be conducted to identify the genes associated with the disease.

  14. Genetic studies and a search for molecular markers that are linked ...

    African Journals Online (AJOL)

    Molecular markers that are linked to witchweed resistance can expedite the development of resistant cultivars through adoption of appropriate markerassisted selection (MAS) strategies. The objectives of this investigation were to study the inheritance or low germination stimulant (lgs) production in cultivar SAR 29 and to ...

  15. Immunopathophysiology of inflammatory bowel disease: how genetics link barrier dysfunction and innate immunity to inflammation.

    Science.gov (United States)

    Mehta, Minesh; Ahmed, Shifat; Dryden, Gerald

    2017-08-01

    Inflammatory bowel diseases (IBD) comprise a distinct set of clinical symptoms resulting from chronic or relapsing immune activation and corresponding inflammation within the gastrointestinal (GI) tract. Diverse genetic mutations, encoding important aspects of innate immunity and mucosal homeostasis, combine with environmental triggers to create inappropriate, sustained inflammatory responses. Recently, significant advances have been made in understanding the interplay of the intestinal epithelium, mucosal immune system, and commensal bacteria as a foundation of the pathogenesis of inflammatory bowel disease. Complex interactions between specialized intestinal epithelial cells and mucosal immune cells determine different outcomes based on the environmental input: the development of tolerance in the presence of commensal bacterial or the promotion of inflammation upon recognition of pathogenic organisms. This article reviews key genetic abnormalities involved in inflammatory and homeostatic pathways that enhance susceptibility to immune dysregulation and combine with environmental triggers to trigger the development of chronic intestinal inflammation and IBD.

  16. Exploring the genetics underlying autoimmune diseases with network analysis and link prediction

    KAUST Repository

    Alanis Lobato, Gregorio; Cannistraci, Carlo; Ravasi, Timothy

    2014-01-01

    Ever since the first Genome Wide Association Study (GWAS) was carried out we have seen an important number of discoveries of biological and clinical relevance. However, there are some scientists that consider that these research outcomes and their utility are far from what was expected from this experimental design. We instead believe that the thousands of genetic variants associated with complex disorders by means of GWASs are an extremely valuable source of information that needs to be mined in a different way. Based on this philosophy, we followed a holistic perspective to analyze GWAS data and explored the structural properties of the network representation of one of these datasets with the aim to advance our understanding of the genetic intricacies underlying autoimmune human diseases. The simplicity, computational efficiency and precision of the tools proposed in this paper represent a new means to address GWAS data and contribute to the better exploitation of these rich sources of information. © 2014 IEEE.

  17. Exploring the genetics underlying autoimmune diseases with network analysis and link prediction

    KAUST Repository

    Alanis Lobato, Gregorio

    2014-02-01

    Ever since the first Genome Wide Association Study (GWAS) was carried out we have seen an important number of discoveries of biological and clinical relevance. However, there are some scientists that consider that these research outcomes and their utility are far from what was expected from this experimental design. We instead believe that the thousands of genetic variants associated with complex disorders by means of GWASs are an extremely valuable source of information that needs to be mined in a different way. Based on this philosophy, we followed a holistic perspective to analyze GWAS data and explored the structural properties of the network representation of one of these datasets with the aim to advance our understanding of the genetic intricacies underlying autoimmune human diseases. The simplicity, computational efficiency and precision of the tools proposed in this paper represent a new means to address GWAS data and contribute to the better exploitation of these rich sources of information. © 2014 IEEE.

  18. Genetic Variants of Angiotensin-Converting Enzyme Are Linked to Autism: A Case-Control Study.

    Science.gov (United States)

    Firouzabadi, Negar; Ghazanfari, Nima; Alavi Shoushtari, Ali; Erfani, Nasrallah; Fathi, Farshid; Bazrafkan, Mozhdeh; Bahramali, Ehsan

    2016-01-01

    Autism is a disease of complex nature with a significant genetic component. The importance of renin-angiotensin system (RAS) elements in cognition and behavior besides the interaction of angiotensin II (Ang II), the main product of angiotensin-converting enzyme (ACE), with neurotransmitters in CNS, especially dopamine, proposes the involvement of RAS in autism. Since the genetic architecture of autism has remained elusive, here we postulated that genetic variations in RAS are associated with autism. Considering the relation between the three polymorphisms of ACE (I/D, rs4343 and rs4291) with the level of ACE activity, we have investigated this association with autism, in a case-control study. Genotype and allele frequencies of polymorphisms were determined in DNAs extracted from venous blood of 120 autistic patients and their age and sex-matched healthy controls, using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods. There were strong associations between both DD genotype of ACE I/D and the D allele, with autism (P = 0.006, OR = 2.9, 95% CI = 1.64-5.13 and P = 0.006, OR = 2.18, 95% CI = 1.37-3.48 respectively). Furthermore, a significant association between the G allele of rs4343 and autism was observed (P = 0.006, OR = 1.84, 95%CI = 1.26-2.67). Moreover, haplotype analysis revealed an association between DTG haplotype and autism (P = 0.008). Our data suggests the involvement of RAS genetic diversity in increasing the risk of autism.

  19. Genetic Variants of Angiotensin-Converting Enzyme Are Linked to Autism: A Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Negar Firouzabadi

    Full Text Available Autism is a disease of complex nature with a significant genetic component. The importance of renin-angiotensin system (RAS elements in cognition and behavior besides the interaction of angiotensin II (Ang II, the main product of angiotensin-converting enzyme (ACE, with neurotransmitters in CNS, especially dopamine, proposes the involvement of RAS in autism. Since the genetic architecture of autism has remained elusive, here we postulated that genetic variations in RAS are associated with autism.Considering the relation between the three polymorphisms of ACE (I/D, rs4343 and rs4291 with the level of ACE activity, we have investigated this association with autism, in a case-control study. Genotype and allele frequencies of polymorphisms were determined in DNAs extracted from venous blood of 120 autistic patients and their age and sex-matched healthy controls, using polymerase chain reaction (PCR and PCR-restriction fragment length polymorphism (PCR-RFLP methods.There were strong associations between both DD genotype of ACE I/D and the D allele, with autism (P = 0.006, OR = 2.9, 95% CI = 1.64-5.13 and P = 0.006, OR = 2.18, 95% CI = 1.37-3.48 respectively. Furthermore, a significant association between the G allele of rs4343 and autism was observed (P = 0.006, OR = 1.84, 95%CI = 1.26-2.67. Moreover, haplotype analysis revealed an association between DTG haplotype and autism (P = 0.008.Our data suggests the involvement of RAS genetic diversity in increasing the risk of autism.

  20. Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight.

    Science.gov (United States)

    Tyrrell, Jessica; Richmond, Rebecca C; Palmer, Tom M; Feenstra, Bjarke; Rangarajan, Janani; Metrustry, Sarah; Cavadino, Alana; Paternoster, Lavinia; Armstrong, Loren L; De Silva, N Maneka G; Wood, Andrew R; Horikoshi, Momoko; Geller, Frank; Myhre, Ronny; Bradfield, Jonathan P; Kreiner-Møller, Eskil; Huikari, Ville; Painter, Jodie N; Hottenga, Jouke-Jan; Allard, Catherine; Berry, Diane J; Bouchard, Luigi; Das, Shikta; Evans, David M; Hakonarson, Hakon; Hayes, M Geoffrey; Heikkinen, Jani; Hofman, Albert; Knight, Bridget; Lind, Penelope A; McCarthy, Mark I; McMahon, George; Medland, Sarah E; Melbye, Mads; Morris, Andrew P; Nodzenski, Michael; Reichetzeder, Christoph; Ring, Susan M; Sebert, Sylvain; Sengpiel, Verena; Sørensen, Thorkild I A; Willemsen, Gonneke; de Geus, Eco J C; Martin, Nicholas G; Spector, Tim D; Power, Christine; Järvelin, Marjo-Riitta; Bisgaard, Hans; Grant, Struan F A; Nohr, Ellen A; Jaddoe, Vincent W; Jacobsson, Bo; Murray, Jeffrey C; Hocher, Berthold; Hattersley, Andrew T; Scholtens, Denise M; Davey Smith, George; Hivert, Marie-France; Felix, Janine F; Hyppönen, Elina; Lowe, William L; Frayling, Timothy M; Lawlor, Debbie A; Freathy, Rachel M

    2016-03-15

    Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain. To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included. Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level. Offspring birth weight from 18 studies. Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P = .008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P = 7 × 10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P = 1×10(-5)), respectively. A 1-SD ( ≈ 4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD ( ≈ 7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD ( ≈ 10 mm Hg) genetically higher maternal SBP was associated with a 208-g

  1. Evidence for Within-Host Genetic Recombination among the Human Pegiviral Strains in HIV Infected Subjects.

    Science.gov (United States)

    Wu, Haoming; Padhi, Abinash; Xu, Junqiang; Gong, Xiaoyan; Tien, Po

    2016-01-01

    The non-pathogenic Human Pegivirus (HPgV, formerly GBV-C/HGV), the most prevalent RNA virus worldwide, is known to be associated with reduced morbidity and mortality in HIV-infected individuals. Although previous studies documented its ubiquity and important role in HIV-infected individuals, little is known about the underlying genetic mechanisms that maintain high genetic diversity of HPgV within the HIV-infected individuals. To assess the within-host genetic diversity of HPgV and forces that maintain such diversity within the co-infected hosts, we performed phylogenetic analyses taking into account 229 HPgV partial E1-E2 clonal sequences representing 15 male and 8 female co-infected HIV patients from Hubei province of central China. Our results revealed the presence of eleven strongly supported clades. While nine clades belonged to genotype 3, two clades belonged to genotype 2. Additionally, four clades that belonged to genotype 3 exhibited inter-clade recombination events. The presence of clonal sequences representing multiple clades within the HIV-infected individual provided the evidence of co-circulation of HPgV strains across the region. Of the 23 patients, six patients (i.e., five males and one female) were detected to have HPgV recombinant sequences. Our results also revealed that while male patients shared the viral strains with other patients, viral strains from the female patients had restricted dispersal. Taken together, the present study revealed that multiple infections with divergent HPgV viral strains may have caused within-host genetic recombination, predominantly in male patients, and therefore, could be the major driver in shaping genetic diversity of HPgV.

  2. Genetic variation in South Indian castes: evidence from Y-chromosome, mitochondrial, and autosomal polymorphisms

    Directory of Open Access Journals (Sweden)

    Tirupati S

    2008-12-01

    Full Text Available Abstract Background Major population movements, social structure, and caste endogamy have influenced the genetic structure of Indian populations. An understanding of these influences is increasingly important as gene mapping and case-control studies are initiated in South Indian populations. Results We report new data on 155 individuals from four Tamil caste populations of South India and perform comparative analyses with caste populations from the neighboring state of Andhra Pradesh. Genetic differentiation among Tamil castes is low (RST = 0.96% for 45 autosomal short tandem repeat (STR markers, reflecting a largely common origin. Nonetheless, caste- and continent-specific patterns are evident. For 32 lineage-defining Y-chromosome SNPs, Tamil castes show higher affinity to Europeans than to eastern Asians, and genetic distance estimates to the Europeans are ordered by caste rank. For 32 lineage-defining mitochondrial SNPs and hypervariable sequence (HVS 1, Tamil castes have higher affinity to eastern Asians than to Europeans. For 45 autosomal STRs, upper and middle rank castes show higher affinity to Europeans than do lower rank castes from either Tamil Nadu or Andhra Pradesh. Local between-caste variation (Tamil Nadu RST = 0.96%, Andhra Pradesh RST = 0.77% exceeds the estimate of variation between these geographically separated groups (RST = 0.12%. Low, but statistically significant, correlations between caste rank distance and genetic distance are demonstrated for Tamil castes using Y-chromosome, mtDNA, and autosomal data. Conclusion Genetic data from Y-chromosome, mtDNA, and autosomal STRs are in accord with historical accounts of northwest to southeast population movements in India. The influence of ancient and historical population movements and caste social structure can be detected and replicated in South Indian caste populations from two different geographic regions.

  3. Genetic and biochemical analysis reveals linked QTLs determining natural variation for fruit post-harvest water loss in pepper (Capsicum).

    Science.gov (United States)

    Popovsky-Sarid, Sigal; Borovsky, Yelena; Faigenboim, Adi; Parsons, Eugene P; Lohrey, Gregory T; Alkalai-Tuvia, Sharon; Fallik, Elazar; Jenks, Matthew A; Paran, Ilan

    2017-02-01

    Molecular markers linked to QTLs controlling post-harvest fruit water loss in pepper may be utilized to accelerate breeding for improved shelf life and inhibit over-ripening before harvest. Bell pepper (Capsicum annuum L.) is an important vegetable crop world-wide. However, marketing is limited by the relatively short shelf life of the fruit due to water loss and decay that occur during prolonged storage. Towards breeding pepper with reduced fruit post-harvest water loss (PWL), we studied the genetic, physiological and biochemical basis for natural variation of PWL. We performed quantitative trait locus (QTL) mapping of fruit PWL in multiple generations of an interspecific cross of pepper, which resulted in the identification of two linked QTLs on chromosome 10 that control the trait. We further developed near-isogenic lines (NILs) for characterization of the QTL effects. Transcriptome analysis of the NILs allowed the identification of candidate genes associated with fruit PWL-associated traits such as cuticle biosynthesis, cell wall metabolism and fruit ripening. Significant differences in PWL between the NILs in the immature fruit stage, differentially expressed cuticle-associated genes and differences in the content of specific chemical constituents of the fruit cuticle, indicated a likely influence of cuticle composition on the trait. Reduced PWL in the NILs was associated with delayed over-ripening before harvest, low total soluble solids before storage, and reduced fruit softening after storage. Our study enabled a better understanding of the genetic and biological processes controlling natural variation in fruit PWL in pepper. Furthermore, the genetic materials and molecular markers developed in this study may be utilized to breed peppers with improved shelf life and inhibited over-ripening before harvest.

  4. Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight

    DEFF Research Database (Denmark)

    Tyrrell, Jessica; Richmond, Rebecca C; Palmer, Tom M

    2016-01-01

    IMPORTANCE: Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain. OBJECTIVE: To test for genetic evidence...... of causal associations of maternal body mass index (BMI) and related traits with birth weight. DESIGN, SETTING, AND PARTICIPANTS: Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies...

  5. Mycobacterium bovis in Burkina Faso: epidemiologic and genetic links between human and cattle isolates.

    Directory of Open Access Journals (Sweden)

    Adama Sanou

    2014-10-01

    Full Text Available In sub-Saharan Africa, bovine tuberculosis (bTB is a potential hazard for animals and humans health. The goal of this study was to improve our understanding of bTB epidemiology in Burkina Faso and especially Mycobacterium bovis transmission within and between the bovine and human populations.Twenty six M. bovis strains were isolated from 101 cattle carcasses with suspected bTB lesions during routine meat inspections at the Bobo Dioulasso and Ouagadougou slaughterhouses. In addition, 7 M. bovis strains were isolated from 576 patients with pulmonary tuberculosis. Spoligotyping, RDAf1 deletion and MIRU-VNTR typing were used for strains genotyping. The isolation of M. bovis strains was confirmed by spoligotyping and 12 spoligotype signatures were detected. Together, the spoligotyping and MIRU-VNTR data allowed grouping the 33 M. bovis isolates in seven clusters including isolates exclusively from cattle (5 or humans (1 or from both (1. Moreover, these data (genetic analyses and phenetic tree showed that the M. bovis isolates belonged to the African 1 (Af1 clonal complex (81.8% and the putative African 5 (Af5 clonal complex (18.2%, in agreement with the results of RDAf1 deletion typing.This is the first detailed molecular characterization of M. bovis strains from humans and cattle in Burkina Faso. The distribution of the two Af1 and putative Af5 clonal complexes is comparable to what has been reported in neighbouring countries. Furthermore, the strain genetic profiles suggest that M. bovis circulates across the borders and that the Burkina Faso strains originate from different countries, but have a country-specific evolution. The genetic characterization suggests that, currently, M. bovis transmission occurs mainly between cattle, occasionally between cattle and humans and potentially between humans. This study emphasizes the bTB risk in cattle but also in humans and the difficulty to set up proper disease control strategies in Burkina Faso.

  6. Mycobacterium bovis in Burkina Faso: epidemiologic and genetic links between human and cattle isolates.

    Science.gov (United States)

    Sanou, Adama; Tarnagda, Zekiba; Kanyala, Estelle; Zingué, Dezemon; Nouctara, Moumini; Ganamé, Zakaria; Combary, Adjima; Hien, Hervé; Dembele, Mathurin; Kabore, Antoinette; Meda, Nicolas; Van de Perre, Philippe; Neveu, Dorine; Bañuls, Anne Laure; Godreuil, Sylvain

    2014-10-01

    In sub-Saharan Africa, bovine tuberculosis (bTB) is a potential hazard for animals and humans health. The goal of this study was to improve our understanding of bTB epidemiology in Burkina Faso and especially Mycobacterium bovis transmission within and between the bovine and human populations. Twenty six M. bovis strains were isolated from 101 cattle carcasses with suspected bTB lesions during routine meat inspections at the Bobo Dioulasso and Ouagadougou slaughterhouses. In addition, 7 M. bovis strains were isolated from 576 patients with pulmonary tuberculosis. Spoligotyping, RDAf1 deletion and MIRU-VNTR typing were used for strains genotyping. The isolation of M. bovis strains was confirmed by spoligotyping and 12 spoligotype signatures were detected. Together, the spoligotyping and MIRU-VNTR data allowed grouping the 33 M. bovis isolates in seven clusters including isolates exclusively from cattle (5) or humans (1) or from both (1). Moreover, these data (genetic analyses and phenetic tree) showed that the M. bovis isolates belonged to the African 1 (Af1) clonal complex (81.8%) and the putative African 5 (Af5) clonal complex (18.2%), in agreement with the results of RDAf1 deletion typing. This is the first detailed molecular characterization of M. bovis strains from humans and cattle in Burkina Faso. The distribution of the two Af1 and putative Af5 clonal complexes is comparable to what has been reported in neighbouring countries. Furthermore, the strain genetic profiles suggest that M. bovis circulates across the borders and that the Burkina Faso strains originate from different countries, but have a country-specific evolution. The genetic characterization suggests that, currently, M. bovis transmission occurs mainly between cattle, occasionally between cattle and humans and potentially between humans. This study emphasizes the bTB risk in cattle but also in humans and the difficulty to set up proper disease control strategies in Burkina Faso.

  7. Genetic and environmental links between cognitive and physical functions in old age

    DEFF Research Database (Denmark)

    Johnson, Wendy; Deary, Ian J; McGue, Matt

    2009-01-01

    of twins from the Longitudinal Study of Aging Danish Twins. Cognitive function was measured using forward and backward digit span, immediate and delayed memory, and fluency tasks. Physical function was measured using self-report of ability to carry out physical activities including walking, running......In old age, cognitive and physical functions are correlated. Knowing the correlations between genetic and environmental influences underlying this correlation can help to clarify the reasons for the observable (phenotypic) correlation. We estimated these correlations in a sample of 1,053 pairs...

  8. Morphological and genetic evidence for early Holocene cattle management in northeastern China

    DEFF Research Database (Denmark)

    Zhang, Hucai; Paijmans, Johanna L. A.; Chang, Fengqin

    2013-01-01

    The domestication of cattle is generally accepted to have taken place in two independent centres: around 10,500 years ago in the Near East, giving rise to modern taurine cattle, and two millennia later in southern Asia, giving rise to zebu cattle. Here we provide firmly dated morphological...... and genetic evidence for early Holocene management of taurine cattle in northeastern China. We describe conjoining mandibles from this region that show evidence of oral stereotypy, dated to the early Holocene by two independent (14)C dates. Using Illumina high-throughput sequencing coupled with DNA...... hybridization capture, we characterize 15,406 bp of the mitogenome with on average 16.7-fold coverage. Phylogenetic analyses reveal a hitherto unknown mitochondrial haplogroup that falls outside the known taurine diversity. Our data suggest that the first attempts to manage cattle in northern China predate...

  9. Linking research to practice: the rise of evidence-based health sciences librarianship.

    Science.gov (United States)

    Marshall, Joanne Gard

    2014-01-01

    The lecture explores the origins of evidence-based practice (EBP) in health sciences librarianship beginning with examples from the work of Janet Doe and past Doe lecturers. Additional sources of evidence are used to document the rise of research and EBP as integral components of our professional work. FOUR SOURCES OF EVIDENCE ARE USED TO EXAMINE THE RISE OF EBP: (1) a publication by Doe and research-related content in past Doe lectures, (2) research-related word usage in articles in the Bulletin of the Medical Library Association and Journal of the Medical Library Association between 1961 and 2010, (3) Medical Library Association activities, and (4) EBP as an international movement. These sources of evidence confirm the rise of EBP in health sciences librarianship. International initiatives sparked the rise of evidence-based librarianship and continue to characterize the movement. This review shows the emergence of a unique form of EBP that, although inspired by evidence-based medicine (EBM), has developed its own view of evidence and its application in library and information practice. Health sciences librarians have played a key role in initiating, nurturing, and spreading EBP in other branches of our profession. Our close association with EBM set the stage for developing our own EBP. While we relied on EBM as a model for our early efforts, we can observe the continuing evolution of our own unique approach to using, creating, and applying evidence from a variety of sources to improve the quality of health information services.

  10. Genetic Evidence Highlights Potential Impacts of By-Catch to Cetaceans

    Science.gov (United States)

    Mendez, Martin; Rosenbaum, Howard C.; Wells, Randall S.; Stamper, Andrew; Bordino, Pablo

    2010-01-01

    Incidental entanglement in fishing gear is arguably the most serious threat to many populations of small cetaceans, judging by the alarming number of captured animals. However, other aspects of this threat, such as the potential capture of mother-offspring pairs or reproductive pairs, could be equally or even more significant but have rarely been evaluated. Using a combination of demographic and genetic data we provide evidence that i) Franciscana dolphin pairs that are potentially reproductive and mother-offspring pairs form temporal bonds, and ii) are entangled simultaneously. Our results highlight potential demographic and genetic impacts of by-catch to cetacean populations: the joint entanglement of mother-offspring or reproductive pairs, compared to random individuals, might exacerbate the demographic consequences of by-catch, and the loss of groups of relatives means that significant components of genetic diversity could be lost together. Given the social nature of many odontocetes (toothed cetaceans), we suggest that these potential impacts could be rather general to the group and therefore by-catch could be more detrimental than previously considered. PMID:21179542

  11. Genetic evidence for a novel competence inhibitor in the industrially important Bacillus licheniformis.

    Science.gov (United States)

    Muth, Christine; Buchholz, Meike; Schmidt, Christina; Volland, Sonja; Meinhardt, Friedhelm

    2017-12-01

    Natural genetic competence renders bacteria able to take up and, in case there is sufficient homology to the recipient's chromosome, integrate exogenously supplied DNA. Well studied in Bacillus subtilis, genetic competence is-in several aspects-known to be differently regulated in Bacillus licheniformis. We now report on the identification of a novel, chromosomally encoded homolog of a competence inhibitor in B. licheniformis (ComI) that has hitherto only been described as a plasmid borne trait in the ancestral B. subtilis NCIB3610. Bioinformatical analysis that included 80 Bacillus strains covering 20 different species revealed a ComI encoding gene in all of the examined B. licheniformis representatives, and was identified in few among the other species investigated. The predicted ComI of B. licheniformis is a highly conserved peptide consisting of 28 amino acids. Since deletion of comI in B. licheniformis DSM13 resulted in twofold increased transformation efficiency by genetic competence and overexpression resulted in threefold decreased transformability, the function as a competence inhibitor became evident.

  12. Maturation Constrains the Effect of Exposure in Linking Language and Thought: Evidence from Healthy Preterm Infants

    Science.gov (United States)

    Perszyk, Danielle R.; Ferguson, Brock; Waxman, Sandra R.

    2018-01-01

    The power of human language rests upon its intricate links to human cognition. By 3 months of age, listening to language supports infants' ability to form object categories, a building block of cognition. Moreover, infants display a systematic shift between 3 and 4 months--a shift from familiarity to novelty preferences--in their expression of…

  13. Linking Mitigation and Adaptation in Carbon Forestry Projects: Evidence from Belize

    DEFF Research Database (Denmark)

    Kongsager, Rico; Corbera, Esteve

    2015-01-01

    that linking mitigation and adaptation has not been possible, because the mandate of forest carbon markets does not incorporate adaptation concerns. The projects’ contribution to forest ecosystems’ adaptation, for instance, by reducing human encroachments and by increasing ecosystem connectivity, has been...... instead to promote more holistic and territorial-based approaches targeting both mitigation and adaptation goals....

  14. Preliminary Evidence for an Automatic Link between Sex and Power among Men Who Molest Children

    Science.gov (United States)

    Kamphuis, Jan H.; De Ruiter, Corine; Janssen, Bas; Spiering, Mark

    2005-01-01

    Understanding critical motivational processes of sexual offenders may ultimately provide important clues to more effective treatments. Implicit, automatic cognitive processes have received minimal attention; however, a lexical decision experiment revealed automatic links between the concepts of power and sex among participants who self-reported…

  15. Indirect evidence for genetic differentiation in vulnerability to embolism in Pinus halepensis

    Directory of Open Access Journals (Sweden)

    Rakefet eDavid-Schwartz

    2016-06-01

    Full Text Available Climate change is increasing mean temperatures and in the eastern Mediterranean is expected to decrease annual precipitation. The resulting increase in aridity may be too rapid for adaptation of tree species unless their gene pool already possesses variation in drought resistance. Vulnerability to embolism, estimated by the pressure inducing 50% loss of xylem hydraulic conductivity (P50, is strongly associated with drought stress resistance in trees. Yet, previous studies on various tree species reported low intraspecific genetic variation for this trait, and therefore limited adaptive capacities to increasing aridity. Here we quantified differences in hydraulic efficiency (xylem hydraulic conductance and safety (resistance to embolism in four contrasting provenances of Pinus halepensis (Aleppo pine in a provenance trial, which is indirect evidence for genetic differences. Results obtained with three techniques (bench dehydration, centrifugation and X-ray micro-CT evidenced significant differentiation with similar ranking between provenances. Inter-provenance variation in P50 correlated with pit anatomical properties (torus overlap and pit aperture size. These results suggest that adaptation of P. halepensis to xeric habitats has been accompanied by modifications of bordered pit function driven by variation in pit aperture. This study thus provides evidence that appropriate exploitation of provenance differences will allow continued forestry with P. halepensis in future climates of the Eastern Mediterranean.

  16. Evidence for weak genetic recombination at the PTP2 locus of Nosema ceranae.

    Science.gov (United States)

    Gómez-Moracho, Tamara; Bartolomé, Carolina; Martín-Hernández, Raquel; Higes, Mariano; Maside, Xulio

    2015-04-01

    The microsporidian Nosema ceranae is an emergent pathogen that threatens the health of honeybees and other pollinators all over the world. Its recent rapid spread across a wide variety of host species and environments demonstrated an enhanced ability of adaptation, which seems to contradict the lack of evidence for genetic recombination and the absence of a sexual stage in its life cycle. Here we retrieved fresh data of the patterns of genetic variation at the PTP2 locus in naturally infected Apis mellifera colonies, by means of single genome amplification. This technique, designed to prevent the formation of chimeric haplotypes during polymerase chain reaction (PCR), provides more reliable estimates of the diversity levels and haplotype structure than standard PCR-cloning methods. Our results are consistent with low but significant rates of recombination in the history of the haplotypes detected: estimates of the population recombination rate are of the order of 30 and support recent evidence for unexpectedly high levels of variation of the parasites within honeybee colonies. These observations suggest the existence of a diploid stage at some point in the life cycle of this parasite and are relevant for our understanding of the dynamics of its expanding population. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  17. No evidence for female discrimination against male house mice carrying a selfish genetic element.

    Science.gov (United States)

    Sutter, Andreas; Lindholm, Anna K

    2016-12-01

    Meiotic drivers distort transmission to the next generation in their favor, with detrimental effects on the fitness of their homologues and the rest of the genome. Male carriers of meiotic drivers commonly inflict costs on their mates through genetic incompatibility, reduced fecundity, or biased brood sex ratios. Given these costs, evidence for female discrimination against male carriers is surprisingly rare. One of few examples is the t haplotype in house mice, a meiotic driver that shows strong transmission distortion in males and is typically homozygote lethal. As a consequence, mating between 2 t heterozygous (+/ t ) mice leads to high embryo mortality. Previous experiments showing that +/ t females avoid this incompatibility cost by preferring +/+ versus +/ t males have inferred preference based on olfactory cues or brief social interactions. Evidence from mating contexts in laboratory settings and semi-natural populations has been inconclusive. Here, we investigated female choice from a large number of no-choice mating trials. We found no evidence for discrimination against +/ t males based on mating, remating, and copulatory behavior. Further, we found no evidence for avoidance of incompatibility through selective interactions between gametes. The likelihood of mating showed significant effects of female weight and genotype, suggesting that our test paradigm enabled females to exhibit mate choice. We discuss the strengths and limitations of our approach. By explicitly considering selection at both the individual and gene level, we argue why precopulatory female discrimination by +/ t females may be less evolutionarily stable than discrimination by all females based on postcopulatory mechanisms.

  18. Genetic Diversity and Evidence for Transmission of Streptococcus mutans by DiversiLab rep-PCR.

    Science.gov (United States)

    Momeni, Stephanie S; Whiddon, Jennifer; Cheon, Kyounga; Ghazal, Tariq; Moser, Stephen A; Childers, Noel K

    2016-09-01

    This two-part study investigated the genetic diversity and transmission of Streptococcus mutans using the DiversiLab repetitive extragenic palindromic PCR (rep-PCR) approach. For children with S. mutans and participating household members, analysis for evidence of unrelated child-to-child as well as intra-familial transmission was evaluated based on commonality of genotypes. A total of 169 index children and 425 household family members from Uniontown, Alabama were evaluated for genetic diversity using rep-PCR. Thirty-four unique rep-PCR genotypes were observed for 13,906 S. mutans isolates. For transmission, 117 child and household isolates were evaluated for shared genotype (by child and by genotype cases, multiple matches possible for each child). Overall, children had 1-9 genotypes and those with multiple genotypes were 2.3 times more likely to have caries experience (decayed, missing and filled teeth/surfaces>0). Only 28% of children shared all genotypes within the household, while 72% had at least 1 genotype not shared with anyone in the household. Children had genotype(s) not shared with any household members in 157 cases. In 158 cases children and household members shared a genotype in which 55% (87/158 cases) were shared with more than one family member. Children most frequently shared genotypes with their mothers (54%; 85/158), siblings (46%; 72/158) and cousins (23%; 37/158). A reference library for S. mutans for epidemiological surveillance using the DiversiLab rep-PCR approach is detailed. The genetic diversity of S. mutans in this population demonstrated frequent commonality of genotypes. Evidence for both child-to-child and intra-familial transmission of S. mutans was observed by rep-PCR. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Characterization, genetic diversity, and evolutionary link of Cucumber mosaic virus strain New Delhi from India.

    Science.gov (United States)

    Koundal, Vikas; Haq, Qazi Mohd Rizwanul; Praveen, Shelly

    2011-02-01

    The genome of Cucumber mosaic virus New Delhi strain (CMV-ND) from India, obtained from tomato, was completely sequenced and compared with full genome sequences of 14 known CMV strains from subgroups I and II, for their genetic diversity. Sequence analysis suggests CMV-ND shares maximum sequence identity at the nucleotide level with a CMV strain from Taiwan. Among all 15 strains of CMV, the encoded protein 2b is least conserved, whereas the coat protein (CP) is most conserved. Sequence identity values and phylogram results indicate that CMV-ND belongs to subgroup I. Based on the recombination detection program result, it appears that CMV is prone to recombination, and different RNA components of CMV-ND have evolved differently. Recombinational analysis of all 15 CMV strains detected maximum recombination breakpoints in RNA2; CP showed the least recombination sites.

  20. Epidemiological Evidence on the Link Between Drug Use and Suicidal Behaviors Among Adolescents

    OpenAIRE

    Wilcox, Holly C.

    2004-01-01

    Depression, substance abuse, and aggressive behavior disorders have shown to be among the most influential risk factors for suicide in community and clinical studies of adolescents and adults. Increasing evidence suggests that adolescents who use and abuse alcohol and drugs are at increased risk for suicidal ideation, attempted suicide, and completed suicide, although conclusive evidence has not yet been presented suggesting that drug use causes suicidal thoughts and behaviors. This paper rev...

  1. Linking research to practice: the rise of evidence-based health sciences librarianship*

    Science.gov (United States)

    Marshall, Joanne Gard

    2014-01-01

    Purpose: The lecture explores the origins of evidence-based practice (EBP) in health sciences librarianship beginning with examples from the work of Janet Doe and past Doe lecturers. Additional sources of evidence are used to document the rise of research and EBP as integral components of our professional work. Methods: Four sources of evidence are used to examine the rise of EBP: (1) a publication by Doe and research-related content in past Doe lectures, (2) research-related word usage in articles in the Bulletin of the Medical Library Association and Journal of the Medical Library Association between 1961 and 2010, (3) Medical Library Association activities, and (4) EBP as an international movement. Results: These sources of evidence confirm the rise of EBP in health sciences librarianship. International initiatives sparked the rise of evidence-based librarianship and continue to characterize the movement. This review shows the emergence of a unique form of EBP that, although inspired by evidence-based medicine (EBM), has developed its own view of evidence and its application in library and information practice. Implications: Health sciences librarians have played a key role in initiating, nurturing, and spreading EBP in other branches of our profession. Our close association with EBM set the stage for developing our own EBP. While we relied on EBM as a model for our early efforts, we can observe the continuing evolution of our own unique approach to using, creating, and applying evidence from a variety of sources to improve the quality of health information services. PMID:24415915

  2. Warfarin resistance associated with genetic polymorphism of VKORC1: linking clinical response to molecular mechanism using computational modeling.

    Science.gov (United States)

    Lewis, Benjamin C; Nair, Pramod C; Heran, Subash S; Somogyi, Andrew A; Bowden, Jeffrey J; Doogue, Matthew P; Miners, John O

    2016-01-01

    The variable response to warfarin treatment often has a genetic basis. A protein homology model of human vitamin K epoxide reductase, subunit 1 (VKORC1), was generated to elucidate the mechanism of warfarin resistance observed in a patient with the Val66Met mutation. The VKORC1 homology model comprises four transmembrane (TM) helical domains and a half helical lid domain. Cys132 and Cys135, located in the N-terminal end of TM-4, are linked through a disulfide bond. Two distinct binding sites for warfarin were identified. Site-1, which binds vitamin K epoxide (KO) in a catalytically favorable orientation, shows higher affinity for S-warfarin compared with R-warfarin. Site-2, positioned in the domain occupied by the hydrophobic tail of KO, binds both warfarin enantiomers with similar affinity. Displacement of Arg37 occurs in the Val66Met mutant, blocking access of warfarin (but not KO) to Site-1, consistent with clinical observation of warfarin resistance.

  3. UV-induced mitotic co-segregation of genetic markers in Candida albicans: Evidence for linkage

    International Nuclear Information System (INIS)

    Crandall, M.

    1983-01-01

    Parasexual genetic studies of the medically important yeast Candida albicans were performed using the method of UV-induced mitotic segregation. UV-irradiation of the Hoffmann-La Roche type culture of C. albicans yielded a limited spectrum of mutants at a relatively high fequency. This observation suggested natural heterozygosity. Canavanine-sensitive (CanS) segregants were induced at a frequency of 7.6 . 10 -3 . Double mutants that were both CanS and methionine (Met - ) auxotrophs were induced at a frequency of 7.4 . 10 -3 . The single Met - segregant class was missing indicating linkage. UV-induced CanS or Met - CanS segregants occurred occasionally in twin-sectored colonies. Analyses of the sectors as well as the observed and missing classes of segregants indicated that genes met and can are linked in the cis configuration. The proposed gene order is: centromere - met - can. Thus, it is concluded that the Hoffmann-La Roche strain of C. albicans is naturally heterozygous at two linked loci. These findings are consistent with diploidy. (orig.)

  4. A genetic polymorphism in the sex-linked ATP5A1 gene is associated with individual fitness in Ovenbirds (Seiurus aurocapilla)

    Science.gov (United States)

    Judith D. Toms; Lori S. Eggert; Wayne J. Arendt; John Faaborg

    2012-01-01

    While testing genetic sexing techniques in Ovenbirds (Seiurus aurocapilla),we found a genetic polymorphism in the ATP5A1 gene in 38% of individuals. The Z ' allele included changes in both intronic and exonic portions of the sequenced region, but there was no evidence that this changed the resulting ATP synthase product. Males that had one or more copies of...

  5. Antibiotic and antiseptic resistance genes are linked on a novel mobile genetic element: Tn6087

    Science.gov (United States)

    Ciric, Lena; Mullany, Peter; Roberts, Adam P.

    2011-01-01

    Objectives Tn916-like elements are one of the most common types of integrative and conjugative element (ICE). In this study we aimed to determine whether novel accessory genes, i.e. genes whose products are not involved in mobility or regulation, were present on a Tn916-like element (Tn6087) isolated from Streptococcus oralis from the human oral cavity. Methods A minocycline-resistant isolate was analysed using restriction fragment length polymorphism (RFLP) analysis on amplicons derived from Tn916 and DNA sequencing to determine whether there were genetic differences in Tn6087 compared with Tn916. Mutational analysis was used to determine whether the novel accessory gene found was responsible for an observed extra phenotype. Results A novel Tn916-like element, Tn6087, is described that encodes both antibiotic and antiseptic resistance. The antiseptic resistance protein is encoded by a novel small multidrug resistance gene, designated qrg, that was shown to encode resistance to cetyltrimethylammonium bromide (CTAB), also known as cetrimide bromide. Conclusions This is the first Tn916-like element described that confers both antibiotic and antiseptic resistance, suggesting that selection of either antibiotic or antiseptic resistance will also select for the other and further highlights the need for prudent use of both types of compound. PMID:21816764

  6. Genetic risk scores link body fat distribution with specific cardiometabolic profiles

    DEFF Research Database (Denmark)

    Svendstrup, Mathilde; Sandholt, Camilla H; Andersson Galijatovic, Ehm Astrid

    2016-01-01

    , including fasting serum triglyceride (β = 0.98% mmol/L, P = 3.33 × 10(-) (8) ) and Matsuda index (β = -0.74%, P = 1.29 × 10(-) (4) ). No similar associations for Clusters 2 and 3 were found. The three clusters showed different patterns of association with waist circumference, hip circumference, and height......OBJECTIVE: Forty-nine known single nucleotide polymorphisms (SNPs) associating with body mass index (BMI)-adjusted waist-hip-ratio (WHR) (WHRadjBMI) were recently suggested to cluster into three groups with different associations to cardiometabolic traits. Genetic risk scores of the clusters...... risk scores and anthropometry and blood samples at fasting and during an oral glucose tolerance test were tested. Analyses were adjusted for age, sex, and BMI. RESULTS: Cluster 1 associated with an increased risk of diabetes (HR = 1.05, P = 2.74 × 10(-) (4) ) and with a poor metabolic profile...

  7. Genetic Correlates of Maladaptive Beliefs: COMT VAL(158)MET and Irrational Cognitions Linked Depending on Distress.

    Science.gov (United States)

    Podina, Ioana; Popp, Radu; Pop, Ioan; David, Daniel

    2015-11-01

    Maladaptive/irrational beliefs are significant cognitive vulnerability mechanisms in psychopathology. They are more likely to be associated with a genetic vulnerability marker under conditions of emotional distress when irrational beliefs are more salient. Therefore, in the current study we investigated the COMT Val(158)Met gene variation in relation to irrational beliefs, assuming this relationship depended on the level of emotional distress. Two hundred and sixty-seven genotyped volunteers were assessed for core/general maladaptive beliefs, as well as trait emotional distress. We focused on context-independent measures of irrational beliefs and emotional distress in the absence of a stressor. As expected, the relationship between COMT Val(158)Met and irrational beliefs depended on the level of emotional distress (f(2)=.314). The COMT Val(158)Met-irrationality association was significant only when individuals fell in the average to above average range of emotional distress. Furthermore, within this range the Met allele seemed to relate to higher irrational beliefs. These results were significant for overall irrational beliefs and its subtypes, but not for rational beliefs, the functional counterpart of irrationality. In light of the study's limitations, the results should be considered as preliminary. If replicable, these findings have potential implications for therapygenetics, changing the view that COMT Val(158)Met might be of greater relevance when treatment modality does not rely on cognitive variables. Copyright © 2015. Published by Elsevier Ltd.

  8. Sex linked versus autosomal inbreeding coefficient in close consanguineous marriages in the Basque country and Castile (Spain): genetic implications.

    Science.gov (United States)

    Calderón, R; Morales, B; Peña, J A; Delgado, J

    1995-10-01

    Pedigree structures of 161 uncle/niece-aunt/nephew and 4420 first cousin consanguineous marriages registered during the 19th and 20th centuries in two large and very different Spanish regions have been analysed and their genetic consequences evaluated. The frequencies of the different pedigree subtypes within each degree of relationship were quite similar in both populations despite significant heterogeneity in inbreeding patterns. The mean X-linked inbreeding coefficient (Fx) for each type of cousin mating was calculated and compared to that expected for autosomal genes (F). The effect of genealogical structure on the Fx/F ratio was compared to different cultural populations worldwide. Preferentiality and avoidance of close consanguinity along with specific types of pedigrees are discussed on the basis of premarital migration and sociocultural rules still deeply rooted in certain human groups. By admitting that the observed Fx coefficient is usually higher than F in most human populations some remarks have been made in terms of population genetic risk.

  9. Sex-linked dominant

    Science.gov (United States)

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

  10. Generation of a monoclonal antibody against the glycosylphosphatidylinositol-linked protein Rae-1 using genetically engineered tumor cells.

    Science.gov (United States)

    Hu, Jiemiao; Vien, Long T; Xia, Xueqing; Bover, Laura; Li, Shulin

    2014-02-04

    Although genetically engineered cells have been used to generate monoclonal antibodies (mAbs) against numerous proteins, no study has used them to generate mAbs against glycosylphosphatidylinositol (GPI)-anchored proteins. The GPI-linked protein Rae-1, an NKG2D ligand member, is responsible for interacting with immune surveillance cells. However, very few high-quality mAbs against Rae-1 are available for use in multiple analyses, including Western blotting, immunohistochemistry, and flow cytometry. The lack of high-quality mAbs limits the in-depth analysis of Rae-1 fate, such as shedding and internalization, in murine models. Moreover, currently available screening approaches for identifying high-quality mAbs are excessively time-consuming and costly. We used Rae-1-overexpressing CT26 tumor cells to generate 60 hybridomas that secreted mAbs against Rae-1. We also developed a streamlined screening strategy for selecting the best anti-Rae-1 mAb for use in flow cytometry assay, enzyme-linked immunosorbent assay, Western blotting, and immunostaining. Our cell line-based immunization approach can yield mAbs against GPI-anchored proteins, and our streamlined screening strategy can be used to select the ideal hybridoma for producing such mAbs.

  11. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

    Science.gov (United States)

    Horikoshi, Momoko; Yaghootkar, Hanieh; Mook-Kanamori, Dennis O.; Sovio, Ulla; Taal, H. Rob; Hennig, Branwen J.; Bradfield, Jonathan P.; St. Pourcain, Beate; Evans, David M.; Charoen, Pimphen; Kaakinen, Marika; Cousminer, Diana L.; Lehtimäki, Terho; Kreiner-Møller, Eskil; Warrington, Nicole M.; Bustamante, Mariona; Feenstra, Bjarke; Berry, Diane J.; Thiering, Elisabeth; Pfab, Thiemo; Barton, Sheila J.; Shields, Beverley M.; Kerkhof, Marjan; van Leeuwen, Elisabeth M.; Fulford, Anthony J.; Kutalik, Zoltán; Zhao, Jing Hua; den Hoed, Marcel; Mahajan, Anubha; Lindi, Virpi; Goh, Liang-Kee; Hottenga, Jouke-Jan; Wu, Ying; Raitakari, Olli T.; Harder, Marie N.; Meirhaeghe, Aline; Ntalla, Ioanna; Salem, Rany M.; Jameson, Karen A.; Zhou, Kaixin; Monies, Dorota M.; Lagou, Vasiliki; Kirin, Mirna; Heikkinen, Jani; Adair, Linda S.; Alkuraya, Fowzan S.; Al-Odaib, Ali; Amouyel, Philippe; Andersson, Ehm Astrid; Bennett, Amanda J.; Blakemore, Alexandra I.F.; Buxton, Jessica L.; Dallongeville, Jean; Das, Shikta; de Geus, Eco J. C.; Estivill, Xavier; Flexeder, Claudia; Froguel, Philippe; Geller, Frank; Godfrey, Keith M.; Gottrand, Frédéric; Groves, Christopher J.; Hansen, Torben; Hirschhorn, Joel N.; Hofman, Albert; Hollegaard, Mads V.; Hougaard, David M.; Hyppönen, Elina; Inskip, Hazel M.; Isaacs, Aaron; Jørgensen, Torben; Kanaka-Gantenbein, Christina; Kemp, John P.; Kiess, Wieland; Kilpeläinen, Tuomas O.; Klopp, Norman; Knight, Bridget A.; Kuzawa, Christopher W.; McMahon, George; Newnham, John P.; Niinikoski, Harri; Oostra, Ben A.; Pedersen, Louise; Postma, Dirkje S.; Ring, Susan M.; Rivadeneira, Fernando; Robertson, Neil R.; Sebert, Sylvain; Simell, Olli; Slowinski, Torsten; Tiesler, Carla M.T.; Tönjes, Anke; Vaag, Allan; Viikari, Jorma S.; Vink, Jacqueline M.; Vissing, Nadja Hawwa; Wareham, Nicholas J.; Willemsen, Gonneke; Witte, Daniel R.; Zhang, Haitao; Zhao, Jianhua; Wilson, James F.; Stumvoll, Michael; Prentice, Andrew M.; Meyer, Brian F.; Pearson, Ewan R.; Boreham, Colin A.G.; Cooper, Cyrus; Gillman, Matthew W.; Dedoussis, George V.; Moreno, Luis A; Pedersen, Oluf; Saarinen, Maiju; Mohlke, Karen L.; Boomsma, Dorret I.; Saw, Seang-Mei; Lakka, Timo A.; Körner, Antje; Loos, Ruth J.F.; Ong, Ken K.; Vollenweider, Peter; van Duijn, Cornelia M.; Koppelman, Gerard H.; Hattersley, Andrew T.; Holloway, John W.; Hocher, Berthold; Heinrich, Joachim; Power, Chris; Melbye, Mads; Guxens, Mònica; Pennell, Craig E.; Bønnelykke, Klaus; Bisgaard, Hans; Eriksson, Johan G.; Widén, Elisabeth; Hakonarson, Hakon; Uitterlinden, André G.; Pouta, Anneli; Lawlor, Debbie A.; Smith, George Davey; Frayling, Timothy M.; McCarthy, Mark I.; Grant, Struan F.A.; Jaddoe, Vincent W.V.; Jarvelin, Marjo-Riitta; Timpson, Nicholas J.; Prokopenko, Inga; Freathy, Rachel M.

    2012-01-01

    Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood1. Previous genome-wide association studies identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes, and a second variant, near CCNL1, with no obvious link to adult traits2. In an expanded genome-wide association meta-analysis and follow-up study (up to 69,308 individuals of European descent from 43 studies), we have now extended the number of genome-wide significant loci to seven, accounting for a similar proportion of variance to maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes; ADRB1 with adult blood pressure; and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism. PMID:23202124

  12. Diversity of management strategies in Mesoamerican turkeys: archaeological, isotopic and genetic evidence

    Science.gov (United States)

    Manin, Aurelie; Corona-M, Eduardo; Craig, Abigail; Thornton, Erin Kennedy; Yang, Dongya Y.; Richards, Michael

    2018-01-01

    The turkey (Meleagris gallopavo) represents one of the few domestic animals of the New World. While current research points to distinct domestication centres in the Southwest USA and Mesoamerica, several questions regarding the number of progenitor populations, and the timing and intensity of turkey husbandry remain unanswered. This study applied ancient mitochondrial DNA and stable isotope (δ13C, δ15N) analysis to 55 archaeological turkey remains from Mexico to investigate pre-contact turkey exploitation in Mesoamerica. Three different (sub)species of turkeys were identified in the archaeological record (M. g. mexicana, M. g. gallopavo and M. ocellata), indicating the exploitation of diverse local populations, as well as the trade of captively reared birds into the Maya area. No evidence of shared maternal haplotypes was observed between Mesoamerica and the Southwest USA, in contrast with archaeological evidence for trade of other domestic products. Isotopic analysis indicates a range of feeding behaviours in ancient Mesoamerican turkeys, including wild foraging, human provisioning and mixed feeding ecologies. This variability in turkey diet decreases through time, with archaeological, genetic and isotopic evidence all pointing to the intensification of domestic turkey management and husbandry, culminating in the Postclassic period. PMID:29410864

  13. Diversity of management strategies in Mesoamerican turkeys: archaeological, isotopic and genetic evidence.

    Science.gov (United States)

    Manin, Aurelie; Corona-M, Eduardo; Alexander, Michelle; Craig, Abigail; Thornton, Erin Kennedy; Yang, Dongya Y; Richards, Michael; Speller, Camilla F

    2018-01-01

    The turkey ( Meleagris gallopavo ) represents one of the few domestic animals of the New World. While current research points to distinct domestication centres in the Southwest USA and Mesoamerica, several questions regarding the number of progenitor populations, and the timing and intensity of turkey husbandry remain unanswered. This study applied ancient mitochondrial DNA and stable isotope ( δ 13 C, δ 15 N) analysis to 55 archaeological turkey remains from Mexico to investigate pre-contact turkey exploitation in Mesoamerica. Three different (sub)species of turkeys were identified in the archaeological record ( M. g. mexicana , M. g. gallopavo and M. ocellata ), indicating the exploitation of diverse local populations, as well as the trade of captively reared birds into the Maya area. No evidence of shared maternal haplotypes was observed between Mesoamerica and the Southwest USA, in contrast with archaeological evidence for trade of other domestic products. Isotopic analysis indicates a range of feeding behaviours in ancient Mesoamerican turkeys, including wild foraging, human provisioning and mixed feeding ecologies. This variability in turkey diet decreases through time, with archaeological, genetic and isotopic evidence all pointing to the intensification of domestic turkey management and husbandry, culminating in the Postclassic period.

  14. Plot-scale evidence of tundra vegetation change and links to recent summer warming

    Science.gov (United States)

    Sarah C. Elmendorf; Gregory H.R. Henry; Robert D. Hollister; Robert G. Bjork; Noemie Boulanger-Lapointe; Elisabeth J. Cooper; Johannes H.C. Cornelissen; Thomas A. Day; Ellen Dorrepaal; Tatiana G. Elumeeva; Mike Gill; William A. Gould; John Harte; David S. Hik; Annika Hofgaard; David R. Johnson; Jill F. Johnstone; Ingijorg Svala Jonsdottir; Janet C. Jorgenson; Kari Klanderud; Julia A. Klein; Saewan Koh; Gaku Kudo; Mark Lara; Esther Levesque; Borgthor Magnusson; Jeremy L. May; Joel A. Mercado; Anders Michelsen; Ulf Molau; Isla H. Myers-Smith; Steven F. Oberbauer; Vladimir G. Onipchenko; Christian Rixen; Niels Martin Schmidt; Gaius R. Shaver; Marko J. Spasojevic; Pora Ellen Porhallsdottir; Anne Tolvanen; Tiffany Troxler; Craig E. Tweedie; Sandra Villareal; Carl-Henrik Wahren; Xanthe Walker; Patrick J. Webber; Jeffrey M. Welker; Sonja Wipf

    2012-01-01

    Temperature is increasing at unprecedented rates across most of the tundra biome1. Remote-sensing data indicate that contemporary climate warming has already resulted in increased productivity over much of the Arctic2,3, but plot-based evidence for vegetation transformation is not widespread. We analysed change in tundra vegetation surveyed between 1980 and 2010 in 158...

  15. Newborn screening for X-linked adrenoleukodystrophy: further evidence high throughput screening is feasible.

    Science.gov (United States)

    Theda, Christiane; Gibbons, Katy; Defor, Todd E; Donohue, Pamela K; Golden, W Christopher; Kline, Antonie D; Gulamali-Majid, Fizza; Panny, Susan R; Hubbard, Walter C; Jones, Richard O; Liu, Anita K; Moser, Ann B; Raymond, Gerald V

    2014-01-01

    X-linked adrenoleukodystrophy (ALD) is characterized by adrenal insufficiency and neurologic involvement with onset at variable ages. Plasma very long chain fatty acids are elevated in ALD; even in asymptomatic patients. We demonstrated previously that liquid chromatography tandem mass spectrometry measuring C26:0 lysophosphatidylcholine reliably identifies affected males. We prospectively applied this method to 4689 newborn blood spot samples; no false positives were observed. We show that high throughput neonatal screening for ALD is methodologically feasible. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Othmane, K.B.; Speer, M.C.; Stauffer, J. [Duke Univ. Medical Center, Durham, NC (United States)] [and others

    1995-09-01

    Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive Limb Girdle muscular dystrophy (LGMD2C) characterized by late age of onset, proximal muscle weakness leading to disability, high creatine kinase values, normal intelligence and normal dystrophin in muscle biopsy. We have shown previously that three DLMD families from Tunisia are linked to chromosome 13q12. To further localize the LGMD2C gene, we have investigated seven additional families (119 individuals). Both genotyping and two-point linkage analysis were performed as described elsewhere. 7 refs., 1 fig., 1 tab.

  17. X linked neonatal centronuclear/myotubular myopathy: evidence for linkage to Xq28 DNA marker loci.

    OpenAIRE

    Thomas, N S; Williams, H; Cole, G; Roberts, K; Clarke, A; Liechti-Gallati, S; Braga, S; Gerber, A; Meier, C; Moser, H

    1990-01-01

    We have studied the inheritance of several polymorphic Xq27/28 DNA marker loci in two three generation families with the X linked neonatal lethal form of centronuclear/myotubular myopathy (XL MTM). We found complete linkage of XLMTM to all four informative Xq28 markers analysed, with GCP/RCP (Z = 3.876, theta = 0.00), with DXS15 (Z = 3.737, theta = 0.00), with DXS52 (Z = 2.709, theta = 0.00), and with F8C (Z = 1.020, theta = 0.00). In the absence of any observable recombination, we are unable...

  18. Application of plant DNA markers in forensic botany: genetic comparison of Quercus evidence leaves to crime scene trees using microsatellites.

    Science.gov (United States)

    Craft, Kathleen J; Owens, Jeffrey D; Ashley, Mary V

    2007-01-05

    As highly polymorphic DNA markers become increasingly available for a wide range of plant and animal species, there will be increasing opportunities for applications to forensic investigations. To date, however, relatively few studies have reported using DNA profiles of non-human species to place suspects at or near crime scenes. Here we describe an investigation of a double homicide of a female and her near-term fetus. Leaf material taken from a suspect's vehicle was identified to be that of sand live oak, Quercus geminata, the same tree species that occurred near a shallow grave where the victims were found. Quercus-specific DNA microsatellites were used to genotype both dried and fresh material from trees located near the burial site and from the material taken from the suspect's car. Samples from the local population of Q. geminata were also collected and genotyped in order to demonstrate that genetic variation at four microsatellite loci was sufficient to assign leaves to an individual tree with high statistical certainty. The cumulative average probability of identity for these four loci was 2.06x10(-6). DNA was successfully obtained from the dried leaf material although PCR amplification was more difficult than amplification of DNA from fresh leaves. The DNA profiles of the dried leaves from the suspect's car did not match those of the trees near the crime scene. Although this investigation did not provide evidence that could be used against the suspect, it does demonstrate the potential for plant microsatellite markers providing physical evidence that links plant materials to live plants at or near crime scenes.

  19. Putting the five-factor model into context: evidence linking big five traits to narrative identity.

    Science.gov (United States)

    Raggatt, Peter

    2006-10-01

    The study examined relationships between the Big Five personality traits and thematic content extracted from self-reports of life history data. One hundred and five "mature age" university students (M=30.1 years) completed the NEO PI-R trait measure, and the Personality Web Protocol. The protocol examines constituents of identity by asking participants to describe 24 key "attachments" from their life histories (significant events, people, places, objects, and possessions). Participants sorted these attachments into clusters and provided a self-descriptive label for each cluster (e.g., "adventurous self"). It was predicted that the thematic content of these cluster labels would be systematically related to Big Five trait scores (e.g., that labels referring to strength or positive emotions would be linked to Extraversion). The hypothesized links were obtained for each of the Big Five trait domains except Conscientiousness. Results are discussed with a view to broadening our understanding of the Five-Factor Model in relation to units of personality other than traits.

  20. Assimilation and Health: Evidence From Linked Birth Records of Second- and Third-Generation Hispanics.

    Science.gov (United States)

    Giuntella, Osea

    2016-12-01

    This study explores the effects of assimilation on the health of Hispanics in the United States, using ethnic intermarriage as a metric of acculturation. I exploit a unique data set of linked confidential use birth records in California and Florida from 1970-2009. The confidential data allow me to link mothers giving birth in 1989-2009 to their own birth certificate records in 1970-1985 and to identify second-generation siblings. Thus, I can analyze the relationship between the parental exogamy of second-generation Hispanic women and the birth outcomes of their offspring controlling for grandmother fixed effects as well as indicators for second generation's birth weight. Despite their higher socioeconomic status, third-generation children of second-generation intermarried Hispanic women are more likely to have poor health at birth, even after I account for second-generation health at birth and employ only within-family variations in the extent of assimilation. I find that a second-generation Hispanic woman married to a non-Hispanic man is 9 % more likely to have a child with low birth weight relative to a second-generation woman married to another Hispanic. These results largely reflect the higher incidence of risky behaviors (e.g., smoking during pregnancy) among intermarried Hispanic women.

  1. Lung cancer mortality among silicotic workers in Hong Kong--no evidence for a link.

    Science.gov (United States)

    Yu, I T S; Tse, L A; Leung, C C; Wong, T W; Tam, C M; Chan, A C K

    2007-06-01

    The link between silica dust/silicosis and lung cancer is still very controversial. We examined the relationship between silica dust exposure and/or silicosis and lung cancer in a large cohort of silicotic workers in Hong Kong. All workers with silicosis in Hong Kong diagnosed during the period 1981-1998 were followed up till the end of 1999 to ascertain their vital status and causes of death. Standardized mortality ratio (SMR) for lung cancer and other major causes of death were calculated. Axelson's indirect method was used to adjust for smoking effect. Multiple Cox regression models were carried out to examine the exposure-response relationship between silica dust and lung cancer. About 10% (86) of all 853 deaths were from lung cancer, giving a SMR of 1.69 [95% confidence interval (CI) 1.35-2.09]. Lung cancer SMR for caisson and surface construction workers were 2.39 (95% CI 1.50-3.62) and 1.61 (95% CI 1.21-2.10), respectively, which became 1.56 (95% CI 0.98-2.36) and 1.09 (95% CI 0.82-1.42) after adjusting for smoking. No consistent exposure-response relationship was detected between silica dust or severity of silicosis and lung cancer death. Our cohort study did not offer positive support to a link between silica or silicosis and lung cancer.

  2. Genetic Evidence for Elevated Pathogenicity of Mitochondrial DNA Heteroplasmy in Autism Spectrum Disorder.

    Directory of Open Access Journals (Sweden)

    Yiqin Wang

    2016-10-01

    Full Text Available Increasing clinical and biochemical evidence implicate mitochondrial dysfunction in the pathophysiology of Autism Spectrum Disorder (ASD, but little is known about the biological basis for this connection. A possible cause of ASD is the genetic variation in the mitochondrial DNA (mtDNA sequence, which has yet to be thoroughly investigated in large genomic studies of ASD. Here we evaluated mtDNA variation, including the mixture of different mtDNA molecules in the same individual (i.e., heteroplasmy, using whole-exome sequencing data from mother-proband-sibling trios from simplex families (n = 903 where only one child is affected by ASD. We found that heteroplasmic mutations in autistic probands were enriched at non-polymorphic mtDNA sites (P = 0.0015, which were more likely to confer deleterious effects than heteroplasmies at polymorphic mtDNA sites. Accordingly, we observed a ~1.5-fold enrichment of nonsynonymous mutations (P = 0.0028 as well as a ~2.2-fold enrichment of predicted pathogenic mutations (P = 0.0016 in autistic probands compared to their non-autistic siblings. Both nonsynonymous and predicted pathogenic mutations private to probands conferred increased risk of ASD (Odds Ratio, OR[95% CI] = 1.87[1.14-3.11] and 2.55[1.26-5.51], respectively, and their influence on ASD was most pronounced in families with probands showing diminished IQ and/or impaired social behavior compared to their non-autistic siblings. We also showed that the genetic transmission pattern of mtDNA heteroplasmies with high pathogenic potential differed between mother-autistic proband pairs and mother-sibling pairs, implicating developmental and possibly in utero contributions. Taken together, our genetic findings substantiate pathogenic mtDNA mutations as a potential cause for ASD and synergize with recent work calling attention to their unique metabolic phenotypes for diagnosis and treatment of children with ASD.

  3. Genetic data provide evidence for wind-mediated transmission of highly pathogenic avian influenza.

    Science.gov (United States)

    Ypma, Rolf J F; Jonges, Marcel; Bataille, Arnaud; Stegeman, Arjan; Koch, Guus; van Boven, Michiel; Koopmans, Marion; van Ballegooijen, W Marijn; Wallinga, Jacco

    2013-03-01

    Outbreaks of highly pathogenic avian influenza in poultry can cause severe economic damage and represent a public health threat. Development of efficient containment measures requires an understanding of how these influenza viruses are transmitted between farms. However, the actual mechanisms of interfarm transmission are largely unknown. Dispersal of infectious material by wind has been suggested, but never demonstrated, as a possible cause of transmission between farms. Here we provide statistical evidence that the direction of spread of avian influenza A(H7N7) is correlated with the direction of wind at date of infection. Using detailed genetic and epidemiological data, we found the direction of spread by reconstructing the transmission tree for a large outbreak in the Netherlands in 2003. We conservatively estimate the contribution of a possible wind-mediated mechanism to the total amount of spread during this outbreak to be around 18%.

  4. Genetic evidence for natural selection in humans in the contemporary United States.

    Science.gov (United States)

    Beauchamp, Jonathan P

    2016-07-12

    Recent findings from molecular genetics now make it possible to test directly for natural selection by analyzing whether genetic variants associated with various phenotypes have been under selection. I leverage these findings to construct polygenic scores that use individuals' genotypes to predict their body mass index, educational attainment (EA), glucose concentration, height, schizophrenia, total cholesterol, and (in females) age at menarche. I then examine associations between these scores and fitness to test whether natural selection has been occurring. My study sample includes individuals of European ancestry born between 1931 and 1953 who participated in the Health and Retirement Study, a representative study of the US population. My results imply that natural selection has been slowly favoring lower EA in both females and males, and are suggestive that natural selection may have favored a higher age at menarche in females. For EA, my estimates imply a rate of selection of about -1.5 mo of education per generation (which pales in comparison with the increases in EA observed in contemporary times). Although they cannot be projected over more than one generation, my results provide additional evidence that humans are still evolving-albeit slowly, especially compared with the rapid changes that have occurred over the past few generations due to cultural and environmental factors.

  5. Evidence of genetic heterogeneity in Alberta Hutterites with Usher syndrome type I.

    Science.gov (United States)

    Zhou, Qi; Lenger, Chaeli; Smith, Richard; Kimberling, William J; Ye, Ming; Lehmann, Ordan; MacDonald, Ian

    2012-01-01

    To identify the genetic defect in a Hutterite population from northern Alberta with Usher syndrome type I. Complete ophthalmic examinations were conducted on two boys and two girls from two related Hutterite families diagnosed with Usher syndrome type I. DNA from patients and their parents was first evaluated for a mutation in exon 10 of the protocadherin-related 15 (PCDH15) gene (c.1471delG), previously reported in southern Alberta Hutterite patients with Usher syndrome (USH1F). Single nucleotide polymorphic linkage analysis was then used to confirm another locus, and DNA was analyzed with the Usher Chip v4.0 platform. Severe hearing impairment, unintelligible speech, and retinitis pigmentosa with varying degrees of visual acuity and visual field loss established a clinical diagnosis of Usher syndrome type I. The patients did not carry the exon 10 mutation in the PCDH15 gene; however, with microarray analysis, a previously reported mutation (c.52C>T; p.Q18X) in the myosin VIIA (MYO7A) gene was found in the homozygous state in the affected siblings. The finding of a MYO7A mutation in two related Hutterite families from northern Alberta provides evidence of genetic heterogeneity in Hutterites affected by Usher syndrome type I.

  6. Molecular genetic evidence for the place of origin of the Pacific rat, Rattus exulans.

    Directory of Open Access Journals (Sweden)

    Vicki Thomson

    Full Text Available Commensal plants and animals have long been used to track human migrations, with Rattus exulans (the Pacific rat a common organism for reconstructing Polynesian dispersal in the Pacific. However, with no knowledge of the homeland of R. exulans, the place of origin of this human-commensal relationship is unknown. We conducted a mitochondrial DNA phylogeographic survey of R. exulans diversity across the potential natural range in mainland and Island Southeast Asia in order to establish the origin of this human-commensal dyad. We also conducted allozyme electrophoresis on samples from ISEA to obtain a perspective on patterns of genetic diversity in this critical region. Finally, we compared molecular genetic evidence with knowledge of prehistoric rodent faunas in mainland and ISEA. We find that ISEA populations of R. exulans contain the highest mtDNA lineage diversity including significant haplotype diversity not represented elsewhere in the species range. Within ISEA, the island of Flores in the Lesser Sunda group contains the highest diversity in ISEA (across all loci and also has a deep fossil record of small mammals that appears to include R. exulans. Therefore, in addition to Flores harboring unusual diversity in the form of Homo floresiensis, dwarfed stegodons and giant rats, this island appears to be the homeland of R. exulans.

  7. BIG data - BIG gains? Empirical evidence on the link between big data analytics and innovation

    OpenAIRE

    Niebel, Thomas; Rasel, Fabienne; Viete, Steffen

    2017-01-01

    This paper analyzes the relationship between firms’ use of big data analytics and their innovative performance in terms of product innovations. Since big data technologies provide new data information practices, they create novel decision-making possibilities, which are widely believed to support firms’ innovation process. Applying German firm-level data within a knowledge production function framework we find suggestive evidence that big data analytics is a relevant determinant for the likel...

  8. Forensic DNA identification of animal-derived trace evidence: tools for linking victims and suspects.

    Science.gov (United States)

    Halverson, Joy L; Basten, Christopher

    2005-08-01

    To evaluate the population substructure of purebred dogs and cats in order to estimate the true significance of a microsatellite-based DNA match for use as evidence in legal proceedings. The high frequency of animal hair as a forensic evidence submission necessitates the development of mitochondrial analysis tools as well. Random samples from a large convenience collection of veterinary diagnostic submissions from the western USA were used, as well as contributed samples of unrelated purebred cats and dogs. Dogs (n=558) were profiled with 17 microsatellites and the data evaluated for Hardy Weinberg and linkage equilibrium. The mitochondrial control region (D loop) of dogs (n=348) and cats (n=167) was sequenced to determine the haplotype distribution. Domestic dogs in the western United States showed significant population substructure with marked associations within loci but no disequilibrium between loci. A population substructure coefficient Theta=0.11 is recommended for calculating genotype frequencies. Mitochondrial haplotypes in cats and dogs show less variation than human haplotypes. Although population substructure occurs in domestic dogs (and can be inferred in cats), the discriminatory power of microsatellite analysis is dramatic with even partial DNA types, strongly supporting the prosecution of perpetrators in five discussed cases. Mitochondrial analysis, while less powerful, adds a layer of evidence in four discussed cases.

  9. Barbie or Betty? Preschool children's preference for branded products and evidence for gender-linked differences.

    Science.gov (United States)

    Pine, Karen J; Nash, Avril

    2003-08-01

    Children in the United Kingdom watch more television and are exposed to more advertising than children in any other European country. This article investigates the extent to which preschool children (aged 4-5 years) prefer brands advertised on television. Seventy-five children were interviewed and given a choice task in which they had to select the product, from eight pairs each comprising a branded and nonbranded product, that children of their own age and gender preferred. Products included popular drinks, snacks, toys, breakfast cereals, and sportswear. Nonbranded control products were carefully selected as close perceptual matches for the branded advertised products. Yet, on 68% of occasions, children chose the branded, advertised product in preference to the nonbranded product. This preference was reliably higher for girls (78%) than boys (58%). Gender-linked differences are discussed in relation to socialization theory and to girls' greater verbal ability and emotional sensitivity.

  10. Evidence on a link between the intensity of Schumann resonance and global surface temperature

    Directory of Open Access Journals (Sweden)

    M. Sekiguchi

    2006-08-01

    Full Text Available A correlation is investigated between the intensity of the global electromagnetic oscillations (Schumann resonance with the planetary surface temperature. The electromagnetic signal was monitored at Moshiri (Japan, and temperature data were taken from surface meteorological observations. The series covers the period from November 1998 to May 2002. The Schumann resonance intensity is found to vary coherently with the global ground temperature in the latitude interval from 45° S to 45° N: the relevant cross-correlation coefficient reaches the value of 0.9. It slightly increases when the high-latitude temperature is incorporated. Correspondence among the data decreases when we reduce the latitude interval, which indicates the important role of the middle-latitude lightning in the Schumann resonance oscillations. We apply the principal component (or singular spectral analysis to the electromagnetic and temperature records to extract annual, semiannual, and interannual variations. The principal component analysis (PCA clarifies the links between electromagnetic records and meteorological data.

  11. Medical Management of Endometriosis: Emerging Evidence Linking Inflammation to Disease Pathophysiology

    Science.gov (United States)

    Bruner-Tran, Kaylon L.; Herington, Jennifer L.; Duleba, Antoni J.; Taylor, Hugh S.; Osteen, Kevin G.

    2013-01-01

    Progesterone action normally mediates the balance between anti-inflammatory and pro-inflammatory processes throughout the female reproductive tract. However, in women with endometriosis, endometrial progesterone resistance, characterized by alterations in progesterone responsive gene and protein expression, is now considered a central element in disease pathophysiology. Recent studies additionally suggest that the peritoneal microenvironment of endometriosis patients exhibits altered physiological characteristics that may further promote inflammation-driven disease development and progression. Within this review, we summarize our current understanding of the pathogenesis of endometriosis with an emphasis on the role that inflammation plays in generating not only the progesterone-resistant eutopic endometrium but also a peritoneal microenvironment that may contribute significantly to disease establishment. Viewing endometriosis from the emerging perspective that a progesterone resistant endometrium and an immunologically compromised peritoneal microenvironment are biologically linked risk factors for disease development provides a novel mechanistic framework to identify new therapeutic targets for appropriate medical management. PMID:23598784

  12. Genetic Evidence Supports the Multiethnic Character of Teopancazco, a Neighborhood Center of Teotihuacan, Mexico (AD 200-600.

    Directory of Open Access Journals (Sweden)

    Brenda A Álvarez-Sandoval

    Full Text Available Multiethnicity in Teopancazco, Teotihuacan, is supported by foreign individuals found in the neighborhood center as well as by the diversity observed in funerary rituals at the site. Studies of both stable and strontium isotopes as well as paleodietary analysis, suggest that the population of Teopancazco was composed by three population groups: people from Teotihuacan, people from nearby sites (Tlaxcala-Hidalgo-Puebla, and people from afar, including the coastal plains. In an attempt to understand the genetic dynamics in Teopancazco we conducted an ancient DNA (aDNA analysis based on mtDNA. Our results show that the level of genetic diversity is consistent with the multiethnicity phenomenon at the neighborhood center. Levels of genetic diversity at different time periods of Teopancazco's history show that multiethnicity was evident since the beginning and lasted until the collapse of the neighborhood center. However, a PCA and a Neighbor-Joining tree suggested the presence of a genetically differentiated group (buried at the Transitional phase compared to the population from the initial phase (Tlamimilolpa as well as the population from the final phase (Xolalpan of the history of Teopancazco. Genetic studies showed no differences in genetic diversity between males and females in the adult population of Teopancazco, this data along with ample archaeological evidence, suggest a neolocal post-marital pattern of residence in Teopancazco. Nevertheless, genetic analyses on the infant population showed that the males are significantly more heterogeneous than the females suggesting a possible differential role in cultural practices by sex in the infant sector. Regarding interpopulation analysis, we found similar indices of genetic diversity between Teopancazco and heterogeneous native groups, which support the multiethnic character of Teopancazco. Finally, our data showed a close genetic relationship between Teopancazco and populations from the

  13. An 'integrative neuroscience' perspective on ADHD: linking cognition, emotion, brain and genetic measures with implications for clinical support.

    Science.gov (United States)

    Williams, Leanne M; Tsang, Tracey W; Clarke, Simon; Kohn, Michael

    2010-10-01

    There remains a translational gap between research findings and their implementation in clinical practice that applies to attention-deficit/hyperactivity disorder (ADHD), as well as to other major disorders of brain health in childhood, adolescence and adulthood. Research studies have identified potential 'markers' to support diagnostic, functional assessment and treatment decisions, but there is little consensus about these markers. Of these potential markers, cognitive measures of thinking functions, such as sustaining attention and associated electrical brain activity, show promise in complementing the clinical management process. Emerging evidence highlights the relevance of emotional, as well as thinking, functions to ADHD. Here, we outline an integrative neuroscience framework for ADHD that offers one means to bring together cognitive measures of thinking functions with measures of emotion, and their brain and genetic correlates. Understanding these measures and the relationships between them is a first step towards the development of tools that will help to assess the heterogeneity of ADHD, and aid in tailoring treatment choices.

  14. Identification of the missing links in prokaryotic pentose oxidation pathways: evidence for enzyme recruitment.

    Science.gov (United States)

    Brouns, Stan J J; Walther, Jasper; Snijders, Ambrosius P L; van de Werken, Harmen J G; Willemen, Hanneke L D M; Worm, Petra; de Vos, Marjon G J; Andersson, Anders; Lundgren, Magnus; Mazon, Hortense F M; van den Heuvel, Robert H H; Nilsson, Peter; Salmon, Laurent; de Vos, Willem M; Wright, Phillip C; Bernander, Rolf; van der Oost, John

    2006-09-15

    The pentose metabolism of Archaea is largely unknown. Here, we have employed an integrated genomics approach including DNA microarray and proteomics analyses to elucidate the catabolic pathway for D-arabinose in Sulfolobus solfataricus. During growth on this sugar, a small set of genes appeared to be differentially expressed compared with growth on D-glucose. These genes were heterologously overexpressed in Escherichia coli, and the recombinant proteins were purified and biochemically studied. This showed that D-arabinose is oxidized to 2-oxoglutarate by the consecutive action of a number of previously uncharacterized enzymes, including a D-arabinose dehydrogenase, a D-arabinonate dehydratase, a novel 2-keto-3-deoxy-D-arabinonate dehydratase, and a 2,5-dioxopentanoate dehydrogenase. Promoter analysis of these genes revealed a palindromic sequence upstream of the TATA box, which is likely to be involved in their concerted transcriptional control. Integration of the obtained biochemical data with genomic context analysis strongly suggests the occurrence of pentose oxidation pathways in both Archaea and Bacteria, and predicts the involvement of additional enzyme components. Moreover, it revealed striking genetic similarities between the catabolic pathways for pentoses, hexaric acids, and hydroxyproline degradation, which support the theory of metabolic pathway genesis by enzyme recruitment.

  15. Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies.

    Science.gov (United States)

    Mocellin, Simone; Tropea, Saveria; Benna, Clara; Rossi, Carlo Riccardo

    2018-02-19

    Dysfunction of the circadian clock and single polymorphisms of some circadian genes have been linked to cancer susceptibility, although data are scarce and findings inconsistent. We aimed to investigate the association between circadian pathway genetic variation and risk of developing common cancers based on the findings of genome-wide association studies (GWASs). Single nucleotide polymorphisms (SNPs) of 17 circadian genes reported by three GWAS meta-analyses dedicated to breast (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Consortium; cases, n = 15,748; controls, n = 18,084), prostate (Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium; cases, n = 14,160; controls, n = 12,724) and lung carcinoma (Transdisciplinary Research In Cancer of the Lung (TRICL) Consortium; cases, n = 12,160; controls, n = 16,838) in patients of European ancestry were utilized to perform pathway analysis by means of the adaptive rank truncated product (ARTP) method. Data were also available for the following subgroups: estrogen receptor negative breast cancer, aggressive prostate cancer, squamous lung carcinoma and lung adenocarcinoma. We found a highly significant statistical association between circadian pathway genetic variation and the risk of breast (pathway P value = 1.9 × 10 -6 ; top gene RORA, gene P value = 0.0003), prostate (pathway P value = 4.1 × 10 -6 ; top gene ARNTL, gene P value = 0.0002) and lung cancer (pathway P value = 6.9 × 10 -7 ; top gene RORA, gene P value = 2.0 × 10 -6 ), as well as all their subgroups. Out of 17 genes investigated, 15 were found to be significantly associated with the risk of cancer: four genes were shared by all three malignancies (ARNTL, CLOCK, RORA and RORB), two by breast and lung cancer (CRY1 and CRY2) and three by prostate and lung cancer (NPAS2, NR1D1 and PER3), whereas four genes were specific for lung cancer

  16. The missing link between sleep disorders and age-related dementia: recent evidence and plausible mechanisms.

    Science.gov (United States)

    Zhang, Feng; Zhong, Rujia; Li, Song; Chang, Raymond Chuen-Chung; Le, Weidong

    2017-05-01

    Sleep disorders are among the most common clinical problems and possess a significant concern for the geriatric population. More importantly, while around 40% of elderly adults have sleep-related complaints, sleep disorders are more frequently associated with co-morbidities including age-related neurodegenerative diseases and mild cognitive impairment. Recently, increasing evidence has indicated that disturbed sleep may not only serve as the consequence of brain atrophy, but also contribute to the pathogenesis of dementia and, therefore, significantly increase dementia risk. Since the current therapeutic interventions lack efficacies to prevent, delay or reverse the pathological progress of dementia, a better understanding of underlying mechanisms by which sleep disorders interact with the pathogenesis of dementia will provide possible targets for the prevention and treatment of dementia. In this review, we briefly describe the physiological roles of sleep in learning/memory, and specifically update the recent research evidence demonstrating the association between sleep disorders and dementia. Plausible mechanisms are further discussed. Moreover, we also evaluate the possibility of sleep therapy as a potential intervention for dementia.

  17. Assessing links between energy consumption, freight transport, and economic growth: evidence from dynamic simultaneous equation models.

    Science.gov (United States)

    Nasreen, Samia; Saidi, Samir; Ozturk, Ilhan

    2018-06-01

    We investigate this study to examine the relationship between economic growth, freight transport, and energy consumption for 63 developing countries over the period of 1990-2016. In order to make the panel data analysis more homogeneous, we apply the income level of countries to divide the global panel into three sub-panels, namely, lower-middle income countries (LMIC), upper-middle income countries (UMIC), and high-income countries (HIC). Using the generalized method of moments (GMM), the results prove evidence of bidirectional causal relationship between economic growth and freight transport for all selected panels and between economic growth and energy consumption for the high- and upper-middle income panels. For the lower-middle income panel, the causality is unidirectional running from energy consumption to economic growth. Also, the results indicate that the relationship between freight transport and energy use is bidirectional for the high-income countries and unidirectional from freight transport to energy consumption for the upper-middle and lower-middle income countries. Empirical evidence demonstrates the importance of energy for economic activity and rejects the neo-classical assumption that energy is neutral for growth. An important policy recommendation is that there is need of advancements in vehicle technology which can reduce energy intensity from transport sector and improve the energy efficiency in transport activity which in turn allows a greater positive role of transport in global economic activity.

  18. Genetic evidence for the association between the early growth response 3 (EGR3 gene and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Rui Zhang

    Full Text Available Recently, two genome scan meta-analysis studies have found strong evidence for the association of loci on chromosome 8p with schizophrenia. The early growth response 3 (EGR3 gene located in chromosome 8p21.3 was also found to be involved in the etiology of schizophrenia. However, subsequent studies failed to replicate this finding. To investigate the genetic role of EGR3 in Chinese patients, we genotyped four SNPs (average interval ∼2.3 kb in the chromosome region of EGR3 in 470 Chinese schizophrenia patients and 480 healthy control subjects. The SNP rs35201266 (located in intron 1 of EGR3 showed significant differences between cases and controls in both genotype frequency distribution (P = 0.016 and allele frequency distribution (P = 0.009. Analysis of the haplotype rs35201266-rs3750192 provided significant evidence for association with schizophrenia (P = 0.0012; a significant difference was found for the common haplotype AG (P = 0.0005. Furthermore, significant associations were also found in several other two-, and three-SNP tests of haplotype analyses. The meta-analysis revealed a statistically significant association between rs35201266 and schizophrenia (P = 0.0001. In summary, our study supports the association of EGR3 with schizophrenia in our Han Chinese sample, and further functional exploration of the EGR3 gene will contribute to the molecular basis for the complex network underlying schizophrenia pathogenesis.

  19. Explaining health care expenditure variation: large-sample evidence using linked survey and health administrative data.

    Science.gov (United States)

    Ellis, Randall P; Fiebig, Denzil G; Johar, Meliyanni; Jones, Glenn; Savage, Elizabeth

    2013-09-01

    Explaining individual, regional, and provider variation in health care spending is of enormous value to policymakers but is often hampered by the lack of individual level detail in universal public health systems because budgeted spending is often not attributable to specific individuals. Even rarer is self-reported survey information that helps explain this variation in large samples. In this paper, we link a cross-sectional survey of 267 188 Australians age 45 and over to a panel dataset of annual healthcare costs calculated from several years of hospital, medical and pharmaceutical records. We use this data to distinguish between cost variations due to health shocks and those that are intrinsic (fixed) to an individual over three years. We find that high fixed expenditures are positively associated with age, especially older males, poor health, obesity, smoking, cancer, stroke and heart conditions. Being foreign born, speaking a foreign language at home and low income are more strongly associated with higher time-varying expenditures, suggesting greater exposure to adverse health shocks. Copyright © 2013 John Wiley & Sons, Ltd.

  20. The causal link between energy and output growth: Evidence from Markov switching Granger causality

    International Nuclear Information System (INIS)

    Kandemir Kocaaslan, Ozge

    2013-01-01

    In this paper we empirically investigate the causal link between energy consumption and economic growth employing a Markov switching Granger causality analysis. We carry out our investigation using annual U.S. real GDP, total final energy consumption and total primary energy consumption data which cover the period between 1968 and 2010. We find that there are significant changes in the causal relation between energy consumption and economic growth over the sample period under investigation. Our results show that total final energy consumption and total primary energy consumption have significant predictive content for real economic activity in the U.S. economy. Furthermore, the causality running from energy consumption to output growth seems to be strongly apparent particularly during the periods of economic downturn and energy crisis. We also document that output growth has predictive power in explaining total energy consumption. Furthermore, the power of output growth in predicting total energy consumption is found to diminish after the mid of 1980s. - Highlights: • Total energy consumption has predictive content for real economic activity. • The causality from energy to output growth is apparent in the periods of recession. • The causality from energy to output growth is strong in the periods of energy crisis. • Output growth has predictive power in explaining total energy consumption. • The power of output growth in explaining energy diminishes after the mid of 1980s

  1. Nature, nurture, and capital punishment: How evidence of a genetic-environment interaction, future dangerousness, and deliberation affect sentencing decisions.

    Science.gov (United States)

    Gordon, Natalie; Greene, Edie

    2018-01-01

    Research has shown that the low-activity MAOA genotype in conjunction with a history of childhood maltreatment increases the likelihood of violent behaviors. This genetic-environment (G × E) interaction has been introduced as mitigation during the sentencing phase of capital trials, yet there is scant data on its effectiveness. This study addressed that issue. In a factorial design that varied mitigating evidence offered by the defense [environmental (i.e., childhood maltreatment), genetic, G × E, or none] and the likelihood of the defendant's future dangerousness (low or high), 600 mock jurors read sentencing phase evidence in a capital murder trial, rendered individual verdicts, and half deliberated as members of a jury to decide a sentence of death or life imprisonment. The G × E evidence had little mitigating effect on sentencing preferences: participants who received the G × E evidence were no less likely to sentence the defendant to death than those who received evidence of childhood maltreatment or a control group that received neither genetic nor maltreatment evidence. Participants with evidence of a G × E interaction were more likely to sentence the defendant to death when there was a high risk of future dangerousness than when there was a low risk. Sentencing preferences were more lenient after deliberation than before. We discuss limitations and future directions. Copyright © 2017 John Wiley & Sons, Ltd.

  2. New evidence for "far-field" Holocene sea level oscillations and links to global climate records

    Science.gov (United States)

    Leonard, N. D.; Welsh, K. J.; Clark, T. R.; Feng, Y.-x.; Pandolfi, J. M.; Zhao, J.-x.

    2018-04-01

    Rising sea level in the coming century is of significant concern, yet predicting relative sea level change in response to eustatic sea level variability is complex. Potential analogues are provided by the recent geological past but, until recently, many sea level reconstructions have been limited to millennial scale interpretations due to age uncertainties and paucity in proxy derived records. Here we present a sea level history for the tectonically stable "far-field" Great Barrier Reef, Australia, derived from 94 high precision uranium-thorium dates of sub-fossil coral microatolls. Our results provide evidence for at least two periods of relative sea level instability during the Holocene. These sea level oscillations are broadly synchronous with Indo-Pacific negative sea surface temperature anomalies, rapid global cooling events and glacial advances. We propose that the pace and magnitude of these oscillations are suggestive of eustatic/thermosteric processes operating in conjunction with regional climatic controls.

  3. Evidences linking ENSO and coral growth in the Southwestern-South Atlantic

    Energy Technology Data Exchange (ETDEWEB)

    Evangelista, H. [LARAMG, Laboratorio de Radioecologia e Mudancas Globais/DBB/UERJ. Pav. HLC, Subsolo, Maracana, RJ (Brazil); Godiva, D. [LARAMG, Laboratorio de Radioecologia e Mudancas Globais/DBB/UERJ. Pav. HLC, Subsolo, Maracana, RJ (Brazil); Universidade Federal Fluminense, Outeiro Sao Joao Batista, s/n, Centro, Departamento de Geoquimica Ambiental, Niteroi, RJ (Brazil); Sifeddine, A. [IRD, Institut de Recherche Pour le Developpement, UR055 Paleotropique, Bondy (France); Universidade Federal Fluminense, Outeiro Sao Joao Batista, s/n, Centro, Departamento de Geoquimica Ambiental, Niteroi, RJ (Brazil); Leao, Z.M.A.N.; Kikuchi, R.K.P. [UFBA/Instituto de Geociencias. Rua Barao de Geremoabo, s/n, Federacao, Salvador, BA (Brazil); Rigozo, N.R. [LARAMG, Laboratorio de Radioecologia e Mudancas Globais/DBB/UERJ. Pav. HLC, Subsolo, Maracana, RJ (Brazil); FAETEC, Faculdade de Educacao e Tecnologia Thereza Porto Marques, Jacarei, SP (Brazil); Segal, B. [UFRJ/Museu Nacional/Setor de Celenterologia/Departamento de Invertebrados, Quinta da Boa Vista s/n, Sao Cristovao, RJ (Brazil); Ambrizzi, T. [USP/Department of Atmospheric Sciences, Sao Paulo, SP (Brazil); Kampel, M. [INPE/Divisao de Sensoriamento Remoto, Sao Paulo, SP (Brazil); Cornec, F. le [Universidade Federal Fluminense, Outeiro Sao Joao Batista, s/n, Centro, Departamento de Geoquimica Ambiental, Niteroi, RJ (Brazil)

    2007-12-15

    Physical and biological changes in the marine environment, induced by oceanic-atmospheric processes, can be imprinted in massive coral skeletons. Herein, we present an evidence of potential El Nino impacts at the Southwestern South Atlantic Ocean (SWSA) inferred from the sclerochronology of the reef coral Favia leptophylla. The application of spectral analysis (wavelet decomposition and the iterative regression) to coral growth length and to meteorological-oceanographic parameters (air temperature, sea surface temperature and precipitation) as well as to Southern Oscillation Index (SOI) and solar irradiation indicated a major significant inverse relationship between SOI and coral growth length at the 4-8 years frequency band. We propose here that coral growth length from the SWSA could be affected by El Nino Southern Oscillation (ENSO) events through an ''atmospheric bridge'', in contrast to its direct effect at the Pacific Ocean, related to the increase in sea surface temperature. (orig.)

  4. Empirical Evidence on the Link Between Compliance with Governance of Best Practice and Firms' Operating Results

    Directory of Open Access Journals (Sweden)

    Tek B. Lama

    2012-12-01

    Full Text Available This study provides robust evidence in support of the agency theory argument that corporate governancematters for a firm’s operating performance. Using the corporate governance ratings as the governance proxyfrom Horwath 2006 Corporate Governance Report (mid-sized Australian ASX companies andMid-CapCorporate Governance Report 2007 (The University of Newcastle 2006; 2007, I examine 60 sample firms toreveal that a firm’s governance is positively and significantly related to firm performance as measured by returnon equity, earning yield and return on assets. This study extends the findings of these two reports which founda disturbing trend in the corporate governance practice of Australian mid-cap companies – both a decrease incompanies with excellent corporate governance, and an increase in companies with significant corporategovernance deficiencies. The findings of this study suggest that those mid-size companies who have allowedcorporate governance to deteriorate have adversely affected their shareholder returns.

  5. Evidence of a prominent genetic basis for associations between psychoneurometric traits and common mental disorders.

    Science.gov (United States)

    Venables, Noah C; Hicks, Brian M; Yancey, James R; Kramer, Mark D; Nelson, Lindsay D; Strickland, Casey M; Krueger, Robert F; Iacono, William G; Patrick, Christopher J

    2017-05-01

    Threat sensitivity (THT) and weak inhibitory control (or disinhibition; DIS) are trait constructs that relate to multiple types of psychopathology and can be assessed psychoneurometrically (i.e., using self-report and physiological indicators combined). However, to establish that psychoneurometric assessments of THT and DIS index biologically-based liabilities, it is important to clarify the etiologic bases of these variables and their associations with clinical problems. The current work addressed this important issue using data from a sample of identical and fraternal adult twins (N=454). THT was quantified using a scale measure and three physiological indicators of emotional reactivity to visual aversive stimuli. DIS was operationalized using scores on two scale measures combined with two brain indicators from cognitive processing tasks. THT and DIS operationalized in these ways both showed appreciable heritability (0.45, 0.68), and genetic variance in these traits accounted for most of their phenotypic associations with fear, distress, and substance use disorder symptoms. Our findings suggest that, as indices of basic dispositional liabilities for multiple forms of psychopathology with direct links to neurophysiology, psychoneurometric assessments of THT and DIS represent novel and important targets for biologically-oriented research on psychopathology. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia.

    Science.gov (United States)

    Devor, A; Andreassen, O A; Wang, Y; Mäki-Marttunen, T; Smeland, O B; Fan, C-C; Schork, A J; Holland, D; Thompson, W K; Witoelar, A; Chen, C-H; Desikan, R S; McEvoy, L K; Djurovic, S; Greengard, P; Svenningsson, P; Einevoll, G T; Dale, A M

    2017-06-01

    The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ. Here, we review these findings from the standpoint of classical neurobiological knowledge of neuronal synaptic transmission and regulation of electrical excitability. We show that a substantial proportion of the identified genes are involved in intracellular cascades known to integrate 'slow' (G-protein-coupled receptors) and 'fast' (ionotropic receptors) neurotransmission converging on the protein DARPP-32. Inspection of the Human Brain Transcriptome Project database confirms that that these genes are indeed expressed in the brain, with the expression profile following specific developmental trajectories, underscoring their relevance to brain organization and function. These findings extend the existing pathophysiology hypothesis by suggesting a unifying role of dysregulation in neuronal excitability and synaptic integration in SCZ. This emergent model supports the concept of SCZ as an 'associative' disorder-a breakdown in the communication across different slow and fast neurotransmitter systems through intracellular signaling pathways-and may unify a number of currently competing hypotheses of SCZ pathophysiology.

  7. Application of a genetic algorithm in the conformational analysis of methylene-acetal-linked thymine dimers in DNA: Comparison with distance geometry calculations

    International Nuclear Information System (INIS)

    Beckers, Mischa L.M.; Buydens, Lutgarde M.C.; Pikkemaat, Jeroen A.; Altona, Cornelis

    1997-01-01

    The three-dimensional spatial structure of a methylene-acetal-linked thymine dimer present in a 10 base-pair (bp) sense-antisense DNA duplex was studied with a genetic algorithm designed to interpret NOE distance restraints. Trial solutions were represented by torsion angles. This means that bond angles for the dimer trial structures are kept fixed during the genetic algorithm optimization. Bond angle values were extracted from a 10 bp sense-antisense duplex model that was subjected to energy minimization by means of a modified AMBER force field. A set of 63 proton-proton distance restraints defining the methylene-acetal-linked thymine dimer was available. The genetic algorithm minimizes the difference between distances in the trial structures and distance restraints. A large conformational search space could be covered in the genetic algorithm optimization by allowing a wide range of torsion angles. The genetic algorithm optimization in all cases led to one family of structures. This family of the methylene-acetal-linked thymine dimer in the duplex differs from the family that was suggested from distance geometry calculations. It is demonstrated that the bond angle geometry around the methylene-acetal linkage plays an important role in the optimization

  8. The link between motor and cognitive development in children born preterm and/or with low birth weight : A review of current evidence

    NARCIS (Netherlands)

    Oudgenoeg-Paz, Ora; Mulder, Hanna; Jongmans, Marian J.; van der Ham, Ineke J.M.; Van der Stigchel, Stefan

    2017-01-01

    The current review focuses on evidence for a link between early motor development and later cognitive skills in children born preterm or with Low Birth Weight (LBW). Studies with term born children consistently show such a link. Motor and cognitive impairments or delays are often seen in children

  9. Genetic evidence of paleolithic colonization and neolithic expansion of modern humans on the tibetan plateau.

    Science.gov (United States)

    Qi, Xuebin; Cui, Chaoying; Peng, Yi; Zhang, Xiaoming; Yang, Zhaohui; Zhong, Hua; Zhang, Hui; Xiang, Kun; Cao, Xiangyu; Wang, Yi; Ouzhuluobu; Basang; Ciwangsangbu; Bianba; Gonggalanzi; Wu, Tianyi; Chen, Hua; Shi, Hong; Su, Bing

    2013-08-01

    Tibetans live on the highest plateau in the world, their current population size is approximately 5 million, and most of them live at an altitude exceeding 3,500 m. Therefore, the Tibetan Plateau is a remarkable area for cultural and biological studies of human population history. However, the chronological profile of the Tibetan Plateau's colonization remains an unsolved question of human prehistory. To reconstruct the prehistoric colonization and demographic history of modern humans on the Tibetan Plateau, we systematically sampled 6,109 Tibetan individuals from 41 geographic populations across the entire region of the Tibetan Plateau and analyzed the phylogeographic patterns of both paternal (n = 2,354) and maternal (n = 6,109) lineages as well as genome-wide single nucleotide polymorphism markers (n = 50) in Tibetan populations. We found that there have been two distinct, major prehistoric migrations of modern humans into the Tibetan Plateau. The first migration was marked by ancient Tibetan genetic signatures dated to approximately 30,000 years ago, indicating that the initial peopling of the Tibetan Plateau by modern humans occurred during the Upper Paleolithic rather than Neolithic. We also found evidences for relatively young (only 7-10 thousand years old) shared Y chromosome and mitochondrial DNA haplotypes between Tibetans and Han Chinese, suggesting a second wave of migration during the early Neolithic. Collectively, the genetic data indicate that Tibetans have been adapted to a high altitude environment since initial colonization of the Tibetan Plateau in the early Upper Paleolithic, before the last glacial maximum, followed by a rapid population expansion that coincided with the establishment of farming and yak pastoralism on the Plateau in the early Neolithic.

  10. Multimodal neuroimaging evidence linking memory and attention systems during visual search cued by context.

    Science.gov (United States)

    Kasper, Ryan W; Grafton, Scott T; Eckstein, Miguel P; Giesbrecht, Barry

    2015-03-01

    Visual search can be facilitated by the learning of spatial configurations that predict the location of a target among distractors. Neuropsychological and functional magnetic resonance imaging (fMRI) evidence implicates the medial temporal lobe (MTL) memory system in this contextual cueing effect, and electroencephalography (EEG) studies have identified the involvement of visual cortical regions related to attention. This work investigated two questions: (1) how memory and attention systems are related in contextual cueing; and (2) how these systems are involved in both short- and long-term contextual learning. In one session, EEG and fMRI data were acquired simultaneously in a contextual cueing task. In a second session conducted 1 week later, EEG data were recorded in isolation. The fMRI results revealed MTL contextual modulations that were correlated with short- and long-term behavioral context enhancements and attention-related effects measured with EEG. An fMRI-seeded EEG source analysis revealed that the MTL contributed the most variance to the variability in the attention enhancements measured with EEG. These results support the notion that memory and attention systems interact to facilitate search when spatial context is implicitly learned. © 2015 New York Academy of Sciences.

  11. Intense-personal celebrity worship and body image: evidence of a link among female adolescents.

    Science.gov (United States)

    Maltby, John; Giles, David C; Barber, Louise; McCutcheon, Lynn E

    2005-02-01

    The aim of the present study was to examine the relationship between celebrity worship and body image within the theoretical perspective of intense para-social relationships with celebrities. Correlation and multiple regression analyses were used to examine the relationships between celebrity worship and body image. Three samples, 229 (102 males and 127 females) adolescents, 183 (88 males and 95 females) full-time university undergraduate students, and 289 (126 males and 163 females) adults were administered an amended version of the Celebrity Attitude Scale, the Attention to Body Shape Scale, and the Body Shape Questionnaire-Revised. Significant relationships were found between attitudes toward celebrities and body image only among female adolescents. Multiple regression analyses suggested that Intense-personal celebrity worship accounted for unique variance in scores in body image. Findings suggest that in female adolescents, there is an interaction between Intense-personal celebrity worship and body image between the ages of 14 and 16 years, and some tentative evidence has been found to suggest that this relationship disappears at the onset of adulthood, 17 to 20 years. Results are consistent with those authors who stress the importance of the formation of para-social relationships with media figures, and suggest that para-social relationships with celebrities perceived as having a good body shape may lead to a poor body image in female adolescents.

  12. A review of evidence for the link between sleep duration and hypertension.

    Science.gov (United States)

    Gangwisch, James E

    2014-10-01

    There are lines of evidence from experimental sleep deprivation studies, population-based epidemiological studies, and an interventional study that point to the potential efficacy of adequate quality sleep to prevent and treat hypertension. Experimental sleep restriction has been shown to raise blood pressure and heart rate. Insufficient sleep on a chronic basis can raise average 24-hour blood pressure and lead to structural adaptations that entrain the cardiovascular system to operate at an elevated blood pressure equilibrium and increase the risk for hypertension. Disruptions in the timing and duration of sleep could also disrupt circadian rhythmicity and autonomic balance, which can increase the prevalence of the nondipping pattern, disturb diurnal rhythm of cardiac output, and increase blood pressure variability. Short sleep duration has been found to be associated with higher blood pressure and hypertension in both cross-sectional and longitudinal epidemiological studies. The association appears stronger in middle-aged adults and in women. Experimental sleep extension has been shown to significantly reduce blood pressure in individuals with prehypertension or stage 1 hypertension. The observed association between sleep duration and hypertension raises the hypothesis that interventions to extend sleep and improve sleep quality could serve as effective primary, secondary, and tertiary preventive measures for hypertension. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Validity of Quinpirole Sensitization Rat Model of OCD: Linking Evidence from Animal and Clinical Studies.

    Science.gov (United States)

    Stuchlik, Ales; Radostová, Dominika; Hatalova, Hana; Vales, Karel; Nekovarova, Tereza; Koprivova, Jana; Svoboda, Jan; Horacek, Jiri

    2016-01-01

    Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with 1-3% prevalence. OCD is characterized by recurrent thoughts (obsessions) and repetitive behaviors (compulsions). The pathophysiology of OCD remains unclear, stressing the importance of pre-clinical studies. The aim of this article is to critically review a proposed animal model of OCD that is characterized by the induction of compulsive checking and behavioral sensitization to the D2/D3 dopamine agonist quinpirole. Changes in this model have been reported at the level of brain structures, neurotransmitter systems and other neurophysiological aspects. In this review, we consider these alterations in relation to the clinical manifestations in OCD, with the aim to discuss and evaluate axes of validity of this model. Our analysis shows that some axes of validity of quinpirole sensitization model (QSM) are strongly supported by clinical findings, such as behavioral phenomenology or roles of brain structures. Evidence on predictive validity is contradictory and ambiguous. It is concluded that this model is useful in the context of searching for the underlying pathophysiological basis of the disorder because of the relatively strong biological similarities with OCD.

  14. Genetic Variation and Association Analysis of the SSR Markers Linked to the Major Drought-Yield QTLs of Rice.

    Science.gov (United States)

    Tabkhkar, Narjes; Rabiei, Babak; Samizadeh Lahiji, Habibollah; Hosseini Chaleshtori, Maryam

    2018-02-24

    Drought is one of the major abiotic stresses, which hampers the production of rice worldwide. Informative molecular markers are valuable tools for improving the drought tolerance in various varieties of rice. The present study was conducted to evaluate the informative simple sequence repeat (SSR) markers in a diverse set of rice genotypes. The genetic diversity analyses of the 83 studied rice genotypes were performed using 34 SSR markers closely linked to the major quantitative trait loci (QTLs) of grain yield under drought stress (qDTYs). In general, our results indicated high levels of polymorphism. In addition, we screened these rice genotypes at the reproductive stage under both drought stress and nonstressful conditions. The results of the regression analysis demonstrated a significant relationship between 11 SSR marker alleles and the plant paddy weight under stressful conditions. Under the nonstressful conditions, 16 SSR marker alleles showed a significant correlation with the plant paddy weight. Finally, four markers (RM279, RM231, RM166, and RM231) demonstrated a significant association with the plant paddy weight under both stressful and nonstressful conditions. These informative-associated alleles may be useful for improving the crop yield under both drought stress and nonstressful conditions in breeding programs.

  15. First evidence of genetic intraspecific variability and occurrence of Entamoeba gingivalis in HIV(+/AIDS.

    Directory of Open Access Journals (Sweden)

    Sibeli B S Cembranelli

    Full Text Available Entamoeba gingivalis is considered an oral commensal but demonstrates a pathogenic potential associated with periodontal disease in immunocompromised individuals. Therefore, this study evaluated the occurrence, opportunistic conditions, and intraspecific genetic variability of E. gingivalis in HIV(+/AIDS patients. Entamoeba gingivalis was studied using fresh examination (FE, culture, and PCR from bacterial plaque samples collected from 82 HIV(+/AIDS patients. Genetic characterization of the lower ribosomal subunit of region 18S (18S-SSU rRNA was conducted in 9 positive samples using low-stringency single specific primer PCR (LSSP-PCR and sequencing analysis. Entamoeba gingivalis was detected in 63.4% (52/82 of the samples. No association was detected between the presence of E. gingivalis and the CD4(+ lymphocyte count (≤200 cells/mm(3 (p = 0.912 or viral load (p = 0.429. The LSSP-PCR results helped group E. gingivalis populations into 2 polymorphic groups (68.3% similarity: group I, associated with 63.6% (7/11 of the samples, and group II, associated with 36.4% (4/11 of the samples, which shared 74% and 83.7% similarity and association with C and E isolates from HIV(- individuals, respectively. Sequencing of 4 samples demonstrated 99% identity with the reference strain ATCC 30927 and also showed 2 divergent clusters, similar to those detected by LSSP-PCR. Opportunistic behavior of E. gingivalis was not detected, which may be related to the use of highly active antiretroviral therapy by all HIV(+/AIDS patients. The high occurrence of E. gingivalis in these patients can be influenced by multifactorial components not directly related to the CD4(+ lymphocyte counts, such as cholesterol and the oral microbiota host, which could mask the potential opportunistic ability of E. gingivalis. The identification of the 18S SSU-rRNA polymorphism by LSSP-PCR and sequencing analysis provides the first evidence of genetic variability in E. gingivalis

  16. Seasonality shows evidence for polygenic architecture and genetic correlation with schizophrenia and bipolar disorder – a meta-analysis of genetic studies

    Science.gov (United States)

    Byrne, Enda M; Raheja, Uttam; Stephens, Sarah H.; Heath, Andrew C; Madden, Pamela AF; Vaswani, Dipika; Nijjar, Gagan V.; Ryan, Kathleen A.; Youssufi, Hassaan; Gehrman, Philip R; Shuldiner, Alan R; Martin, Nicholas G; Montgomery, Grant W; Wray, Naomi R; Nelson, Elliot C; Mitchell, Braxton D; Postolache, Teodor T

    2015-01-01

    Objective To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality. Methods A meta-analysis of genome-wide association studies (GWAS) conducted in Australian and Amish populations in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered. The total sample size was 4,156 individuals. Genetic risk scores based on results from prior large GWAS studies of bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ) were calculated to test for overlap in risk between psychiatric disorders and seasonality. Results The most significant association was with rs11825064 (p = 1.7 × 10−6, β = 0.64, S.E = 0.13), an intergenic SNP found on chromosome 11. The evidence for overlap in risk factors was strongest for SCZ and seasonality, with the SCZ genetic profile scores explaining 3% of the variance in log-transformed GSS. BD genetic profile scores were also significantly associated with seasonality, although at much weaker levels, and no evidence for overlap in risk was detected between MDD and seasonality. Conclusions Common SNPs of very large effect likely do not exist for seasonality in the populations examined. As expected, there was overlapping genetic risk factors for BD (but not MDD) with seasonality. Unexpectedly, the risk for SCZ and seasonality had the largest overlap, an unprecedented finding that requires replication in other populations, and has potential clinical implications considering overlapping cognitive deficits in seasonal affective disorders and SCZ PMID:25562672

  17. Indirect Evidence Link PCB Dehalogenation with Geobacteraceae in Anaerobic Sediment-Free Microcosms.

    Science.gov (United States)

    Praveckova, Martina; Brennerova, Maria V; Holliger, Christof; De Alencastro, Felippe; Rossi, Pierre

    2016-01-01

    Although polychlorinated biphenyls (PCBs) production was brought to a halt 30 years ago, recalcitrance to degradation makes them a major environmental pollutant at a global scale. Previous studies confirmed that organohalide-respiring bacteria (OHRB) were capable of utilizing chlorinated congeners as electron acceptor. OHRB belonging to the Phyla Chloroflexi and Firmicutes are nowadays considered as the main PCB-dechlorinating organisms. In this study, we aimed at exploring the involvement of other taxa in PCB dechlorination using sediment-free microcosms (SFMs) and the Delor PCB mixture. High rates of congener dehalogenation (up to 96%) were attained in long-term incubations of up to 692 days. Bacterial communities were dominated by Chloroflexi, Proteobacteria, and Firmicutes, among strictly simplified community structures composed of 12 major phyla only. In a first batch of SFMs, Dehalococcoides mccartyi closely affiliated with strains CG4 and CBDB1 was considered as the main actor associated with congener dehalogenation. Addition of 2-bromoethanesulfonate (BES), a known inhibitor of methanogenic activity in a second batch of SFMs had an adverse effect on the abundance of Dehalococcoides sp. Only two sequences affiliated to this Genus could be detected in two (out of six) BES-treated SFMs, contributing to a mere 0.04% of the communities. BES-treated SFMs showed very different community structures, especially in the contributions of organisms involved in fermentation and syntrophic activities. Indirect evidence provided by both statistical and phylogenetic analysis validated the implication of a new cluster of actors, distantly affiliated with the Family Geobacteraceae (Phylum δ-Proteobacteria), in the dehalogenation of low chlorinated PCB congeners. Members of this Family are known already for their dehalogenation capacity of chlorinated solvents. As a result, the present study widens the knowledge for the phylogenetic reservoir of indigenous PCB dechlorinating

  18. Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins.

    Science.gov (United States)

    Moreno, Estefanía; Canet, Júlia; Gracia, Eduard; Lluís, Carme; Mallol, Josefa; Canela, Enric I; Cortés, Antoni; Casadó, Vicent

    2018-01-01

    Adenosine is an endogenous purine nucleoside that acts in all living systems as a homeostatic network regulator through many pathways, which are adenosine receptor (AR)-dependent and -independent. From a metabolic point of view, adenosine deaminase (ADA) is an essential protein in the regulation of the total intracellular and extracellular adenosine in a tissue. In addition to its cytosolic localization, ADA is also expressed as an ecto-enzyme on the surface of different cells. Dipeptidyl peptidase IV (CD26) and some ARs act as binding proteins for extracellular ADA in humans. Since CD26 and ARs interact with ADA at opposite sites, we have investigated if ADA can function as a cell-to-cell communication molecule by bridging the anchoring molecules CD26 and A 2A R present on the surfaces of the interacting cells. By combining site-directed mutagenesis of ADA amino acids involved in binding to A 2A R and a modification of the bioluminescence resonance energy transfer (BRET) technique that allows detection of interactions between two proteins expressed in different cell populations with low steric hindrance (NanoBRET), we show direct evidence of the specific formation of trimeric complexes CD26-ADA-A 2A R involving two cells. By dynamic mass redistribution assays and ligand binding experiments, we also demonstrate that A 2A R-NanoLuc fusion proteins are functional. The existence of this ternary complex is in good agreement with the hypothesis that ADA could bridge T-cells (expressing CD26) and dendritic cells (expressing A 2A R). This is a new metabolic function for ecto-ADA that, being a single chain protein, it has been considered as an example of moonlighting protein, because it performs more than one functional role (as a catalyst, a costimulator, an allosteric modulator and a cell-to-cell connector) without partitioning these functions in different subunits.

  19. Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins

    Directory of Open Access Journals (Sweden)

    Estefanía Moreno

    2018-02-01

    Full Text Available Adenosine is an endogenous purine nucleoside that acts in all living systems as a homeostatic network regulator through many pathways, which are adenosine receptor (AR-dependent and -independent. From a metabolic point of view, adenosine deaminase (ADA is an essential protein in the regulation of the total intracellular and extracellular adenosine in a tissue. In addition to its cytosolic localization, ADA is also expressed as an ecto-enzyme on the surface of different cells. Dipeptidyl peptidase IV (CD26 and some ARs act as binding proteins for extracellular ADA in humans. Since CD26 and ARs interact with ADA at opposite sites, we have investigated if ADA can function as a cell-to-cell communication molecule by bridging the anchoring molecules CD26 and A2AR present on the surfaces of the interacting cells. By combining site-directed mutagenesis of ADA amino acids involved in binding to A2AR and a modification of the bioluminescence resonance energy transfer (BRET technique that allows detection of interactions between two proteins expressed in different cell populations with low steric hindrance (NanoBRET, we show direct evidence of the specific formation of trimeric complexes CD26-ADA-A2AR involving two cells. By dynamic mass redistribution assays and ligand binding experiments, we also demonstrate that A2AR-NanoLuc fusion proteins are functional. The existence of this ternary complex is in good agreement with the hypothesis that ADA could bridge T-cells (expressing CD26 and dendritic cells (expressing A2AR. This is a new metabolic function for ecto-ADA that, being a single chain protein, it has been considered as an example of moonlighting protein, because it performs more than one functional role (as a catalyst, a costimulator, an allosteric modulator and a cell-to-cell connector without partitioning these functions in different subunits.

  20. Spread of butternut canker in North America, host range, evidence of resistance within butternut populations and conservation genetics

    Science.gov (United States)

    M. E. Ostry; K. Woeste

    2004-01-01

    Butternut canker is killing trees throughout the range of butternut in North America and is threatening the viability of many populations in several areas. Although butternut is the primary host, other Juglans species and some hardwood species also are potential hosts. Evidence is building that genetic resistance within butternut populations may be...

  1. Evidence of Allopolyploidy in Urochloa humidicola Based on Cytological Analysis and Genetic Linkage Mapping.

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    Bianca B Z Vigna

    Full Text Available The African species Urochloa humidicola (Rendle Morrone & Zuloaga (syn. Brachiaria humidicola (Rendle Schweick. is an important perennial forage grass found throughout the tropics. This species is polyploid, ranging from tetra to nonaploid, and apomictic, which makes genetic studies challenging; therefore, the number of currently available genetic resources is limited. The genomic architecture and evolution of U. humidicola and the molecular markers linked to apomixis were investigated in a full-sib F1 population obtained by crossing the sexual accession H031 and the apomictic cultivar U. humidicola cv. BRS Tupi, both of which are hexaploid. A simple sequence repeat (SSR-based linkage map was constructed for the species from 102 polymorphic and specific SSR markers based on simplex and double-simplex markers. The map consisted of 49 linkage groups (LGs and had a total length of 1702.82 cM, with 89 microsatellite loci and an average map density of 10.6 cM. Eight homology groups (HGs were formed, comprising 22 LGs, and the other LGs remained ungrouped. The locus that controls apospory (apo-locus was mapped in LG02 and was located 19.4 cM from the locus Bh027.c.D2. In the cytological analyses of some hybrids, bi- to hexavalents at diakinesis were observed, as well as two nucleoli in some meiocytes, smaller chromosomes with preferential allocation within the first metaphase plate and asynchronous chromosome migration to the poles during anaphase. The linkage map and the meiocyte analyses confirm previous reports of hybridization and suggest an allopolyploid origin of the hexaploid U. humidicola. This is the first linkage map of an Urochloa species, and it will be useful for future quantitative trait locus (QTL analysis after saturation of the map and for genome assembly and evolutionary studies in Urochloa spp. Moreover, the results of the apomixis mapping are consistent with previous reports and confirm the need for additional studies to search for

  2. Missing Links Between Genetically Inherited Molecules in Split Cord Malformation and Other Anomaly: A Bench to Bedside Approach.

    Science.gov (United States)

    Barik, Mayadhar; Mishra, Pravash R; Mohapatra, Ashok Kumar

    2018-01-01

    Split cord malformation (SCM) is associated with extensive vertebral fusions (Klippel-Feil anomaly). In light of previous embryological theories and recent research findings, we attempt to document the origin of split cord, and vertebral fusions involvement of spectrum of genes is necessary to know better the etiopathogenesis of SCM and its associated diseases. We used the various databases such as PubMed/MEDLINE, Cochrane Review, Hinari, and Google Scholar for the recently published medical literature. The women had been living and still born infants had SCM. The relative risk (RR) and possible molecular mechanism are described details of major genes and its variants in details. Although molecular genetics involvement including with recent advances of study add an evidence of both Mendelian and Non-Mendelian fashion is discussed with all genetic components. We mentioned our earlier experience and responsibility of SCM and its associated diseases. Although different mechanisms are suggested for the development of SCM observed in our experience, there is a midline lesion bisecting the neuroepithelium and the notochordal plate, which is responsible for complete splitting of the cervical cord with anterior bony defect. The localized disturbance of cervical neural tube closure accounts for SCM with partial dorsal splitting of the cord with posterior vertebral defect and associated diseases. According to the best of our knowledge, this report is the first one to be documented by wider spectrum of variants from (experimental studies to human subject). This add a complex interaction of mutant variants drive toward an additional second-hit alterations for the SCM. The up-to-date information, documented in proper order, derived the bench-to-bedside approach to overcome this burden of SCM, which is globally noticed with other additional diseases.

  3. A genetic basis for infectious mononucleosis: evidence from a family study of hospitalized cases in Denmark.

    Science.gov (United States)

    Rostgaard, Klaus; Wohlfahrt, Jan; Hjalgrim, Henrik

    2014-06-01

    Circumstantial evidence from genome-wide association and family studies of various Epstein-Barr virus-associated diseases suggests a substantial genetic component in infectious mononucleosis (IM) etiology. However, familial aggregation of IM has scarcely been studied. We used data from the Danish Civil Registration System and the Danish National Hospital Discharge Register to study rate ratios of IM in a cohort of 2 823 583 Danish children born between 1971 and 2011. Specifically, we investigated the risk of IM in twins and in first-, second-, and third-degree relatives of patients with IM. In the analyses, IM was defined as a diagnosis of IM in a hospital contact. Effects of contagion between family members were dealt with by excluding follow-up time the first year after the occurrence of IM in a relative. A total of 16 870 cases of IM were observed during 40.4 million person-years of follow-up from 1977 to 2011. The rate ratios and the associated 95% confidence intervals were 9.3 (3.0-29) in same-sex twins, 3.0 (2.6-3.5) in siblings, 1.9 (1.6-2.2) in children, 1.4 (1.3-1.6) in second-degree relatives, and 1.0 (0.9-1.2) in third-degree relatives of IM patients. The rate ratios were very similar for IM in children (aged 0-6 years) and older children/adolescents (aged 7-19 years). We found evidence of familial aggregation of IM that warrants genome-wide association studies on IM disease etiology, especially to examine commonalities with causal pathways in other Epstein-Barr virus-related diseases. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Evidence of genetic differentiation and karyotype evolution of the sedges Cyperus ligularis L. and C. odoratus L. (Cyperaceae

    Directory of Open Access Journals (Sweden)

    Geyner Alves dos Santos Cruz

    2018-01-01

    Full Text Available ABSTRACT The taxonomy of Cyperaceae is complex, with genera like Cyperus harboring species complexes. We analyzed the genetic similarity between Cyperus ligularis L. and C. odoratus L. based on DNA fingerprinting and cytogenetics. Significative genetic differentiation (G ST = 0.363 and low gene flow (N m = 0.877 indicated a clear genetic distinction between the two species. Moreover, the clustering analysis showed two distinct genetic groups, suggesting a lack of evidence for hybridization. The phenogram revealed two different lineages, and although all individuals of C. odoratus were collected from plots close to each other, they possessed greater genetic diversity than that observed among individuals of C. ligularis, which were sampled over a wider geographic range. Variation in chromosome number within the two species exhibited the opposite pattern, indicating greater karyotype stability in C. odoratus with 2n = 72 and 2n = 76, while the diploid number for C. ligularis varied from 2n = 66 to 88. The lower genetic variation in C. ligularis may be a result of the founder effect associated with seed dispersion and clonal reproduction. Field observations and analysis of reproductive biology should enrich the understanding of the genetic structure of the investigated populations and their role in successional processes.

  5. Genetic variability, local selection and demographic history: genomic evidence of evolving towards allopatric speciation in Asian seabass.

    Science.gov (United States)

    Wang, Le; Wan, Zi Yi; Lim, Huan Sein; Yue, Gen Hua

    2016-08-01

    Genomewide analysis of genetic divergence is critically important in understanding the genetic processes of allopatric speciation. We sequenced RAD tags of 131 Asian seabass individuals of six populations from South-East Asia and Australia/Papua New Guinea. Using 32 433 SNPs, we examined the genetic diversity and patterns of population differentiation across all the populations. We found significant evidence of genetic heterogeneity between South-East Asian and Australian/Papua New Guinean populations. The Australian/Papua New Guinean populations showed a rather lower level of genetic diversity. FST and principal components analysis revealed striking divergence between South-East Asian and Australian/Papua New Guinean populations. Interestingly, no evidence of contemporary gene flow was observed. The demographic history was further tested based on the folded joint site frequency spectrum. The scenario of ancient migration with historical population size changes was suggested to be the best fit model to explain the genetic divergence of Asian seabass between South-East Asia and Australia/Papua New Guinea. This scenario also revealed that Australian/Papua New Guinean populations were founded by ancestors from South-East Asia during mid-Pleistocene and were completely isolated from the ancestral population after the last glacial retreat. We also detected footprints of local selection, which might be related to differential ecological adaptation. The ancient gene flow was examined and deemed likely insufficient to counteract the genetic differentiation caused by genetic drift. The observed genomic pattern of divergence conflicted with the 'genomic islands' scenario. Altogether, Asian seabass have likely been evolving towards allopatric speciation since the split from the ancestral population during mid-Pleistocene. © 2016 John Wiley & Sons Ltd.

  6. Molecular genetic analysis of two families with keratosis follicularis spinulosa decalvans : refinement of gene localization and evidence for genetic heterogeneity

    NARCIS (Netherlands)

    Oosterwijk, JC; Richard, G; vanderWielen, MJR; van de Vosse, E; Harth, W; Sandkuijl, LA; Bakker, E; vanOmmen, GJB

    1997-01-01

    X-linked keratosis follicularis spinulosa decalvans (KFSD) is a rare disorder affecting both skin and eyes, In the two extended KFSD families analysed to date, the gene was mapped to Xp22.13-p22.2. By analyzing several new markers in this region, we were able to narrow the candidate region to a 1-Mb

  7. 'Faceness' and affectivity: evidence for genetic contributions to distinct components of electrocortical response to human faces.

    Science.gov (United States)

    Shannon, Robert W; Patrick, Christopher J; Venables, Noah C; He, Sheng

    2013-12-01

    The ability to recognize a variety of different human faces is undoubtedly one of the most important and impressive functions of the human perceptual system. Neuroimaging studies have revealed multiple brain regions (including the FFA, STS, OFA) and electrophysiological studies have identified differing brain event-related potential (ERP) components (e.g., N170, P200) possibly related to distinct types of face information processing. To evaluate the heritability of ERP components associated with face processing, including N170, P200, and LPP, we examined ERP responses to fearful and neutral face stimuli in monozygotic (MZ) and dizygotic (DZ) twins. Concordance levels for early brain response indices of face processing (N170, P200) were found to be stronger for MZ than DZ twins, providing evidence of a heritable basis to each. These findings support the idea that certain key neural mechanisms for face processing are genetically coded. Implications for understanding individual differences in recognition of facial identity and the emotional content of faces are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Genetic evidence for intra- and interspecific slavery in honey ants (genus Myrmecocystus).

    Science.gov (United States)

    Kronauer, D J C; Gadau, J; Hölldobler, B

    2003-04-22

    The New World honey ant species Myrmecocystus mimicus is well known for its highly stereotyped territorial tournaments, and for the raids on conspecific nests that can lead to intraspecific slavery. Our results from mitochondrial and nuclear markers show that the raided brood emerges in the raiding colony and is subsequently incorporated into the colony's worker force. We also found enslaved conspecifics in a second honey ant species, M. depilis, the sister taxon of M. mimicus, which occurs in sympatry with M. mimicus at the study site. Colonies of this species furthermore contained raided M. mimicus workers. Both species have an effective mating frequency that is not significantly different from 1. This study provides genetic evidence for facultative intra- and interspecific slavery in the genus Myrmecocystus. Slavery in ants has evolved repeatedly and supposedly by different means. We propose that, in honey ants, secondary contact between two closely related species that both exhibit intraspecific slavery gave rise to an early form of facultative interspecific slavery.

  9. Genetic and phenotypic evidence of the Salmonella enterica serotype Enteritidis human-animal interface in Chile

    Directory of Open Access Journals (Sweden)

    Patricio eRetamal

    2015-05-01

    Full Text Available Salmonella enterica serotype Enteritidis is a worldwide zoonotic agent that has been recognized as a very important food-borne bacterial pathogen, mainly associated with consumption of poultry products. The aim of this work was to determine genotypic and phenotypic evidence of S. Enteritidis transmission among seabirds, poultry and humans in Chile. Genotyping was performed using PCR-based virulotyping, pulse-field gel electrophoresis (PFGE and multi-locus sequence typing (MLST. Pathogenicity-associated phenotypes were determined with survival to free radicals, acidic pH, starvation, antimicrobial resistance, and survival within human dendritic cells. As result of PCR and PFGE assays, some isolates from the three hosts showed identical genotypic patterns, and through MLST it was determined that all of them belong to sequence type 11. Results of phenotypic assays showed diversity of survival capabilities among isolates. When results were analyzed according to bacterial host, statistical differences were identified in starvation and dendritic cells survival assays. In addition, isolates from seabirds showed the highest rates of resistance to gentamycin, tetracycline and ampicillin. Overall, the very close genetic and phenotypic traits shown by isolates from humans, poultry and seabirds suggest the inter-species transmission of S. Enteritidis bacteria between hosts, likely through anthropogenic environmental contamination that determines infection of seabirds with bacteria that are potentially pathogenic for other susceptible organism, including humans.

  10. There is no evidence for a temporal link between pathogen arrival and frog extinctions in north-eastern Australia.

    Directory of Open Access Journals (Sweden)

    Ben L Phillips

    Full Text Available Pathogen spread can cause population declines and even species extinctions. Nonetheless, in the absence of tailored monitoring schemes, documenting pathogen spread can be difficult. In the case of worldwide amphibian declines the best present understanding is that the chytrid fungus Batrachochytrium dendrobatidis (Bd has recently spread, causing amphibian declines and extinction in the process. However, good evidence demonstrating pathogen arrival followed by amphibian decline is rare, and analysis of putative evidence is often inadequate. Here we attempt to examine the relationship between Bd arrival and amphibian decline across north-eastern Australia, using sites where a wave-like pattern of amphibian decline was first noticed and at which intensive research has since been conducted. We develop an analytical framework that allows rigorous estimation of pathogen arrival date, which can then be used to test for a correlation between the time of pathogen arrival and amphibian decline across sites. Our results show that, with the current dataset, the earliest possible arrival date of Bd in north-eastern Australia is completely unresolved; Bd could have arrived immediately before sampling commenced or may have arrived thousands of years earlier, the present data simply cannot say. The currently available data are thus insufficient to assess the link between timing of pathogen arrival and population decline in this part of the world. This data insufficiency is surprising given that there have been decades of research on chytridiomycosis in Australia and that there is a general belief that the link between Bd arrival and population decline is well resolved in this region. The lack of data on Bd arrival currently acts as a major impediment to determining the role of environmental factors in driving the global amphibian declines, and should be a major focus of future research.

  11. Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study.

    Science.gov (United States)

    Iacovazzo, Donato; Caswell, Richard; Bunce, Benjamin; Jose, Sian; Yuan, Bo; Hernández-Ramírez, Laura C; Kapur, Sonal; Caimari, Francisca; Evanson, Jane; Ferraù, Francesco; Dang, Mary N; Gabrovska, Plamena; Larkin, Sarah J; Ansorge, Olaf; Rodd, Celia; Vance, Mary L; Ramírez-Renteria, Claudia; Mercado, Moisés; Goldstone, Anthony P; Buchfelder, Michael; Burren, Christine P; Gurlek, Alper; Dutta, Pinaki; Choong, Catherine S; Cheetham, Timothy; Trivellin, Giampaolo; Stratakis, Constantine A; Lopes, Maria-Beatriz; Grossman, Ashley B; Trouillas, Jacqueline; Lupski, James R; Ellard, Sian; Sampson, Julian R; Roncaroli, Federico; Korbonits, Márta

    2016-06-01

    Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly.We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants.We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes in found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic of familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases.In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101

  12. Mutational analyses of molecularly cloned satellite tobacco mosaic virus during serial passage in plants: Evidence for hotspots of genetic change

    Science.gov (United States)

    Kurath, G.; Dodds, J.A.

    1995-01-01

    The high level of genetic diversity and rapid evolution of viral RNA genomes are well documented, but few studies have characterized the rate and nature of ongoing genetic change over time under controlled experimental conditions, especially in plant hosts. The RNA genome of satellite tobacco mosaic virus (STMV) was used as an effective model for such studies because of advantageous features of its genome structure and because the extant genetic heterogeneity of STMV has been characterized previously. In the present study, the process of genetic change over time was studied by monitoring multiple serial passage lines of STMV populations for changes in their consensus sequences. A total of 42 passage lines were initiated by inoculation of tobacco plants with a helper tobamovirus and one of four STMV RNA inocula that were transcribed from full-length infectious STMV clones or extracted from purified STMV type strain virions. Ten serial passages were carried out for each line and the consensus genotypes of progeny STMV populations were assessed for genetic change by RNase protection analyses of the entire 1,059-nt STMV genome. Three different types of genetic change were observed, including the fixation of novel mutations in 9 of 42 lines, mutation at the major heterogeneity site near nt 751 in 5 of the 19 lines inoculated with a single genotype, and selection of a single major genotype in 6 of the 23 lines inoculated with mixed genotypes. Sequence analyses showed that the majority of mutations were single base substitutions. The distribution of mutation sites included three clusters in which mutations occurred at or very near the same site, suggesting hot spots of genetic change in the STMV genome. The diversity of genetic changes in sibling lines is clear evidence for the important role of chance and random sampling events in the process of genetic diversification of STMV virus populations.

  13. Linking Genetic Variation in Adaptive Plant Traits to Climate in Tetraploid and Octoploid Basin Wildrye [Leymus cinereus (Scribn. & Merr.) A. Love] in the Western U.S.

    Science.gov (United States)

    Johnson, R C; Vance-Borland, Ken

    2016-01-01

    Few studies have assessed how ploidy type within a species affects genetic variation among populations in relation to source climates. Basin wildrye (Leymus cinereus (Scribn. & Merr.) A. Love) is a large bunchgrass common in the intermountain Western U.S. found in both octoploid and tetraploid types. In common gardens at two sites over two years differences in both ploidy type and genetic variation within ploidy were observed in phenology, morphology, and production traits on 57 octoploid and 52 tetraploid basin wildrye from the intermountain Western U.S. (Ptypes. Still, among populations octoploids often had greater genetic variation for traits and occupied more diverse climates than tetraploids. Genetic variation for both ploidy types was linked to source climates in canonical correlation analysis, with the first two variates explaining 70% of the variation. Regression of those canonical variates with seed source climate variables produced models that explained 64% and 38% of the variation, respectively, and were used to map 15 seed zones covering 673,258 km2. Utilization of these seed zones will help ensure restoration with adaptive seed sources for both ploidy types. The link between genetic traits and seed source climates suggests climate driven natural selection and adaptive evolution in basin wildrye. The more diverse climates occupied by octoploids and higher trait variation suggests a higher capacity for ecological differentiation than tetraploids in the intermountain Western U.S.

  14. A parametric interpretation of Bayesian Nonparametric Inference from Gene Genealogies: Linking ecological, population genetics and evolutionary processes.

    Science.gov (United States)

    Ponciano, José Miguel

    2017-11-22

    Using a nonparametric Bayesian approach Palacios and Minin (2013) dramatically improved the accuracy, precision of Bayesian inference of population size trajectories from gene genealogies. These authors proposed an extension of a Gaussian Process (GP) nonparametric inferential method for the intensity function of non-homogeneous Poisson processes. They found that not only the statistical properties of the estimators were improved with their method, but also, that key aspects of the demographic histories were recovered. The authors' work represents the first Bayesian nonparametric solution to this inferential problem because they specify a convenient prior belief without a particular functional form on the population trajectory. Their approach works so well and provides such a profound understanding of the biological process, that the question arises as to how truly "biology-free" their approach really is. Using well-known concepts of stochastic population dynamics, here I demonstrate that in fact, Palacios and Minin's GP model can be cast as a parametric population growth model with density dependence and environmental stochasticity. Making this link between population genetics and stochastic population dynamics modeling provides novel insights into eliciting biologically meaningful priors for the trajectory of the effective population size. The results presented here also bring novel understanding of GP as models for the evolution of a trait. Thus, the ecological principles foundation of Palacios and Minin (2013)'s prior adds to the conceptual and scientific value of these authors' inferential approach. I conclude this note by listing a series of insights brought about by this connection with Ecology. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

  15. Role of creatine kinase isoenzymes on muscular and cardiorespiratory endurance: genetic and molecular evidence.

    Science.gov (United States)

    Echegaray, M; Rivera, M A

    2001-01-01

    polymorphism, distinguished by the NcoI restriction enzyme, and an increase in cardiorespiratory endurance as indexed by maximal oxygen uptake following 20 weeks of training. In conclusion, there is now evidence at the tissue, cell and molecular level indicating that the CK-PCr system plays an important role in determining the phenotypes of muscular and cardiorespiratory endurance. It is envisioned that newer technologies will help determine how the genetic variability of these genes (and many others) impact on performance and health-related phenotypes.

  16. Miocene uplift of the NE Greenland margin linked to plate tectonics: Seismic evidence from the Greenland Fracture Zone, NE Atlantic

    DEFF Research Database (Denmark)

    Døssing Andreasen, Arne; Japsen, Peter; Watts, Anthony B.

    2016-01-01

    Tectonic models predict that, following breakup, rift margins undergo only decaying thermal subsidence during their post-rift evolution. However, post-breakup stratigraphy beneath the NE Atlantic shelves shows evidence of regional-scale unconformities, commonly cited as outer margin responses to ...... by plate tectonic forces, induced perhaps by a change in the Iceland plume (a hot pulse) and/or by changes in intra-plate stresses related to global tectonics.......Tectonic models predict that, following breakup, rift margins undergo only decaying thermal subsidence during their post-rift evolution. However, post-breakup stratigraphy beneath the NE Atlantic shelves shows evidence of regional-scale unconformities, commonly cited as outer margin responses...... backstripping. We explain the thermo-mechanical coupling and the deposition of contourites by the formation of a continuous plate boundary along the Mohns and Knipovich ridges, leading to an accelerated widening of the Fram Strait. We demonstrate that the IMU event is linked to onset of uplift and massive shelf...

  17. Mortality In Rural China Declined As Health Insurance Coverage Increased, But No Evidence The Two Are Linked.

    Science.gov (United States)

    Zhou, Maigeng; Liu, Shiwei; Kate Bundorf, M; Eggleston, Karen; Zhou, Sen

    2017-09-01

    Health insurance holds the promise of improving population health and survival and protecting people from catastrophic health spending. Yet evidence from lower- and middle-income countries on the impact of health insurance is limited. We investigated whether insurance expansion reduced adult mortality in rural China, taking advantage of differences across Chinese counties in the timing of the introduction of the New Cooperative Medical Scheme (NCMS). We assembled and analyzed newly collected data on NCMS implementation, linked to data from the Chinese Center for Disease Control and Prevention on cause-specific, age-standardized death rates and variables specific to county-year combinations for seventy-two counties in the period 2004-12. While mortality rates declined among rural residents during this period, we found little evidence that the expansion of health insurance through the NCMS contributed to this decline. However, our relatively large standard errors leave open the possibility that the NCMS had effects on mortality that we could not detect. Moreover, mortality benefits might arise only after many years of accumulated coverage. Project HOPE—The People-to-People Health Foundation, Inc.

  18. Yangtze River, an insignificant genetic boundary in tufted deer (Elaphodus cephalophus): the evidence from a first population genetics study.

    Science.gov (United States)

    Sun, Zhonglou; Pan, Tao; Wang, Hui; Pang, Mujia; Zhang, Baowei

    2016-01-01

    Great rivers were generally looked at as the geographical barrier to gene flow for many taxonomic groups. The Yangtze River is the third largest river in the world, and flows across South China and into the East China Sea. Up until now, few studies have been carried out to evaluate its effect as a geographical barrier. In this study, we attempted to determine the barrier effect of the Yangtze River on the tufted deer ( Elaphodus cephalophus ) using the molecular ecology approach. Using mitochondrial DNA control region (CR) sequences and 13 nuclear microsatellite loci, we explored the genetic structure and gene flow in two adjacent tufted deer populations (Dabashan and Wulingshan populations), which are separated by the Yangtze River. Results indicated that there are high genetic diversity levels in the two populations, but no distinguishable haplotype group or potential genetic cluster was detected which corresponded to specific geographical population. At the same time, high gene flow was observed between Wulingshan and Dabashan populations. The tufted deer populations experienced population decrease from 0.3 to 0.09 Ma BP, then followed by a distinct population increase. A strong signal of recent population decline ( T = 4,396 years) was detected in the Wulingshan population by a Markov-Switching Vector Autoregressions(MSVAR) process population demography analysis. The results indicated that the Yangtze River may not act as an effective barrier to gene flow in the tufted deer. Finally, we surmised that the population demography of the tufted deer was likely affected by Pleistocene climate fluctuations and ancient human activities.

  19. Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16

    Science.gov (United States)

    Djoussé, Luc; Knowlton, Beth; Hayden, Michael R.; Almqvist, Elisabeth W.; Brinkman, Ryan R.; Ross, Christopher A.; Margolis, Russel L.; Rosenblatt, Adam; Durr, Alexandra; Dode, Catherine; Morrison, Patrick J.; Novelletto, Andrea; Frontali, Marina; Trent, Ronald J. A.; McCusker, Elizabeth; Gómez-Tortosa, Estrella; Mayo Cabrero, David; Jones, Randi; Zanko, Andrea; Nance, Martha; Abramson, Ruth K.; Suchowersky, Oksana; Paulsen, Jane S.; Harrison, Madaline B.; Yang, Qiong; Cupples, L. Adrienne; Mysore, Jayalakshmi; Gusella, James F.; MacDonald, Marcy E.

    2007-01-01

    Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Δ2642 (within the HD coding sequence), and BJ56 (D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Δ2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker. PMID:15029481

  20. Genetics and mapping of the R₁₁ gene conferring resistance to recently emerged rust races, tightly linked to male fertility restoration, in sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Qi, L L; Seiler, G J; Vick, B A; Gulya, T J

    2012-09-01

    , and 11 as it was evident that no recombination occurred in the introgressed regions of LGs 2, 9, and 11 detected by 5, 9, and 22 SSR markers, respectively. R ( 11 ) is genetically independent from the rust R-genes R ( 1 ), R ( 2 ), and R ( 5 ), but may be closely linked to the rust R-gene R ( adv ) derived from wild Helianthus argophyllus, forming a large rust R-gene cluster of R ( adv )/R ( 11 )/R ( 4 ) in the lower end of LG13. The relationship of Rf5 with Rf1 is discussed based on the marker association analysis.

  1. Population genetics of Phytophthora infestans in Denmark reveals dominantly clonal populations and specific alleles linked to metalaxyl-M resistance

    DEFF Research Database (Denmark)

    Montes, M. S.; Nielsen, Bent Jørgen; Schmidt, S. G.

    2016-01-01

    population of P. infestans was characterized over the course of the 2013 growing season, as was the population genetic structure, using simple sequence repeat (SSR) genotypes and single nucleotide polymorphism (SNP)-based mitochondrial haplotyping of over 80 isolates. Both mating types A1 and A2 were present...... in most fields, but tests for recombination showed that clonal reproduction dominates in Danish populations. Genotype was not linked to haplotype and no differentiation was observed at the haplotype level, but rather between fields. Resistance phenotypes were linked to specific SSR alleles, demonstrating...

  2. Statistical and population genetics issues of two Hungarian datasets from the aspect of DNA evidence interpretation.

    Science.gov (United States)

    Szabolcsi, Zoltán; Farkas, Zsuzsa; Borbély, Andrea; Bárány, Gusztáv; Varga, Dániel; Heinrich, Attila; Völgyi, Antónia; Pamjav, Horolma

    2015-11-01

    When the DNA profile from a crime-scene matches that of a suspect, the weight of DNA evidence depends on the unbiased estimation of the match probability of the profiles. For this reason, it is required to establish and expand the databases that reflect the actual allele frequencies in the population applied. 21,473 complete DNA profiles from Databank samples were used to establish the allele frequency database to represent the population of Hungarian suspects. We used fifteen STR loci (PowerPlex ESI16) including five, new ESS loci. The aim was to calculate the statistical, forensic efficiency parameters for the Databank samples and compare the newly detected data to the earlier report. The population substructure caused by relatedness may influence the frequency of profiles estimated. As our Databank profiles were considered non-random samples, possible relationships between the suspects can be assumed. Therefore, population inbreeding effect was estimated using the FIS calculation. The overall inbreeding parameter was found to be 0.0106. Furthermore, we tested the impact of the two allele frequency datasets on 101 randomly chosen STR profiles, including full and partial profiles. The 95% confidence interval estimates for the profile frequencies (pM) resulted in a tighter range when we used the new dataset compared to the previously published ones. We found that the FIS had less effect on frequency values in the 21,473 samples than the application of minimum allele frequency. No genetic substructure was detected by STRUCTURE analysis. Due to the low level of inbreeding effect and the high number of samples, the new dataset provides unbiased and precise estimates of LR for statistical interpretation of forensic casework and allows us to use lower allele frequencies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Conservation of Sex-Linked Markers among Conspecific Populations of a Viviparous Skink, Niveoscincus ocellatus, Exhibiting Genetic and Temperature-Dependent Sex Determination

    Science.gov (United States)

    Burridge, Christopher P; Ezaz, Tariq; Wapstra, Erik

    2018-01-01

    Abstract Sex determination systems are exceptionally diverse and have undergone multiple and independent evolutionary transitions among species, particularly reptiles. However, the mechanisms underlying these transitions have not been established. Here, we tested for differences in sex-linked markers in the only known reptile that is polymorphic for sex determination system, the spotted snow skink, Niveoscincus ocellatus, to quantify the genomic differences that have accompanied this transition. In a highland population, sex is determined genetically, whereas in a lowland population, offspring sex ratio is influenced by temperature. We found a similar number of sex-linked loci in each population, including shared loci, with genotypes consistent with male heterogamety (XY). However, population-specific linkage disequilibrium suggests greater differentiation of sex chromosomes in the highland population. Our results suggest that transitions between sex determination systems can be facilitated by subtle genetic differences. PMID:29659810

  4. Impact of estrogenic compounds on DNA integrity in human spermatozoa: Evidence for cross-linking and redox cycling activities

    International Nuclear Information System (INIS)

    Bennetts, L.E.; De Iuliis, G.N.; Nixon, B.; Kime, M.; Zelski, K.; McVicar, C.M.; Lewis, S.E.; Aitken, R.J.

    2008-01-01

    A great deal of circumstantial evidence has linked DNA damage in human spermatozoa with adverse reproductive outcomes including reduced fertility and high rates of miscarriage. Although oxidative stress is thought to make a significant contribution to DNA damage in the male germ line, the factors responsible for creating this stress have not been elucidated. One group of compounds that are thought to be active in this context are the estrogens, either generated as a result of the endogenous metabolism of androgens within the male reproductive tract or gaining access to the latter as a consequence of environmental exposure. In this study, a wide variety of estrogenic compounds were assessed for their direct effects on human spermatozoa in vitro. DNA integrity was assessed using the Comet and TUNEL assays, lesion frequencies were quantified by QPCR using targets within the mitochondrial and nuclear (β-globin) genomes, DNA adducts were characterized by mass spectrometry and redox activity was monitored using dihydroethidium (DHE) as the probe. Of the estrogenic and estrogen analogue compounds evaluated, catechol estrogens, quercetin, diethylstilbestrol and pyrocatechol stimulated intense redox activity while genistein was only active at the highest doses tested. Other estrogens and estrogen analogues, such as 17β-estradiol, nonylphenol, bisphenol A and 2,3-dihydroxynaphthalene were inactive. Estrogen-induced redox activity was associated with a dramatic loss of motility and, in the case of 2-hydroxyestradiol, the induction of significant DNA fragmentation. Mass spectrometry also indicated that catechol estrogens were capable of forming dimers that can cross-link the densely packed DNA strands in sperm chromatin, impairing nuclear decondensation. These results highlight the potential importance of estrogenic compounds in creating oxidative stress and DNA damage in the male germ line and suggest that further exploration of these compounds in the aetiology of male

  5. Impact of estrogenic compounds on DNA integrity in human spermatozoa: Evidence for cross-linking and redox cycling activities

    Energy Technology Data Exchange (ETDEWEB)

    Bennetts, L.E.; De Iuliis, G.N.; Nixon, B.; Kime, M.; Zelski, K. [ARC Centre of Excellence in Biotechnology and Development and Discipline of Biological Sciences, University of Newcastle, NSW (Australia); McVicar, C.M.; Lewis, S.E. [Obstetrics and Gynaecology, Queen' s University, Belfast (United Kingdom); Aitken, R.J. [ARC Centre of Excellence in Biotechnology and Development and Discipline of Biological Sciences, University of Newcastle, NSW (Australia)], E-mail: jaitken@mail.newcastle.edu.au

    2008-05-10

    A great deal of circumstantial evidence has linked DNA damage in human spermatozoa with adverse reproductive outcomes including reduced fertility and high rates of miscarriage. Although oxidative stress is thought to make a significant contribution to DNA damage in the male germ line, the factors responsible for creating this stress have not been elucidated. One group of compounds that are thought to be active in this context are the estrogens, either generated as a result of the endogenous metabolism of androgens within the male reproductive tract or gaining access to the latter as a consequence of environmental exposure. In this study, a wide variety of estrogenic compounds were assessed for their direct effects on human spermatozoa in vitro. DNA integrity was assessed using the Comet and TUNEL assays, lesion frequencies were quantified by QPCR using targets within the mitochondrial and nuclear ({beta}-globin) genomes, DNA adducts were characterized by mass spectrometry and redox activity was monitored using dihydroethidium (DHE) as the probe. Of the estrogenic and estrogen analogue compounds evaluated, catechol estrogens, quercetin, diethylstilbestrol and pyrocatechol stimulated intense redox activity while genistein was only active at the highest doses tested. Other estrogens and estrogen analogues, such as 17{beta}-estradiol, nonylphenol, bisphenol A and 2,3-dihydroxynaphthalene were inactive. Estrogen-induced redox activity was associated with a dramatic loss of motility and, in the case of 2-hydroxyestradiol, the induction of significant DNA fragmentation. Mass spectrometry also indicated that catechol estrogens were capable of forming dimers that can cross-link the densely packed DNA strands in sperm chromatin, impairing nuclear decondensation. These results highlight the potential importance of estrogenic compounds in creating oxidative stress and DNA damage in the male germ line and suggest that further exploration of these compounds in the aetiology of

  6. Somatic and germline mosaicism for a mutation of the PHEX gene can lead to genetic transmission of X-linked hypophosphatemic rickets that mimics an autosomal dominant trait.

    Science.gov (United States)

    Goji, Katsumi; Ozaki, Kayo; Sadewa, Ahmad H; Nishio, Hisahide; Matsuo, Masafumi

    2006-02-01

    Familial hypophosphatemic rickets is usually transmitted as an X-linked dominant disorder (XLH), although autosomal dominant forms have also been observed. Genetic studies of these disorders have identified mutations in PHEX and FGF23 as the causes of X-linked dominant disorder and autosomal dominant forms, respectively. The objective of the study was to describe the molecular genetic findings in a family affected by hypophosphatemic rickets with presumed autosomal dominant inheritance. We studied a family in which the father and the elder of his two daughters, but not the second daughter, were affected by hypophosphatemic rickets. The pedigree interpretation of the family suggested that genetic transmission of the disorder occurred as an autosomal dominant trait. Direct nucleotide sequencing of FGF23 and PHEX revealed that the elder daughter was heterozygous for an R567X mutation in PHEX, rather than FGF23, suggesting that the genetic transmission occurred as an X-linked dominant trait. Unexpectedly, the father was heterozygous for this mutation. Single-nucleotide primer extension and denaturing HPLC analysis of the father using DNA from single hair roots revealed that he was a somatic mosaic for the mutation. Haplotype analysis confirmed that the father transmitted the genotypes for 18 markers on the X chromosome equally to his two daughters. The fact that the father transmitted the mutation to only one of his two daughters indicated that he was a germline mosaic for the mutation. Somatic and germline mosaicism for an X-linked dominant mutation in PHEX may mimic autosomal dominant inheritance.

  7. Genetic Risk by Experience Interaction for Childhood Internalizing Problems: Converging Evidence across Multiple Methods

    Science.gov (United States)

    Vendlinski, Matthew K.; Lemery-Chalfant, Kathryn; Essex, Marilyn J.; Goldsmith, H. Hill

    2011-01-01

    Background: Identifying how genetic risk interacts with experience to predict psychopathology is an important step toward understanding the etiology of mental health problems. Few studies have examined genetic risk by experience interaction (GxE) in the development of childhood psychopathology. Methods: We used both co-twin and parent mental…

  8. The correlation of fecundability among twins: Evidence of a genetic effect on fertility?

    DEFF Research Database (Denmark)

    Christensen, Kaare; Kohler, Hans-Peter; Basso, Olga

    2003-01-01

    BACKGROUND: Numerous rare genetic conditions are known to influence fecundability in both males and females. It is less clear to what extent more subtle genetic differences influence fecundability on a population level. METHODS: In 1994 a population-based survey was conducted among Danish twins b...

  9. Genetics

    International Nuclear Information System (INIS)

    Hubitschek, H.E.

    1975-01-01

    Progress is reported on the following research projects: genetic effects of high LET radiations; genetic regulation, alteration, and repair; chromosome replication and the division cycle of Escherichia coli; effects of radioisotope decay in the DNA of microorganisms; initiation and termination of DNA replication in Bacillus subtilis; mutagenesis in mouse myeloma cells; lethal and mutagenic effects of near-uv radiation; effect of 8-methoxypsoralen on photodynamic lethality and mutagenicity in Escherichia coli; DNA repair of the lethal effects of far-uv; and near uv irradiation of bacterial cells

  10. Genetic structure of populations of whale sharks among ocean basins and evidence for their historic rise and recent decline

    KAUST Repository

    Vignaud, Thomas M.

    2014-05-01

    This study presents genetic evidence that whale sharks, Rhincodon typus, are comprised of at least two populations that rarely mix and is the first to document a population expansion. Relatively high genetic structure is found when comparing sharks from the Gulf of Mexico with sharks from the Indo-Pacific. If mixing occurs between the Indian and Atlantic Oceans, it is not sufficient to counter genetic drift. This suggests whale sharks are not all part of a single global metapopulation. The significant population expansion we found was indicated by both microsatellite and mitochondrial DNA. The expansion may have happened during the Holocene, when tropical species could expand their range due to sea-level rise, eliminating dispersal barriers and increasing plankton productivity. However, the historic trend of population increase may have reversed recently. Declines in genetic diversity are found for 6 consecutive years at Ningaloo Reef in Australia. The declines in genetic diversity being seen now in Australia may be due to commercial-scale harvesting of whale sharks and collision with boats in past decades in other countries in the Indo-Pacific. The study findings have implications for models of population connectivity for whale sharks and advocate for continued focus on effective protection of the world\\'s largest fish at multiple spatial scales. © 2014 John Wiley & Sons Ltd.

  11. Sensation seeking, peer deviance, and genetic influences on adolescent delinquency: Evidence for person-environment correlation and interaction.

    Science.gov (United States)

    Mann, Frank D; Patterson, Megan W; Grotzinger, Andrew D; Kretsch, Natalie; Tackett, Jennifer L; Tucker-Drob, Elliot M; Harden, K Paige

    2016-07-01

    Both sensation seeking and affiliation with deviant peer groups are risk factors for delinquency in adolescence. In this study, we use a sample of adolescent twins (n = 549), 13 to 20 years old (M age = 15.8 years), in order to test the interactive effects of peer deviance and sensation seeking on delinquency in a genetically informative design. Consistent with a socialization effect, affiliation with deviant peers was associated with higher delinquency even after controlling for selection effects using a co-twin-control comparison. At the same time, there was evidence for person-environment correlation; adolescents with genetic dispositions toward higher sensation seeking were more likely to report having deviant peer groups. Genetic influences on sensation seeking substantially overlapped with genetic influences on adolescent delinquency. Finally, the environmentally mediated effect of peer deviance on adolescent delinquency was moderated by individual differences in sensation seeking. Adolescents reporting high levels of sensation seeking were more susceptible to deviant peers, a Person × Environment interaction. These results are consistent with both selection and socialization processes in adolescent peer relationships, and they highlight the role of sensation seeking as an intermediary phenotype for genetic risk for delinquency. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  12. Genetic structure of populations of whale sharks among ocean basins and evidence for their historic rise and recent decline.

    Science.gov (United States)

    Vignaud, Thomas M; Maynard, Jeffrey A; Leblois, Raphael; Meekan, Mark G; Vázquez-Juárez, Ricardo; Ramírez-Macías, Dení; Pierce, Simon J; Rowat, David; Berumen, Michael L; Beeravolu, Champak; Baksay, Sandra; Planes, Serge

    2014-05-01

    This study presents genetic evidence that whale sharks, Rhincodon typus, are comprised of at least two populations that rarely mix and is the first to document a population expansion. Relatively high genetic structure is found when comparing sharks from the Gulf of Mexico with sharks from the Indo-Pacific. If mixing occurs between the Indian and Atlantic Oceans, it is not sufficient to counter genetic drift. This suggests whale sharks are not all part of a single global metapopulation. The significant population expansion we found was indicated by both microsatellite and mitochondrial DNA. The expansion may have happened during the Holocene, when tropical species could expand their range due to sea-level rise, eliminating dispersal barriers and increasing plankton productivity. However, the historic trend of population increase may have reversed recently. Declines in genetic diversity are found for 6 consecutive years at Ningaloo Reef in Australia. The declines in genetic diversity being seen now in Australia may be due to commercial-scale harvesting of whale sharks and collision with boats in past decades in other countries in the Indo-Pacific. The study findings have implications for models of population connectivity for whale sharks and advocate for continued focus on effective protection of the world's largest fish at multiple spatial scales. © 2014 John Wiley & Sons Ltd.

  13. Maternal smoking during pregnancy and offspring conduct problems: Evidence from three independent genetically-sensitive research designs

    Science.gov (United States)

    Gaysina, Darya; Fergusson, David M.; Leve, Leslie D.; Horwood, John; Reiss, David; Shaw, Daniel S.; Elam, Kit K.; Natsuaki, Misaki N.; Neiderhiser, Jenae M.; Harold, Gordon T.

    2013-01-01

    Context A number of studies report an association between maternal smoking during pregnancy and offspring conduct disorder. However, past research evidences difficulty disaggregating prenatal environmental from genetic and postnatal environmental influences. Objective To examine the relationship between maternal smoking during pregnancy and offspring conduct problems among children reared by genetically-related and genetically-unrelated mothers. Design, Setting and Participants Three studies employing distinct but complementary research designs were utilized: The Christchurch Health and Development Study (a longitudinal cohort study that includes biological and adopted children), the Early Growth and Development Study (a longitudinal adoption at birth study), and the Cardiff IVF Study (genetically-related and -unrelated families; an adoption at conception study). Maternal smoking during pregnancy was measured as the average number of cigarettes/day (0, 1–9 or 10+) smoked during pregnancy. A number of possible covariates (child gender, ethnicity, birth weight, breast feeding, maternal age at birth, maternal education, family SES, family breakdown, placement age, and parenting practices) were controlled in the analyses. Main Outcome Measure Child conduct problems (age 4–10 years) reported by parents and/or teachers using the Rutter and Conners behaviour scales, the Child Behavior Checklist and Children's Behavior Questionnaire, and the Strengths and Difficulties Questionnaire. Results A significant association between maternal smoking during pregnancy and child conduct problems was observed among children reared by genetically-related and genetically-unrelated mothers. Results from a meta-analysis affirmed this pattern of findings across pooled study samples. Conclusions Findings across the three studies using a complement of genetically-sensitive research designs suggest smoking during pregnancy is a prenatal risk factor for offspring conduct problems, when

  14. Adiponectin and its receptors in the ovary: further evidence for a link between obesity and hyperandrogenism in polycystic ovary syndrome.

    Directory of Open Access Journals (Sweden)

    Fabio V Comim

    Full Text Available Polycystic ovary syndrome (PCOS, characterized by ovarian androgen excess, is the commonest endocrine disorder in women. Obesity increases androgen synthesis, a phenomenon attributed to the accompanying hyperinsulinemia. Our hypothesis was that adipokines, fat cell-derived hormones, play a direct role in modulating ovarian androgen secretion. Therefore, the aims of this study were to explore the effects of adipokines (in particular, adiponectin on ovarian steroidogenesis and compare the expression of adiponectin receptors in ovaries from women with and without PCO. Sections of archived human ovaries (nine from women with normal ovaries and 16 with PCOS, classified histologically, with reference to menstrual history and ultrasound were analysed by quantitative morphometry and the proportion of positive-labelling cells compared. In addition, studies of androgen production in relation to adipokine function in primary bovine theca cell culture were also performed. A significantly lower proportion of theca cells expressed adiponectin receptors 1 and 2 (AdipoR1, AdipoR2 in polycystic ovaries than in normal ovaries. In cultured theca cells, adiponectin suppressed androstenedione production and gene expression of LH receptor and key enzymes in the androgen synthesis pathway. Moreover, knockdown of genes for AdipoR1 and AdipoR2 was associated with increased androstenedione secretion by bovine theca cells. These results provide evidence for a direct link between fat cell metabolism and ovarian steroidogenesis, suggesting that disruption of adiponectin and/or its receptors plays a key role in pathogenesis of hyperandrogenism in PCOS.

  15. Adiponectin and Its Receptors in the Ovary: Further Evidence for a Link between Obesity and Hyperandrogenism in Polycystic Ovary Syndrome

    Science.gov (United States)

    Comim, Fabio V.; Hardy, Kate; Franks, Stephen

    2013-01-01

    Polycystic ovary syndrome (PCOS), characterized by ovarian androgen excess, is the commonest endocrine disorder in women. Obesity increases androgen synthesis, a phenomenon attributed to the accompanying hyperinsulinemia. Our hypothesis was that adipokines, fat cell-derived hormones, play a direct role in modulating ovarian androgen secretion. Therefore, the aims of this study were to explore the effects of adipokines (in particular, adiponectin) on ovarian steroidogenesis and compare the expression of adiponectin receptors in ovaries from women with and without PCO. Sections of archived human ovaries (nine from women with normal ovaries and 16 with PCOS, classified histologically, with reference to menstrual history and ultrasound) were analysed by quantitative morphometry and the proportion of positive-labelling cells compared. In addition, studies of androgen production in relation to adipokine function in primary bovine theca cell culture were also performed. A significantly lower proportion of theca cells expressed adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) in polycystic ovaries than in normal ovaries. In cultured theca cells, adiponectin suppressed androstenedione production and gene expression of LH receptor and key enzymes in the androgen synthesis pathway. Moreover, knockdown of genes for AdipoR1 and AdipoR2 was associated with increased androstenedione secretion by bovine theca cells. These results provide evidence for a direct link between fat cell metabolism and ovarian steroidogenesis, suggesting that disruption of adiponectin and/or its receptors plays a key role in pathogenesis of hyperandrogenism in PCOS. PMID:24260388

  16. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  17. Genetic and environmental etiology of stability and changes in self-esteem linked to personality: A Japanese twin study

    OpenAIRE

    Shikishima, Chizuru; Hiraishi, Kai; Takahashi, Yusuke; Yamagata, Shinji; Yamaguchi, Susumu; Ando, Juko

    2018-01-01

    This study used a behavioral genetic approach to examine the genetic and environmental etiology of stability and changes in self-esteem in relation to personality. Multiple genetic analyses were conducted on a longitudinal dataset of self-esteem and Big Five personality scores among young adult Japanese twins over the course of a decade. There were 1221 individuals for whom data were available on both self-esteem and the Big Five personality test at Time 1 and 365 at Time 2. The mean interval...

  18. Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

    Science.gov (United States)

    ... Conditions XMEN X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia Printable PDF Open All Close ... boxes. Description X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym ...

  19. The Genetics Underlying Natural Variation in the Biotic Interactions of Arabidopsis thaliana: The Challenges of Linking Evolutionary Genetics and Community Ecology.

    Science.gov (United States)

    Roux, F; Bergelson, J

    2016-01-01

    In the context of global change, predicting the responses of plant communities in an ever-changing biotic environment calls for a multipronged approach at the interface of evolutionary genetics and community ecology. However, our understanding of the genetic basis of natural variation involved in mediating biotic interactions, and associated adaptive dynamics of focal plants in their natural communities, is still in its infancy. Here, we review the genetic and molecular bases of natural variation in the response to biotic interactions (viruses, bacteria, fungi, oomycetes, herbivores, and plants) in the model plant Arabidopsis thaliana as well as the adaptive value of these bases. Among the 60 identified genes are a number that encode nucleotide-binding site leucine-rich repeat (NBS-LRR)-type proteins, consistent with early examples of plant defense genes. However, recent studies have revealed an extensive diversity in the molecular mechanisms of defense. Many types of genetic variants associate with phenotypic variation in biotic interactions, even among the genes of large effect that tend to be identified. In general, we found that (i) balancing selection rather than directional selection explains the observed patterns of genetic diversity within A. thaliana and (ii) the cost/benefit tradeoffs of adaptive alleles can be strongly dependent on both genomic and environmental contexts. Finally, because A. thaliana rarely interacts with only one biotic partner in nature, we highlight the benefit of exploring diffuse biotic interactions rather than tightly associated host-enemy pairs. This challenge would help to improve our understanding of coevolutionary quantitative genetics within the context of realistic community complexity. © 2016 Elsevier Inc. All rights reserved.

  20. A genetic link between magnetite mineralization and diorite intrusion at the El Romeral iron oxide-apatite deposit, northern Chile

    Science.gov (United States)

    Rojas, Paula A.; Barra, Fernando; Reich, Martin; Deditius, Artur; Simon, Adam; Uribe, Francisco; Romero, Rurik; Rojo, Mario

    2018-01-01

    El Romeral is one of the largest iron oxide-apatite (IOA) deposits in the Coastal Cordillera of northern Chile. The Cerro Principal magnetite ore body at El Romeral comprises massive magnetite intergrown with actinolite, with minor apatite, scapolite, and sulfides (pyrite ± chalcopyrite). Several generations of magnetite were identified by using a combination of optical and electron microscopy techniques. The main mineralization event is represented by zoned magnetite grains with inclusion-rich cores and inclusion-poor rims, which form the massive magnetite ore body. This main magnetite stage was followed by two late hydrothermal events that are represented by magnetite veinlets that crosscut the massive ore body and by disseminated magnetite in the andesite host rock and in the Romeral diorite. The sulfur stable isotope signature of the late hydrothermal sulfides indicates a magmatic origin for sulfur (δ34S between - 0.8 and 2.9‰), in agreement with previous δ34S data reported for other Chilean IOA and iron oxide-copper-gold deposits. New 40Ar/39Ar dating of actinolite associated with the main magnetite ore stage yielded ages of ca. 128 Ma, concordant within error with a U-Pb zircon age for the Romeral diorite (129.0 ± 0.9 Ma; mean square weighted deviation = 1.9, n = 28). The late hydrothermal magnetite-biotite mineralization is constrained at ca. 118 Ma by 40Ar/39Ar dating of secondary biotite. This potassic alteration is about 10 Ma younger than the main mineralization episode, and it may be related to post-mineralization dikes that crosscut and remobilize Fe from the main magnetite ore body. These data reveal a clear genetic association between magnetite ore formation, sulfide mineralization, and the diorite intrusion at El Romeral (at 129 Ma), followed by a late and more restricted stage of hydrothermal alteration associated with the emplacement of post-ore dikes at ca. 118 Ma. Therefore, this new evidence supports a magmatic-hydrothermal model for the

  1. Linking Genetic Variation in Adaptive Plant Traits to Climate in Tetraploid and Octoploid Basin Wildrye [Leymus cinereus (Scribn. & Merr. A. Love] in the Western U.S.

    Directory of Open Access Journals (Sweden)

    R C Johnson

    Full Text Available Few studies have assessed how ploidy type within a species affects genetic variation among populations in relation to source climates. Basin wildrye (Leymus cinereus (Scribn. & Merr. A. Love is a large bunchgrass common in the intermountain Western U.S. found in both octoploid and tetraploid types. In common gardens at two sites over two years differences in both ploidy type and genetic variation within ploidy were observed in phenology, morphology, and production traits on 57 octoploid and 52 tetraploid basin wildrye from the intermountain Western U.S. (P<0.01. Octoploids had larger leaves, longer culms, and greater crown circumference than tetraploids but the numerical ranges of plant traits and their source climates overlapped between ploidy types. Still, among populations octoploids often had greater genetic variation for traits and occupied more diverse climates than tetraploids. Genetic variation for both ploidy types was linked to source climates in canonical correlation analysis, with the first two variates explaining 70% of the variation. Regression of those canonical variates with seed source climate variables produced models that explained 64% and 38% of the variation, respectively, and were used to map 15 seed zones covering 673,258 km2. Utilization of these seed zones will help ensure restoration with adaptive seed sources for both ploidy types. The link between genetic traits and seed source climates suggests climate driven natural selection and adaptive evolution in basin wildrye. The more diverse climates occupied by octoploids and higher trait variation suggests a higher capacity for ecological differentiation than tetraploids in the intermountain Western U.S.

  2. Evident?

    DEFF Research Database (Denmark)

    Plant, Peter

    2012-01-01

    Quality assurance and evidence in career guidance in Europe are often seen as self-evident approaches, but particular interests lie behind......Quality assurance and evidence in career guidance in Europe are often seen as self-evident approaches, but particular interests lie behind...

  3. The ABCs of Math: A Genetic Analysis of Mathematics and Its Links With Reading Ability and General Cognitive Ability

    Science.gov (United States)

    Hart, Sara A.; Petrill, Stephen A.; Thompson, Lee A.; Plomin, Robert

    2009-01-01

    The goal of this first major report from the Western Reserve Reading Project Math component is to explore the etiology of the relationship among tester-administered measures of mathematics ability, reading ability, and general cognitive ability. Data are available on 314 pairs of monozygotic and same-sex dizygotic twins analyzed across 5 waves of assessment. Univariate analyses provide a range of estimates of genetic (h2 = .00 –.63) and shared (c2 = .15–.52) environmental influences across math calculation, fluency, and problem solving measures. Multivariate analyses indicate genetic overlap between math problem solving with general cognitive ability and reading decoding, whereas math fluency shares significant genetic overlap with reading fluency and general cognitive ability. Further, math fluency has unique genetic influences. In general, math ability has shared environmental overlap with general cognitive ability and decoding. These results indicate that aspects of math that include problem solving have different genetic and environmental influences than math calculation. Moreover, math fluency, a timed measure of calculation, is the only measured math ability with unique genetic influences. PMID:20157630

  4. Genetic Drift Linked to Heterogeneous Landscape and Ecological Specialization Drives Diversification in the Alpine Endemic Columbine Aquilegia thalictrifolia.

    Science.gov (United States)

    Lega, Margherita; Fior, Simone; Li, Mingai; Leonardi, Stefano; Varotto, Claudio

    2014-01-01

    The European Alpine system is an extensive mountain range, whose heterogeneous landscape together with Quaternary climatic oscillations significantly affected organismal diversity and distribution in Europe. The model genus Aquilegia represents a textbook example of a rapid and recent radiation through the Northern hemisphere, with the majority of the European taxa occuring in the Alpine system. However, the processes governing genetic differentiation of the genus in this complex geographic area are still widely unexplored. In this work, we used 9 microsatellite loci to study the genetic structure and diversity of 11 populations of Aquilegia thalictrifolia Schott & Kotschy, an alpine taxon characterized by a marked ecological specificity. We found that, despite the endemic and fragmented distribution, A. thalictrifolia has overall high levels of heterozygosity, which is consistent to the substantial inbreeding depression that characterizes the genus. Strong spatial genetic structuring of populations suggests a historical prevalence of genetic drift over gene flow, with natural barriers and ecological niche hindering migration. An analytical comparison of fixation and population differentiation indexes allowed us to infer hypotheses of the postglacial history and more recent demographic events that have influenced the genetics of the species. Overall, our results indicate allopatry as a major force of differentiation in the European scenario, likely to underlie the development of taxonomic boundaries in a broader geographic context. This adds to previous notions on the primary evolutionary forces shaping the Aquilegia radiation in Europe. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Topology of genetic associations between regional gray matter volume and intellectual ability: Evidence for a high capacity network.

    Science.gov (United States)

    Bohlken, Marc M; Brouwer, Rachel M; Mandl, René C W; Hedman, Anna M; van den Heuvel, Martijn P; van Haren, Neeltje E M; Kahn, René S; Hulshoff Pol, Hilleke E

    2016-01-01

    Intelligence is associated with a network of distributed gray matter areas including the frontal and parietal higher association cortices and primary processing areas of the temporal and occipital lobes. Efficient information transfer between gray matter regions implicated in intelligence is thought to be critical for this trait to emerge. Genetic factors implicated in intelligence and gray matter may promote a high capacity for information transfer. Whether these genetic factors act globally or on local gray matter areas separately is not known. Brain maps of phenotypic and genetic associations between gray matter volume and intelligence were made using structural equation modeling of 3T MRI T1-weighted scans acquired in 167 adult twins of the newly acquired U-TWIN cohort. Subsequently, structural connectivity analyses (DTI) were performed to test the hypothesis that gray matter regions associated with intellectual ability form a densely connected core. Gray matter regions associated with intellectual ability were situated in the right prefrontal, bilateral temporal, bilateral parietal, right occipital and subcortical regions. Regions implicated in intelligence had high structural connectivity density compared to 10,000 reference networks (p=0.031). The genetic association with intelligence was for 39% explained by a genetic source unique to these regions (independent of total brain volume), this source specifically implicated the right supramarginal gyrus. Using a twin design, we show that intelligence is genetically represented in a spatially distributed and densely connected network of gray matter regions providing a high capacity infrastructure. Although genes for intelligence have overlap with those for total brain volume, we present evidence that there are genes for intelligence that act specifically on the subset of brain areas that form an efficient brain network. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Evidence of high genetic connectivity for the longnose spurdog Squalus blainville in the Mediterranean Sea

    Directory of Open Access Journals (Sweden)

    V. KOUSTENI

    2015-04-01

    Full Text Available Squalus blainville is one of the least studied Mediterranean shark species. Despite being intensively fished in several locations, biological knowledge is limited and no genetic structure information is available. This is the first study to examine the genetic structure of S. blainville in the Mediterranean Sea. Considering the high dispersal potential inferred for other squalid sharks, the hypothesis of panmixia was tested based on a 585 bp fragment of the mitochondrial DNA cytochrome c oxidase subunit I gene from 107 individuals and six nuclear microsatellite loci from 577 individuals. Samples were collected across the Ionian, Aegean and Libyan Seas and off the Balearic Islands. Twenty three additional sequences of Mediterranean and South African origin were retrieved from GenBank and included in the mitochondrial DNA analysis. The overall haplotype diversity was high, in contrast to the low nucleotide diversity. Low and non-significant pairwise ΦST and FST values along with a Bayesian cluster analysis suggested high connectivity with subsequent genetic homogeneity among the populations studied, and thus a high dispersal potential for S. blainville similar to other squalids. The historical demography of the species was also assessed, revealing a pattern of population expansion since the middle Pleistocene. These findings could be considered in species-specific conservation plans, although sampling over a larger spatial scale and more genetic markers are required to fully elucidate the genetic structure and dispersal potential of S. blainville.

  7. Low interbasin connectivity in a facultatively diadromous fish: evidence from genetics and otolith chemistry.

    Science.gov (United States)

    Hughes, Jane M; Schmidt, Daniel J; Macdonald, Jed I; Huey, Joel A; Crook, David A

    2014-03-01

    Southern smelts (Retropinna spp.) in coastal rivers of Australia are facultatively diadromous, with populations potentially containing individuals with diadromous or wholly freshwater life histories. The presence of diadromous individuals is expected to reduce genetic structuring between river basins due to larval dispersal via the sea. We use otolith chemistry to distinguish between diadromous and nondiadromous life histories and population genetics to examine interbasin connectivity resulting from diadromy. Otolith strontium isotope ((87) Sr:(86) Sr) transects identified three main life history patterns: amphidromy, freshwater residency and estuarine/marine residency. Despite the potential for interbasin connectivity via larval mixing in the marine environment, we found unprecedented levels of genetic structure for an amphidromous species. Strong hierarchical structure along putative taxonomic boundaries was detected, along with highly structured populations within groups using microsatellites (FST  = 0.046-0.181), and mtDNA (ΦST  = 0.498-0.816). The presence of strong genetic subdivision, despite the fact that many individuals reside in saline water during their early life history, appears incongruous. However, analysis of multielemental signatures in the otolith cores of diadromous fish revealed strong discrimination between river basins, suggesting that diadromous fish spend their early lives within chemically distinct estuaries rather than the more homogenous marine environment, thus avoiding dispersal and maintaining genetic structure. © 2014 John Wiley & Sons Ltd.

  8. Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers.

    Directory of Open Access Journals (Sweden)

    Luke C Pilling

    Full Text Available Variability in red blood cell volumes (distribution width, RDW increases with age and is strongly predictive of mortality, incident coronary heart disease and cancer. We investigated inherited genetic variation associated with RDW in 116,666 UK Biobank human volunteers.A large proportion RDW is explained by genetic variants (29%, especially in the older group (60+ year olds, 33.8%, <50 year olds, 28.4%. RDW was associated with 194 independent genetic signals; 71 are known for conditions including autoimmune disease, certain cancers, BMI, Alzheimer's disease, longevity, age at menopause, bone density, myositis, Parkinson's disease, and age-related macular degeneration. Exclusion of anemic participants did not affect the overall findings. Pathways analysis showed enrichment for telomere maintenance, ribosomal RNA, and apoptosis. The majority of RDW-associated signals were intronic (119 of 194, including SNP rs6602909 located in an intron of oncogene GAS6, an eQTL in whole blood.Although increased RDW is predictive of cardiovascular outcomes, this was not explained by known CVD or related lipid genetic risks, and a RDW genetic score was not predictive of incident disease. The predictive value of RDW for a range of negative health outcomes may in part be due to variants influencing fundamental pathways of aging.

  9. Mitochondrial DNA variability among eight Tikúna villages: evidence for an intratribal genetic heterogeneity pattern.

    Science.gov (United States)

    Mendes-Junior, Celso Teixeira; Simões, Aguinaldo Luiz

    2009-11-01

    To study the genetic structure of the Tikúna tribe, four major Native American mitochondrial DNA (mtDNA) founder haplogroups were analyzed in 187 Amerindians from eight Tikúna villages located in the Brazilian Amazon. The central position of these villages in the continent makes them relevant for attempts to reconstruct population movements in South America. In this geographic region, there is particular concern regarding the genetic structure of the Tikúna tribe, formerly designated "enigmatic" due to its remarkable degree of intratribal homogeneity and the scarcity of private protein variants. In spite of its large population size and geographic distribution, the Tikúna tribe presents marked genetic and linguistic isolation. All individuals presented indigenous mtDNA haplogroups. An intratribal genetic heterogeneity pattern characterized by two highly homogeneous Tikúna groups that differ considerably from each other was observed. Such a finding was unexpected, since the Tikúna tribe is characterized by a social system that favors intratribal exogamy and patrilocality that would lead to a higher female migration rate and homogenization of the mtDNA gene pool. Demographic explosions and religious events, which significantly changed the sizes and compositions of many Tikúna villages, may be reflected in the genetic results presented here.

  10. Genetic-linked Inattentiveness Protects Individuals from Internet Overuse: A Genetic Study of Internet Overuse Evaluating Hypotheses Based on Addiction, Inattention, Novelty-seeking and Harm-avoidance

    Directory of Open Access Journals (Sweden)

    Cheng Sun

    2016-06-01

    Full Text Available The all-pervasive Internet has created serious problems, such as Internet overuse, which has triggered considerable debate over its relationship with addiction. To further explore its genetic susceptibilities and alternative explanations for Internet overuse, we proposed and evaluated four hypotheses, each based on existing knowledge of the biological bases of addiction, inattention, novelty-seeking, and harm-avoidance. Four genetic loci including DRD4 VNTR, DRD2 Taq1A, COMT Val158Met and 5-HTTLPR length polymorphisms were screened from seventy-three individuals. Our results showed that the DRD4 4R/4R individuals scored significantly higher than the 2R or 7R carriers in Internet Addiction Test (IAT. The 5-HTTLPR short/short males scored significantly higher in IAT than the long variant carriers. Bayesian analysis showed the most compatible hypothesis with the observed genetic results was based on attention (69.8%, whereas hypotheses based harm-avoidance (21.6%, novelty-seeking (7.8% and addiction (0.9% received little support. Our study suggests that carriers of alleles (DRD4 2R and 7R, 5-HTTLPR long associated with inattentiveness are more likely to experience disrupted patterns and reduced durations of Internet use, protecting them from Internet overuse. Furthermore, our study suggests that Internet overuse should be categorized differently from addiction due to the lack of shared genetic contributions.

  11. Possible genetic link between I-type granite and orogenic gold deposits in Egypt (metamorphic-magmatic interaction?)

    Science.gov (United States)

    Abd El Monsef, Mohamed

    2015-04-01

    ores revealed two main groups of fluid inclusions in both areas: A) Aqueous inclusions (H2O-NaCl±KCl system), and B) Carbonic inclusions (H2O-CO2-NaCl±CH4). A drop of pressure during the migration of these fluids to shallower depths along the shear zones was the main reason for phase separation. Isochores calculation from microthermometric results proved that, the P-T boundary conditions outlined for Fatira gold deposits are of 275° to 297° C and between (0.2 - 1.2 Kbar); and of 277° to 300° C and between (0.2 - 1 Kbar) for Gidami gold deposits. The normalization Chondrite patterns of rare earth elements (REEs) for the gold-ore deposits with the surrounding I-type granitic rocks exhibit an obvious similarity and positive correlation. The geological, mineralogical, geochemical and fluid inclusions studies revealed a genetic link between gold mineralization and intrusion of calc-alkaine granitic magma. Whereas, The granitic magma acts as a supplier for the ore-bearing fluid and as a heat source for metamorphic processes, leading to hydrothermal convection currents.

  12. Lack of serologic evidence to link IgA nephropathy with celiac disease or immune reactivity to gluten.

    Directory of Open Access Journals (Sweden)

    Sina Moeller

    Full Text Available IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99, unaffected controls of similar age, gender, and race (n = 96, and patients with biopsy-proven celiac disease (n = 30. All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2. Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy.

  13. Lack of serologic evidence to link IgA nephropathy with celiac disease or immune reactivity to gluten.

    Science.gov (United States)

    Moeller, Sina; Canetta, Pietro A; Taylor, Annette K; Arguelles-Grande, Carolina; Snyder, Holly; Green, Peter H; Kiryluk, Krzysztof; Alaedini, Armin

    2014-01-01

    IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age, gender, and race (n = 96), and patients with biopsy-proven celiac disease (n = 30). All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy.

  14. Genomic evidence for the evolution of Streptococcus equi: host restriction, increased virulence, and genetic exchange with human pathogens.

    Directory of Open Access Journals (Sweden)

    Matthew T G Holden

    2009-03-01

    Full Text Available The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus. These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A(2 toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci.

  15. Evidence that periweaning failure-to-thrive syndrome (PFTS) has a genetic predisposition.

    Science.gov (United States)

    Ramis, G; Marco, E; Magaña, V; González-Contreras, P; Swierczynski, G; Abellaneda, J M; Sáez-Acosta, A; Mrowiec, A; Pallarés, F J

    2015-06-06

    Genetic susceptibility or resistance to diseases is currently drawing increasing attention. This work describes two different breeding herds showing signs of periweaning failure-to-thrive syndrome (PFTS), an emergent swine disease. The disease was diagnosed based on clinical picture and confirmed by histopathology. The possibility of main infectious pathogens was ruled out by immunohistochemistry and PCR. In a simple approach, sires of the affected piglets have been determined using microsatellite paternity analysis, including a healthy group in each case. In each of the two farms, a single boar was found to have sired 45-50 per cent sick animals. Removal of this sire from two farms resulted in a significant decrease in the prevalence of the disease among the offspring, in accordance with other two cases diagnosed, although without including a control group. Since the analysed animals belonged to three different genetic lines, these findings point to the existence of individual genetic susceptibility to this syndrome. British Veterinary Association.

  16. Three genetically divergent lineages of the Oryx in eastern Africa: Evidence for an ancient introgressive hybridization

    DEFF Research Database (Denmark)

    Masembe, Charles; Muwanika, Vincent B.; Nyakaana, Silvester

    2006-01-01

    Phylogeographic and population genetic studies using sequence information are frequently used to infer species boundaries and history; and to assess hybridization and population level processes. In this study, partial mitochondrial DNA (mtDNA) control region (423 bp) and cytochrome b sequences (666...... bp) of Oryx beisa sampled from five isolated localities in its entire current range in Africa were analyzed to investigate the extent of genetic variation and differentiation between populations. We observed high nucleotide diversity at the control region in the total sample (6.3%) but within...... populations, it varied considerably ranging from 1.6% to 8.1%. Population pairwise genetic differentiation was generally significantly high (ranging from F ST¿=¿0.15, P

  17. Evidence of a genetic instability induced by the incorporation of a DNA precursor marked with tritium

    International Nuclear Information System (INIS)

    Saintigny, Y.; Laurent, D.; Lahayel, J.B.; Roche, St.; Meynard, D.; Lopez, B.S.

    2009-01-01

    The authors report a molecular geno-toxicology investigation which allowed molecular events induced par intracellular incorporation of tritium to be studied, and the genetic instability resulting from a chronic exposure even at low dose to be analysed. For this purpose, they developed cell models (hamster tumorous cells and human fibroblasts) in which they know how to incorporate given quantities of marked nucleotides in the DNA. They show that the incorporation of tritium, even with doses which are said to be non toxic, causes a prolonged exposure of the cell to a genotoxic stress, and maybe a genetic instability due to a too great number of recombination events

  18. Genetic Evidence of Importation of Drug-Resistant Plasmodium falciparum to Guatemala from the Democratic Republic of the Congo.

    Science.gov (United States)

    Patel, Jaymin C; Taylor, Steve M; Juliao, Patricia C; Parobek, Christian M; Janko, Mark; Gonzalez, Luis Demetrio; Ortiz, Lucia; Padilla, Norma; Tshefu, Antoinette K; Emch, Michael; Udhayakumar, Venkatachalam; Lindblade, Kim; Meshnick, Steven R

    2014-06-01

    Imported malaria threatens control and elimination efforts in countries that have low rates of transmission. In 2010, an outbreak of Plasmodium falciparum malaria was reported among United Nations peacekeeping soldiers from Guatemala who had recently returned from the Democratic Republic of the Congo (DRC). Epidemiologic evidence suggested that the soldiers were infected in the DRC, but local transmission could not be ruled out in all cases. We used population genetic analyses of neutral microsatellites to determine the outbreak source. Genetic relatedness was compared among parasites found in samples from the soldiers and parasite populations collected in the DRC and Guatemala; parasites identified in the soldiers were more closely related to those from the DRC. A phylogenetic clustering analysis confirms this identification with >99.9% confidence. Thus, results support the hypothesis that the soldiers likely imported malaria from the DRC. This study demonstrates the utility of molecular genotyping in outbreak investigations.

  19. Identification of novel genetic risk loci in Maltese dogs with necrotizing meningoencephalitis and evidence of a shared genetic risk across toy dog breeds.

    Science.gov (United States)

    Schrauwen, Isabelle; Barber, Renee M; Schatzberg, Scott J; Siniard, Ashley L; Corneveaux, Jason J; Porter, Brian F; Vernau, Karen M; Keesler, Rebekah I; Matiasek, Kaspar; Flegel, Thomas; Miller, Andrew D; Southard, Teresa; Mariani, Christopher L; Johnson, Gayle C; Huentelman, Matthew J

    2014-01-01

    Necrotizing meningoencephalitis (NME) affects toy and small breed dogs causing progressive, often fatal, inflammation and necrosis in the brain. Genetic risk loci for NME previously were identified in pug dogs, particularly associated with the dog leukocyte antigen (DLA) class II complex on chromosome 12, but have not been investigated in other susceptible breeds. We sought to evaluate Maltese and Chihuahua dogs, in addition to pug dogs, to identify novel or shared genetic risk factors for NME development. Genome-wide association testing of single nucleotide polymorphisms (SNPs) in Maltese dogs with NME identified 2 regions of genome-wide significance on chromosomes 4 (chr4:74522353T>A, p = 8.1×10-7) and 15 (chr15:53338796A>G, p = 1.5×10-7). Haplotype analysis and fine-mapping suggests that ILR7 and FBXW7, respectively, both important for regulation of immune system function, could be the underlying associated genes. Further evaluation of these regions and the previously identified DLA II locus across all three breeds, revealed an enrichment of nominal significant SNPs associated with chromosome 15 in pug dogs and DLA II in Maltese and Chihuahua dogs. Meta-analysis confirmed effect sizes the same direction in all three breeds for both the chromosome 15 and DLA II loci (p = 8.6×10-11 and p = 2.5×10-7, respectively). This suggests a shared genetic background exists between all breeds and confers susceptibility to NME, but effect sizes might be different among breeds. In conclusion, we identified the first genetic risk factors for NME development in the Maltese, chromosome 4 and chromosome 15, and provide evidence for a shared genetic risk between breeds associated with chromosome 15 and DLA II. Last, DLA II and IL7R both have been implicated in human inflammatory diseases of the central nervous system such as multiple sclerosis, suggesting that similar pharmacotherapeutic targets across species should be investigated.

  20. Identification of novel genetic risk loci in Maltese dogs with necrotizing meningoencephalitis and evidence of a shared genetic risk across toy dog breeds.

    Directory of Open Access Journals (Sweden)

    Isabelle Schrauwen

    Full Text Available Necrotizing meningoencephalitis (NME affects toy and small breed dogs causing progressive, often fatal, inflammation and necrosis in the brain. Genetic risk loci for NME previously were identified in pug dogs, particularly associated with the dog leukocyte antigen (DLA class II complex on chromosome 12, but have not been investigated in other susceptible breeds. We sought to evaluate Maltese and Chihuahua dogs, in addition to pug dogs, to identify novel or shared genetic risk factors for NME development. Genome-wide association testing of single nucleotide polymorphisms (SNPs in Maltese dogs with NME identified 2 regions of genome-wide significance on chromosomes 4 (chr4:74522353T>A, p = 8.1×10-7 and 15 (chr15:53338796A>G, p = 1.5×10-7. Haplotype analysis and fine-mapping suggests that ILR7 and FBXW7, respectively, both important for regulation of immune system function, could be the underlying associated genes. Further evaluation of these regions and the previously identified DLA II locus across all three breeds, revealed an enrichment of nominal significant SNPs associated with chromosome 15 in pug dogs and DLA II in Maltese and Chihuahua dogs. Meta-analysis confirmed effect sizes the same direction in all three breeds for both the chromosome 15 and DLA II loci (p = 8.6×10-11 and p = 2.5×10-7, respectively. This suggests a shared genetic background exists between all breeds and confers susceptibility to NME, but effect sizes might be different among breeds. In conclusion, we identified the first genetic risk factors for NME development in the Maltese, chromosome 4 and chromosome 15, and provide evidence for a shared genetic risk between breeds associated with chromosome 15 and DLA II. Last, DLA II and IL7R both have been implicated in human inflammatory diseases of the central nervous system such as multiple sclerosis, suggesting that similar pharmacotherapeutic targets across species should be investigated.

  1. No evidence that common genetic risk variation is shared between schizophrenia and autism

    NARCIS (Netherlands)

    Vorstman, Jacob A. S.; Anney, Richard J. L.; Derks, Eske M.; Gallagher, Louise; Gill, Michael; de Jonge, Maretha V.; van Engeland, Herman; Kahn, René S.; Ophoff, Roel A.

    2013-01-01

    The similarity between aspects of the clinical presentation of schizophrenia and autism spectrum disorders (ASD) suggests that elements of the biological etiology may also be shared between these two disorders. Recently, an increasing number of rare, mostly structural genetic variants are reported

  2. Genetic evidence for causal relationships between maternal obesity-related traits and birth weight

    NARCIS (Netherlands)

    A.W.R. Tyrrell; R.C. Richmond (Rebecca C.); T.M. Palmer (Tom); B. Feenstra (Bjarke); J. Rangarajan (Janani); S. Metrustry (Sarah); A. Cavadino (Alana); L. Paternoster (Lavinia); L.L. Armstrong (Loren L.); N.M.G. De Silva (N. Maneka G.); A.R. Wood (Andrew); M. Horikoshi (Momoko); F. Geller (Frank); R. Myhre (Ronny); J.P. Bradfield (Jonathan); E. Kreiner-Møller (Eskil); I. Huikari (Ille); J.N. Painter (Jodie N.); J.J. Hottenga (Jouke Jan); C. Allard (Catherine); D. Berry (Diane); L. Bouchard (Luigi); S. Das (Shikta); D.M. Evans (David); H. Hakonarson (Hakon); M.G. Hayes (M. Geoffrey); J. Heikkinen (Jani); A. Hofman (Albert); B.A. Knight (Bridget); P.A. Lind (Penelope); M.I. McCarthy (Mark); G. Mcmahon (George); S.E. Medland (Sarah Elizabeth); M. Melbye (Mads); A.P. Morris (Andrew); M. Nodzenski (Michael); C. Reichetzeder (Christoph); S.M. Ring (Susan); S. Sebert (Sylvain); V. Sengpiel (Verena); T.I.A. Sørensen (Thorkild); G.A.H.M. Willemsen (Gonneke); E.J.C. de Geus (Eco); N.G. Martin (Nicholas); T.D. Spector (Timothy); C. Power (Christine); M.-R. Jarvelin (Marjo-Riitta); H. Bisgaard (Hans); S.F.A. Grant (Struan); C. Nohr (Christian); V.W.V. Jaddoe (Vincent); B. Jacobsson (Bo); J.C. Murray (Jeffrey C.); B. Hocher (Berthold); A.T. Hattersley (Andrew); D.M. Scholtens (Denise M.); G.D. Smith; M.-F. Hivert (Marie-France); J.F. Felix (Janine); E. Hypponen (Elina); W.L. Lowe Jr. (William); T.M. Frayling (Timothy); D.A. Lawlor (Debbie); R.M. Freathy (Rachel)

    2016-01-01

    textabstractIMPORTANCE Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain. OBJECTIVE To test for genetic

  3. Genetic evidence and integration of various data sources for classifying uncertain variants into a single model.

    NARCIS (Netherlands)

    Goldgar, D.E.; Easton, D.F.; Byrnes, G.B.; Spurdle, A.B.; Iversen, E.S.; Greenblatt, M.S.; Boffetta, P.; Couch, F.J.; Wind, N. de; Eccles, D.; Foulkes, W.D.; Genuardi, M.; Hofstra, R.M.; Hogervorst, F.; Hoogerbrugge-van der Linden, N.; Plon, S.E.; Radice, P.; Rasmussen, L.; Sinilnikova, O.M.; Tavtigian, S.V.

    2008-01-01

    Genetic testing often results in the finding of a variant whose clinical significance is unknown. A number of different approaches have been employed in the attempt to classify such variants. For some variants, case-control, segregation, family history, or other statistical studies can provide

  4. Toward Evidence-Based Genetic Research on Lifelong Premature Ejaculation: A Critical Evaluation of Methodology

    Science.gov (United States)

    2011-01-01

    Recently, four premature ejaculation (PE) subtypes have been distinguished on the basis of the duration of the intravaginal ejaculation latency time (IELT). These four PE subtypes have different etiologies and pathogeneses. Genetic research on PE should consider the existence of these PE subtypes and the accurate measurement of the IELT with a stopwatch. Currently, three methods of genetic research on PE have been used. They differ in the investigated population, tool of measurement, study design, and variables of PE. From animal and human research, it is derived that the central serotonergic system "modulates" ejaculation, whereas the ejaculation (reflex) itself is probably not under direct influence of the serotonergic system, but rather under the influence of other neurotransmitter systems in the spinal cord. For genetic research on PE, it is important to take into account that the (serotonergic) modulation of the IELT is variable among men and may even be absent. This means that serotonergic genetic polymorphisms may only be found in men with PE who respond with an ejaculation delay treatment with a selective serotonin reuptake inhibitor. PMID:21344023

  5. Weight of the evidence of genetic investigations of ancestry informative markers

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Eriksen, Poul Svante; Mogensen, Helle Smidt

    2018-01-01

    Ancestry-informative markers (AIMs) are markers that give information about the ancestry of individuals. They are used in forensic genetics for predicting the geographic origin of the investigated individual in crime and identification cases. In the exploration of the genogeographic origin...

  6. Evidence for genetic association between chromosome 1q loci and predisposition to colorectal neoplasia.

    Czech Academy of Sciences Publication Activity Database

    Schubert, S.A.; Ruano, D.; Elsayed, F.A.; Boot, A.; Crobach, S.; Sarasqueta, A.F.; Wolffenbuttel, B.; van der Klauw, M.M.; Oosting, J.; Tops, C.M.; van Eijk, R.; Vasen, H.F.; Vossen, R.H.; Nielsen, M.; Castellví-Bel, S.; Ruiz-Ponte, C.; Tomlinson, I.; Dunlop, M.G.; Vodička, Pavel; Wijnen, J.T.; Hes, F.J.; Morreau, H.; de Miranda, N.F.; Sijmons, R.H.; van Wezel, T.

    2017-01-01

    Roč. 117, č. 8 (2017), s. 1215-1223 ISSN 0007-0920 R&D Projects: GA MŠk(CZ) LD14050 Institutional support: RVO:68378041 Keywords : hereditary colorectal cancer * colorectal polyps * homozygosity mapping Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 6.176, year: 2016

  7. A Danish Twin Study of Schizophrenia Liability: Investigation from Interviewed Twins for Genetic Links to Affective Psychoses and for Cross-Cohort Comparisons.

    Science.gov (United States)

    Kläning, Ulla; Trumbetta, Susan L; Gottesman, Irving I; Skytthe, Axel; Kyvik, Kirsten O; Bertelsen, Aksel

    2016-03-01

    We studied schizophrenia liability in a Danish population-based sample of 44 twin pairs (13 MZ, 31 DZ, SS plus OS) in order to replicate previous twin study findings using contemporary diagnostic criteria, to examine genetic liability shared between schizophrenia and other disorders, and to explore whether variance in schizophrenia liability attributable to environmental factors may have decreased with successive cohorts exposed to improvements in public health. ICD-10 diagnoses were determined by clinical interview. Although the best-fitting, most parsimonious biometric model of schizophrenia liability specified variance attributable to additive genetic and non-shared environmental factors, this model did not differ significantly from a model that also included non-additive genetic factors, consistent with recent interview-based twin studies. Schizophrenia showed strong genetic links to other psychotic disorders but much less so for the broader category of psychiatric disorders in general. We also observed a marginally significant decline in schizophrenia variance attributable to environmental factors over successive Western European cohorts, consistent perhaps with improvements in diagnosis and in prenatal and perinatal care and with a secular decline in the prevalence of schizophrenia in that region.

  8. Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects

    NARCIS (Netherlands)

    Bauters, M.; Frints, S.G.; Esch, H. van; Spruijt, L.; Baldewijns, M.M.; Die-Smulders, C.E.M. de; Fryns, J.P.; Marynen, P.; Froyen, G.

    2014-01-01

    Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from

  9. Explaining individual differences in alcohol intake in adults: evidence for genetic and cultural transmission?

    Science.gov (United States)

    van Beek, Jenny H D A; de Moor, Marleen H M; Geels, Lot M; Willemsen, Gonneke; Boomsma, Dorret I

    2014-03-01

    The current study aimed to describe what proportion of variation in adult alcohol intake is attributable to genetic differences among individuals and what proportion to differences in environmental experiences individuals have been exposed to. Effects of age, gender, spousal resemblance, and cultural transmission of alcohol intake from parents to offspring were taken into account. In a twin-family design, the effects of genetic and cultural transmission and shared and nonshared environment on alcohol intake were estimated with genetic structural equation models. Data originated from adult twins, their siblings, parents (n = 12,587), and spouses (n = 429) registered with the population-based Netherlands Twin Register (63.5% female; ages 18-97 years). Alcohol intake (grams per day) was higher among men than women and increased with age. Broad-sense heritability estimates were similar across sex and age (53%). Spousal resemblance was observed (r = .39) but did not significantly affect the heritability estimates. No effects of cultural transmission were detected. In total, 23% of the variation in alcohol intake was explained by additive genetic effects, 30% by dominant (nonadditive) gene action, and 47% by environmental effects that were not shared among family members. Individual differences in adult alcohol intake are explained by genetic and individual-specific environmental effects. The same genes are expressed in males and females and in younger and older participants. A substantial part of the heritability of alcohol intake is attributable to nonadditive gene action. Effects of cultural transmission that have been reported in adolescence are not present in adulthood.

  10. Genetic characterization of Moroccan and the exotic bread wheat cultivars using functional and random DNA markers linked to the agronomic traits for genomics-assisted improvement.

    Science.gov (United States)

    Henkrar, Fatima; El-Haddoury, Jamal; Ouabbou, Hassan; Bendaou, Najib; Udupa, Sripada M

    2016-06-01

    Genetic characterization, diversity analysis and estimate of the genetic relationship among varieties using functional and random DNA markers linked to agronomic traits can provide relevant guidelines in selecting parents and designing new breeding strategies for marker-assisted wheat cultivar improvement. Here, we characterize 20 Moroccan and 19 exotic bread wheat (Triticum aestivum L.) cultivars using 47 functional and 7 linked random DNA markers associated with 21 loci of the most important traits for wheat breeding. The functional marker analysis revealed that 35, 45, and 10 % of the Moroccan cultivars, respectively have the rust resistance genes (Lr34/Yr18/Pm38), dwarfing genes (Rht1b or Rht2b alleles) and the leaf rust resistance gene (Lr68). The marker alleles for genes Lr37/Yr17/Sr38, Sr24 and Yr36 were present only in the exotic cultivars and absent in Moroccan cultivars. 25 % of cultivars had 1BL.1RS translocation. 70 % of the wheat cultivars had Ppo-D1a and Ppo-A1b associated with low polyphenol oxidase activity. 10 % of cultivars showed presence of a random DNA marker allele (175 bp) linked to Hessian fly resistance gene H22. The majority of the Moroccan cultivars were carrying alleles that impart good bread making quality. Neighbor joining (NJ) and principal coordinate analysis based on the marker data revealed a clear differentiation between elite Moroccan and exotic wheat cultivars. The results of this study are useful for selecting suitable parents for making targeted crosses in marker-assisted wheat breeding and enhancing genetic diversity in the wheat cultivars.

  11. ABO alleles are linked with haplotypes of an erythroid cell-specific regulatory element in intron 1 with a few exceptions attributable to genetic recombination.

    Science.gov (United States)

    Nakajima, T; Sano, R; Takahashi, Y; Watanabe, K; Kubo, R; Kobayashi, M; Takahashi, K; Takeshita, H; Kominato, Y

    2016-01-01

    Recent investigation of transcriptional regulation of the ABO genes has identified a candidate erythroid cell-specific regulatory element, named the +5·8-kb site, in the first intron of ABO. Six haplotypes of the site have been reported previously. The present genetic population study demonstrated that each haplotype was mostly linked with specific ABO alleles with a few exceptions, possibly as a result of hybrid formation between common ABO alleles. Thus, investigation of these haplotypes could provide a clue to further elucidation of ABO alleles. © 2015 International Society of Blood Transfusion.

  12. Strong evidence for a genetic contribution to late-onset Alzheimer's disease mortality: a population-based study.

    Directory of Open Access Journals (Sweden)

    John S K Kauwe

    Full Text Available Alzheimer's disease (AD is an international health concern that has a devastating effect on patients and families. While several genetic risk factors for AD have been identified much of the genetic variance in AD remains unexplained. There are limited published assessments of the familiality of Alzheimer's disease. Here we present the largest genealogy-based analysis of AD to date.We assessed the familiality of AD in The Utah Population Database (UPDB, a population-based resource linking electronic health data repositories for the state with the computerized genealogy of the Utah settlers and their descendants. We searched UPDB for significant familial clustering of AD to evaluate the genetic contribution to disease. We compared the Genealogical Index of Familiality (GIF between AD individuals and randomly selected controls and estimated the Relative Risk (RR for a range of family relationships. Finally, we identified pedigrees with a significant excess of AD deaths.The GIF analysis showed that pairs of individuals dying from AD were significantly more related than expected. This excess of relatedness was observed for both close and distant relationships. RRs for death from AD among relatives of individuals dying from AD were significantly increased for both close and more distant relatives. Multiple pedigrees had a significant excess of AD deaths.These data strongly support a genetic contribution to the observed clustering of individuals dying from AD. This report is the first large population-based assessment of the familiality of AD mortality and provides the only reported estimates of relative risk of AD mortality in extended relatives to date. The high-risk pedigrees identified show a true excess of AD mortality (not just multiple cases and are greater in depth and width than published AD pedigrees. The presence of these high-risk pedigrees strongly supports the possibility of rare predisposition variants not yet identified.

  13. Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity

    NARCIS (Netherlands)

    Cousminer, Diana L.; Berry, Diane J.; Timpson, Nicholas J.; Ang, Wei; Thiering, Elisabeth; Byrne, Enda M.; Taal, H. Rob; Huikari, Ville; Bradfield, Jonathan P.; Kerkhof, Marjan; Groen-Blokhuis, Maria M.; Kreiner-Moller, Eskil; Marinelli, Marcella; Holst, Claus; Leinonen, Jaakko T.; Perry, John R. B.; Surakka, Ida; Pietilainen, Olli; Kettunen, Johannes; Anttila, Verneri; Kaakinen, Marika; Sovio, Ulla; Pouta, Anneli; Das, Shikta; Lagou, Vasiliki; Power, Chris; Prokopenko, Inga; Evans, David M.; Kemp, John P.; St Pourcain, Beate; Ring, Susan; Palotie, Aarno; Kajantie, Eero; Osmond, Clive; Lehtimaki, Terho; Viikari, Jorma S.; Kahonen, Mika; Warrington, Nicole M.; Lye, Stephen J.; Palmer, Lyle J.; Tiesler, Carla M. T.; Flexeder, Claudia; Montgomery, Grant W.; Medland, Sarah E.; Hofman, Albert; Hakonarson, Hakon; Guxens, Monica; Bartels, Meike; Salomaa, Veikko; Koppelman, Gerard H.

    2013-01-01

    The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and

  14. Time dependent genetic analysis links field and controlled environment phenotypes in the model C4 grass Setaria.

    Directory of Open Access Journals (Sweden)

    Max J Feldman

    2017-06-01

    Full Text Available Vertical growth of plants is a dynamic process that is influenced by genetic and environmental factors and has a pronounced effect on overall plant architecture and biomass composition. We have performed six controlled growth trials of an interspecific Setaria italica x Setaria viridis recombinant inbred line population to assess how the genetic architecture of plant height is influenced by developmental queues, water availability and planting density. The non-destructive nature of plant height measurements has enabled us to monitor height throughout the plant life cycle in both field and controlled environments. We find that plant height is reduced under water limitation and high density planting and affected by growth environment (field vs. growth chamber. The results support a model where plant height is a heritable, polygenic trait and that the major genetic loci that influence plant height function independent of growth environment. The identity and contribution of loci that influence height changes dynamically throughout development and the reduction of growth observed in water limited environments is a consequence of delayed progression through the genetic program which establishes plant height in Setaria. In this population, alleles inherited from the weedy S. viridis parent act to increase plant height early, whereas a larger number of small effect alleles inherited from the domesticated S. italica parent collectively act to increase plant height later in development.

  15. Time dependent genetic analysis links field and controlled environment phenotypes in the model C4 grass Setaria.

    Science.gov (United States)

    Feldman, Max J; Paul, Rachel E; Banan, Darshi; Barrett, Jennifer F; Sebastian, Jose; Yee, Muh-Ching; Jiang, Hui; Lipka, Alexander E; Brutnell, Thomas P; Dinneny, José R; Leakey, Andrew D B; Baxter, Ivan

    2017-06-01

    Vertical growth of plants is a dynamic process that is influenced by genetic and environmental factors and has a pronounced effect on overall plant architecture and biomass composition. We have performed six controlled growth trials of an interspecific Setaria italica x Setaria viridis recombinant inbred line population to assess how the genetic architecture of plant height is influenced by developmental queues, water availability and planting density. The non-destructive nature of plant height measurements has enabled us to monitor height throughout the plant life cycle in both field and controlled environments. We find that plant height is reduced under water limitation and high density planting and affected by growth environment (field vs. growth chamber). The results support a model where plant height is a heritable, polygenic trait and that the major genetic loci that influence plant height function independent of growth environment. The identity and contribution of loci that influence height changes dynamically throughout development and the reduction of growth observed in water limited environments is a consequence of delayed progression through the genetic program which establishes plant height in Setaria. In this population, alleles inherited from the weedy S. viridis parent act to increase plant height early, whereas a larger number of small effect alleles inherited from the domesticated S. italica parent collectively act to increase plant height later in development.

  16. Evidence for genetic variation in human mate preferences for sexually dimorphic physical traits.

    Directory of Open Access Journals (Sweden)

    Karin J H Verweij

    Full Text Available Intersexual selection has been proposed as an important force in shaping a number of morphological traits that differ between human populations and/or between the sexes. Important to these accounts is the source of mate preferences for such traits, but this has not been investigated. In a large sample of twins, we assess forced-choice, dichotomous mate preferences for height, skin colour, hair colour and length, chest hair, facial hair, and breast size. Across the traits, identical twins reported more similar preferences than nonidentical twins, suggesting genetic effects. However, the relative magnitude of estimated genetic and environmental effects differed greatly and significantly between different trait preferences, with heritability estimates ranging from zero to 57%.

  17. Molecular evidence and high genetic diversity of shrew-borne Seewis virus in Slovenia.

    Science.gov (United States)

    Resman, Katarina; Korva, Miša; Fajs, Luka; Zidarič, Tanja; Trilar, Tomi; Zupanc, Tatjana Avšič

    2013-10-01

    Seewis virus, the shrew-borne hantavirus from Sorex araneus, has been molecularly detected in reservoir hosts in many different central European countries and Russia. Slovenia is a known endemic country for rodent-borne hantaviruses, therefore the aim of the study was to investigate the presence of shrew-borne hantaviruses in insectivores. Viral L, S and M segment have been recovered only from tissue samples of 7 S. araneus, despite several shrew species were tested. Phylogenetic analysis showed high genetic diversity of SWSV in Slovenia, ranging from 3 to 19.4% for different viral segments. The most divergent were M segment sequences, with 19.4% nucleotide divergence among Slovenian strains. Above that, different SWSV strains from Slovenia do not group into separate geographic clusters. While three separate genetic clades were determined, two of them were simultaneously present in one location at the same time. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Linking transcriptional and genetic tumor heterogeneity through allele analysis of single-cell RNA-seq data.

    Science.gov (United States)

    Fan, Jean; Lee, Hae-Ock; Lee, Soohyun; Ryu, Da-Eun; Lee, Semin; Xue, Catherine; Kim, Seok Jin; Kim, Kihyun; Barkas, Nikolas; Park, Peter J; Park, Woong-Yang; Kharchenko, Peter V

    2018-06-13

    Characterization of intratumoral heterogeneity is critical to cancer therapy, as presence of phenotypically diverse cell populations commonly fuels relapse and resistance to treatment. Although genetic variation is a well-studied source of intratumoral heterogeneity, the functional impact of most genetic alterations remains unclear. Even less understood is the relative importance of other factors influencing heterogeneity, such as epigenetic state or tumor microenvironment. To investigate the relationship between genetic and transcriptional heterogeneity in a context of cancer progression, we devised a computational approach called HoneyBADGER to identify copy number variation and loss-of-heterozygosity in individual cells from single-cell RNA-sequencing data. By integrating allele and normalized expression information, HoneyBADGER is able to identify and infer the presence of subclone-specific alterations in individual cells and reconstruct underlying subclonal architecture. Examining several tumor types, we show that HoneyBADGER is effective at identifying deletion, amplifications, and copy-neutral loss-of-heterozygosity events, and is capable of robustly identifying subclonal focal alterations as small as 10 megabases. We further apply HoneyBADGER to analyze single cells from a progressive multiple myeloma patient to identify major genetic subclones that exhibit distinct transcriptional signatures relevant to cancer progression. Surprisingly, other prominent transcriptional subpopulations within these tumors did not line up with the genetic subclonal structure, and were likely driven by alternative, non-clonal mechanisms. These results highlight the need for integrative analysis to understand the molecular and phenotypic heterogeneity in cancer. Published by Cold Spring Harbor Laboratory Press.

  19. Host use evolution in Chrysochus milkweed beetles: evidence from behaviour, population genetics and phylogeny.

    Science.gov (United States)

    Dobler, S; Farrell, B D

    1999-08-01

    In two sister species of leaf beetles with overlapping host associations, Chrysochus auratus and C. cobaltinus, we established diet breadth and food preference of local populations for evaluation together with genetic differentiation between populations. While C. auratus turned out to be monophagous on the same plant wherever we collected the beetles, the studied populations of C. cobaltinus fed on three different plant species in the field. Plant preference and ranking of the potential host plants significantly differed between these populations. The amount of genetic differentiation between populations was measured by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay of a 1300 bp mitochondrial DNA (mtDNA) sequence. In addition, the dominant genotypes of all populations were sequenced. No genetic differentiation between the populations of C. auratus could be detected in the RFLP assay and sequence divergence was low (= 0.3%). In C. cobaltinus, on the other hand, genetic differentiation between populations was high, revealing a lack of gene flow over a much smaller scale and a maximum of 1.3% sequence divergence. C. cobaltinus thereby has the prerequisites for host race formation on different plants from the original host spectrum. Our sequence-based phylogeny estimate allows us to reconstruct historical diet evolution in Chrysochus. Starting from an original association with Asclepiadaceae, the common ancestor of C. auratus and C. cobaltinus included Apocynaceae in its diet. The strict specialization on Apocynum and the loss of acceptance of Asclepiadaceae observed in C. auratus could have resulted from a process similar to that displayed by C. cobaltinus populations.

  20. Can abnormal returns be earned on bandwidth-bounded currencies? Evidence from a genetic algorithm

    OpenAIRE

    Pedro Godinho

    2012-01-01

    Most of the studies about the Foreign Exchange market (Forex) analyse the behaviour of currencies that are allowed to float freely (or almost freely), but some currencies are still bounded by bandwidths (either disclosed or undisclosed). In this paper, I try to find out whether two bandwidth-bounded currencies, the Hong Kong dollar (HKD) and the Singapore dollar (SGD), present opportunities for abnormal returns. I consider a set of trading rules, and I use a genetic algorithm to optimise both...

  1. Genetic evidence reveals improvement opportunities for tissue preparation in forensic analysis

    OpenAIRE

    Romero, Rosa Elena; Sandoval, Alejandro; Arango, Juliana; Camargo, Martha Lucia

    2016-01-01

    Introduction: Paraffin embedded tissues are an excellent alternative to obtain dna, especially when it is not possible to have fresh samples or when the tissue storage and preservation is not feasible; therefore, this sample is the only item available for matching purposes. The success in any genetic analysis implies having adequate tissue fixation and suitable dna extraction methods that allow to obtain good quality and quantity molecules, free of biological, chemical and microbiological con...

  2. Low genetic variation and evidence of limited dispersal in the regionally important Belize manatee

    Science.gov (United States)

    Hunter, M.E.; Auil-Gomez, N. E.; Tucker, K.P.; Bonde, R.K.; Powell, J.; McGuire, P.M.

    2010-01-01

    The Antillean subspecies of the West Indian manatee Trichechus manatus is found throughout Central and South America and the Caribbean. Because of severe hunting pressure during the 17th through 19th centuries, only small populations of the once widespread aquatic mammal remain. Fortunately, protections in Belize reduced hunting in the 1930s and allowed the country's manatee population to become the largest breeding population in the Wider Caribbean. However, increasing and emerging anthropogenic threats such as coastal development, pollution, watercraft collision and net entanglement represent challenges to this ecologically important population. To inform conservation and management decisions, a comprehensive molecular investigation of the genetic diversity, relatedness and population structure of the Belize manatee population was conducted using mitochondrial and microsatellite DNA. Compared with other mammal populations, a low degree of genetic diversity was detected (HE=0.455; NA=3.4), corresponding to the small population size and long-term exploitation. Manatees from the Belize City Cayes and Southern Lagoon system were genetically different, with microsatellite and mitochondrial FST values of 0.029 and 0.078, respectively (P≤0.05). This, along with the distinct habitats and threats, indicates that separate protection of these two groups would best preserve the region's diversity. The Belize population and Florida subspecies appear to be unrelated with microsatellite and mitochondrial FST values of 0.141 and 0.63, respectively (P≤0.001), supporting the subspecies designations and suggesting low vagility throughout the northern Caribbean habitat. Further monitoring and protection may allow an increase in the Belize manatee genetic diversity and population size. A large and expanding Belize population could potentially assist in the recovery of other threatened or functionally extinct Central American Antillean manatee populations.

  3. Genetic evidence for a worldwide chaotic dispersion pattern of the arbovirus vector, Aedes albopictus.

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    Mosè Manni

    2017-01-01

    Full Text Available Invasive species represent a global concern for their rapid spread and the possibility of infectious disease transmission. This is the case of the global invader Aedes albopictus, the Asian tiger mosquito. This species is a vector of medically important arboviruses, notably chikungunya (CHIKV, dengue (DENV and Zika (ZIKV. The reconstruction of the complex colonization pattern of this mosquito has great potential for mitigating its spread and, consequently, disease risks.Classical population genetics analyses and Approximate Bayesian Computation (ABC approaches were combined to disentangle the demographic history of Aedes albopictus populations from representative countries in the Southeast Asian native range and in the recent and more recently colonized areas. In Southeast Asia, the low differentiation and the high co-ancestry values identified among China, Thailand and Japan indicate that, in the native range, these populations maintain high genetic connectivity, revealing their ancestral common origin. China appears to be the oldest population. Outside Southeast Asia, the invasion process in La Réunion, America and the Mediterranean Basin is primarily supported by a chaotic propagule distribution, which cooperates in maintaining a relatively high genetic diversity within the adventive populations.From our data, it appears that independent and also trans-continental introductions of Ae. albopictus may have facilitated the rapid establishment of adventive populations through admixture of unrelated genomes. As a consequence, a great amount of intra-population variability has been detected, and it is likely that this variability may extend to the genetic mechanisms controlling vector competence. Thus, in the context of the invasion process of this mosquito, it is possible that both population ancestry and admixture contribute to create the conditions for the efficient transmission of arboviruses and for outbreak establishment.

  4. Molybdenum isotopic evidence for the origin of chondrules and a distinct genetic heritage of carbonaceous and non-carbonaceous meteorites

    Science.gov (United States)

    Budde, Gerrit; Burkhardt, Christoph; Brennecka, Gregory A.; Fischer-Gödde, Mario; Kruijer, Thomas S.; Kleine, Thorsten

    2016-11-01

    Nucleosynthetic isotope anomalies are powerful tracers to determine the provenance of meteorites and their components, and to identify genetic links between these materials. Here we show that chondrules and matrix separated from the Allende CV3 chondrite have complementary nucleosynthetic Mo isotope anomalies. These anomalies result from the enrichment of a presolar carrier enriched in s-process Mo into the matrix, and the corresponding depletion of this carrier in the chondrules. This carrier most likely is a metal and so the uneven distribution of presolar material probably results from metal-silicate fractionation during chondrule formation. The Mo isotope anomalies correlate with those reported for W isotopes on the same samples in an earlier study, suggesting that the isotope variations for both Mo and W are caused by the heterogeneous distribution of the same carrier. The isotopic complementary of chondrules and matrix indicates that both components are genetically linked and formed together from one common reservoir of solar nebula dust. As such, the isotopic data require that most chondrules formed in the solar nebula and are not a product of protoplanetary impacts. Allende chondrules and matrix together with bulk carbonaceous chondrites and some iron meteorites (groups IID, IIIF, and IVB) show uniform excesses in 92Mo, 95Mo, and 97Mo that result from the addition of supernova material to the solar nebula region in which these carbonaceous meteorites formed. Non-carbonaceous meteorites (enstatite and ordinary chondrites as well as most iron meteorites) do not contain this material, demonstrating that two distinct Mo isotope reservoirs co-existed in the early solar nebula that remained spatially separated for several million years. This separation was most likely achieved through the formation of the gas giants, which cleared the disk between the inner and outer solar system regions parental to the non-carbonaceous and carbonaceous meteorites. The Mo isotope

  5. Population Genetic Structure and Evidence of Demographic Expansion of the Ayu (Plecoglossus altivelis in East Asia

    Directory of Open Access Journals (Sweden)

    Ye-Seul Kwan

    2012-10-01

    Full Text Available Plecoglossus altivelis (ayu is an amphidromous fish widely distributed in Northeastern Asia from the East China Sea to the northern Japanese coastal waters, encompassing the Korean Peninsula within its range. The shore lines of northeastern region in Asia have severely fluctuated following glaciations in the Quaternary. In the present study, we investigate the population genetic structure and historical demographic change of P. altivelis at a population level in East Asia. Analysis of molecular variance (AMOVA based on 244 mitochondrial control region DNA sequences clearly showed that as the sampling scope extended to a larger geographic area, genetic differentiation began to become significant, particularly among Northeastern populations. A series of hierarchical AMOVA could detect the genetic relationship of three closely located islands between Korea and Japan that might have been tightly connected by the regional Tsushima current. Neutrality and mismatch distribution analyses revealed a strong signature of a recent population expansion of P. altivelis in East Asia, estimated at 126 to 391 thousand years ago during the late Pleistocene. Therefore it suggests that the present population of P. altivelis traces back to its approximate demographic change long before the last glacial maximum. This contrasts our a priori expectation that the most recent glacial event might have the most crucial effect on the present day demography of marine organisms through bottleneck and subsequent increase of effective population size in this region.

  6. Genetic evidence for landscape effects on dispersal in the army ant Eciton burchellii.

    Science.gov (United States)

    Soare, Thomas W; Kumar, Anjali; Naish, Kerry A; O'Donnell, Sean

    2014-01-01

    Inhibited dispersal, leading to reduced gene flow, threatens populations with inbreeding depression and local extinction. Fragmentation may be especially detrimental to social insects because inhibited gene flow has important consequences for cooperation and competition within and among colonies. Army ants have winged males and permanently wingless queens; these traits imply male-biased dispersal. However, army ant colonies are obligately nomadic and have the potential to traverse landscapes. Eciton burchellii, the most regularly nomadic army ant, is a forest interior species: colony raiding activities are limited in the absence of forest cover. To examine whether nomadism and landscape (forest clearing and elevation) affect population genetic structure in a montane E. burchellii population, we reconstructed queen and male genotypes from 25 colonies at seven polymorphic microsatellite loci. Pairwise genetic distances among individuals were compared to pairwise geographical and resistance distances using regressions with permutations, partial Mantel tests and random forests analyses. Although there was no significant spatial genetic structure in queens or males in montane forest, dispersal may be male-biased. We found significant isolation by landscape resistance for queens based on land cover (forest clearing), but not on elevation. Summed colony emigrations over the lifetime of the queen may contribute to gene flow in this species and forest clearing impedes these movements and subsequent gene dispersal. Further forest cover removal may increasingly inhibit Eciton burchellii colony dispersal. We recommend maintaining habitat connectivity in tropical forests to promote population persistence for this keystone species. © 2013 John Wiley & Sons Ltd.

  7. Expectations and experiences of gamete donors and donor-conceived adults searching for genetic relatives using DNA linking through a voluntary register.

    Science.gov (United States)

    van den Akker, O B A; Crawshaw, M A; Blyth, E D; Frith, L J

    2015-01-01

    What are the experiences of donor-conceived adults and donors who are searching for a genetic link through the use of a DNA-based voluntary register service? Donor-conceived adults and donors held positive beliefs about their search and although some concerns in relation to finding a genetically linked relative were reported, these were not a barrier to searching. Research with donor-conceived people has consistently identified their interest in learning about-and in some cases making contact with-their donor and other genetic relatives. However, donor-conceived individuals or donors rarely have the opportunity to act on these desires. A questionnaire was administered for online completion using Bristol Online Surveys. The survey was live for 3 months and responses were collected anonymously. The survey was completed by 65 donor-conceived adults, 21 sperm donors and 5 oocyte donors who had registered with a DNA-based voluntary contact register in the UK. The questionnaire included socio-demographic questions, questions specifically developed for the purposes of this study and the standardized Aspects of Identity Questionnaire (AIQ). Motivations for searching for genetic relatives were varied, with the most common reasons being curiosity and passing on information. Overall, participants who were already linked and those awaiting a link were positive about being linked and valued access to a DNA-based register. Collective identity (reflecting self-defining feelings of continuity and uniqueness), as assessed by the AIQ, was significantly lower for donor-conceived adults when compared with the donor groups (P 0.05) for donor-conceived adults. Participants were members of a UK DNA-based registry which is unique. It was therefore not possible to determine how representative participants were of those who did not register for the service, those in other countries or of those who do not seek information exchange or contact. This is the first survey exploring the

  8. Neuroimmune Pathways in Alcohol Consumption: Evidence from Behavioral and Genetic Studies in Rodents and Humans

    Science.gov (United States)

    Robinson, Gizelle; Most, Dana; Ferguson, Laura B.; Mayfield, Jody; Harris, R. Adron; Blednov, Yuri A.

    2014-01-01

    Immune or brain proinflammatory signaling has been linked to some of the behavioral effects of alcohol. Immune signaling appears to regulate voluntary ethanol intake in rodent models, and ethanol intake activates the immune system in multiple models. This bidirectional link raises the possibility that consumption increases immune signaling, which in turn further increases consumption in a feed-forward cycle. Data from animal and human studies provide overlapping support for the involvement of immune-related genes and proteins in alcohol action, and combining animal and human data is a promising approach to systematically evaluate and nominate relevant pathways. Based on rodent models, neuroimmune pathways may represent unexplored, nontraditional targets for medication development to reduce alcohol consumption and prevent relapse. Peroxisome proliferator-activated receptor agonists are one class of anti-inflammatory medications that demonstrate antiaddictive properties for alcohol and other drugs of abuse. Expression of immune-related genes is altered in animals and humans following chronic alcohol exposure, and the regulatory influences of specific mRNAs, microRNAs, and activated cell types are areas of intense study. Ultimately, the use of multiple datasets combined with behavioral validation will be needed to link specific neuroimmune pathways to addiction vulnerability. PMID:25175860

  9. Preschoolers’ Genetic, Physiological, and Behavioral Sensitivity Factors Moderate Links Between Parenting Stress and Child Internalizing, Externalizing, and Sleep Problems

    Science.gov (United States)

    Davis, Molly; Thomassin, Kristel; Bilms, Joanie; Suveg, Cynthia; Shaffer, Anne; Beach, Steven R. H.

    2017-01-01

    This study examined three potential moderators of the relations between maternal parenting stress and preschoolers’ adjustment problems: a genetic polymorphism - the short allele of the serotonin transporter (5-HTTLPR, ss/sl allele) gene, a physiological indicator - children’s baseline respiratory sinus arrhythmia (RSA), and a behavioral indicator - mothers’ reports of children’s negative emotionality. A total of 108 mothers (Mage = 30.68 years, SDage = 6.06) reported on their parenting stress as well as their preschoolers’ (Mage = 3.50 years, SDage = .51, 61% boys) negative emotionality and internalizing, externalizing, and sleep problems. Results indicated that the genetic sensitivity variable functioned according to a differential susceptibility model; however, the results involving physiological and behavioral sensitivity factors were most consistent with a diathesis-stress framework. Implications for prevention and intervention efforts to counter the effects of parenting stress are discussed. PMID:28295263

  10. Low genetic variation in the MHC class II DRB gene and MHC-linked microsatellites in endangered island populations of the leopard cat (Prionailurus bengalensis) in Japan.

    Science.gov (United States)

    Saka, Toshinori; Nishita, Yoshinori; Masuda, Ryuichi

    2018-02-01

    Isolated populations of the leopard cat (Prionailurus bengalensis) on Tsushima and Iriomote islands in Japan are classified as subspecies P. b. euptilurus and P. b. iriomotensis, respectively. Because both populations have decreased to roughly 100, an understanding of their genetic diversity is essential for conservation. We genotyped MHC class II DRB exon 2 and MHC-linked microsatellite loci to evaluate the diversity of MHC genes in the Tsushima and Iriomote cat populations. We detected ten and four DRB alleles in these populations, respectively. A phylogenetic analysis showed DRB alleles from both populations to be closely related to those in other felid DRB lineages, indicating trans-species polymorphism. The MHC-linked microsatellites were more polymorphic in the Tsushima than in the Iriomote population. The MHC diversity of both leopard cat populations is much lower than in the domestic cat populations on these islands, probably due to inbreeding associated with founder effects, geographical isolation, or genetic drift. Our results predict low resistance of the two endangered populations to new pathogens introduced to the islands.

  11. Valenced action/inhibition learning in humans is modulated by a genetic variant linked to dopamine D2 receptor expression

    Directory of Open Access Journals (Sweden)

    Anni eRichter

    2014-08-01

    Full Text Available Motivational salience plays an important role in shaping human behavior, but recent studies demonstrate that human performance is not uniformly improved by motivation. Instead, action has been shown to dominate valence in motivated tasks, and it is particularly difficult for humans to learn the inhibition of an action to obtain a reward, but the neural mechanism behind this behavioral specificity is yet unclear. In all mammals, including humans, the monoamine neurotransmitter dopamine is particularly important in the neural manifestation of appetitively motivated behavior, and the human dopamine system is subject to considerable genetic variability. The well-studied TaqIA restriction fragment length polymorphism (rs1800497 has previously been shown to affect striatal dopamine metabolism. In this study we investigated a potential effect of this genetic variation on motivated action/inhibition learning. Two independent cohorts consisting of 87 and 95 healthy participants, respectively, were tested using the previously described valenced go/no-go learning paradigm in which participants learned the reward-associated no-go condition significantly worse than all other conditions. This effect was modulated by the TaqIA polymorphism, with carriers of the A1 allele showing a diminished learning-related performance enhancement in the rewarded no-go condition compared to the A2 homozygotes. This result highlights a modulatory role for genetic variability of the dopaminergic system in individual learning differences of action-valence interaction.

  12. Linking neocortical, cognitive, and genetic variability in autism with alterations of brain plasticity: the Trigger-Threshold-Target model.

    Science.gov (United States)

    Mottron, Laurent; Belleville, Sylvie; Rouleau, Guy A; Collignon, Olivier

    2014-11-01

    The phenotype of autism involves heterogeneous adaptive traits (strengths vs. disabilities), different domains of alterations (social vs. non-social), and various associated genetic conditions (syndromic vs. nonsyndromic autism). Three observations suggest that alterations in experience-dependent plasticity are an etiological factor in autism: (1) the main cognitive domains enhanced in autism are controlled by the most plastic cortical brain regions, the multimodal association cortices; (2) autism and sensory deprivation share several features of cortical and functional reorganization; and (3) genetic mutations and/or environmental insults involved in autism all appear to affect developmental synaptic plasticity, and mostly lead to its upregulation. We present the Trigger-Threshold-Target (TTT) model of autism to organize these findings. In this model, genetic mutations trigger brain reorganization in individuals with a low plasticity threshold, mostly within regions sensitive to cortical reallocations. These changes account for the cognitive enhancements and reduced social expertise associated with autism. Enhanced but normal plasticity may underlie non-syndromic autism, whereas syndromic autism may occur when a triggering mutation or event produces an altered plastic reaction, also resulting in intellectual disability and dysmorphism in addition to autism. Differences in the target of brain reorganization (perceptual vs. language regions) account for the main autistic subgroups. In light of this model, future research should investigate how individual and sex-related differences in synaptic/regional brain plasticity influence the occurrence of autism. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Strong Genetic Differentiation of Submerged Plant Populations across Mountain Ranges: Evidence from Potamogeton pectinatus in Iran.

    Science.gov (United States)

    Abbasi, Shabnam; Afsharzadeh, Saeed; Saeidi, Hojjatollah; Triest, Ludwig

    2016-01-01

    Biogeographic barriers for freshwater biota can be effective at various spatial scales. At the largest spatial scale, freshwater organisms can become genetically isolated by their high mountain ranges, vast deserts, and inability to cross oceans. Isolation by distance of aquatic plants is expected to be stronger across than alongside mountain ridges whereas the heterogeneity of habitats among populations and temporary droughts may influence connectivity and hamper dispersal. Suitable aquatic plant habitats became reduced, even for the widespread submerged Potamogeton pectinatus L. (also named Stuckenia pectinata) giving structure to various aquatic habitats. We compared the level of genetic diversity in a heterogeneous series of aquatic habitats across Iran and tested their differentiation over distances and across mountain ranges (Alborz and Zagros) and desert zones (Kavir), with values obtained from temperate region populations. The diversity of aquatic ecosystems across and along large geographic barriers provided a unique ecological situation within Iran. P. pectinatus were considered from thirty-six sites across Iran at direct flight distances ranging from 20 to 1,200 km. Nine microsatellite loci revealed a very high number of alleles over all sites. A PCoA, NJT clustering and STRUCTURE analysis revealed a separate grouping of individuals of southeastern Iranian sites and was confirmed by their different nuclear ITS and cpDNA haplotypes thereby indicating an evolutionary significant unit (ESU). At the level of populations, a positive correlation between allelic differentiation Dest with geographic distance was found. Individual-based STRUCTURE analysis over 36 sites showed 7 genetic clusters. FST and RST values for ten populations reached 0.343 and 0.521, respectively thereby indicating that allele length differences are more important and contain evolutionary information. Overall, higher levels of diversity and a stronger differentiation was revealed among

  14. Evidence for Genetic Similarity of Vegetative Compatibility Groupings in Sclerotinia homoeocarpa

    Directory of Open Access Journals (Sweden)

    Seog Won Chang

    2014-12-01

    Full Text Available Vegetative compatibility groups (VCGs are determined for many fungi to test for the ability of fungal isolates to undergo heterokaryon formation. In several fungal plant pathogens, isolates belonging to a VCG have been shown to share significantly higher genetic similarity than those of different VCGs. In this study we sought to examine the relationship between VCG and genetic similarity of an important cool season turfgrass pathogen, Sclerotinia homoeocarpa. Twenty-two S. homoeocarpa isolates from the Midwest and Eastern US, which were previously characterized in several studies, were all evaluated for VCG using an improved nit mutant assay. These isolates were also genotyped using 19 microsatellites developed from partial genome sequence of S. homoeocarpa. Additionally, partial sequences of mitochondrial genes cytochrome oxidase II and mitochondrial small subunit (mtSSU rRNA, and the atp6-rns intergenic spacer, were generated for isolates from each nit mutant VCG to determine if mitochondrial haplotypes differed among VCGs. Of the 22 isolates screened, 15 were amenable to the nit mutant VCG assay and were grouped into six VCGs. The 19 microsatellites gave 57 alleles for this set. Unweighted pair group methods with arithmetic mean (UPGMA tree of binary microsatellite data were used to produce a dendrogram of the isolate genotypes based on microsatellite alleles, which showed high genetic similarity of nit mutant VCGs. Analysis of molecular variance of microsatellite data demonstrates that the current nit mutant VCGs explain the microsatellite genotypic variation among isolates better than the previous nit mutant VCGs or the conventionally determined VCGs. Mitochondrial sequences were identical among all isolates, suggesting that this marker type may not be informative for US populations of S. homoeocarpa.

  15. Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications

    International Nuclear Information System (INIS)

    Nugoli, Mélanie; Theillet, Charles; Chuchana, Paul; Vendrell, Julie; Orsetti, Béatrice; Ursule, Lisa; Nguyen, Catherine; Birnbaum, Daniel; Douzery, Emmanuel JP; Cohen, Pascale

    2003-01-01

    Both phenotypic and cytogenetic variability have been reported for clones of breast carcinoma cell lines but have not been comprehensively studied. Despite this, cell lines such as MCF-7 cells are extensively used as model systems. In this work we documented, using CGH and RNA expression profiles, the genetic variability at the genomic and RNA expression levels of MCF-7 cells of different origins. Eight MCF-7 sublines collected from different sources were studied as well as 3 subclones isolated from one of the sublines by limit dilution. MCF-7 sublines showed important differences in copy number alteration (CNA) profiles. Overall numbers of events ranged from 28 to 41. Involved chromosomal regions varied greatly from a subline to another. A total of 62 chromosomal regions were affected by either gains or losses in the 11 sublines studied. We performed a phylogenetic analysis of CGH profiles using maximum parsimony in order to reconstruct the putative filiation of the 11 MCF-7 sublines. The phylogenetic tree obtained showed that the MCF-7 clade was characterized by a restricted set of 8 CNAs and that the most divergent subline occupied the position closest to the common ancestor. Expression profiles of 8 MCF-7 sublines were analyzed along with those of 19 unrelated breast cancer cell lines using home made cDNA arrays comprising 720 genes. Hierarchical clustering analysis of the expression data showed that 7/8 MCF-7 sublines were grouped forming a cluster while the remaining subline clustered with unrelated breast cancer cell lines. These data thus showed that MCF-7 sublines differed at both the genomic and phenotypic levels. The analysis of CGH profiles of the parent subline and its three subclones supported the heteroclonal nature of MCF-7 cells. This strongly suggested that the genetic plasticity of MCF-7 cells was related to their intrinsic capacity to generate clonal heterogeneity. We propose that MCF-7, and possibly the breast tumor it was derived from, evolved

  16. Fossil and Genetic Evidence for the Polyphyletic Nature of the Planktonic Foraminifera "Globigerinoides", and Description of the New Genus Trilobatus

    Science.gov (United States)

    Spezzaferri, Silvia; Kucera, Michal; Pearson, Paul Nicholas; Wade, Bridget Susan; Rappo, Sacha; Poole, Christopher Robert; Morard, Raphaël; Stalder, Claudio

    2015-01-01

    Planktonic foraminifera are one of the most abundant and diverse protists in the oceans. Their utility as paleo proxies requires rigorous taxonomy and comparison with living and genetically related counterparts. We merge genetic and fossil evidence of “Globigerinoides”, characterized by supplementary apertures on spiral side, in a new approach to trace their “total evidence phylogeny” since their first appearance in the latest Paleogene. Combined fossil and molecular genetic data indicate that this genus, as traditionally understood, is polyphyletic. Both datasets indicate the existence of two distinct lineages that evolved independently. One group includes “Globigerinoides” trilobus and its descendants, the extant “Globigerinoides” sacculifer, Orbulina universa and Sphaeroidinella dehiscens. The second group includes the Globigerinoides ruber clade with the extant G. conglobatus and G. elongatus and ancestors. In molecular phylogenies, the trilobus group is not the sister taxon of the ruber group. The ruber group clusters consistently together with the modern Globoturborotalita rubescens as a sister taxon. The re-analysis of the fossil record indicates that the first “Globigerinoides” in the late Oligocene are ancestral to the trilobus group, whereas the ruber group first appeared at the base of the Miocene with representatives distinct from the trilobus group. Therefore, polyphyly of the genus "Globigerinoides" as currently defined can only be avoided either by broadening the genus concept to include G. rubescens and a large number of fossil species without supplementary apertures, or if the trilobus group is assigned to a separate genus. Since the former is not feasible due to the lack of a clear diagnosis for such a broad genus, we erect a new genus Trilobatus for the trilobus group (type species Globigerina triloba Reuss) and amend Globoturborotalita and Globigerinoides to clarify morphology and wall textures of these genera. In the new

  17. Genetics Home Reference: isolated growth hormone deficiency

    Science.gov (United States)

    ... can be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (4 links) Genetic Testing Registry: Ateleiotic dwarfism Genetic Testing Registry: Autosomal dominant isolated somatotropin deficiency ...

  18. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel

    NARCIS (Netherlands)

    Ference, Brian A.; Ginsberg, Henry N.; Graham, Ian; Ray, Kausik K.; Packard, Chris J.; Bruckert, Eric; Hegele, Robert A.; Krauss, Ronald M.; Raal, Frederick J.; Schunkert, Heribert; Watts, Gerald F.; Boren, Jan; Fazio, Sergio; Horton, Jay D.; Masana, Luis; Nicholls, Stephen J.; Nordestgaard, Borge G.; van de Sluis, Bart; Taskinen, Marja-Riitta; Tokgozoglu, Lale; Landmesser, Ulf; Laufs, Ulrich; Wiklund, Olov; Stock, Jane K.; Chapman, M. John; Catapano, Alberico L.

    2017-01-01

    Aims: To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results: We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from

  19. A constructionist review of morality and emotions: no evidence for specific links between moral content and discrete emotions.

    Science.gov (United States)

    Cameron, C Daryl; Lindquist, Kristen A; Gray, Kurt

    2015-11-01

    Morality and emotions are linked, but what is the nature of their correspondence? Many "whole number" accounts posit specific correspondences between moral content and discrete emotions, such that harm is linked to anger, and purity is linked to disgust. A review of the literature provides little support for these specific morality-emotion links. Moreover, any apparent specificity may arise from global features shared between morality and emotion, such as affect and conceptual content. These findings are consistent with a constructionist perspective of the mind, which argues against a whole number of discrete and domain-specific mental mechanisms underlying morality and emotion. Instead, constructionism emphasizes the flexible combination of basic and domain-general ingredients such as core affect and conceptualization in creating the experience of moral judgments and discrete emotions. The implications of constructionism in moral psychology are discussed, and we propose an experimental framework for rigorously testing morality-emotion links. © 2015 by the Society for Personality and Social Psychology, Inc.

  20. Evidence for coordinate genetic control of Na,K pump density in erythrocytes and lymphocytes

    International Nuclear Information System (INIS)

    DeLuise, M.; Flier, J.S.

    1985-01-01

    The erythrocyte is widely used as a model cell for studies of the Na,K pump in health and disease. However, little is known about the factors that control the number of Na,K pumps expressed on the erythrocytes of a given individual, nor about the extent to which erythrocytes can be used to validly assess the pump density on other cell types. In this report, the authors have compared the interindividual variance of Na,K pump density in erythrocytes of unrelated individuals to that seen with identical twins. Unlike unrelated individuals, in whom pump parameters, i.e., ouabain binding sites, 86 Rb uptake, and cell Na concentration vary widely, identical twin pairs showed no significant intrapair variation for these values. Thus, a role for genetic factors is suggested. In addition, the authors established and validated a method for determining Na,K pump density and pump-mediated 86 Rb uptake in human peripheral lymphocytes. Using this method, they show that whereas Na,K pump density differs markedly between erythrocytes (mean of 285 sites per cell) and lymphocytes (mean 40,600 sites per cell), there is a strong and highly significant correlation (r = 0.79, P less than 0.001) between the pump density in these cell types in any given individual. Taken together, these studies suggest that genetic factors are important determinants of Na,K pump expression, and that pump density appears to be coordinately regulated in two cell types in healthy individuals

  1. Genetic structure of Mount Huang honey bee (Apis cerana) populations: evidence from microsatellite polymorphism.

    Science.gov (United States)

    Liu, Fang; Shi, Tengfei; Huang, Sisi; Yu, Linsheng; Bi, Shoudong

    2016-01-01

    The Mount Huang eastern honey bees ( Apis cerana ) are an endemic population, which is well adapted to the local agricultural and ecological environment. In this study, the genetic structure of seven eastern honey bees ( A. cerana ) populations from Mount Huang in China were analyzed by SSR (simple sequence repeat) markers. The results revealed that 16 pairs of primers used amplified a total of 143 alleles. The number of alleles per locus ranged from 6 to 13, with a mean value of 8.94 alleles per locus. Observed and expected heterozygosities showed mean values of 0.446 and 0.831 respectively. UPGMA cluster analysis grouped seven eastern honey bees in three groups. The results obtained show a high genetic diversity in the honey bee populations studied in Mount Huang, and high differentiation among all the populations, suggesting that scarce exchange of honey bee species happened in Mount Huang. Our study demonstrated that the Mount Huang honey bee populations still have a natural genome worth being protected for conservation.

  2. Evidence that hippocampal-parahippocampal dysfunction is related to genetic risk for schizophrenia.

    Science.gov (United States)

    Di Giorgio, A; Gelao, B; Caforio, G; Romano, R; Andriola, I; D'Ambrosio, E; Papazacharias, A; Elifani, F; Bianco, L Lo; Taurisano, P; Fazio, L; Popolizio, T; Blasi, G; Bertolino, A

    2013-08-01

    Abnormalities in hippocampal-parahippocampal (H-PH) function are prominent features of schizophrenia and have been associated with deficits in episodic memory. However, it remains unclear whether these abnormalities represent a phenotype related to genetic risk for schizophrenia or whether they are related to disease state. We investigated H-PH-mediated behavior and physiology, using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), during episodic memory in a sample of patients with schizophrenia, clinically unaffected siblings and healthy subjects. Patients with schizophrenia and unaffected siblings displayed abnormalities in episodic memory performance. During an fMRI memory encoding task, both patients and siblings demonstrated a similar pattern of reduced H-PH engagement compared with healthy subjects. Our findings suggest that the pathophysiological mechanism underlying the inability of patients with schizophrenia to properly engage the H-PH during episodic memory is related to genetic risk for the disorder. Therefore, H-PH dysfunction can be assumed as a schizophrenia susceptibility-related phenotype.

  3. Genetic Evidence for Contrasting Wetland and Savannah Habitat Specializations in Different Populations of Lions (Panthera leo).

    Science.gov (United States)

    Moore, Andy E; Cotterill, Fenton P D Woody; Winterbach, Christiaan W; Winterbach, Hanlie E K; Antunes, Agostinho; O'Brien, Stephen J

    2016-03-01

    South-central Africa is characterized by an archipelago of wetlands, which has evolved in time and space since at least the Miocene, providing refugia for animal species during Pleistocene arid episodes. Their importance for biodiversity in the region is reflected in the evolution of a variety of specialist mammal and bird species, adapted to exploit these wetland habitats. Populations of lions (Panthera leo) across south-central and east Africa have contrasting signatures of mitochondrial DNA haplotypes and biparental nuclear DNA in wetland and savannah habitats, respectively, pointing to the evolution of distinct habitat preferences. This explains the absence of genetic admixture of populations from the Kalahari savannah of southwest Botswana and the Okavango wetland of northern Botswana, despite separation by only 500 km. We postulate that ancestral lions were wetland specialists and that the savannah lions evolved from populations that were isolated during arid Pleistocene episodes. Expansion of grasslands and the resultant increase in herbivore populations during mesic Pleistocene climatic episodes provided the stimulus for the rapid population expansion and diversification of the highly successful savannah lion specialists. Our model has important implications for lion conservation. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Fragile X-associated primary ovarian insufficiency: evidence for additional genetic contributions to severity.

    Science.gov (United States)

    Hunter, Jessica Ezzell; Epstein, Michael P; Tinker, Stuart W; Charen, Krista H; Sherman, Stephanie L

    2008-09-01

    The fragile X mental retardation gene (FMR1) contains a CGG repeat sequence in its 5' untranslated region that can become unstable and expand in length from generation to generation. Alleles with expanded repeats in the range of approximately 55-199, termed premutation alleles, are associated with an increased risk for fragile-X-associated primary ovarian insufficiency (FXPOI). However, not all women who carry the premutation develop FXPOI. To determine if additional genes could explain variability in onset and severity, we used a random-effects Cox proportional hazards model to analyze age at menopause on 680 women from 225 families who have a history of fragile X syndrome and 321 women from 219 families from the general population. We tested for the presence of a residual additive genetic effect after adjustment for FMR1 repeat length, race, smoking, body mass index, and method of ascertainment. Results showed significant familial aggregation of age at menopause with an estimated additive genetic variance of 0.55-0.96 depending on the parameterization of FMR1 repeat size and definition of age at menopause (P-values ranging between 0.0002 and 0.0027). This is the first study to analyze familial aggregation of FXPOI. This result is important for proper counseling of women who carry FMR1 premutation alleles and for guidance of future studies to identify additional genes that influence ovarian insufficiency. (c) 2008 Wiley-Liss, Inc.

  5. Characterization of the Genetic Program Linked to the Development of Atrial Fibrillation in CREM-IbΔC-X Mice.

    Science.gov (United States)

    Seidl, Matthias D; Stein, Juliane; Hamer, Sabine; Pluteanu, Florentina; Scholz, Beatrix; Wardelmann, Eva; Huge, Andreas; Witten, Anika; Stoll, Monika; Hammer, Elke; Völker, Uwe; Müller, Frank U

    2017-08-01

    Reduced expression of genes regulated by the transcription factors CREB/CREM (cAMP response element-binding protein/modulator) is linked to atrial fibrillation (AF) susceptibility in patients. Cardiomyocyte-directed expression of the inhibitory CREM isoform CREM-IbΔC-X in transgenic mice (TG) leads to spontaneous-onset AF preceded by atrial dilatation and conduction abnormalities. Here, we characterized the altered gene program linked to atrial remodeling and development of AF in CREM-TG mice. Atria of young (TGy, before AF onset) and old (TGo, after AF onset) TG mice were investigated by mRNA microarray profiling in comparison with age-matched wild-type controls (WTy/WTo). Proteomic alterations were profiled in young mice (8 TGy versus 8 WTy). Annotation of differentially expressed genes revealed distinct differences in biological functions and pathways before and after onset of AF. Alterations in metabolic pathways, some linked to altered peroxisome proliferator-activated receptor signaling, muscle contraction, and ion transport were already present in TGy. Electron microscopy revealed significant loss of sarcomeres and mitochondria and increased collagen and glycogen deposition in TG mice. Alterations in electrophysiological pathways became prominent in TGo, concomitant with altered gene expression of K + -channel subunits and ion channel modulators, relevant in human AF. The most prominent alterations of the gene program linked to CREM-induced atrial remodeling were identified in the expression of genes related to structure, metabolism, contractility, and electric activity regulation, suggesting that CREM transgenic mice are a valuable experimental model for human AF pathophysiology. © 2017 American Heart Association, Inc.

  6. Using the realist perspective to link theory from qualitative evidence synthesis to quantitative studies: Broadening the matrix approach.

    Science.gov (United States)

    van Grootel, Leonie; van Wesel, Floryt; O'Mara-Eves, Alison; Thomas, James; Hox, Joop; Boeije, Hennie

    2017-09-01

    This study describes an approach for the use of a specific type of qualitative evidence synthesis in the matrix approach, a mixed studies reviewing method. The matrix approach compares quantitative and qualitative data on the review level by juxtaposing concrete recommendations from the qualitative evidence synthesis against interventions in primary quantitative studies. However, types of qualitative evidence syntheses that are associated with theory building generate theoretical models instead of recommendations. Therefore, the output from these types of qualitative evidence syntheses cannot directly be used for the matrix approach but requires transformation. This approach allows for the transformation of these types of output. The approach enables the inference of moderation effects instead of direct effects from the theoretical model developed in a qualitative evidence synthesis. Recommendations for practice are formulated on the basis of interactional relations inferred from the qualitative evidence synthesis. In doing so, we apply the realist perspective to model variables from the qualitative evidence synthesis according to the context-mechanism-outcome configuration. A worked example shows that it is possible to identify recommendations from a theory-building qualitative evidence synthesis using the realist perspective. We created subsets of the interventions from primary quantitative studies based on whether they matched the recommendations or not and compared the weighted mean effect sizes of the subsets. The comparison shows a slight difference in effect sizes between the groups of studies. The study concludes that the approach enhances the applicability of the matrix approach. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Complete genome sequences of two avian infectious bronchitis viruses isolated in Egypt: Evidence for genetic drift and genetic recombination in the circulating viruses.

    Science.gov (United States)

    Abozeid, Hassanein H; Paldurai, Anandan; Khattar, Sunil K; Afifi, Manal A; El-Kady, Magdy F; El-Deeb, Ayman H; Samal, Siba K

    2017-09-01

    Avian infectious bronchitis virus (IBV) is highly prevalent in chicken populations and is responsible for severe economic losses to poultry industry worldwide. In this study, we report the complete genome sequences of two IBV field strains, CU/1/2014 and CU/4/2014, isolated from vaccinated chickens in Egypt in 2014. The genome lengths of the strains CU/1/2014 and CU/4/2014 were 27,615 and 27,637 nucleotides, respectively. Both strains have a common genome organization in the order of 5'-UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-UTR-poly(A) tail-3'. Interestingly, strain CU/1/2014 showed a novel 15-nt deletion in the 4b-4c gene junction region. Phylogenetic analysis of the full S1 genes showed that the strains CU/1/2014 and CU/4/2014 belonged to IBV genotypes GI-1 lineage and GI-23 lineage, respectively. The genome of strain CU/1/2014 is closely related to vaccine strain H120 but showed genome-wide point mutations that lead to 27, 14, 11, 1, 1, 2, 2, and 2 amino acid differences between the two strains in 1a, 1b, S, 3a, M, 4b, 4c, and N proteins, respectively, suggesting that strain CU/1/2014 is probably a revertant of the vaccine strain H120 and evolved by accumulation of point mutations. Recombination analysis of strain CU/4/2014 showed evidence for recombination from at least three different IBV strains, namely, the Italian strain 90254/2005 (QX-like strain), 4/91, and H120. These results indicate the continuing evolution of IBV field strains by genetic drift and by genetic recombination leading to outbreaks in the vaccinated chicken populations in Egypt. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Phylogeographic Evidence for 2 Genetically Distinct Zoonotic Plasmodium knowlesi Parasites, Malaysia.

    Science.gov (United States)

    Yusof, Ruhani; Ahmed, Md Atique; Jelip, Jenarun; Ngian, Hie Ung; Mustakim, Sahlawati; Hussin, Hani Mat; Fong, Mun Yik; Mahmud, Rohela; Sitam, Frankie Anak Thomas; Japning, J Rovie-Ryan; Snounou, Georges; Escalante, Ananias A; Lau, Yee Ling

    2016-08-01

    Infections of humans with the zoonotic simian malaria parasite Plasmodium knowlesi occur throughout Southeast Asia, although most cases have occurred in Malaysia, where P. knowlesi is now the dominant malaria species. This apparently skewed distribution prompted an investigation of the phylogeography of this parasite in 2 geographically separated regions of Malaysia, Peninsular Malaysia and Malaysian Borneo. We investigated samples collected from humans and macaques in these regions. Haplotype network analyses of sequences from 2 P. knowlesi genes, type A small subunit ribosomal 18S RNA and cytochrome c oxidase subunit I, showed 2 genetically distinct divergent clusters, 1 from each of the 2 regions of Malaysia. We propose that these parasites represent 2 distinct P. knowlesi types that independently became zoonotic. These types would have evolved after the sea-level rise at the end of the last ice age, which separated Malaysian Borneo from Peninsular Malaysia.

  9. Evidence of new risk genetic factor to systemic lupus erythematosus: the UBASH3A gene.

    Directory of Open Access Journals (Sweden)

    Lina-Marcela Diaz-Gallo

    Full Text Available The ubiquitin associated and Src-homology 3 (SH3 domain containing A (UBASH3a is a suppressor of T-cell receptor signaling, underscoring antigen presentation to T-cells as a critical shared mechanism of diseases pathogenesis. The aim of the present study was to determine whether the UBASH3a gene influence the susceptibility to systemic lupus erythematosus (SLE in Caucasian populations. We evaluated five UBASH3a polymorphisms (rs2277798, rs2277800, rs9976767, rs13048049 and rs17114930, using TaqMan® allelic discrimination assays, in a discovery cohort that included 906 SLE patients and 1165 healthy controls from Spain. The SNPs that exhibit statistical significance difference were evaluated in a German replication cohort of 360 SLE patients and 379 healthy controls. The case-control analysis in the Spanish population showed a significant association between the rs9976767 and SLE (Pc = 9.9E-03 OR = 1.21 95%CI = 1.07-1.37 and a trend of association for the rs2277798 analysis (P = 0.09 OR = 0.9 95%CI = 0.79-1.02. The replication in a German cohort and the meta-analysis confirmed that the rs9976767 (Pc = 0.02; Pc = 2.4E-04, for German cohort and meta-analysis, respectively and rs2277798 (Pc = 0.013; Pc = 4.7E-03, for German cohort and meta-analysis, respectively UBASH3a variants are susceptibility factors for SLE. Finally, a conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs9976767 polymorphism. Our results suggest that UBASH3a gene plays a role in the susceptibility to SLE. Moreover, our study indicates that UBASH3a can be considered as a common genetic factor in autoimmune diseases.

  10. Genetic Relationships among Hylocereus and Selenicereus Vine Cacti (Cactaceae): Evidence from Hybridization and Cytological Studies

    Science.gov (United States)

    TEL-ZUR, NOEMI; ABBO, SHAHAL; BAR-ZVI, DUDY; MIZRAHI, YOSEF

    2004-01-01

    • Background and Aims Hylocereus and Selenicereus are native to tropical and sub-tropical America. Based on its taxonomic status and crossability relations it was postulated that H. megalanthus (syn. S. megalanthus) is an allotetraploid (2n = 4x = 44) derived from natural hybridization between two closely related diploid taxa. The present work aimed at elucidating the genetic relationships between species of the two genera. • Methods Crosses were performed and the putative hybrids were analysed by chromosome counts and morphological traits. The ploidy level of hybrids was confirmed by fluorescent in situ hybridization (FISH) of rDNA sites. Genomic in situ hybridization (GISH) was used in an attempt to identify the putative diploid genome donors of H. megalanthus and an artificial interploid hybrid. • Key Results Reciprocal crosses among four diploid Hylocereus species (H. costaricensis, H. monacanthus (syn. H. polyrhizus), H. undatus and Hylocereus sp.) yielded viable diploid hybrids, with regular chromosome pairing. Reciprocal crosses between these Hylocereus spp. and H. megalanthus yielded viable triploid, pentaploid, hexaploid and aneuploid hybrids. Morphological and phenological traits confirm the hybrid origin. In situ detection of rDNA sites was in accord with the ploidy status of the species and hybrid studied. GISH results indicated that overall sequence composition of H. megalanthus is similar to that of H. ocamponis and S. grandiflorus. High sequence similarity was also found between the parental genomes of H. monacanthus and H. megalanthus in one triploid hybrid. • Conclusions The ease of obtaining partially fertile F1 hybrids and the relative sequence similarity (in GISH study) suggest close genetic relationships among the taxa analysed. PMID:15329334

  11. Genetic and Functional Evidence Supports LPAR1 as a Susceptibility Gene for Hypertension.

    Science.gov (United States)

    Xu, Ke; Ma, Lu; Li, Yang; Wang, Fang; Zheng, Gu-Yan; Sun, Zhijun; Jiang, Feng; Chen, Yundai; Liu, Huirong; Dang, Aimin; Chen, Xi; Chun, Jerold; Tian, Xiao-Li

    2015-09-01

    Essential hypertension is a complex disease affected by genetic and environmental factors and serves as a major risk factor for cardiovascular diseases. Serum lysophosphatidic acid correlates with an elevated blood pressure in rats, and lysophosphatidic acid interacts with 6 subtypes of receptors. In this study, we assessed the genetic association of lysophosphatidic acid receptors with essential hypertension by genotyping 28 single-nucleotide polymorphisms from genes encoding for lysophosphatidic acid receptors, LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, and LPAR6 and their flanking sequences, in 3 Han Chinese cohorts consisting of 2630 patients and 3171 controls in total. We identified a single-nucleotide polymorphism, rs531003 in the 3'-flanking genomic region of LPAR1, associated with hypertension (the Bonferroni corrected P=1.09×10(-5), odds ratio [95% confidence interval]=1.23 [1.13-1.33]). The risk allele C of rs531003 is associated with the increased expression of LPAR1 and the susceptibility of hypertension, particularly in those with a shortage of sleep (P=4.73×10(-5), odds ratio [95% confidence interval]=1.75 [1.34-2.28]). We further demonstrated that blood pressure elevation caused by sleep deprivation and phenylephrine-induced vasoconstriction was both diminished in LPAR1-deficient mice. Together, we show that LPAR1 is a novel susceptibility gene for human essential hypertension and that stress, such as shortage of sleep, increases the susceptibility of patients with risk allele to essential hypertension. © 2015 American Heart Association, Inc.

  12. Preschoolers' genetic, physiological, and behavioral sensitivity factors moderate links between parenting stress and child internalizing, externalizing, and sleep problems.

    Science.gov (United States)

    Davis, Molly; Thomassin, Kristel; Bilms, Joanie; Suveg, Cynthia; Shaffer, Anne; Beach, Steven R H

    2017-05-01

    This study examined three potential moderators of the relations between maternal parenting stress and preschoolers' adjustment problems: a genetic polymorphism-the short allele of the serotonin transporter (5-HTTLPR, ss/sl allele) gene, a physiological indicator-children's baseline respiratory sinus arrhythmia (RSA), and a behavioral indicator-mothers' reports of children's negative emotionality. A total of 108 mothers (M age  = 30.68 years, SD age  = 6.06) reported on their parenting stress as well as their preschoolers' (M age  = 3.50 years, SD age  = 0.51, 61% boys) negative emotionality and internalizing, externalizing, and sleep problems. Results indicated that the genetic sensitivity variable functioned according to a differential susceptibility model; however, the results involving physiological and behavioral sensitivity factors were most consistent with a diathesis-stress framework. Implications for prevention and intervention efforts to counter the effects of parenting stress are discussed. © 2017 Wiley Periodicals, Inc.

  13. Personal Values as Mitigating Factors in the Link between Income and Life Satisfaction: Evidence from the European Social Survey

    Science.gov (United States)

    Georgellis, Yannis; Tsitsianis, Nicholas; Yin, Ya Ping

    2009-01-01

    Using data from the first two rounds of the European Social Survey, we examine the link between income, reference income and life satisfaction across Western Europe. We find that whilst there is a strong positive relationship between income and life satisfaction, reference or comparison income exerts a strong negative influence. Interestingly, our…

  14. Cytoplasmic-genetic male sterility gene provides direct evidence for some hybrid rice recently evolving into weedy rice

    Science.gov (United States)

    Zhang, Jingxu; Lu, Zuomei; Dai, Weimin; Song, Xiaoling; Peng, Yufa; Valverde, Bernal E.; Qiang, Sheng

    2015-01-01

    Weedy rice infests paddy fields worldwide at an alarmingly increasing rate. There is substantial evidence indicating that many weedy rice forms originated from or are closely related to cultivated rice. There is suspicion that the outbreak of weedy rice in China may be related to widely grown hybrid rice due to its heterosis and the diversity of its progeny, but this notion remains unsupported by direct evidence. We screened weedy rice accessions by both genetic and molecular marker tests for the cytoplasmic male sterility (CMS) genes (Wild abortive, WA, and Boro type, BT) most widely used in the production of indica and japonica three-line hybrid rice as a diagnostic trait of direct parenthood. Sixteen weedy rice accessions of the 358 tested (4.5%) contained the CMS-WA gene; none contained the CMS-BT gene. These 16 accessions represent weedy rices recently evolved from maternal hybrid rice derivatives, given the primarily maternal inheritance of this trait. Our results provide key direct evidence that hybrid rice can be involved in the evolution of some weedy rice accessions, but is not a primary factor in the recent outbreak of weedy rice in China. PMID:26012494

  15. Cytoplasmic-genetic male sterility gene provides direct evidence for some hybrid rice recently evolving into weedy rice.

    Science.gov (United States)

    Zhang, Jingxu; Lu, Zuomei; Dai, Weimin; Song, Xiaoling; Peng, Yufa; Valverde, Bernal E; Qiang, Sheng

    2015-05-27

    Weedy rice infests paddy fields worldwide at an alarmingly increasing rate. There is substantial evidence indicating that many weedy rice forms originated from or are closely related to cultivated rice. There is suspicion that the outbreak of weedy rice in China may be related to widely grown hybrid rice due to its heterosis and the diversity of its progeny, but this notion remains unsupported by direct evidence. We screened weedy rice accessions by both genetic and molecular marker tests for the cytoplasmic male sterility (CMS) genes (Wild abortive, WA, and Boro type, BT) most widely used in the production of indica and japonica three-line hybrid rice as a diagnostic trait of direct parenthood. Sixteen weedy rice accessions of the 358 tested (4.5%) contained the CMS-WA gene; none contained the CMS-BT gene. These 16 accessions represent weedy rices recently evolved from maternal hybrid rice derivatives, given the primarily maternal inheritance of this trait. Our results provide key direct evidence that hybrid rice can be involved in the evolution of some weedy rice accessions, but is not a primary factor in the recent outbreak of weedy rice in China.

  16. Genetic evidence for gonochoristic reproduction in gynogenetic silver crucian carp (Carassius auratus gibelio bloch) as revealed by RAPD assays.

    Science.gov (United States)

    Zhou, L; Wang, Y; Gui, J F

    2000-11-01

    Sex evolution has been a debating focus in evolutionary genetics. In lower vertebrates of reptiles, amphibians, and fish, a species or a bioform reproduces either sexually or asexually but never both. A few species were found to consist of all females in fish. These all-female species can propagate by asexual reproduction modes, such as gynogenesis and hybridogenesis. However, the coexistence of sexuality and asexuality in a single species was recently noted only in a cyprinid fish silver crucian carp, Carassius auratus gibelio. This fish had been demonstrated to be capable of gynogenesis stimulated by sperm from other related species. Surprisingly, natural populations of this fish consist of a minor but significant portion (approx. 20%) of males. As different clones with specific phenotypic and genetic characteristics have been found, and RAPD markers specific to each clone have recently been identified, this fish offers many advantages for analyzing whether or not genetic recombination occurs between different clones. In this study, artificial propagation was performed in clone F and clone D. Ovulated eggs from clone F were divided into two parts and respectively inseminated with sperm from a clone D male and from a red common carp (Cyprinus carpio) male. The control clone D individuals were selected from gynogenetic offspring of clone D activated by sperm of red common carp. The phenotype and sex ratio in the experimental groups were also observed. Using RAPD molecular markers, which allow for reliable discrimination and genetic analysis of different clones, we have revealed direct molecular evidence for gonochoristic reproduction in the gynogenetic silver crucian carp and confirmed a previous hypothesis that the silver crucian carp might reproduce both gynogenetically and gonochoristically. Therefore, we conclude that the silver crucian carp possesses two reproductive modes, i.e., gynogenetic and gonochoristic reproduction. The response mechanism of two

  17. The power of the age standardized incidence rate to discover the gene link between cancer diseases: development of a new epidemiological method to save money, time, and effort for genetic scientists.

    Science.gov (United States)

    Alghamdi, Ibrahim G; Hussain, Issam I; Alghamdi, Mohamed S; El-Sheemy, Mohammed A

    2015-01-01

    This study provides an incipient epidemiological rule using the concept of direct method of standardization to determine the genetic link between cancer diseases. The overall 8 or 10 years age standardized incidence rate (ASIR) for both cancer diseases, for example (A) and (B) should be calculated for all regions of the country. A line chart should be used to display the overall ASIR trend of both diseases (A and B). Pearson's correlation can be used to determine the strength of the association between the overall ASIRs of both diseases. The overlap or opposite direction of the overall ASIR trend of both diseases (A and B) should be determined and studied for possible associations between cancer diseases. If the trend of the overall 8 or 10 years ASIR of a disease (A) follows that of disease (B) in all regions of the country, then the genes of patients with both diseases (A and B) will be highly homogeneous, and they should be studied in the region with the highest and lowest overall ASIR for both diseases (A and B). In addition, if there is an opposite direction or overlapping trend for both diseases (A and B) in certain regions of the country or among specific groups of people with the same demographic characteristics, then the genes of patients will be investigated for both diseases to identify the potential gene link between cancer diseases. This study revealed that the overall ASIR trends of female breast cancer, prostate cancer, and ovarian cancer are very similar in all regions of Saudi Arabia and England. Our epidemiological evidence helps to save money, time, and effort for testing the potential gene link between cancer diseases.

  18. The power of the age standardized incidence rate to discover the gene link between cancer diseases: development of a new epidemiological method to save money, time, and effort for genetic scientists

    Science.gov (United States)

    Alghamdi, Ibrahim G; Hussain, Issam I; Alghamdi, Mohamed S; El-Sheemy, Mohammed A

    2015-01-01

    Background This study provides an incipient epidemiological rule using the concept of direct method of standardization to determine the genetic link between cancer diseases. Methods The overall 8 or 10 years age standardized incidence rate (ASIR) for both cancer diseases, for example (A) and (B) should be calculated for all regions of the country. A line chart should be used to display the overall ASIR trend of both diseases (A and B). Pearson’s correlation can be used to determine the strength of the association between the overall ASIRs of both diseases. The overlap or opposite direction of the overall ASIR trend of both diseases (A and B) should be determined and studied for possible associations between cancer diseases. Results If the trend of the overall 8 or 10 years ASIR of a disease (A) follows that of disease (B) in all regions of the country, then the genes of patients with both diseases (A and B) will be highly homogeneous, and they should be studied in the region with the highest and lowest overall ASIR for both diseases (A and B). In addition, if there is an opposite direction or overlapping trend for both diseases (A and B) in certain regions of the country or among specific groups of people with the same demographic characteristics, then the genes of patients will be investigated for both diseases to identify the potential gene link between cancer diseases. Conclusion This study revealed that the overall ASIR trends of female breast cancer, prostate cancer, and ovarian cancer are very similar in all regions of Saudi Arabia and England. Our epidemiological evidence helps to save money, time, and effort for testing the potential gene link between cancer diseases. PMID:25878508

  19. APOE moderates the association between lifestyle activities and cognitive performance: evidence of genetic plasticity in aging.

    Science.gov (United States)

    Runge, Shannon K; Small, Brent J; McFall, G Peggy; Dixon, Roger A

    2014-05-01

    The current study examined independent and interactive effects between Apolipoprotein E (APOE) genotype and two types of cognitively-stimulating lifestyle activities (CSLA)-integrated information processing (CSLA-II) and novel information processing (CSLA-NI)-on concurrent and longitudinal changes in cognition. Three-wave data across 6 years of follow-up from the Victoria Longitudinal Study (n=278; ages 55-94) and linear mixed model analyses were used to characterize the effects of APOE genotype and participation in CSLA-II and CSLA-NI in four cognitive domains. Significant CSLA effects on cognition were observed. More frequent participation in challenging activities (i.e., CSLA-NI) was associated with higher baseline scores on word recall, fact recall, vocabulary and verbal fluency. Conversely, higher participation in less cognitively-challenging activities (i.e., CSLA-II) was associated with lower scores on fact recall and verbal fluency. No longitudinal CSLA-cognition effects were found. Two significant genetic effects were observed. First, APOE moderated CSLA-II and CSLA-NI associations with baseline verbal fluency and fact recall scores. Second, APOE non-ɛ4 carriers' baseline performance were more likely to be moderated by CSLA participation, compared to APOE-ɛ4 carriers. Our findings suggest APOE may be a "plasticity" gene that makes individuals more or less amenable to the influence of protective factors such as CSLA.

  20. POPULATION GENETICS. Genomic evidence for the Pleistocene and recent population history of Native Americans.

    Science.gov (United States)

    Raghavan, Maanasa; Steinrücken, Matthias; Harris, Kelley; Schiffels, Stephan; Rasmussen, Simon; DeGiorgio, Michael; Albrechtsen, Anders; Valdiosera, Cristina; Ávila-Arcos, María C; Malaspinas, Anna-Sapfo; Eriksson, Anders; Moltke, Ida; Metspalu, Mait; Homburger, Julian R; Wall, Jeff; Cornejo, Omar E; Moreno-Mayar, J Víctor; Korneliussen, Thorfinn S; Pierre, Tracey; Rasmussen, Morten; Campos, Paula F; de Barros Damgaard, Peter; Allentoft, Morten E; Lindo, John; Metspalu, Ene; Rodríguez-Varela, Ricardo; Mansilla, Josefina; Henrickson, Celeste; Seguin-Orlando, Andaine; Malmström, Helena; Stafford, Thomas; Shringarpure, Suyash S; Moreno-Estrada, Andrés; Karmin, Monika; Tambets, Kristiina; Bergström, Anders; Xue, Yali; Warmuth, Vera; Friend, Andrew D; Singarayer, Joy; Valdes, Paul; Balloux, Francois; Leboreiro, Ilán; Vera, Jose Luis; Rangel-Villalobos, Hector; Pettener, Davide; Luiselli, Donata; Davis, Loren G; Heyer, Evelyne; Zollikofer, Christoph P E; Ponce de León, Marcia S; Smith, Colin I; Grimes, Vaughan; Pike, Kelly-Anne; Deal, Michael; Fuller, Benjamin T; Arriaza, Bernardo; Standen, Vivien; Luz, Maria F; Ricaut, Francois; Guidon, Niede; Osipova, Ludmila; Voevoda, Mikhail I; Posukh, Olga L; Balanovsky, Oleg; Lavryashina, Maria; Bogunov, Yuri; Khusnutdinova, Elza; Gubina, Marina; Balanovska, Elena; Fedorova, Sardana; Litvinov, Sergey; Malyarchuk, Boris; Derenko, Miroslava; Mosher, M J; Archer, David; Cybulski, Jerome; Petzelt, Barbara; Mitchell, Joycelynn; Worl, Rosita; Norman, Paul J; Parham, Peter; Kemp, Brian M; Kivisild, Toomas; Tyler-Smith, Chris; Sandhu, Manjinder S; Crawford, Michael; Villems, Richard; Smith, David Glenn; Waters, Michael R; Goebel, Ted; Johnson, John R; Malhi, Ripan S; Jakobsson, Mattias; Meltzer, David J; Manica, Andrea; Durbin, Richard; Bustamante, Carlos D; Song, Yun S; Nielsen, Rasmus; Willerslev, Eske

    2015-08-21

    How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericúes and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model. Copyright © 2015, American Association for the Advancement of Science.

  1. Genetic evidence from mitochondrial DNA corroborates the origin of Tibetan chickens.

    Directory of Open Access Journals (Sweden)

    Long Zhang

    Full Text Available Chicken is the most common poultry species and is important to human societies. Tibetan chicken (Gallus gallus domesticus is a breed endemic to China that is distributed mainly on the Qinghai-Tibet Plateau. However, its origin has not been well characterized. In the present study, we sequenced partial mitochondrial DNA (mtDNA control region of 239 and 283 samples from Tibetan and Sichuan indigenous chickens, respectively. Incorporating 1091 published sequences, we constructed the matrilineal genealogy of Tibetan chickens to further document their domestication history. We found that the genetic structure of the mtDNA haplotypes of Tibetan chickens are dominated by seven major haplogroups (A-G. In addition, phylogenetic and network analyses showed that Tibetan chickens are not distinguishable from the indigenous chickens in surrounding areas. Furthermore, some clades of Tibetan chickens may have originated from game fowls. In summary, our results collectively indicated that Tibetan chickens may have diverged from indigenous chickens in the adjacent regions and hybridized with various chickens.

  2. Pendred syndrome: evidence for genetic homogeneity and further refinement of linkage.

    Science.gov (United States)

    Gausden, E; Coyle, B; Armour, J A; Coffey, R; Grossman, A; Fraser, G R; Winter, R M; Pembrey, M E; Kendall-Taylor, P; Stephens, D; Luxon, L M; Phelps, P D; Reardon, W; Trembath, R

    1997-02-01

    Pendred syndrome is the association between congenital sensorineural deafness and goitre. The disorder is characterised by the incomplete discharge of radioiodide from a primed thyroid following perchlorate challenge. However, the molecular basis of the association between hearing loss and a defect in organification of iodide remains unclear. Pendred syndrome is inherited as an autosomal recessive trait and has recently been mapped to 7q31 coincident with the non-syndromic deafness locus DFNB4. To define the critical linkage interval for Pendred syndrome we have studied five kindreds, each with members affected by Pendred syndrome. All families support linkage to the chromosome 7 region, defined by the microsatellite markers D7S501-D7S523. Detailed haplotype analysis refines the Pendred syndrome linkage interval to a region flanked by the marker loci D7S501 and D7S525, separated by a genetic distance estimated to be 2.5 cM. As potential candidate genes have as yet not been mapped to this interval, these data will contribute to a positional cloning approach for the identification of the Pendred syndrome gene.

  3. Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association.

    Science.gov (United States)

    Brems, Hilde; Park, Caroline; Maertens, Ophélia; Pemov, Alexander; Messiaen, Ludwine; Messia, Ludwine; Upadhyaya, Meena; Claes, Kathleen; Beert, Eline; Peeters, Kristel; Mautner, Victor; Sloan, Jennifer L; Yao, Lawrence; Lee, Chyi-Chia Richard; Sciot, Raf; De Smet, Luc; Legius, Eric; Stewart, Douglas R

    2009-09-15

    Neurofibromatosis type 1 (NF1) is a common disorder that arises secondary to mutations in the tumor suppressor gene NF1. Glomus tumors are small, benign but painful tumors that originate from the glomus body, a thermoregulatory shunt concentrated in the fingers and toes. We report 11 individuals with NF1 who harbored 20 glomus tumors of the fingers and 1 in the toe; 5 individuals had multiple glomus tumors. We hypothesized that biallelic inactivation of NF1 underlies the pathogenesis of these tumors. In 12 NF1-associated glomus tumors, we used cell culture and laser capture microdissection to isolate DNA. We also analyzed two sporadic (not NF1-associated) glomus tumors. Genetic analysis showed germ line and somatic NF1 mutations in seven tumors. RAS mitogen-activated protein kinase hyperactivation was observed in cultured NF1(-/-) glomus cells, reflecting a lack of inhibition of the pathway by functional neurofibromin, the protein product of NF1. No abnormalities in NF1 or RAS mitogen-activated protein kinase activation were found in sporadic glomus tumors. By comparative genomic hybridization, we observed amplification of the 3'-end of CRTAC1 and a deletion of the 5'-end of WASF1 in two NF1-associated glomus tumors. For the first time, we show that loss of neurofibromin function is crucial in the pathogenesis of glomus tumors in NF1. Glomus tumors of the fingers or toes should be considered as part of the tumor spectrum of NF1.

  4. Morphological and genetic evidence of contemporary intersectional hybridisation in Mediterranean Helichrysum (Asteraceae, Gnaphalieae).

    Science.gov (United States)

    Galbany-Casals, M; Carnicero-Campmany, P; Blanco-Moreno, J M; Smissen, R D

    2012-09-01

    Hybridisation is considered an important evolutionary phenomenon in Gnaphalieae, but contemporary hybridisation has been little explored within the tribe. Here, hybridisation between Helichrysum orientale and Helichrysum stoechas is studied at two different localities in the islands of Crete and Rhodes (Greece). Using three different types of molecular data (AFLP, nrDNA ITS sequences and cpDNA ndhF sequences) and morphological data, the aim is to provide simultaneous and direct comparisons between molecular and morphological variation among the parental species and the studied hybrid populations. AFLP profiles, ITS sequences and morphological data support the existence of hybrids at the two localities studied, shown as morphological and genetic intermediates between the parental species. Chloroplast DNA sequences show that both parental species can act either as pollen donor or as maternal parent. Fertility of hybrids is demonstrated by the viability of seeds produced by hybrids from both localities, and the detection of a backcross specimen to H. orientale. Although there is general congruence of morphological and molecular data, the analysis of morphology and ITS sequences can fail to detect backcross hybrids. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

  5. Genetic risk for schizophrenia, obstetric complications, and adolescent school outcome: evidence for gene-environment interaction.

    Science.gov (United States)

    Forsyth, Jennifer K; Ellman, Lauren M; Tanskanen, Antti; Mustonen, Ulla; Huttunen, Matti O; Suvisaari, Jaana; Cannon, Tyrone D

    2013-09-01

    Low birth weight (LBW) and hypoxia are among the environmental factors most reliably associated with schizophrenia; however, the nature of this relationship is unclear and both gene-environment interaction and gene-environment covariation models have been proposed as explanations. High-risk (HR) designs that explore whether obstetric complications differentially predict outcomes in offspring at low risk (LR) vs HR for schizophrenia, while accounting for differences in rates of maternal risk factors, may shed light on this question. This study used prospectively obtained data to examine relationships between LBW and hypoxia on school outcome at age 15-16 years in a Finnish sample of 1070 offspring at LR for schizophrenia and 373 offspring at HR for schizophrenia, based on parental psychiatric history. Controlling for offspring sex, maternal smoking, social support, parity, age, and number of prenatal care visits, HR offspring performed worse than LR offspring across academic, nonacademic, and physical education domains. LBW predicted poorer academic and physical education performance in HR offspring, but not in LR offspring, and this association was similar for offspring of fathers vs mothers with schizophrenia. Hypoxia predicted poorer physical education score across risk groups. Rates of LBW and hypoxia were similar for LR and HR offspring and for offspring of fathers vs mothers with schizophrenia. Results support the hypothesis that genetic susceptibility to schizophrenia confers augmented vulnerability of the developing brain to the effects of obstetric complications, possibly via epigenetic mechanisms.

  6. Evidence of genetic predisposition for metabolically healthy obesity and metabolically obese normal weight

    DEFF Research Database (Denmark)

    Huang, Lam Opal; Loos, Ruth JF; Oskari Kilpeläinen, Tuomas

    2018-01-01

    Obesity has evolved into a global pandemic that constitutes a major threat to public health. The majority of obesity-related health care costs are due to cardiometabolic complications, such as insulin resistance, dyslipidemia, and hypertension, which are risk factors for Type 2 diabetes and cardi......Obesity has evolved into a global pandemic that constitutes a major threat to public health. The majority of obesity-related health care costs are due to cardiometabolic complications, such as insulin resistance, dyslipidemia, and hypertension, which are risk factors for Type 2 diabetes...... are located in or near genes that implicate pathways involved in adipogenesis, fat distribution, insulin signaling, and insulin resistance. It has been suggested that a threshold for subcutaneous adipose tissue expandability may be at play in the manifestation of MHO and MONW, where expiry of adipose tissue...... storage capacity could lead to ectopic lipid accumulation in non-adipose tissues such as liver, muscle, heart, and pancreatic beta cells. Understanding the genetic aspects of the mechanisms that underpin MHO and MONW is crucial to define appropriate public health action points and to develop effective...

  7. In search of the Boston Strangler: genetic evidence from the exhumation of Mary Sullivan.

    Science.gov (United States)

    Foran, David R; Starrs, James E

    2004-01-01

    The Boston Strangler was one of the United States' most notorious serial killers, raping and strangling with decorative ligatures thirteen woman in Boston during the early 1960s. Albert DeSalvo, never a suspect in the slayings, confessed in prison (where he was later murdered) to being the Boston Strangler, and the investigation largely ended. Mary Sullivan was the last victim of the Boston Strangler, found sexually assaulted and strangled in her Boston apartment in 1964. Recently, a team of forensic scientists undertook the exhumation and subsequent scientific analysis of Mary Sullivan's remains, in hope of finding consistencies or inconsistencies between DeSalvo's confessed description of the murder and any evidence left behind. Included in these analyses was extensive DNA testing of all UV fluorescent material associated with the body. The large majority of results were negative, however, fluorescent material located on the underwear and entwined in her pubic hair generated two human mitochondrial DNA sequences. Neither of these matched the victim nor members of the forensic team who worked on the evidence. Most importantly, neither DNA sequence could have originated from Albert DeSalvo.

  8. Valuing productivity loss due to absenteeism: firm-level evidence from a Canadian linked employer-employee survey

    OpenAIRE

    Zhang, Wei; Sun, Huiying; Woodcock, Simon; Anis, Aslam H.

    2017-01-01

    In health economic evaluation studies, to value productivity loss due to absenteeism, existing methods use wages as a proxy value for marginal productivity. This study is the first to test the equality between wage and marginal productivity losses due to absenteeism separately for team workers and non-team workers. Our estimates are based on linked employer-employee data from Canada. Results indicate that team workers are more productive and earn higher wages than non-team workers. However, t...

  9. The complex biogeography of the plant pathogen Xylella fastidiosa: genetic evidence of introductions and Subspecific introgression in Central America.

    Science.gov (United States)

    Nunney, Leonard; Ortiz, Beatriz; Russell, Stephanie A; Ruiz Sánchez, Rebeca; Stouthamer, Richard

    2014-01-01

    The bacterium Xylella fastidiosa is a plant pathogen with a history of economically damaging introductions of subspecies to regions where its other subspecies are native. Genetic evidence is presented demonstrating the introduction of two new taxa into Central America and their introgression into the native subspecies, X. fastidiosa subsp. fastidiosa. The data are from 10 genetic outliers detected by multilocus sequence typing (MLST) of isolates from Costa Rica. Six (five from oleander, one from coffee) defined a new sequence type (ST53) that carried alleles at six of the eight loci sequenced (five of the seven MLST loci) diagnostic of the South American subspecies Xylella fastidiosa subsp. pauca which causes two economically damaging plant diseases, citrus variegated chlorosis and coffee leaf scorch. The two remaining loci of ST53 carried alleles from what appears to be a new South American form of X. fastidiosa. Four isolates, classified as X. fastidiosa subsp. fastidiosa, showed a low level of introgression of non-native DNA. One grapevine isolate showed introgression of an allele from X. fastidiosa subsp. pauca while the other three (from citrus and coffee) showed introgression of an allele with similar ancestry to the alleles of unknown origin in ST53. The presence of X. fastidiosa subsp. pauca in Central America is troubling given its disease potential, and establishes another route for the introduction of this economically damaging subspecies into the US or elsewhere, a threat potentially compounded by the presence of a previously unknown form of X. fastidiosa.

  10. The complex biogeography of the plant pathogen Xylella fastidiosa: genetic evidence of introductions and Subspecific introgression in Central America.

    Directory of Open Access Journals (Sweden)

    Leonard Nunney

    Full Text Available The bacterium Xylella fastidiosa is a plant pathogen with a history of economically damaging introductions of subspecies to regions where its other subspecies are native. Genetic evidence is presented demonstrating the introduction of two new taxa into Central America and their introgression into the native subspecies, X. fastidiosa subsp. fastidiosa. The data are from 10 genetic outliers detected by multilocus sequence typing (MLST of isolates from Costa Rica. Six (five from oleander, one from coffee defined a new sequence type (ST53 that carried alleles at six of the eight loci sequenced (five of the seven MLST loci diagnostic of the South American subspecies Xylella fastidiosa subsp. pauca which causes two economically damaging plant diseases, citrus variegated chlorosis and coffee leaf scorch. The two remaining loci of ST53 carried alleles from what appears to be a new South American form of X. fastidiosa. Four isolates, classified as X. fastidiosa subsp. fastidiosa, showed a low level of introgression of non-native DNA. One grapevine isolate showed introgression of an allele from X. fastidiosa subsp. pauca while the other three (from citrus and coffee showed introgression of an allele with similar ancestry to the alleles of unknown origin in ST53. The presence of X. fastidiosa subsp. pauca in Central America is troubling given its disease potential, and establishes another route for the introduction of this economically damaging subspecies into the US or elsewhere, a threat potentially compounded by the presence of a previously unknown form of X. fastidiosa.

  11. Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects.

    Science.gov (United States)

    Bauters, Marijke; Frints, Suzanna G; Van Esch, Hilde; Spruijt, Liesbeth; Baldewijns, Marcella M; de Die-Smulders, Christine E M; Fryns, Jean-Pierre; Marynen, Peter; Froyen, Guy

    2014-08-01

    Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects. © 2014 Wiley Periodicals, Inc.

  12. DNA methylation links genetics, fetal environment, and an unhealthy lifestyle to the development of type 2 diabetes.

    Science.gov (United States)

    Nilsson, Emma; Ling, Charlotte

    2017-01-01

    Type 2 diabetes is a complex trait with both environmental and hereditary factors contributing to the overall pathogenesis. One link between genes, environment, and disease is epigenetics influencing gene transcription and, consequently, organ function. Genome-wide studies have shown altered DNA methylation in tissues important for glucose homeostasis including pancreas, liver, skeletal muscle, and adipose tissue from subjects with type 2 diabetes compared with nondiabetic controls. Factors predisposing for type 2 diabetes including an adverse intrauterine environment, increasing age, overweight, physical inactivity, a family history of the disease, and an unhealthy diet have all shown to affect the DNA methylation pattern in target tissues for insulin resistance in humans. Epigenetics including DNA methylation may therefore improve our understanding of the type 2 diabetes pathogenesis, contribute to development of novel treatments, and be a useful tool to identify individuals at risk for developing the disease.

  13. Genetic variation in the extended major histocompatibility complex and susceptibility to childhood acute lymphoblastic leukemia: a review of the evidence

    Directory of Open Access Journals (Sweden)

    Kevin Y Urayama

    2013-12-01

    Full Text Available The enduring suspicion that infections and immunologic response may play a role in the etiology of childhood leukemia, particularly acute lymphoblastic leukemia (ALL, is now supported, albeit still indirectly, by numerous epidemiological studies. The cumulative evidence includes, for example, descriptive observations of a peculiar peak incidence at age 2-5 years for ALL in economically developed countries, clustering of cases in situations of population mixing associated with unusual patterns of personal contacts, associations with various proxy measures for immune modulatory exposures early in life, and genetic susceptibility conferred by variation in genes involved in the immune system. In this review, our focus is the extended major histocompatibility complex (xMHC, an approximately 7.6 megabase region that is well-known for its high density of expressed genes, extensive polymorphisms exhibiting complex linkage disequilibrium patterns, and its disproportionately large number of immune-related genes, including human leukocyte antigen (HLA. First discovered through the role they play in transplant rejection, the classical HLA class I (HLA-A, -B, and -C and class II (HLA-DR, HLA-DQ, and HLA-DP molecules reside at the epicenter of the immune response pathways and are now the targets of many disease susceptibility studies, including those for childhood leukemia. The genes encoding the HLA molecules are only a minority of the over 250 expressed genes in the xMHC, and a growing number of studies are beginning to evaluate other loci through targeted investigations or utilizing a mapping approach with a comprehensive screen of the entire region. Here, we review the current epidemiologic evidence available to date regarding genetic variation contained within this highly unique region of the genome and its relationship with childhood ALL risk.

  14. Genetic analysis of autoimmune gld mice. I. Identification of a restriction fragment length polymorphism closely linked to the gld mutation within a conserved linkage group

    Science.gov (United States)

    1988-01-01

    A linkage map of distal mouse chromosome 1 was generated using restriction fragment length polymorphism (RFLP) analysis of DNA prepared from 95 [C3H-gld/gld X Mus spretus)F1 X C3H-gld/gld] backcross mice. The gene order was: (centromere) C4bp, Ren-1,2, Ly-5, [At-3/gld], Apoa-2/Ly-17, Spna-1 (telomere). All mice expressing the phenotype of gld homozygotes were homozygous for the At-3 RFLP characteristic of C3H mice and none of the mice heterozygous for At-3 RFLPs had characteristics of gld homozygotes, demonstrating close linkage between these genes. The identification of an RFLP closely linked to the gld gene provides a starting point for the identification of a genetic defect that results in abnormal T cells and autoimmune disease. PMID:2894402

  15. Genetic localisation of MRX27 to Xq24-26 defines another discrete gene for non-specific X-linked mental retardation

    Energy Technology Data Exchange (ETDEWEB)

    Gedeon, A.K.; Connor, J.M.; Mulley, J.C. [Univ. of Adelaide (Australia); Connor, J.M. [Duncan Guthrie Inst. of Medical Genetics, Yorkhill (United Kingdom); Glass, I.A. [Univ. of California, San Franciso, CA (United States)

    1996-07-12

    A large family with non-specific X-linked mental retardation (MRX) was first described in 1991, with a suggestion of linkage to Xq26-27. The maximum lod score was 1.60 ({theta} = 0.10) with the F9 locus. The localization of this MRX gene has now been established by linkage to microsatellite markers. Peak pairwise lod scores of 4.02 and 4.01 ({theta} = 0.00) were attained at the DXS1114 and DXS994 loci respectively. This MRX gene is now designated MRX27 and is localized to Xq24-26 by recombination events detected by DXS424 and DXS102. This regional localization spans 26.2 cM on the genetic background map and defines another distinct MRX interval by linkage to a specific region of the X chromosome. 25 refs., 1 fig., 1 tab.

  16. Phylogeography and postglacial recolonization of Europe by Rhinolophus hipposideros: evidence from multiple genetic markers.

    Science.gov (United States)

    Dool, Serena E; Puechmaille, Sébastien J; Dietz, Christian; Juste, Javier; Ibáñez, Carlos; Hulva, Pavel; Roué, Stéphane G; Petit, Eric J; Jones, Gareth; Russo, Danilo; Toffoli, Roberto; Viglino, Andrea; Martinoli, Adriano; Rossiter, Stephen J; Teeling, Emma C

    2013-08-01

    The demographic history of Rhinolophus hipposideros (lesser horseshoe bat) was reconstructed across its European, North African and Middle-Eastern distribution prior to, during and following the most recent glaciations by generating and analysing a multimarker data set. This data set consisted of an X-linked nuclear intron (Bgn; 543 bp), mitochondrial DNA (cytb-tRNA-control region; 1630 bp) and eight variable microsatellite loci for up to 373 individuals from 86 localities. Using this data set of diverse markers, it was possible to determine the species' demography at three temporal stages. Nuclear intron data revealed early colonization into Europe from the east, which pre-dates the Quaternary glaciations. The mtDNA data supported multiple glacial refugia across the Mediterranean, the largest of which were found in the Ibero-Maghreb region and an eastern location (Anatolia/Middle East)-that were used by R. hipposideros during the most recent glacial cycles. Finally, microsatellites provided the most recent information on these species' movements since the Last Glacial Maximum and suggested that lineages that had diverged into glacial refugia, such as in the Ibero-Maghreb region, have remained isolated. These findings should be used to inform future conservation management strategies for R. hipposideros and show the power of using a multimarker data set for phylogeographic studies. © 2013 John Wiley & Sons Ltd.

  17. Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels.

    Science.gov (United States)

    Mahendran, Yuvaraj; Jonsson, Anna; Have, Christian T; Allin, Kristine H; Witte, Daniel R; Jørgensen, Marit E; Grarup, Niels; Pedersen, Oluf; Kilpeläinen, Tuomas O; Hansen, Torben

    2017-05-01

    Fasting plasma levels of branched-chain amino acids (BCAAs) are associated with insulin resistance, but it remains unclear whether there is a causal relation between the two. We aimed to disentangle the causal relations by performing a Mendelian randomisation study using genetic variants associated with circulating BCAA levels and insulin resistance as instrumental variables. We measured circulating BCAA levels in blood plasma by NMR spectroscopy in 1,321 individuals from the ADDITION-PRO cohort. We complemented our analyses by using previously published genome-wide association study (GWAS) results from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 46,186) and from a GWAS of serum BCAA levels (n = 24,925). We used a genetic risk score (GRS), calculated using ten established fasting serum insulin associated variants, as an instrumental variable for insulin resistance. A GRS of three variants increasing circulating BCAA levels was used as an instrumental variable for circulating BCAA levels. Fasting plasma BCAA levels were associated with higher HOMA-IR in ADDITION-PRO (β 0.137 [95% CI 0.08, 0.19] p = 6 × 10 -7 ). However, the GRS for circulating BCAA levels was not associated with fasting insulin levels or HOMA-IR in ADDITION-PRO (β -0.011 [95% CI -0.053, 0.032] p = 0.6 and β -0.011 [95% CI -0.054, 0.031] p = 0.6, respectively) or in GWAS results for HOMA-IR from MAGIC (β for valine-increasing GRS -0.012 [95% CI -0.069, 0.045] p = 0.7). By contrast, the insulin-resistance-increasing GRS was significantly associated with increased BCAA levels in ADDITION-PRO (β 0.027 [95% CI 0.005, 0.048] p = 0.01) and in GWAS results for serum BCAA levels (β 1.22 [95% CI 0.71, 1.73] p = 4 × 10 -6 , β 0.96 [95% CI 0.45, 1.47] p = 3 × 10 -4 , and β 0.67 [95% CI 0.16, 1.18] p = 0.01 for isoleucine, leucine and valine levels, respectively) and instrumental variable analyses in ADDITION

  18. No evidence of association of MUC-1 genetic polymorphism with embryo implantation failure

    Directory of Open Access Journals (Sweden)

    D.B. Dentillo

    2007-06-01

    Full Text Available Pregnancy loss can be caused by several factors involved in human reproduction. Although up to 50% of cases remain unexplained, it has been postulated that the major cause of failed pregnancy is an error of embryo implantation. Transmembrane mucin-1 (MUC-1 is a glycoprotein expressed on the endometrial cell surface which acts as a barrier to implantation. The gene that codes for this molecule is composed of a polymorphic tandem repeat of 60 nucleotides. Our objective was to determine if MUC-1 genetic polymorphism is associated with implantation failure in patients with a history of recurrent abortion. The study was conducted on 10 women aged 25 to 35 years with no history of successful pregnancy and with a diagnosis of infertility. The control group consisted of 32 patients aged 25 to 35 years who had delivered at least two full-term live children and who had no history of abortions or fetal losses. MUC-1 amplicons were obtained by PCR and observed on agarose and polyacrylamide gel after electrophoresis. Statistical analysis showed no significant difference in the number of MUC-1 variable number of tandem repeats between these groups (P > 0.05. Our results suggest that there is no effect of the polymorphic MUC-1 sequence on the implantation failure. However, the data do not exclude MUC-1 relevance during embryo implantation. The process is related to several associated factors such as the mechanisms of gene expression in the uterus, specific MUC-1 post-translational modifications and appropriate interactions with other molecules during embryo implantation.

  19. Genetic Evidence of Tiger Population Structure and Migration within an Isolated and Fragmented Landscape in Northwest India

    Science.gov (United States)

    Bhavanishankar, Maradani; Jaggi, Kanika; Hussain, Shaik Mohammed; Harika, Katakam; Shivaji, Sisinthy

    2012-01-01

    Background Majority of the tiger habitat in Indian subcontinent lies within high human density landscapes and is highly sensitive to surrounding pressures. These forests are unable to sustain healthy tiger populations within a tiger-hostile matrix, despite considerable conservation efforts. Ranthambore Tiger Reserve (RTR) in Northwest India is one such isolated forest which is rapidly losing its links with other tiger territories in the Central Indian landscape. Non-invasive genetic sampling for individual identification is a potent technique to understand the relationships between threatened tiger populations in degraded habitats. This study is an attempt to establish tiger movement across a fragmented landscape between RTR and its neighboring forests, Kuno-Palpur Wildlife Sanctuary (KPWLS) and Madhav National Park (MNP) based on non-invasively obtained genetic data. Methods Data from twelve microsatellite loci was used to define population structure and also to identify first generation migrants and admixed individuals in the above forests. Results Population structure was consistent with the Central Indian landscape and we could determine significant gene flow between RTR and MNP. We could identify individuals of admixed ancestry in both these forests, as well as first generation migrants from RTR to KPWLS and MNP. Conclusions Our results indicate reproductive mixing between animals of RTR and MNP in the recent past and migration of animals even today, despite fragmentation and poaching risk, from RTR towards MNP. Substantial conservation efforts should be made to maintain connectivity between these two subpopulations and also higher protection status should be conferred on Madhav National Park. PMID:22253791

  20. Genetic evidence of tiger population structure and migration within an isolated and fragmented landscape in Northwest India.

    Directory of Open Access Journals (Sweden)

    Patlolla Anuradha Reddy

    Full Text Available Majority of the tiger habitat in Indian subcontinent lies within high human density landscapes and is highly sensitive to surrounding pressures. These forests are unable to sustain healthy tiger populations within a tiger-hostile matrix, despite considerable conservation efforts. Ranthambore Tiger Reserve (RTR in Northwest India is one such isolated forest which is rapidly losing its links with other tiger territories in the Central Indian landscape. Non-invasive genetic sampling for individual identification is a potent technique to understand the relationships between threatened tiger populations in degraded habitats. This study is an attempt to establish tiger movement across a fragmented landscape between RTR and its neighboring forests, Kuno-Palpur Wildlife Sanctuary (KPWLS and Madhav National Park (MNP based on non-invasively obtained genetic data.Data from twelve microsatellite loci was used to define population structure and also to identify first generation migrants and admixed individuals in the above forests.Population structure was consistent with the Central Indian landscape and we could determine significant gene flow between RTR and MNP. We could identify individuals of admixed ancestry in both these forests, as well as first generation migrants from RTR to KPWLS and MNP.Our results indicate reproductive mixing between animals of RTR and MNP in the recent past and migration of animals even today, despite fragmentation and poaching risk, from RTR towards MNP. Substantial conservation efforts should be made to maintain connectivity between these two subpopulations and also higher protection status should be conferred on Madhav National Park.

  1. Genetics Home Reference: osteopetrosis

    Science.gov (United States)

    ... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. ... infantile neuroaxonal dystrophy Genetic Testing Registry: Osteopetrosis autosomal dominant type 1 Genetic Testing Registry: Osteopetrosis autosomal dominant ...

  2. Evidence for mito-nuclear and sex-linked reproductive barriers between the hybrid Italian sparrow and its parent species.

    Directory of Open Access Journals (Sweden)

    Cassandra N Trier

    2014-01-01

    Full Text Available Studies of reproductive isolation between homoploid hybrid species and their parent species have rarely been carried out. Here we investigate reproductive barriers between a recently recognized hybrid bird species, the Italian sparrow Passer italiae and its parent species, the house sparrow P. domesticus and Spanish sparrow P. hispaniolensis. Reproductive barriers can be difficult to study in hybrid species due to lack of geographical contact between taxa. However, the Italian sparrow lives parapatrically with the house sparrow and both sympatrically and parapatrically with the Spanish sparrow. Through whole-transcriptome sequencing of six individuals of each of the two parent species we identified a set of putatively parent species-diagnostic single nucleotide polymorphism (SNP markers. After filtering for coverage, genotyping success (>97% and multiple SNPs per gene, we retained 86 species-informative, genic, nuclear and mitochondrial SNP markers from 84 genes for analysis of 612 male individuals. We show that a disproportionately large number of sex-linked genes, as well as the mitochondria and nuclear genes with mitochondrial function, exhibit sharp clines at the boundaries between the hybrid and the parent species, suggesting a role for mito-nuclear and sex-linked incompatibilities in forming reproductive barriers. We suggest that genomic conflict via interactions between mitochondria and sex-linked genes with mitochondrial function ("mother's curse" at one boundary and centromeric drive at the other may best explain our findings. Hybrid speciation in the Italian sparrow may therefore be influenced by mechanisms similar to those involved in non-hybrid speciation, but with the formation of two geographically separated species boundaries instead of one. Spanish sparrow alleles at some loci have spread north to form reproductive barriers with house sparrows, while house sparrow alleles at different loci, including some on the same chromosome

  3. Familial clustering of epilepsy and behavioral disorders: Evidence for a shared genetic basis

    Science.gov (United States)

    Hesdorffer, Dale C.; Caplan, Rochelle; Berg, Anne T.

    2011-01-01

    Purpose To examine whether family history of unprovoked seizures is associated with behavioral disorders in epilepsy probands, thereby supporting the hypothesis of shared underlying genetic susceptibility to these disorders. Methods We conducted an analysis of the 308 probands with childhood onset epilepsy from the Connecticut Study of Epilepsy with information on first degree family history of unprovoked seizures and of febrile seizures whose parents completed the Child Behavior Checklist (CBCL) at the 9-year follow-up. Clinical cut-offs for CBCL problem and DSM-Oriented scales were examined. The association between first degree family history of unprovoked seizure and behavioral disorders was assessed separately in uncomplicated and complicated epilepsy and separately for first degree family history of febrile seizures. A subanalysis, accounting for the tendency for behavioral disorders to run in families, adjusted for siblings with the same disorder as the proband. Prevalence ratios were used to describe the associations. Key findings In probands with uncomplicated epilepsy, first degree family history of unprovoked seizure was significantly associated with clinical cut-offs for Total Problems and Internalizing Disorders. Among Internalizing Disorders, clinical cut-offs for Withdrawn/Depressed, and DSM-Oriented scales for Affective Disorder and Anxiety Disorder were significantly associated with family history of unprovoked seizures. Clinical cut-offs for Aggressive Behavior and Delinquent Behavior, and DSM-Oriented scales for Conduct Disorder and Oppositional Defiant Disorder were significantly associated with family history of unprovoked seizure. Adjustment for siblings with the same disorder revealed significant associations for the relationship between first degree family history of unprovoked seizure and Total Problems and Agressive Behavior in probands with uncomplicated epilepsy; marginally significant results were seen for Internalizing Disorder

  4. [Genetic evidence for recombination and mutation in the emergence of human enterovirus 71].

    Science.gov (United States)

    Liu, Ai-Ping; Tan, Hui; Xie, Qun; Chen, Bai-Tang; Liu, Xiao-Feng; Zhang, Yong

    2014-09-01

    We wished to understand the genetic recombination and phylogenetic characteristics of human en- terovirus A71 (EV-A71) and to explore its potential virulence-related sites. Full-length genomes of three EV-A71 strains isolated from patients in Chenzhou City (China) were sequenced and analyzed. Possible re- combination events and crossover sites were analyzed with Recombination Detection Program v4. 1. 6 by comparison with the complete genome sequences of 231 strains of EV-A71. Similarly, plot and bootscanning analyses were undertaken with SimPlot v3. 5. 1. Phylogenetic trees based on the sequences of VP1 regions were constructed with MEGA v5. 2 using the Kimura two-parameter model and neighbor-joining method. Results suggested that recombination events were detected among the three EV-A71 isolates from Chenzhou City. The common main parent sequence was from JF799986 isolated from samples in Guang- zhou City (China) in 2009, and the minor parent sequence was TW/70516/08. Intertypic recombination e- vents were found in the C4b strain (strain SHZH98 isolated in 1998) and C4a strain (Fuyang strain isola- ted in 2008) with the prototype strains of CVA4 and CVA14 in the 3D region. The chi-square test was used to screen-out potential virulence-related sites with nucleotide substitutions of different types of hand, foot, and mouth disease (HFMD) cases using SPSS v19.0. Results suggested that there were no significant nucleotide substitutions between death cases and severe-HFMD cases. Eighteen significant nucleotide substitutions were found between death/severe-HFMD cases and mild-HFMD cases, and all these 18 substitutions were distributed only in P2 and P3 regions. Intertypic recombination among the predominant circulating EV-A71 strains in the Chinese mainland and other EV-A strains probably dates before 1998, and intratypic recombination might have occurred frequently in the HFMD outbreak from 2008 to 2012. Substitutions in the non-capsid region may be correlated with the

  5. Using the realist perspective to link theory from qualitative evidence synthesis to quantitative studies: broadening the matrix approach.

    NARCIS (Netherlands)

    Grootel, L. van; Wesel, F. van; O'Mara-Eves, A.; Thomas, J.; Hox, J.; Boeije, H.

    2017-01-01

    Background: This study describes an approach for the use of a specific type of qualitative evidence synthesis in the matrix approach, a mixed studies reviewing method. The matrix approach compares quantitative and qualitative data on the review level by juxtaposing concrete recommendations from the

  6. Prospective Links between Friendship and Early Physical Aggression: Preliminary Evidence Supporting the Role of Friendship Quality through a Dyadic Intervention

    Science.gov (United States)

    Salvas, Marie-Claude; Vitaro, Frank; Brendgen, Mara; Cantin, Ste´phane

    2016-01-01

    Positive friendships have been related to decreasing levels of children's physical aggression over time. While this evidence calls for interventions aimed at helping children build good-quality friendships, tests of causality through experimental manipulations are still needed. The goal of this study was to examine whether an intervention aimed to…

  7. GLOBAL FINANCIAL CRISIS AND UNIT-LINKED INSURANCE MARKETS EFFICIENCY: EMPIRICAL EVIDENCE FROM CENTRAL AND EASTERN EUROPEAN COUNTRIES

    Directory of Open Access Journals (Sweden)

    Botoş Horia Mircea

    2012-12-01

    Full Text Available This paper empirically investigates the impact of the Global financial crisis on the efficiency of four Central and Eastern European emerging unit-linked insurance markets, applying the automatic variance ratio (AVR test of Kim (2009 and variance ratio tests using ranks and signs by Wright (2000 for entire, pre-crisis and crisis periods. This study contributes to the existing literature on efficient market hypothesis with several distinct features: it provides a systematic review of the weak-form market efficiency literature that examines return predictability of the daily ING unit-linked funds prices; also the article aims at monitoring any improvement in the degree of efficiency in time and also examines the relative efficiency of unit-linked insurance markets in pre-crisis and crisis periods. Unit linked insurance are life insurance policies with investment component. In the literature there are few studies investigating the effects of a financial crisis on the potential of predictability and implicitly on the degree of efficiency of financial markets. The occurrence of a market crash or financial crisis is a possible contributing factor of market inefficiency. Most of the studies are focused on the Asian crisis in 1997: Holden et al. (2005 examined the weak-form efficiency of eight emerging Asian stock markets using VR tests before, during and after the Asian crisis; Kim and Shamsuddin (2008 used three different types of multiple VR tests for nine Asian stock markets; the findings reported by Lim et al. (2008 are consistent with those reported by Cheong et al. (2007, in which the highest inefficiency occurs during the crisis period. Todea and Lazar (2010 investigated the effects of the Global crisis on the relative efficiency of ten CEE stock markets, using Generalized Spectral test of Escanciano and Velasco (2006. Wright (2000 proposes the alternative non-parametric variance ratio tests using ranks and signs of return and demonstrates that

  8. Occupational trichloroethylene exposure and renal carcinoma risk: evidence of genetic susceptibility by reductive metabolism gene variants

    Science.gov (United States)

    Moore, Lee E.; Boffetta, Paolo; Karami, Sara; Brennan, Paul; Stewart, Patricia S; Hung, Rayjean; Zaridze, David; Matveev, Vsevolod; Janout, Vladimir; Kollarova, Helena; Bencko, Vladimir; Navratilova, Marie; Szeszenia-Dabrowska, Neonila; Mates, Dana; Gromiec, Jan; Holcatova, Ivana; Merino, Maria; Chanock, Stephen; Chow, Wong-Ho; Rothman, Nathaniel

    2010-01-01

    Trichloroethylene (TCE) is a suspected renal carcinogen. TCE-associated renal genotoxicity occurs predominantly through glutathione S-transferase (GST) conjugation and bioactivation by renal cysteine beta-lyase (CCBL1). We conducted a case-control study in Central Europe (1,097 cases/1,476 controls), specifically designed to assess risk associated with occupational exposure to TCE through analysis of detailed job histories. All jobs were coded for organic/chlorinated solvent and TCE exposure (ever/never) as well as the frequency and intensity of exposure based on detailed occupational questionnaires, specialized questionnaires, and expert assessments. Increased risk was observed among subjects ever TCE-exposed (OR=1.63, 95% CI: 1.04–2.54). Exposure-response trends were observed among subjects above and below the median exposure [average intensity (OR=1.38, 95% CI:0.81–2.35; OR=2.34, 95% CI:1.05–5.21, p-trend=0.02)]. A significant association was found among TCE-exposed subjects with at least one intact GSTT1 allele (active genotype) (OR=1.88, 95% CI:1.06–3.33) but not among subjects with two deleted alleles (null genotype) (OR=0.93, 95% CI:0.35–2.44, p-interaction=0.18). Similar associations for all exposure metrics including average intensity were observed among GSTT1 active subjects (OR=1.56, 95% CI:0.79–3.10; OR=2.77, 95% CI:1.01–7.58, p-trend=0.02) but not among GSTT1 nulls (OR=0.81, 95% CI:0.24–2.72; OR=1.16, 95% CI:0.27–5.04, p-trend=1.00, p-interaction=0.34). Further evidence of heterogeneity was seen among TCE-exposed subjects with ≥1 minor allele of several CCBL1 tagging SNPs: [rs2293968, rs2280841, rs2259043, rs941960]. These findings provide the strongest evidence to date that TCE exposure is associated with increased renal cancer risk, particularly among individuals carrying polymorphisms in genes that are important in the reductive metabolism of this chemical, and provides biological plausibility of the association in humans. PMID

  9. Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant).

    Science.gov (United States)

    Bichet, Daniel G; Bockenhauer, Detlef

    2016-03-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Evidence of low dimensional chaos in renal blood flow control in genetic and experimental hypertension

    Science.gov (United States)

    Yip, K.-P.; Marsh, D. J.; Holstein-Rathlou, N.-H.

    1995-01-01

    We applied a surrogate data technique to test for nonlinear structure in spontaneous fluctuations of hydrostatic pressure in renal tubules of hypertensive rats. Tubular pressure oscillates at 0.03-0.05 Hz in animals with normal blood pressure, but the fluctuations become irregular with chronic hypertension. Using time series from rats with hypertension we produced surrogate data sets to test whether they represent linearly correlated noise or ‘static’ nonlinear transforms of a linear stochastic process. The correlation dimension and the forecasting error were used as discriminating statistics to compare surrogate with experimental data. The results show that the original experimental time series can be distinguished from both linearly and static nonlinearly correlated noise, indicating that the nonlinear behavior is due to the intrinsic dynamics of the system. Together with other evidence this strongly suggests that a low dimensional chaotic attractor governs renal hemodynamics in hypertension. This appears to be the first demonstration of a transition to chaotic dynamics in an integrated physiological control system occurring in association with a pathological condition.

  11. Bilateral first branchial cleft anomaly with evidence of a genetic aetiology.

    Science.gov (United States)

    Gonzalez-Perez, L M; Prats-Golczer, V E; Montes Carmona, J F; Heurtebise Saavedra, J M

    2014-03-01

    Anomalies of the first branchial cleft (FBC) are uncommon, and recognizing them can be difficult. Although present at birth, many cases do not become evident until later in childhood or adolescence, with an initial clinical presentation in adulthood being encountered only rarely. Typically, FBC anomalies present as a unilateral cyst, sinus, or fistula associated with the external auditory canal, or with swelling or an inflammatory opening in the peri-auricular/parotid area. They are commonly misdiagnosed and are often treated inadequately before being excised completely. A 40-year-old woman presented to the maxillofacial outpatient clinic with an episode of bilateral pre-auricular tumefaction, initially diagnosed as temporomandibular dysfunction syndrome. This was associated with bilateral pre-auricular pain that increased with mandibular movements. In relation to the patient's history, and given the bilateral presence of a pre-auricular pit, a diagnosis of FBC anomaly was made. Further investigation showed a related asymptomatic history in five other cases across four generations of the same family. The authors describe here the case, the diagnostic methodology, and the wide local excision technique used for removal of the branchial sinus. Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  12. Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Lesley Jones

    2010-11-01

    Full Text Available Late Onset Alzheimer's disease (LOAD is the leading cause of dementia. Recent large genome-wide association studies (GWAS identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.

  13. Mitogenomic phylogenetics of fin whales (Balaenoptera physalus spp.: genetic evidence for revision of subspecies.

    Directory of Open Access Journals (Sweden)

    Frederick I Archer

    Full Text Available There are three described subspecies of fin whales (Balaenoptera physalus: B. p. physalus Linnaeus, 1758 in the Northern Hemisphere, B. p. quoyi Fischer, 1829 in the Southern Hemisphere, and a recently described pygmy form, B. p. patachonica Burmeister, 1865. The discrete distribution in the North Pacific and North Atlantic raises the question of whether a single Northern Hemisphere subspecies is valid. We assess phylogenetic patterns using ~16 K base pairs of the complete mitogenome for 154 fin whales from the North Pacific, North Atlantic--including the Mediterranean Sea--and Southern Hemisphere. A Bayesian tree of the resulting 136 haplotypes revealed several well-supported clades representing each ocean basin, with no haplotypes shared among ocean basins. The North Atlantic haplotypes (n = 12 form a sister clade to those from the Southern Hemisphere (n = 42. The estimated time to most recent common ancestor (TMRCA for this Atlantic/Southern Hemisphere clade and 81 of the 97 samples from the North Pacific was approximately 2 Ma. 14 of the remaining North Pacific samples formed a well-supported clade within the Southern Hemisphere. The TMRCA for this node suggests that at least one female from the Southern Hemisphere immigrated to the North Pacific approximately 0.37 Ma. These results provide strong evidence that North Pacific and North Atlantic fin whales should not be considered the same subspecies, and suggest the need for revision of the global taxonomy of the species.

  14. Links between white matter microstructure and cortisol reactivity to stress in early childhood: evidence for moderation by parenting.

    Science.gov (United States)

    Sheikh, Haroon I; Joanisse, Marc F; Mackrell, Sarah M; Kryski, Katie R; Smith, Heather J; Singh, Shiva M; Hayden, Elizabeth P

    2014-01-01

    Activity of the hypothalamic-pituitary-adrenal axis (measured via cortisol reactivity) may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls' cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at age 3. White matter integrity was assessed by calculating fractional anisotropy (FA) of diffusion-weighted magnetic resonance imaging scans. Parenting styles were measured via a standardized parent-child interaction task. Significant associations were found between FA in white matter regions adjacent to the left thalamus, the right anterior cingulate cortex, and the right superior frontal gyrus (all ps parent positive affect showing white matter structure more similar to that of low stress reactive girls. Results show associations between white matter integrity of various limbic regions of the brain and early cortisol reactivity to stress and provide preliminary support for the notion that parenting may moderate associations.

  15. Links between white matter microstructure and cortisol reactivity to stress in early childhood: Evidence for moderation by parenting

    Directory of Open Access Journals (Sweden)

    Haroon I. Sheikh

    2014-01-01

    Full Text Available Activity of the hypothalamic–pituitary–adrenal axis (measured via cortisol reactivity may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls' cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at age 3. White matter integrity was assessed by calculating fractional anisotropy (FA of diffusion-weighted magnetic resonance imaging scans. Parenting styles were measured via a standardized parent–child interaction task. Significant associations were found between FA in white matter regions adjacent to the left thalamus, the right anterior cingulate cortex, and the right superior frontal gyrus (all ps < .001. Further, positive early caregiving moderated the effect of high cortisol reactivity on white matter FA (all ps ≤ .05, with high stress reactive girls who received greater parent positive affect showing white matter structure more similar to that of low stress reactive girls. Results show associations between white matter integrity of various limbic regions of the brain and early cortisol reactivity to stress and provide preliminary support for the notion that parenting may moderate associations.

  16. Common heritable effects underpin concerns over norm maintenance and in-group favoritism: evidence from genetic analyses of right-wing authoritarianism and traditionalism.

    Science.gov (United States)

    Lewis, Gary J; Bates, Timothy C

    2014-08-01

    Research has shown that in-group favoritism is associated with concerns over the maintenance of social norms. Here we present two studies examining whether genetic factors underpin this association. A classical twin design was used to decompose phenotypic variance into genetic and environmental components in two studies. Study 1 used 812 pairs of adult U.S. twins from the nationally representative MIDUS II sample. Study 2 used 707 pairs of middle-age twins from the Minnesota Twin Registry. In-group favoritism was measured with scales tapping preferences for in-group (vs. out-group) individuals; norm concerns were measured with the Multidimensional Personality Questionnaire-Traditionalism (Study 1) and Right-Wing Authoritarianism (RWA; Study 2) scales. In Study 1, heritable effects underlying traditionalism were moderately (c. 35%) overlapping with the genetic variance underpinning in-group favoritism. In Study 2, heritable influences on RWA were entirely shared with the heritable effects on in-group favoritism. Moreover, we observed that Big Five Openness shared common genetic links to both RWA and in-group favoritism. These results suggest that, at the genetic level, in-group favoritism is linked with a system related to concern over normative social practices, which is, in turn, partially associated with trait Openness. © 2013 Wiley Periodicals, Inc.

  17. Genetics Coupled to Quantitative Intact Proteomics Links Heritable Aphid and Endosymbiont Protein Expression to Circulative Polerovirus Transmission▿ †

    Science.gov (United States)

    Cilia, M.; Tamborindeguy, C.; Fish, T.; Howe, K.; Thannhauser, T. W.; Gray, S.

    2011-01-01

    Yellow dwarf viruses in the family Luteoviridae, which are the causal agents of yellow dwarf disease in cereal crops, are each transmitted most efficiently by different species of aphids in a circulative manner that requires the virus to interact with a multitude of aphid proteins. Aphid proteins differentially expressed in F2 Schizaphis graminum genotypes segregating for the ability to transmit Cereal yellow dwarf virus-RPV (CYDV-RPV) were identified using two-dimensional difference gel electrophoresis (DIGE) coupled to either matrix-assisted laser desorption ionization-tandem mass spectrometry or online nanoscale liquid chromatography coupled to electrospray tandem mass spectrometry. A total of 50 protein spots, containing aphid proteins and proteins from the aphid's obligate and maternally inherited bacterial endosymbiont, Buchnera, were identified as differentially expressed between transmission-competent and refractive aphids. Surprisingly, in virus transmission-competent F2 genotypes, the isoelectric points of the Buchnera proteins did not match those in the maternal Buchnera proteome as expected, but instead they aligned with the Buchnera proteome of the transmission-competent paternal parent. Among the aphid proteins identified, many were involved in energy metabolism, membrane trafficking, lipid signaling, and the cytoskeleton. At least eight aphid proteins were expressed as heritable, isoelectric point isoform pairs, one derived from each parental lineage. In the F2 genotypes, the expression of aphid protein isoforms derived from the competent parental lineage aligned with the virus transmission phenotype with high precision. Thus, these isoforms are candidate biomarkers for CYDV-RPV transmission in S. graminum. Our combined genetic and DIGE approach also made it possible to predict where several of the proteins may be expressed in refractive aphids with different barriers to transmission. Twelve proteins were predicted to act in the hindgut of the aphid

  18. Genetics coupled to quantitative intact proteomics links heritable aphid and endosymbiont protein expression to circulative polerovirus transmission.

    Science.gov (United States)

    Cilia, M; Tamborindeguy, C; Fish, T; Howe, K; Thannhauser, T W; Gray, S

    2011-03-01

    Yellow dwarf viruses in the family Luteoviridae, which are the causal agents of yellow dwarf disease in cereal crops, are each transmitted most efficiently by different species of aphids in a circulative manner that requires the virus to interact with a multitude of aphid proteins. Aphid proteins differentially expressed in F2 Schizaphis graminum genotypes segregating for the ability to transmit Cereal yellow dwarf virus-RPV (CYDV-RPV) were identified using two-dimensional difference gel electrophoresis (DIGE) coupled to either matrix-assisted laser desorption ionization-tandem mass spectrometry or online nanoscale liquid chromatography coupled to electrospray tandem mass spectrometry. A total of 50 protein spots, containing aphid proteins and proteins from the aphid's obligate and maternally inherited bacterial endosymbiont, Buchnera, were identified as differentially expressed between transmission-competent and refractive aphids. Surprisingly, in virus transmission-competent F2 genotypes, the isoelectric points of the Buchnera proteins did not match those in the maternal Buchnera proteome as expected, but instead they aligned with the Buchnera proteome of the transmission-competent paternal parent. Among the aphid proteins identified, many were involved in energy metabolism, membrane trafficking, lipid signaling, and the cytoskeleton. At least eight aphid proteins were expressed as heritable, isoelectric point isoform pairs, one derived from each parental lineage. In the F2 genotypes, the expression of aphid protein isoforms derived from the competent parental lineage aligned with the virus transmission phenotype with high precision. Thus, these isoforms are candidate biomarkers for CYDV-RPV transmission in S. graminum. Our combined genetic and DIGE approach also made it possible to predict where several of the proteins may be expressed in refractive aphids with different barriers to transmission. Twelve proteins were predicted to act in the hindgut of the aphid

  19. Genetic architecture of the Delis-Kaplan Executive Function System Trail Making Test: evidence for distinct genetic influences on executive function.

    Science.gov (United States)

    Vasilopoulos, Terrie; Franz, Carol E; Panizzon, Matthew S; Xian, Hong; Grant, Michael D; Lyons, Michael J; Toomey, Rosemary; Jacobson, Kristen C; Kremen, William S

    2012-03-01

    To examine how genes and environments contribute to relationships among Trail Making Test (TMT) conditions and the extent to which these conditions have unique genetic and environmental influences. Participants included 1,237 middle-aged male twins from the Vietnam Era Twin Study of Aging. The Delis-Kaplan Executive Function System TMT included visual searching, number and letter sequencing, and set-shifting components. Phenotypic correlations among TMT conditions ranged from 0.29 to 0.60, and genes accounted for the majority (58-84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. A common genetic factor, most likely representing a combination of speed and sequencing, accounted for most of the correlation among TMT 1-4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in nonpatient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes.

  20. Survivor-Defined Practice in Domestic Violence Work: Measure Development and Preliminary Evidence of Link to Empowerment.

    Science.gov (United States)

    Goodman, Lisa A; Thomas, Kristie; Cattaneo, Lauren Bennett; Heimel, Deborah; Woulfe, Julie; Chong, Siu Kwan

    2016-01-01

    Survivor-defined practice, characterized by an emphasis on client choice, partnership, and sensitivity to the unique needs, contexts, and coping strategies of individual survivors, is an aspirational goal of the domestic violence (DV) movement, assumed to be a key contributor to empowerment and other positive outcomes among survivors. Despite its central role in DV program philosophy, training, and practice, however, our ability to assess its presence and its presumed link to well-being has been hampered by the absence of a way to measure it from survivors' perspectives. As part of a larger university-community collaboration, this study had two aims: (a) to develop a measure of survivor-defined practice from the perspective of participants, and (b) to assess its relationship to safety-related empowerment after controlling for other contributors to survivor well-being (e.g., financial stability and social support). Results supported the reliability and validity of the Survivor-Defined Practice Scale (SDPS), a nine-item measure that assesses participants' perception of the degree to which their advocates help them achieve goals they set for themselves, facilitate a spirit of partnership, and show sensitivity to their individual needs and styles. The items combined to form one factor indicating that the three theoretical aspects of survivor-defined practice may be different manifestations of one underlying construct. Results also support the hypothesized link between survivor-defined practice and safety-related empowerment. The SDPS offers DV programs a mechanism for process evaluation that is rigorous and rooted in the feminist empowerment philosophy that so many programs espouse. © The Author(s) 2014.

  1. The genetics of dementias. Part 1: Molecular basis of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17

    Directory of Open Access Journals (Sweden)

    Anna Kowalska

    2009-06-01

    Full Text Available Frontotemporal dementia (FTD, characterized by neurodegeneration mainly in the frontal and temporal lobes, accounts for ca. 10–15�0of all dementias. In 1892 the Czech-German neuropsychiatrist Arnold Pick reported the first case of FTD in a 71-year-old patient suffering from progressive dementia, memory disturbances, and aphasia associated with frontal and temporal lobe atrophy and the presence of neuronal inclusions. Later the inclusions were named Pick bodies. The neuropathological hallmark of FTD is very differentiated. In contrast to Alzheimer’s disease (AD, there are neither senile plaques nor neurofibrillary tangles in the brains of FTD patients. Frontotemporal dementias are tauopathies, a group of disorders caused by aberrant metabolism of tau protein, a family of proteins associated with microtubules (MAPT: macrotubule-associated tau protein. In the nervous system the protein stabilizes microtubules in neuronal axons and is thus responsible for crucial processes in neuron metabolism, such as signal transduction, plasticity, and intracellular transport. In the human brain, six isoforms are produced from the MAPT gene (chromosome 17 q21.2 by alternative mRNA splicing. The isoforms differ in the number of amino acids in the protein chain, the presence of three (3R tau type or four (4R tau type domains responsible for binding to microtubules, and one or two inserts containing from 29 to 58 amino acids. The isoforms are modified posttranslationally by hyperphosphorylation, glycation, or oxidation, which can change the protein’s properties and disturb its normal function. Altered metabolism of tau protein changes its interactions with tubulin, leading to destabilization of the microtubule structure and initiating the generation of toxic tau aggregates. The first mutations in the MAPT gene responsible for frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17 were found in 1998. So far over 40 mutations in the MAPT

  2. Group A Rotaviruses in Chinese Bats: Genetic Composition, Serology, and Evidence for Bat-to-Human Transmission and Reassortment.

    Science.gov (United States)

    He, Biao; Huang, Xiaohong; Zhang, Fuqiang; Tan, Weilong; Matthijnssens, Jelle; Qin, Shaomin; Xu, Lin; Zhao, Zihan; Yang, Ling'en; Wang, Quanxi; Hu, Tingsong; Bao, Xiaolei; Wu, Jianmin; Tu, Changchun

    2017-06-15

    Bats are natural reservoirs for many pathogenic viruses, and increasing evidence supports the notion that bats can also harbor group A rotaviruses (RVAs), important causative agents of diarrhea in children and young animals. Currently, 8 RVA strains possessing completely novel genotype constellations or genotypes possibly originating from other mammals have been identified from African and Chinese bats. However, all the data were mainly based on detection of RVA RNA, present only during acute infections, which does not permit assessment of the true exposure of a bat population to RVA. To systematically investigate the genetic diversity of RVAs, 547 bat anal swabs or gut samples along with 448 bat sera were collected from five South Chinese provinces. Specific reverse transcription-PCR (RT-PCR) screening found four RVA strains. Strain GLRL1 possessed a completely novel genotype constellation, whereas the other three possessed a constellation consistent with the MSLH14-like genotype, a newly characterized group of viruses widely prevalent in Chinese insectivorous bats. Among the latter, strain LZHP2 provided strong evidence of cross-species transmission of RVAs from bats to humans, whereas strains YSSK5 and BSTM70 were likely reassortants between typical MSLH14-like RVAs and human RVAs. RVA-specific antibodies were detected in 10.7% (48/448) of bat sera by an indirect immunofluorescence assay (IIFA). Bats in Guangxi and Yunnan had a higher RVA-specific antibody prevalence than those from Fujian and Zhejiang provinces. These observations provide evidence for cross-species transmission of MSLH14-like bat RVAs to humans, highlighting the impact of bats as reservoirs of RVAs on public health. IMPORTANCE Bat viruses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), Ebola, Hendra, and Nipah viruses, are important pathogens causing outbreaks of severe emerging infectious diseases. However, little is known about bat viruses capable

  3. The aminoacyl-tRNA synthetases had only a marginal role in the origin of the organization of the genetic code: Evidence in favor of the coevolution theory.

    Science.gov (United States)

    Di Giulio, Massimo

    2017-11-07

    The coevolution theory of the origin of the genetic code suggests that the organization of the genetic code coevolved with the biosynthetic relationships between amino acids. The mechanism that allowed this coevolution was based on tRNA-like molecules on which-this theory-would postulate the biosynthetic transformations between amino acids to have occurred. This mechanism makes a prediction on how the role conducted by the aminoacyl-tRNA synthetases (ARSs), in the origin of the genetic code, should have been. Indeed, if the biosynthetic transformations between amino acids occurred on tRNA-like molecules, then there was no need to link amino acids to these molecules because amino acids were already charged on tRNA-like molecules, as the coevolution theory suggests. In spite of the fact that ARSs make the genetic code responsible for the first interaction between a component of nucleic acids and that of proteins, for the coevolution theory the role of ARSs should have been entirely marginal in the genetic code origin. Therefore, I have conducted a further analysis of the distribution of the two classes of ARSs and of their subclasses-in the genetic code table-in order to perform a falsification test of the coevolution theory. Indeed, in the case in which the distribution of ARSs within the genetic code would have been highly significant, then the coevolution theory would be falsified since the mechanism on which it is based would not predict a fundamental role of ARSs in the origin of the genetic code. I found that the statistical significance of the distribution of the two classes of ARSs in the table of the genetic code is low or marginal, whereas that of the subclasses of ARSs statistically significant. However, this is in perfect agreement with the postulates of the coevolution theory. Indeed, the only case of statistical significance-regarding the classes of ARSs-is appreciable for the CAG code, whereas for its complement-the UNN/NUN code-only a marginal

  4. Linking online gaming and addictive behavior: Converging evidence for a general reward deficiency in frequent online gamers

    Directory of Open Access Journals (Sweden)

    Tim eHahn

    2014-11-01

    Full Text Available Millions of people regularly play so-called Massively Multiplayer Online Role Playing Games (MMORPGs. Recently, it has been argued that MMORPG overuse is becoming a significant health problem worldwide. Symptoms such as tolerance, withdrawal and craving have been described. Based on behavioral, resting state and task-related neuroimaging data, we test whether frequent players of the MMORPG World of Warcraft (WoW – similar to drug addicts and individuals with an increased risk for addictions – show a generally deficient reward system. In frequent players of the MMORPG World of Warcraft (WoW-players and in a control group of non-gamers we assessed 1 trait sensitivity to reward, 2 BOLD responses during monetary reward processing in the ventral striatum and 3 ventral-striatal resting state dynamics. We find a decreased neural activation in the ventral striatum during the anticipation of both small and large monetary rewards. Additionally, we show generally altered neurodynamics in this region independent of any specific task for WoW players (resting state. On the behavioral level, we found differences in trait sensitivity to reward, suggesting that the reward processing deficiencies found in this study are not a consequence of gaming, but predisposed to it. These findings empirically support a direct link between frequent online gaming and the broad field of behavioral and drug addiction research, thus opening new avenues for clinical interventions in addicted gamers and potentially improving the assessment of addiction-risk in the vast population of frequent gamers.

  5. Associations linking parenting styles and offspring personality disorder are moderated by parental personality disorder, evidence from China.

    Science.gov (United States)

    Cheng, Hui Green; Huang, Yueqin; Liu, Zhaorui; Liu, Baohua

    2011-08-30

    The aim of the study is to examine the association linking parenting and personality disorder controlling for parental personality disorder, and whether this association is moderated by parental PD. Data were from community-dwelling high school students aged 18 and above and their parents living in Beijing, China. A total of 181 cases and 2,605 controls were included in this study. Personality disorder in students was assessed via a two-stage approach, Personality Diagnostic Questionnaire as a screening tool and International Personality Disorder Examination as the diagnostic tool. Information about parenting was collected from students using Egna Minnen av. Betraffande Uppfostran. Negative parenting styles, e.g. rejective or over-protective parenting, were found to be associated with the occurrence of personality disorder. Conflictive parenting styles were also found to be associated with personality disorder. Generally stronger associations were found for students with parental personality disorder as compared to students without parental personality disorder. Findings from this study support the role of parenting in the occurrence of PD, especially for children with family history of personality disorder. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Linking online gaming and addictive behavior: converging evidence for a general reward deficiency in frequent online gamers.

    Science.gov (United States)

    Hahn, Tim; Notebaert, Karolien Hilde; Dresler, Thomas; Kowarsch, Linda; Reif, Andreas; Fallgatter, Andreas J

    2014-01-01

    Millions of people regularly play so-called massively multiplayer online role playing games (MMORPGs). Recently, it has been argued that MMORPG overuse is becoming a significant health problem worldwide. Symptoms such as tolerance, withdrawal, and craving have been described. Based on behavioral, resting state, and task-related neuroimaging data, we test whether frequent players of the MMORPG "World of Warcraft" (WoW) - similar to drug addicts and individuals with an increased risk for addictions - show a generally deficient reward system. In frequent players of the MMORPG "World of Warcraft" (WoW-players) and in a control group of non-gamers we assessed (1) trait sensitivity to reward (SR), (2) BOLD responses during monetary reward processing in the ventral striatum, and (3) ventral-striatal resting-state dynamics. We found a decreased neural activation in the ventral striatum during the anticipation of both small and large monetary rewards. Additionally, we show generally altered neurodynamics in this region independent of any specific task for WoW players (resting state). On the behavioral level, we found differences in trait SR, suggesting that the reward processing deficiencies found in this study are not a consequence of gaming, but predisposed to it. These findings empirically support a direct link between frequent online gaming and the broad field of behavioral and drug addiction research, thus opening new avenues for clinical interventions in addicted gamers and potentially improving the assessment of addiction-risk in the vast population of frequent gamers.

  7. Valuing productivity loss due to absenteeism: firm-level evidence from a Canadian linked employer-employee survey.

    Science.gov (United States)

    Zhang, Wei; Sun, Huiying; Woodcock, Simon; Anis, Aslam H

    2017-12-01

    In health economic evaluation studies, to value productivity loss due to absenteeism, existing methods use wages as a proxy value for marginal productivity. This study is the first to test the equality between wage and marginal productivity losses due to absenteeism separately for team workers and non-team workers. Our estimates are based on linked employer-employee data from Canada. Results indicate that team workers are more productive and earn higher wages than non-team workers. However, the productivity gap between these two groups is considerably larger than the wage gap. In small firms, employee absenteeism results in lower productivity and wages, and the marginal productivity loss due to team worker absenteeism is significantly higher than the wage loss. No similar wage-productivity gap exists for large firms. Our findings suggest that productivity loss or gain is most likely to be underestimated when valued according to wages for team workers. The findings help to value the burden of illness-related absenteeism. This is important for economic evaluations that seek to measure the productivity gain or loss of a health care technology or intervention, which in turn can impact policy makers' funding decisions.

  8. Linking forms of inbound open innovation to a driver-based typology of environmental innovation: Evidence from French manufacturing firms

    DEFF Research Database (Denmark)

    Li-Ying, Jason; Mothe, Caroline; Nguyen, Thi Thuc Uyen

    2017-01-01

    Environmental innovation research has not yet clarified how different forms of inbound innovation might exert effects. The current article proposes four driver-based EI types according to two main dimensions: compliance versus voluntary and own value capture versus customer value capture. With a ......Environmental innovation research has not yet clarified how different forms of inbound innovation might exert effects. The current article proposes four driver-based EI types according to two main dimensions: compliance versus voluntary and own value capture versus customer value capture....... With a problem-solving perspective, we develop links from different forms of inbound innovation to various types of EI and test the related hypotheses with two waves of the French Community Innovation Survey. On a short-term basis, R&D cooperation and technology acquisition correlate positively with all four...... types of EI, but over time, persistent R&D cooperation and technology acquisition are associated with EI only at the production stage, according to voluntary/strategic or compliance drivers. Inbound innovation enables quick responses to market demands for EI in the final use stage....

  9. Toward an evidence-based patient-provider communication in rehabilitation: linking communication elements to better rehabilitation outcomes.

    Science.gov (United States)

    Jesus, Tiago Silva; Silva, Isabel Lopes

    2016-04-01

    There is a growing interest in linking aspects of patient-provider communication to rehabilitation outcomes. However, the field lacks a conceptual understanding on: (a) 'how' rehabilitation outcomes can be improved by communication; and (b) through 'which' elements in particular. This article elaborates on the conceptual developments toward informing further practice and research. Existing models of communication in healthcare were adapted to rehabilitation, and its outcomes through a comprehensive literature review. After depicting mediating mechanisms and variables (e.g. therapeutic engagement, adjustment toward disability), this article presents the '4 Rehab Communication Elements' deemed likely to underpin rehabilitation outcomes. The four elements are: (a) knowing the person and building a supportive relationship; (b) effective information exchange and education; (c) shared goal-setting and action planning; and (d) fostering a more positive, yet realistic, cognitive and self-reframing. This article describes an unprecedented, outcomes-oriented approach toward the design of rehabilitation communication, which has resulted in the development of a new intervention model: the '4 Rehab Communication Elements'. Further trials are needed to evaluate the impact of this whole intervention model on rehabilitation outcomes. © The Author(s) 2015.

  10. Finding the Link between CSR Reporting and Corporate Financial Performance: Evidence on Czech and Estonian Listed Companies

    Directory of Open Access Journals (Sweden)

    Jiří Strouhal

    2015-09-01

    Full Text Available Despite the fact that obligations to publish reports on corporate social responsibility will come into force in the European Union from 2018, an increasing number of companies are starting to implement corporate social responsibility (CSR policy into their everyday business practices, and as a result the information of this activity is disclosed in CSR reports or within annual reports. As the disclosure of such information is currently voluntarily based, we believe that the growing popularity of CSR leads to a direct link between the sustainability of the company and its financial performance. The purpose of this paper is therefore to determine the linkage between CSR and financial performance within two countries in the CEE region – Czech and Estonia – using data from 2012 - 2013. We compare return on assets and normalized market value added of listed companies. Based on the results, we can state that the implementation of a standalone CSR report does not have any direct linkage with the financial performance of the tested companies.

  11. Does Current Scientific Evidence Support a Link Between Light at Night and Breast Cancer Among Female Night-Shift Nurses?

    Science.gov (United States)

    Dickerman, Barbra; Liu, Jianghong

    2014-01-01

    Breast cancer is increasingly prevalent in industrialized regions of the world, and exposure to light at night (LAN) has been proposed as a potential risk factor. Epidemiological observations have documented an increased breast cancer risk among female night-shift workers, and strong experimental evidence for this relationship has also been found in rodent models. Indirect support for the LAN hypothesis comes from studies involving blind women, sleep duration, bedroom light levels, and community nighttime light levels. This article reviews the literature, discusses possible mechanisms of action, and provides recommendations for occupational health nursing research, practice, and education. Research is needed to further explore the relationship between exposure to LAN and breast cancer risk and elucidate the mechanisms underlying this relationship before interventions can be designed for prevention and mitigation of breast cancer. PMID:22658734

  12. Making the links between domestic violence and child safeguarding: an evidence-based pilot training for general practice.

    Science.gov (United States)

    Szilassy, Eszter; Drinkwater, Jess; Hester, Marianne; Larkins, Cath; Stanley, Nicky; Turner, William; Feder, Gene

    2017-11-01

    We describe the development of an evidence-based training intervention on domestic violence and child safeguarding for general practice teams. We aimed - in the context of a pilot study - to improve knowledge, skills, attitudes and self-efficacy of general practice clinicians caring for families affected by domestic violence. Our evidence sources included: a systematic review of training interventions aiming to improve professional responses to children affected by domestic violence; content mapping of relevant current training in England; qualitative assessment of general practice professionals' responses to domestic violence in families; and a two-stage consensus process with a multi-professional stakeholder group. Data were collected between January and December 2013. This paper reports key research findings and their implications for practice and policy; describes how the research findings informed the training development and outlines the principal features of the training intervention. We found lack of cohesion and co-ordination in the approach to domestic violence and child safeguarding. General practice clinicians have insufficient understanding of multi-agency work, a limited competence in gauging thresholds for child protection referral to children's services and little understanding of outcomes for children. While prioritising children's safety, they are more inclined to engage directly with abusive parents than with affected children. Our research reveals uncertainty and confusion surrounding the recording of domestic violence cases in families' medical records. These findings informed the design of the RESPONDS training, which was developed in 2014 to encourage general practice clinicians to overcome barriers and engage more extensively with adults experiencing abuse, as well as responding directly to the needs of children. We conclude that general practice clinicians need more support in managing the complexity of this area of practice. We need to

  13. Allelic heterogeneity and genetic modifier loci contribute to clinical variation in males with X-linked retinitis pigmentosa due to RPGR mutations.

    Directory of Open Access Journals (Sweden)

    Abigail T Fahim

    Full Text Available Mutations in RPGR account for over 70% of X-linked retinitis pigmentosa (XlRP, characterized by retinal degeneration and eventual blindness. The clinical consequences of RPGR mutations are highly varied, even among individuals with the same mutation: males demonstrate a wide range of clinical severity, and female carriers may or may not be affected. This study describes the phenotypic diversity in a cohort of 98 affected males from 56 families with RPGR mutations, and demonstrates the contribution of genetic factors (i.e., allelic heterogeneity and genetic modifiers to this diversity. Patients were categorized as grade 1 (mild, 2 (moderate or 3 (severe according to specific clinical criteria. Patient DNAs were genotyped for coding SNPs in 4 candidate modifier genes with products known to interact with RPGR protein: RPGRIP1, RPGRIP1L, CEP290, and IQCB1. Family-based association testing was performed using PLINK. A wide range of clinical severity was observed both between and within families. Patients with mutations in exons 1-14 were more severely affected than those with ORF15 mutations, and patients with predicted null alleles were more severely affected than those predicted to make RPGR protein. Two SNPs showed association with severe disease: the minor allele (N of I393N in IQCB1 (p = 0.044 and the common allele (R of R744Q in RPGRIP1L (p = 0.049. These data demonstrate that allelic heterogeneity contributes to phenotypic diversity in XlRP and suggest that this may depend on the presence or absence of RPGR protein. In addition, common variants in 2 proteins known to interact with RPGR are associated with severe disease in this cohort.

  14. Genetic Discrimination

    Science.gov (United States)

    ... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

  15. Dengue viruses in Papua New Guinea: evidence of endemicity and phylogenetic variation, including the evolution of new genetic lineages.

    Science.gov (United States)

    Moore, Peter R; van den Hurk, Andrew F; Mackenzie, John S; Pyke, Alyssa T

    2017-12-20

    Dengue is the most common cause of mosquito-borne viral disease in humans, and is endemic in more than 100 tropical and subtropical countries. Periodic outbreaks of dengue have been reported in Papua New Guinea (PNG), but there is only limited knowledge of its endemicity and disease burden. To help elucidate the status of the dengue viruses (DENVs) in PNG, we performed envelope (E) gene sequencing of DENV serotypes 1-4 (DENV 1-4) obtained from infected patients who traveled to Australia or from patients diagnosed during local DENV transmission events between 2001 and 2016. Phylogenetic analysis and comparison with globally available DENV sequences revealed new endemic PNG lineages for DENV 1-3 which have emerged within the last decade. We also identified another possible PNG lineage for DENV-4 from 2016. The DENV-1 and 3 PNG lineages were most closely related to recent lineages circulating on Pacific island nations while the DENV-2 lineage and putative DENV-4 PNG lineage were most similar to Indonesian sequences. This study has demonstrated for the first time the co-circulation of DENV 1-4 strains in PNG and provided molecular evidence of endemic DENV transmission. Our results provide an important platform for improved surveillance and monitoring of DENVs in PNG and broaden the global understanding of DENV genetic diversity.

  16. Can small wildlife conservancies maintain genetically stable populations of large mammals? Evidence for increased genetic drift in geographically restricted populations of Cape buffalo in East Africa

    DEFF Research Database (Denmark)

    Heller, R; Okello, J B A; Siegismund, H

    2010-01-01

    populations, the level of genetic differentiation found here is comparable to that among pan-African populations. Overall, correlations between conservancy area and indices of genetic diversity suggest buffalo populations inhabiting small parks are showing signs of genetic erosion, stressing the need for more......The Cape buffalo (Syncerus caffer caffer) is one of the dominant and most widespread herbivores in sub-Saharan Africa. High levels of genetic diversity and exceptionally low levels of population differentiation have been found in the Cape buffalo compared to other African savannah ungulates...... active management of such populations. Our findings raise concerns about the future of other African savannah ungulates with lower population sizes and inferior dispersal capabilities compared with the buffalo....

  17. Breaking The Link Between Legal Access To Alcohol And Motor Vehicle Accidents: Evidence From New South Wales.

    Science.gov (United States)

    Lindo, Jason M; Siminski, Peter; Yerokhin, Oleg

    2016-07-01

    A large literature has documented significant public health benefits associated with the minimum legal drinking age in the USA, particularly because of the resulting effects on motor vehicle accidents. These benefits form the primary basis for continued efforts to restrict youth access to alcohol. It is important to keep in mind that policymakers have a wide variety of alcohol-control options available to them, and understanding how these policies may complement or substitute for one another can improve policy making moving forward. Towards this end, we propose that investigating the causal effects of the minimum legal drinking age in New South Wales, Australia, provides a particularly informative case study, because Australian states are among the world leaders in their efforts against drunk driving. Using an age-based regression discontinuity design applied to restricted-use data from several sources, we find no evidence that legal access to alcohol has effects on motor vehicle accidents of any type in New South Wales, despite having large effects on drinking and on hospitalizations due to alcohol abuse. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Electrophysiological evidence for a direct link between the main and accessory olfactory bulbs in the adult rat

    Directory of Open Access Journals (Sweden)

    Victor eVargas-Barroso

    2016-01-01

    Full Text Available It is accepted that the main- and accessory- olfactory systems exhibit overlapping responses to pheromones and odorants. We performed whole-cell patch-clamp recordings in adult rat olfactory bulb slices to define a possible interaction between the first central relay of these systems: the accessory olfactory bulb (AOB and the main olfactory bulb (MOB. This was tested by applying electrical field stimulation in the dorsal part of the MOB while recording large principal cells (LPCs of the anterior AOB (aAOB. Additional recordings of LPCs were performed at either side of the plane of intersection between the aAOB and posterior-AOB (pAOB halves, or linea alba, while applying field stimulation to the opposite half. A total of 92 recorded neurons were filled during whole-cell recordings with biocytin and studied at the light microscope. Neurons located in the aAOB (n = 6, 8% send axon collaterals to the MOB since they were antidromically activated in the presence of glutamate receptor antagonists (APV and CNQX. Recorded LPCs evoked orthodromic excitatory post-synaptic responses (n = 6, aAOB; n = 1, pAOB or antidromic action potentials (n = 8, aAOB; n = 7, pAOB when applying field stimulation to the opposite half of the recording site (e.g. recording in aAOB; stimulating in pAOB and vice-versa. Observation of the filled neurons revealed that indeed, LPCs send axon branches that cross the linea alba to resolve in the internal cellular layer. Additionally, LPCs of the aAOB send axon collaterals to dorsal-MOB territory. Notably, while performing AOB recordings we found a sub-population of neurons (24 % of the total that exhibited voltage-dependent bursts of action potentials. Our findings support the existence of: 1. a direct projection from aAOB LPCs to dorsal-MOB, 2. physiologically active synapses linking aAOB and pAOB, and 3. pacemaker-like neurons in both AOB halves. This work was presented in the form of an Abstract on SfN 2014 (719.14/EE17.

  19. Diagnostic investigation of porcine periweaning failure-to-thrive syndrome: lack of compelling evidence linking to common porcine pathogens.

    Science.gov (United States)

    Huang, Yanyun; Gauvreau, Henry; Harding, John

    2012-01-01

    Porcine periweaning failure-to-thrive syndrome (PFTS), an increasingly recognized syndrome in the swine industry of North America, is characterized by the anorexia of nursery pigs noticeable within 1 week of weaning, and progressive loss of body condition and lethargy during the next 1-2 weeks. Morbidity caused by PFTS is moderate, but case fatality is high. The etiology of PFTS is presently unknown and may include infectious agent(s), noninfectious factors, or both. PFTS was identified in a high health status farm with good management in early 2007. A diagnostic investigation was undertaken to identify the pathological lesions of, and infectious agents associated with, pigs demonstrating typical clinical signs. Affected (PFTS-SICK) and unaffected (PFTS-HLTHY) pigs from an affected farm, and unaffected pigs from 2 unaffected farms, were examined. The most prevalent lesions in PFTS-SICK pigs were superficial lymphocytic fundic gastritis, atrophic enteritis, superficial colitis, lymphocytic and neutrophilic rhinitis, mild nonsuppurative meningoencephalitis, and thymic atrophy. Rotavirus A and Betacoronavirus 1 (Porcine hemagglutinating encephalomyelitis virus) were identified only in PFTS-SICK pigs, but the significance of the viruses is uncertain because PFTS is not consistent with the typical presentation following infection by these pathogens. Porcine reproductive and respiratory syndrome virus, Porcine circovirus-2, Influenza A virus, Alphacoronavirus 1 (Transmissible gastroenteritis virus), Torque teno virus 1, Brachyspira hyodysenteriae, and Brachyspira pilosicoli were not identified in PFTS-SICK pigs. Suid herpesvirus 2 (Porcine cytomegalovirus), Porcine enteric calicivirus, Torque teno virus 2, pathogenic Escherichia coli, and coccidia were detected in both PFTS-SICK and PFTS-HLTHY pigs. It was concluded that there is a lack of compelling evidence that PFTS is caused by any of these pathogens.

  20. Evidence for a link between changes to gaze behaviour and risk of falling in older adults during adaptive locomotion.

    Science.gov (United States)

    Chapman, G J; Hollands, M A

    2006-11-01

    There is increasing evidence that gaze stabilization with respect to footfall targets plays a crucial role in the control of visually guided stepping and that there are significant changes to gaze behaviour as we age. However, past research has not measured if age-related changes in gaze behaviour are associated with changes to stepping performance. This paper aims to identify differences in gaze behaviour between young (n=8) adults, older adults determined to be at a low-risk of falling (low-risk, n=4) and older adults prone to falling (high-risk, n=4) performing an adaptive locomotor task and attempts to relate observed differences in gaze behaviour to decline in stepping performance. Participants walked at a self-selected pace along a 9m pathway stepping into two footfall target locations en route. Gaze behaviour and lower limb kinematics were recorded using an ASL 500 gaze tracker interfaced with a Vicon motion analysis system. Results showed that older adults looked significantly sooner to targets, and fixated the targets for longer, than younger adults. There were also significant differences in these measures between high and low-risk older adults. On average, high-risk older adults looked away from targets significantly sooner and demonstrated less accurate and more variable foot placements than younger adults and low-risk older adults. These findings suggest that, as we age, we need more time to plan precise stepping movements and clearly demonstrate that there are differences between low-risk and high-risk older adults in both where and when they look at future stepping targets and the precision with which they subsequently step. We propose that high-risk older adults may prioritize the planning of future actions over the accurate execution of ongoing movements and that adoption of this strategy may contribute to an increased likelihood of falls. Copyright 2005 Elsevier B.V.