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Sample records for factors including genetics

  1. Does and should breast cancer genetic counselling include lifestyle advice?

    NARCIS (Netherlands)

    Albada, A.; Vernooij, M.; Osch, L. van; Pijpe, A.; Dulmen, S. van; Ausems, M.G.E.M.

    2014-01-01

    To optimally inform counselees about their and their relatives' risks, information about lifestyle risk factors, e.g. physical activity and alcohol consumption, might be discussed in breast cancer genetic counselling. This study explored whether lifestyle was discussed, on whose initiative, whether

  2. Landscape genetics and limiting factors

    Science.gov (United States)

    Samuel A. Cushman; Andrew J. Shirk; Erin L. Landguth

    2013-01-01

    Population connectivity is mediated by the movement of organisms or propagules through landscapes. However, little is known about how variation in the pattern of landscape mosaics affects the detectability of landscape genetic relationships. The goal of this paper is to explore the impacts of limiting factors on landscape genetic processes using simulation...

  3. Stroke Risk Factors, Genetics, and Prevention.

    Science.gov (United States)

    Boehme, Amelia K; Esenwa, Charles; Elkind, Mitchell S V

    2017-02-03

    Stroke is a heterogeneous syndrome, and determining risk factors and treatment depends on the specific pathogenesis of stroke. Risk factors for stroke can be categorized as modifiable and nonmodifiable. Age, sex, and race/ethnicity are nonmodifiable risk factors for both ischemic and hemorrhagic stroke, while hypertension, smoking, diet, and physical inactivity are among some of the more commonly reported modifiable risk factors. More recently described risk factors and triggers of stroke include inflammatory disorders, infection, pollution, and cardiac atrial disorders independent of atrial fibrillation. Single-gene disorders may cause rare, hereditary disorders for which stroke is a primary manifestation. Recent research also suggests that common and rare genetic polymorphisms can influence risk of more common causes of stroke, due to both other risk factors and specific stroke mechanisms, such as atrial fibrillation. Genetic factors, particularly those with environmental interactions, may be more modifiable than previously recognized. Stroke prevention has generally focused on modifiable risk factors. Lifestyle and behavioral modification, such as dietary changes or smoking cessation, not only reduces stroke risk, but also reduces the risk of other cardiovascular diseases. Other prevention strategies include identifying and treating medical conditions, such as hypertension and diabetes, that increase stroke risk. Recent research into risk factors and genetics of stroke has not only identified those at risk for stroke but also identified ways to target at-risk populations for stroke prevention. © 2017 American Heart Association, Inc.

  4. Liver fibrogenesis and genetic factors.

    Science.gov (United States)

    Boursier, Jérôme; Louvet, Alexandre

    2011-06-01

    Chronic liver diseases lead to the accumulation of fibrosis in the liver with eventual progression to cirrhosis and its complications. However, there is a wide range of inter-individual variation in the liver fibrogenesis process, thus posing a challenge to physicians to identify patients with poor prognosis. As demographic and environmental factors only account for a small portion of fibrogenesis variability, host genetic factors have been suggested as playing an important role. Due to technical limitations, the first genetic studies were restricted to the evaluation of candidate genes having a known or supposed function in liver fibrogenesis. Recently, technological improvements have made it possible to study the whole human genome in a single scan. Genome-wide association studies have considerably heightened the interest in genetics as part of the study of liver fibrogenesis through their identification of previously unsuspected genes that are statistically associated with liver fibrosis. It is thus possible to determine new diagnostic or prognostic genetic markers for the management of patients with chronic liver diseases. Moreover, functional analyses of these genes may provide new insights into the pathophysiology of liver fibrogenesis.

  5. The Genetic and Environmental Factors for Keratoconus

    Science.gov (United States)

    Gordon-Shaag, Ariela; Millodot, Michel; Shneor, Einat; Liu, Yutao

    2015-01-01

    Keratoconus (KC) is the most common cornea ectatic disorder. It is characterized by a cone-shaped thin cornea leading to myopia, irregular astigmatism, and vision impairment. It affects all ethnic groups and both genders. Both environmental and genetic factors may contribute to its pathogenesis. This review is to summarize the current research development in KC epidemiology and genetic etiology. Environmental factors include but are not limited to eye rubbing, atopy, sun exposure, and geography. Genetic discoveries have been reviewed with evidence from family-based linkage analysis and fine mapping in linkage region, genome-wide association studies, and candidate genes analyses. A number of genes have been discovered at a relatively rapid pace. The detailed molecular mechanism underlying KC pathogenesis will significantly advance our understanding of KC and promote the development of potential therapies. PMID:26075261

  6. Human genetic factors in tuberculosis: an update.

    Science.gov (United States)

    van Tong, Hoang; Velavan, Thirumalaisamy P; Thye, Thorsten; Meyer, Christian G

    2017-09-01

    Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB. © 2017 John Wiley & Sons Ltd.

  7. Genetic engineering and coagulation factors.

    Science.gov (United States)

    Fass, D N; Toole, J J

    1985-06-01

    It is unfortunate that we cannot report, in the area of coagulation, advances that have been seen in related fields such as thrombolytic therapy. The reported progress (Gold et al, 1984; Van de Werf et al, 1984) with human recombinant tissue plasminogen activator (Pennica et al, 1983) augers well for the application of recombinant technology to the problems faced by patients with coagulation defects. While plasminogen activator is being assessed in an acute therapeutic setting, its use signals a beginning of the application of the technology to abnormalities of the haemostatic mechanism. Chronic administration of coagulation factors for prophylaxis and replacement therapy would appear to be just one more step down the pathway illuminated by the biochemists, microbiologists and cell biologists who have preceded the clinicians in this promising area. There is no record of the use of genetically engineered materials in the treatment of coagulation defects, primarily because the body of knowledge and refined techniques have only recently been acquired. For this reason we have had to project developments in other areas onto the problems that exist for the haemostatically compromised patient. In describing the potential usefulness of these technologies, it is difficult to ascertain where the logical projection, from a fully investigated model system, diverges from flights of imaginative fancy. Cloning projects considered overly ambitious and grandiose at the beginning of this decade are already accomplished feats. The feasibility of gene therapy in the mammalian system has been demonstrated, and trade publications now discuss governmental approval for investigative use of this procedure in 1985. Panels of physicians, scientists and even politicians now seriously contemplate and promulgate views and regulations pertaining to the efficacy and ethics of the use of genetic engineering in the treatment of human disease. The haemophilias will certainly be among the first

  8. Shared genetic factors in migraine and depression

    Science.gov (United States)

    Stam, A H.; de Vries, B; Janssens, A C.J.W.; Vanmolkot, K R.J.; Aulchenko, Y S.; Henneman, P; Oostra, B A.; Frants, R R.; van den Maagdenberg, A M.J.M.; Ferrari, M D.; van Duijn, C M.; Terwindt, G M.

    2010-01-01

    Objective: To investigate the co-occurrence of migraine and depression and assess whether shared genetic factors may underlie both diseases. Methods: Subjects were 2,652 participants of the Erasmus Rucphen Family genetic isolate study. Migraine was diagnosed using a validated 3-stage screening method that included a telephone interview. Symptoms of depression were assessed using the Center for Epidemiologic Studies Depression scale and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). The contribution of shared genetic factors in migraine and depression was investigated by comparing heritability estimates for migraine with and without adjustment for symptoms of depression, and by comparing the heritability scores of depression between migraineurs and controls. Results: We identified 360 migraine cases: 209 had migraine without aura (MO) and 151 had migraine with aura (MA). Odds ratios for depression in patients with migraine were 1.29 (95% confidence interval [CI] 0.98–1.70) for MO and 1.70 (95% CI 1.28–2.24) for MA. Heritability estimates were significant for all migraine (0.56), MO (0.77), and MA (0.96), and decreased after adjustment for symptoms of depression or use of antidepressant medication, in particular for MA. Comparison of the heritability scores for depression between patients with migraine and controls showed a genetic correlation between HADS-D score and MA. Conclusions: There is a bidirectional association between depression and migraine, in particular migraine with aura, which can be explained, at least partly, by shared genetic factors. GLOSSARY CES-D = Center for Epidemiologic Studies Depression Scale; CI = confidence interval; ERF = Erasmus Rucphen Family; HADS-D = Hospital Anxiety and Depression Scale; IHS = International Headache Society; MA = migraine with aura; MO = migraine without aura; OR = odds ratio. PMID:20071666

  9. Environmental and genetical factors in airway allergies

    Directory of Open Access Journals (Sweden)

    Katarzyna Idzik

    2012-12-01

    Full Text Available It is estimated that approximately 23% of the European population is clinically diagnosed with allergies. In the past three decades, an increase in the incidence of respiratory allergies was noted. At the beginning of the 20th century allergic inflammations affected only around 1% of the world population. Medical symptoms of allergic airway inflammation are variable for different patients. Airways allergy are complex phenotypes, which are determined by both genetic and environmental factors. Potential environmental factors include air pollution, tobacco smoke, diet and hygienic habits. The base of phenotypes diversity is still unknown. Genetic studies of allergic disease are complex , the disease derives from the global effect of a series of genes considered individually. What is more, there are epigenetic effects and interactions among the possible causal genes and a range of environmental factors. Single nucleotide polymorphism (SNP in genes encoding chemokines and their receptors, interleukins and their receptors, eosinophil peroxidase and leukotrienes have been found as a possible factor for a development of allergic airway inflammation. It is known that SNPs are specific for different cohort.

  10. Genetic risk factors for hypertrophic scar development.

    Science.gov (United States)

    Thompson, Callie M; Hocking, Anne M; Honari, Shari; Muffley, Lara A; Ga, Maricar; Gibran, Nicole S

    2013-01-01

    Hypertrophic scars (HTSs) occur in 30 to 72% patients after thermal injury. Risk factors include skin color, female sex, young age, burn site, and burn severity. Recent correlations between genetic variations and clinical conditions suggest that single-nucleotide polymorphisms (SNPs) may be associated with HTS formation. The authors hypothesized that an SNP in the p27 gene (rs36228499) previously associated with decreased restenosis after coronary stenting would be associated with lower Vancouver Scar Scale (VSS) measurements and decreased itching. Patient and injury characteristics were collected from adults with thermal burns. VSS scores were calculated at 4 to 9 months after injury. Genotyping was performed using real-time polymerase chain reaction. Logistic regression was used to determine risk factors for HTS as measured by a VSS score >7. Three hundred subjects had a median age of 39 years (range, 18-91); 69% were male and median burn size was 7% TBSA (range, 0.25-80). Consistent with literature, the p27 variant SNP had an allele frequency of 40%, but was not associated with reduced HTS formation or lower itch scores in any genetic model. HTS formation was associated with American Indian/Alaskan Native race (odds ratio [OR], 12.2; P = .02), facial burns (OR, 9.4; P = .04), and burn size ≥20% TBSA (OR, 1.99; P = .03). Although the p27 SNP may protect against vascular fibroproliferation, the effect cannot be generalized to cutaneous scars. This study suggests that American Indian/Alaskan Native race, facial burns, and higher %TBSA are independent risk factors for HTS. The American Indian/Alaskan Native association suggests that there are potentially yet-to-be-identified genetic variants.

  11. Genetic Factors of Ophthalmic Importance.

    Science.gov (United States)

    Pollard, Zane F.

    Reviewed are chromosomal anomalies affecting one's eyes. Brief descriptions are given of the genetic etiology of bilateral retinoblastoma (malignant tumors), aniridia (absence of the iris), cataracts, congenital glaucoma, Reginitis Pigmentosa (progressive deterioration of the visual cells), Choroidermia (degeneration of the vascular coat of the…

  12. Genetic Factors of Ophthalmic Importance.

    Science.gov (United States)

    Pollard, Zane F.

    Reviewed are chromosomal anomalies affecting one's eyes. Brief descriptions are given of the genetic etiology of bilateral retinoblastoma (malignant tumors), aniridia (absence of the iris), cataracts, congenital glaucoma, Reginitis Pigmentosa (progressive deterioration of the visual cells), Choroidermia (degeneration of the vascular coat of the…

  13. Factors affecting student performance in an undergraduate genetics course.

    Science.gov (United States)

    Bormann, J Minick; Moser, D W; Bates, K E

    2013-05-01

    The objective of this study was to determine some of the factors that affect student success in a genetics course. Genetics for the Kansas State University College of Agriculture is taught in the Department of Animal Sciences and Industry and covers Mendelian inheritance, molecular genetics, and quantitative/population genetics. Data collected from 1,516 students over 7 yr included year and semester of the course; age; gender; state of residence; population of hometown; Kansas City metro resident or not; instructor of course; American College Testing Program (ACT) scores; number of transfer credits; major; college; preveterinary student or not; freshman, sophomore, junior, and senior grade point average (GPA); semester credits when taking genetics; class standing when enrolled in genetics; cumulative GPA before and after taking genetics; semester GPA in semester taking genetics, number of semesters between the biology prerequisite and genetics; grade in biology; location of biology course; and final percentage in genetics. Final percentage in genetics did not differ due to instructor, gender, state of residence, major, or college (P > 0.16). Transfer students tended to perform better than nontransfer students (P = 0.09), and students from the Kansas City metro outscored students from other areas (P = 0.03). Preveterinary option students scored higher in genetics than non-preveterinary students (P genetics (P = 0.06). Students who took biology at Kansas State University performed better in genetics than students who transferred the credit (P genetics (P genetics, students should take biology from Kansas State, perform well in biology, and wait until at least sophomore standing to enroll in genetics.

  14. Genetic risk factors for autoimmune diseases

    NARCIS (Netherlands)

    Feltkamp, T.E.W.; Aarden, L.A.; Lucas, C.J.; Verweij, C.L.; Vries, R.R.P. de

    1999-01-01

    In most autoimmune diseases multigenic factors play a significant role in pathogenesis. Progress in identifying these genetic factors, many of which are located outside the major histocompatibility complex, was the subject of a recent meeting. Chemicals/CAS: Interleukin-10, 130068-27-8; Transforming

  15. Risk Factors for Breast Cancer, Including Occupational Exposures

    Directory of Open Access Journals (Sweden)

    Elisabete Weiderpass

    2011-03-01

    Full Text Available The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr. For breast cancer the following substances have been classified as “carcinogenic to humans” (Group 1: alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure. Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification “probably carcinogenic to humans” (Group 2A includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women.

  16. Risk factors for breast cancer, including occupational exposures.

    Science.gov (United States)

    Weiderpass, Elisabete; Meo, Margrethe; Vainio, Harri

    2011-03-01

    The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr). For breast cancer the following substances have been classified as "carcinogenic to humans" (Group 1): alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure). Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification "probably carcinogenic to humans" (Group 2A) includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women.

  17. Genetic factors affecting dental caries risk.

    Science.gov (United States)

    Opal, S; Garg, S; Jain, J; Walia, I

    2015-03-01

    This article reviews the literature on genetic aspects of dental caries and provides a framework for the rapidly changing disease model of caries. The scope is genetic aspects of various dental factors affecting dental caries. The PubMed database was searched for articles with keywords 'caries', 'genetics', 'taste', 'diet' and 'twins'. This was followed by extensive handsearching using reference lists from relevant articles. The post-genomic era will present many opportunities for improvement in oral health care but will also present a multitude of challenges. We can conclude from the literature that genes have a role to play in dental caries; however, both environmental and genetic factors have been implicated in the aetiology of caries. Additional studies will have to be conducted to replicate the findings in a different population. Identification of genetic risk factors will help screen and identify susceptible patients to better understand the contribution of genes in caries aetiopathogenesis. Information derived from these diverse studies will provide new tools to target individuals and/or populations for a more efficient and effective implementation of newer preventive measures and diagnostic and novel therapeutic approaches in the management of this disease.

  18. [Environmental and genetic risk factors for endometrial carcinoma].

    Science.gov (United States)

    Sénéchal, Claire; Cottereau, Edouard; de Pauw, Antoine; Elan, Camille; Dagousset, Isabelle; Fourchotte, Virginie; Gauthier-Villars, Marion; Lae, Marick; Stoppa-Lyonnet, Dominique; Buecher, Bruno

    2015-03-01

    In France, endometrial cancer is at the first rank of gynecological cancers for cancer incidence, before ovarian and cervical cancers. In fact, the number of incident cases has been estimated to 7275 for the year 2012; the number of death due to endometrial cancer to 2025. This cancer is hormone-dependent and endogenous (reproductive factors) or exogenous (oral combined contraceptives, hormone replacement therapy) causes of exposition to estrogens are the major environmental risk factors for both types of endometrial cancers: type I or well-differentiated endometrioid adenocarcinomas; and type II including all other histological types: papillary serous adenocarcinomas, clear cell adenocarcinomas and carcinosarcomas, also known as malignant mixed Mullerian tumor, MMMT. Obesity, diabetes mellitus and adjuvant treatment of breast cancer with tamoxifen are also associated with an increased risk of endometrial cancer. Genetic factors may also be implicated in the pathogenesis of endometrial cancer either as "minor genetic factors" (susceptibility factors), which remain largely unknown and are responsible for the increased observed risk in relatives of women affected with endometrial cancer; or as major genetic factors responsible for hereditary forms and namely for Lynch syndrome whose genetic transmission is of autosomic dominant type. The appropriate recognition of Lynch syndrome is of critical importance because affected patients and their relatives should benefit from specific care. The aims of this review is to describe major environmental and genetic risk factors for endometrial cancer with specific attention to most recent advances in this field and to describe recommendations for care of at-risk women.

  19. Genetic and environmental factors of atopy

    Directory of Open Access Journals (Sweden)

    Akiko Otsu

    2002-01-01

    Full Text Available Atopy is a common immune disorder characterized by raised IgE levels, which lead to clinical disorders (i.e. primarily bronchial asthma, atopic dermatitis and allergic rhinoconjuctivitis. Interleukin (IL-4 and IL-13, derived from T-helper cell type 2 (Th2 subsets, are central in mediating IgE production and development of immediate hypersensitivity. Atopy is also characterized by Th1/Th2 skewing that derives from genetic and environmental factors. The prevalence of atopy has increased in recent decades, especially in developed countries among children and young adults. In the present review, we first discuss the relationship between the Th1/Th2 imbalance and the recent rise of allergy. Second, we present evidence that human genetic variation is also a key factor responsible for atopy.

  20. Environmental and genetic risk factors in obesity.

    Science.gov (United States)

    Hebebrand, Johannes; Hinney, Anke

    2009-01-01

    Because of its high prevalence and the associated medical and psychosocial risks, research into the causes of childhood obesity has experienced a tremendous upswing. Formal genetic data based on twin, adoption, and family studies lead to the conclusion that at least 50% of the interindividual variance of the body mass index (BMI; defined as weight in kilograms divided by height in meters squared) is due to genetic factors. As a result of the recent advent of genome-wide association studies, the first polygenes involved in body weight regulation have been detected. Each of the predisposing alleles explain a few hundred grams of body weight. More polygenes will be detected in the near future, thus for the first time allowing in-depth analyses of gene-gene and gene-environment interactions. They also will enable developmental studies to assess the effect of such alleles throughout childhood and adulthood. The recent increase in obesity prevalence rates illustrates the extreme relevance of environmental factors for body weight. Similar to polygenes, the effect sizes of most such environmental factors are likely to be small, thus rendering their detection difficult. In addition, the validation of the true causality of such factors is not a straightforward task. Important factors are socioeconomic status and television consumption. The authors conclude by briefly assessing implications for treatment and prevention of childhood obesity.

  1. Genetic variation of a global germplasm collection of chickpea (Cicer arietinum L.) including Italian accessions at risk of genetic erosion.

    Science.gov (United States)

    De Giovanni, C; Pavan, S; Taranto, F; Di Rienzo, V; Miazzi, M M; Marcotrigiano, A R; Mangini, G; Montemurro, C; Ricciardi, L; Lotti, C

    2017-01-01

    Chickpea (Cicer arietinum L.) is one of the most important legumes worldwide. We addressed this study to the genetic characterization of a germplasm collection from main chickpea growing countries. Several Italian traditional landraces at risk of genetic erosion were included in the analysis. Twenty-two simple sequence repeat (SSR) markers, widely used to explore genetic variation in plants, were selected and yielded 218 different alleles. Structure analysis and hierarchical clustering indicated that a model with three distinct subpopulations best fits the data. The composition of two subpopulations, named K1 and K2, broadly reflects the commercial classification of chickpea in the two types desi and kabuli, respectively. The third subpopulation (K3) is composed by both desi and kabuli genotypes. Italian accessions group both in K2 and K3. Interestingly, this study highlights genetic distance between desi genotypes cultivated in Asia and Ethiopia, which respectively represent the chickpea primary and the secondary centres of diversity. Moreover, European desi are closer to the Ethiopian gene pool. Overall, this study will be of importance for chickpea conservation genetics and breeding, which is limited by the poor characterization of germplasm collection.

  2. Perinatal risk factors including malformation; Perinatale Risikofaktoren einschliesslich Fehlbildungen

    Energy Technology Data Exchange (ETDEWEB)

    Brachner, A.; Grosche, B.

    1991-10-01

    The study gives a survey of the factors most frequently mentioned in the literature as factors likely to adversely affect a pregnancy. One essential aspect is the discussion of those factors that can be counted among the causes of malformations, as among others, prenatal radiation exposure. The study prepared within the framework of the research project `Radiobiological environmental monitoring in Bavaria` is intended to serve as a basis for a retrospective and prospective evaluation of infant mortality, perinatal conditions and occurrence of malformations in Bavaria, with the principal idea of drawing up an environment - related health survey. The study therefore, in addition to ionizing radiation also takes into account other detectable risks within the ecologic context, as e.g. industrial installations, refuse incineration plants or waste dumps, or urbanity. (orig./MG). [Deutsch] In der vorliegenden Arbeit wird ein Ueberblick ueber die haeufigsten in der Literatur beschriebenen Faktoren, die einen unguenstigen Einfluss auf den Schwangerschaftsverlauf ausueben koennen, gegeben. Ein Hauptgewicht liegt dabei auf der Beschreibung von solchen Faktoren, die mit der Induktion von Fehlbildungen in Zusammenhang gebracht werden koennen, so unter anderem auch der praenatalen Strahlenexposition. Diese Arbeit, die im Rahmen des Forschungsvorhabens `Strahlenbiologisches Umweltmonitoring Bayern` angefertigt wurde, bildet die Grundlage einer im Sinne einer umweltbezogenen Gesundheitsberichterstattung retro- bzw. prospektiv angelegten Auswertung der Saeuglingssterblichkeit, des Perinatalgeschehens und der Fehlbildungshaeufigkeit in Bayern, wobei neben der ionisierenden Strahlung als Risikofaktor auch andere im Rahmen einer oekologischen Studie erfassbare Risiken, wie beispielsweise Industrieansiedlungen, Muellverbrennungsanlagen und -deponien oder Urbanitaet beruecksichtigt werden sollen. (orig./MG).

  3. Genetic and physiological factors affecting repair and mutagenesis in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Lemontt, J F

    1979-01-01

    Current views of DNA repair and mutagenesis in the yeast Saccharomyces cerevisiae are discussed in the light of recent data and with emphasis on the isolation and characterization of genetically well-defined mutations that affect DNA metabolism in general (including replication and recombination). Various pathways of repair are described, particularly in relation to their imvolvement in mutagenic mechanisms. In addition to genetic control, certain physiological factors such as cell age, DNA replication, and the regulatory state of the mating-type locus are shown to also play a role in repair and mutagenesis.

  4. Genetic and physiological factors affecting repair and mutagenesis in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Lemontt, J F

    1979-01-01

    Current views of DNA repair and mutagenesis in the yeast Saccharomyces cerevisiae are discussed in the light of recent data, and with emphasis on the isolation and characterization of genetically well-defined mutations that affect DNA metabolism in general (including replication and recombination). Various pathways of repair are described particularly in relation to their involvement in mutagenic mechanisms. In addition to genetic control, certain physiological factors such as cell age, DNA replication, and the regulatory state of the mating-type locus, are shown to also play a role in repair and mutagenesis.

  5. Factors influencing uptake of familial long QT syndrome genetic testing.

    Science.gov (United States)

    Burns, Charlotte; McGaughran, Julie; Davis, Andrew; Semsarian, Christopher; Ingles, Jodie

    2016-02-01

    Ongoing challenges of clinical assessment of long QT syndrome (LQTS) highlight the importance of genetic testing in the diagnosis of asymptomatic at-risk family members. Effective access, uptake, and communication of genetic testing are critical for comprehensive cascade family screening and prevention of disease complications such as sudden cardiac death. The aim of this study was to describe factors influencing uptake of LQTS genetic testing, including those relating to access and family communication. We show those who access genetic testing are overrepresented by the socioeconomically advantaged, and that although overall family communication is good, there are some important barriers to be addressed. There were 75 participants (aged 18 years or more, with a clinical and/or genetic diagnosis of LQTS; response rate 71%) who completed a survey including a number of validated scales; demographics; and questions about access, uptake, and communication. Mean age of participants was 46 ± 16 years, 20 (27%) were males and 60 (80%) had genetic testing with a causative gene mutation in 42 (70%). Overall uptake of cascade testing within families was 60% after 4 years from proband genetic diagnosis. All participants reported at least one first-degree relative had been informed of their risk, whereas six (10%) reported at least one first-degree relative had not been informed. Those who were anxious or depressed were more likely to perceive barriers to communicating. Genetic testing is a key aspect of care in LQTS families and intervention strategies that aim to improve equity in access and facilitate effective family communication are needed.

  6. Genetics Home Reference: factor X deficiency

    Science.gov (United States)

    ... deficiency occurs in approximately 1 per million individuals worldwide. Related Information What information about a genetic condition can statistics provide? Why are some genetic conditions more common ...

  7. Sleep bruxism - genetic factors and psychoactive substances : Studies in Finnish twins

    OpenAIRE

    Rintakoski, Katariina

    2014-01-01

    Background: Genetic and environmental factors have a varying influence on oral health-related problems. Although studies have been conducted, the contribution of genetic factors to sleep-related bruxism remains obscure. Bruxism causes several physical problems, including abnormal tooth wear, pain in the temporomandibular joint or jaw muscles, and headaches, as well as social problems. The detailed aetiology of bruxism is unknown. In addition to genetic factors, psychoactive substances are con...

  8. GENETIC FACTORS ASSOCIATED WITH AMYOTROPHIC LATERAL SCLEROSIS

    Directory of Open Access Journals (Sweden)

    Katarina Vrabec

    2015-10-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a rare complex neurodegenerative disease characterized by degeneration of motor neurons in the cerebral cortex, brainstem and spinal cord. The disease mainly occurs in adults, typically between 50. and 60. years and presents with symptoms like muscular weakness, atrophy and later on paralysis which lead to death due to respiratory failure within 2-5 years from onset and remains incurable. The symptoms typically start in the muscles of arms or legs (spinal onset or bulbary (bulbar onset. Most ALS cases are sporadic although about 5% are familiar. Genetic factors contribute to the disease in sporadic form as well as in familial form. Mutations have been found in 116 genes among which SOD1, TARDBP, FUS and C9ORF72 are represented in highest frequencies. Besides those four genes we are also describing 13 other genes involved in the disease process. Oligogenic model has been proposed for ALS that considers mutations in two or more genes in one patient. We emphasize the convergence between hereditary and sporadic form, which are clinically inseparable, and other neurodegenerative diseases that share with ALS genetic and clinical characteristics. Because about 2/3 of familial cases and only about 11% of sporadic cases are explained by mutations the research have been aimed at discovering new candidate genes using  genome –wide association studies and at the epigenetic causes of the disease. We have recently completed the first representative genetic analysis of patients with ALS in Slovenia and research on methylation and microRNAs is currently in progress.

  9. Genetic factors in Threatened Species Recovery Plans on three continents

    Science.gov (United States)

    Threatened species' recovery planning is applied globally to stem the current species extinction crisis. Evidence supports a key role of genetic processes, such as inbreeding depression, in determining species viability. We examined whether genetic factors are considered in threa...

  10. Risk factors for Alzheimer's disease : a genetic-epidemiologic study

    NARCIS (Netherlands)

    C.M. van Duijn (Cock)

    1992-01-01

    textabstractThe work presented in this thesis has been motivated by the Jack of knowledge of risk factors for Alzheimer's disease. It has been long recognised that genetic factors are implicated, in particular in early-onset Alzheimer's disease.4 But to what extent are genetic factors involved? Are

  11. The ontology of genetic susceptibility factors (OGSF) and its application in modeling genetic susceptibility to vaccine adverse events.

    Science.gov (United States)

    Lin, Yu; He, Yongqun

    2014-01-01

    Due to human variations in genetic susceptibility, vaccination often triggers adverse events in a small population of vaccinees. Based on our previous work on ontological modeling of genetic susceptibility to disease, we developed an Ontology of Genetic Susceptibility Factors (OGSF), a biomedical ontology in the domain of genetic susceptibility and genetic susceptibility factors. The OGSF framework was then applied in the area of vaccine adverse events (VAEs). OGSF aligns with the Basic Formal Ontology (BFO). OGSF defines 'genetic susceptibility' as a subclass of BFO:disposition and has a material basis 'genetic susceptibility factor'. The 'genetic susceptibility to pathological bodily process' is a subclasses of 'genetic susceptibility'. A VAE is a type of pathological bodily process. OGSF represents different types of genetic susceptibility factors including various susceptibility alleles (e.g., SNP and gene). A general OGSF design pattern was developed to represent genetic susceptibility to VAE and associated genetic susceptibility factors using experimental results in genetic association studies. To test and validate the design pattern, two case studies were populated in OGSF. In the first case study, human gene allele DBR*15:01 is susceptible to influenza vaccine Pandemrix-induced Multiple Sclerosis. The second case study reports genetic susceptibility polymorphisms associated with systemic smallpox VAEs. After the data of the Case Study 2 were represented using OGSF-based axioms, SPARQL was successfully developed to retrieve the susceptibility factors stored in the populated OGSF. A network of data from the Case Study 2 was constructed by using ontology terms and individuals as nodes and ontology relations as edges. Different social network analys is (SNA) methods were then applied to verify core OGSF terms. Interestingly, a SNA hub analysis verified all susceptibility alleles of SNPs and a SNA closeness analysis verified the susceptibility genes in Case

  12. Shared Genetic Factors Influence Amygdala Volumes and Risk for Alcoholism

    Science.gov (United States)

    Dager, Alecia D; McKay, D Reese; Kent, Jack W; Curran, Joanne E; Knowles, Emma; Sprooten, Emma; Göring, Harald HH; Dyer, Thomas D; Pearlson, Godfrey D; Olvera, Rene L; Fox, Peter T; Lovallo, William R; Duggirala, Ravi; Almasy, Laura; Blangero, John; Glahn, David C

    2015-01-01

    Alcohol abuse and dependence (alcohol use disorders, AUDs) are associated with brain shrinkage. Subcortical structures including the amygdala, hippocampus, ventral striatum, dorsal striatum, and thalamus subserve reward functioning and may be particularly vulnerable to alcohol-related damage. These structures may also show pre-existing deficits impacting the development and maintenance of AUD. It remains unclear whether there are common genetic features underlying both subcortical volumes and AUD. In this study, structural brain images were acquired from 872 Mexican-American individuals from extended pedigrees. Subcortical volumes were obtained using FreeSurfer, and quantitative genetic analyses were performed in SOLAR. We hypothesized the following: (1) reduced subcortical volumes in individuals with lifetime AUD relative to unrelated controls; (2) reduced subcortical volumes in individuals with current relative to past AUD; (3) in non-AUD individuals, reduced subcortical volumes in those with a family history of AUD compared to those without; and (4) evidence for common genetic underpinnings (pleiotropy) between AUD risk and subcortical volumes. Results showed that individuals with lifetime AUD showed larger ventricular and smaller amygdala volumes compared to non-AUD individuals. For the amygdala, there were no differences in volume between current vs past AUD, and non-AUD individuals with a family history of AUD demonstrated reductions compared to those with no such family history. Finally, amygdala volume was genetically correlated with the risk for AUD. Together, these results suggest that reduced amygdala volume reflects a pre-existing difference rather than alcohol-induced neurotoxic damage. Our genetic correlation analysis provides evidence for a common genetic factor underlying both reduced amygdala volumes and AUD risk. PMID:25079289

  13. Shared genetic factors influence amygdala volumes and risk for alcoholism.

    Science.gov (United States)

    Dager, Alecia D; McKay, D Reese; Kent, Jack W; Curran, Joanne E; Knowles, Emma; Sprooten, Emma; Göring, Harald H H; Dyer, Thomas D; Pearlson, Godfrey D; Olvera, Rene L; Fox, Peter T; Lovallo, William R; Duggirala, Ravi; Almasy, Laura; Blangero, John; Glahn, David C

    2015-01-01

    Alcohol abuse and dependence (alcohol use disorders, AUDs) are associated with brain shrinkage. Subcortical structures including the amygdala, hippocampus, ventral striatum, dorsal striatum, and thalamus subserve reward functioning and may be particularly vulnerable to alcohol-related damage. These structures may also show pre-existing deficits impacting the development and maintenance of AUD. It remains unclear whether there are common genetic features underlying both subcortical volumes and AUD. In this study, structural brain images were acquired from 872 Mexican-American individuals from extended pedigrees. Subcortical volumes were obtained using FreeSurfer, and quantitative genetic analyses were performed in SOLAR. We hypothesized the following: (1) reduced subcortical volumes in individuals with lifetime AUD relative to unrelated controls; (2) reduced subcortical volumes in individuals with current relative to past AUD; (3) in non-AUD individuals, reduced subcortical volumes in those with a family history of AUD compared to those without; and (4) evidence for common genetic underpinnings (pleiotropy) between AUD risk and subcortical volumes. Results showed that individuals with lifetime AUD showed larger ventricular and smaller amygdala volumes compared to non-AUD individuals. For the amygdala, there were no differences in volume between current vs past AUD, and non-AUD individuals with a family history of AUD demonstrated reductions compared to those with no such family history. Finally, amygdala volume was genetically correlated with the risk for AUD. Together, these results suggest that reduced amygdala volume reflects a pre-existing difference rather than alcohol-induced neurotoxic damage. Our genetic correlation analysis provides evidence for a common genetic factor underlying both reduced amygdala volumes and AUD risk.

  14. Genetics Home Reference: factor V Leiden thrombophilia

    Science.gov (United States)

    ... Conditions factor V Leiden thrombophilia factor V Leiden thrombophilia Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Factor V Leiden thrombophilia is an inherited disorder of blood clotting . Factor ...

  15. Motivating factors for physician ordering of factor V Leiden genetic tests.

    Science.gov (United States)

    Hindorff, Lucia A; Burke, Wylie; Laberge, Anne-Marie; Rice, Kenneth M; Lumley, Thomas; Leppig, Kathleen; Rosendaal, Frits R; Larson, Eric B; Psaty, Bruce M

    2009-01-12

    The factor V Leiden (FVL) genetic test is used by many physicians despite its uncertain clinical utility. We investigate whether self-reported motivations and behaviors concerning FVL genetic testing differ between 2 groups of primary care physicians defined by frequency of previous FVL test use. In January 2007, 112 physicians (60 frequent and 52 infrequent FVL test users) at Group Health, a large health care delivery system, were surveyed. Survey content areas included primary reasons and motivating factors for ordering the FVL test, the likelihood of ordering the FVL test for hypothetical patients, potential barriers to genetic testing, and practices and skills regarding FVL test ordering. Responses between groups agreed concerning most clinical- and patient-related factors. Frequent-FVL physicians were more likely than infrequent-FVL physicians to report ordering the FVL test for hypothetical patients with mesenteric venous thrombosis (adjusted odds ratio, 4.57; 95% confidence interval, 1.55-13.53) or venous thrombosis after hospital discharge (adjusted odds ratio, 3.42; 95% confidence interval, 1.30-8.95). Frequent-FVL physicians were also less likely to identify several items on the survey as barriers to genetic testing and were more likely to report high confidence in interpreting and explaining FVL test results. Generally, both physician groups reported similar motivating factors for ordering FVL tests, and reported behaviors were consistent with existing guidelines. More striking differences were observed for measures such as barriers to and confidence in using genetic tests. Although additional research is necessary to evaluate the impact of these results, they inform several knowledge-to-practice translation issues that are important for the successful integration of genetic testing into primary care.

  16. Motivating factors for physician ordering of Factor V Leiden genetic tests

    Science.gov (United States)

    Hindorff, Lucia A.; Burke, Wylie; Laberge, Anne-Marie; Rice, Kenneth M.; Lumley, Thomas; Leppig, Kathleen; Rosendaal, Frits R.; Larson, Eric B.; Psaty, Bruce M.

    2009-01-01

    Background The Factor V Leiden (FVL) genetic test is used by many physicians despite its uncertain clinical utility. This study investigated whether self-reported motivations and behaviors concerning FVL genetic testing differed between two groups of primary care physicians defined by frequency of prior FVL test use. Methods In January 2007, 112 primary care physicians (60 frequent, 52 infrequent FVL test users) at Group Health, a large health care delivery system, were surveyed. Survey content areas included: primary reasons and motivating factors for ordering FVL; likelihood of ordering FVL for hypothetical patients; potential barriers to genetic testing, and practices and skills regarding FVL test ordering. Results Responses between groups agreed concerning most clinical- or patient-related factors. Frequent-FVL physicians were more likely than infrequent-FVL physicians to report ordering FVL for hypothetical patients with mesenteric venous thrombosis (adjusted OR 4.57, 95% CI 1.55, 13.53) or venous thrombosis following hospital discharge (adjusted OR 3.42, 95% CI 1.30, 8.95). Frequent-FVL physicians were also less likely to agree with several potential barriers to genetic testing and more likely to report high confidence in interpreting and explaining FVL test results. Conclusions Generally, both groups of physicians reported similar motivating factors for ordering FVL, and reported behaviors were consistent with existing guidelines. More striking differences were observed for measures such as barriers to and confidence in using genetic tests. Though additional research is necessary to evaluate their impact, these results inform several knowledge-to-practice translation issues that are important to the successful integration of genetic testing into primary care. PMID:19139326

  17. Analysis of genetics and risk factors of Alzheimer's Disease.

    Science.gov (United States)

    Panpalli Ates, M; Karaman, Y; Guntekin, S; Ergun, M A

    2016-06-14

    Alzheimer's Disease is the leading neurodegenerative cause of dementia. The pathogenesis is not clearly understood yet, is believed to be the complex interaction between genetic and environmental factors. Consequently vascular risk factors and Apolipoprotein E genotyping are increasingly gaining importance. This study aimed at assessing the relationships between Alzheimer's Disease and Apolipoprotein E phenotype and vascular risk factors. Patients diagnosed with "possible Alzheimer's Disease" in the Gazi University, Department of Neurology, were included in the study and age-matched volunteer patients who attended the polyclinic were included as a control group. In this study, the risk factors including low education level, smoking, hyperlipidemia, higher serum total cholesterol levels, and hyperhomocysteinemia were found to be statistically significantly more common in the Alzheimer's Disease group in comparison to the Control Group, while all Apolipoprotein E ε4/ε4 genotypes were found in the Alzheimer's Disease group. The presence of the Apolipoprotein E ε4 allele is believed to increase vascular risk factors as well as to affect Alzheimer's Disease directly. The biological indicators which are used in identifying the patients' genes will be probably used in the treatment plan of the patients in the future.

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

    Science.gov (United States)

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

    2009-10-01

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

  19. Stochastic dynamic simulation modeling including multitrait genetics to estimate genetic, technical, and financial consequences of dairy farm reproduction and selection strategies

    Science.gov (United States)

    The objective of this study was to develop a daily stochastic dynamic dairy simulation model which included multi-trait genetics, and to evaluate the effects of various reproduction and selection strategies on the genetic, technical and financial performance of a dairy herd. The 12 correlated geneti...

  20. Pathogenesis of coronary artery disease: focus on genetic risk factors and identification of genetic variants

    Directory of Open Access Journals (Sweden)

    Sayols-Baixeras S

    2014-01-01

    Full Text Available Sergi Sayols-Baixeras, Carla Lluís-Ganella, Gavin Lucas, Roberto ElosuaCardiovascular Epidemiology and Genetics Research Group, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, SpainAbstract: Coronary artery disease (CAD is the leading cause of death and disability worldwide, and its prevalence is expected to increase in the coming years. CAD events are caused by the interplay of genetic and environmental factors, the effects of which are mainly mediated through cardiovascular risk factors. The techniques used to study the genetic basis of these diseases have evolved from linkage studies to candidate gene studies and genome-wide association studies. Linkage studies have been able to identify genetic variants associated with monogenic diseases, whereas genome-wide association studies have been more successful in determining genetic variants associated with complex diseases. Currently, genome-wide association studies have identified approximately 40 loci that explain 6% of the heritability of CAD. The application of this knowledge to clinical practice is challenging, but can be achieved using various strategies, such as genetic variants to identify new therapeutic targets, personal genetic information to improve disease risk prediction, and pharmacogenomics. The main aim of this narrative review is to provide a general overview of our current understanding of the genetics of coronary artery disease and its potential clinical utility.Keywords: coronary artery disease, pathogenesis, genetic risk factors, genetic variants

  1. Genetics and behavioral medicine: Risk factors for cardiovascular disease

    NARCIS (Netherlands)

    Vogler, G.P.; McClearn, G.E.; Snieder, H.; Boomsma, D.I.; Palmer, R.; Knijff, P. de; Slagboom, P.E.

    1997-01-01

    This is the second in a series of three articles addressing the intersection of interests in behavioral genetics and behavioral medicine. In this article, we use risk factors for cardiovascular disease as a prototypical trait for which behavioral genetic approaches provide powerful tools for underst

  2. Genetics and behavioral medicine: Risk factors for cardiovascular disease

    NARCIS (Netherlands)

    Vogler, G.P.; McClearn, G.E.; Snieder, H.; Boomsma, D.I.; Palmer, R.; Knijff, P. de; Slagboom, P.E.

    1997-01-01

    This is the second in a series of three articles addressing the intersection of interests in behavioral genetics and behavioral medicine. In this article, we use risk factors for cardiovascular disease as a prototypical trait for which behavioral genetic approaches provide powerful tools for

  3. Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors

    Directory of Open Access Journals (Sweden)

    Neragi-Miandoab Siyamek

    2008-01-01

    Full Text Available Abstract Malignant pleural mesothelioma (MPM is a rare, aggressive tumor for which no effective therapy exists despite the discovery of many possible molecular and genetic targets. Many risk factors for MPM development have been recognized including environmental exposures, genetic susceptibility, viral contamination, and radiation. However, the late stage of MPM diagnosis and the long latency that exists between some exposures and diagnosis have made it difficult to comprehensively evaluate the role of risk factors and their downstream molecular effects. In this review, we discuss the current molecular and genetic contributors in MPM pathogenesis and the risk factors associated with these carcinogenic processes.

  4. Risk factors for amyotrophic lateral sclerosis : Lifestyle, environment and genetics

    NARCIS (Netherlands)

    Seelen, M.

    2015-01-01

    In this thesis the results of studies aiming to identify risk factors for amyotrophic lateral sclerosis (ALS) are described. A population-based case-control design was used to perform (1) epidemiological risk factor studies, examining lifestyle factors and environmental exposures, and (2) genetic st

  5. Risk factors for amyotrophic lateral sclerosis : Lifestyle, environment and genetics

    NARCIS (Netherlands)

    Seelen, M.

    2015-01-01

    In this thesis the results of studies aiming to identify risk factors for amyotrophic lateral sclerosis (ALS) are described. A population-based case-control design was used to perform (1) epidemiological risk factor studies, examining lifestyle factors and environmental exposures, and (2) genetic st

  6. Obesity in childhood and adolescence, genetic factors.

    Science.gov (United States)

    Memedi, Rexhep; Tasic, Velibor; Nikolic, Erieta; Jancevska, Aleksandra; Gucev, Zoran

    2013-01-01

    Obesity and overweight are a pandemic phenomenon in the modern world. Childhood and adolescent obesity often ends up in obesity in adults. The costs of obesity and its consequences are staggering for any society, crippling for countries in development. The etiology is complex, but most often idiopathic. Hormonal, syndromic and medication-induced obesity are well investigated. Genetic causes are increasingly described. Novel technologies such as whole exome sequencing identify ever more candidate genes influencing or causing obesity. All insights into the complex problem of obesity in a team approach to treatment: diet, psychology, medications and surgery. We briefly review epidemiology, etiology, consequences and treatment approaches in childhood and adolescent obesity, with special emphasis on emerging knowledge of its genetics.

  7. Environmental and genetical factors in airway allergies

    OpenAIRE

    Katarzyna Idzik

    2012-01-01

    It is estimated that approximately 23% of the European population is clinically diagnosed with allergies. In the past three decades, an increase in the incidence of respiratory allergies was noted. At the beginning of the 20th century allergic inflammations affected only around 1% of the world population. Medical symptoms of allergic airway inflammation are variable for different patients. Airways allergy are complex phenotypes, which are determined by both genetic and...

  8. Genetic, molecular and functional analyses of complement factor I deficiency

    DEFF Research Database (Denmark)

    Nilsson, S.C.; Trouw, L.A.; Renault, N.;

    2009-01-01

    Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three...

  9. Genetic factors involves in intracranial aneurysms--actualities

    National Research Council Canada - National Science Library

    Mohan, D; Munteanu, V; Coman, T; Ciurea, A V

    2015-01-01

    ...% of all IAs in the population. Cerebral aneurysm disease is related to hemodynamic and genetic factors, associated with structural weakness in the arterial wall, which was acquired by a specific, often unknown, event...

  10. Is Ankyrin a genetic risk factor for psychiatric phenotypes?

    Directory of Open Access Journals (Sweden)

    Stöber Gerald

    2011-06-01

    Full Text Available Abstract Background Genome wide association studies reported two single nucleotide polymorphisms in ANK3 (rs9804190 and rs10994336 as independent genetic risk factors for bipolar disorder. Another SNP in ANK3 (rs10761482 was associated with schizophrenia in a large European sample. Within the debate on common susceptibility genes for schizophrenia and bipolar disorder, we tried to investigate common findings by analyzing association of ANK3 with schizophrenia, bipolar disorder and unipolar depression. Methods We genotyped three single nucleotide polymorphisms (SNPs in ANK3 (rs9804190, rs10994336, and rs10761482 in a case-control sample of German descent including 920 patients with schizophrenia, 400 with bipolar affective disorder, 220 patients with unipolar depression according to ICD 10 and 480 healthy controls. Sample was further differentiated according to Leonhard's classification featuring disease entities with specific combination of bipolar and psychotic syndromes. Results We found no association of rs9804190 and rs10994336 with bipolar disorder, unipolar depression or schizophrenia. In contrast to previous findings rs10761482 was associated with bipolar disorder (p = 0.015 but not with schizophrenia or unipolar depression. We observed no association with disease entities according to Leonhard's classification. Conclusion Our results support a specific genetic contribution of ANK3 to bipolar disorder though we failed to replicate findings for schizophrenia. We cannot confirm ANK3 as a common risk factor for different diseases.

  11. Biology, Genetics, and Environment: Underlying Factors Influencing Alcohol Metabolism.

    Science.gov (United States)

    Wall, Tamara L; Luczak, Susan E; Hiller-Sturmhöfel, Susanne

    2016-01-01

    Gene variants encoding several of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence. Certain genetic variants (i.e., alleles)--particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles--have been associated with lower rates of alcohol dependence. These alleles may lead to an accumulation of acetaldehyde during alcohol metabolism, which can result in heightened subjective and objective effects. The prevalence of these alleles differs among ethnic groups; ADH1B*2 is found frequently in northeast Asians and occasionally Caucasians, ADH1B*3 is found predominantly in people of African ancestry, ADH1C*1 varies substantially across populations, and ALDH2*2 is found almost exclusively in northeast Asians. Differences in the prevalence of these alleles may account at least in part for ethnic differences in alcohol consumption and alcohol use disorder (AUD). However, these alleles do not act in isolation to influence the risk of AUD. For example, the gene effects of ALDH2*2 and ADH1B*2 seem to interact. Moreover, other factors have been found to influence the extent to which these alleles affect a person's alcohol involvement, including developmental stage, individual characteristics (e.g., ethnicity, antisocial behavior, and behavioral undercontrol), and environmental factors (e.g., culture, religion, family environment, and childhood adversity).

  12. Common Genetic and Nonshared Environmental Factors Contribute to the Association between Socioemotional Dispositions and the Externalizing Factor in Children

    Science.gov (United States)

    Taylor, Jeanette; Allan, Nicholas; Mikolajewski, Amy J.; Hart, Sara A.

    2013-01-01

    Background: Childhood behavioral disorders including conduct disorder (CD), oppositional defiant disorder (ODD), and attention-deficit/hyperactivity disorder (ADHD) often co-occur. Prior twin research shows that common sets of genetic and environmental factors are associated with these various disorders and they form a latent factor called…

  13. Orthodontic Treatment, Genetic Factors and Risk of Temporomandibular Disorder

    OpenAIRE

    Slade, Gary D.; Diatchenko, Luda; Ohrbach, Richard; Maixner, William

    2008-01-01

    Traditionally, four groups of factors have been identified in the etiology of temporomandibular disorder (TMD): anatomical variation in the masticatory system; psychosocial characteristics; pain in other body regions; and demographics. Orthodontic treatment has been variously cited both as a protective and harmful factor in TMD etiology. Recently, a search has begun for a genetic influence on TMD etiology. Genetic markers can be of additional value in identifying gene-environment interactions...

  14. [Genetic and epigenetic factors of polycystic ovary syndrome].

    Science.gov (United States)

    Herczeg, Zita; Vanya, Melinda; Szili, Károly; Dézsi, Csilla; Nagy, Zsolt; Szabó, János

    2016-08-01

    The development of polycystic ovary syndrome and its exact pathophysiological mechanism is still unclear, but environmental and genetic factors likely play a role. Exposition to teratogenic effects during the prenatal development can lead to chronic diseases in the postnatal period. This finding confirms the common familial aggregation as well. A literature search was conducted up to January 1, 2016 for articles dealing with the genetic or epigenetic factors of polycystic ovary syndrome. This review will discuss the current understanding of the genetic basis and clinical presentation of this disease. Orv. Hetil., 2016, 157(32), 1275-1281.

  15. Influence Factors on Consumers’ Cognition Level to Genetically Modified Food-taking Huangshi as an Example

    OpenAIRE

    Ruishan Chen; Yazhou Xiong; Jing Mo

    2015-01-01

    This study aims to analyze the influence factors on consumers’ cognition level to genetically modified food and improve the consumers’ cognition level. In recent years, genetically modified foods in people’s daily life are becoming more and more common, but there is a lot of controversy about them. Based on the analysis of influence factors on consumers’ cognition level to GMF, a comprehensive system is established from four aspects, including the consumers’ personal characteristics, social-e...

  16. Thrombosis and inflammatory bowel disease-the role of genetic risk factors

    Institute of Scientific and Technical Information of China (English)

    Georgia Tsiolakidou; Ioannis E Koutroubakis

    2008-01-01

    Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel dis-ease (IBD). Recent data suggest thromboembolism as a disease-specific extraintestinal manifestation of IBD,which is developed as the result of multiple interac-tions between acquired and genetic risk factors. There is evidence indicating an imbalance of procoagulant,anticoagulant and fibrinolitic factors predisposing in thrombosis in patients with IBD. The genetic factors that have been suggested to interfere in the thrombotic manifestations of IBD include factor V Leiden, factor Ⅱ (prothrombin, G20210A), methylenetetrahydrofolate reductase gene mutation (MTHFR, 6777T), plasminogen activator inhibitor type 1 (PAI-1) gene mutation and fac-tor ⅩⅢ (va1341eu). In this article we review the current data and future prospects on the role of genetic risk factors in the development of thromboembolism in IBD.

  17. Genetics Home Reference: factor VII deficiency

    Science.gov (United States)

    ... VII deficiency , is caused by mutations in the F7 gene, which provides instructions for making a protein ... about the gene associated with factor VII deficiency F7 Related Information What is a gene? What is ...

  18. The structure of genetic and environmental risk factors for fears and phobias.

    Science.gov (United States)

    Loken, E K; Hettema, J M; Aggen, S H; Kendler, K S

    2014-08-01

    Although prior genetic studies of interview-assessed fears and phobias have shown that genetic factors predispose individuals to fears and phobias, they have been restricted to the DSM-III to DSM-IV aggregated subtypes of phobias rather than to individual fearful and phobic stimuli. We examined the lifetime history of fears and/or phobias in response to 21 individual phobic stimuli in 4067 personally interviewed twins from same-sex pairs from the Virginia Adult Twin Study of Psychiatric and Substance Abuse Disorders (VATSPSUD). We performed multivariate statistical analyses using Mx and Mplus. The best-fitting model for the 21 phobic stimuli included four genetic factors (agora-social-acrophobia, animal phobia, blood-injection-illness phobia and claustrophobia) and three environmental factors (agora-social-hospital phobia, animal phobia, and situational phobia). This study provides the first view of the architecture of genetic and environmental risk factors for phobic disorders and their subtypes. The genetic factors of the phobias support the DSM-IV and DSM-5 constructs of animal and blood-injection-injury phobias but do not support the separation of agoraphobia from social phobia. The results also do not show a coherent genetic factor for the DSM-IV and DSM-5 situational phobia. Finally, the patterns of co-morbidity across individual fears and phobias produced by genetic and environmental influences differ appreciably.

  19. Progress in the identification of genetic factors in periodontitis

    NARCIS (Netherlands)

    Laine, M.L.; Jepsen, S.; Loos, B.G.

    2014-01-01

    The susceptibility to periodontitis is determined by a complex interplay between bacteria, the immune system, and life-style factors, and is mainly regulated by genes. The genetic factors contributing to the pathogenesis of periodontitis are still not fully defined. The aim of the present review is

  20. Genetic and environmental factors affecting the coumarin anticoagulant level

    NARCIS (Netherlands)

    L.E. Visser (Loes)

    2004-01-01

    textabstractThis introductory chapter has illustrated that various factors, such as genetic factors, drugs, diet and intercurrent diseases may affect anticoagulation levels. Most of the clinical and pharmacological data related to coumarin anticoagulants have so far been obtained from studying warfa

  1. Genetic inflammatory factors predict restenosis after percutaneous coronary interventions

    NARCIS (Netherlands)

    Monraats, PS; Pires, NMM; Agema, WRP; Zwinderman, AH; Schepers, A; de Maat, MPM; Doevendans, PA; de Winter, RJ; Tio, RA; Waltenberger, J; Frants, RR; Quax, PHA; van Vlijmen, BJM; Atsma, DE; van der Laarse, A; van der Wall, EE; Jukema, JW

    2005-01-01

    Background - Restenosis is a negative effect of percutaneous coronary intervention (PCI). No clinical factors are available that allow good risk stratification. However, evidence exists that genetic factors are important in the restenotic process as well as in the process of inflammation, a pivotal

  2. Progress in the identification of genetic factors in periodontitis

    NARCIS (Netherlands)

    Laine, M.L.; Jepsen, S.; Loos, B.G.

    2014-01-01

    The susceptibility to periodontitis is determined by a complex interplay between bacteria, the immune system, and life-style factors, and is mainly regulated by genes. The genetic factors contributing to the pathogenesis of periodontitis are still not fully defined. The aim of the present review is

  3. The Genetic Basis of the Polycystic Ovary Syndrome: A Literature Review Including Discussion of PPAR-γ

    OpenAIRE

    Cetin Kocaefe; Yildiz, Bulent O.; Ugur Unluturk; Ayla Harmanci

    2007-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of the women of reproductive age. Familial clustering of PCOS has been consistently reported suggesting that genetic factors play a role in the development of the syndrome although PCOS cases do not exhibit a clear pattern of Mendelian inheritance. It is now well established that PCOS represents a complex trait similar to type-2 diabetes and obesity, and that both inherited and environmental factors contribute to the PCOS ...

  4. Genetics Home Reference: factor XI deficiency

    Science.gov (United States)

    ... common feature of factor XI deficiency is prolonged bleeding after trauma or surgery, especially involving the inside of the mouth and ... nasal cavities ) or the urinary tract . If the bleeding is left untreated after surgery, solid swellings consisting of congealed blood (hematomas) can ...

  5. Genetic risk factors of cisplatin induced ototoxicity in adult patients.

    Science.gov (United States)

    Talach, T; Rottenberg, J; Gal, B; Kostrica, R; Jurajda, M; Kocak, I; Lakomy, R; Vogazianos, E

    2016-01-01

    Ototoxicity is an important adverse effect of using Cisplatin (cis-diamminedichloroplatinum) (CDDP) as a form of chemotherapy. The clinical picture of CDDP induced ototoxicity includes perceptive hearing impairment (reversible or permanent) and tinnitus. Ototoxicity manifests with considerable variability between patients. The objective of this prospective study was to investigate a possible genetic background to this variability. We assessed ototoxicity induced by therapeutic doses of CDDP in adult patients with germinative testicular tumors, or other tumors treated with an identical CDDP dosage scheme. Audiological examination before, during and after the treatment has shown deterioration in hearing; first in the high-frequencies and with increased CDDP cumulative doses, impairment in other frequencies as well. Occurrence of tinnitus was not dependent on the administered dose of CDDP, or the other risk factors examined in this study. The association of CDDP induced ototoxicity with genetic polymorphisms in candidate genes was examined. Our study has demonstrated an association of early onset of CDDP induced ototoxicity with the presence of two copies of GSTT1 gene (p=0,009) and with T allele of rs9332377 polymorphism in COMT gene (p=0,001).

  6. The epidemiology of eating disorders: genetic, environmental, and societal factors

    Directory of Open Access Journals (Sweden)

    Mitchison D

    2014-02-01

    Full Text Available Deborah Mitchison,1 Phillipa J Hay2,3 1School of Medicine, University of Western Sydney, Sydney, NSW, Australia; 2Centre for Health Research, School of Medicine, University of Western Sydney, Sydney, NSW, Australia; 3School of Medicine, James Cook University, Townsville City, QLD, Australia Background: The aim of this review was to summarize the literature to date regarding the sociodemographic, environmental, and genetic correlates of eating disorders (EDs in adults. Method: A keyword search was entered into Scopus (SciVerse, Elsevier to identify relevant articles published in English up until June 2013. Articles were assessed against a range of a priori inclusion and exclusion criteria. Results: A total of 149 full-text articles were found to be eligible for the review and included 86 articles with data on sociodemographic correlates, 57 on environmental correlates, and 13 on genetic correlates. Female sex, younger age, sexual and physical abuse, participation in esthetic or weight-oriented sports, and heritability were found to be most consistently associated with higher ED prevalence and incidence. Conversely, ethnicity, socioeconomic status, education, and urbanicity did not appear to have strong associations with ED epidemiology. Conclusion: More community-based research, with an equal representation of males, needs to be conducted to confirm the current findings and provide evidence for emerging factors that may be related to EDs. Keywords: demographic, environment, abuse, prevalence, socioeconomic status, heritability

  7. Analysis of genetic and non genetic risk factors for cisplatin ototoxicity in pediatric patients.

    Science.gov (United States)

    Olgun, Yüksel; Aktaş, Safiye; Altun, Zekiye; Kırkım, Günay; Kızmazoğlu, Deniz Çakır; Erçetin, Ayşe Pınar; Demir, Banu; İnce, Dilek; Mutafoğlu, Kamer; Demirağ, Bengü; Ellidokuz, Hülya; Olgun, Nur; Güneri, Enis Alpin

    2016-11-01

    The aim of this study was to analyse the genetic and non genetic risk factors for cisplatin ototoxicity. This study was conducted on 72 children who received cisplatin based chemotherapy. Brock and Muenster classifications were used to evaluate ototoxicity seen in these children. 6 single nucleotide polymorphisms (SNP); ERCC1 rs 11615, GSTP1 rs1138272, GSTP1 rs1695, LRP2 rs 2075252, TPMT rs 12201199, COMT rs 9332377, were evaluated as genetic factors by real time PCR. Non genetic factors such as cranial irradiation, cumulative doses of cisplatin, age, gender, administration of other ototoxic drugs were analysed as well. By using Chi-square test, risk factors were matched with the ototoxicity classifications. Significant risk factors were reevaluated using logistic regression modelling. According to univariate analyses, male gender, co-treatment with aminoglycosides and mutant genotype of GSTP1 rs1695 were significantly related with cisplatin ototoxicity. Logistic regression modelling analyses also showed that male gender, co-treatment with aminoglycosides were found to be significantly related with cisplatin ototoxicity. Mutant genotype of GSTP1 rs1695 was not found to be significant, but close to the level of statistical significance. Male gender, co-treatment with aminoglycosides are significant risk factors for cisplatin ototoxicity in pediatric patients. Mutant genotype of GSTP1 rs1695 seems to be a genetic risk factor in univariate analyses, although not confirmed by multivariate analyses. Therefore, GSTP1 rs1695 SNP needs to be studied in larger series. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Short communication. An improved intersubspecific genetic map in Lens including functional markers

    Directory of Open Access Journals (Sweden)

    R. de la Puente

    2012-12-01

    Full Text Available A previous Lens genetic map was improved by adding 31 molecular genetic markers, reaching a total of 190 markers with undistorted segregation. Data were obtained from the segregational analysis of 113 F2 plants generated from a single hybrid of Lens culinaris ssp. culinaris × L. c. ssp. orientalis. The added markers are predominantly codominant (15 SSRs, five CAPSs, four presence-absence polymorphisms, three length polymorphisms, two RAPDs, and two SRAPs. At a LOD score of 3.0, the 190 markers were grouped into eight linkage groups (LG covering 2,234.4 cM, with an average distance between markers of 12.28 cM. This linkage map has reduced the numbers of linkage groups from ten in the previous map to eight. Most of the added markers must be functional markers since primers were mostly designed to amplify transcribed sequences. Some of the amplicons were sequenced to test if they were functional markers. One of the sequences showed homology with the Pisum TFL1a gene, involved in the transition from vegetative to flowering stages. This lentil gene was located in the LG 1 thanks to the presence of a polymorphic microsatellite in the first intron of the gene. Since L. culinaris ssp. orientalis is the primary source of additional genetic variability for lentil, this improved map could help in the use of such variability in lentil breeding programs.

  9. Genetic Factors in Systemic Lupus Erythematosus: Contribution to Disease Phenotype

    Science.gov (United States)

    Ceccarelli, Fulvia; Perricone, Carlo; Borgiani, Paola; Ciccacci, Cinzia; Rufini, Sara; Cipriano, Enrica; Alessandri, Cristiano; Spinelli, Francesca Romana; Sili Scavalli, Antonio; Novelli, Giuseppe; Valesini, Guido; Conti, Fabrizio

    2015-01-01

    Genetic factors exert an important role in determining Systemic Lupus Erythematosus (SLE) susceptibility, interplaying with environmental factors. Several genetic studies in various SLE populations have identified numerous susceptibility loci. From a clinical point of view, SLE is characterized by a great heterogeneity in terms of clinical and laboratory manifestations. As widely demonstrated, specific laboratory features are associated with clinical disease subset, with different severity degree. Similarly, in the last years, an association between specific phenotypes and genetic variants has been identified, allowing the possibility to elucidate different mechanisms and pathways accountable for disease manifestations. However, except for Lupus Nephritis (LN), no studies have been designed to identify the genetic variants associated with the development of different phenotypes. In this review, we will report data currently known about this specific association. PMID:26798662

  10. Genetic and epigenetic factors: Role in male infertility

    Directory of Open Access Journals (Sweden)

    M B Shamsi

    2011-01-01

    Full Text Available Genetic factors contribute upto 15%-30% cases of male infertility. Formation of spermatozoa occurs in a sequential manner with mitotic, meiotic, and postmeiotic differentiation phases each of which is controlled by an intricate genetic program. Genes control a variety of physiologic processes, such as hypothalamus-pituitary-gonadal axis, germ cell development, and differentiation. In the era of assisted reproduction technology, it is important to understand the genetic basis of infertility to provide maximum adapted therapeutics and counseling to the couple.

  11. Genetic factors associated with the development of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Crohn's disease (CD) and ulcerative colitis (UC) are complex polygenic disorders, characterized by several genes together with environmental factors contributing to the development of inflammatory bowel disease (IBD). Recent advances in research on genetic susceptibility have allowed the identification of diverse genes at different levels: (1) Innate immunity; (2) Antigen presentation molecules; (3) Epithelial integrity; (4) Drug transporter; (5) Cell adhesion. The application of genetic testing into clinical practice is close and all genetic markers may have several clinical implications: prediction of disease phenotype, molecular classification, prevention of complications, and prognosis.

  12. Prevention of carcinogen and inflammation-induced dermal cancer by oral rapamycin includes reducing genetic damage.

    Science.gov (United States)

    Dao, Vinh; Pandeswara, Srilakshmi; Liu, Yang; Hurez, Vincent; Dodds, Sherry; Callaway, Danielle; Liu, Aijie; Hasty, Paul; Sharp, Zelton D; Curiel, Tyler J

    2015-05-01

    Cancer prevention is a cost-effective alternative to treatment. In mice, the mTOR inhibitor rapamycin prevents distinct spontaneous, noninflammatory cancers, making it a candidate broad-spectrum cancer prevention agent. We now show that oral microencapsulated rapamycin (eRapa) prevents skin cancer in dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) carcinogen-induced, inflammation-driven carcinogenesis. eRapa given before DMBA/TPA exposure significantly increased tumor latency, reduced papilloma prevalence and numbers, and completely inhibited malignant degeneration into squamous cell carcinoma. Rapamycin is primarily an mTORC1-specific inhibitor, but eRapa did not reduce mTORC1 signaling in skin or papillomas, and did not reduce important proinflammatory factors in this model, including p-Stat3, IL17A, IL23, IL12, IL1β, IL6, or TNFα. In support of lack of mTORC1 inhibition, eRapa did not reduce numbers or proliferation of CD45(-)CD34(+)CD49f(mid) skin cancer initiating stem cells in vivo and marginally reduced epidermal hyperplasia. Interestingly, eRapa reduced DMBA/TPA-induced skin DNA damage and the hras codon 61 mutation that specifically drives carcinogenesis in this model, suggesting reduction of DNA damage as a cancer prevention mechanism. In support, cancer prevention and DNA damage reduction effects were lost when eRapa was given after DMBA-induced DNA damage in vivo. eRapa afforded picomolar concentrations of rapamycin in skin of DMBA/TPA-exposed mice, concentrations that also reduced DMBA-induced DNA damage in mouse and human fibroblasts in vitro. Thus, we have identified DNA damage reduction as a novel mechanism by which rapamycin can prevent cancer, which could lay the foundation for its use as a cancer prevention agent in selected human populations.

  13. A common genetic factor underlies hypertension and other cardiovascular disorders

    Directory of Open Access Journals (Sweden)

    Spector Tim D

    2004-11-01

    Full Text Available Abstract Background Certain conditions characterised by blood vessel occlusion or vascular spasm have been found to cluster together in epidemiological studies. However the biological causes for these associations remain controversial. This study used a classical twin design to examine whether these conditions are linked through shared environmental exposures or by a common underlying genetic propensity to vasospasm. Methods We investigated the association between hypertension, migraine, Raynaud's phenomenon and coronary artery disease in twins from a national register. Phenotype status was determined using a questionnaire and the genetic and environmental association between phenotypes was estimated through variance components analysis. Results Responses were obtained from 2,204 individuals comprising 525 monozygotic and 577 dizygotic pairs. There was a significant genetic contribution to all four traits with heritabilities ranging from 0.34 to 0.64. Multivariate model-fitting demonstrated that a single common genetic factor underlies the four conditions. Conclusions We have confirmed an association between hypertension, migraine, Raynaud's phenomenon and coronary artery disease, and shown that a single genetic factor underlies them. The demonstration of a shared genetic factor explains the association between them and adds weight to the theory of an inherited predisposition to vasospasm.

  14. Men's values-based factors on prostate cancer risk genetic testing: A telephone survey

    Directory of Open Access Journals (Sweden)

    Li Yuelin

    2004-12-01

    Full Text Available Abstract Background While a definitive genetic test for Hereditary Prostate Cancer (HPC is not yet available, future HPC risk testing may become available. Past survey data have shown high interest in HPC testing, but without an in-depth analysis of its underlying rationale to those considering it. Methods Telephone computer-assisted interviews of 400 men were conducted in a large metropolitan East-coast city, with subsequent development of psychometric scales and their correlation with intention to receive testing. Results Approximately 82% of men interviewed expressed that they "probably" or "definitely" would get genetic testing for prostate cancer risk if offered now. Factor analysis revealed four distinct, meaningful factors for intention to receive genetic testing for prostate cancer risk. These factors reflected attitudes toward testing and were labeled "motivation to get testing," "consequences and actions after knowing the test result," "psychological distress," and "beliefs of favorable outcomes if tested" (α = 0.89, 0.73, 0.73, and 0.60, respectively. These factors accounted for 70% of the total variability. The domains of motivation (directly, consequences (inversely, distress (inversely, and positive expectations (directly all correlated with intention to receive genetic testing (p Conclusions Men have strong attitudes favoring genetic testing for prostate cancer risk. The factors most associated with testing intention include those noted in past cancer genetics studies, and also highlights the relevance in considering one's motivation and perception of positive outcomes in genetic decision-making.

  15. Relationship between genetic and environmental factors and hypercholesterolemia in children.

    Science.gov (United States)

    Robledo, Jorge A; Siccardi, Leonardo J

    2016-10-01

    Pediatric hypercholesterolemia has increased over the past decades. Knowing the environmental and genetic factors that have an impact on it would allow establishing more adequate screening guidelines. To determine if there is an association between genetic and environmental factors and hypercholesterolemia in children. To assess the predictive qualities of outcome measures associated with hypercholesterolemia. Observational, analytical, cross-sectional study. students from all schools located in Jovita. Age: > 6 and nutritional status. A survey was administered to children to identify their level of physical activity and their eating habits. The association was assessed by estimating the OR value (p students were included. Their mean cholesterol level was 168 mg/dL, and 13.4% had hypercholesterolemia. A sedentary lifestyle was observed in 22.8%, and obesity, in 10.5%. A positive FMH, a high/ middle SEL, and obesity were associated with hypercholesterolemia (OR: 2.10, 2.10 and 2.05, respectively). No association was found between physical activity and fat/cholesterol intake and hypercholesterolemia. A positive FMH and a high/middle SEL were sensitive enough (75% and 88%) to predict hypercholesterolemia. The presence of hypercholesterolemia inboth parents in relation to hypercholesterolemia in their child showed an OR of 9.59, a sensitivity of 73%, a specificity of 71%, a positive predictive value of 57%, and a negative predictive value of 83%. A positive FMH, a high/ middle SEL, and obesity were associated with hypercholesterolemia in children. The presence of hypercholesterolemia in both parents was associated with hypercholesterolemia in their child and showed itself to be a great potential predictor and screening criterion. Sociedad Argentina de Pediatría.

  16. Current Changes in Pubertal Timing: Revised Vision in Relation with Environmental Factors Including Endocrine Disruptors.

    Science.gov (United States)

    Parent, Anne-Simone; Franssen, Delphine; Fudvoye, Julie; Pinson, Anneline; Bourguignon, Jean-Pierre

    2016-01-01

    The aim of this chapter is to revise some common views on changes in pubertal timing. This revision is based on recent epidemiological findings on the clinical indicators of pubertal timing and data on environmental factor effects and underlying mechanisms. A current advancement in timing of female puberty is usually emphasized. It appears, however, that timing is also changing in males. Moreover, the changes are towards earliness for initial pubertal stages and towards lateness for final stages in both sexes. Such observations indicate the complexity of environmental influences on pubertal timing. The mechanisms of changes in pubertal timing may involve both the central neuroendocrine control and peripheral effects at tissues targeted by gonadal steroids. While sufficient energy availability is a clue to the mechanism of pubertal development, changes in the control of both energy balance and reproduction may vary under the influence of common determinants such as endocrine-disrupting chemicals (EDCs). These effects can take place right before puberty as well as much earlier, during fetal and neonatal life. Finally, environmental factors can interact with genetic factors in determining changes in pubertal timing. Therefore, the variance in pubertal timing is no longer to be considered under absolutely separate control by environmental and genetic determinants. Some recommendations are provided for evaluation of EDC impact in the management of pubertal disorders and for possible reduction of EDC exposure along the precautionary principle.

  17. Intrauterine and genetic factors in early childhood sensitization

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus

    2010-01-01

    The allergy-associated (atopic) diseases; asthma, eczema and rhinoconjunctivitis, are the most common chronic diseases in childhood. A large number of environmental and genetic risk factors have been suggested, but still our understanding of the underlying disease mechanisms and etiologies...... of opportunity” for prevention. The aim of this thesis was to increase the understanding of sensitization in early life. We studied indicators of sensitization in the newborn, and early development of sensitization and disease associated with a newly discovered genetic risk factor. Such insight may increase our...... and identifying the environmental risk factors interacting with this genetic susceptibility and the age at which intervention should be initiated. We found a FLG-associated pattern of atopic disease in early childhood characterized by early onset of eczema, early onset of asthma with severe exacerbations...

  18. Intrauterine and genetic factors in early childhood sensitization

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus

    2010-01-01

    predictive value of elevated cord blood IgE found in recent studies. Future studies should control for materno-fetal transfer of IgE or preferably use other markers of atopy. Variation in the gene coding for the skin barrier protein filaggrin (FLG) is the strongest known genetic risk factor for eczema. FLG......The allergy-associated (atopic) diseases; asthma, eczema and rhinoconjunctivitis, are the most common chronic diseases in childhood. A large number of environmental and genetic risk factors have been suggested, but still our understanding of the underlying disease mechanisms and etiologies...... of opportunity” for prevention. The aim of this thesis was to increase the understanding of sensitization in early life. We studied indicators of sensitization in the newborn, and early development of sensitization and disease associated with a newly discovered genetic risk factor. Such insight may increase our...

  19. Host susceptibility factors in mycobacterial infection. Genetics and body morphotype.

    Science.gov (United States)

    Guide, Shireen V; Holland, Steven M

    2002-03-01

    Through identification and evaluation of mutations and polymorphisms in components of the IFN gamma response pathways, a better understanding of the mechanisms and risk factors influencing the development of mycobacterial disease is gained. This may lead the way for development of therapeutic and preventative strategies. Although conventional science has focused on identifying discrete mutations, greater awareness of the impact of subtle changes, both at the genetic (polymorphisms) and physical levels (body morphotype), may prove critical in the investigative process. There has been extraordinary progress in the understanding of mycobacterial susceptibility factors over the last few years. The recognition of characteristic phenotypes will lead to the identification of new genetic bases for disease.

  20. Genetic and environmental factors influencing the Placental Growth Factor (PGF) variation in two populations

    DEFF Research Database (Denmark)

    Sorice, Rossella; Ruggiero, Daniela; Nutile, Teresa

    2012-01-01

    . However, to date, no information is available regarding the genetics of PGF variability. Furthermore, even though the effect of environmental factors (e.g.: cigarette smoking) on angiogenesis has been explored, no data on the influence of these factors on PGF levels have been reported so far. Here we have...... strongly replicated in the Danish sample. These results, for the first time, support the hypothesis of the presence of genetic and environmental factors influencing PGF plasma variability....

  1. Stochastic dynamic simulation modeling including multitrait genetics to estimate genetic, technical, and financial consequences of dairy farm reproduction and selection strategies.

    Science.gov (United States)

    Kaniyamattam, K; Elzo, M A; Cole, J B; De Vries, A

    2016-10-01

    The objective of this study was to develop a daily stochastic dynamic dairy simulation model that included multitrait genetics and to evaluate the effects of reduced genetic models and various reproduction and selection strategies on the genetic, technical, and financial performance of a dairy herd. The 12 correlated genetic traits included in the 2014 lifetime net merit (NM$) index were modeled for each animal. For each animal, a true breeding value (TBV) for each trait was calculated as the average of the sire's and dam's TBV, plus a fraction of the inbreeding and Mendelian sampling variability. Similarly, an environmental component for each trait was calculated and was partitioned into a permanent and a daily (temporary) effect. The combined TBV and environmental effects were converted into the phenotypic performance of each animal. Hence, genetics and phenotypic performances were associated. Estimated breeding values (EBV) were also simulated. Genetic trends for each trait for the service sire were based on expected trends in US Holsteins. Surplus heifers were culled based on various ranking criteria to maintain a herd size of 1,000 milking cows. In the first 8 scenarios, culling of surplus heifers was either random or based on the EBV of NM$. Four different genetic models, depending on the presence or absence of genetic trends or genetic and environmental correlations, or both, were evaluated to measure the effect of excluding multitrait genetics on animal performance. In the last 5 scenarios, the full genetic model was used and culling of surplus heifers was either random or based on the EBV of NM$ or the EBV of milk. Sexed semen use and reliability of the EBV were also varied. Each scenario was simulated for 15yr into the future. Results showed that genetic models without all 12 genetic trends and genetic and environmental correlations provided biased estimates of the genetic, technical, and financial performance of the dairy herd. Average TBV of NM$ of all

  2. Genetic and non-genetic factors affecting semen production traits in Karan Fries crossbred bulls.

    Science.gov (United States)

    Chauhan, Indra Sen; Gupta, Ashok K; Khate, Keviletsu; Chauhan, Anuj; Rao, Thakur Krishna Shankar; Pathak, Shivendra; Hazra, Ritwik; Singh, Maneesh

    2010-12-01

    The objective of the study was to evaluate the effects of genetic and non-genetic factors on production of breeding bulls and semen quality parameters in Karan Fries crossbred male by fitting least squares analysis. Genetically, the animals were divided into three subclasses. The non-genetic factors were season of birth, period of birth, and age group with three subclasses each for season of birth and period of birth. Age group was classified into four subclasses. The traits generated in the study were number of males reaching semen donation stage (AFSC) and first freezing (AFSF), age at last semen collection (ALSC) and last freezing (ALSF), age at disposal (AD), and lifetime semen production traits (up to 1 year after first freezing). The effect of period of birth was significant for AFSC, AFSF, ALSC, and AD. It was also significant for total ejaculates produced in a year. The age group had significant effect on AFSF. Effect of genetic group was significant for freezable ejaculates produced in a year, for frozen semen doses produced in a year, and for number of ejaculates cryoprocessed in a year. Season had no statistically significant effect on any of the traits studied. The influence of period revealed that the most of the traits of breeding bulls improved after intermediate period, which could be due to better care, training, feeding, and other management practices in the latter years. However, no consistent trend could be established for the effects of genetic groups and other non-genetic causes on the traits considered.

  3. Non-insect crustacean models in developmental genetics including an encomium to Parhyale hawaiensis.

    Science.gov (United States)

    Stamataki, Evangelia; Pavlopoulos, Anastasios

    2016-08-01

    The impressive diversity of body plans, lifestyles and segmental specializations exhibited by crustaceans (barnacles, copepods, shrimps, crabs, lobsters and their kin) provides great material to address longstanding questions in evolutionary developmental biology. Recent advances in forward and reverse genetics and in imaging approaches applied in the amphipod Parhyale hawaiensis and other emerging crustacean model species have made it possible to probe the molecular and cellular basis of crustacean diversity. A number of biological and technical qualities like the slow tempo and holoblastic cleavage mode, the stereotypy of many cellular processes, the functional and morphological diversity of limbs along the body axis, and the availability of various experimental manipulations, have made Parhyale a powerful system to study normal development and regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Genetic factors associated with cancer male breast: a literature review

    Directory of Open Access Journals (Sweden)

    Nathalia Maria Tomaz Silveira

    2016-10-01

    Full Text Available The male breast cancer is a rare neoplastic framework, covers 1% of cases of breast cancer worldwide, 1% of malignant tumors in men and has an annual incidence of 1 per 100,000 men. Information was gathered about the current studies related to genetic character in addressed condition, in which the goal was to analyze aspects of predisposition and association, using 16 original articles indexed in the period between January 2011 to February 2016, written in English and Spanish, with experimental design or observational, using male breast cancer descriptors, breast cancer and genetic factor for breast cancer, as well as their English translations male breast cancer, cancer treatment, breast cancer and genetic factors. It was mainly discussed the genetic influence on the occurrence of male breast cancer, such as changes in suppressors BRCA genes, relationships with CHECK2 checkpoint, family history and links with Klinefelter syndrome, among other factors. Environmental aspects are also suggested by the literature on the clinical neoplasic manifestation, but with less conclusive emphases. Although the literature on the subject still need growth and deepening, we observe scientific reassurances about the importance of genetic influence, especially the BRCA 1, about the Multifactorial etiology of the neoplasia.

  5. The role of genetics in stroke risk factors; the discussion of two rare genetic syndroms associated with stroke and review of the literature

    Directory of Open Access Journals (Sweden)

    Eda Kılıç Çoban

    2015-09-01

    Full Text Available Stroke is defined as a focal or at times global neurological impairment of sudden onset, that lasts more than 24 hours or that leads to death. The nonmodifiable risk factors for stroke include age, race, gender and acquired risk factors include smoking, hypertension, diabetes and obesity. Previous studies have shown that these mentioned risk factors might be responsible for approximately 50% of patients presenting stroke. However for the remaining half of the stroke patients no risk factors could be detected and genetics might be responsible for this group. In this manuscript we would like to present 2 cases who were being followed-up with the rare genetic syndromes as Marfan syndrome and Robinow syndrome respectively. These patients presented to our clinic with stroke and no identifiable risk factors other than these genetic syndromes could be detected. By this case-series we would like to further discuss the relationship between genetic syndromes and stroke.

  6. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer.

    Science.gov (United States)

    Voorwinden, Jan S; Jaspers, Jan P C

    2016-06-01

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors that can predict which counselees are most likely to develop psychological problems after presymptomatic genetic testing. Counselees with a 50 % risk of BRCA1/2 or Lynch syndrome completed questionnaires at three time-points: after receiving a written invitation for a genetic counseling intake (T1), 2-3 days after receiving their DNA test result (T2), and 4-6 weeks later (T3). The psychological impact of the genetic test result was examined shortly and 4-6 weeks after learning their test result. Subsequently, the influence of various potentially prognostic factors on psychological impact were examined in the whole group. Data from 165 counselees were analyzed. Counselees with an unfavorable outcome did not have more emotional distress, but showed significantly more cancer worries 4-6 weeks after learning their test result. Prognostic factors for cancer worries after genetic testing were pre-existing cancer worries, being single, a high risk perception of getting cancer, and an unfavorable test result. Emotional distress was best predicted by pre-existing cancer worries and pre-existing emotional distress. The psychological impact of an unfavorable genetic test result appears considerable if it is measured as "worries about cancer." Genetic counselors should provide additional guidance to counselees with many cancer worries, emotional distress, a high risk perception or a weak social network.

  7. THE ROLES OF INDUSTRY AND SCIENCE, INCLUDING GENETIC SELECTION, IN IMPROVING ANIMAL WELFARE

    Directory of Open Access Journals (Sweden)

    D.M. BROOM

    2013-07-01

    Full Text Available Animal producers have to predict future situations and be aware of changing public views. At present, those in the animal industry are often trying to fight off change rather than preparing for and pre-empting it. As a consequence, many animal producers have bad public images. It is better to be proactive than reactive. Producer groups should be aware of new developments in knowledge and in public attitudes to animal-related activities. They should inform their members about how to manage animals in such a way that the welfare of the animals is good and the people involved in animal care are well-respected in society. This is especially important also for those who design and manufacture housing and equipment and those who breed animals for they can have substantial effects on animal welfare. It is important for animal welfare scientists to provide objective information about the welfare of animals, so that decisions can be taken about how animals should be bred, housed and treated. Animals use a wide range of coping mechanisms and these involve high-level brain function, with associated good and bad feelings. Where welfare is poor, the best overall assessment of welfare is a function of how bad is the effect on the individual and the duration of that effect. Conventional breeding, cloning and transgenesis can all have effects on the welfare of the animals produced. Selection for fast growth and high feed conversion efficiency in broiler chickens and other meat producing animals leads to too high an incidence of leg and other disorders. Selection for high milk yield in dairy cows leads to poor welfare associated with leg disorders, mastitis and reproductive disorders. These effects should be evaluated using a range of animal welfare measures and if there are adverse effects of genetic engineering, the usage of the animals should not be permitted except for research. In the case of genetically modified or cloned animals, any effects on function

  8. Resource and environmental factors should be included in economic analytical framework

    Institute of Scientific and Technical Information of China (English)

    金碚

    2009-01-01

    In the economic analysis framework,natural resources and environmental factors are included in the category of capital or land.Hence,the explanatory variables of the production function only include capital,labor and the residue term technology.Such framework may be designed for methodological reasons,but it is determined

  9. Genetic, Maternal, and Environmental Risk Factors for Cryptorchidism

    DEFF Research Database (Denmark)

    Barthold, Julia Spencer; Reinhardt, Susanne; Thorup, Jorgen

    2016-01-01

    Unilateral or bilateral cryptorchidism is an isolated anomaly in the majority of cases, with evidence to date suggesting that it is a complex disorder resulting from interactions between genetic and environmental factors. Population, family, and limited genome-wide association data suggest modera...

  10. Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

    NARCIS (Netherlands)

    van 't Hof, Femke N G; Ruigrok, Ynte M; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F; Blankensteijn, Jan D; Böttinger, Erwin P; Bown, Matthew J; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S; Crawford, Dana C; Crosslin, David R; Ebeling, Christian; Eriksson, Johan G; Fornage, Myriam; Foroud, Tatiana; von Und Zu Fraunberg, Mikael; Friedrich, Christoph M; Gaál, Emília I; Gottesman, Omri; Guo, Dong-Chuan; Harrison, Seamus C; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E; Jones, Gregory T; Kiemeney, Lambertus A L M; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J; Kuivaniemi, Helena; Kurki, Mitja I; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M; Lehto, Hanna; LeMaire, Scott A; Low, Siew-Kee; Malinowski, Jennifer; McCarty, Catherine A; Milewicz, Dianna M; Mosley, Thomas H; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L; Pera, Joanna; Rasmussen-Torvik, Laura; Ritchie, Marylyn D; Rivadeneira, Fernando; van Rij, Andre M; Santos-Cortez, Regie Lyn P; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G; Verma, Shefali S; Vermeulen, Sita H; Wang, Gao T; Han, Buhm; Rinkel, Gabriël J E; de Bakker, Paul I W

    2016-01-01

    BACKGROUND: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. METHODS AND RE

  11. The genetic factors influencing the development of trichotillomania

    Indian Academy of Sciences (India)

    Koushik Chatterjee

    2012-08-01

    Trichotillomania (TTM), an obsessive–compulsive spectrum disorder (OCSD), is a psychiatric condition characterized by repetitive hair pulling. Evidence from family and twin studies suggest a heritable link of TTM. Functional polymorphisms in genes involved in neuronal pathways might influence the susceptibility to TTM. This review is an attempt to compile the genetic factors reported to modify the development of TTM.

  12. Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

    NARCIS (Netherlands)

    van 't Hof, Femke N G|info:eu-repo/dai/nl/341753610; Ruigrok, Ynte M|info:eu-repo/dai/nl/303621222; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F; Blankensteijn, Jan D; Böttinger, Erwin P; Bown, Matthew J; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S; Crawford, Dana C; Crosslin, David R; Ebeling, Christian; Eriksson, Johan G; Fornage, Myriam; Foroud, Tatiana; von Und Zu Fraunberg, Mikael; Friedrich, Christoph M; Gaál, Emília I; Gottesman, Omri; Guo, Dong-Chuan; Harrison, Seamus C; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E; Jones, Gregory T; Kiemeney, Lambertus A L M; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J; Kuivaniemi, Helena; Kurki, Mitja I; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M; Lehto, Hanna; LeMaire, Scott A; Low, Siew-Kee; Malinowski, Jennifer; McCarty, Catherine A; Milewicz, Dianna M; Mosley, Thomas H; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L; Pera, Joanna; Rasmussen-Torvik, Laura; Ritchie, Marylyn D; Rivadeneira, Fernando; van Rij, Andre M; Santos-Cortez, Regie Lyn P; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G; Verma, Shefali S; Vermeulen, Sita H; Wang, Gao T; Han, Buhm; Rinkel, Gabriël J E|info:eu-repo/dai/nl/085712000; de Bakker, Paul I W|info:eu-repo/dai/nl/342957082

    2016-01-01

    BACKGROUND: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. METHODS AND RE

  13. A Strong Case for Viral Genetic Factors in HIV Virulence

    Directory of Open Access Journals (Sweden)

    Joshua T. Herbeck

    2011-03-01

    Full Text Available HIV infections show great variation in the rate of progression to disease, and the role of viral genetic factors in this variation had remained poorly characterized until recently. Now a series of four studies [1–4] published within a year has filled this important gap and has demonstrated a robust effect of the viral genotype on HIV virulence.

  14. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer

    NARCIS (Netherlands)

    Voorwinden, Jan S; Jaspers, Jan P C

    2015-01-01

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors tha

  15. Resiliency to Victimization: The Role of Genetic Factors

    Science.gov (United States)

    Beaver, Kevin M.; Mancini, Christina; DeLisi, Matt; Vaughn, Michael G.

    2011-01-01

    There is a burgeoning line of criminological research examining the genetic underpinnings to a wide array of antisocial phenotypes. From this perspective, genes are typically viewed as risk factors that increase the odds of various maladaptive behaviors. However, genes can also have protective effects that insulate against the deleterious effects…

  16. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer

    NARCIS (Netherlands)

    Voorwinden, Jan S.; Jaspers, Jan P C

    2016-01-01

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors tha

  17. The role of genetic factors in age at natural menopause

    NARCIS (Netherlands)

    Bruin, de J.P.; Bovenhuis, H.; Noord, van P.A.H.; Pearson, P.; Arendonk, van J.A.M.; Velde, ter E.R.; Kuurman, W.W.

    2001-01-01

    Background: Environmental factors explain only a small part of the age variance at which menopause commences. The variation in natural menopause is a trait predominantly determined by interaction of multiple genes, whose identity and causative genetic variation remains to be determined. Menopause is

  18. Congenital diaphragmatic hernia : the importance of genetic and environmental factors

    NARCIS (Netherlands)

    M.F. van Dooren (Marieke)

    2004-01-01

    textabstractFor the studies described in this thesis we used a study protocol 'Environmental and Genetic factors in Congenital Diaphragmatic Hernia and Esophageal Atresia', approved by the Institutional Review Board, in collaboration with the parent support groups, 'Stichting Hernia Diafragrnatica'

  19. Microsatellite DNA reveals population genetic differentiation among sprat (Sprattus sprattus) sampled throughout the Northeast Atlantic, including Norwegian fjords

    DEFF Research Database (Denmark)

    Glover, Kevin A.; Skaala, Øystein; Limborg, Morten;

    2011-01-01

    Glover, K. A., Skaala, Ø., Limborg, M., Kvamme, C., and Torstensen, E. Microsatellite DNA reveals population genetic differentiation among sprat (Sprattus sprattus) sampled throughout the Northeast Atlantic, including Norwegian fjords. – ICES Journal of Marine Science, 68: 2145–2151. Sprat...... (Sprattus sprattus), small pelagic shoaling fish, were sampled from the Celtic, North, and Baltic seas, and 10 Norwegian fjords. Significant overall genetic differentiation was observed among samples when analysed with eight microsatellite DNA loci (Global FST = 0.0065, p ... differences were observed between the Baltic and all other samples (largest pairwise FST = 0.043, p sample from the Celtic Sea (CEL) and the North Sea (NSEA; FST = 0.001, p = 0.16), but variable levels of genetic differentiation were...

  20. Psychological mechanisms in hyperactivity: II. The role of genetic factors.

    Science.gov (United States)

    Kuntsi, J; Stevenson, J

    2001-02-01

    The main aim of this study was to combine two research approaches to hyperactivity: the behaviour genetic approach and the testing of psychological theories of hyperactivity. For a sample of 268 twin pairs aged 7-11 years we obtained ratings on the Conners' scales from both teachers (CTRS-28) and parents (CPRS-48). Forty-six hyperactive twin pairs (pairs in which at least one twin was pervasively hyperactive) and 47 control twin pairs were assessed on a psychological test battery. Confirming findings from previous twin studies, a substantial proportion of the variance in hyperactivity considered as a dimension was due to genetic effects. There was significant evidence of genetic effects also on extreme hyperactivity, although the present group heritability estimates were somewhat lower than those reported in most previous studies. We investigated the possibility that the psychological mechanisms we reported to be associated with hyperactivity (Kuntsi, Oosterlaan, & Stevenson, 2001) share common genetic factors with hyperactive behaviour. The data produced significant evidence of such shared genetic effects only on hyperactivity and the variability of reaction times. Given that the high variability in speed of responding would indicate a state-regulation problem, this is the psychological mechanism that could possibly be the "link" between genetic effects and hyperactive behaviour.

  1. Genetic factors in exercise adoption, adherence and obesity.

    Science.gov (United States)

    Herring, M P; Sailors, M H; Bray, M S

    2014-01-01

    Physical activity and exercise play critical roles in energy balance. While many interventions targeted at increasing physical activity have demonstrated efficacy in promoting weight loss or maintenance in the short term, long term adherence to such programmes is not frequently observed. Numerous factors have been examined for their ability to predict and/or influence physical activity and exercise adherence. Although physical activity has been demonstrated to have a strong genetic component in both animals and humans, few studies have examined the association between genetic variation and exercise adherence. In this review, we provide a detailed overview of the non-genetic and genetic predictors of physical activity and adherence to exercise. In addition, we report the results of analysis of 26 single nucleotide polymorphisms in six candidate genes examined for association to exercise adherence, duration, intensity and total exercise dose in young adults from the Training Interventions and Genetics of Exercise Response (TIGER) Study. Based on both animal and human research, neural signalling and pleasure/reward systems in the brain may drive in large part the propensity to be physically active and to adhere to an exercise programme. Adherence/compliance research in other fields may inform future investigation of the genetics of exercise adherence. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

  2. Rule-based models of the interplay between genetic and environmental factors in childhood allergy.

    Directory of Open Access Journals (Sweden)

    Susanne Bornelöv

    Full Text Available Both genetic and environmental factors are important for the development of allergic diseases. However, a detailed understanding of how such factors act together is lacking. To elucidate the interplay between genetic and environmental factors in allergic diseases, we used a novel bioinformatics approach that combines feature selection and machine learning. In two materials, PARSIFAL (a European cross-sectional study of 3113 children and BAMSE (a Swedish birth-cohort including 2033 children, genetic variants as well as environmental and lifestyle factors were evaluated for their contribution to allergic phenotypes. Monte Carlo feature selection and rule based models were used to identify and rank rules describing how combinations of genetic and environmental factors affect the risk of allergic diseases. Novel interactions between genes were suggested and replicated, such as between ORMDL3 and RORA, where certain genotype combinations gave odds ratios for current asthma of 2.1 (95% CI 1.2-3.6 and 3.2 (95% CI 2.0-5.0 in the BAMSE and PARSIFAL children, respectively. Several combinations of environmental factors appeared to be important for the development of allergic disease in children. For example, use of baby formula and antibiotics early in life was associated with an odds ratio of 7.4 (95% CI 4.5-12.0 of developing asthma. Furthermore, genetic variants together with environmental factors seemed to play a role for allergic diseases, such as the use of antibiotics early in life and COL29A1 variants for asthma, and farm living and NPSR1 variants for allergic eczema. Overall, combinations of environmental and life style factors appeared more frequently in the models than combinations solely involving genes. In conclusion, a new bioinformatics approach is described for analyzing complex data, including extensive genetic and environmental information. Interactions identified with this approach could provide useful hints for further in-depth studies

  3. Mutagen sensitivity: a genetic predisposition factor for cancer.

    Science.gov (United States)

    Wu, Xifeng; Gu, Jian; Spitz, Margaret R

    2007-04-15

    Mutagen sensitivity, measured by quantifying the chromatid breaks induced by mutagens in short-term cultures of peripheral blood lymphocytes, has been used as an indirect measure of DNA repair capacity. Numerous epidemiologic studies have suggested that mutagen sensitivity is a cancer susceptibility factor for a variety of epithelial cancers. A recent classic twin study examined systematically the role of genetic and environmental factors on the mutagen sensitivity phenotype and provided compelling evidence that mutagen sensitivity is highly heritable. A new prospective analysis provides further support to the notion that mutagen sensitivity increases the risk of cancer. In this review, we briefly summarize nearly two decades of epidemiologic and genetic studies linking mutagen sensitivity and cancer risk. The evidence is becoming increasingly convincing that mutagen sensitivity is a risk factor for cancer development.

  4. The Genetic Basis of the Polycystic Ovary Syndrome: A Literature Review Including Discussion of PPAR-γ

    Directory of Open Access Journals (Sweden)

    Ugur Unluturk

    2007-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrine disorder of the women of reproductive age. Familial clustering of PCOS has been consistently reported suggesting that genetic factors play a role in the development of the syndrome although PCOS cases do not exhibit a clear pattern of Mendelian inheritance. It is now well established that PCOS represents a complex trait similar to type-2 diabetes and obesity, and that both inherited and environmental factors contribute to the PCOS pathogenesis. A large number of functional candidate genes have been tested for association or linkage with PCOS phenotypes with more negative than positive findings. Lack of universally accepted diagnostic criteria, difficulties in the assignment of male phenotype, obscurity in the mode of inheritance, and particularly small sample size of the study populations appear to be major limitations for the genetic studies of PCOS. In the near future, utilizing the genome-wide scan approach and the HapMap project will provide a stronger potential for the genetic analysis of the syndrome.

  5. Host factors and genetic susceptibility to infections due to intracellular bacteria and fastidious organisms.

    Science.gov (United States)

    Asner, S A; Morré, S A; Bochud, P-Y; Greub, G

    2014-12-01

    While genetic polymorphisms play a paramount role in tuberculosis (TB), less is known about their contribution to the severity of diseases caused by other intracellular bacteria and fastidious microorganisms. We searched electronic databases for observational studies reporting on host factors and genetic predisposition to infections caused by intracellular fastidious bacteria published up to 30 May 2014. The contribution of genetic polymorphisms was documented for TB. This includes genetic defects in the mononuclear phagocyte/T helper cell type 1 (Th1) pathway contributing to disseminated TB disease in children and genome-wide linkage analysis (GWAS) in reactivated pulmonary TB in adults. Similarly, experimental studies supported the role of host genetic factors in the clinical presentation of illnesses resulting from other fastidious intracellular bacteria. These include IL-6 -174G/C or low mannose-binding (MBL) polymorphisms, which are incriminated in chronic pulmonary conditions triggered by C. pneumoniae, type 2-like cytokine secretion polymorphisms, which are correlated with various clinical patterns of M. pneumoniae infections, and genetic variation in the NOD2 gene, which is an indicator of tubal pathology resulting from Chamydia trachomatis infections. Monocyte/macrophage migration and T lymphocyte recruitment defects are corroborated to ineffective granuloma formation observed among patients with chronic Q fever. Similar genetic polymorphisms have also been suggested for infections caused by T. whipplei although not confirmed yet. In conclusion, this review supports the paramount role of genetic factors in clinical presentations and severity of infections caused by intracellular fastidious bacteria. Genetic predisposition should be further explored through such as exome sequencing.

  6. Genetic and environmental influences on cardiovascular risk factors and cognitive function

    DEFF Research Database (Denmark)

    Xu, Chunsheng; Tian, Xiaocao; Sun, Jianping

    2017-01-01

    AIM: To explore the genetic and environmental influences on cardiovascular risk factors (CVRF) and cognitive function in the world's largest and rapidly aging Chinese population. METHODS: Cognitive function and CVRF, including body mass index, systolic blood pressure, diastolic blood pressure, pu...

  7. Genetic, behavioral, and sociodemographic risk factors for second eye progression in age-related macular degeneration

    NARCIS (Netherlands)

    Lechanteur, Y.T.; Ven, J.P. van de; Smailhodzic, D.; Boon, C.J.F.; Klevering, B.J.; Fauser, S.; Groenewoud, J.M.; Wilt, G.J. van der; Hollander, A.I. den; Hoyng, C.B.

    2012-01-01

    PURPOSE: This study was conducted to investigate the correlation of genetic, sociodemographic, and behavioral risk factors with second eye progression to end-stage AMD. METHODS: One hundred and eight patients with end-stage AMD in one or both eyes were included in a retrospective time-to-event analy

  8. BELFAST nonagenarians: nature or nurture? Immunological, cardiovascular and genetic factors

    Directory of Open Access Journals (Sweden)

    Rea I M

    2010-05-01

    Full Text Available Abstract Nonagenarians are the fastest growing sector of populations across Western European and the developed world. They are some of the oldest members of our societies and survivors of their generation and may help us understand how to age not only longer, but better. The Belfast Longevity Group enlisted the help of 500 community-living, mobile, mentally competent, 'elite' nonagenarians, as part of an ongoing study of ageing. We assessed some immunological, cardiovascular, nutritional and genetic factors and some aspects of their interaction in this group of 'oldest old'. Here we present some of the evidence related to genetic and nutritional factors which seem to be important for good quality ageing in nonagenarians from the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST.

  9. A Study of Factors Promoting Success in Computer Science Including Gender Differences

    Science.gov (United States)

    Cantwell Wilson, Brenda

    2002-03-01

    This study was conducted to determine factors that promote success in an introductory college computer science course and to determine what, if any, differences appear between genders on those factors. The model included math background, attribution for success/failure, self-efficacy, encouragement, comfort level in the course, work style preference, previous programming experience, previous non-programming computer experience, and gender as possible predictive factors for success in the computer science course. Subjects included 105 students enrolled in an introductory computer science course. The study revealed three predictive factors in the following order of importance: comfort level (with a positive influence), math background (with a positive influence), and attribution to luck (with a negative influence). No significant gender differences were found in these three factors. The study also revealed that both a formal class in programming (which had a positive correlation) and game playing (which had a negative correlation) were predictive of success. The study revealed a significant gender difference in game playing with males reporting more experience with playing games on the computer than females reported.

  10. Genetic and environmental factors in breakfast eating patterns.

    Science.gov (United States)

    Keski-Rahkonen, Anna; Viken, Richard J; Kaprio, Jaakko; Rissanen, Aila; Rose, Richard J

    2004-09-01

    Despite many studies on the prevalence of breakfast eating, we know little about factors that determine breakfast eating patterns. Our aim was to find out to which extent breakfast eating frequency is influenced by genetic and environmental factors using twin and twin-family models in a population sample of 16-year-old twins (n = 5250) and their parents (n = 4663). In common effects sex-limitation models, additive genetic effects explained 41% (95% CI: 21-63%) of the variance in breakfast eating in girls and 66% (95% CI: 47-79%) in boys, and common environmental effects 45% (95% CI: 23-62%) in girls and 14% (95% CI: 5-29%) in boys. Of twin-family models, phenotypic assortment models fitted the data best. Heritability estimates increased somewhat (72%, 95% CI: 46-98% in girls and 63%, 95% CI: 38-89%) in boys. Common family environment remained substantial in both sexes. Cultural transmission was nonsignificant. The relative influence of genetic and family factors on adolescent breakfast eating frequency differs by sex and is generation-specific.

  11. Plant Oils and Cardiometabolic Risk Factors: The Role of Genetics.

    Science.gov (United States)

    Smith, Caren E

    2012-09-01

    More than 25 years have passed since Ancel Keys and others observed that high intake of monounsaturated fatty acids, especially as supplied by plants (eg, olive oil) was associated with lower cardiovascular and overall mortality. About 15 years later, advances in genotyping technologies began to facilitate widespread study of relationships between dietary fats and genetic variants, illuminating the role of genetic variation in modulating human responses to fatty acids. More recently, microarray technologies evaluate the ways in which minor, bioactive compounds in plant oils (including olive, thyme, lemongrass, clove, eucalyptus, and others) alter gene expression to mediate anti-inflammatory and antioxidant effects. Results from a range of diverse technologies and approaches are coalescing to improve understanding of the role of the genome in shaping our responses to plant oils, and to clarify the genetic mechanisms underlying the cardioprotective benefits we derive from a wide range of plant oil constituents.

  12. Genetic and non-genetic factors affecting morphometry of Sirohi goats

    Directory of Open Access Journals (Sweden)

    S. D. Dudhe

    2015-11-01

    Full Text Available Aim: The aim was to estimate genetic and non-genetic factors affecting morphometric traits of Sirohi goats under field condition. Materials and Methods: The detailed information of all animals on body measurements at birth, 3, 6, 9, and 12 months of age was collected from farmer’s flock under field condition born during 2007-2013 to analyze the effect of genetic and non-genetic factors. The least squares maximum likelihood program was used to estimate genetic and non-genetic parameters affecting morphometric traits. Results and Discussion: Effect of sire, cluster, year of birth, and sex was found to be highly significant (p<0.01 on all three morphometric traits, parity was highly significant (p<0.01 for body height (BH and body girth (BG at birth. The h2 estimates for morphometric traits ranged among 0.528±0.163 to 0.709±0.144 for BH, 0.408±0.159 to 0.605±0.192 for body length (BL, and 0.503±0.197 to 0.695±0.161 for BG. Conclusion: The effect of sire was highly significant (p<0.01 and also h² estimate of all morphometric traits were medium to high; therefore, it could be concluded on the basis of present findings that animals with higher body measurements at initial phases of growth will perform better with respect to even body weight traits at later stages of growth.

  13. Noninheritable Maternal Factors Useful for Genetic Manipulation in Mammals.

    Science.gov (United States)

    Sakurai, Takayuki; Shindo, Takayuki; Sato, Masahiro

    2017-01-01

    Mammalian early embryogenesis is supported by maternal factors, such as messenger RNA (mRNA) and proteins, produced and accumulated during oogenesis at least up to the stage when zygotic activation commences. These maternal factors are involved in biologically important events such as epigenetic activation, reprogramming, and mitochondrial growth. Most of these maternal mRNAs are degraded by the 2-cell to 4 ~ 8-cell stages. Maternal proteins, which are produced during oogenesis or by the maternal mRNAs, are degraded by the 4 ~ 8-cell stage. In other words, the maternal factors exist during specific stages of early embryogenesis. In this chapter, we will briefly summarize the property of these maternal factors and mention possible applications of these factors for developing new reproduction engineering-related technologies and producing genetically modified animals. More specifically, we will show the usefulness of maternally accumulated Cas9 protein as a promising tool for CRISPR-/Cas9-based simultaneous genetic modification of multiple loci in mammals.

  14. TUMOR NECROSIS FACTOR-α INHIBITORS IN THE TREATMENT OF AXIAL SPONDYLOARTHRITIS, INCLUDING ANKYLOSING SPONDYLITIS

    Directory of Open Access Journals (Sweden)

    S. A. Lapshina

    2016-01-01

    Full Text Available The paper provides guidelines for the use of tumor necrosis factor-α  (TNF-α inhibitors in the treatment of patients with axial spondyloarthritis  (axSpA, including ankylosing spondylitis. It gives data on the efficacy of TNF-α inhibitors in patients with non-radiographic axSpA. By using international and Russian guidelines, the authors lay down indications for this therapy and criteria for evaluation of its efficiency and safety.

  15. Neuroblastoma: morphological pattern, molecular genetic features, and prognostic factors

    Directory of Open Access Journals (Sweden)

    A. M. Stroganova

    2016-01-01

    Full Text Available Neuroblastoma, the most common extracranial tumor of childhood, arises from the developing neurons of the sympathetic nervous system (neural cress stem cells and has various biological and clinical characteristics. The mean age at disease onset is 18 months. Neuroblastoma has a number of unique characteristics: a capacity for spontaneous regression in babies younger than 12 months even in the presence of distant metastases, for differentiation (maturation into ganglioneuroma in infants after the first year of life, and for swift aggressive development and rapid metastasis. There are 2 clinical classifications of neuroblastoma: the International neuroblastoma staging system that is based on surgical results and the International Neuroblastoma Risk Group Staging System. One of the fundamentally important problems for the clinical picture of neuroblastoma is difficulties making its prognosis. Along with clinical parameters (a patient’s age, tumor extent and site, some histological, molecular biochemical (ploidy and genetic (chromosomal aberrations, MYCN gene status, deletion of the locus 1p36 and 11q, the longer arm of chromosome 17, etc. characteristics of tumor cells are of considerable promise. MYCN gene amplification is observed in 20–30 % of primary neuroblastomas and it is one of the major indicators of disease aggressiveness, early chemotherapy resistance, and a poor prognosis. There are 2 types of MYCN gene amplification: extrachromosomal (double acentric chromosomes and intrachromosomal (homogenically painted regions. Examination of double acentric chromosomes revealed an interesting fact that it may be eliminated (removed from the nucleus through the formation of micronuclei. MYCN oncogene amplification is accompanied frequently by 1p36 locus deletion and longer 17q arm and less frequently by 11q23 deletion; these are poor prognostic factors for the disease. The paper considers in detail the specific, unique characteristics of the

  16. Genetic factors contributing to human primary ciliary dyskinesia and male infertility.

    Science.gov (United States)

    Ji, Zhi-Yong; Sha, Yan-Wei; Ding, Lu; Li, Ping

    2016-06-07

    Primary ciliary dyskinesia (PCD) is an autosomal-recessive disorder resulting from the loss of normal ciliary function. Symptoms include neonatal respiratory distress, chronic sinusitis, bronchiectasis, situs inversus, and infertility. However, only 15 PCD-associated genes have been identified to cause male infertility to date. Owing to the genetic heterogeneity of PCD, comprehensive molecular genetic testing is not considered the standard of care. Here, we provide an update of the progress on the identification of genetic factors related to PCD associated with male infertility, summarizing the underlying molecular mechanisms, and discuss the clinical implications of these findings. Further research in this field will impact the diagnostic strategy for male infertility, enabling clinicians to provide patients with informed genetic counseling, and help to adopt the best course of treatment for developing directly targeted personalized medicine.

  17. [Influence of genetic factors on human sexual orientation. Review].

    Science.gov (United States)

    Rodríguez-Larralde, Alvaro; Paradisi, Irene

    2009-09-01

    Human sexual orientation is a complex trait, influenced by several genes, experiential and sociocultural factors. These elements interact and produce a typical pattern of sexual orientation towards the opposite sex. Some exceptions exist, like bisexuality and homosexuality, which seem to be more frequent in males than females. Traditional methods for the genetic study of behavior multifactorial characteristics consist in detecting the presence of familial aggregation. In order to identify the importance of genetic and environmental factors in this aggregation, the concordance of the trait for monozygotic and dizygotic twins and for adopted sibs, reared together and apart, is compared. These types of studies have shown that familial aggregation is stronger for male than for female homosexuality. Based on the threshold method for multifactorial traits, and varying the frequency of homosexuality in the population between 4 and 10%, heritability estimates between 0.27 and 0.76 have been obtained. In 1993, linkage between homosexuality and chromosomal region Xq28 based on molecular approaches was reported. Nevertheless, this was not confirmed in later studies. Recently, a wide search of the genome has given significant or close to significant linkage values with regions 7q36, 8p12 and 10q26, which need to be studied more closely. Deviation in the proportion of X chromosome inactivation in mothers of homosexuals seems to favor the presence of genes related with sexual orientation in this chromosome. There is still much to be known about the genetics of human homosexuality.

  18. Improvement in genetic evaluation of female fertility in dairy cattle using multiple-trait models including milk production traits

    DEFF Research Database (Denmark)

    Sun, C; Madsen, P; Lund, M S

    2010-01-01

    This study investigated the improvement in genetic evaluation of fertility traits by using production traits as secondary traits (MILK = 305-d milk yield, FAT = 305-d fat yield, and PROT = 305-d protein yield). Data including 471,742 records from first lactations of Denmark Holstein cows, covering...... the years of inseminations during first lactations from 1995 to 2004, were analyzed. Six fertility traits (i.e., interval in days from calving to first insemination, calving interval, days open, interval in days from first to last insemination, numbers of inseminations per conception, and nonreturn rate...

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

    Science.gov (United States)

    Smerecnik, Chris M R

    2010-08-01

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

  20. Z' factor including siRNA design quality parameter in RNAi screening experiments.

    Science.gov (United States)

    Mazur, Sławomir; Kozak, Karol

    2012-05-01

    RNA interference (RNAi) high-content screening (HCS) enables massive parallel gene silencing and is increasingly being used to reveal novel connections between genes and disease-relevant phenotypes. The application of genome-scale RNAi relies on the development of high quality HCS assays. The Z' factor statistic provides a way to evaluate whether or not screening run conditions (reagents, protocols, instrumentation, kinetics, and other conditions not directly related to the test compounds) are optimized. Z' factor, introduced by Zhang et al., ( 1) is a dimensionless value that represents both the variability and the dynamic range between two sets of sample control data. This paper describe a new extension of the Z' factor, which integrates bioinformatics RNAi non-target compounds for screening quality assessment. Currently presented Z' factor is based on positive and negative control, which may not be sufficient for RNAi experiments including oligonucleotides (oligo) with lack of knock-down. This paper proposes an algorithm which extends existing algorithm by using additional controls generetaed from on-target analysis.

  1. Ethical implications of including children in a large biobank for genetic-epidemiologic research: a qualitative study of public opinion.

    Science.gov (United States)

    Kaufman, David; Geller, Gail; Leroy, Lisa; Murphy, Juli; Scott, Joan; Hudson, Kathy

    2008-02-15

    The National Institutes of Health and other federal agencies are considering initiating a cohort study of 500,000 people, including 120,000 children, to measure genetic and environmental influences on common diseases. A community engagement pilot study was conducted to identify public attitudes and concerns about the proposed cohort study, including the ethics of involving children. The pilot included 15 focus groups where the inclusion of children in the proposed cohort study was discussed. Focus groups, conducted in six cities, included 141 adults of different ages, incomes, genders, ethnicities, and races. Many of the concerns expressed by participants mirrored those addressed in pediatric research guidelines. These concerns included minimizing children's fear, pain, and burdens; whether to include young children; and how to obtain children's assent. There was little agreement about which children can assent. Some voiced concern about children's privacy, but most expected that parents would have access to children's study results. Some believed children would not benefit from participating, while others identified personal and societal benefits that might accrue. A few people believed that children's participation would not advance the study's goals. To successfully include children, proposed cohort study would need to address children's changing capabilities and rights as they grow and reach the age of consent.

  2. Behavioral factors to include in guidelines for lifelong oral healthiness: an observational study in Japanese adults

    Directory of Open Access Journals (Sweden)

    Shimozato Miho

    2006-12-01

    Full Text Available Abstract Background The aim of this study was to determine which behavioral factors to include in guidelines for the Japanese public to achieve an acceptable level of oral healthiness. The objective was to determine the relationship between oral health related behaviors and symptoms related to oral disease and tooth loss in a Japanese adult community. Methods Oral health status and lifestyle were investigated in 777 people aged 20 years and older (390 men and 387 women. Subjects were asked to complete a postal questionnaire concerning past diet and lifestyle. The completed questionnaires were collected when they had health examinations. The 15 questions included their preference for sweets, how many between-meal snacks they usually had per day, smoking and drinking habits, presence of oral symptoms, and attitudes towards dental visits. Participants were asked about their behaviors at different stages of their life. The oral health examinations included examination of the oral cavity and teeth performed by dentists using WHO criteria. Odds ratios were calculated for all subjects, all 10 year age groups, and for subjects 30 years or older, 40 years or older, 50 years or older, and 60 years or older. Results Frequency of tooth brushing (OR = 3.98, having your own toothbrush (OR = 2.11, smoking (OR = 2.71 and bleeding gums (OR = 2.03 were significantly associated with number of retained teeth in males. Frequency of between-meal snacks was strongly associated with number of retained teeth in females (OR = 4.67. Having some hobbies (OR = 2.97, having a family dentist (OR = 2.34 and consulting a dentist as soon as symptoms occurred (OR = 1.74 were significantly associated with number of retained teeth in females. Factors that were significantly associated with tooth loss in both males and females included alcohol consumption (OR = 11.96, males, OR = 3.83, females, swollen gums (OR = 1.93, males, OR = 3.04, females and toothache (OR = 3.39, males, OR

  3. Factors influencing and modifying the decision to pursue genetic testing for skin cancer risk.

    Science.gov (United States)

    Fogel, Alexander L; Jaju, Prajakta D; Li, Shufeng; Halpern-Felsher, Bonnie; Tang, Jean Y; Sarin, Kavita Y

    2017-05-01

    Across cancers, the decision to pursue genetic testing is influenced more by subjective than objective factors. However, skin cancer, which is more prevalent, visual, and multifactorial than many other malignancies, may offer different motivations for pursuing such testing. The primary objective was to determine factors influencing the decision to receive genetic testing for skin cancer risk. A secondary objective was to assess the impact of priming with health questions on the decision to receive testing. We distributed anonymous online surveys through ResearchMatch.org to assess participant health, demographics, motivations, and interest in pursuing genetic testing for skin cancer risk. Two surveys with identical questions but different question ordering were used to assess the secondary objective. We received 3783 responses (64% response rate), and 85.8% desired testing. Subjective factors, including curiosity, perceptions of skin cancer, and anxiety, were the most statistically significant determinants of the decision to pursue testing (P skin cancer (odds ratio 0.5, P = .01). Age and family history of skin cancer did not influence this decision. Participants increasingly chose testing if first queried about health behaviors (P skin cancer is primarily determined by subjective factors, such as anxiety and curiosity. Health factors, including skin cancer history, also influenced decision-making. Priming with consideration of objective health factors can increase the desire to pursue testing. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  4. Identifying Common Genetic Risk Factors of Diabetic Neuropathies

    Science.gov (United States)

    Witzel, Ini-Isabée; Jelinek, Herbert F.; Khalaf, Kinda; Lee, Sungmun; Khandoker, Ahsan H.; Alsafar, Habiba

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a global public health problem of epidemic proportions, with 60–70% of affected individuals suffering from associated neurovascular complications that act on multiple organ systems. The most common and clinically significant neuropathies of T2DM include uremic neuropathy, peripheral neuropathy, and cardiac autonomic neuropathy. These conditions seriously impact an individual’s quality of life and significantly increase the risk of morbidity and mortality. Although advances in gene sequencing technologies have identified several genetic variants that may regulate the development and progression of T2DM, little is known about whether or not the variants are involved in disease progression and how these genetic variants are associated with diabetic neuropathy specifically. Significant missing heritability data and complex disease etiologies remain to be explained. This article is the first to provide a review of the genetic risk variants implicated in the diabetic neuropathies and to highlight potential commonalities. We thereby aim to contribute to the creation of a genetic-metabolic model that will help to elucidate the cause of diabetic neuropathies, evaluate a patient’s risk profile, and ultimately facilitate preventative and targeted treatment for the individual. PMID:26074879

  5. Revised emission factors for gas engines including start/stop emissions

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Malene; Boll Illerup, J.; Birr-Petersen, K.

    2008-06-15

    Liberalisation of the electricity market has led to Danish gas engine plants increasingly converting to the spot and regulating power markets. In order to offer regulating power, plants need to be able to start and stop the engines at the plants quickly. The liberalisation causes a considerable change of operation practice of the engines e.g. less full load operation hours /year. The project provides an inventory determining the scale of the emissions during the start and stop sequence as well as proposals for engine modifications aimed at reducing start/stop emissions. This report includes calculation of emission factors as well as an inventory of total emissions and reduction potentials. (au)

  6. Factores de riesgo de la enfermedad periodontal: factores genéticos Risks factors in periodontal diseases: genetic factors

    Directory of Open Access Journals (Sweden)

    M. Rioboo Crespo

    2005-08-01

    factor de resistencia y susceptibilidad de la enfermedad periodontal así como los polimorfismos del gen de la vitamina D, del receptor fMLP , del receptor FcIIIb de los neutrófilos, del receptor FcgRII y de la N-acetyltransferasa (NAT2.Periodontitis is nowadays accepted as a multi-factorial disease with microbial agent as the initiator ,necessary but not enough , and a wide variety of determinants and factors that influence the manifestation and progression of the disease. The potencial importance of genetics and heredity to the knowledge about the pathogenesis and the clinic dental practice of periodontal diseases has been recognized since the earliest days of dentistry and medicine, but the relative complexity resulting from the interaction among the exposure to oral bacteria and the host response promote the dificulty of the genetics factors role clarification. Even so, genetic factors influence in periodontal diseases are suggest for several forms of periodontitis. In general, it’s considered the existence of sufficient scientific basis in favour of the genetic factors presence in Aggressive Periodontitis, whereas, the evidence of the genetic participation in Chronic Periodontitis isn’t so manifest. A multitude of host factors are involved in responses to microbial challenge and in the subsequent immune responses of the periodontal diseases, so, genetics polymorphisms probably exist in many of if not most of the inflammatory and immune mediators such as demonstrated by the IL-1,IL-4, IL-10,TNF, PGE2, specific HLA antigens (Human Leukocite Antigen, Vitamine D receptor, fMLP receptor, IgG Fc receptors (FcIIIb and FcgRII and the N-acetyltransferase (NAT2 receptor. Correlation of these genetic polymorphisms with phenotypic characteristics of periodontitis patients groups may provide the frame work for identification of individual risk profiles.

  7. Autism genetic database (AGD: a comprehensive database including autism susceptibility gene-CNVs integrated with known noncoding RNAs and fragile sites

    Directory of Open Access Journals (Sweden)

    Talebizadeh Zohreh

    2009-09-01

    Full Text Available Abstract Background Autism is a highly heritable complex neurodevelopmental disorder, therefore identifying its genetic basis has been challenging. To date, numerous susceptibility genes and chromosomal abnormalities have been reported in association with autism, but most discoveries either fail to be replicated or account for a small effect. Thus, in most cases the underlying causative genetic mechanisms are not fully understood. In the present work, the Autism Genetic Database (AGD was developed as a literature-driven, web-based, and easy to access database designed with the aim of creating a comprehensive repository for all the currently reported genes and genomic copy number variations (CNVs associated with autism in order to further facilitate the assessment of these autism susceptibility genetic factors. Description AGD is a relational database that organizes data resulting from exhaustive literature searches for reported susceptibility genes and CNVs associated with autism. Furthermore, genomic information about human fragile sites and noncoding RNAs was also downloaded and parsed from miRBase, snoRNA-LBME-db, piRNABank, and the MIT/ICBP siRNA database. A web client genome browser enables viewing of the features while a web client query tool provides access to more specific information for the features. When applicable, links to external databases including GenBank, PubMed, miRBase, snoRNA-LBME-db, piRNABank, and the MIT siRNA database are provided. Conclusion AGD comprises a comprehensive list of susceptibility genes and copy number variations reported to-date in association with autism, as well as all known human noncoding RNA genes and fragile sites. Such a unique and inclusive autism genetic database will facilitate the evaluation of autism susceptibility factors in relation to known human noncoding RNAs and fragile sites, impacting on human diseases. As a result, this new autism database offers a valuable tool for the research

  8. [Endemic goiter in Latium: environmental and genetic factors].

    Science.gov (United States)

    Paggi, A

    1998-01-01

    Most studies on the pathogenesis of endemic goiter focus above all on iodine deficiency. In some endemic goiter areas (i.e. Nigeria) there is no evidence of iodine deficiency; therefore, we suggest the taking into account of various factors, both environmental and non-environmental. We report the results of two studies carried out in three different areas in Latium: one of them (Cerveteri, RM) could be classified as high prevalence of goiter area, while the two others (Roccasecca dei Volsci, LT and Castel San Pietro Romano, RM) are true endemic goiter areas. The role of environmental factors, radioactivity and electromagnetism, foodstuff, the hydrogeological and chemical composition of natural water and the importance of genetics are here discussed, assuming that the endemic goiter could have a multifactorial pathogenesis.

  9. Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke.

    Science.gov (United States)

    Hanscombe, Ken B; Traylor, Matthew; Hysi, Pirro G; Bevan, Stephen; Dichgans, Martin; Rothwell, Peter M; Worrall, Bradford B; Seshadri, Sudha; Sudlow, Cathie; Williams, Frances M K; Markus, Hugh S; Lewis, Cathryn M

    2015-08-01

    Abnormal coagulation has been implicated in the pathogenesis of ischemic stroke, but how this association is mediated and whether it differs between ischemic stroke subtypes is unknown. We determined the shared genetic risk between 14 coagulation factors and ischemic stroke and its subtypes. Using genome-wide association study results for 14 coagulation factors from the population-based TwinsUK sample (N≈2000 for each factor), meta-analysis results from the METASTROKE consortium ischemic stroke genome-wide association study (12 389 cases, 62 004 controls), and genotype data for 9520 individuals from the WTCCC2 ischemic stroke study (3548 cases, 5972 controls-the largest METASTROKE subsample), we explored shared genetic risk for coagulation and stroke. We performed three analyses: (1) a test for excess concordance (or discordance) in single nucleotide polymorphism effect direction across coagulation and stroke, (2) an estimation of the joint effect of multiple coagulation-associated single nucleotide polymorphisms in stroke, and (3) an evaluation of common genetic risk between coagulation and stroke. One coagulation factor, factor XIII subunit B (FXIIIB), showed consistent effects in the concordance analysis, the estimation of polygenic risk, and the validation with genotype data, with associations specific to the cardioembolic stroke subtype. Effect directions for FXIIIB-associated single nucleotide polymorphisms were significantly discordant with cardioembolic disease (smallest P=5.7×10(-04)); the joint effect of FXIIIB-associated single nucleotide polymorphisms was significantly predictive of ischemic stroke (smallest P=1.8×10(-04)) and the cardioembolic subtype (smallest P=1.7×10(-04)). We found substantial negative genetic covariation between FXIIIB and ischemic stroke (rG=-0.71, P=0.01) and the cardioembolic subtype (rG=-0.80, P=0.03). Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype. © 2015 The

  10. Genetic and non-iodine-related factors in the aetiology of nodular goitre

    DEFF Research Database (Denmark)

    Knudsen, Nils; Brix, Thomas Heiberg

    2014-01-01

    Genetic and a large number of environmental non-iodine-related factors play a role in the cause of nodular goitre. Most evidence for the influence of genetic and environmental factors in the cause of goitre is from cross-sectional, population-based studies. Only a few studies have included...... prospective data on risk factors for nodular goitre, although few prospective data are available on the effect of iodine and tobacco smoking on goitre development. Goitre is not one single phenotype. Many epidemiological studies do not distinguish diffuse from nodular goitre, as the investigated parameter...... is often thyroid volume or frequency with increased thyroid volume. Moreover, information on the presence and effect of gene-environment, gene-gene, and environment-environment effect modifications is limited. Thus, firm conclusions about the relative contributions and causality of the investigated risk...

  11. Prognostic factors of infantile spasms: role of treatment options including a ketogenic diet.

    Science.gov (United States)

    Lee, Jeehun; Lee, Jun Hwa; Yu, Hee Jun; Lee, Munhyang

    2013-09-01

    The aim of this study was to provide additional evidences on prognostic factors for infantile spasms and the possible role of a ketogenic diet. A retrospective analysis was performed for patients with infantile spasms who had been followed up for more than 6months between January 2000 and July 2012 at Samsung Medical Center (Seoul, Republic of Korea). We analyzed the association between possible prognostic factors and seizure/developmental outcomes. Sixty-nine patients were included in this study and their mean follow-up duration was 52.5 (9-147) months. In the patients who had been followed up for more than 2years, 53.6% (n=30/57) remained seizure-free at the last visit. Sixty patients (86.9%) showed developmental delay at last follow-up. Forty-two patients (60.9%) became spasm-free with one or two antiepileptic drugs, one patient with epilepsy surgery for a tumor, and seven patients with a ketogenic diet after the failure of two or more antiepileptic drugs. The etiology and age of seizure onset were the significant prognostic factors. In this study, about 60% of the patients became spasm-free with vigabatrin and topiramate. Ketogenic diet increased the rate by 10% in the remaining antiepileptic drug resistant patients. However, 86.9% of the patients showed developmental delay, mostly a severe degree. Early diagnosis and prompt application of treatment options such as antiepileptic drugs, a ketogenic diet or epilepsy surgery can improve outcomes in patients with infantile spasms. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  12. Macroenvironmental factors including GDP per capita and physical activity in Europe.

    Science.gov (United States)

    Cameron, Adrian J; Van Stralen, Maartje M; Kunst, Anton E; Te Velde, Saskia J; Van Lenthe, Frank J; Salmon, Jo; Brug, Johannes

    2013-02-01

    Socioeconomic inequalities in physical activity at the individual level are well reported. Whether inequalities in economic development and other macroenvironmental variables between countries are also related to physical activity at the country level is comparatively unstudied. We examined the relationship between country-level data on macroenvironmental factors (gross domestic product (GDP) per capita, public sector expenditure on health, percentage living in urban areas, and cars per 1000 population) with country-level physical activity prevalence obtained from previous pan-European studies. Studies that assessed leisuretime physical activity (n = 3 studies including 27 countries in adults, n = 2 studies including 28 countries in children) and total physical activity (n = 3 studies in adults including 16 countries) were analyzed separately as were studies among adults and children. Strong and consistent positive correlations were observed between country prevalence of leisure-time physical activity and country GDP per capita in adults (average r = 0.70; all studies, P G 0.05). In multivariate analysis, country prevalence of leisure-time physical activity among adults remained associated with country GDP per capita (two of three studies) but not urbanization or educational attainment. Among school-age populations, no association was found between country GDP per capita and country prevalence of leisure-time physical activity. In those studies that assessed total physical activity (which also includes occupational and transport physical activity), no association with country GDP per capita was observed. Clear differences in national leisure-time physical activity levels throughout Europe may be a consequence of economic development. Lack of economic development of some countries in Europe may make increasing leisure-time physical activity more difficult. Further examination of the link between country GDP per capita and national physical activity levels (across

  13. Genetic and environmental factors influencing the Placental Growth Factor (PGF) variation in two populations

    DEFF Research Database (Denmark)

    Sorice, Rossella; Ruggiero, Daniela; Nutile, Teresa

    2012-01-01

    . However, to date, no information is available regarding the genetics of PGF variability. Furthermore, even though the effect of environmental factors (e.g.: cigarette smoking) on angiogenesis has been explored, no data on the influence of these factors on PGF levels have been reported so far. Here we have...... first investigated PGF variability in two cohorts focusing on non-genetic risk factors: a study sample from two isolated villages in the Cilento region, South Italy (N=871) and a replication sample from the general Danish population (N=1,812). A significant difference in PGF mean levels was found...... between the two cohorts. However, in both samples, we observed a strong correlation of PGF levels with ageing and sex, men displaying PGF levels significantly higher than women. Interestingly, smoking was also found to influence the trait in the two populations, although differently. We have then focused...

  14. Genetic and environmental factors influencing the Placental Growth Factor (PGF variation in two populations.

    Directory of Open Access Journals (Sweden)

    Rossella Sorice

    Full Text Available Placental Growth Factor (PGF is a key molecule in angiogenesis. Several studies have revealed an important role of PGF primarily in pathological conditions (e.g.: ischaemia, tumour formation, cardiovascular diseases and inflammatory processes suggesting its use as a potential therapeutic agent. However, to date, no information is available regarding the genetics of PGF variability. Furthermore, even though the effect of environmental factors (e.g.: cigarette smoking on angiogenesis has been explored, no data on the influence of these factors on PGF levels have been reported so far. Here we have first investigated PGF variability in two cohorts focusing on non-genetic risk factors: a study sample from two isolated villages in the Cilento region, South Italy (N=871 and a replication sample from the general Danish population (N=1,812. A significant difference in PGF mean levels was found between the two cohorts. However, in both samples, we observed a strong correlation of PGF levels with ageing and sex, men displaying PGF levels significantly higher than women. Interestingly, smoking was also found to influence the trait in the two populations, although differently. We have then focused on genetic risk factors. The association between five single nucleotide polymorphisms (SNPs located in the PGF gene and the plasma levels of the protein was investigated. Two polymorphisms (rs11850328 and rs2268614 were associated with the PGF plasma levels in the Cilento sample and these associations were strongly replicated in the Danish sample. These results, for the first time, support the hypothesis of the presence of genetic and environmental factors influencing PGF plasma variability.

  15. Genetic update on inflammatory factors in ulcerative colitis: Review of the current literature

    Institute of Scientific and Technical Information of China (English)

    Patricia; Sarlos; Erzsebet; Kovesdi; Lili; Magyari; Zsolt; Banfai; Andras; Szabo; Andras; Javorhazy; Bela; Melegh

    2014-01-01

    Ulcerative colitis(UC) is one of the main types of inflammatory bowel disease, which is caused by dysregulated immune responses in genetically predisposed individuals. Several genetic factors, including interleukin and interleukin receptor gene polymorphisms and other inflammation-related genes play central role in mediating and modulating the inflammation in the human body, thereby these can be the main cause of development of the disease. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but summarized literature is exiguous for challenge health specialist that can used in the clinical practice nowadays. This review summarizes the current literature on inflammationrelated genetic polymorphisms which are associated with UC. We performed an electronic search of Pubmed Database among publications of the last 10 years, using the following medical subject heading terms: UC, ulcerative colitis, inflammation, genes, polymorphisms, and susceptibility.

  16. Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico.

    Science.gov (United States)

    Ramos-Lopez, Omar; Martinez-Lopez, Erika; Roman, Sonia; Fierro, Nora A; Panduro, Arturo

    2015-11-07

    Liver cirrhosis (LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features.

  17. Genetic and non-iodine-related factors in the aetiology of nodular goitre.

    Science.gov (United States)

    Knudsen, Nils; Brix, Thomas Heiberg

    2014-08-01

    Genetic and a large number of environmental non-iodine-related factors play a role in the cause of nodular goitre. Most evidence for the influence of genetic and environmental factors in the cause of goitre is from cross-sectional, population-based studies. Only a few studies have included prospective data on risk factors for nodular goitre, although few prospective data are available on the effect of iodine and tobacco smoking on goitre development. Goitre is not one single phenotype. Many epidemiological studies do not distinguish diffuse from nodular goitre, as the investigated parameter is often thyroid volume or frequency with increased thyroid volume. Moreover, information on the presence and effect of gene-environment, gene-gene, and environment-environment effect modifications is limited. Thus, firm conclusions about the relative contributions and causality of the investigated risk factors should be made with caution. Smoking seems to be an established risk factor for nodular goitre, possibly with effect modification from iodine intake, as the risk associated with smoking is smaller or absent in areas with sufficient iodine intake. The use of oral contraceptives might have protective effects against goitre, and childbirth is an increased risk factor for goitre in areas with non-optimal iodine intake. Insulin resistance is a recently investigated risk factor, and the risk of goitre may be reversible with metformin treatment. Iodine remains the major environmental risk factor for nodular goitre.

  18. Fever in trauma patients: evaluation of risk factors, including traumatic brain injury.

    Science.gov (United States)

    Bengualid, Victoria; Talari, Goutham; Rubin, David; Albaeni, Aiham; Ciubotaru, Ronald L; Berger, Judith

    2015-03-01

    The role of fever in trauma patients remains unclear. Fever occurs as a response to release of cytokines and prostaglandins by white blood cells. Many factors, including trauma, can trigger release of these factors. To determine whether (1) fever in the first 48 hours is related to a favorable outcome in trauma patients and (2) fever is more common in patients with head trauma. Retrospective study of trauma patients admitted to the intensive care unit for at least 2 days. Data were analyzed by using multivariate analysis. Of 162 patients studied, 40% had fever during the first 48 hours. Febrile patients had higher mortality rates than did afebrile patients. When adjusted for severity of injuries, fever did not correlate with mortality. Neither the incidence of fever in the first 48 hours after admission to the intensive care unit nor the number of days febrile in the unit differed between patients with and patients without head trauma (traumatic brain injury). About 70% of febrile patients did not have a source found for their fever. Febrile patients without an identified source of infection had lower peak white blood cell counts, lower maximum body temperature, and higher minimum platelet counts than did febrile patients who had an infectious source identified. The most common infection was pneumonia. No relationship was found between the presence of fever during the first 48 hours and mortality. Patients with traumatic brain injury did not have a higher incidence of fever than did patients without traumatic brain injury. About 30% of febrile patients had an identifiable source of infection. Further studies are needed to understand the origin and role of fever in trauma patients. ©2015 American Association of Critical-Care Nurses.

  19. Genetic diversity and haplotype structure of 21 Y-STRs, including nine noncore loci, in South Tunisian Population: Forensic relevance.

    Science.gov (United States)

    Makki-Rmida, Faten; Kammoun, Arwa; Mahfoudh, Nadia; Ayadi, Adnene; Gibriel, Abdullah Ahmed; Mallek, Bakhta; Maalej, Leila; Hammami, Zouheir; Maatoug, Samir; Makni, Hafedh; Masmoudi, Saber

    2015-12-01

    Y chromosome STRs (Y-STRs) are being used frequently in forensic laboratories. Previous studies of Y-STR polymorphisms in different groups of the Tunisian population identified low levels of diversity and discrimination capacity (DC) using various commercial marker sets. This definitely limits the use of such systems for Y-STRs genotyping in Tunisia. In our investigation on South Tunisia, 200 unrelated males were typed for the 12 conventional Y-STRs included in the PowerPlex® Y System. Additional set of nine noncore Y-STRs including DYS446, DYS456, DYS458, DYS388, DYS444, DYS445, DYS449, DYS710, and DYS464 markers were genotyped and evaluated for their potential in improving DC. Allele frequency, gene diversity, haplotype diversity (HD), and DC calculation revealed that DYS464 was the most diverse marker followed by DYS710 and DYS449 markers. The standard panel of 12 Y-STRs (DC = 80.5%) and the nine markers were combined to obtain DC of 99%. Among the 198 different haplotypes observed, 196 haplotypes were unique (HD = 99.999). Out of the nine noncore set, six Y-STRs (DYS458, DYS456, DYS449, DYS710, DYS444, and DYS464) had the greatest impact on enhancing DC. Our data provided putative Y-STRs combination to be used for genetic and forensic applications.

  20. Identification of genetic risk factors for maxillary lateral incisor agenesis.

    Science.gov (United States)

    Alves-Ferreira, M; Pinho, T; Sousa, A; Sequeiros, J; Lemos, C; Alonso, I

    2014-05-01

    Tooth agenesis affects 20% of the world population, and maxillary lateral incisors agenesis (MLIA) is one of the most frequent subtypes, characterized by the absence of formation of deciduous or permanent lateral incisors. Odontogenesis is a complex mechanism regulated by sequential and reciprocal epithelial-mesenchymal interactions, controlled by activators and inhibitors involved in several pathways. Disturbances in these signaling cascades can lead to abnormalities in odontogenesis, resulting in alterations in the formation of the normal teeth number. Our aim was to study a large number of genes encoding either transcription factors or key components in signaling pathways shown to be involved in tooth odontogenesis. We selected 8 genes-MSX1, PAX9, AXIN2, EDA, SPRY2, TGFA, SPRY4, and WNT10A-and performed one of the largest case-control studies taking into account the number of genes and variants assessed, aiming at the identification of MLIA susceptibility factors. We show the involvement of PAX9, EDA, SPRY2, SPRY4, and WNT10A as risk factors for MLIA. Additionally, we uncovered 3 strong synergistic interactions between MLIA liability and MSX1-TGFA, AXIN2-TGFA, and SPRY2-SPRY4 gene pairs. We report the first evidence of the involvement of sprouty genes in MLIA susceptibility. This large study results in a better understanding of the genetic components and mechanisms underlying this trait.

  1. Genetic factors and asthma in aluminum smelter workers.

    Science.gov (United States)

    Arnaiz, Nilo O; Kaufman, Joel D; Daroowalla, Feroza M; Quigley, Sean; Farin, Federico; Checkoway, Harvey

    2003-04-01

    An asthma-like condition has been reported among aluminum smelter potroom workers. The pathophysiologic mechanisms and the causative agent involved are unknown. Inasmuch as gene polymorphisms are associated with asthma in the general population, the authors of this case-control study examined whether polymorphisms were associated with the development of potroom asthma. Genotyping was performed for the beta2-adrenoreceptor, high-affinity Ig (immunoglobulin) E receptor, and Tumor Necrosis Factor on potroom workers who developed a new asthma-like condition and on individuals who did not develop respiratory problems. No associations were found between potroom asthma case status and genotype. The asthma-like condition associated with potroom work remains poorly understood. Future investigations of genetic susceptibility and occupational asthma may provide pathophysiologic insights into these work-related conditions, but larger numbers of subjects will be required.

  2. Genetic and pharmacological factors that influence reproductive aging in nematodes.

    Directory of Open Access Journals (Sweden)

    Stacie E Hughes

    2007-02-01

    Full Text Available Age-related degenerative changes in the reproductive system are an important aspect of aging, because reproductive success is the major determinant of evolutionary fitness. Caenorhabditis elegans is a prominent organism for studies of somatic aging, since many factors that extend adult lifespan have been identified. However, mechanisms that control reproductive aging in nematodes or other animals are not well characterized. To use C. elegans to measure reproductive aging, we analyzed mated hermaphrodites that do not become sperm depleted and monitored the duration and level of progeny production. Mated hermaphrodites display a decline of progeny production that culminates in reproductive cessation before the end of the lifespan, demonstrating that hermaphrodites undergo reproductive aging. To identify factors that influence reproductive aging, we analyzed genetic, environmental, and pharmacological factors that extend lifespan. Dietary restriction and reduced insulin/insulin-like growth factor signaling delayed reproductive aging, indicating that nutritional status and a signaling pathway that responds to environmental stress influence reproductive aging. Cold temperature delayed reproductive aging. The anticonvulsant medicine ethosuximide, which affects neural activity, delayed reproductive aging, indicating that neural activity can influence reproductive aging. Some of these factors decrease early progeny production, but there is no consistent relationship between early progeny production and reproductive aging in strains with an extended lifespan. To directly examine the effects of early progeny production on reproductive aging, we used sperm availability to modulate the level of early reproduction. Early progeny production neither accelerated nor delayed reproductive aging, indicating that reproductive aging is not controlled by use-dependent mechanisms. The implications of these findings for evolutionary theories of aging are discussed.

  3. Genetic risk factors in infertile men with severe oligozoospermia and azoospermia

    NARCIS (Netherlands)

    G.R. Dohle (Gert); D.J.J. Halley (Dicky); J.O. van Hemel; A.M. van den Ouwel; M.H. Pieters; R.F.A. Weber (Robert); L.C. Govaerts (Lutgarde)

    2002-01-01

    textabstractBACKGROUND: Male infertility due to severe oligozoospermia and azoospermia has been associated with a number of genetic risk factors. METHODS: In this study 150 men from couples requesting ICSI were investigated for genetic abnormalities, such as constitutive chromosome

  4. Genetic risk factors in infertile men with severe oligozoospermia and azoospermia

    NARCIS (Netherlands)

    G.R. Dohle (Gert); D.J.J. Halley (Dicky); J.O. van Hemel; A.M. van den Ouwel; M.H. Pieters; R.F.A. Weber (Robert); L.C. Govaerts (Lutgarde)

    2002-01-01

    textabstractBACKGROUND: Male infertility due to severe oligozoospermia and azoospermia has been associated with a number of genetic risk factors. METHODS: In this study 150 men from couples requesting ICSI were investigated for genetic abnormalities, such as constitutive chromosome

  5. Health Promotion Behavior of Chinese International Students in Korea Including Acculturation Factors: A Structural Equation Model.

    Science.gov (United States)

    Kim, Sun Jung; Yoo, Il Young

    2016-03-01

    The purpose of this study was to explain the health promotion behavior of Chinese international students in Korea using a structural equation model including acculturation factors. A survey using self-administered questionnaires was employed. Data were collected from 272 Chinese students who have resided in Korea for longer than 6 months. The data were analyzed using structural equation modeling. The p value of final model is .31. The fitness parameters of the final model such as goodness of fit index, adjusted goodness of fit index, normed fit index, non-normed fit index, and comparative fit index were more than .95. Root mean square of residual and root mean square error of approximation also met the criteria. Self-esteem, perceived health status, acculturative stress and acculturation level had direct effects on health promotion behavior of the participants and the model explained 30.0% of variance. The Chinese students in Korea with higher self-esteem, perceived health status, acculturation level, and lower acculturative stress reported higher health promotion behavior. The findings can be applied to develop health promotion strategies for this population. Copyright © 2016. Published by Elsevier B.V.

  6. Genetics University of Toronto Thrombophilia Study in Women (GUTTSI: genetic and other risk factors for venous thromboembolism in women

    Directory of Open Access Journals (Sweden)

    Evrovski Jovan

    2001-05-01

    Full Text Available Abstract Background Women may be at increased risk for venous thromboembolism (VTE as compared with men. We studied the effects of genetic and biochemical markers of thrombophilia in women, in conjunction with other established risk factors for VTE. Method The present retrospective case-control study was conducted in a thrombosis treatment programme at a large Toronto hospital. The cases were 129 women aged 16-79 years with objectively confirmed VTE. Age-matched control individuals were women who were free of venous thrombosis. Neither cases nor control individuals had known cardiovascular disease. Participants were interviewed regarding personal risk factors for VTE, including smoking, history of malignancy, pregnancy, and oestrogen or oral contraceptive use. Blood specimens were analyzed for common single nucleotide polymorphisms of prothrombin, factor V and methylenetetrahydrofolate reductase (MTHFR; C677T, A1298C and T1317C, and the A66G polymorphism for methionine synthase reductase (MTRR.Fasting plasma homocysteine was also analyzed. Results Women with VTE were significantly more likely than female control individuals to carry the prothrombin polymorphism and the factor V polymorphism, or to have fasting hyperhomocysteinaemia. Homozygosity for the C677T MTHFR gene was not a significant risk factor for VTE, or were the A1298C or T1317C MTHFR homozygous variants. Also, the A66G MTRR homozygous state did not confer an increased risk for VTE. Conclusion Prothrombin and factor V polymorphisms increased the risk for VTE in women, independent from other established risk factors. Although hyperhomocysteinaemia also heightens this risk, common polymorphisms in two genes that are responsible for homocysteine remethylation do not. These findings are consistent with previous studies that included both men and women.

  7. Influence Factors on Consumers’ Cognition Level to Genetically Modified Food-taking Huangshi as an Example

    Directory of Open Access Journals (Sweden)

    Ruishan Chen

    2015-07-01

    Full Text Available This study aims to analyze the influence factors on consumers’ cognition level to genetically modified food and improve the consumers’ cognition level. In recent years, genetically modified foods in people’s daily life are becoming more and more common, but there is a lot of controversy about them. Based on the analysis of influence factors on consumers’ cognition level to GMF, a comprehensive system is established from four aspects, including the consumers’ personal characteristics, social-economic characteristics, household characteristics and awareness of risk. And Analytic Hierarchy Process (AHP method is used to make the quantitative research via investigation data of Huangshi, analyze the major influence on consumers’ cognition level to GMF. Finally some suggestions are proposed to promote the consumers’ cognition level to GMF.

  8. Importance of genetic factors in the occurrence of epilepsy syndrome type: a twin study

    DEFF Research Database (Denmark)

    Corey, Linda A; Pellock, John M; Kjeldsen, Marianne J

    2011-01-01

    Although there is strong evidence that genetic factors contribute to risk for epilepsy, their role in the determination of syndrome type is less clear. This study was undertaken to address this question. Information related to epilepsy was obtained from twins included in 455 monozygotic and 868...... dizygotic pairs ascertained from population-based twin registries in Denmark, Norway and the United States. Syndrome type was determined based on medical record information and detailed clinical interviews and classified using the International Classification Systems for the Epilepsies and Epileptic...... Syndromes. Concordance rates were significantly increased in monozygotic versus dizygotic pairs for all major syndrome groups except localization-related cryptogenic epilepsy. Among generalized epilepsies, genetic factors were found to play an important role in the determination of childhood absence...

  9. Asian flushing: genetic and sociocultural factors of alcoholism among East asians.

    Science.gov (United States)

    Lee, Haeok; Kim, Sun S; You, Kwang Soo; Park, Wanju; Yang, Jin Hyang; Kim, Minjin; Hayman, Laura L

    2014-01-01

    Alcohol use can lead to a cascade of problems such as increased chances of risky behavior and negative health consequences, including alcoholic liver disease and upper gastric and liver cancer. Ethanol is metabolized mainly by 2 major enzymes: alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). Genetic variations of genes encoding the 2 enzymes are very common among East Asians but relatively rare for most other populations. Facial flushing and other physical discomforts after alcohol drinking triggered by accumulation of acetaldehyde through defective genes for ADH and ALDH have been reported. Approximately 40% of East Asians (Chinese, Japanese, and Korean) show facial flushing after drinking alcohol, known as "Asian flush," which is characterized by adverse reactions on alcohol drinking in individuals possessing the fasting metabolizing alleles for ADH, ADH1B*2, and ADH1C*1, and the null allele for ALDH and ALDH2*2. Alcoholism is determined not only by the genetic deficiency but also by behaviors that involve complex interactions between genetic and sociocultural factors. The purpose of this article was to provide nurses with the most current information about genetic and sociocultural influences on alcoholism and alcohol-related health problems specifically for East Asians and implications of this knowledge to nursing practice. The physiological phenomenon of genes and genetics in relation to alcohol metabolism in this special population is emphasized.

  10. Genetic risk factors for Parkinson’s disease in Ukraine

    Directory of Open Access Journals (Sweden)

    A. K. Koliada

    2015-03-01

    Full Text Available The paper focuses on the genetic risk factors for Parkinson’s disease (PD such as polymorphisms in genes CYP1A1, GSTM1 and APOE. A total number of 516 people were examined. 300 persons were in the control group (mean age 67,0 ± 0,4 years; 200 males and 100 females and 216 persons were patients with PD (mean age 65,0 ± 0,7 years, 116 males and 100 females. Whole blood samples collected from each person were genotyped using PCR-RFLP. Amplification and restriction results were assessed by conducting vertical agarose gel electrophoresis. The study analyzed marker с.2452C>A in the CYP1A1 gene. In the control group, allele C frequency was 0.79, and allele A frequency – 0.21. Genotype frequencies were: CC – 0.61, AC – 0.36, AA – 0.03. In the group of patients alleles C and A frequencies were 0.64 and 0.36 correspondingly. Genotype frequencies were: CC – 0.35, AC – 0.58, AA – 0.07. There was a significant difference between both groups in allele A frequency. It is considered that 0/0 genotype for the GSTM1 gene is a risk factor for PD. In the controls, +/+ and 0/0 genotypes frequencies were 0.67 and 0.33 correspondingly. In the group of patients +/+ genotype frequency was 0.55 and 0/0 genotype frequency – 0.45. The difference was statistically significant. In the control group genotype frequencies for the АРОЕ gene were 0.715 (Е3/Е3, 0.077 (Е3/Е4, 0.009 (Е4/Е4, 0.167 (Е2/Е3, 0.031 (Е2/Е4 and 0.000 (Е2/Е2. In the group of patients with PD they were 0.634 (Е3/Е3, 0.148 (Е3/Е4, 0.032 (Е4/Е4, 0.157 (Е2/Е3, 0.023 (Е2/Е4 and 0.000 (Е2/Е2. Е3/Е4 genotype frequency was significantly higher in the group of patients with PD than in the control group. Pathogenic allele с.2452C>A of the CYP1A1 gene is associated with increased risk of PD (OR = 1.72. 0/0 genotype carriers have higher risk to develop PD (OR = 1.72. Allele έ4 of the АРОЕ gene may be associated with increased risk of PD. Risk of the disease is

  11. Genetically Determined Chronic Pancreatitis but not Alcoholic Pancreatitis Is a Strong Risk Factor for Pancreatic Cancer.

    Science.gov (United States)

    Midha, Shallu; Sreenivas, Vishnubhatla; Kabra, Madhulika; Chattopadhyay, Tushar Kanti; Joshi, Yogendra Kumar; Garg, Pramod Kumar

    2016-11-01

    To study if chronic pancreatitis (CP) is a risk factor for pancreatic cancer. Through a cohort and a case-control study design, CP and other important risk factors including smoking, diabetes, alcohol, obesity, and genetic mutations were studied for their association with pancreatic cancer. In the cohort study, 402 patients with CP were included. During 3967.74 person-years of exposure, 5 of the 402 patients (4 idiopathic CP, 1 hereditary CP) developed pancreatic cancer after 16.60 ± 3.51 years of CP. The standardized incidence ratio was 121. In the case-control study, 249 pancreatic cancer patients and 1000 healthy controls were included. Of the 249 patients with pancreatic cancer, 24 had underlying idiopathic CP, and none had alcoholic pancreatitis. SPINK1 gene mutation was present in 16 of 26 patients with idiopathic CP who had pancreatic cancer. Multivariable analysis showed CP (odds ratio [OR], 97.67; 95% confidence interval [CI], 12.69-751.36), diabetes (>4 years duration) (OR, 3.05; 95% CI, 1.79-5.18), smoking (OR, 1.93; 95% CI, 1.38-2.69) as significant risk factors for pancreatic cancer. The population attributable risk was 9.41, 9.06, and 9.50 for diabetes, CP, and smoking, respectively. Genetically determined CP but not alcoholic CP is a strong risk factor for pancreatic cancer.

  12. 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...

  13. Effect of including genetic Progress in milk yield on evaluating the use of sexed semen and other reproduction strategies in a dairy herd

    DEFF Research Database (Denmark)

    Ettema, Jehan F.; Østergaard, Søren; Sørensen, Morten Kargo

    2011-01-01

    The objective of this study was to explore the importance of including genetic progress in milk yield when evaluating different reproductive strategies in a dairy herd by simulation modeling. The model used in this study was SimHerd V, a dynamic and mechanistic Monte Carlo simulation model...... effect with regard to postponing first insemination. This study has proven that it is important to include genetic progress in decisions on reproduction strategies in a dairy herd....

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

    Science.gov (United States)

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

    2014-01-01

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

  15. [Progress in studies on the genetic risk factors for nonsyndromic cleft lip or palate in China].

    Science.gov (United States)

    Huang, Y Q

    2017-04-09

    Cleft lip and palate is the most common congenital defects of oral and maxillofacial region in human beings. The etiology of this malformation is complex, with both genetic and environmental causal factors are involved. To provide a better understanding in the genetic etiology of cleft lip or palate, the author summarized recent years studies based on Chinese population. Those researches included validation of some candidate genes for cleft lip or palate, using genome wide association analysis which included six independent cohorts from China to elucidate the genetic architecture of non-syndromic cleft lip with or without cleft palate in Chinese population and finally found a new susceptibility locus. This locus was on the 16p13.3 (rs8049367) between CREBBP and ADCY9. It has been mentioned common methods of genetic analysis involved in the researches on cleft lip or palate in this paper. Furthermore, we try to discuss new methods to illustrate the etiology of cleft lip and palate that could provide more inspiration on future researches.

  16. Factorization of Radiative Leptonic Decays of $B^-$ and $D^-$ Mesons Including the Soft Photon Region

    CERN Document Server

    Yang, Ji-Chong

    2016-01-01

    In this work, we study the radiative leptonic decays of $B^-$ and $D^-$ mesons using factorization approach. Factorization is proved to be valid explicitly at 1-loop level at any order of $O(\\Lambda _{\\rm QCD}\\left/m_Q\\right.)$. We consider the contribution in the soft photon region that $E_{\\gamma} \\sim \\left. \\Lambda^2 _{\\rm QCD} /\\right. m_Q$. The numerical results shows that, the soft photon region is very important for both the $B$ and $D$ mesons. The branching ratios of $B\\to \\gamma e\

  17. Novel Ciliate Genetic Code Variants Including the Reassignment of All Three Stop Codons to Sense Codons in Condylostoma magnum.

    Science.gov (United States)

    Heaphy, Stephen M; Mariotti, Marco; Gladyshev, Vadim N; Atkins, John F; Baranov, Pavel V

    2016-11-01

    mRNA translation in many ciliates utilizes variant genetic codes where stop codons are reassigned to specify amino acids. To characterize the repertoire of ciliate genetic codes, we analyzed ciliate transcriptomes from marine environments. Using codon substitution frequencies in ciliate protein-coding genes and their orthologs, we inferred the genetic codes of 24 ciliate species. Nine did not match genetic code tables currently assigned by NCBI. Surprisingly, we identified a novel genetic code where all three standard stop codons (TAA, TAG, and TGA) specify amino acids in Condylostoma magnum We provide evidence suggesting that the functions of these codons in C. magnum depend on their location within mRNA. They are decoded as amino acids at internal positions, but specify translation termination when in close proximity to an mRNA 3' end. The frequency of stop codons in protein coding sequences of closely related Climacostomum virens suggests that it may represent a transitory state. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  18. Situational effects of the school factors included in the dynamic model of educational effectiveness

    NARCIS (Netherlands)

    Creerners, Bert; Kyriakides, Leonidas

    2009-01-01

    We present results of a longitudinal study in which 50 schools, 113 classes and 2,542 Cypriot primary students participated. We tested the validity of the dynamic model of educational effectiveness and especially its assumption that the impact of school factors depends on the current situation of th

  19. Latina Resilience in Higher Education: Contributing Factors Including Seasonal Farmworker Experiences

    Science.gov (United States)

    Graff, Cristina Santamaria; McCain, Terrence; Gomez-Vilchis, Veronica

    2013-01-01

    Many Latina students overcome multiple obstacles to earn university degrees. Five married Latina women with children and seasonal farmworker backgrounds are the focus of this study which is analyzed through resiliency theory to understand factors contributing to their academic resilience. Variables connected to academic success are explored and…

  20. Simultaneous Spectrophotometric Determination of Four Components including Acetaminophen by Taget Factor Analysis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    UV Spectrophotometric Target Factor Analysis (TFA) was used for the simultaneous determination of four components (acetaminophen, guuaifenesin, caffeine, Chlorphenamine maleate) in cough syrup. The computer program of TFA is based on VC++ language. The difficulty of overlapping of absorption spectra of four compounds was overcome by this procedure. The experimental results show that the average recovery of each component is all in the range from 98.9% to 106.8% and each component obtains satisfactory results without any pre-separation.

  1. The N(H2/I(CO Conversion Factor: A Treatment that Includes Radiative Transfer

    Directory of Open Access Journals (Sweden)

    W. F. Wall

    2006-01-01

    Full Text Available Se presenta un tratamiento que explica mejor el factor de conversión N(H2=I(CO y que incluye la transferencia radiativa. A primera vista, incluir la transferencia radiativa parece superfluo para una línea óptimamente gruesa como CO J = 1 0. No obstante, dado que el medio interestelar es inhomogéneo, los fragmentos de gas (es decir, grumos todavía pueden ser óptimamente delgadas hacia sus bordes y en las alas de los pérfiles de la línea. El tratamiento estadístico de Martin et al. (1984 de la transferencia radiativa a través una nube molecular con grumos se usa para derivar una expresión para el factor de conversión que su- pera los defectos de las explicaciones más tradicionales basadas en Dickman et al. (1986. Por un lado, el tratamiento presentado aquí posiblemente representa un avance importante al entender el factor de conversión N(H2=I(CO pero, por otro lado, tiene sus propios defectos, que son discutidos aquí brevemente.

  2. Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Shiga

    2016-01-01

    Full Text Available Aims. To evaluate the prognostic significance of serum interleukin-6 (IL-6 in colorectal cancer (CRC. Patients and Methods. Preoperative serum IL-6 was measured in 233 CRC patients and 13 healthy controls. Relationships between IL-6 and various clinicopathological factors were evaluated, and the overall survival (OS and disease-free survival (DFS rates according to IL-6 status were calculated for all patients and according to disease stage. Results. The mean IL-6 level was 6.6 pg/mL in CRC patients and 2.6 pg/mL in healthy controls. Using a cutoff of 6.3 pg/mL, obtained using receiver operating characteristic curve analysis, 57 patients had a high IL-6 level. The mean value was higher for stage II disease than for stage III disease. IL-6 status correlated with C-reactive protein (CRP and carcinoembryonic antigen levels, obstruction, and pT4 disease. The OS differed according to the IL-6 status for all patients, whereas the DFS differed for all patients and for those with stage II disease. The Cox proportional hazards model showed that pT4 disease was an independent risk factor for recurrence in all CRC patients; IL-6, CRP, and pT4 were significant risk factors in stage II patients. Conclusions. The preoperative IL-6 level influences the risk of CRC recurrence.

  3. A genetic map of melon highly enriched with fruit quality QTLs and EST markers, including sugar and carotenoid metabolism genes

    Science.gov (United States)

    A genetic map of melon enriched for fruit traits was constructed, using a recombinant inbred (RI) population developed from a cross between representatives of the two subspecies of Cucumis melo L.: PI 414723 (subspecies agrestis) and 'Dulce' (subspecies melo). Phenotyping of 99 RI lines was conducte...

  4. Coeliac disease : investigation of the genetic factors underlying coeliac disease

    NARCIS (Netherlands)

    Belzen, M.J. (Martine Juliana) van

    2003-01-01

    Coeliac disease is a common food intolerance with a complex genetic aetiology. It is caused by ingestion of gluten peptides from wheat and related proteins from barley and rye in genetically susceptible individuals. The disease affects the small intestine and leads to abnormalities ranging from the

  5. Coeliac disease : investigation of the genetic factors underlying coeliac disease

    NARCIS (Netherlands)

    Belzen, M.J. (Martine Juliana) van

    2004-01-01

    Coeliac disease is a common food intolerance with a complex genetic aetiology. It is caused by ingestion of gluten peptides from wheat and related proteins from barley and rye in genetically susceptible individuals. The disease affects the small intestine and leads to abnormalities ranging from the

  6. Mapping genetic factors controlling potato/cyst nematode interactions.

    NARCIS (Netherlands)

    Rouppe van der Voort, J.N.A.M.

    1998-01-01

    The thesis describes strategies for genetic mapping of the genomes of the potato cyst nematode and potato. Mapping in cyst nematodes was achieved by AFLP genotyping of single cysts and subsequent segregation analysis in a family of sibling populations. The genetic map of Globodera rostochiensis comp

  7. Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.

    Science.gov (United States)

    Corominas, Roser; Yang, Xinping; Lin, Guan Ning; Kang, Shuli; Shen, Yun; Ghamsari, Lila; Broly, Martin; Rodriguez, Maria; Tam, Stanley; Trigg, Shelly A; Fan, Changyu; Yi, Song; Tasan, Murat; Lemmens, Irma; Kuang, Xingyan; Zhao, Nan; Malhotra, Dheeraj; Michaelson, Jacob J; Vacic, Vladimir; Calderwood, Michael A; Roth, Frederick P; Tavernier, Jan; Horvath, Steve; Salehi-Ashtiani, Kourosh; Korkin, Dmitry; Sebat, Jonathan; Hill, David E; Hao, Tong; Vidal, Marc; Iakoucheva, Lilia M

    2014-04-11

    Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors. The Autism Spliceform Interaction Network reveals that almost half of the detected interactions and about 30% of the newly identified interacting partners represent contribution from splicing variants, emphasizing the importance of isoform networks. Isoform interactions greatly contribute to establishing direct physical connections between proteins from the de novo autism CNVs. Our findings demonstrate the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases.

  8. Nuclear monopole charge form factor calculation for relativistic models including center-of-mass corrections

    Energy Technology Data Exchange (ETDEWEB)

    Avancini, S.S.; Marinelli, J.R. [Universidade Federal de Santa Catarina Florianopolis, Depto de Fisica - CFM, Florianopolis (Brazil); Carlson, B.V. [Instituto Tecnologico de Aeronautica, Sao Jose dos Campos (Brazil)

    2013-06-15

    Relativistic models for finite nuclei contain spurious center-of-mass motion in most applications for the nuclear many-body problem, where the nuclear wave function is taken as a single Slater determinant within a space-fixed frame description. We use the Peierls-Yoccoz projection method, previously developed for relativistic approaches together with a reparametrization of the coupling constants that fits binding energies and charge radius and apply our results to calculate elastic electron scattering monopole charge form factors for light nuclei. (orig.)

  9. SUBSTANTIATION OF THE COST OF HOUSING CONSTRUCTION INCLUDING THE FACTOR OF INVESTMENT ATTRACTIVENESS OF TERRITORIES

    Directory of Open Access Journals (Sweden)

    ZAIATS Yi. I.

    2015-11-01

    Full Text Available Problem statement. For planning and organization of urban construction is necessary to analyze the use of areas. Territorial resources of the city, being used for construction and other urban purposes, consists of plots of land: disposable, reserved and undeveloped in previous years of construction in progress; residential districts and blocks of obsolete housing fund; industrial and municipal and warehouse enterprises being used irrationally or stopped to work; the defence department, where the amortized warehouses and other main funds are that are not used by purpose; agricultural enterprises where the obsolete industrial funds, haying, nurseries, greenhouses. The number of free areas suitable for future urban development is extremely limited. However a considerable part of the territories of almost all functional zones is used inefficiently. Purpose. Formalization of a factor of investment attractiveness of territories for the further identification and research of the connection between it and the cost of housing construction is necessary. Conclusion. The identification of regularities of influence of the factor of investment attractiveness of territories on the cost of construction of high-rise buildings allow to obtain a quantitative estimate of this effect and can be used in the development of the methodology of substantiation of the expediency and effectiveness of the implementation of highrise construction projects, based on organizational and technological aspects.

  10. Genetic factors influencing inhibitor development in a cohort of South African haemophilia A patients.

    Science.gov (United States)

    Lochan, A; Macaulay, S; Chen, W C; Mahlangu, J N; Krause, A

    2014-09-01

    A critical complication of factor VIII (FVIII) replacement therapy in Haemophilia A (HA) treatment is inhibitor development. Known genetic factors predisposing to inhibitor development include FVIII (F8) gene mutations, ethnicity, a family history of inhibitors and FVIII haplotype mismatch. The aim of this study was to characterize and correlate these genetic factors in a cohort of South African HA patients. This was a retrospective study that included 229 patients and involved the analysis of patient files, HA molecular and clinical databases and molecular analysis of the F8 gene haplotype. Of the 229 patients, 51% were of black ethnicity, 49% were white, 5% had mild HA, 4% were moderate and 91% were severe, 36% were int22 positive and 13% were inhibitor positive. Of the inhibitor positive patients, 72% were black patients. Inhibitors were reported in 27% of black int22 positive patients, 13% of black int22 negative patients, 9% of white int22 positive patients and 7% of white int22 negative. The H1 haplotype was more common in whites (75%) and H2 was more common in blacks (74%). H3 and H5 were only found in black patients and had a higher frequency of inhibitor development than H1 and H2. In this small HA cohort, black patients had a significantly higher frequency of inhibitor development and the results were indicative of an association between inhibitor development, ethnicity and haplotype. © 2014 John Wiley & Sons Ltd.

  11. CD24: from a Hematopoietic Differentiation Antigen to a Genetic Risk Factor for Multiple Autoimmune Diseases.

    Science.gov (United States)

    Tan, Yixin; Zhao, Ming; Xiang, Bo; Chang, Christopher; Lu, Qianjin

    2016-02-01

    The autoantibody is an essential characteristic of inflammatory disorders, including autoimmune diseases. Although the exact pathogenic mechanisms of these diseases remain elusive, accumulated evidence has implicated that genetic factors play important roles in autoimmune inflammation. Among these factors, CD24 was first identified as a heat-stable antigen in 1978 and first successfully cloned in 1990. Thereafter, its functional roles have been intensively investigated in various human diseases, especially autoimmune diseases and cancers. It is currently known that CD24 serves as a costimulatory factor of T cells that regulate their homeostasis and proliferation, while in B cells, CD24 is functionally involved in cell activation and differentiation. CD24 can enhance autoimmune diseases in terms of its protective role in the clonal deletion of autoreactive thymocytes. Furthermore, CD24 deficiency has been linked to mouse experimental autoimmune encephalomyelitis. Finally, CD24 genetic variants, including single-nucleotide polymorphisms and deletions, are etiologically relevant to autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus. Therefore, CD24 is a promising biomarker and novel therapeutic target for autoimmune diseases.

  12. Adrenomedullin A Novel Peptide Requires Coordination Of Genetic Physiologic And Environmental Factors

    Directory of Open Access Journals (Sweden)

    K. R. Padma

    2015-08-01

    Full Text Available A healthy pregnancy requires strict coordination of genetic physiologic and environmental factors. The relatively common incidence of infertility and pregnancy complications has resulted in increased interest in understanding the mechanisms that underlie normal versus abnormal pregnancy. The peptide hormone adrenomedullin has recently been the focus of some exciting breakthroughs in the pregnancy field. Adrenomedullin ADM is a 52-amino acid peptide with structural homology to calcitonin gene-related peptide CGRP initially isolated from human pheochromocytoma. ADM is synthesized by many mammalian tissues including the adrenal medulla endothelial and vascular smooth muscle cells myocardium and central nervous system. ADM binds to plasma membrane receptors composed of calcitonin receptor-like receptor CRLR a member of serpentine receptor superfamily and receptor activity modifying protein RAMP type 2 or 3. ADM has also some affinity for CGRP receptor composed of CRLR and RAMP1. Supported by mechanistic studies in genetic animal models there continues to be a growing body of evidence demonstrating the importance of adrenomedullin protein levels in a variety of human pregnancy complications. With measurement of foetal resorption sites we can examine the importance of adrenomedullin a peptide hormone in pregnancy which alters due to genetic physiologic and environmental factors. A growing body of evidence illustrates AM as a pivotal component in normal physiology and disease with marked beneficial effects in the host defense mechanism.

  13. Modelling of safety barriers including human and organisational factors to improve process safety

    DEFF Research Database (Denmark)

    Markert, Frank; Duijm, Nijs Jan; Thommesen, Jacob

    2013-01-01

    explosion, and the Mont Blanc Tunnel Fire, such an approach may have helped to maintain the integrity of the designed provisions against major deviations resulting in these disasters. In order to make this paradigm operational, safety management and in particular risk assessment tools need to be refined....... A valuable approach is the inclusion of human and organisational factors into the simulation of the reliability of the technical system using event trees and fault trees and the concept of safety barriers. This has been demonstrated e.g. in the former European research project ARAMIS (Accidental Risk...... Assessment Methodology for IndustrieS, see Salvi et al 2006). ARAMIS employs the bow-tie approach to modelling hazardous scenarios, and it suggests the outcome of auditing safety management to be connected to a semi-quantitative assessment of the quality of safety barriers. ARAMIS discriminates a number...

  14. Interaction between genetic and environmental risk factors for Alzheimer's disease: A reanalysis of case-control studies

    NARCIS (Netherlands)

    C.M. van Duijn (Cock); D.G. Clayton (David); V. Chandra; L. Fratiglioni (Laura); A.B. Graves; A. Heyman; A.F. Jorm; E. Kokmen (Emre); K. Kondo; J.A. Mortimer; W.A. Rocca (Walter); S.L. Shalat; H. Soininen (H.); A. Hofman (Albert)

    1994-01-01

    textabstractTo study the interaction among genetic and environmental risk factors, a reanalysis of case-control studies of Alzheimer's disease (AD) was conducted based on the original data of all studies carried out to January 1, 1990. Seven studies were included in the present analysis, comprising

  15. Interaction between genetic and environmental risk factors for Alzheimer's disease: a re-analysis of case-control studies

    NARCIS (Netherlands)

    C.M. van Duijn (Cock); D.G. Clayton (David); V. Chandra; L. Fratiglioni (Laura); A.B. Graves; A. Heyman; A.F. Jorm; E. Kokmen (Emre); K. Kondo; J.A. Mortimer; W.A. Rocca; S.L. Shalat; H. Soininen; A. Hofman (Albert)

    1994-01-01

    textabstractTo study the interaction among genetic and environmental risk factors, a reanalysis of case-control studies of Alzheimer's disease (AD) was conducted based on the original data of all studies carried out to January 1, 1990. Seven studies were included in the present analysis, comprising

  16. A genetically diverse but distinct North American population of Sarcocystis neurona includes an overrepresented clone described by 12 microsatellite alleles.

    Science.gov (United States)

    Asmundsson, Ingrid M; Dubey, J P; Rosenthal, Benjamin M

    2006-09-01

    The population genetics and systematics of most coccidians remain poorly defined despite their impact on human and veterinary health. Non-recombinant parasite clones characterized by distinct transmission and pathogenesis traits persist in the coccidian Toxoplasma gondii despite opportunities for sexual recombination. In order to determine whether this may be generally true for tissue-cyst forming coccidia, and to address evolutionary and taxonomic problems within the genus Sarcocystis, we characterized polymorphic microsatellite markers in Sarcocystis neurona, the major causative agent of equine protozoal myeloencephalitis (EPM). Bayesian statistical modeling, phylogenetic reconstruction based on genotypic chord distances, and analyses of linkage disequilibrium were employed to examine the population structure within S. neurona and closely related Sarcocystis falcatula isolates from North and South America. North American S. neurona were clearly differentiated from those of South America and also from isolates of S. falcatula. Although S. neurona is characterized by substantial allelic and genotypic diversity typical of interbreeding populations, one genotype occurs with significantly excessive frequency; thus, some degree of asexual propagation of S. neurona clones may naturally occur. Finally, S. neurona isolated from disparate North American localities and diverse hosts (opossums, a Southern sea otter, and horses) comprise a single genetic population. Isolates associated with clinical neurological disease bear no obvious distinction as measured by these presumably neutral genetic markers.

  17. A propensity score approach to correction for bias due to population stratification using genetic and non-genetic factors.

    Science.gov (United States)

    Zhao, Huaqing; Rebbeck, Timothy R; Mitra, Nandita

    2009-12-01

    Confounding due to population stratification (PS) arises when differences in both allele and disease frequencies exist in a population of mixed racial/ethnic subpopulations. Genomic control, structured association, principal components analysis (PCA), and multidimensional scaling (MDS) approaches have been proposed to address this bias using genetic markers. However, confounding due to PS can also be due to non-genetic factors. Propensity scores are widely used to address confounding in observational studies but have not been adapted to deal with PS in genetic association studies. We propose a genomic propensity score (GPS) approach to correct for bias due to PS that considers both genetic and non-genetic factors. We compare the GPS method with PCA and MDS using simulation studies. Our results show that GPS can adequately adjust and consistently correct for bias due to PS. Under no/mild, moderate, and severe PS, GPS yielded estimated with bias close to 0 (mean=-0.0044, standard error=0.0087). Under moderate or severe PS, the GPS method consistently outperforms the PCA method in terms of bias, coverage probability (CP), and type I error. Under moderate PS, the GPS method consistently outperforms the MDS method in terms of CP. PCA maintains relatively high power compared to both MDS and GPS methods under the simulated situations. GPS and MDS are comparable in terms of statistical properties such as bias, type I error, and power. The GPS method provides a novel and robust tool for obtaining less-biased estimates of genetic associations that can consider both genetic and non-genetic factors.

  18. Contribution of Environmental Risk Factors Including Lifestyle to Inequalities Noncommunicable (Chronic Diseases such as Diabetes

    Directory of Open Access Journals (Sweden)

    Elzbieta Grochowska Niedworok

    2015-06-01

    Full Text Available Health inequalities: differences in health status or in the distribution of health determinants between different population groups. Some health inequalities are attributable to biological variations or free choice and others are attributable to the external environment and conditions mainly outside the control of the individuals concerned. 347 million people worldwide have diabetes. In 2012 an estimated 1.5 million deaths were directly caused by diabetes. More than 80% of diabetes deaths occur in low- and middle-income countries. WHO projects that diabetes will be the 7th leading cause of death in 2030. Healthy diet, regular physical activity and maintaining a normal body weight can prevent or delay the onset of type 2 diabetes. Risk factors: 1. Age- the prevalence of diabetes rises steeply with age: *one in twenty people over the age of 65 have diabetes, *and this rises to one in five people over the age of 85 years. The diagnosis of diabetes may be delayed in older people, with symptoms of diabetes being wrongly attributed to ageing. 2. Ethnic: type 2 diabetes is up to six times more common in people of South Asian descent and up to three times more common in those of African and African-Caribbean descent then in the white population. It is also more common in people of Chinese descent and other non-Caucasian groups. 3. Gender: the frequency of diabetes usually is higher in men than in women. This may be because gender compounds other aspects of inequality- women often bear the brunt of poverty, and socio-economic differences in the prevalence of diabetes are more marked for women, probably because of differences in smoking rates, food choices and the prevalence of obesity. 4. Overweight/Obesity: every 1 kg/m2 more causes increase risk: cardiovascular diseases 2%, coronary artery disease- 3% , myocardial infarction- 5% , heart failure- 5% , peripheral vascular disease- 5%. Health inqualities important in diabetes -- modifiable:  social

  19. Genetic Factors that Affect Tumorigenesis in NF1

    Science.gov (United States)

    2004-11-01

    Boles, R. and Korf, B. (1995) Sanitarias de la Seguridad Social (98-0992) and Institut Catali Deletion of the entire NFI gene detected by FISH: four...Washington, Medical Genetics, Seattle, WA, USA, 2Medical and Molecular Genetics Center- IRO, Hospital Duran i Reynals, Barcelona, Spain, 3Servizio di... Hospital . Western blot analysis, using an anti-NF1 antibody (NFIGRD(D)) (Santa Cruz Biotechnology Inc, Santa Cruz, NF1 mutation analysis CA) and

  20. Plant Oils and Cardiometabolic Risk Factors: The Role of Genetics

    OpenAIRE

    Smith, Caren E.

    2012-01-01

    More than 25 years have passed since Ancel Keys and others observed that high intake of monounsaturated fatty acids, especially as supplied by plants (eg, olive oil) was associated with lower cardiovascular and overall mortality. About 15 years later, advances in genotyping technologies began to facilitate widespread study of relationships between dietary fats and genetic variants, illuminating the role of genetic variation in modulating human responses to fatty acids. More recently, microarr...

  1. Non-genetic risk factors and their influence on the management of patients in the clinic.

    Science.gov (United States)

    Álvarez, Teresa; Soto, Immaculada; Astermark, Jan

    2015-02-01

    The development of inhibitors is the most serious iatrogenic complication affecting patients with haemophilia. This complication is associated with impaired vital or functional prognosis, reduced quality of life and increased cost of treatment. The reasons why some patients develop antibodies to factor replacement and others do not remain unclear. It is however clear that inhibitor development results from a complex multifactorial interaction between genetic and non-genetic risk factors. Environmental influences implicated in increasing the risk of inhibitor formation can be viewed as modifiable risk factors. Therefore, identification of the non-genetic risk factors may offer the possibility of personalising haemophilia therapy by modifying treatment strategies in high-risk patients in the critical early phase of factor VIII exposure. In this article, we review the non-genetic factors reported as well as the potential impact of danger signals and the different scores for inhibitor development risk stratification.

  2. Genetic factors explain half of all variance in serum eosinophil cationic protein

    DEFF Research Database (Denmark)

    Elmose, Camilla; Sverrild, Asger; van der Sluis, Sophie

    2014-01-01

    , exhaled nitric oxide, and skin test reactivity, measured. Linear regression analysis and variance component models were used to study factors associated with variation in ECP and the relative genetic influence on ECP levels. RESULTS: Sex (regression coefficient = -0.107, P ... to the most parsimonious variance component model, genetic factors accounted for 57% (CI: 42-72%, P variance in ECP levels, whereas the remainder (43%) was ascribable to non-shared environmental factors. The genetic correlation between ECP and airway responsiveness to methacholine...... was statistically non-significant (r = -0.11, P = 0.50). CONCLUSION: Around half of all variance in serum ECP is explained by genetic factors. Serum ECP is influenced by sex, BMI, and airway responsiveness. Serum ECP and airway responsiveness seem not to share genetic variance....

  3. Chemical Genetics Uncovers Novel Inhibitors of Lignification, Including p-Iodobenzoic Acid Targeting CINNAMATE-4-HYDROXYLASE1[OPEN

    Science.gov (United States)

    Van de Wouwer, Dorien; Decou, Raphaël; Audenaert, Dominique; Nguyen, Long

    2016-01-01

    Plant secondary-thickened cell walls are characterized by the presence of lignin, a recalcitrant and hydrophobic polymer that provides mechanical strength and ensures long-distance water transport. Exactly the recalcitrance and hydrophobicity of lignin put a burden on the industrial processing efficiency of lignocellulosic biomass. Both forward and reverse genetic strategies have been used intensively to unravel the molecular mechanism of lignin deposition. As an alternative strategy, we introduce here a forward chemical genetic approach to find candidate inhibitors of lignification. A high-throughput assay to assess lignification in Arabidopsis (Arabidopsis thaliana) seedlings was developed and used to screen a 10-k library of structurally diverse, synthetic molecules. Of the 73 compounds that reduced lignin deposition, 39 that had a major impact were retained and classified into five clusters based on the shift they induced in the phenolic profile of Arabidopsis seedlings. One representative compound of each cluster was selected for further lignin-specific assays, leading to the identification of an aromatic compound that is processed in the plant into two fragments, both having inhibitory activity against lignification. One fragment, p-iodobenzoic acid, was further characterized as a new inhibitor of CINNAMATE 4-HYDROXYLASE, a key enzyme of the phenylpropanoid pathway synthesizing the building blocks of the lignin polymer. As such, we provide proof of concept of this chemical biology approach to screen for inhibitors of lignification and present a broad array of putative inhibitors of lignin deposition for further characterization. PMID:27485881

  4. Neuropathology and Animal Models of Autism: Genetic and Environmental Factors

    Directory of Open Access Journals (Sweden)

    Bharathi S. Gadad

    2013-01-01

    Full Text Available Autism is a heterogeneous behaviorally defined neurodevelopmental disorder. It is defined by the presence of marked social deficits, specific language abnormalities, and stereotyped repetitive patterns of behavior. Because of the variability in the behavioral phenotype of the disorder among patients, the term autism spectrum disorder has been established. In the first part of this review, we provide an overview of neuropathological findings from studies of autism postmortem brains and identify the cerebellum as one of the key brain regions that can play a role in the autism phenotype. We review research findings that indicate possible links between the environment and autism including the role of mercury and immune-related factors. Because both genes and environment can alter the structure of the developing brain in different ways, it is not surprising that there is heterogeneity in the behavioral and neuropathological phenotypes of autism spectrum disorders. Finally, we describe animal models of autism that occur following insertion of different autism-related genes and exposure to environmental factors, highlighting those models which exhibit both autism-like behavior and neuropathology.

  5. Optimization of Q-factor of AFM cantilevers using genetic algorithms.

    Science.gov (United States)

    Perez-Cruz, Angel; Dominguez-Gonzalez, Aurelio; Stiharu, Ion; Osornio-Rios, Roque A

    2012-04-01

    Micro cantilever beams have been intensively used in sensing applications including to scanning profiles and surfaces where there resolution and imaging speed are critical. Force resolution is related to the Q-factor. When the micro-cantilever operates in air with small separation gaps, the Q-factor is even more reduced due to the squeeze-film damping effect. Thus, the optimization of the configuration of an AFM micro-cantilever is presented in this work with the objective of improving its Q-factor. To accomplish this task, we propose the inclusion of holes as breathing chimneys in the initial design to reduce the squeeze-film damping effect. The evaluation of the Q-factor was carried out using finite element model, which is implemented to work together with the squeeze-film damping model. The methodology applied in the optimization process was genetic algorithms, which considers as constraints the maximum allowable stress, fundamental frequency and spring constant with respect to the initial design. The results show that the optimum design, which includes holes with an optimal location, increases the Q-factor almost five times compared to the initial design.

  6. Genetic and environmental risk factors for primary open-angle glaucoma

    Institute of Scientific and Technical Information of China (English)

    范宝剑; 梁旭辉; 汪宁; 林顺潮; 刘瑶; 谭霭仙; 彭智培

    2004-01-01

    Background Primary open-angle glaucoma (POAG) is characterized by optic nerve damage and consists of a group of genetically heterogeneous disorders. This study was to investigate the associations of genetic and environmental factors with POAG in a hospital-based Chinese population.Methods Thirty-two adult onset POAG patients and 96 age-sex matched control subjects were studied by multivariable logistic regression analysis for the relationships between POAG and its risk factors including family history, diabetes, hypertension, cardiovascular diseases, cigarette smoking, alcohol consumption and polymorphisms of the myocilin and the optineurin genes.Results Univariate analysis showed that POAG was related to family history, cardiovascular disease, alcohol consumption and a myocilin sequence alteration (T353I) (P<0.04). Multivariable logistic regression analysis confirmed that POAG was significantly associated with family history (OR=20.2), hypertension (OR=3.58), cigarette smoking (OR=10.8), alcohol consumption (OR=0.028) and T353I (OR=6.03, all P<0.05).Conclusions Family history, hypertension, cigarette smoking and T353I in the myocilin gene are risk factors for POAG. Alcohol consumption, however, has a protective effect.

  7. The relative contribution of environmental and genetic factors to phenotypic variation in familial Mediterranean fever (FMF).

    Science.gov (United States)

    Ben-Zvi, Ilan; Brandt, Benny; Berkun, Yackov; Lidar, Merav; Livneh, Avi

    2012-01-10

    Familial Mediterranean fever (FMF) is an autosomal recessive disease, caused by mutations in the FMF gene MEFV (MEditerranean FeVer). It has a large phenotypic diversity even in patients with similar genotypes. Despite evidence that environmental factors (EFs) and genetic factors, including MEFV mutations (such as M694V, E148Q) and background modifier genes (MGs), affect the clinical manifestations of FMF, the relative contribution of each remains unknown. To investigate the relative contribution of environmental and genetic factors to the phenotype of FMF, we compared the intra-pair clinical concordance of 10 mono and 7 dizygotic twins with FMF. The part played by EFs was determined by the phenotypic discordance of the monozygous twins, and the MGs effect was determined by deducing the environmental effect, computed for MZ twins, from the phenotypic discordance of the dizygous twins. The mean±SD of intra-pair concordance was higher in the MZ than in DZ twin group (88.1±13.2 vs. 70.7±14.1 respectively, P valueFMF is estimated as 11.9%±6.6% and the MGs effect as 17.4%±15.5% in average. In FMF the phenotype is affected by MEFV mutations, MGs and EFs in an estimated ratio of about 6:1.5:1 respectively. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Genetic algorithm approaches for conceptual design of spacecraft systems including multi-objective optimization and design under uncertainty

    Science.gov (United States)

    Hassan, Rania A.

    In the design of complex large-scale spacecraft systems that involve a large number of components and subsystems, many specialized state-of-the-art design tools are employed to optimize the performance of various subsystems. However, there is no structured system-level concept-architecting process. Currently, spacecraft design is heavily based on the heritage of the industry. Old spacecraft designs are modified to adapt to new mission requirements, and feasible solutions---rather than optimal ones---are often all that is achieved. During the conceptual phase of the design, the choices available to designers are predominantly discrete variables describing major subsystems' technology options and redundancy levels. The complexity of spacecraft configurations makes the number of the system design variables that need to be traded off in an optimization process prohibitive when manual techniques are used. Such a discrete problem is well suited for solution with a Genetic Algorithm, which is a global search technique that performs optimization-like tasks. This research presents a systems engineering framework that places design requirements at the core of the design activities and transforms the design paradigm for spacecraft systems to a top-down approach rather than the current bottom-up approach. To facilitate decision-making in the early phases of the design process, the population-based search nature of the Genetic Algorithm is exploited to provide computationally inexpensive---compared to the state-of-the-practice---tools for both multi-objective design optimization and design optimization under uncertainty. In terms of computational cost, those tools are nearly on the same order of magnitude as that of standard single-objective deterministic Genetic Algorithm. The use of a multi-objective design approach provides system designers with a clear tradeoff optimization surface that allows them to understand the effect of their decisions on all the design objectives

  9. Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

    Science.gov (United States)

    Rotger, Margalida; Glass, Tracy R.; Junier, Thomas; Lundgren, Jens; Neaton, James D.; Poloni, Estella S.; van 't Wout, Angélique B.; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F.; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A.; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P.; Li, Xiuhong; Kingsley, Lawrence A.; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S.; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M.; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H.; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R.; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A.; Reiss, Peter; Weber, Rainer; Bucher, Heiner C.; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E.

    2013-01-01

    Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. PMID:23532479

  10. Identification of new genetic risk factors for prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Michelle Guy; Helen I.Field; Melissa C.Southey; Gianluca Severi; Jenny L.Donovan; Freddie C.Hamdy; David P.Dearnaley; Kenneth R.Muir; Charmaine Smith; Melisa Bagnato; Audrey T.Ardern-Jones; Zsofia Kote-Jarai; Amanda L.Hall; Lynne T.O'Brien; Beatrice N.Gehr-Swain; Rosemary A.Wilkinson; Angela Cox; Sarah Lewis; Paul M.Brown; Sameer G.Jhavar; Malgorzata Tymrakiewicz; Artitaya Lophatananon; Graham G.Giles; Sarah L.Bryant; The UK Genetic Prostate Cancer Study Collaborators; British Association of Urological Surgeons' Sectio; Alan Horwich; Robert A.Huddart; Vincent S.Khoo; Christopher C.Parker; Christopher J.Woodhouse; Alan Thompson; Tim Christmas; Ali Amin Al Olama; Chris Ogden; Cyril Fisher; Charles Jameson; Colin S.Cooper; Dallas R.English; John L.Hopper; David E.Neal; Douglas E Easton; Rosalind A.Eeles; Sarah K.Jugurnauth; Shani Mulholland; Daniel A.Leongamomlert; Stephen M.Edwards; Jonathan Morrison

    2009-01-01

    There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies.We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified.Three of these loci contain candidate susceptibility genes:MSMB,LMTK2 and KLK2/3.The MSMB and KLK2/3 genes may he useful for PCa screening,and the LMTK2 gene might provide a potential therapeutic target.Together with results from other groups,there are now 23 germline genetic variants which have been reported.These results have the potential to be developed into a genetic test.However,we consider that marketing of tests to the public is premature,as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed.Follow-up validation studies,as well as studies to explore the psychological implications of genetic profile testing,will be vital prior to roll out into healthcare.

  11. The Contribution of Epigenetics to Understanding Genetic Factors in Autism

    Science.gov (United States)

    Hall, Layla; Kelley, Elizabeth

    2014-01-01

    Autism spectrum disorder is a grouping of neurodevelopmental disorders characterized by deficits in social communication and language, as well as by repetitive and stereotyped behaviors. While the environment is believed to play a role in the development of autism spectrum disorder, there is now strong evidence for a genetic link to autism.…

  12. Exploring Genetic Factors Involved in Huntington Disease Age of Onset

    DEFF Research Database (Denmark)

    Valcárcel-Ocete, Leire; Alkorta-Aranburu, Gorka; Iriondo, Mikel;

    2015-01-01

    Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of ...

  13. The Contribution of Epigenetics to Understanding Genetic Factors in Autism

    Science.gov (United States)

    Hall, Layla; Kelley, Elizabeth

    2014-01-01

    Autism spectrum disorder is a grouping of neurodevelopmental disorders characterized by deficits in social communication and language, as well as by repetitive and stereotyped behaviors. While the environment is believed to play a role in the development of autism spectrum disorder, there is now strong evidence for a genetic link to autism.…

  14. Environmental and genetic factors affecting faecal worm egg counts ...

    African Journals Online (AJOL)

    2015-12-09

    Dec 9, 2015 ... The basic principle of animal breeding and genetics is to improve ..... that FWEC can be influenced by seasonal variation, management practice .... Molento, M.B., Fortes, F.S., Pondelek, D.A.S., Borges, F.A., Chagas, A.C.S., ...

  15. Genetic factors explain half of all variance in serum eosinophil cationic protein.

    Science.gov (United States)

    Elmose, C; Sverrild, A; van der Sluis, S; Kyvik, K O; Backer, V; Thomsen, S F

    2014-12-01

    Eosinophil cationic protein (ECP) is one of four basic proteins of the secretory granules of eosinophils. It has a variety of functions associated with inflammatory responses. Little is known about the causes for variation in serum ECP levels. To identify factors associated with variation in serum ECP and to determine the relative proportion of the variation in ECP due to genetic and non-genetic factors, in an adult twin sample. A sample of 575 twins, selected through a proband with self-reported asthma, had serum ECP, lung function, airway responsiveness to methacholine, exhaled nitric oxide, and skin test reactivity, measured. Linear regression analysis and variance component models were used to study factors associated with variation in ECP and the relative genetic influence on ECP levels. Sex (regression coefficient = -0.107, P variance component model, genetic factors accounted for 57% (CI: 42-72%, P variance in ECP levels, whereas the remainder (43%) was ascribable to non-shared environmental factors. The genetic correlation between ECP and airway responsiveness to methacholine was statistically non-significant (r = -0.11, P = 0.50). Around half of all variance in serum ECP is explained by genetic factors. Serum ECP is influenced by sex, BMI, and airway responsiveness. Serum ECP and airway responsiveness seem not to share genetic variance. © 2014 John Wiley & Sons Ltd.

  16. Genetics of ischemic stroke, stroke-related risk factors, stroke precursors and treatments.

    Science.gov (United States)

    Della-Morte, David; Guadagni, Fiorella; Palmirotta, Raffaele; Testa, Gianluca; Caso, Valeria; Paciaroni, Maurizio; Abete, Pasquale; Rengo, Franco; Ferroni, Patrizia; Sacco, Ralph L; Rundek, Tatjana

    2012-04-01

    Stroke remains a leading cause of death worldwide and the first cause of disability in the western world. Ischemic stroke (IS) accounts for almost 80% of the total cases of strokes and is a complex and multifactorial disease caused by the combination of vascular risk factors, environment and genetic factors. Investigations of the genetics of atherosclerosis and IS has greatly enhanced our knowledge of this complex multifactorial disease. In this article we sought to review common single-gene disorders relevant to IS, summarize candidate gene and genome-wide studies aimed at discovering genetic stroke risk factors and subclinical phenotypes, and to briefly discuss pharmacogenetics related to stroke treatments. Genetics of IS is, in fact, one of the most promising research frontiers and genetic testing may be helpful for novel drug discoveries as well as for appropriate drug and dose selection for treatment of patients with cerebrovascular disease.

  17. Environmental factors influence both abundance and genetic diversity in a widespread bird species.

    Science.gov (United States)

    Liu, Yang; Webber, Simone; Bowgen, Katharine; Schmaltz, Lucie; Bradley, Katharine; Halvarsson, Peter; Abdelgadir, Mohanad; Griesser, Michael

    2013-11-01

    Genetic diversity is one of the key evolutionary variables that correlate with population size, being of critical importance for population viability and the persistence of species. Genetic diversity can also have important ecological consequences within populations, and in turn, ecological factors may drive patterns of genetic diversity. However, the relationship between the genetic diversity of a population and how this interacts with ecological processes has so far only been investigated in a few studies. Here, we investigate the link between ecological factors, local population size, and allelic diversity, using a field study of a common bird species, the house sparrow (Passer domesticus). We studied sparrows outside the breeding season in a confined small valley dominated by dispersed farms and small-scale agriculture in southern France. Population surveys at 36 locations revealed that sparrows were more abundant in locations with high food availability. We then captured and genotyped 891 house sparrows at 10 microsatellite loci from a subset of these locations (N = 12). Population genetic analyses revealed weak genetic structure, where each locality represented a distinct substructure within the study area. We found that food availability was the main factor among others tested to influence the genetic structure between locations. These results suggest that ecological factors can have strong impacts on both population size per se and intrapopulation genetic variation even at a small scale. On a more general level, our data indicate that a patchy environment and low dispersal rate can result in fine-scale patterns of genetic diversity. Given the importance of genetic diversity for population viability, combining ecological and genetic data can help to identify factors limiting population size and determine the conservation potential of populations.

  18. Environmental factors influence both abundance and genetic diversity in a widespread bird species

    NARCIS (Netherlands)

    Liu, Yang; Webber, Simone; Bowgen, Katharine; Schmaltz, Lucie; Bradley, Katharine; Halvarsson, Peter; Abdelgadir, Mohanad; Griesser, Michael

    2013-01-01

    Genetic diversity is one of the key evolutionary variables that correlate with population size, being of critical importance for population viability and the persistence of species. Genetic diversity can also have important ecological consequences within populations, and in turn, ecological factors

  19. Environmental factors influence both abundance and genetic diversity in a widespread bird species

    NARCIS (Netherlands)

    Liu, Yang; Webber, Simone; Bowgen, Katharine; Schmaltz, Lucie; Bradley, Katharine; Halvarsson, Peter; Abdelgadir, Mohanad; Griesser, Michael

    2013-01-01

    Genetic diversity is one of the key evolutionary variables that correlate with population size, being of critical importance for population viability and the persistence of species. Genetic diversity can also have important ecological consequences within populations, and in turn, ecological factors

  20. The influence of clinical and genetic factors on the development of obesity in children with type 1 diabetes.

    Science.gov (United States)

    Łuczyński, Włodzimierz; Głowińska-Olszewska, Barbara; Bossowski, Artur

    2016-10-01

    The exact cause of the obesity epidemic remains unknown; however, both environmental and genetic factors are involved. People at risk of developing obesity include children with type 1 diabetes mellitus (T1DM), which in turn increases their cardiovascular disease risk. Here, we discuss the clinical and genetic factors influencing weight in patients with T1DM. In children with T1DM, the presence of obesity depends mainly on sex, metabolic control, and disease duration. However, genetic factors, including the fat mass and obesity-associated (FTO) gene, are also associated with body weight. Indeed, children with the FTO gene rs9939609 obesity-risk allele (homozygous = AA or heterozygous = AT) are predisposed to a higher body mass index and have a greater risk of being overweight or obese. However, in this review, we show that FTO gene polymorphisms only have a small effect on body weight in children, much weaker than the effect of clinical factors. The association between FTO gene polymorphisms and body weight is only statistically significant in children without severe obesity. Moreover, other genetic factors had no effect on weight in patients with T1DM, and further research involving larger populations is required to confirm the genetic basis of diabetes and obesity. Therefore, identifying the clinical features of children with T1DM, such as their initial body mass index, sex, metabolic control, and disease duration, will still have the strongest effect on reducing risk factors for cardiovascular diseases. Physicians should pay close attention to modifiable elements of these relationships, for example, metabolic control and energy and insulin intake, when caring for patients with T1DM. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Effect of including genetic progress in milk yield on evaluating the use of sexed semen and other reproduction strategies in a dairy herd

    DEFF Research Database (Denmark)

    Ettema, Jehan Frans; Østergaard, Søren; Sørensen, M K

    2010-01-01

    Herd simulation modelling has been recognized as a relevant method to study reproduction management strategies in a dairy herd (Dijkhuizen et al., 1997; Marsh et al., 1987; Østergaard et al., 2005a). These models estimate the technical and economic effects of certain replacement and breeding...... strategies based on the phenotypical states of the individual animals over a number of years. Typically, the genetic levels of replacement heifers in these models are not different from those of the culling candidates in the herd; continuous genetic improvement in the population is ignored. The importance...... of including genetic progress when evaluating reproductive strategies with simulation models has not been explored. Improved reproductive efficiency does allow a higher selection intensity of which cows to stay in the herd and give birth to own young stock....

  2. Quantifying effects of environmental and geographical factors on patterns of genetic differentiation.

    Science.gov (United States)

    Lee, Cheng-Ruei; Mitchell-Olds, Thomas

    2011-11-01

    Elucidating the factors influencing genetic differentiation is an important task in biology, and the relative contribution from natural selection and genetic drift has long been debated. In this study, we used a regression-based approach to simultaneously estimate the quantitative contributions of environmental adaptation and isolation by distance on genetic variation in Boechera stricta, a wild relative of Arabidopsis. Patterns of discrete and continuous genetic differentiation coexist within this species. For the discrete differentiation between two major genetic groups, environment has larger contribution than geography, and we also identified a significant environment-by-geography interaction effect. Elsewhere in the species range, we found a latitudinal cline of genetic variation reflecting only isolation by distance. To further confirm the effect of environmental selection on genetic divergence, we identified the specific environmental variables predicting local genotypes in allopatric and sympatric regions. Water availability was identified as the possible cause of differential local adaptation in both geographical regions, confirming the role of environmental adaptation in driving and maintaining genetic differentiation between the two major genetic groups. In addition, the environment-by-geography interaction is further confirmed by the finding that water availability is represented by different environmental factors in the allopatric and sympatric regions. In conclusion, this study shows that geographical and environmental factors together created stronger and more discrete genetic differentiation than isolation by distance alone, which only produced a gradual, clinal pattern of genetic variation. These findings emphasize the importance of environmental selection in shaping patterns of species-wide genetic variation in the natural environment.

  3. Impact of Outliers Arising from Unintended and Unknowingly Included Subpopulations on the Decisions about the Number of Factors in Exploratory Factor Analysis

    Science.gov (United States)

    Liu, Yan; Zumbo, Bruno D.

    2012-01-01

    There is a lack of research on the effects of outliers on the decisions about the number of factors to retain in an exploratory factor analysis, especially for outliers arising from unintended and unknowingly included subpopulations. The purpose of the present research was to investigate how outliers from an unintended and unknowingly included…

  4. Genetic factors affecting patient responses to pancreatic cancer treatment

    Science.gov (United States)

    Fotopoulos, George; Syrigos, Konstantinos; Saif, Muhammad Wasif

    2016-01-01

    Cancer of the exocrine pancreas is a malignancy with a high lethal rate. Surgical resection is the only possible curative mode of treatment. Metastatic pancreatic cancer is incurable with modest results from the current treatment options. New genomic information could prove treatment efficacy. An independent review of PubMed and ScienceDirect databases was performed up to March 2016, using combinations of terms such pancreatic exocrine cancer, chemotherapy, genomic profile, pancreatic cancer pharmacogenomics, genomics, molecular pancreatic pathogenesis, and targeted therapy. Recent genetic studies have identified new markers and therapeutic targets. Our current knowledge of pancreatic cancer genetics must be further advanced to elucidate the molecular basis and pathogenesis of the disease, improve the accuracy of diagnosis, and guide tailor-made therapies. PMID:27708512

  5. Genetic Factors Explain the Association Between Pain Catastrophizing and Chronic Widespread Pain.

    Science.gov (United States)

    Ogata, Soshiro; Williams, Frances; Burri, Andrea

    2017-09-01

    This study aimed to clarify whether there are shared genetic and/or environmental factors explaining the strong link between pain catastrophizing (PC) and chronic widespread pain (CWP). Data were available for N = 1,109 female twins from TwinsUK. Information on self-reported CWP and PC was subject to variance component twin analysis. Heritabilities were 40% for PC and 77% for CWP. The genetic correlation between PC and CWP was .40%, whereas no evidence of an environmental correlation could be detected (.0). According to the best-fitting additive genetic, non-shared environmental (AE) Cholesky model, an additive genetic factor loading on PC as well as CWP, as well as an additive genetic factor loading on CWP alone was found. In terms of environmental influences, 2 individual environmental factors could be identified, loading separately on PC and CWP. Overall, the results add to the knowledge on the nature of CWP and the basis of its close relationship with PC by suggesting a shared genetic etiological structure. The findings highlight a potential avenue for future research and may provide useful insight for the clinical management of pain and pain coping. Results suggest a shared genetic etiological structure between CWP and PC with no shared influence of environmental factors. Clinicians should be aware of this biological link within the context of clinical management of pain and pain coping. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

  6. The epidemiology of eating disorders: genetic, environmental, and societal factors

    OpenAIRE

    Mitchison D; Hay PJ

    2014-01-01

    Deborah Mitchison,1 Phillipa J Hay2,3 1School of Medicine, University of Western Sydney, Sydney, NSW, Australia; 2Centre for Health Research, School of Medicine, University of Western Sydney, Sydney, NSW, Australia; 3School of Medicine, James Cook University, Townsville City, QLD, Australia Background: The aim of this review was to summarize the literature to date regarding the sociodemographic, environmental, and genetic correlates of eating disorders (EDs) in adults. Method: A keyword sear...

  7. Identification of Immune-Relevant Factors Conferring Sarcoidosis Genetic Risk

    Science.gov (United States)

    Fischer, Annegret; Ellinghaus, David; Nutsua, Marcel; Hofmann, Sylvia; Montgomery, Courtney G.; Iannuzzi, Michael C.; Rybicki, Benjamin A.; Petrek, Martin; Mrazek, Frantisek; Pabst, Stefan; Grohé, Christian; Grunewald, Johan; Ronninger, Marcus; Eklund, Anders; Padyukov, Leonid; Mihailovic-Vucinic, Violeta; Jovanovic, Dragana; Sterclova, Martina; Homolka, Jiri; Nöthen, Markus M.; Herms, Stefan; Gieger, Christian; Strauch, Konstantin; Winkelmann, Juliane; Boehm, Bernhard O.; Brand, Stephan; Büning, Carsten; Schürmann, Manfred; Ellinghaus, Eva; Baurecht, Hansjörg; Lieb, Wolfgang; Nebel, Almut; Müller-Quernheim, Joachim; Franke, Andre

    2015-01-01

    Rationale: Genetic variation plays a significant role in the etiology of sarcoidosis. However, only a small fraction of its heritability has been explained so far. Objectives: To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene association study of immune-associated loci. Methods: Altogether the study population comprised over 19,000 individuals. In a two-stage design, 1,726 German sarcoidosis cases and 5,482 control subjects were genotyped for 128,705 single-nucleotide polymorphisms using the Illumina Immunochip for the screening step. The remaining 3,955 cases, 7,514 control subjects, and 684 parents of affected offspring were used for validation and replication of 44 candidate and two established risk single-nucleotide polymorphisms. Measurements and Main Results: Four novel susceptibility loci were identified with genome-wide significance in the European case-control populations, located on chromosomes 12q24.12 (rs653178; ATXN2/SH2B3), 5q33.3 (rs4921492; IL12B), 4q24 (rs223498; MANBA/NFKB1), and 2q33.2 (rs6748088; FAM117B). We further defined three independent association signals in the HLA region with genome-wide significance, peaking in the BTNL2 promoter region (rs5007259), at HLA-B (rs4143332/HLA-B*0801) and at HLA-DPB1 (rs9277542), and found another novel independent signal near IL23R (rs12069782) on chromosome 1p31.3. Conclusions: Functional predictions and protein network analyses suggest a prominent role of the drug-targetable IL23/Th17 signaling pathway in the genetic etiology of sarcoidosis. Our findings reveal a substantial genetic overlap of sarcoidosis with diverse immune-mediated inflammatory disorders, which could be of relevance for the clinical application of modern therapeutics PMID:26051272

  8. Genetic Factors Affecting Performance Traits of Sahiwal Cattle in Pakistan

    Directory of Open Access Journals (Sweden)

    Z. Rehman*§ and M. S. Khan1

    2012-06-01

    Full Text Available Data on 23925 lactations of 5897 Sahiwal cows in five Government herds of Punjab province were collected to estimate the genetic control and genetic correlations among performance traits. A repeatability animal model having herd-year-season and parity was used for this purpose. The repeatability estimates for 305-d milk yield, total milk yield, lactation length, dry period, calving interval and service period were 0.40±0.015, 0.40±0.016, 0.33±0.013, 0.14±0.005, 0.15±0.004, and 0.14±0.005 respectively. The heritability estimates for these traits were 0.10±0.016, 0.09±0.016, 0.06±0.013, 0.14±0.009, 0.15±0.010, and 0.14±0.010, respectively. The phenotypic, genetic and environmental correlation of 305-d milk yield with lactation length was 0.71, 0.48 and 0.70, respectively, with dry period was -0.31, -0.43 and -0.22, respectively while with calving interval and service period exhibited similar pattern (0.08, 0.25 and 0.08, respectively. The estimated breeding values ranged from -447 to 1254 kg, -442 to 1265 kg, -24 to 38, -78 to 116, -84 to 107 and -81 to 91, days for 305-day milk yield, total milk yield, lactation length, dry period, calving interval and service period, respectively. No specific genetic trend was observed for performance traits during the period under study. Cows have not improved in their ability to perform in various economic traits. Accurate recording of pedigree and performance is necessary for improving the performance traits of Sahiwal. Due to high repeatability estimates of yield traits selection or culling may be practised from first few records.

  9. Nephrolithiasis and Nephrocalcinosis in Children - Metabolic and Genetic Factors.

    Science.gov (United States)

    Tasic, Velibor; Gucev, Zoran

    2015-09-01

    Diagnosis and management of pediatric nephrolithiasis/nephrocalcinosis is a very complex and challenging task for every pediatrician. It is based on correct. disease history taking, which may guide to the mode of inheritance (dominant, recessive, x-linked). Ethnicity and consanguinity should also be investigated since they predispose to high prevalence of certain disorders. One should always begin with cheap and available screening tests. Herein we will review clinical, biochemical, metabolic and genetic characteristics of the inherited diseases which lead to nephrolithiasis/nephrocalcinosis, such as: idiopathic hypercalciuria, renal hypophosphatemia, renal tubular acidosis, idiopathic infantile hypercalcemia, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis, hypocitraturia, cystinuria, primary hyperoxaluria and renal hypouricemia. Modern genetic techniques such as next generation sequencing enable nowadays diagnosis of rare disease using only a blood sample, trough massive parallel resequencing of many genes. This is very helpful for anuric patients or on dialysis where blood and urine biochemistry are not informative. Genetic testing also replaces invasive liver biopsy or unpleasant acidification tests and enables prenatal or early postnatal diagnosis.

  10. [Combined Effect of Genetic Factors, Age, and Smoking on the Risk of Developing Myocardial Infarction].

    Science.gov (United States)

    Osmak G, J; Matveeva, N A; Titov, B V; Nasibullin, T R; Mustafina, O E; Shakhnovich, R M; Kukava, N G; Ruda, M Ya; Favorova, O O

    2016-12-01

    to elaborate a complex model for myocardial infarction (MI) risk assessment considering the combined effect of genetic predisposition, age and smoking. The study included two independent samples of ethnic Russians: 325 patients with MI and 185 individuals without history of cardiovascular diseases (controls) from the Moscow region, and 220 patients and 197 controls from the Republic of Bashkortostan. Genotyping of polymorphic loci of genes CRP (rs1130864), IFNG (rs2430561), TGFB1 (rs1982073), FGB (rs1800788) and PTGS1 (rs3842787) was performed. To construct the predictive models, we used logistic regression with stepwise inclusion of variables. The predictive value was evaluated by the area under the curve (AUC) in a ROC-analysis. The factor was considered as a marker at pAUC 0.60. Three separate genetic variants FGB rs1800788*T, TGFB1 rs1982073*TT, CRP rs1130864*TT, and biallelic combination IFNG rs2430561*A + PTGS1 rs3842787*T whose association with MI we described earlier, were used to construct the composite genetic marker (AUC=0.66 in the training and test samples) by the logistic regression method. Adding to the obtained composite genetic marker such parameters as age and smoking allowed to create a complex MI risk marker, which was characterized by the predictive value stability (AUC=0.77 in the training sample and 0.82 in the test sample). The obtained complex model for MI risk assessment was reproduced in two independent samples of Russian ethnicity individuals from different regions of Russia with different gender identities, and allowed to have a reasonable chance (about 80%) of distinguishing patients and healthy individuals.

  11. Genetic and clinical risk factors for fluid overload following open-heart surgery.

    Science.gov (United States)

    Enger, T B; Pleym, H; Stenseth, R; Wahba, A; Videm, V

    2014-05-01

    Post-operative fluid overload following cardiac surgery is associated with increased morbidity and mortality. We hypothesised that genetic variations and pre-operative clinical factors predispose some patients to post-operative fluid overload. Perioperative variables were collected prospectively for 1026 consecutive adults undergoing open-heart surgery at St. Olavs University Hospital, Norway from 2008-2010. Post-operative fluid overload was defined as a post-operative fluid balance/kg ≥ the 90th percentile of the study population. Genotyping was performed for 31 single-nucleotide polymorphisms related to inflammatory/vascular responses or previously associated with complications following open-heart surgery. Data were analysed using logistic regression modelling, and the findings were internally validated by bootstrapping (n = 100). Homozygous carriers of the common G allele of rs12917707 in the UMOD gene had a 2.2 times greater risk of post-operative fluid overload (P = 0.005) after adjustment for significant clinical variables (age, duration of cardiopulmonary bypass, and intraoperative red cell transfusion). A genetic risk score including 14 single-nucleotide polymorphisms was independently associated with post-operative fluid overload (P = 0.001). The number of risk alleles was linearly associated with the frequency of fluid overload (odds ratio per risk allele 1.153, 95 % confidence interval 1.056-1.258). Nagelkerke's R(2) increased with 7.5% to a total of 25% for the combined clinical and genetic model. Hemofiltration did not reduce the risk. A common variation in the UMOD gene previously shown to be related to renal function was associated with increased risk of post-operative fluid overload following cardiac surgery. Our findings support a genetic susceptibility to disturbed fluid handling following cardiac surgery. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  12. Genetics and Other Risk Factors for Past Concussions in Active-Duty Soldiers.

    Science.gov (United States)

    Dretsch, Michael N; Silverberg, Noah; Gardner, Andrew J; Panenka, William J; Emmerich, Tanja; Crynen, Gogce; Ait-Ghezala, Ghania; Chaytow, Helena; Mathura, Venkat; Crawford, Fiona C; Iverson, Grant L

    2017-02-15

    Risk factors for concussion in active-duty military service members are poorly understood. The present study examined the association between self-reported concussion history and genetics (apolipoprotein E [APOE], brain-derived neurotrophic factor [BDNF], and D2 dopamine receptor genes [DRD2]), trait personality measures (impulsive-sensation seeking and trait aggression-hostility), and current alcohol use. The sample included 458 soldiers who were preparing to deploy for Operation Iraqi Freedom/Operation Enduring Freedom. For those with the BDNF Met/Met genotype, 57.9% (11/19) had a history of one or more prior concussions, compared with 35.6% (154/432) of those with other BDNF genotypes (p = 0.049, odds ratio [OR] = 2.48). APOE and DRD2 genotypes were not associated with risk for past concussions. Those with the BDNF Met/Met genotype also reported greater aggression and hostility personality characteristics. When combined in a predictive model, prior military deployments, being male, and having the BDNF Met/Met genotype were independently associated with increased lifetime history of concussions in active-duty soldiers. Replication in larger independent samples is necessary to have more confidence in both the positive and negative genetic associations reported in this study.

  13. Host genetic risk factors for West Nile virus infection and disease progression.

    Directory of Open Access Journals (Sweden)

    Abigail W Bigham

    Full Text Available West Nile virus (WNV, a category B pathogen endemic in parts of Africa, Asia and Europe, emerged in North America in 1999, and spread rapidly across the continental U.S. Outcomes of infection with WNV range from asymptomatic to severe neuroinvasive disease manifested as encephalitis, paralysis, and/or death. Neuroinvasive WNV disease occurs in less than one percent of cases, and although host genetic factors are thought to influence risk for symptomatic disease, the identity of these factors remains largely unknown. We tested 360 common haplotype tagging and/or functional SNPs in 86 genes that encode key regulators of immune function in 753 individuals infected with WNV including: 422 symptomatic WNV cases and 331 cases with asymptomatic infections. After applying a Bonferroni correction for multiple tests and controlling for population stratification, SNPs in IRF3 (OR 0.54, p = 0.035 and MX1, (OR 0.19, p = 0.014 were associated with symptomatic WNV infection and a single SNP in OAS1 (OR 9.79, p = 0.003 was associated with increased risk for West Nile encephalitis and paralysis (WNE/P. Together, these results suggest that genetic variation in the interferon response pathway is associated with both risk for symptomatic WNV infection and WNV disease progression.

  14. Genetic diversity of bovine papillomavirus types, including two putative new types, in teat warts from dairy cattle herds.

    Science.gov (United States)

    Lunardi, Michele; de Camargo Tozato, Claudia; Alfieri, Alice Fernandes; de Alcântara, Brígida Kussumoto; Vilas-Boas, Laurival Antonio; Otonel, Rodrigo Alejandro Arellano; Headley, Selwyn Arlington; Alfieri, Amauri Alcindo

    2016-06-01

    Teat papillomatosis affects dairy cows worldwide. Milking can become difficult due to teat warts, and maintaining affected cows in the herds may diminish economic profit in the dairy industry. Currently, 13 bovine papillomavirus (BPV) types have been fully characterized, and numerous putative BPV types have been identified through partial L1 gene PCR. In order to identify the viral types present in warts on the udders of dairy cows, 40 teat lesions from 24 cows from 13 cattle farms in three States of Brazil were evaluated by PV L1 gene PCR. The warts that were evaluated contained sequences from BPVs 6-10, the putative BPV types BAPV9 and BAPV4, and two unreported putative papillomavirus (PV) types, named BPV/BR-UEL6 and BPV/BR-UEL7. In addition, mixed infections and coinfections were identified, since more than one lesion was observed on the udders of 13 cows. Phylogenetic analysis showed that BPV/BR-UEL6 is closely related to BPVs belonging to the genus Xipapillomavirus, while BPV/BR-UEL7 clustered with the previously reported strains Cervus timorensis and Pudu puda PVs, which represent a putative new PV type, and it was only distantly related to xi-, epsilon-, delta- and dyoxi-PVs. These results provide information that will assist in the understanding of the association of BPVs 6, 7, 8, 9, and 10, as well as putative BPV types BAPV4 and BAPV9, with mammary papillomatosis. This is the first characterization of putative novel PV types BPV/BR-UEL6 and BPV/BR-UEL7 in teat warts of dairy cows, highlighting the high genetic diversity of BPVs associated with teat papillomatosis.

  15. Genetic and environmental factors affecting peak bone mass in premenopausal Japanese women

    OpenAIRE

    Hayakawa, Yoshika; Yanagi, Hisako; Hara, Shuichi; Amagai, Hitoshi; Endo, Kazue; Hamaguchi, Hideo; Tomura, Shigeo

    2001-01-01

    The purpose of this study was to examine the relationships between peak bone mass and genetic and environmental factors. We measured whole-body bone mineral density (BMD), lumbar spine BMD, and radius BMD with dual-energy X-ray absorptiometry (DXA) and analyzed eight genetic factors: vitamin D receptor (VDR)-3′, VDR-5′, estrogen receptor (ER), calcitonin receptor (CTR), parathyroid hormone (PTH), osteocalcin (OC), apolipoprotein E (ApoE), and fatty acid binding protein 2 (FABP2) allelic polym...

  16. Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?

    DEFF Research Database (Denmark)

    Benyamin, B.; Sørensen, T.I.A.; Schousboe, K.

    2007-01-01

    AIMS/HYPOTHESIS: The cluster of obesity, insulin resistance, dyslipidaemia and hypertension, called the metabolic syndrome, has been suggested as a risk factor for cardiovascular disease and type 2 diabetes. The aim of the present study was to evaluate whether there are common genetic...... and environmental factors influencing this cluster in a general population of twin pairs. MATERIALS AND METHODS: A multivariate genetic analysis was performed on nine endophenotypes associated with the metabolic syndrome from 625 adult twin pairs of the GEMINAKAR study of the Danish Twin Registry. RESULTS: All......, the endophenotypes associated with the metabolic syndrome apparently do not share a substantial common genetic or familial environmental background....

  17. Genetics

    Science.gov (United States)

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

  18. Generating induced pluripotent stem cells from common marmoset (Callithrix jacchus) fetal liver cells using defined factors, including Lin28.

    Science.gov (United States)

    Tomioka, Ikuo; Maeda, Takuji; Shimada, Hiroko; Kawai, Kenji; Okada, Yohei; Igarashi, Hiroshi; Oiwa, Ryo; Iwasaki, Tsuyoshi; Aoki, Mikio; Kimura, Toru; Shiozawa, Seiji; Shinohara, Haruka; Suemizu, Hiroshi; Sasaki, Erika; Okano, Hideyuki

    2010-09-01

    Although embryonic stem (ES) cell-like induced pluripotent stem (iPS) cells have potential therapeutic applications in humans, they are also useful for creating genetically modified human disease models in nonhuman primates. In this study, we generated common marmoset iPS cells from fetal liver cells via the retrovirus-mediated introduction of six human transcription factors: Oct-3/4, Sox2, Klf4, c-Myc, Nanog, and Lin28. Four to five weeks after introduction, several colonies resembling marmoset ES cells were observed and picked for further expansion in ES cell medium. Eight cell lines were established, and validation analyses of the marmoset iPS cells followed. We detected the expression of ES cell-specific surface markers. Reverse transcription-PCR showed that these iPS cells expressed endogenous Oct-3/4, Sox2, Klf4, c-Myc, Nanog and Lin28 genes, whereas all of the transgenes were silenced. Karyotype analysis showed that two of three iPS cell lines retained a normal karyotype after a 2-month culture. Both embryoid body and teratoma formation showed that marmoset iPS cells had the developmental potential to give rise to differentiated derivatives of all three primary germ layers. In summary, we generated marmoset iPS cells via the transduction of six transcription factors; this provides a powerful preclinical model for studies in regenerative medicine.

  19. The influence of the genetic and non-genetic factors on bone mineral density and osteoporotic fractures in Chinese women.

    Science.gov (United States)

    Deng, Yan-Hua; Zhao, Lin; Zhang, Min-Jia; Pan, Chun-Ming; Zhao, Shuang-Xia; Zhao, Hong-Yan; Sun, Li-Hao; Tao, Bei; Song, Huai-Dong; Wang, Wei-Qing; Ning, Guang; Liu, Jian-Min

    2013-02-01

    To investigate the effects of genetic and non-genetic factors on bone mineral densities (BMDs) and osteoporotic fractures. This was a cross-sectional study to investigate the relationships between 18 SNPs and non-genetic factors with BMDs and osteoporotic fractures in 1012 Chinese Han women. Five SNPs in genes GPR177, CTNNB1, MEF2C, SOX6, and TNFRSF11B were associated with L1-4 or total hip BMDs. rs11898505 in SPTBN1 gene was associated with osteoporotic fractures. Subjects carrying the largest number of risk alleles (highest 10 %) not only had lower BMD values as compared to those carrying the least number of risk alleles (lowest 10 %), they also had a higher risk of fracture [P = 0.002, OR = 2.252, 95 %CI (1.136, 4.463)]. Results from multivariate stepwise regression analysis revealed that age [P < 0.001, OR = 1.038, 95 % CI (1.018, 1.058)], number of falls in a year [P < 0.001, OR = 2.347, 95 % CI (1.459, 3.774)], the G risk allele in rs11898505 [P = 0.023, OR = 1.559, 95 % CI (1.062, 2.290)], and the L1-4 BMD [P = 0.017, OR = 0.286, 95 % CI (0.102, 0.798)] were associated with the occurrence of osteoporotic fractures. Genetic (rs11898505) and non-genetic factors (age, number of falls in a year and L1-4 BMD) could work in concert to contribute to the risk of osteoporotic fractures.

  20. Genetic factors influencing risk to orofacial clefts: today's challenges and tomorrow's opportunities.

    Science.gov (United States)

    Beaty, Terri H; Marazita, Mary L; Leslie, Elizabeth J

    2016-01-01

    Orofacial clefts include cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP), which combined represent the largest group of craniofacial malformations in humans with an overall prevalence of one per 1,000 live births. Each of these birth defects shows strong familial aggregation, suggesting a major genetic component to their etiology. Genetic studies of orofacial clefts extend back centuries, but it has proven difficult to define any single etiologic mechanism because many genes appear to influence risk. Both linkage and association studies have identified several genes influencing risk, but these differ across families and across populations. Genome-wide association studies have identified almost two dozen different genes achieving genome-wide significance, and there are broad classes of 'causal genes' for orofacial clefts: a few genes strongly associated with risk and possibly directly responsible for Mendelian syndromes which include orofacial clefts as a key phenotypic feature of the syndrome, and multiple genes with modest individual effects on risk but capable of disrupting normal craniofacial development under the right circumstances (which may include exposure to environmental risk factors). Genomic sequencing studies are now underway which will no doubt reveal additional genes/regions where variants (sequence and structural) can play a role in controlling risk to orofacial clefts. The real challenge to medicine and public health is twofold: to identify specific genes and other etiologic factors in families with affected members and then to devise effective interventions for these different biological mechanisms controlling risk to complex and heterogeneous birth defects such as orofacial clefts.

  1. Genetic factors influencing risk to orofacial clefts: today’s challenges and tomorrow’s opportunities

    Science.gov (United States)

    Beaty, Terri H.; Marazita, Mary L.; Leslie, Elizabeth J.

    2016-01-01

    Orofacial clefts include cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP), which combined represent the largest group of craniofacial malformations in humans with an overall prevalence of one per 1,000 live births. Each of these birth defects shows strong familial aggregation, suggesting a major genetic component to their etiology. Genetic studies of orofacial clefts extend back centuries, but it has proven difficult to define any single etiologic mechanism because many genes appear to influence risk. Both linkage and association studies have identified several genes influencing risk, but these differ across families and across populations. Genome-wide association studies have identified almost two dozen different genes achieving genome-wide significance, and there are broad classes of ‘causal genes’ for orofacial clefts: a few genes strongly associated with risk and possibly directly responsible for Mendelian syndromes which include orofacial clefts as a key phenotypic feature of the syndrome, and multiple genes with modest individual effects on risk but capable of disrupting normal craniofacial development under the right circumstances (which may include exposure to environmental risk factors). Genomic sequencing studies are now underway which will no doubt reveal additional genes/regions where variants (sequence and structural) can play a role in controlling risk to orofacial clefts. The real challenge to medicine and public health is twofold: to identify specific genes and other etiologic factors in families with affected members and then to devise effective interventions for these different biological mechanisms controlling risk to complex and heterogeneous birth defects such as orofacial clefts. PMID:27990279

  2. Genetic mouse models for otitis media

    Institute of Scientific and Technical Information of China (English)

    Qingyin Zheng; Ken R Johnson

    2003-01-01

    @@ Genetics of Otitis Media (OM): OM is affected by multiple factors including eustachian tube (ET) structure and function, immune status, innate mucosal defense, genetic susceptibility, and pathogens.

  3. Dissection of genetic factors associated with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Leblond, Claire S; Kaneb, Hannah M; Dion, Patrick A; Rouleau, Guy A

    2014-12-01

    Amyotrophic lateral sclerosis (ALS) is a fatal late onset neurological disorder characterized by motor neuron degeneration in the primary motor cortex, brainstem and spinal cord. The majority of cases are sporadic (SALS) and only 5-10% have a family history (FALS). FALS cases show a high heritability and this has enabled the identification of several genetic triggers, of which mutations in SOD1, FUS, TARDBP and C9ORF72 are the most frequent. While such advances have contributed to our current understanding of the causes of most cases of FALS and their underlying pathophysiological consequences, they only explain a small fraction of SALS with the etiology of most SALS cases remaining unexplained. Here, we review past and current methods used for the identification of FALS and SALS associated genes and propose a risk-based classification for these. We also discuss how the growing number of whole exome/genome sequencing datasets prepared from SALS cases, and control individuals, may reveal novel insights into the genetic etiology of SALS; for instance through revealing increased mutation burden rates across genes or genomic regions that were not previously associated with ALS or through allowing the examination of a potential "oligogenic" mechanism of the disease. Finally we summarize the three most recently discovered 'high risk' genes in ALS.

  4. Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk.

    Directory of Open Access Journals (Sweden)

    Celia G Walker

    Full Text Available The risk of developing type 2 diabetes mellitus (T2DM is determined by a complex interplay involving lifestyle factors and genetic predisposition. Despite this, many studies do not consider the relative contributions of this complex array of factors to identify relationships which are important in progression or prevention of complex diseases. We aimed to describe the integrated effect of a number of lifestyle changes (weight, diet and physical activity in the context of genetic susceptibility, on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme. A sample of 353 participants from a behavioural weight management intervention were included in this study. A graphical Markov model was used to describe the impact of the intervention, by dividing the effects into various pathways comprising changes in proportion of dietary saturated fat, physical activity and weight loss, and a genetic predisposition score (T2DM-GPS, on changes in insulin sensitivity (HOMA-IR, insulin secretion (HOMA-B and short and long term glycaemia (glucose and HbA1c. We demonstrated the use of graphical Markov modelling to identify the importance and interrelationships of a number of possible variables changed as a result of a lifestyle intervention, whilst considering fixed factors such as genetic predisposition, on changes in traits. Paths which led to weight loss and change in dietary saturated fat were important factors in the change of all glycaemic traits, whereas the T2DM-GPS only made a significant direct contribution to changes in HOMA-IR and plasma glucose after considering the effects of lifestyle factors. This analysis shows that modifiable factors relating to body weight, diet, and physical activity are more likely to impact on glycaemic traits than genetic predisposition during a behavioural intervention.

  5. batman Interacts with polycomb and trithorax group genes and encodes a BTB/POZ protein that is included in a complex containing GAGA factor.

    Science.gov (United States)

    Faucheux, M; Roignant, J-Y; Netter, S; Charollais, J; Antoniewski, C; Théodore, L

    2003-02-01

    Polycomb and trithorax group genes maintain the appropriate repressed or activated state of homeotic gene expression throughout Drosophila melanogaster development. We have previously identified the batman gene as a Polycomb group candidate since its function is necessary for the repression of Sex combs reduced. However, our present genetic analysis indicates functions of batman in both activation and repression of homeotic genes. The 127-amino-acid Batman protein is almost reduced to a BTB/POZ domain, an evolutionary conserved protein-protein interaction domain found in a large protein family. We show that this domain is involved in the interaction between Batman and the DNA binding GAGA factor encoded by the Trithorax-like gene. The GAGA factor and Batman codistribute on polytene chromosomes, coimmunoprecipitate from nuclear embryonic and larval extracts, and interact in the yeast two-hybrid assay. Batman, together with the GAGA factor, binds to MHS-70, a 70-bp fragment of the bithoraxoid Polycomb response element. This binding, like that of the GAGA factor, requires the presence of d(GA)n sequences. Together, our results suggest that batman belongs to a subset of the Polycomb/trithorax group of genes that includes Trithorax-like, whose products are involved in both activation and repression of homeotic genes.

  6. Genetic identification of a network of factors that functionally interact with the nucleosome remodeling ATPase ISWI.

    Directory of Open Access Journals (Sweden)

    Giosalba Burgio

    2008-06-01

    Full Text Available Nucleosome remodeling and covalent modifications of histones play fundamental roles in chromatin structure and function. However, much remains to be learned about how the action of ATP-dependent chromatin remodeling factors and histone-modifying enzymes is coordinated to modulate chromatin organization and transcription. The evolutionarily conserved ATP-dependent chromatin-remodeling factor ISWI plays essential roles in chromosome organization, DNA replication, and transcription regulation. To gain insight into regulation and mechanism of action of ISWI, we conducted an unbiased genetic screen to identify factors with which it interacts in vivo. We found that ISWI interacts with a network of factors that escaped detection in previous biochemical analyses, including the Sin3A gene. The Sin3A protein and the histone deacetylase Rpd3 are part of a conserved histone deacetylase complex involved in transcriptional repression. ISWI and the Sin3A/Rpd3 complex co-localize at specific chromosome domains. Loss of ISWI activity causes a reduction in the binding of the Sin3A/Rpd3 complex to chromatin. Biochemical analysis showed that the ISWI physically interacts with the histone deacetylase activity of the Sin3A/Rpd3 complex. Consistent with these findings, the acetylation of histone H4 is altered when ISWI activity is perturbed in vivo. These findings suggest that ISWI associates with the Sin3A/Rpd3 complex to support its function in vivo.

  7. Disentangling genetic and environmental risk factors for individual diseases from multiplex comorbidity networks

    CERN Document Server

    Klimek, Peter; Thurner, Stefan

    2016-01-01

    Most disorders are caused by a combination of multiple genetic and/or environmental factors. If two diseases are caused by the same molecular mechanism, they tend to co-occur in patients. Here we provide a quantitative method to disentangle how much genetic or environmental risk factors contribute to the pathogenesis of 358 individual diseases, respectively. We pool data on genetic, pathway-based, and toxicogenomic disease-causing mechanisms with disease co-occurrence data obtained from almost two million patients. From this data we construct a multilayer network where nodes represent disorders that are connected by links that either represent phenotypic comorbidity of the patients or the involvement of a certain molecular mechanism. From the similarity of phenotypic and mechanism-based networks for each disorder we derive measure that allows us to quantify the relative importance of various molecular mechanisms for a given disease. We find that most diseases are dominated by genetic risk factors, while envir...

  8. Genetic factors associated with small for gestational age birth and the use of human growth hormone in treating the disorder

    Directory of Open Access Journals (Sweden)

    Saenger Paul

    2012-05-01

    Full Text Available Abstract The term small for gestational age (SGA refers to infants whose birth weights and/or lengths are at least two standard deviation (SD units less than the mean for gestational age. This condition affects approximately 3%–10% of newborns. Causes for SGA birth include environmental factors, placental factors such as abnormal uteroplacental blood flow, and inherited genetic mutations. In the past two decades, an enhanced understanding of genetics has identified several potential causes for SGA. These include mutations that affect the growth hormone (GH/insulin-like growth factor (IGF-1 axis, including mutations in the IGF-1 gene and acid-labile subunit (ALS deficiency. In addition, select polymorphisms observed in patients with SGA include those involved in genes associated with obesity, type 2 diabetes, hypertension, ischemic heart disease and deletion of exon 3 growth hormone receptor (d3-GHR polymorphism. Uniparental disomy (UPD and imprinting effects may also underlie some of the phenotypes observed in SGA individuals. The variety of genetic mutations associated with SGA births helps explain the diversity of phenotype characteristics, such as impaired motor or mental development, present in individuals with this disorder. Predicting the effectiveness of recombinant human GH (hGH therapy for each type of mutation remains challenging. Factors affecting response to hGH therapy include the dose and method of hGH administration as well as the age of initiation of hGH therapy. This article reviews the results of these studies and summarizes the success of hGH therapy in treating this difficult and genetically heterogenous disorder.

  9. Genetic factors associated with small for gestational age birth and the use of human growth hormone in treating the disorder.

    Science.gov (United States)

    Saenger, Paul; Reiter, Edward

    2012-05-15

    The term small for gestational age (SGA) refers to infants whose birth weights and/or lengths are at least two standard deviation (SD) units less than the mean for gestational age. This condition affects approximately 3%-10% of newborns. Causes for SGA birth include environmental factors, placental factors such as abnormal uteroplacental blood flow, and inherited genetic mutations. In the past two decades, an enhanced understanding of genetics has identified several potential causes for SGA. These include mutations that affect the growth hormone (GH)/insulin-like growth factor (IGF)-1 axis, including mutations in the IGF-1 gene and acid-labile subunit (ALS) deficiency. In addition, select polymorphisms observed in patients with SGA include those involved in genes associated with obesity, type 2 diabetes, hypertension, ischemic heart disease and deletion of exon 3 growth hormone receptor (d3-GHR) polymorphism. Uniparental disomy (UPD) and imprinting effects may also underlie some of the phenotypes observed in SGA individuals. The variety of genetic mutations associated with SGA births helps explain the diversity of phenotype characteristics, such as impaired motor or mental development, present in individuals with this disorder. Predicting the effectiveness of recombinant human GH (hGH) therapy for each type of mutation remains challenging. Factors affecting response to hGH therapy include the dose and method of hGH administration as well as the age of initiation of hGH therapy. This article reviews the results of these studies and summarizes the success of hGH therapy in treating this difficult and genetically heterogenous disorder.

  10. Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

    OpenAIRE

    Randall, J. C.; Winkler, T.W.; Kutalik, Z.; Berndt, S.I.; Jackson, A.U.; Monda, K.L.; Kilpelainen, T.O.; Esko, T; Magi, R.; Li, S.; Workalemahu, T; Feitosa,M. F.; Croteau-Chonka, D.C.; Day, F. R.; Fall, T.

    2013-01-01

    Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previousl...

  11. The Effect of Ivermectin in Seven Strains of Aedes aegypti (Diptera: Culicidae) Including a Genetically Diverse Laboratory Strain and Three Permethrin Resistant Strains

    OpenAIRE

    Deus, K. M.; Saavedra-rodriguez, K.; Butters, M. P.; Black, W C; Foy, B.D.

    2012-01-01

    Seven different strains of Aedes aegypti (L.), including a genetically diverse laboratory strain, three laboratory-selected permethrin-resistant strains, a standard reference strain, and two recently colonized strains were fed on human blood containing various concentrations of ivermectin. Ivermectin reduced adult survival, fecundity, and hatch rate of eggs laid by ivermectin-treated adults in all seven strains. The LC50 of ivermectin for adults and the concentration that prevented 50% of egg...

  12. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.

    Directory of Open Access Journals (Sweden)

    Joshua C Randall

    2013-06-01

    Full Text Available Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals and took forward 348 SNPs into follow-up (additional 137,052 individuals in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%, including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9 and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG, all of which were genome-wide significant in women (P<5×10(-8, but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

  13. The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Defraene, Gilles, E-mail: gilles.defraene@uzleuven.be [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Van den Bergh, Laura [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Al-Mamgani, Abrahim [Department of Radiation Oncology, Erasmus Medical Center - Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Haustermans, Karin [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Heemsbergen, Wilma [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Van den Heuvel, Frank [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Lebesque, Joos V. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2012-03-01

    Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was 'previous abdominal surgery.' As second significant (p = 0.012-0.016) factor, 'cardiac history' was included in all three rectal bleeding fits, whereas including 'diabetes' was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D{sub 50}. Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints

  14. Genetic mapping of resistance factors to Phytophthora palmivora in cocoa.

    Science.gov (United States)

    Flament, M H; Kebe, I; Clément, D; Pieretti, I; Risterucci, A M; N'Goran, J A; Cilas, C; Despréaux, D; Lanaud, C

    2001-02-01

    Phytophthora palmivora causes pod rot, a serious disease on cocoa widespread throughout the producing regions. In order to ascertain the genetic determination of cocoa resistance to P. palmivora, a study was carried out on two progenies derived from crosses between a heterozygous, moderately resistant Forastero clone, T60/887, and two closely related and highly susceptible Forastero clones, one completely homozygous, IFC2, and one partially heterozygous, IFC5. The cumulative size of both progenies was 112 individuals. Plants were subjected to natural and artificial inoculation of P. palmivora in C te d'Ivoire. The genetic maps of T60/887 and of IFC5 were constructed using amplified fragment length polymorphism (AFLP) markers and microsatellites. The map of T60/887 comprised 198 markers assembled in 11 linkage groups and representing a total length of 793 cM. The map of IFC5 comprised 55 AFLP markers that were assembled into six linkage groups for a total length of 244 cM. Ratio of rotten over total number of fruit under natural infection was measured for each tree over two harvests. Artificial inoculations were performed on leaves and pods. These tests were weakly correlated with the pod rot rate in the field. Five quantitative trait loci (QTLs) of resistance were detected for T60/887 but none were common between the three traits measured. Stability and reliability of the experimental procedures are discussed and revealed the difficult use of these artificial tests on adult trees for a good prediction of field resistance.

  15. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

    Directory of Open Access Journals (Sweden)

    Pangilinan Faith

    2012-08-01

    Full Text Available Abstract Background Neural tube defects (NTDs are common birth defects (~1 in 1000 pregnancies in the US and Europe that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T and MTHFD1 rs2236225 (R653Q have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk. Methods A tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents, including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects. Results Nearly 70 SNPs in 30 genes were found to be associated with NTDs at the p MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury and included the known NTD risk factor MTHFD1 R653Q (rs2236225. The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele. Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing. Conclusions To our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive

  16. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

    LENUS (Irish Health Repository)

    Pangilinan, Faith

    2012-08-02

    AbstractBackgroundNeural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate\\/B12 pathway genes contribute to NTD risk.MethodsA tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate\\/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects.ResultsNearly 70 SNPs in 30 genes were found to be associated with NTDs at the p < 0.01 level. The ten strongest association signals (p-value range: 0.0003–0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing.ConclusionsTo our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the

  17. Sex differences in genetic and environmental risk factors for irrational fears and phobias.

    Science.gov (United States)

    Kendler, K S; Jacobson, K C; Myers, J; Prescott, C A

    2002-02-01

    For irrational fears and their associated phobias, epidemiological studies suggest sex differences in prevalence and twin studies report significant genetic effects. How does sex impact on the familial transmission of liability to fears and phobias? In personal interviews with over 3000 complete pairs (of whom 1058 were opposite-sex dizygotic pairs), ascertained from a population-based registry, we assessed the lifetime prevalence of five phobias and their associated irrational fears analysed using a multiple threshold model. Twin resemblance was assessed by polychoric correlations and biometrical model-fitting incorporating sex-specific effects. For agoraphobia, situational and blood/injury fear/phobia, the best fit model suggested equal heritability in males and females and genetic correlations between the sexes of less than +0.50. For animal fear/phobias by contrast, the best fit model suggested equal heritability in males and females and a genetic correlation of unity. No evidence was found for an impact of family environment on liability to these fears or phobias. For social phobias, twin resemblance in males was explained by genetic factors and in females by familial-environmental factors. The impact of sex on genetic risk may differ meaningfully across phobia subtypes. Sex-specific genetic risk factors may exist for agoraphobia, social, situational and blood-injury phobias but not for animal fear/phobia. These results should be interpreted in the context of the limited power of twin studies, even with large sample sizes, to resolve sex-specific genetic effects.

  18. Factores de riesgo de la enfermedad periodontal: factores genéticos Risks factors in periodontal diseases: genetic factors

    OpenAIRE

    2005-01-01

    Hoy en día y tras numerosos estudios epidemiológicos, se acepta el concepto de la existencia de determinados factores de riesgo que van a modular la susceptibilidad o resistencia del hospedador a padecer enfermedad periodontal, por lo tanto, en el desarrollo van a intervenir varias causas considerándose dicha patología de etiología multifactorial. De este modo, las enfermedades periodontales son producidas por una interacción de un agente microbiano único o múltiple considerado como el factor...

  19. Moderation of genetic factors by parental divorce in adolescents' evaluations of family functioning and subjective wellbeing.

    Science.gov (United States)

    van der Aa, Niels; Boomsma, Dorret I; Rebollo-Mesa, Irene; Hudziak, James J; Bartels, Meike

    2010-04-01

    Adolescents' evaluations of family functioning may have a significant impact on their subjective well-being and adjustment. The aim of the study was to investigate the degree to which genetic and environmental influences affect variation in evaluations of general family functioning, family conflict, and quality of life and the overlap between them. We assessed whether genetic and environmental influences are moderated by parental divorce by analyzing self-report data from 6,773 adolescent twins and their non-twin siblings. Genetic, shared, and nonshared environmental influences accounted for variation in general family functioning and family conflict, with genetic influences being relatively more important in girls than boys in general family functioning. Genetic and nonshared environmental influences accounted for variation in quality of life, with genetic influences being relatively more important in girls. Evidence was found for interaction between genetic factors and parental divorce: genetic influence on general family functioning was larger in participants from divorced families. The overlap between general family functioning and quality of life, and family conflict and quality of life was accounted for the largest part by genetic effects, with nonshared environmental effects accounting for the remaining part. By examining the data from monozygotic twins, we found evidence for interaction between genotype and nonshared, non-measured, environmental influences on evaluations of general family functioning, family conflict, and quality of life.

  20. Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk

    DEFF Research Database (Denmark)

    Pearce, Celeste Leigh; Doherty, Jennifer A; Van Den Berg, David J

    2011-01-01

    The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. We hypothesized that genetic variation in this pathway may influence risk of ovarian cancer. A three-center study of non-Hispanic whites including 1880 control women, 1135 women with invasive epithelial...... as an important gene for ovarian cancer; additional genotyping is warranted to further confirm these associations with IGF2 and to narrow down the region harboring the causal SNP....

  1. Frequent respiratory tract infections in children. The role of environmental and genetic factors.

    NARCIS (Netherlands)

    Ruskamp, J.M.

    2009-01-01

    Respiratory tract infections (RTI), presenting as common cold, pharyngitis, tonsillitis, acute otitis media, bronchitis or pneumonia are a major health problem in children. In this thesis common environmental and host factors, as well as plausible genetic factors were evaluated in a large birth coho

  2. A guide to murine coagulation factor structure, function, assays, and genetic alterations

    NARCIS (Netherlands)

    Emeis, J.J.; Jirouskova, M.; Muchitsch, E.-M.; Shet, A.S.; Smyth, S.S.; Johnson, G.J.

    2007-01-01

    Murine blood coagulation factors and function are quite similar to those of humans. Because of this similarity and the adaptability of mice to genetic manipulation, murine coagulation factors and inhibitors have been extensively studied. These studies have provided significant insights into human

  3. An acenocoumarol dosing algorithm exploiting clinical and genetic factors in South Indian (Dravidian) population.

    Science.gov (United States)

    Krishna Kumar, Dhakchinamoorthi; Shewade, Deepak Gopal; Loriot, Marie-Anne; Beaune, Philippe; Sai Chandran, B V; Balachander, Jayaraman; Adithan, Chandrasekaran

    2015-02-01

    The objective of this study was to determine the influence of CYP2C9, VKORC1, CYP4F2, and GGCX genetic polymorphisms on mean daily dose of acenocoumarol in South Indian patients and to develop a new pharmacogenetic algorithm based on clinical and genetic factors. Patients receiving acenocoumarol maintenance therapy (n = 230) were included in the study. Single nucleotide polymorphisms (SNP) of CYP2C9, VKORC1, CYP4F2, and GGCX were genotyped by real-time polymerase chain reaction (RT-PCR) method. The mean daily acenocoumarol maintenance dose was found to be 3.7 ± 2.3 (SD) mg/day. The CYP2C9 *1*2, CYP2C9 *1*3, and CYP2C9 *2*3 variant genotypes significantly reduced the dose by 56.7 % (2.0 mg), 67.6 % (1.6 mg), and 70.3 % (1.5 mg) than wild-type carriers 4.1 mg, p genetic variants of CYP2C9 and GGCX (rs11676382) were found to be associated with lower acenocoumarol dose, whereas CYP4F2 (rs2108622) was associated with higher doses. Age, body mass index (BMI), variation of CYP2C9, VKORC1, CYP4F2, and GGCX were the major determinants of acenocoumarol maintenance dose, accounting for 61.8 % of its variability (adjusted r (2) = 0.615, p algorithm was established to determine the acenocoumarol dose in South Indian population.

  4. Genetic factors that increase male facial masculinity decrease facial attractiveness of female relatives.

    Science.gov (United States)

    Lee, Anthony J; Mitchem, Dorian G; Wright, Margaret J; Martin, Nicholas G; Keller, Matthew C; Zietsch, Brendan P

    2014-02-01

    For women, choosing a facially masculine man as a mate is thought to confer genetic benefits to offspring. Crucial assumptions of this hypothesis have not been adequately tested. It has been assumed that variation in facial masculinity is due to genetic variation and that genetic factors that increase male facial masculinity do not increase facial masculinity in female relatives. We objectively quantified the facial masculinity in photos of identical (n = 411) and nonidentical (n = 782) twins and their siblings (n = 106). Using biometrical modeling, we found that much of the variation in male and female facial masculinity is genetic. However, we also found that masculinity of male faces is unrelated to their attractiveness and that facially masculine men tend to have facially masculine, less-attractive sisters. These findings challenge the idea that facially masculine men provide net genetic benefits to offspring and call into question this popular theoretical framework.

  5. Alcoholism and liver disease in Mexico: genetic and environmental factors.

    Science.gov (United States)

    Roman, Sonia; Zepeda-Carrillo, Eloy Alfonso; Moreno-Luna, Laura Eugenia; Panduro, Arturo

    2013-11-28

    Alcoholism and cirrhosis, which are two of the most serious health problems worldwide, have a broad spectrum of clinical outcomes. Both diseases are influenced by genetic susceptibility and cultural traits that differ globally but are specific for each population. In contrast to other regions around the world, Mexicans present the highest drinking score and a high mortality rate for alcoholic liver disease with an intermediate category level of per capita alcohol consumption. Mexico has a unique history of alcohol consumption that is linked to profound anthropological and social aspects. The Mexican population has an admixture genome inherited from different races, Caucasian, Amerindian and African, with a heterogeneous distribution within the country. Thus, genes related to alcohol addiction, such as dopamine receptor D2 in the brain, or liver alcohol-metabolizing enzymes, such as alcohol dehydrogenase class I polypeptide B, cytochrome P450 2E1 and aldehyde dehydrogenase class 2, may vary from one individual to another. Furthermore, they may be inherited as risk or non-risk haplogroups that confer susceptibility or resistance either to alcohol addiction or abusive alcohol consumption and possibly liver disease. Thus, in this era of genomics, personalized medicine will benefit patients if it is directed according to individual or population-based data. Additional association studies will be required to establish novel strategies for the prevention, care and treatment of liver disease in Mexico and worldwide.

  6. Exploration and implementation for the construction of the quaternary teaching system of medical genetics including teaching, practice, research and clinical application.

    Science.gov (United States)

    Fengjuan, Zhou; Wenmei, Xie; Qiang, Wang; Xiaorong, Zhao

    2015-09-01

    Medical genetics, the connection between basic and clinical medicine, is a subject with strong applicability and plays important role in modern medical education system. Based on years of teaching experience and during the construction of state-level top quality course, our teaching team has established the quaternary teaching system of medical genetics which includes teaching, practice, research and clinical application. The four elements of the system interpenetrate, complement and reinforce each other. Specifically, classroom teaching is the basics which is further complemented by social practice, improved by research and promoted by clinical application. The quaternary teaching system provides a feasible way to integrate theoretical and clinical courses. After years of implementation, the teaching system has got great effects on the obvious improvement of research ability, social reputation and clinical service capacities of the research team.

  7. Factor V leiden and ischemic stroke risk: the Genetics of Early Onset Stroke (GEOS) study.

    Science.gov (United States)

    Hamedani, Ali G; Cole, John W; Cheng, Yuching; Sparks, Mary J; O'Connell, Jeffrey R; Stine, Oscar C; Wozniak, Marcella A; Stern, Barney J; Mitchell, Braxton D; Kittner, Steven J

    2013-05-01

    Factor V Leiden (FVL) has been associated with ischemic stroke in children but not in adults. Although the FVL mutation is associated with increased risk for venous thrombosis, its association with ischemic stroke in young adults remains uncertain. Therefore, we examined the association between FVL and ischemic stroke in participants of the Genetics of Early Onset Stroke (GEOS) study. A population-based case control study identified 354 women and 476 men 15 to 49 years of age with first-ever ischemic stroke and 907 controls. Participant-specific data included vascular risk factors, FVL genotype and, for cases, the ischemic stroke subtype by modified Trial of ORG 10172 in Acute Stroke criteria. Logistic regression was used to calculate odds ratios for the entire population and for subgroups stratified by risk factors and ischemic stroke subtype. The frequency of the FVL mutation was similar between ischemic stroke patients (3.6%; 95% confidence interval [CI] 2.5%-5.1%) and nonstroke controls (3.8%; 95% CI 2.7%-5.2%). This frequency did not change significantly when cases were restricted to patients with stroke of undetermined etiology (4.1%; 95% CI 2.6%-6.4%). Among young adults, we found no evidence for an association between FVL and either all ischemic stroke or the subgroup with stroke of undetermined etiology. Published by Elsevier Inc.

  8. Factor analysis models for structuring covariance matrices of additive genetic effects: a Bayesian implementation

    Directory of Open Access Journals (Sweden)

    Gianola Daniel

    2007-09-01

    Full Text Available Abstract Multivariate linear models are increasingly important in quantitative genetics. In high dimensional specifications, factor analysis (FA may provide an avenue for structuring (covariance matrices, thus reducing the number of parameters needed for describing (codispersion. We describe how FA can be used to model genetic effects in the context of a multivariate linear mixed model. An orthogonal common factor structure is used to model genetic effects under Gaussian assumption, so that the marginal likelihood is multivariate normal with a structured genetic (covariance matrix. Under standard prior assumptions, all fully conditional distributions have closed form, and samples from the joint posterior distribution can be obtained via Gibbs sampling. The model and the algorithm developed for its Bayesian implementation were used to describe five repeated records of milk yield in dairy cattle, and a one common FA model was compared with a standard multiple trait model. The Bayesian Information Criterion favored the FA model.

  9. Influence of Environmental and Genetic Factors Linked to Celiac Disease Risk on Infant Gut Colonization by Bacteroides Species▿

    Science.gov (United States)

    Sánchez, Ester; De Palma, Giada; Capilla, Amalia; Nova, Esther; Pozo, Tamara; Castillejo, Gemma; Varea, Vicente; Marcos, Ascensión; Garrote, José Antonio; Polanco, Isabel; López, Ana; Ribes-Koninckx, Carmen; García-Novo, Maria Dolores; Calvo, Carmen; Ortigosa, Luis; Palau, Francesc; Sanz, Yolanda

    2011-01-01

    Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors whose interaction might influence disease risk. The aim of this study was to determine the effects of milk-feeding practices and the HLA-DQ genotype on intestinal colonization of Bacteroides species in infants at risk of CD development. This study included 75 full-term newborns with at least one first-degree relative suffering from CD. Infants were classified according to milk-feeding practice (breast-feeding or formula feeding) and HLA-DQ genotype (high or low genetic risk). Stools were analyzed at 7 days, 1 month, and 4 months by PCR and denaturing gradient gel electrophoresis (DGGE). The Bacteroides species diversity index was higher in formula-fed infants than in breast-fed infants. Breast-fed infants showed a higher prevalence of Bacteroides uniformis at 1 and 4 months of age, while formula-fed infants had a higher prevalence of B. intestinalis at all sampling times, of B. caccae at 7 days and 4 months, and of B. plebeius at 4 months. Infants with high genetic risk showed a higher prevalence of B. vulgatus, while those with low genetic risk showed a higher prevalence of B. ovatus, B. plebeius, and B. uniformis. Among breast-fed infants, the prevalence of B. uniformis was higher in those with low genetic risk than in those with high genetic risk. Among formula-fed infants, the prevalence of B. ovatus and B. plebeius was increased in those with low genetic risk, while the prevalence of B. vulgatus was higher in those with high genetic risk. The results indicate that both the type of milk feeding and the HLA-DQ genotype influence the colonization process of Bacteroides species, and possibly the disease risk. PMID:21642397

  10. Influence of environmental and genetic factors linked to celiac disease risk on infant gut colonization by Bacteroides species.

    Science.gov (United States)

    Sánchez, Ester; De Palma, Giada; Capilla, Amalia; Nova, Esther; Pozo, Tamara; Castillejo, Gemma; Varea, Vicente; Marcos, Ascensión; Garrote, José Antonio; Polanco, Isabel; López, Ana; Ribes-Koninckx, Carmen; García-Novo, Maria Dolores; Calvo, Carmen; Ortigosa, Luis; Palau, Francesc; Sanz, Yolanda

    2011-08-01

    Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors whose interaction might influence disease risk. The aim of this study was to determine the effects of milk-feeding practices and the HLA-DQ genotype on intestinal colonization of Bacteroides species in infants at risk of CD development. This study included 75 full-term newborns with at least one first-degree relative suffering from CD. Infants were classified according to milk-feeding practice (breast-feeding or formula feeding) and HLA-DQ genotype (high or low genetic risk). Stools were analyzed at 7 days, 1 month, and 4 months by PCR and denaturing gradient gel electrophoresis (DGGE). The Bacteroides species diversity index was higher in formula-fed infants than in breast-fed infants. Breast-fed infants showed a higher prevalence of Bacteroides uniformis at 1 and 4 months of age, while formula-fed infants had a higher prevalence of B. intestinalis at all sampling times, of B. caccae at 7 days and 4 months, and of B. plebeius at 4 months. Infants with high genetic risk showed a higher prevalence of B. vulgatus, while those with low genetic risk showed a higher prevalence of B. ovatus, B. plebeius, and B. uniformis. Among breast-fed infants, the prevalence of B. uniformis was higher in those with low genetic risk than in those with high genetic risk. Among formula-fed infants, the prevalence of B. ovatus and B. plebeius was increased in those with low genetic risk, while the prevalence of B. vulgatus was higher in those with high genetic risk. The results indicate that both the type of milk feeding and the HLA-DQ genotype influence the colonization process of Bacteroides species, and possibly the disease risk.

  11. Genetic and environmental factors in alexithymia: A population-based study of 8.785 Danish twin pairs

    DEFF Research Database (Denmark)

    Jørgensen, Michael Martini; Zachariae, Robert; Skytthe, Axel

    2007-01-01

    BACKGROUND: The role of genetic and environmental factors for developing alexithymia is still unclear, and the aim of this study was to examine these factors in a large population-based sample of twins. METHODS: The Toronto Alexithymia Scale-20 (TAS-20) was included in a mail survey of 46,418 ind...

  12. Genetic factors in familial aggregation of blood pressure of Portuguese nuclear families.

    Science.gov (United States)

    Fermino, Rogério César; Seabra, André; Garganta, Rui; Maia, José António Ribeiro

    2009-03-01

    Despite of the increase in the prevalence of hypertension in Portugal, the importance of genetic factors in blood pressure (BP) has not been studied extensively in our country. To verify the indirect presence of vertical transmission of genetic factors between parents and children in BP values, and to estimate the magnitude of genetic factors contributing for variation in BP values in the population. Sample size comprises 367 individuals (164 parents and 203 children) pertaining the 107 nuclear families participating in 'Familias Activas' project, proceeding from different regions of North Portugal. The BP was measured with Omron model M6 (HEM-7001-E) digital device. SPSS 15.0 was used for data analysis; PEDSTATS was used to verify the structure of each family data. Familial correlations and heritability estimates were computed in FCOR and ASSOC modules of S.A.G.E. version 5.3. For systolic BP (SBP), correlation values were low to moderate (0.21< or = r < or =0.35); for diastolic BP (DBP) values were found to be moderate (0.24< or = r < or =0. 50). Genetic factors explain 43 and 49% of the total variation in SBP and DBP, respectively. A moderate amount of the SBP and the DBP is accounted for by genetic factors.

  13. Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes

    Science.gov (United States)

    Nagaishi, Kanna; Mizue, Yuka; Chikenji, Takako; Otani, Miho; Nakano, Masako; Konari, Naoto; Fujimiya, Mineko

    2016-01-01

    Bone marrow-derived mesenchymal stem cells (MSCs) have contributed to the improvement of diabetic nephropathy (DN); however, the actual mediator of this effect and its role has not been characterized thoroughly. We investigated the effects of MSC therapy on DN, focusing on the paracrine effect of renal trophic factors, including exosomes secreted by MSCs. MSCs and MSC-conditioned medium (MSC-CM) as renal trophic factors were administered in parallel to high-fat diet (HFD)-induced type 2 diabetic mice and streptozotocin (STZ)-induced insulin-deficient diabetic mice. Both therapies showed approximately equivalent curative effects, as each inhibited the exacerbation of albuminuria. They also suppressed the excessive infiltration of BMDCs into the kidney by regulating the expression of the adhesion molecule ICAM-1. Proinflammatory cytokine expression (e.g., TNF-α) and fibrosis in tubular interstitium were inhibited. TGF-β1 expression was down-regulated and tight junction protein expression (e.g., ZO-1) was maintained, which sequentially suppressed the epithelial-to-mesenchymal transition of tubular epithelial cells (TECs). Exosomes purified from MSC-CM exerted an anti-apoptotic effect and protected tight junction structure in TECs. The increase of glomerular mesangium substrate was inhibited in HFD-diabetic mice. MSC therapy is a promising tool to prevent DN via the paracrine effect of renal trophic factors including exosomes due to its multifactorial action. PMID:27721418

  14. The role of genetic factors and pre- and perinatal influences in the etiology of autism spectrum disorders – indications for genetic referral

    Directory of Open Access Journals (Sweden)

    Filip Rybakowski

    2016-06-01

    Full Text Available Autism spectrum disorders (ASD are caused by disruptions in early stages of central nervous system development and are usually diagnosed in first years of life. Despite common features such as impairment of socio-communicative development and stereotypical behaviours, ASD are characterised by heterogeneous course and clinical picture. The most important aetiological factors comprise genetic and environmental influences acting at prenatal, perinatal and neonatal period. The role of rare variants with large effect i.e. copy number variants in genes regulating synapse formation and intrasynaptic connections is emphasised. Common variants with small effect may also be involved, i.e. polymorphisms in genes encoding prosocial peptides system – oxytocin and vasopressin. The environmental factors may include harmful effects acting during pregnancy and labour, however their specificity until now is not confirmed, and in some of them a primary genetic origin cannot be excluded. In several instances, especially with comorbid disorders – intellectual disability, epilepsy and dysmorphias – a detailed molecular diagnostics is warranted, which currently may elucidate the genetic background of disorder in about 20% of cases.

  15. QTLs of factors of the metabolic syndrome and echocardiographic phenotypes: the hypertension genetic epidemiology network study

    Directory of Open Access Journals (Sweden)

    de Simone Giovanni

    2008-11-01

    Full Text Available Abstract Background In a previous study of the Hypertension Genetic Epidemiology Network (HyperGEN we have shown that metabolic syndrome (MetS risk factors were moderately and significantly associated with echocardiographic (ECHO left ventricular (LV phenotypes. Methods The study included 1,393 African Americans and 1,133 whites, stratified by type 2 diabetes mellitus (DM status. Heritabilities of seven factor scores based on the analysis of 15 traits were sufficiently high to pursue QTL discovery in this follow-up study. Results Three of the QTLs discovered relate to combined MetS-ECHO factors of "blood pressure (BP-LV wall thickness" on chromosome 3 at 225 cM with a 2.8 LOD score, on chromosome 20 at 2.1 cM with a 2.6 LOD score; and for "LV wall thickness" factor on chromosome 16 at 113.5 with a 2.6 LOD score in whites. The remaining QTLs include one for a "body mass index-insulin (BMI-INS" factor with a LOD score of 3.9 on chromosome 2 located at 64.8 cM; one for the same factor on chromosome 12 at 91.4 cM with a 3.3 LOD score; one for a "BP" factor on chromosome 19 located at 67.8 cM with a 3.0 LOD score. A suggestive linkage was also found for "Lipids-INS" with a 2.7 LOD score located on chromosome 11 at 113.1 cM in African Americans. Of the above QTLs, the one on chromosome 12 for "BMI-INS" is replicated in both ethnicities, (with highest LOD scores in African Americans. In addition, the QTL for "LV wall thickness" on chromosome 16q24.2-q24.3 reached its local maximum LOD score at marker D16S402, which is positioned within the 5th intron of the cadherin 13 gene, implicated in heart and vascular remodeling. Conclusion Our previous study and this follow-up suggest gene loci for some crucial MetS and cardiac geometry risk factors that contribute to the risk of developing heart disease.

  16. Beyond genetics. Influence of dietary factors and gut microbiota on type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Dennis Sandris; Krych, Lukasz; Buschard, Karsten

    2014-01-01

    purely genetic are involved in disease development. Here we review the influence of dietary and environmental factors on T1D development in humans as well as animal models. Even though data are still inconclusive, there are strong indications that gut microbiota dysbiosis plays an important role in T1D...... development and evidence from animal models suggests that gut microbiota manipulation might prove valuable in future prevention of T1D in genetically susceptible individuals....

  17. Breastfeeding and genetic factors in the etiology of inflammatory bowel disease in children

    Institute of Scientific and Technical Information of China (English)

    Theresa A Mikhailov; Sylvia E Furner

    2009-01-01

    Inflammatory bowel disease is a chronic, debilitating disorder of the gastrointestinal tract. The etiology of inflammatory bowel disease has not been elucidated, but is thought to be multifactorial with both environmental and genetic influences. A large body of research has been conducted to elucidate the etiology of inflammatory bowel disease. This article reviews this literature, emphasizing the studies of breastfeeding and the studies of genetic factors, particularly NOD2 polymorphisms.

  18. Shared Genetic Factors Influence Risk for Bipolar Disorder and Alcohol Use Disorders

    Science.gov (United States)

    Carmiol, Nasdia; Peralta, Juan M; Almasy, Laura; Contreras, Javier; Pacheco, Adriana; Escamilla, Michael A; Knowles, Emma E; Raventós, Henriette; Glahn, David C

    2014-01-01

    Bipolar disorder and alcohol use disorder (AUD) have a high rate of comorbidity, more than 50% of individuals with bipolar disorder also receive a diagnosis of AUD in their lifetimes. Although both disorders are heritable, it is unclear if the same genetic factors mediate risk for bipolar disorder and AUD. We examined 733 Costa Rican individuals from 61 bipolar pedigrees. Based on a best-estimate process, 32% of the sample met criteria for bipolar disorder, 17% had a lifetime AUD diagnosis, 32% met criteria for lifetime nicotine dependence, and 21% had an anxiety disorder. AUD, nicotine dependence and anxiety disorders were relatively more common among individuals with bipolar disorder than in their non-bipolar relatives. All illnesses were shown to be heritable and bipolar disorder was genetically correlated with AUD, nicotine dependence and anxiety disorders. The genetic correlation between bipolar and AUD remained when controlling for anxiety, suggesting that unique genetic factors influence risk for comorbid bipolar and AUD independent of anxiety. Our findings provide evidence for shared genetic effects on bipolar disorder and AUD risk. Demonstrating that common genetic factors influence these independent diagnostic constructs could help to refine our diagnostic nosology. PMID:24321773

  19. Genetic vs Environmental Factors That Correlate With Rosacea: A Cohort-Based Survey of Twins.

    Science.gov (United States)

    Aldrich, Nely; Gerstenblith, Meg; Fu, Pingfu; Tuttle, Marie S; Varma, Priya; Gotow, Erica; Cooper, Kevin D; Mann, Margaret; Popkin, Daniel L

    2015-11-01

    To our knowledge, this is the first study on rosacea to formally define genetic and environmental contributions. To study a cohort of identical and fraternal twins to determine whether genetic factors contribute to rosacea development and, if genetic factors are present, quantitatively estimate the genetic contribution, as well as to identify environmental factors that correlate with rosacea by controlling for genetic susceptibility. Identical and fraternal twins were surveyed regarding risk factors implicated in rosacea. Faculty dermatologists determined a rosacea score for each twin participant according to the National Rosacea Society (NRS) grading system. Data were collected at the annual Twins Days Festival in Twinsburg, Ohio, on August 4-5, 2012, and August 2-3, 2013. Analysis was conducted for several months after each meeting. A cohort of 550 twin individuals, with most from Ohio, Pennsylvania, and the northeastern United States, participated. The NRS score and rosacea subtype were assessed using the NRS grading system and physical examination by board-certified dermatologists. Among the 275 twin pairs (550 individuals), there were 233 identical twin pairs with a mean rosacea score of 2.46 and 42 fraternal twin pairs with a mean rosacea score of 0.75. We observed a higher association of NRS scores between identical vs fraternal twins (r = 0.69 vs r = 0.46; P = .04), demonstrating a genetic contribution. Using the ACE model (proportion of variance in a trait heritable secondary to additive genetics [A] vs the proportions due to a common environment [C] and unique environment [E]), we calculated this genetic contribution to be 46%. A higher NRS score was also significantly associated with the following factors: age (r = 0.38; P twins allows us to separate genetic susceptibility and the influence of environmental factors affecting rosacea. We found that approximately half of the contribution to the NRS score could be accounted for by genetics

  20. 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.

  1. Dissection of genetic and environmental factors involved in tomato organoleptic quality

    Directory of Open Access Journals (Sweden)

    Frusciante Luigi

    2011-03-01

    Full Text Available Abstract Background One of the main tomato breeding objectives is to improve fruit organoleptic quality. However, this task is made somewhat challenging by the complex nature of sensory traits and the lack of efficient selection criteria. Sensory quality depends on numerous factors, including fruit colour, texture, aroma, and composition in primary and secondary metabolites. It is also influenced by genotypic differences, the nutritional regime of plants, stage of ripening at harvest and environmental conditions. In this study, agronomic, biochemical and sensory characterization was performed on six Italian heirlooms grown in different environmental conditions. Result We identified a number of links among traits contributing to fruit organoleptic quality and to the perception of sensory attributes. PCA analysis was used to highlight some biochemical, sensory and agronomic discriminating traits: this statistical test allowed us to identify which sensory attributes are more closely linked to environmental conditions and those, instead, linked to the genetic constitution of tomato. Sweetness, sourness, saltiness and tomato flavour are not only grouped in the same PCA factor, but also result in a clear discrimination of tomato ecotypes in the three different fields. The three different traditional varieties cluster on the basis of attributes like juiciness, granulosity, hardness and equatorial diameter, and are therefore more closely related to the genetic background of the cultivar. Conclusion This finding suggests that a different method should be undertaken to improve sensory traits related to taste perception and texture. Our results might be used to ascertain in what direction to steer breeding in order to improve the flavour characteristics of tomato ecotypes.

  2. The impact of childhood maltreatment: A review of neurobiological and genetic factors

    Directory of Open Access Journals (Sweden)

    Eamon eMcCrory

    2011-07-01

    Full Text Available Childhood maltreatment represents a significant risk factor for psychopathology. Recent research has begun to examine both the functional and structural neurobiological correlates of adverse care-giving experiences, including maltreatment, and how these might impact on a child's psychological and emotional development. The relationship between such experiences and risk for psychopathology has been shown to vary as a function of genetic factors. In this review we begin by providing a brief overview of neuroendocrine findings, which indicate an association between maltreatment and atypical development of the hypothalamic-pituitary-adrenal axis stress response, which may predispose to psychiatric vulnerability in adulthood. We then selectively review the magnetic resonance imaging (MRI studies that have investigated possible structural and functional brain differences in children and adults who have experienced childhood maltreatment. Differences in the corpus callosum identified by structural MRI have now been reliably reported in children who have experienced abuse, while differences in the hippocampus have been reported in adults with childhood histories of maltreatment. In addition, there is preliminary evidence from functional MRI studies of adults who have experienced childhood maltreatment of amygdala hyperactivity and atypical activation of frontal regions. These functional differences can be partly understood in the context of the information biases observed in event-related potential and behavioural studies of physically abused children. Finally we consider research that has indicated that the effect of environmental adversity may be moderated by genotype, reviewing pertinent studies pointing to gene by environment (GxE interactions. We conclude by exploring the extent to which the growing evidence base in relation to neurobiological and genetic research may be relevant to clinical practice and intervention.

  3. Ethnicity and Prostate Cancer: Vitamin D Genetic and Sociodemographic Factors

    Science.gov (United States)

    2009-03-01

    Plagiarism is the use of another person’s words or ideas without crediting that person. Plagiarism and cheating will not be tolerated and may lead to...session. This includes working out problems, providing short answers and definitions , and reading assignments. The homework assigned will usually cover

  4. How Genetic and Other Biological Factors Interact with Smoking Decisions.

    Science.gov (United States)

    Bierut, Laura; Cesarini, David

    2015-09-01

    Despite clear links between genes and smoking, effective public policy requires far richer measurement of the feedback between biological, behavioral, and environmental factors. The Kavli HUMAN Project (KHP) plans to exploit the plummeting costs of data gathering and to make creative use of new technologies to construct a longitudinal panel data set that would compare favorably to existing longitudinal surveys, both in terms of the richness of the behavioral measures and the cost-effectiveness of the data collection. By developing a more comprehensive approach to characterizing behavior than traditional methods, KHP will allow researchers to paint a much richer picture of an individual's life-cycle trajectory of smoking, alcohol, and drug use, and interactions with other choices and environmental factors. The longitudinal nature of KHP will be particularly valuable in light of the increasing evidence for how smoking behavior affects physiology and health. The KHP could have a transformative impact on the understanding of the biology of addictive behaviors such as smoking, and of a rich range of prevention and amelioration policies.

  5. Non-genetic risk factors in haemophilia A inhibitor management

    DEFF Research Database (Denmark)

    Löfgren, Karin Maria; Søndergaard, H.; Skov, Søren;

    2016-01-01

    In haemophilia A (HA) management, antidrug antibodies, or inhibitors, are a serious complication that renders factor VIII (FVIII) replacement therapy ineffective, increases morbidity and reduces quality of life for affected patients. Inhibitor development aetiology is multifactorial and covers bo...... with a suspected danger signal aetiology; on-demand treatment, treatment during major bleeds or surgery, and treatment during infection or vaccination. Clinical studies as well as animal experiments addressing these factors will be reviewed......., and explanations for this association are being investigated. A potential explanation is the danger signal effect, where the immune response is activated by endogenous or exogenous danger or damage signals present at the time and site of FVIII administration. The danger theory explains how alarm signals from...... stressed, injured or dying cells can activate an immune reaction, without the involvement of foreign antigens. Bleeds, trauma, surgery or concomitant infection could be events initiating danger signalling in HA patients, resulting in an immune reaction towards administered FVIII that otherwise would pass...

  6. Influence of genetic and environmental factors on oral diseases and function in aged twins.

    Science.gov (United States)

    Kurushima, Y; Ikebe, K; Matsuda, K; Enoki, K; Ogata, S; Yamashita, M; Murakami, S; Hayakawa, K; Maeda, Y

    2015-01-01

    This study was conducted to quantify the genetic and environmental contributions to oral disease and function in twins. Participants were middle-aged and old twins, 116 monozygotic and 16 dizygotic pairs whose mean age was 66·1 ± 10·3 (SD) years. Number of teeth, percentage of decayed, filled and missing teeth and periodontal status were recorded as indicators of oral disease. The widths of upper and lower dental arch served as indicators of morphological figures. Furthermore, stimulated salivary flow rate, occlusal force and masticatory performance were measured as indicators of oral function. Univariate genetic analysis with monozygotic and dizygotic twin pairs was conducted to detect the fittest structural equation model of each outcome. Both number of teeth and periodontal status fitted the model composed of common environmental factor and unique environmental factor. Decayed, filled and missing teeth, morphological figures and measurements of oral function fitted the model composed of additive genetic factor and unique environmental factor. The model fitting of each measurement suggested that periodontal disease was mainly affected by environmental factors, while morphological figures and oral functions were influenced by both genetic and environmental factors.

  7. [Genetic and environmental factors of asthma and allergy: Results of the EGEA study].

    Science.gov (United States)

    Bouzigon, E; Nadif, R; Le Moual, N; Dizier, M-H; Aschard, H; Boudier, A; Bousquet, J; Chanoine, S; Donnay, C; Dumas, O; Gormand, F; Jacquemin, B; Just, J; Margaritte-Jeannin, P; Matran, R; Pison, C; Rage, E; Rava, M; Sarnowski, C; Smit, L A M; Temam, S; Varraso, R; Vignoud, L; Lathrop, M; Pin, I; Demenais, F; Kauffmann, F; Siroux, V

    2015-10-01

    The EGEA study (epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), which combines a case-control and a family-based study of asthma case (n=2120 subjects) with three surveys over 20 years, aims to identify environmental and genetic factors associated with asthma and asthma-related phenotypes. We summarize the results of the phenotypic characterization and the investigation of environmental and genetic factors of asthma and asthma-related phenotypes obtained since 2007 in the EGEA study (42 articles). Both epidemiological and genetic results confirm the heterogeneity of asthma. These results strengthen the role of the age of disease onset, the allergic status and the level of disease activity in the identification of the different phenotypes of asthma. The deleterious role of active smoking, exposure to air pollution, occupational asthmogenic agents and cleaning products on the prevalence and/or activity of asthma has been confirmed. Accounting for gene-environment interactions allowed the identification of new genetic factors underlying asthma and asthma-related traits and better understanding of their mode of action. The EGEA study is contributing to the advances in respiratory research at the international level. The new phenotypic, environmental and biological data available in EGEA study will help characterizing the long-term evolution of asthma and the factors associated to this evolution. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  8. Analysis of Factors That Affects the Capital Structure within Companies Included In the Index of LQ45 During 2011 - 2013

    Directory of Open Access Journals (Sweden)

    Dominica Rufina

    2016-01-01

    Full Text Available This study aims to determine the factors of ROA, Asset Structure, Sales Growth, and Firm Size affecting Capital Structure. The population in this study is the companies included in the Index LQ45 Indonesia Stock Exchange from the period 2011 to 2013, the data of a total of 270 listed companies in LQ45 during that period, only 90 corporate data that successively included in the index LQ45. The data used in this study uses secondary data from the Indonesia Stock Exchange website www.idx.co.id. In the process of data analysis and testing the assumptions of classical hypothesis testing using multiple linear regression analysis using SPSS v20.00. The results showed that partially variable ROA, Asset Structure, and Firm Size has a significant influence on the Capital Structure, Growth Sales whereas variable has no influence on the Capital Structure. Simultaneously ROA, Asset Structure, Sales Growth, and Firm Size effect on Capital Structure.

  9. Systematic genetic analysis of transcription factors to map the fission yeast transcription-regulatory network.

    Science.gov (United States)

    Chua, Gordon

    2013-12-01

    Mapping transcriptional-regulatory networks requires the identification of target genes, binding specificities and signalling pathways of transcription factors. However, the characterization of each transcription factor sufficiently for deciphering such networks remains laborious. The recent availability of overexpression and deletion strains for almost all of the transcription factor genes in the fission yeast Schizosaccharomyces pombe provides a valuable resource to better investigate transcription factors using systematic genetics. In the present paper, I review and discuss the utility of these strain collections combined with transcriptome profiling and genome-wide chromatin immunoprecipitation to identify the target genes of transcription factors.

  10. Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?

    DEFF Research Database (Denmark)

    Benyamin, B; Sørensen, T I A; Schousboe, K

    2007-01-01

    AIMS/HYPOTHESIS: The cluster of obesity, insulin resistance, dyslipidaemia and hypertension, called the metabolic syndrome, has been suggested as a risk factor for cardiovascular disease and type 2 diabetes. The aim of the present study was to evaluate whether there are common genetic...... and environmental factors influencing this cluster in a general population of twin pairs. MATERIALS AND METHODS: A multivariate genetic analysis was performed on nine endophenotypes associated with the metabolic syndrome from 625 adult twin pairs of the GEMINAKAR study of the Danish Twin Registry. RESULTS: All...

  11. Beyond genetics. Influence of dietary factors and gut microbiota on type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Dennis Sandris; Krych, Lukasz; Buschard, Karsten;

    2014-01-01

    Type 1 diabetes (T1D) is an autoimmune disease ultimately leading to destruction of insulin secreting β-cells in the pancreas. Genetic susceptibility plays an important role in T1D etiology, but even mono-zygotic twins only have a concordance rate of around 50%, underlining that other factors than...... purely genetic are involved in disease development. Here we review the influence of dietary and environmental factors on T1D development in humans as well as animal models. Even though data are still inconclusive, there are strong indications that gut microbiota dysbiosis plays an important role in T1D...

  12. Is there a genetic correlation between general factors of intelligence and personality?

    Science.gov (United States)

    Loehlin, John C; Bartels, Meike; Boomsma, Dorret I; Bratko, Denis; Martin, Nicholas G; Nichols, Robert C; Wright, Margaret J

    2015-06-01

    We tested a hypothesis that there is no genetic correlation between general factors of intelligence and personality, despite both having been selected for in human evolution. This was done using twin samples from Australia, the United States, the Netherlands, Great Britain, and Croatia, comprising altogether 1,748 monozygotic and 1,329 same-sex dizygotic twin pairs. Although parameters in the model-fitting differed among the twin samples, the genetic correlation between the two general factors could be set to zero, with a better fit if the U.S. sample was excepted.

  13. Genetic factors for nerve susceptibility to injuries-lessons from PMP22 deifciency

    Institute of Scientific and Technical Information of China (English)

    Jun Li

    2014-01-01

    Genetic factors may be learnt from families with gene mutations that render nerve-injury sus-ceptibility even to ordinary physical activities. A typical example is hereditary neuropathy with liability to pressure palsies (HNPP). HNPP is caused by a heterozygous deletion of PMP22 gene. PMP22 deficiency disrupts myelin junctions (such as tight junction and adherens junctions), leading to abnormally increased myelin permeability that explains the nerve susceptibility to injury. This ifnding should motivate investigators to identify additional genetic factors contribut-ing to nerve vulnerability of injury.

  14. Genetic factors for individual administration of immunosuppressants in organ transplantation

    Institute of Scientific and Technical Information of China (English)

    Song-Feng Yu; Li-Hua Wu; Shu-Sen Zheng

    2006-01-01

    BACKGROUND: The immunosuppressive drugs used worldwide have a narrow therapeutic index, which results in a need to individualize the dose regimen for different recipients. The oxidative enzymes cytochrome P450 (CYP)3A and the drug eflfux pump P-glycoprotein (P-gp) are two potential factors in the processes of metabolism. Pharmacogenetic study of immunosuppressive drugs has focused on these two enzymes. This review was undertaken to assess the role of single nuclear polymorphisms (SNPs) of these two enzymes in the individual administration of immunosuppressive drugs. DATA SOURCES: An English-language literature search was made using MEDLINE for articles on CYP3A and P-gp in organ transplantation. RESULTS: The SNPs of CYP3A and P-gp are closely correlated to the large variations of cyclosporine and tacrolimus dosage between different patients, although conlficting results were obtained by some authors. CONCLUSIONS: More studies should be conducted to elucidate further the pharmacogenetics of immuno-suppressive drugs in organ transplantation, a deep understanding of which would provide an important step toward drug regimen individualization in the posttransplant therapy.

  15. Roles of Vascular and Metabolic Components in Cognitive Dysfunction of Alzheimer disease: Short- and Long-term Modification by Non-genetic Risk Factors

    Directory of Open Access Journals (Sweden)

    Naoyuki eSato

    2013-11-01

    Full Text Available It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD. Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of 1 compromised vascular reactivity, 2 vascular lesions, 3 hypo/hyperglycemia, and 4 exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. Beta-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: 1 functional MRI or SPECT for cerebrovascular reactivity, 2 MRI for ischemic lesions and atrophy, 3 clinical episodes of hypoglycemia and hyperglycemia, 4 amyloid-PET and tau-PET for pathological features of AD, would be required.

  16. Novel genetic risk factors for asthma in African American children: Precision Medicine and the SAGE II Study.

    Science.gov (United States)

    White, M J; Risse-Adams, O; Goddard, P; Contreras, M G; Adams, J; Hu, D; Eng, C; Oh, S S; Davis, A; Meade, K; Brigino-Buenaventura, E; LeNoir, M A; Bibbins-Domingo, K; Pino-Yanes, M; Burchard, E

    2016-07-01

    Asthma, an inflammatory disorder of the airways, is the most common chronic disease of children worldwide. There are significant racial/ethnic disparities in asthma prevalence, morbidity, and mortality among US children. This trend is mirrored in obesity, which may share genetic and environmental risk factors with asthma. The majority of asthma biomedical research has been performed in populations of European decent. We sought to identify genetic risk factors for asthma in African American children. We also assessed the generalizability of genetic variants associated with asthma in European and Asian populations to African American children. Our study population consisted of 1227 (812 asthma cases, 415 controls) African American children with genome-wide single nucleotide polymorphism (SNP) data. Logistic regression was used to identify associations between SNP genotype and asthma status. We identified a novel variant in the PTCHD3 gene that is significantly associated with asthma (rs660498, p = 2.2 × 10(-7)) independent of obesity status. Approximately 5 % of previously reported asthma genetic associations identified in European populations replicated in African Americans. Our identification of novel variants associated with asthma in African American children, coupled with our inability to replicate the majority of findings reported in European Americans, underscores the necessity for including diverse populations in biomedical studies of asthma.

  17. Study of Clinical and Genetic Risk Factors for Aspirin-induced Gastric Mucosal Injury

    Directory of Open Access Journals (Sweden)

    Yun Wu

    2016-01-01

    Full Text Available Background: Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions. Methods: We recruited aspirin takers as the exposed group and healthy volunteers as the control group. The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy, including erosion, ulcer or bleeding of the esophagus, stomach, or duodenum; subgroup B as no injury of the gastric mucosa was detected by gastroscopy. Clinical information was collected, and 53 single nucleotide polymorphisms were evaluated. Results: Among 385 participants, 234 were in the aspirin-exposed group. According to gastroscopy, 82 belonged to subgroup A, 91 belonged to subgroup B, and gastroscopic results of 61 participants were not available. Using the Chi-square test and logistic regression, we found that peptic ulcer history (odds ratio [OR] = 5.924, 95% confidence intervals [CI]: 2.115-16.592, dual anti-platelet medication (OR = 3.443, 95% CI: 1.154-10.271, current Helicobacter pylori infection (OR = 2.242, 95% CI: 1.032-4.870, male gender (OR = 2.211, 95% CI: 1.027-4.760, GG genotype of rs2243086 (OR = 4.516, 95% CI: 1.180-17.278, and AA genotype of rs1330344 (OR = 2.178, 95% CI: 1.016-4.669 were more frequent in subgroup A than subgroup B. In aspirin users who suffered from upper gastrointestinal bleeding, the frequency of the TT genotype of rs2238631 and TT genotype of rs2243100 was higher than in those without upper gastrointestinal bleeding. Conclusions: Peptic ulcer history, dual anti-platelet medication, H. pylori current infection, and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury. GG genotype of rs2243086 and AA genotype of rs1330344 were possible genetic risk factors. TT genotype of rs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in

  18. Study of Clinical and Genetic Risk Factors for Aspirin-induced Gastric Mucosal Injury

    Institute of Scientific and Technical Information of China (English)

    Yun Wu; Ying Hu; Peng You; Yu-Jing Chi; Jian-Hua Zhou; Yuan-Yuan Zhang; Yu-Lan Liu

    2016-01-01

    Background:Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions.Methods:We recruited aspirin takers as the exposed group and healthy volunteers as the control group.The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy,including erosion,ulcer or bleeding of the esophagus,stomach,or duodenum;subgroup B as no injury of the gastric mucosa was detected by gastroscopy.Clinical information was collected,and 53 single nucleotide polymorphisms were evaluated.Results:Among 385 participants,234 were in the aspirin-exposed group.According to gastroscopy,82 belonged to subgroup A,91 belonged to subgroup B,and gastroscopic results of 61 participants were not available.Using the Chi-square test and logistic regression,we found that peptic ulcer history (odds ratio [OR] =5.924,95% confidence intervals [CI]:2.115-16.592),dual anti-platelet medication (OR =3.443,95% CI:1.154-10.271),current Helicobacterpylori infection (OR =2.242,95% CI:1.032-4.870),male gender (OR =2.211,95% CI:1.027-4.760),GG genotype ofrs2243086 (OR =4.516,95% CI:1.180-17.278),and AA genotype ofrs 1330344 (OR =2.178,95% CI:1.016-4.669) were more frequent in subgroup A than subgroup B.In aspirin users who suffered from upper gastrointestinal bleeding,the frequency of the TT genotype ofrs2238631 and TT genotype ofrs2243100 was higher than in those without upper gastrointestinal bleeding.Conclusions:Peptic ulcer history,dual anti-platelet medication,H.pylori current infection,and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury.GG genotype of rs2243086 and AA genotype of rs 1330344 were possible genetic risk factors.TT genotype ofrs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in aspirin users.

  19. Diet, Lifestyle, Biomarkers, Genetic Factors, and Risk of Cardiovascular Disease in the Nurses’ Health Studies

    Science.gov (United States)

    Yu, Edward; Rimm, Eric; Qi, Lu; Rexrode, Kathryn; Albert, Christine M.; Sun, Qi; Willett, Walter C.; Manson, JoAnn E.

    2016-01-01

    Objectives. To review the contributions of the Nurses’ Health Studies (NHSs) to the understanding of cardiovascular disease etiology in women. Methods. We performed a narrative review of the publications of the NHS and NHS II between 1976 and 2016. Results. Diets low in trans fat, saturated fat, refined carbohydrates, and sugar-sweetened beverages and rich in fruits and vegetables, whole grains, and sources of unsaturated fats are associated with reduced risk of cardiovascular disease. Healthy lifestyle choices include smoking avoidance, regular physical activity, maintaining a normal body mass index, and moderate alcohol consumption. Adherence to a combination of these healthy diet and lifestyle behaviors may prevent most vascular events. Studies also covered oral contraceptive use, postmenopausal hormone therapy, shift work, sleep duration, psychosocial factors, and various biomarkers and genetic factors. Findings, such as the association of trans fat with cardiovascular disease, have helped shaped medical guidelines and government policies. Conclusions. The NHS has provided compelling evidence that the majority of vascular events may be prevented by avoiding smoking, participating in regular physical activity, maintaining normal body mass index, and eating a healthy diet. PMID:27459449

  20. The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood

    Science.gov (United States)

    Campos Silva, Soraya Luiza; Marques de Miranda, Débora; Ferreira, Alexandre Rodrigues

    2016-01-01

    Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients. PMID:27882046

  1. Diabetes-Role of epigenetics, genetics,and physiological factors

    Institute of Scientific and Technical Information of China (English)

    Sreerama Krupanidhi; Saikiran K.Sedimbi; Ganesan Vaishnav; Sreerama Sai Madhukar; Carani B.Sanjeevi

    2009-01-01

    Cells of organ systems are endowed with a relatively similar genome while epigenome niches keep varying chronologically and defined explicitly in the respective tissues. The genome of an individual is always influenced by parental, embryonic, tissue-specific, and environmental epigenomes and the same must have been the possible reason for invariable inquiries relating to familial, environmental and life style patterns in the preliminary investigations of diabetic complications. Unprecedented methylation of lysine residues of histones and cytosines of CpG islands of promoter DNA impede the transcription of genes and homocysteine is the metabolic key player of methyl groups. Gck and COX7A1 are the 2 examples in the present review to elucidate the epigenetic influence on the onset of diabetes. miRNAs are additional promising cellular components influencing both at transcriptional and translational levels and promoting either in favour or against (i.e., feed back) TFs, signaling factors and proteins through their pliotropic effects and thus are reported to regulate cellular physiology. miR-124a and miR-9 are primarily endemic to nervous tissue and they are now being exploited in islets for their function in executing exocytosis of insulin, which of course is one of the fundamental canons of diabetes. miR-375 persuades beta cells for glucose-induced insulin gene expression. The current approach to evaluate the constellation of genes and their products involved in diabetes in huge number of samples through GWA studies may unravel intricacies involved in the management of diabetes and its associated consequences.

  2. Genetic liability, prenatal health, stress and family environment: risk factors in the Harvard Adolescent Family High Risk for schizophrenia study.

    Science.gov (United States)

    Walder, Deborah J; Faraone, Stephen V; Glatt, Stephen J; Tsuang, Ming T; Seidman, Larry J

    2014-08-01

    The familial ("genetic") high-risk (FHR) paradigm enables assessment of individuals at risk for schizophrenia based on a positive family history of schizophrenia in first-degree, biological relatives. This strategy presumes genetic transmission of abnormal traits given high heritability of the illness. It is plausible, however, that adverse environmental factors are also transmitted in these families. Few studies have evaluated both biological and environmental factors within a FHR study of adolescents. We conceptualize four precursors to psychosis pathogenesis: two biological (genetic predisposition, prenatal health issues (PHIs)) and two environmental (family environment, stressful life events (SLEs)). Participants assessed between 1998 and 2007 (ages 13-25) included 40 (20F/20M) adolescents at FHR for schizophrenia (FHRs) and 55 (31F/24M) community controls. 'Genetic load' indexed number of affected family members relative to pedigree size. PHI was significantly greater among FHRs, and family cohesion and expressiveness were less (and family conflict was higher) among FHRs; however, groups did not significantly differ in SLE indices. Among FHRs, genetic liability was significantly associated with PHI and family expressiveness. Prenatal and family environmental disruptions are elevated in families with a first-degree relative with schizophrenia. Findings support our proposed 'polygenic neurodevelopmental diathesis-stress model' whereby psychosis susceptibility (and resilience) involves the independent and synergistic confluence of (temporally-sensitive) biological and environmental factors across development. Recognition of biological and social environmental influences across critical developmental periods points to key issues relevant for enhanced identification of psychosis susceptibility, facilitation of more precise models of illness risk, and development of novel prevention strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Pilot Study: Association of Traditional and Genetic Risk Factors and New-Onset Diabetes Mellitus Following Kidney Transplantation

    Science.gov (United States)

    Chakkera, H.A.; Hanson, R.L.; Raza, S.M.; DiStefano, J.K.; Millis, M.P.; Heilman, R.L.; Mulligan, D.C.; Reddy, K.S.; Mazur, M.J.; Hamawi, K.; Moss, A.A.; Mekeel, K.L.; Cerhan, J.R.

    2012-01-01

    Introduction New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are “tipped over” to develop diabetes mellitus in the posttransplant milieu. Methods We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT. Results The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT. Conclusions These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT. PMID:20005362

  4. Molecular genetic analysis of activation-tagged transcription factors thought to be involved in photomorphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Neff, Michael M.

    2011-06-23

    This is a final report for Department of Energy Grant No. DE-FG02-08ER15927 entitled “Molecular Genetic Analysis of Activation-Tagged Transcription Factors Thought to be Involved in Photomorphogenesis”. Based on our preliminary photobiological and genetic analysis of the sob1-D mutant, we hypothesized that OBP3 is a transcription factor involved in both phytochrome and cryptochrome-mediated signal transduction. In addition, we hypothesized that OBP3 is involved in auxin signaling and root development. Based on our preliminary photobiological and genetic analysis of the sob2-D mutant, we also hypothesized that a related gene, LEP, is involved in hormone signaling and seedling development.

  5. Importance of genetic factors in the etiology of atopic dermatitis: a twin study

    DEFF Research Database (Denmark)

    Thomsen, Simon F; Ulrik, Charlotte S; Kyvik, Kirsten O;

    2007-01-01

    ?" Latent factor models of genetic and environmental influences were fitted to the observed data using maximum likelihood methods. The overall lifetime prevalence of atopic dermatitis was 7.3%. A cotwin of an affected identical twin had a sevenfold increased risk of atopic dermatitis compared......The susceptibility to develop atopic dermatitis can be attributed both to genetic and environmental causes. We estimated the relative impact of genetic and environmental factors in the etiology of atopic dermatitis in a population-based sample of twins. From the birth cohorts of 1953-1982 who were...... enrolled in The Danish Twin Registry, a total of 11,515 twin pairs were identified in a nationwide questionnaire survey. Subjects were classified as atopic dermatitis cases when responding affirmatively to the question, "Do you have, or have you ever had, eczema in the folds of your elbows or knees...

  6. Beyond genetics. Influence of dietary factors and gut microbiota on type 1 diabetes.

    Science.gov (United States)

    Nielsen, Dennis S; Krych, Łukasz; Buschard, Karsten; Hansen, Camilla H F; Hansen, Axel K

    2014-11-17

    Type 1 diabetes (T1D) is an autoimmune disease ultimately leading to destruction of insulin secreting β-cells in the pancreas. Genetic susceptibility plays an important role in T1D etiology, but even mono-zygotic twins only have a concordance rate of around 50%, underlining that other factors than purely genetic are involved in disease development. Here we review the influence of dietary and environmental factors on T1D development in humans as well as animal models. Even though data are still inconclusive, there are strong indications that gut microbiota dysbiosis plays an important role in T1D development and evidence from animal models suggests that gut microbiota manipulation might prove valuable in future prevention of T1D in genetically susceptible individuals.

  7. [Transcription Factors in Developmental Genetics and the Evolution of Higher Plants].

    Science.gov (United States)

    Lutova, L A; Dodueva, I E; Lebedeva, M A; Tvorogova, V E

    2015-05-01

    Transcription factors play an essential role in controlling various developmental programs in plants, coordinating the action of any genetic network. Among the most important groups of plant transcription factors are the homeodomain-containing transcription factors, in particular, those belonging to the KNOX and WOX families, the functions of which are associated with regulation of the meristem activity, development of the aboveground and underground parts of plants, and control of embryogenesis. This review examines the role of KNOX and WOX transcription factors in various developmental programs, as well as in the evolutionary complication of the body plan in terrestrial plants.

  8. Genetic and Environmental Risk Factors for Childhood Eczema Development and Allergic Sensitization in the CCAAPS Cohort

    OpenAIRE

    Myers, Jocelyn M. Biagini; Wang, Ning; LeMasters, Grace; Bernstein, David I; Epstein, Tolly; Lindsey, Mark; Ericksen, Mark; Chakraborty, Ranajit; Ryan, Patrick; Villareal, Manuel; Burkle, Jeff; Lockey, James; Reponen, Tiina; Hershey, Gurjit K Khurana

    2009-01-01

    Eczema is very common and increasing in prevalence. Prospective studies investigating environmental and genetic risk factors for eczema in a birth cohort are lacking. We evaluated risk factors that may promote development of childhood eczema in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort (n = 762) of infants with at least one atopic parent. Objective environmental exposure data were available for each participant. At annual physical examinations, children un...

  9. Genetic factors in human reproduction : a trade off between procreation and longevity

    NARCIS (Netherlands)

    Dunné, Frédérique Margo van

    2006-01-01

    Genetic factors play an important role in the regulation of human life span but the exact pathways remain to be elucidated, however they may be interrelated with the regulation of human reproduction. It is argued that an innate cytokine profile supportive of Th1-type T cells favors survival of infec

  10. Breed effect and non-genetic factors affecting growth performance of ...

    African Journals Online (AJOL)

    SARAH

    2013-07-30

    Jul 30, 2013 ... Breed effect and non-genetic factors of growth performance of sheep. 5302. Breed effect and .... consisting of 25% cottonseed cake and 75% maize. The General Liner Model ..... and environmental changes have effect on the quality and quantity of pasture forages, which also affect the provision of food and ...

  11. Spina bifida and genetic factors related to myo-inositol, glucose, and zinc.

    NARCIS (Netherlands)

    Groenen, P.; Klootwijk, E.D.; Schijvenaars, M.M.V.A.P.; Straatman, H.M.P.M.; Mariman, E.C.M.; Franke, B.; Steegers-Theunissen, R.P.M.

    2004-01-01

    BACKGROUND: Myo-inositol, glucose and zinc and related genetic factors are suggested to be implicated in the etiology of spina bifida. We investigated the biochemical concentrations of these nutrients and polymorphisms in the myo-inositol transporter SLC5A11, myo-inositol synthase ISYNA1, and zinc

  12. Parenting Moderates a Genetic Vulnerability Factor in Longitudinal Increases in Youths' Substance Use

    Science.gov (United States)

    Brody, Gene H.; Beach, Steven R. H.; Philibert, Robert A.; Chen, Yi-fu; Lei, Man-Kit; Murry, Velma McBride; Brown, Anita C.

    2009-01-01

    The authors used a longitudinal, prospective design to investigate a moderation effect in the association between a genetic vulnerability factor, a variable nucleotide repeat polymorphism in the promoter region of "5HTT" (5-HTTLPR), and increases in youths' substance use. The primary study hypothesis predicted that involved-supportive parenting…

  13. The bipolar puzzle, adding new pieces. Factors associated with bipolar disorder, Genetic and environmental influences

    NARCIS (Netherlands)

    van der Schot, A.C.

    2009-01-01

    The focus of this thesis is twofold. The first part will discuss the structural brain abnormalities and schoolperformance associated with bipolar disorder and the influence of genetic and/or environmental factors to this association. It is part of a large twin study investigating several potential b

  14. Novel genetic risk factors for venous thrombosis; a haplotype-based candidate gene approach

    NARCIS (Netherlands)

    Uitte de Willige, Shirley

    2007-01-01

    Venous thrombosis (VT) is a common disease, which occurs mostly in the deep veins of the leg. VT clusters within families and is a multicausal disease, in which both genetic and environmental factors interact in the onset of the disease. The aim of the study described in this thesis was to find new

  15. Genetic factors influence the clustering of depression among individuals with lower socioeconomic status

    NARCIS (Netherlands)

    S. López León (Sandra); W.C. Choy (Wing Chi); Y.S. Aulchenko (Yurii); S. Claes (Stephan); B.A. Oostra (Ben); J.P. Mackenbach (Johan); C.M. van Duijn (Cock); A.C.J.W. Janssens (Cécile)

    2009-01-01

    textabstractObjective: To investigate the extent to which shared genetic factors can explain the clustering of depression among individuals with lower socioeconomic status, and to examine if neuroticism or intelligence are involved in these pathways. Methods: In total 2,383 participants (1,028 men a

  16. Estimating interaction between genetic and environmental risk factors efficiency of sampling designs within a cohort

    Science.gov (United States)

    Large prospective cohorts originally assembled to study environmental risk factors are increasingly exploited to study gene-environment interactions. Given the cost of genetic studies in large numbers of subjects, being able to select a sub-sample for genotyping that contains most of the information...

  17. Non-genetic factors influencing early growth traits in the Elsenburg ...

    African Journals Online (AJOL)

    investigate non-genetic factors contributing to early growth traits. The fixed effects ... as age, sex, birth status (type of birth) and age of dam have been well ..... Mutton Sheep Performance and Progeny Testing Scheme for kind permission to use ...

  18. Homocysteine related Nutritional and Genetic Risk Factors for Human Congenital Heart Defects

    NARCIS (Netherlands)

    A.C. Verkleij-Hagoort (Anna)

    2007-01-01

    textabstractCongenital heart defects (CHDs) belong to the most common group of major congenital malformations in newborns. Most CHDs are considered complex diseases with a multifactorial aetiology, which are thought to result from interactions between genetic and environmental factors. This thesis p

  19. Genetic, environmental and cultural factors influencing the resistance to septoria tritici blotch (Mycosphaerella graminicola) in wheat

    NARCIS (Netherlands)

    Simón, M.R.

    2003-01-01

    KeyWord:Genetic, environmental and cultural factors influencing the resistance to septoria tritici blotch (Mycosphaerella

  20. Importance of genetic factors in the etiology of atopic dermatitis: a twin study

    DEFF Research Database (Denmark)

    Thomsen, Simon F; Ulrik, Charlotte S; Kyvik, Kirsten O;

    2007-01-01

    ?" Latent factor models of genetic and environmental influences were fitted to the observed data using maximum likelihood methods. The overall lifetime prevalence of atopic dermatitis was 7.3%. A cotwin of an affected identical twin had a sevenfold increased risk of atopic dermatitis compared...

  1. Genetic and Environmental Factors That Impact Gestation Length in Dairy Cattle

    Science.gov (United States)

    Genetic and environmental factors that might affect gestation length (GL) were investigated. Data from over 9 million parturitions from 1999 through 2006 for 7 dairy breeds were assembled from lactation, reproduction, and dystocia records from across the United States. Effects examined were year of ...

  2. Genetic risk factors for venous thrombosis : key players or minor risk modifiers?

    NARCIS (Netherlands)

    Vossen, Carolina Yvonne

    2005-01-01

    Venous thrombosis is a common disease, which manifests itself mostly in the deep veins of the leg, with a reported incidence of 1-2 per 1000 individuals per year. Several genetic risk factors have been identified for venous thrombosis. It is, however, difficult to predict the risk of venous

  3. Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

    NARCIS (Netherlands)

    S. Reppe (Sjur); Y. Wang (Yunpeng); W.K. Thompson (Wesley K.); L.K. McEvoy (Linda K.); N.J. Schork (Nicholas); V. Zuber (Verena); M. Leblanc (Marissa); F. Bettella (Francesco); I.G. Mills (Ian G.); R.S. Desikan (Rahul S.); S. Djurovic (Srdjan); K.M. Gautvik (Kaare); A.M. Dale (Anders); O.A. Andreassen (Ole A.); K. Estrada Gil (Karol); U. Styrkarsdottir (Unnur); E. Evangelou (Evangelos); Y.-H. Hsu (Yi-Hsiang); E.L. Duncan (Emma); E.E. Ntzani (Evangelia); L. Oei (Ling); O.M.E. Albagha (Omar M.); N. Amin (Najaf); J.P. Kemp (John); D.L. Koller (Daniel); G. Li (Guo); C.-T. Liu (Ching-Ti); R.L. Minster (Ryan); A. Moayyeri (Alireza); L. Vandenput (Liesbeth); D. Willner (Dana); S.-M. Xiao (Su-Mei); L.M. Yerges-Armstrong (Laura); H.-F. Zheng (Hou-Feng); N. Alonso (Nerea); J. Eriksson (Joel); C.M. Kammerer (Candace); S. Kaptoge (Stephen); P.J. Leo (Paul); G. Thorleifsson (Gudmar); S.G. Wilson (Scott); J.F. Wilson (James F); V. Aalto (Ville); M. Alen (Markku); A.K. Aragaki (Aaron); T. Aspelund (Thor); J.R. Center (Jacqueline); Z. Dailiana (Zoe); C. Duggan; M. Garcia (Melissa); N. Garcia-Giralt (Natàlia); S. Giroux (Sylvie); G. Hallmans (Göran); L.J. Hocking (Lynne); L.B. Husted (Lise Bjerre); K. Jameson (Karen); R. Khusainova (Rita); G.S. Kim (Ghi Su); C. Kooperberg (Charles); T. Koromila (Theodora); M. Kruk (Marcin); M. Laaksonen (Marika); A.Z. Lacroix (Andrea Z.); S.H. Lee (Seung Hun); P.C. Leung (Ping C.); J.R. Lewis (Joshua); L. Masi (Laura); S. Mencej-Bedrac (Simona); T.V. Nguyen (Tuan); X. Nogues (Xavier); M.S. Patel (Millan); J. Prezelj (Janez); L.M. Rose (Lynda); S. Scollen (Serena); K. Siggeirsdottir (Kristin); G.D. Smith; O. Svensson (Olle); S. Trompet (Stella); O. Trummer (Olivia); N.M. van Schoor (Natasja); J. Woo (Jean); K. Zhu (Kun); S. Balcells (Susana); M.L. Brandi; B.M. Buckley (Brendan M.); S. Cheng (Sulin); C. Christiansen; C. Cooper (Charles); G.V. Dedoussis (George); I. Ford (Ian); M. Frost (Morten); D. Goltzman (David); J. González-Macías (Jesús); M. Kähönen (Mika); M. Karlsson (Magnus); E.K. Khusnutdinova (Elza); J.-M. Koh (Jung-Min); P. Kollia (Panagoula); B.L. Langdahl (Bente); W.D. Leslie (William D.); P. Lips (Paul); O. Ljunggren (Östen); R. Lorenc (Roman); J. Marc (Janja); D. Mellström (Dan); B. Obermayer-Pietsch (Barbara); D. Olmos (David); U. Pettersson-Kymmer (Ulrika); D.M. Reid (David); J.A. Riancho (José); P.M. Ridker (Paul); M.F. Rousseau (Francois); P.E. Slagboom (Eline); N.L.S. Tang (Nelson L.S.); R. Urreizti (Roser); W. Van Hul (Wim); J. Viikari (Jorma); M.T. Zarrabeitia (María); Y.S. Aulchenko (Yurii); M.C. Castaño Betancourt (Martha); E. Grundberg (Elin); L. Herrera (Lizbeth); T. Ingvarsson (Torvaldur); H. Johannsdottir (Hrefna); T. Kwan (Tony); R. Li (Rui); R.N. Luben (Robert); M.C. Medina-Gomez (Carolina); S.T. Palsson (Stefan Th); J.I. Rotter (Jerome I.); G. Sigurdsson (Gunnar); J.B.J. van Meurs (Joyce); D.J. Verlaan (Dominique); F.M. Williams (Frances); A.R. Wood (Andrew); Y. Zhou (Yanhua); T. Pastinen (Tomi); S. Raychaudhuri (Soumya); J.A. Cauley (Jane); D.I. Chasman (Daniel); G.R. Clark (Graeme); S.R. Cummings (Steven R.); P. Danoy (Patrick); E.M. Dennison (Elaine); R. Eastell (Richard); J.A. Eisman (John); V. Gudnason (Vilmundur); A. Hofman (Albert); R.D. Jackson (Rebecca); G. Jones (Graeme); J.W. Jukema (Jan Wouter); K.T. Khaw; T. Lehtimäki (Terho); Y. Liu (Yongmei); M. Lorentzon (Mattias); E. McCloskey (Eugene); B.D. Mitchell (Braxton); K. Nandakumar (Kannabiran); G.C. Nicholson (Geoffrey); B.A. Oostra (Ben); M. Peacock (Munro); H.A.P. Pols (Huibert A. P.); R.L. Prince (Richard); O. Raitakari (Olli); I.R. Reid (Ian); J. Robbins (John); P.N. Sambrook (Philip); P.C. Sham (Pak Chung); A.R. Shuldiner (Alan); F.A. Tylavsky (Frances); C.M. van Duijn (Cock); N.J. Wareham (Nicholas J.); L.A. Cupples (Adrienne); M.J. Econs (Michael); D.M. Evans (David); T.B. Harris (Tamara B.); A.W.C. Kung (Annie Wai Chee); B.M. Psaty (Bruce); J. Reeve (Jonathan); T.D. Spector (Timothy); E.A. Streeten (Elizabeth); M.C. Zillikens (Carola); U. Thorsteinsdottir (Unnur); C. Ohlsson (Claes); D. Karasik (David); J.B. Richards (J. Brent); M.A. Brown (Matthew); J-A. Zwart (John-Anker); A.G. Uitterlinden (André); S.H. Ralston (Stuart); J.P.A. Ioannidis (John P.A.); D.P. Kiel (Douglas P.); F. Rivadeneira Ramirez (Fernando)

    2015-01-01

    textabstractBone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. W

  4. Genetic, environmental and cultural factors influencing the resistance to septoria tritici blotch (Mycosphaerella graminicola) in wheat

    NARCIS (Netherlands)

    Simón, M.R.

    2003-01-01

    KeyWord:Genetic, environmental and cultural factors influencing the resistance to septoria tritici blotch (Mycosphaerella

  5. Parenting Moderates a Genetic Vulnerability Factor in Longitudinal Increases in Youths' Substance Use

    Science.gov (United States)

    Brody, Gene H.; Beach, Steven R. H.; Philibert, Robert A.; Chen, Yi-fu; Lei, Man-Kit; Murry, Velma McBride; Brown, Anita C.

    2009-01-01

    The authors used a longitudinal, prospective design to investigate a moderation effect in the association between a genetic vulnerability factor, a variable nucleotide repeat polymorphism in the promoter region of "5HTT" (5-HTTLPR), and increases in youths' substance use. The primary study hypothesis predicted that involved-supportive…

  6. A new prognostic model for cancer-specific survival after radical cystectomy including pretreatment thrombocytosis and standard pathological risk factors.

    Science.gov (United States)

    Todenhöfer, Tilman; Renninger, Markus; Schwentner, Christian; Stenzl, Arnulf; Gakis, Georgios

    2012-12-01

    Study Type - Prognosis (cohort series) Level of Evidence 2a What's known on the subject? and What does the study add? Preoperative thrombocytosis has been identified as a predictor of poor outcome in various cancer types. However, the prognostic role of platelet count in patients with invasive bladder cancer undergoing radical cystectomy is unknown. The present study demonstrates that preoperative thrombocytosis is an independent risk factor for decreased cancer-specific survival after radical treatment of invasive bladder cancer. We developed a new prognostic scoring model for cancer-specific outcomes after radical cystectomy including platelet count and established pathological risk factors. Consideration of platelet count in the final model increased its predictive accuracy significantly. Thrombocytosis may be a useful parameter to include within established international bladder cancer nomograms. •  To investigate the oncological significance of preoperative thrombocytosis in patients with invasive bladder cancer undergoing radical cystectomy, as it has been reported as a marker for aggressive tumour biology in a variety of solid tumours. •  The series comprised 258 patients undergoing radical cystectomy between 1999 and 2010 in whom different clinical and histopathological parameters were assessed. •  Elevated platelet count was defined as >450 × 10(9) /L. •  Based on regression estimates of significant parameters in multivariable analysis a new weighted scoring model was developed to predict cancer-specific outcomes. •  The median follow-up was 30 months (6-116). •  Of the 258 patients, 26 (10.1%) had elevated and 232 (89.9%) had normal platelet count. The 3-year cancer-specific survival in patients with normal and elevated platelet count was 61.5% and 32.7%, respectively (P thrombocytosis (2.68, 1.26-5.14; P= 0.011). •  The 3-year cancer-specific survival in patients with a score 0 (low risk), 1-2 (intermediate risk) and 3

  7. MTHFR genetic polymorphism as a risk factor in Egyptian mothers with Down syndrome children.

    Science.gov (United States)

    Meguid, Nagwa A; Dardir, Ahmed A; Khass, Mohamed; Hossieny, Lamia El; Ezzat, Afaf; El Awady, Mostafa K

    2008-01-01

    Recent reports linking Down syndrome (DS) to maternal polymorphisms at the methylenetetrahydrofolate reductase (MTHFR) gene locus have generated great interest among investigators in the field. The present study aimed at evaluation of MTHFR 677C/T and 1298A/C polymorphisms in the MTHFR gene as maternal risk factors for DS. Forty two mothers of proven DS outcomes and forty eight control mothers with normal offspring were included. Complete medical and nutritional histories for all mothers were taken with special emphasis on folate intake. Folic acid intake from food or vitamin supplements was significantly low (below the Recommended Daily Allowance) in the group of case mothers compared to control mothers. Frequencies of MTHFR 677T and MTHFR 1298C alleles were significantly higher among case mothers (32.1% and 57.1%, respectively) compared to control mothers (18.7% and 32.3%, respectively). Heterozygous and homozygous genotype frequencies of MTHFR at position 677 (CT and TT) were higher among case mothers than controls (40.5% versus 25% and 11.9% versus 6.2%, respectively) with an odds ratio of 2.34 (95% confidence interval [CI] 0.93-5.89) and 2.75 (95% CI 0.95-12.77), respectively. Interestingly, the homozygous genotype frequency (CC) at position 1298 was significantly higher in case mothers than in controls (33.3% versus 2.1% respectively) with an odds ratio of 31.5 (95% CI 3.51 to 282.33) indicating that this polymorphism may have more genetic impact than 677 polymorphism. Heterozygous genotype (AC) did not show significant difference between the two groups. We here report on the first pilot study of the possible genetic association between DS and MTHFR 1298A/C genotypes among Egyptians. Further extended studies are recommended to confirm the present work.

  8. MTHFR Genetic Polymorphism As a Risk Factor in Egyptian Mothers with Down Syndrome Children

    Directory of Open Access Journals (Sweden)

    Nagwa A. Meguid

    2008-01-01

    Full Text Available Recent reports linking Down syndrome (DS to maternal polymorphisms at the methylenetetrahydrofolate reductase (MTHFR gene locus have generated great interest among investigators in the field. The present study aimed at evaluation of MTHFR 677C/T and 1298A/C polymorphisms in the MTHFR gene as maternal risk factors for DS. Forty two mothers of proven DS outcomes and forty eight control mothers with normal offspring were included. Complete medical and nutritional histories for all mothers were taken with special emphasis on folate intake. Folic acid intake from food or vitamin supplements was significantly low (below the Recommended Daily Allowance in the group of case mothers compared to control mothers. Frequencies of MTHFR 677T and MTHFR 1298C alleles were significantly higher among case mothers (32.1% and 57.1%, respectively compared to control mothers (18.7% and 32.3%, respectively. Heterozygous and homozygous genotype frequencies of MTHFR at position 677 (CT and TT were higher among case mothers than controls (40.5% versus 25% and 11.9% versus 6.2%, respectively with an odds ratio of 2.34 (95% confidence interval [CI] 0.93–5.89 and 2.75 (95% CI 0.95–12.77, respectively. Interestingly, the homozygous genotype frequency (CC at position 1298 was significantly higher in case mothers than in controls (33.3% versus 2.1% respectively with an odds ratio of 31.5 (95% CI 3.51 to 282.33 indicating that this polymorphism may have more genetic impact than 677 polymorphism. Heterozygous genotype (AC did not show significant difference between the two groups. We here report on the first pilot study of the possible genetic association between DS and MTHFR 1298A/C genotypes among Egyptians. Further extended studies are recommended to confirm the present work.

  9. Metabolic syndrome, alcohol consumption and genetic factors are associated with serum uric acid concentration.

    Directory of Open Access Journals (Sweden)

    Blanka Stibůrková

    Full Text Available OBJECTIVE: Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals. METHODS: The cohort consisted of 589 healthy subjects aged 18-65 years. We studied the associations between the serum uric acid concentration and the following: (i demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii selected genetic variants of the MTHFR (c.665C>T, c.1286A>C, SLC2A9 (c.844G>A, c.881G>A and ABCG2 genes (c.421C>A. A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables. RESULTS: The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations. CONCLUSION: Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.

  10. Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors.

    Science.gov (United States)

    Gianfrancesco, Milena A; Acuna, Brigid; Shen, Ling; Briggs, Farren B S; Quach, Hong; Bellesis, Kalliope H; Bernstein, Allan; Hedstrom, Anna K; Kockum, Ingrid; Alfredsson, Lars; Olsson, Tomas; Schaefer, Catherine; Barcellos, Lisa F

    2014-01-01

    To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (prisk of MS for females with a BMI≥30kg/m(2) was observed (OR=2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20s and MS in males were not observed. Multivariate modelling demonstrated that significant associations between BMI or body size with MS in females persisted after adjusting for history of infectious mononucleosis and genetic risk factors, including HLA-DRB1*15:01 and established non-HLA risk alleles. Results show that childhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  11. Yeast genetic analysis reveals the involvement of chromatin reassembly factors in repressing HIV-1 basal transcription.

    Directory of Open Access Journals (Sweden)

    Manuela Vanti

    2009-01-01

    Full Text Available Rebound of HIV viremia after interruption of anti-retroviral therapy is due to the small population of CD4+ T cells that remain latently infected. HIV-1 transcription is the main process controlling post-integration latency. Regulation of HIV-1 transcription takes place at both initiation and elongation levels. Pausing of RNA polymerase II at the 5' end of HIV-1 transcribed region (5'HIV-TR, which is immediately downstream of the transcription start site, plays an important role in the regulation of viral expression. The activation of HIV-1 transcription correlates with the rearrangement of a positioned nucleosome located at this region. These two facts suggest that the 5'HIV-TR contributes to inhibit basal transcription of those HIV-1 proviruses that remain latently inactive. However, little is known about the cell elements mediating the repressive role of the 5'HIV-TR. We performed a genetic analysis of this phenomenon in Saccharomyces cerevisiae after reconstructing a minimal HIV-1 transcriptional system in this yeast. Unexpectedly, we found that the critical role played by the 5'HIV-TR in maintaining low levels of basal transcription in yeast is mediated by FACT, Spt6, and Chd1, proteins so far associated with chromatin assembly and disassembly during ongoing transcription. We confirmed that this group of factors plays a role in HIV-1 postintegration latency in human cells by depleting the corresponding human orthologs with shRNAs, both in HIV latently infected cell populations and in particular single-integration clones, including a latent clone with a provirus integrated in a highly transcribed gene. Our results indicate that chromatin reassembly factors participate in the establishment of the equilibrium between activation and repression of HIV-1 when it integrates into the human genome, and they open the possibility of considering these factors as therapeutic targets of HIV-1 latency.

  12. [Genetic factors in susceptibility to age- and noise-related hearing loss].

    Science.gov (United States)

    Sliwińiska-Kowalska, Mariola; Pawelczyk, Małgorzata; Kowalski, Tomasz Jarema

    2006-10-01

    Individual susceptibility to age-related hearing loss (AHL) and noise-induced hearing loss (NIHL) varies greatly, and this inter-individual variation is due to an interaction of environmental factors, individual factors, and susceptibility genes. Majority of studies on susceptibility genes for AHL and NIHL have been performed in mice model. These findings suggest the role of the same genes in the development of AHL and NIHL, the more so as the pathogenesis of both diseases is similar with a crucial role of oxidative stress. The alleles responsible for AHL have been localized to the chromosome 10 (Ahl gene). Ahl-/- mice develop hearing impairment at early age and are also oversensitive to noise. Ahl gene is a recessive gene and it is probably responsible for the synthesis of cell junction proteins. In mice ahl codes for cadherin (CDH) proteins. The cadherin of interest is named otocadherin or CDH23, and it is localized to the links between stereocilia of hair cells. A hypomorphic 753G>A single nucleotide polymorphism (SNP) in Cdh 23 is associated with AHL, and the 753A variant is also correlated with susceptibility to NIHL. An increased susceptibility to AHL and NIHL may rely on the SNPs of several other genes, including the groups of oxidative stress genes, K+ ions recycling genes, monogenic deafness genes (including Connexin 26 gene, which mutation is responsible for the most frequent hereditary deafness in Caucasians), as well as mitochondrial genes. Several oxidative stress enzyme (sod1-/-, gpx -/-) knock-out mice have been shown to be more susceptible to NIHL than wild strains. Current large-scale cohort studies on AHL and NIHL performed under the European projects in between-lab collaboration along with a dynamic progress in the field of genetics of deafness open up new opportunities to find human AHL and NIHL susceptibility genes and develop methods for AHUNIHL treatment.

  13. Environmental Factors Shape the Community of Symbionts in the Hoopoe Uropygial Gland More than Genetic Factors

    OpenAIRE

    Ruiz-Rodríguez, Magdalena; Soler, Juan J.; Martín-Vivaldi, Manuel; Martín-Platero, Antonio M.; Méndez, María; Peralta-Sánchez, Juan M.; Ananou, Samir; Valdivia, Eva; Martínez-Bueno, Manuel

    2014-01-01

    Exploring processes of coevolution of microorganisms and their hosts is a new imperative for life sciences. If bacteria protect hosts against pathogens, mechanisms facilitating the intergenerational transmission of such bacteria will be strongly selected by evolution. By disentangling the diversity of bacterial strains from the uropygium of hoopoes (Upupa epops) due to genetic relatedness or to a common environment, we explored the importance of horizontal (from the environment) and vertical ...

  14. The five-factor model of personality and borderline personality disorder: a genetic analysis of comorbidity.

    Science.gov (United States)

    Distel, Marijn A; Trull, Timothy J; Willemsen, Gonneke; Vink, Jacqueline M; Derom, Catherine A; Lynskey, Michael; Martin, Nicholas G; Boomsma, Dorret I

    2009-12-15

    Recently, the nature of personality disorders and their relationship with normal personality traits has received extensive attention. The five-factor model (FFM) of personality, consisting of the personality traits neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness, is one of the proposed models to conceptualize personality disorders as maladaptive variants of continuously distributed personality traits. The present study examined the phenotypic and genetic association between borderline personality and FFM personality traits. Data were available for 4403 monozygotic twins, 4425 dizygotic twins, and 1661 siblings from 6140 Dutch, Belgian, and Australian families. Broad-sense heritability estimates for neuroticism, agreeableness, conscientiousness, extraversion, openness to experience, and borderline personality were 43%, 36%, 43%, 47%, 54%, and 45%, respectively. Phenotypic correlations between borderline personality and the FFM personality traits ranged from .06 for openness to experience to .68 for neuroticism. Multiple regression analyses showed that a combination of high neuroticism and low agreeableness best predicted borderline personality. Multivariate genetic analyses showed the genetic factors that influence individual differences in neuroticism, agreeableness, conscientiousness, and extraversion account for all genetic liability to borderline personality. Unique environmental effects on borderline personality, however, were not completely shared with those for the FFM traits (33% is unique to borderline personality). Borderline personality shares all genetic variation with neuroticism, agreeableness, conscientiousness, and extraversion. The unique environmental influences specific to borderline personality may cause individuals with a specific pattern of personality traits to cross a threshold and develop borderline personality.

  15. How Much Should We Involve Genetic and Environmental Factors in the Risk Assessment of Mycotoxins in Humans?

    Directory of Open Access Journals (Sweden)

    Maria Rosaria Carratu

    2005-04-01

    Full Text Available Despite consented efforts in prevention, mycotoxins remain a problem of human health concern in several parts of the world including developed countries. Within the same range of toxins concentrations in the blood some people develop a disease while others do not. Could this inequality in front of mycotoxins effects be explained by environment factors and/or genetic predisposition? Among recent advances in environmental health research Correlation between chronic diseases and mycotoxins in humans deserves attention through several questions: Are genetic factors involved in disease causation of mycotoxins? How much are these factors currently taken into account for mycotoxins risk assessment and how much should we involve them? Answers are still to come. Genetic and environment factors deserve therefore more attention when dealing with regulatory limits, since among the general population, those who are at risk and will develop specific diseases are likely those bearing genetic predispositions. We have addressed these questions for the specific case of ochratoxin A in humans by investigating in Tunisia, county of Jelma, in four rural families forming a household of 21 persons all exposed to ochratoxin A in diet. Our results confirm that ochratoxin A induces chronic tubular nephropathy in humans and mainly point at those having the HLA haplotype A3, B27/35, DR7 to be more sensitive to the disease for quantitatively similar or lower exposure. Persons with such haplotype were found to bear chronic interstitial nephropathy with tubular karyomegalic cells while others were apparently healthy. Godin et al. (1996 in France have also found in sibling (a sister and her brother from urban area that have similar HLA haplotype B35-patern, OTA-related renal tubulopathy with mild proteinuria including β2-microglobulinuria. Several mechanisms are discussed that could be put ahead to explain how the HLA haplotype could lead to tubular cells lyses and

  16. Genetic factors associated with patient-specific warfarin dose in ethnic Indonesians

    Directory of Open Access Journals (Sweden)

    Utama Andi

    2011-06-01

    Full Text Available Abstract Background CYP2C9 and VKORC1 are two major genetic factors associated with inter-individual variability in warfarin dose. Additionally, genes in the warfarin metabolism pathway have also been associated with dose variance. We analyzed Single Nucleotide Polymorphisms (SNPs in these genes to identify genetic factors that might confer warfarin sensitivity in Indonesian patients. Methods Direct sequencing method was used to identify SNPs in CYP2C9, VKORC1, CYP4F2, EPHX1, PROC and GGCX genes in warfarin-treated patients. Multiple linear regressions were performed to model the relationship warfarin daily dose requirement with genetic and non-genetic variables measured and used to develop a novel algorithm for warfarin dosing. Results From the 40 SNPs analyzed, CYP2C9 rs17847036 and VKORC1 rs9923231 showed significant association with warfarin sensitivity. In our study population, no significant correlation could be detected between CYP2C9*3, CYP2C9C-65 (rs9332127, CYP4F2 rs2108622, GGCX rs12714145, EPHX1 rs4653436 and PROC rs1799809 with warfarin sensitivity. Conclusions VKORC1 rs9923231 AA and CYP2C9 rs17847036 GG genotypes were associated with low dosage requirements of most patients (2.05 ± 0.77 mg/day and 2.09 ± 0.70 mg/day, respectively. CYP2C9 and VKORC1 genetic variants as well as non-genetic factors such as age, body weight and body height account for 15.4% of variance in warfarin dose among our study population. Additional analysis of this combination could allow for personalized warfarin treatment in ethnic Indonesians.

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

    Science.gov (United States)

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

    2013-01-01

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

  18. Demographic histories, isolation and social factors as determinants of the genetic structure of Alpine linguistic groups.

    Science.gov (United States)

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

    2013-01-01

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

  19. Demographic histories, isolation and social factors as determinants of the genetic structure of Alpine linguistic groups.

    Directory of Open Access Journals (Sweden)

    Valentina Coia

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

  20. Sex-specific genetic diversity is shaped by cultural factors in Inner Asian human populations.

    Science.gov (United States)

    Marchi, Nina; Hegay, Tatyana; Mennecier, Philippe; Georges, Myriam; Laurent, Romain; Whitten, Mark; Endicott, Philipp; Aldashev, Almaz; Dorzhu, Choduraa; Nasyrova, Firuza; Chichlo, Boris; Ségurel, Laure; Heyer, Evelyne

    2017-04-01

    Sex-specific genetic structures have been previously documented worldwide in humans, even though causal factors have not always clearly been identified. In this study, we investigated the impact of ethnicity, geography and social organization on the sex-specific genetic structure in Inner Asia. Furthermore, we explored the process of ethnogenesis in multiple ethnic groups. We sampled DNA in Central and Northern Asia from 39 populations of Indo-Iranian and Turkic-Mongolic native speakers. We focused on genetic data of the Y chromosome and mitochondrial DNA. First, we compared the frequencies of haplogroups to South European and East Asian populations. Then, we investigated the genetic differentiation for eight Y-STRs and the HVS1 region, and tested for the effect of geography and ethnicity on such patterns. Finally, we reconstructed the male demographic history, inferred split times and effective population sizes of different ethnic groups. Based on the haplogroup data, we observed that the Indo-Iranian- and Turkic-Mongolic-speaking populations have distinct genetic backgrounds. However, each population showed consistent mtDNA and Y chromosome haplogroups patterns. As expected in patrilocal populations, we found that the Y-STRs were more structured than the HVS1. While ethnicity strongly influenced the genetic diversity on the Y chromosome, geography better explained that of the mtDNA. Furthermore, when looking at various ethnic groups, we systematically found a genetic split time older than historical records, suggesting a cultural rather than biological process of ethnogenesis. This study highlights that, in Inner Asia, specific cultural behaviors, especially patrilineality and patrilocality, leave a detectable signature on the sex-specific genetic structure. © 2017 Wiley Periodicals, Inc.

  1. Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets.

    Science.gov (United States)

    Fazlollahi, Mina; Muroff, Ivor; Lee, Eunjee; Causton, Helen C; Bussemaker, Harmen J

    2016-03-29

    Regulation of gene expression by transcription factors (TFs) is highly dependent on genetic background and interactions with cofactors. Identifying specific context factors is a major challenge that requires new approaches. Here we show that exploiting natural variation is a potent strategy for probing functional interactions within gene regulatory networks. We developed an algorithm to identify genetic polymorphisms that modulate the regulatory connectivity between specific transcription factors and their target genes in vivo. As a proof of principle, we mapped connectivity quantitative trait loci (cQTLs) using parallel genotype and gene expression data for segregants from a cross between two strains of the yeast Saccharomyces cerevisiae We identified a nonsynonymous mutation in the DIG2 gene as a cQTL for the transcription factor Ste12p and confirmed this prediction empirically. We also identified three polymorphisms in TAF13 as putative modulators of regulation by Gcn4p. Our method has potential for revealing how genetic differences among individuals influence gene regulatory networks in any organism for which gene expression and genotype data are available along with information on binding preferences for transcription factors.

  2. Genetic and epigenetic factors affecting meiosis induction in eukaryotes revealed in paramecium research.

    Science.gov (United States)

    Prajer, Małgorzata

    2008-01-01

    This review presents studies of the induction of meiosis undertaken on the ciliate Paramecium, a unicellular model eukaryotic organism. Meiosis in Paramecium, preceding the process of fertilization, appears in starved cells after passing a defined number of divisions (cell generations), starting from the last fertilization. Investigations were performed on clones of cells entering autogamy, a self-fertilization process. Genetic as well as epigenetic factors, i.e. endo- and exogenous factors, affecting the induction ofmeiosis and changing the duration of the interautogamous interval (IAI), were analyzed. The results show that: (1) Meiosis induction is controlled genetically by the somatic macronucleus. However, besides the nuclear factors, the cytoplasmic protein immaturin also affects this process (Haga & Hiwatashi 1981); (2) Epigenetic factors, such as non-genetically disturbed cytoskeleton structures and changes in the cell architecture observed in doublet Paramecium cells, exert internal mechanical stress (Ingber 2003), which constitutes the endogenous impulse accelerating meiosis; (3) Mild osmotic stress, acting as an exogenous factor, can initiate the specific MAP kinases signaling pathway resulting in earlier meiosis induction, as in other unicellular eukaryotes (Seet & Pawson 2004).

  3. Genetic parameters and factors influencing survival to 24 hrs after birth in Danish meat sheep breeds

    DEFF Research Database (Denmark)

    Maxa, J; Sharifi, A R; Pedersen, J;

    2009-01-01

    negative, which will make breeding for this trait more difficult. However, on the basis of estimated genetic parameters, it can be concluded that it is possible to improve survival to 24 h after birth in meat sheep breeds by accounting for both direct and maternal genetic effects in breeding programs......In this study, influential factors and (co)variance components for survival to 24 h after birth were determined and estimated for Texel, Shropshire, and Oxford Down, the most common sheep breeds in Denmark. Data from 1992 to 2006 containing 138,813 survival records were extracted from the sheep...

  4. Effects of genetic and non-genetic factors on growth traits of high yielding dairy seed calves and genetic parameter estimates

    Directory of Open Access Journals (Sweden)

    Syed Mohammad Ashiqur Rahman

    2015-12-01

    Full Text Available The study was conducted to know the effects of several genetic and non-genetic factors like season, sex, year of birth, genotype of calves and milk yield of dam associated with growth performance of crossbred calves. Data were collected from registered farmers during the period of May, 2011 to April, 2013. Birth weight, three-month weight, six-month weight, weaning weight and heritability estimates of those growth performances were performed using a total of 82 registered calves which had pedigree information having the genotypes of 25% Local - 75% Friesian and 37.5% Local - 62.5% Friesian. The average birth, three-month, six-month and weaning weight of calves were 29.33, 64.32, 99.06 and 151.77 kg, respectively. The effects of non-genetic factors like sex, season of birth and genotype were non-significant (P>0.05 for the traits birth weight, three-month, six-month, weaning weight and average daily gain of calves. However, year of birth was found significant on birth (P0.05 on weaning weight and average daily gain of calves. The heritability estimates were 0.40±0.09, 0.46±0.08, 0.39±0.12 and 0.50±0.12 for the traits birth weight, three-month weight, six-month weight and weaning weight, respectively. Estimated heritabilities of live weights suggest that individual own performance basis selection would be more effective for increasing growth and therefore, should be paid more emphasis in cattle improvement program.

  5. Age and lactation specific disposal pattern in Sahiwal cattle and influence of various genetic and non-genetic factors

    Directory of Open Access Journals (Sweden)

    A. Upadhyay

    2014-10-01

    Full Text Available Premature disposal of female calves before reaching milch herd and undesirable disposal of lactating cows are the major constraints in achieving larger herd size. During the early lactations, younger cows are supposed to give higher milk yield and undesirable disposal of early calvers, thereby, greatly hampers profitability of a dairy farm. Knowledge of the incidence of disposal along with reasons in various age groups and at various parities is essential to identify which age group or parity is more vulnerable for disposal. Moreover, knowledge of various genetic and non-genetic factors associated with disposal of animals may also be helpful in developing breeding and management strategies to reduce the incidence of disposal. In most of the studies, it was found that major reasons of disposal of dairy cattle were mortality among female calves and involuntary culling among adult lactating cows. Maximum mortality in female calves was observed during earlier ages and pneumonia, gastro-enteritis and debility were major reasons of female calf mortality. Whereas, most of the adult cows left the herd, due to teat and udder and reproductive problems. Moreover, indigenous breeds were found to be more adapted to Indian tropical climatic conditions in comparison to crossbred and exotic cattle breeds.

  6. Genetic, psychosocial and clinical factors associated with hippocampal volume in the general population.

    Science.gov (United States)

    Janowitz, D; Schwahn, C; Borchardt, U; Wittfeld, K; Schulz, A; Barnow, S; Biffar, R; Hoffmann, W; Habes, M; Homuth, G; Nauck, M; Hegenscheid, K; Lotze, M; Völzke, H; Freyberger, H J; Debette, S; Grabe, H J

    2014-10-14

    The hippocampus--crucial for memory formation, recall and mood regulation--is involved in the pathophysiology of dementia and depressive disorders. Recent genome-wide association studies (GWAS) have identified five genetic loci associated with hippocampal volume (HV). Previous studies have described psychosocial and clinical factors (for example, smoking, type 2 diabetes and hypertension) to have an impact on HV. However, the interplay between genetic, psychosocial and clinical factors on the HV remains unclear. Still, it is likely that genetic variants and clinical or psychosocial factors jointly act in modifying HV; it might be possible they even interact. Knowledge of these factors might help to quantify ones individual risk of or rather resilience against HV loss. We investigated subjects (N=2463; 55.7% women; mean age 53 years) from the Study of Health in Pomerania (SHIP-2; SHIP-TREND-0) who underwent whole-body magnetic resonance imaging (MRI) and genotyping. HVs were estimated with FreeSurfer. For optimal nonlinear model fitting, we used regression analyses with restricted cubic splines. Genetic variants and associated psychosocial or clinical factors were jointly assessed for potential two-way interactions. We observed associations between HV and gender (Psmoking (P=0.0058), diastolic blood pressure (P=0.0211), rs7294919 (P=0.0065), rs17178006 (P=0.0002), rs6581612 (P=0.0036), rs6741949 (P=0.0112) and rs7852872 (P=0.0451). In addition, we found three significant interactions: between rs7294919 and smoking (P=0.0473), rs7294919 and diastolic blood pressure (P=0.0447) and between rs7852872 and rs6581612 (P=0.0114). We suggest that these factors might have a role in the individual susceptibility to hippocampus-associated disorders.

  7. Genetic susceptibility and environmental factors of esophageal cancer in Xi'an

    Institute of Scientific and Technical Information of China (English)

    An-Hui Wang; Chang-Sheng Sun; Liang-Shou Li; Jiu-Yi Huang; Qing-Shu Chen; De-Zhong Xu

    2004-01-01

    AIM: To analyse the role of genetic susceptibility and environmental factors in the process of esophageal cancer (EC) formation in Xi'an, China.METHODS: A hospital based case-control study, combined with molecular epidemiological method, was carried out. A total of 127 EC cases and 101 controls were interviewed with questionnaires containing demographic items, habit of tobacco smoking, alcohol drinking, and family history of EC.Polymorphism of CYP1A1 and GSTM1 of 127 EC cases and 101 controls were detected by PCR method. The interactions between genetic susceptibility and environmental factors were also discussed.RESULTS: Tobacco smoking, alcohol drinking and a family history of EC were risk factors for EC with an OR of 2.04(95% CI 1.15-3.60), 3.45(95% CI 1.74-6.91), 3.14 (95%CI 1.28-7.94), respectively. Individuals carrying CYP1A1 Val/Valgenotype compared to those with CYP1A1 Ile/Ile genotype had an increased risk for EC (OR 3.35, 95% CI 1.49-7.61). GSTM1 deletion genotype was a risk factor for EC (OR1.81, 95% CI 1.03-3.18). Gene-environment interaction analysis showed that CYP1A1 Val/Valgenotype, GSTM1 deletion genotype had synergetic interactions with tobacco smoking, alcohol drinking and family history of EC.CONCLUSION: Tobacco smoking, alcohol drinking and a family history of EC are risk factors for EC. CYP1A1 Val/'Va/and GSTM1 deletion genotypes are genetic susceptibility biomarkers for EC. There are synergic interactions between genetic susceptibility and environmental factors.

  8. Identification of CSK as a systemic sclerosis genetic risk factor through Genome Wide Association Study follow-up

    Science.gov (United States)

    Martin, Jose-Ezequiel; Broen, Jasper C.; Carmona, F. David; Teruel, Maria; Simeon, Carmen P.; Vonk, Madelon C.; van ‘t Slot, Ruben; Rodriguez-Rodriguez, Luis; Vicente, Esther; Fonollosa, Vicente; Ortego-Centeno, Norberto; González-Gay, Miguel A.; García-Hernández, Francisco J.; de la Peña, Paloma García; Carreira, Patricia; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; van Riel, Piet L.C.M.; Kreuter, Alexander; Witte, Torsten; Riemekasten, Gabriella; Airo, Paolo; Scorza, Raffaella; Lunardi, Claudio; Hunzelmann, Nicolas; Distler, Jörg H.W.; Beretta, Lorenzo; van Laar, Jacob; Chee, Meng May; Worthington, Jane; Herrick, Ariane; Denton, Christopher; Tan, Filemon K.; Arnett, Frank C.; Assassi, Shervin; Fonseca, Carmen; Mayes, Maureen D.; Radstake, Timothy R.D.J.; Koeleman, Bobby P.C.; Martin, Javier

    2012-01-01

    Systemic sclerosis (SSc) is complex autoimmune disease affecting the connective tissue; influenced by genetic and environmental components. Recently, we performed the first successful genome-wide association study (GWAS) of SSc. Here, we perform a large replication study to better dissect the genetic component of SSc. We selected 768 polymorphisms from the previous GWAS and genotyped them in seven replication cohorts from Europe. Overall significance was calculated for replicated significant SNPs by meta-analysis of the replication cohorts and replication-GWAS cohorts (3237 cases and 6097 controls). Six SNPs in regions not previously associated with SSc were selected for validation in another five independent cohorts, up to a total of 5270 SSc patients and 8326 controls. We found evidence for replication and overall genome-wide significance for one novel SSc genetic risk locus: CSK [P-value = 5.04 × 10−12, odds ratio (OR) = 1.20]. Additionally, we found suggestive association in the loci PSD3 (P-value = 3.18 × 10−7, OR = 1.36) and NFKB1 (P-value = 1.03 × 10−6, OR = 1.14). Additionally, we strengthened the evidence for previously confirmed associations. This study significantly increases the number of known putative genetic risk factors for SSc, including the genes CSK, PSD3 and NFKB1, and further confirms six previously described ones. PMID:22407130

  9. A patient with refractory shock induced by several factors, including obstruction because of a posterior mediastinal hematoma.

    Science.gov (United States)

    Obinata, Mariko; Ishikawa, Kouhei; Osaka, Hiromichi; Mishima, Kentaro; Omori, Kazuhiko; Oode, Yasumasa; Yanagawa, Youichi

    2015-06-01

    A 44-year-old man who drove a motorcycle experienced a collision with the side of another motorcycle. Because he had sustained a high-energy injury to the spinal cord, he was transferred to our hospital. His circulation was unstable, and received tracheal intubation in addition to thoracostomy for the hemothorax. Whole-body computed tomography (CT) revealed multiple fractures, right hemopneumothorax with pulmonary contusion, and minor liver injury. After infusing 5000 mL of lactated Ringer's solution and 10 units of blood, his circulation remained unstable. On a repeat CT examination, the left atrium was found to be compressed by a posterior mediastinal hematoma induced by the fracture of the thoracic spine, and a diagnosis of shock induced by multiple factors, including hemorrhagic, neurogenic, and obstructive mechanisms, was made. After obtaining stable circulation and respirations, internal fixation of the extremities and extubation were performed on the 12th hospital day. Chest CT performed on the 27th day showed the disappearance of compression of the left atrium by the hematoma.

  10. Genetics Home Reference: cholangiocarcinoma

    Science.gov (United States)

    ... certain lifestyle factors, including smoking, alcohol use, and obesity, may also contribute to the risk of developing cholangiocarcinoma . Studies suggest that a combination of genetic, environmental, and lifestyle factors influence whether a person will develop cholangiocarcinoma . However, ...

  11. Genetic deletion of fibroblast growth factor 14 recapitulates phenotypic alterations underlying cognitive impairment associated with schizophrenia

    Science.gov (United States)

    Alshammari, T K; Alshammari, M A; Nenov, M N; Hoxha, E; Cambiaghi, M; Marcinno, A; James, T F; Singh, P; Labate, D; Li, J; Meltzer, H Y; Sacchetti, B; Tempia, F; Laezza, F

    2016-01-01

    Cognitive processing is highly dependent on the functional integrity of gamma-amino-butyric acid (GABA) interneurons in the brain. These cells regulate excitability and synaptic plasticity of principal neurons balancing the excitatory/inhibitory tone of cortical networks. Reduced function of parvalbumin (PV) interneurons and disruption of GABAergic synapses in the cortical circuitry result in desynchronized network activity associated with cognitive impairment across many psychiatric disorders, including schizophrenia. However, the mechanisms underlying these complex phenotypes are still poorly understood. Here we show that in animal models, genetic deletion of fibroblast growth factor 14 (Fgf14), a regulator of neuronal excitability and synaptic transmission, leads to loss of PV interneurons in the CA1 hippocampal region, a critical area for cognitive function. Strikingly, this cellular phenotype associates with decreased expression of glutamic acid decarboxylase 67 (GAD67) and vesicular GABA transporter (VGAT) and also coincides with disrupted CA1 inhibitory circuitry, reduced in vivo gamma frequency oscillations and impaired working memory. Bioinformatics analysis of schizophrenia transcriptomics revealed functional co-clustering of FGF14 and genes enriched within the GABAergic pathway along with correlatively decreased expression of FGF14, PVALB, GAD67 and VGAT in the disease context. These results indicate that Fgf14−/− mice recapitulate salient molecular, cellular, functional and behavioral features associated with human cognitive impairment, and FGF14 loss of function might be associated with the biology of complex brain disorders such as schizophrenia. PMID:27163207

  12. Behavioral phenotypes in schizophrenic animal models with multiple combinations of genetic and environmental factors.

    Science.gov (United States)

    Hida, Hirotake; Mouri, Akihiro; Noda, Yukihiro

    2013-01-01

    Schizophrenia is a multifactorial psychiatric disorder in which both genetic and environmental factors play a role. Genetic [e.g., Disrupted-in-schizophrenia 1 (DISC1), Neuregulin-1 (NRG1)] and environmental factors (e.g., maternal viral infection, obstetric complications, social stress) may act during the developmental period to increase the incidence of schizophrenia. In animal models, interactions between susceptibility genes and the environment can be controlled in ways not possible in humans; therefore, such models are useful for investigating interactions between or within factors in the pathogenesis and pathophysiology of schizophrenia. We provide an overview of schizophrenic animal models investigating interactions between or within factors. First, we reviewed gene-environment interaction animal models, in which schizophrenic candidate gene mutant mice were subjected to perinatal immune activation or adolescent stress. Next, environment-environment interaction animal models, in which mice were subjected to a combination of perinatal immune activation and adolescent administration of drugs, were described. These animal models showed interaction between or within factors; behavioral changes, which were obscured by each factor, were marked by interaction of factors and vice versa. Appropriate behavioral approaches with such models will be invaluable for translational research on novel compounds, and also for providing insight into the pathogenesis and pathophysiology of schizophrenia.

  13. Aortic root dimensions are predominantly determined by genetic factors: a classical twin study

    Energy Technology Data Exchange (ETDEWEB)

    Celeng, Csilla; Kolossvary, Marton; Kovacs, Attila; Molnar, Andrea Agnes; Szilveszter, Balint; Karolyi, Mihaly; Jermendy, Adam L.; Karady, Julia; Merkely, Bela; Maurovich-Horvat, Pal [Semmelweis University, MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Budapest (Hungary); Horvath, Tamas [Budapest University of Technology and Economics, Department of Hydrodynamic Systems, Budapest (Hungary); Tarnoki, Adam D.; Tarnoki, David L. [Semmelweis University, Department of Radiology and Oncotherapy, Budapest (Hungary); Voros, Szilard [Global Genomics Group, Atlanta, GA (United States); Jermendy, Gyoergy [Bajcsy-Zsilinszky Hospital, Medical Department, Budapest (Hungary)

    2017-06-15

    Previous studies using transthoracic echocardiography (TTE) observed moderate heritability of aortic root dimensions. Computed tomography angiography (CTA) might provide more accurate heritability estimates. Our primary aim was to assess the heritability of the aortic root with CTA. Our secondary aim was to derive TTE-based heritability and compare this with the CTA-based results. In the BUDAPEST-GLOBAL study 198 twin subjects (118 monozygotic, 80 dizygotic; age 56.1 ± 9.4 years; 126 female) underwent CTA and TTE. We assessed the diameter of the left ventricular outflow tract (LVOT), annulus, sinus of Valsalva, sinotubular junction and ascending aorta. Heritability was assessed using ACDE model (A additive genetic, C common environmental, D dominant genetic, E unique environmental factors). Based on CTA, additive genetic effects were dominant (LVOT: A = 0.67, E = 0.33; annulus: A = 0.76, E = 0.24; sinus of Valsalva: A = 0.83, E = 0.17; sinotubular junction: A = 0.82, E = 0.18; ascending aorta: A = 0.75, E = 0.25). TTE-derived measurements showed moderate to no genetic influence (LVOT: A = 0.38, E = 0.62; annulus: C = 0.47, E = 0.53; sinus of Valsalva: C = 0.63, E = 0.37; sinotubular junction: C = 0.45, E = 0.55; ascending aorta: A = 0.67, E = 0.33). CTA-based assessment suggests that aortic root dimensions are predominantly determined by genetic factors. TTE-based measurements showed moderate to no genetic influence. The choice of measurement method has substantial impact on heritability estimates. (orig.)

  14. Demographic factors and genetic variation influence population persistence under environmental change.

    Science.gov (United States)

    Willi, Yvonne; Hoffmann, Ary A

    2009-01-01

    Population persistence has been studied in a conservation context to predict the fate of small or declining populations. Persistence models have explored effects on extinction of random demographic and environmental fluctuations, but in the face of directional environmental change they should also integrate factors affecting whether a population can adapt. Here, we examine the population-size dependence of demographic and genetic factors and their likely contributions to extinction time under scenarios of environmental change. Parameter estimates were derived from experimental populations of the rainforest species, Drosophila birchii, held in the lab for 10 generations at census sizes of 20, 100 and 1000, and later exposed to five generations of heat-knockdown selection. Under a model of directional change in the thermal environment, rapid extinction of populations of size 20 was caused by a combination of low growth rate (r) and high stochasticity in r. Populations of 100 had significantly higher reproductive output, lower stochasticity in r and more additive genetic variance (V(A)) than populations of 20, but they were predicted to persist less well than the largest size class. Even populations of 1000 persisted only a few hundred generations under realistic estimates of environmental change because of low V(A) for heat-knockdown resistance. The experimental results document population-size dependence of demographic and adaptability factors. The simulations illustrate a threshold influence of demographic factors on population persistence, while genetic variance has a more elastic impact on persistence under environmental change.

  15. Genetic risk factors for placental abruption: a HuGE review and meta-analysis.

    Science.gov (United States)

    Zdoukopoulos, Nikos; Zintzaras, Elias

    2008-03-01

    Although the precise pathophysiology that leads to placental abruption is unknown, there is evidence supporting a genetic etiology. We searched PubMed and systematically reviewed all case-control studies that investigated the association between genetic variants and placental abruption. Pooled genetic risks were estimated using fixed and random effects odds ratios. Twenty-two articles, examining a total of 14 gene polymorphisms were identified. Seven polymorphisms (F5 Arg506Gln, F5 Met385Thr, F2 G20210A, MTHFR A1298C, MTHFD1 Arg653Gln, NOS3 Glu298Asp, AGT Met235Thr) show significant association in individual studies. Six of the 7 (all except F5Met385Thr) were studied more than once and we therefore included them in our meta-analyses. A positive association under the dominant model was found for the F5 Arg506Gln and F2 G20210A polymorphisms. The random-effects odds ratio for the F5 Arg506Gln polymorphism was 3.4 (95% confidence interval = 1.4-8.3) and the fixed-effects odds ratio for the F2 G20210A polymorphism was 6.7 (3.2-13). Considering the multifactorial etiology of abruption and the relatively small numbers of studies and participants, this review provides only the first clues of possible genetic causes. Larger case-control studies that include gene-gene and gene-environment interactions may help to elucidate the genetics of placental abruption further.

  16. The nature of creativity: The roles of genetic factors, personality traits, cognitive abilities, and environmental sources.

    Science.gov (United States)

    Kandler, Christian; Riemann, Rainer; Angleitner, Alois; Spinath, Frank M; Borkenau, Peter; Penke, Lars

    2016-08-01

    This multitrait multimethod twin study examined the structure and sources of individual differences in creativity. According to different theoretical and metrological perspectives, as well as suggestions based on previous research, we expected 2 aspects of individual differences, which can be described as perceived creativity and creative test performance. We hypothesized that perceived creativity, reflecting typical creative thinking and behavior, should be linked to specific personality traits, whereas test creativity, reflecting maximum task-related creative performance, should show specific associations with cognitive abilities. Moreover, we tested whether genetic variance in intelligence and personality traits account for the genetic component of creativity. Multiple-rater and multimethod data (self- and peer reports, observer ratings, and test scores) from 2 German twin studies-the Bielefeld Longitudinal Study of Adult Twins and the German Observational Study of Adult Twins-were analyzed. Confirmatory factor analyses yielded the expected 2 correlated aspects of creativity. Perceived creativity showed links to openness to experience and extraversion, whereas tested figural creativity was associated with intelligence and also with openness. Multivariate behavioral genetic analyses indicated that the heritability of tested figural creativity could be accounted for by the genetic component of intelligence and openness, whereas a substantial genetic component in perceived creativity could not be explained. A primary source of individual differences in creativity was due to environmental influences, even after controlling for random error and method variance. The findings are discussed in terms of the multifaceted nature and construct validity of creativity as an individual characteristic. (PsycINFO Database Record

  17. Turner Syndrome: Genetic and Hormonal Factors Contributing to a Specific Learning Disability Profile

    Science.gov (United States)

    Rovet, Joanne

    2004-01-01

    Turner Syndrome (TS) is a genetic disorder affecting primarily females. It arises from a loss of X-chromosome material, most usually one of the two X chromosomes. Affected individuals have a number of distinguishing somatic features, including short stature and ovarian dysgenesis. Individuals with TS show a distinct neurocognitive profile…

  18. Factors Affecting the Incidence of Angel Wing in White Roman Geese: Stocking Density and Genetic Selection.

    Science.gov (United States)

    Lin, M J; Chang, S C; Lin, T Y; Cheng, Y S; Lee, Y P; Fan, Y K

    2016-06-01

    The present study investigated stocking density and genetic lines, factors that may alter the severity and incidence of angel wing (AW), in White Roman geese. Geese (n = 384) from two genetically selected lines (normal- winged line, NL, and angel-winged line, AL, respectively) and one commercial line (CL) were raised in four pens. Following common commercial practice, low-stocking-density (LD), medium-stocking-density, and high-stocking-density treatments were respectively administered to 24, 32, and 40 geese per pen at 0 to 3 weeks (1.92 m(2)/pen) and 4 to 6 weeks (13.2 m(2)/pen) of age and to 24, 30, and 36 geese at 7 to 14 weeks (20.0 m(2)/pen) of age. The results revealed that stocking density mainly affected body weight gain in geese younger than 4 weeks, and that geese subjected to LD had a high body weight at 2 weeks of age. However, the effect of stocking density on the severity score of AW (SSAW) and incidence of AW (IAW) did not differ significantly among the treatments. Differences were observed among the genetic stocks; that is, SSAW and IAW were significantly higher in AL than in NL and CL. Genetic selection generally aggravates AW, complicating its elimination. To effectively reduce IAW, stocking density, a suspected causal factor, should be lower than that presently applied commercially.

  19. Genetic and environmental factors in associations between infant growth and adult cardiometabolic risk profile in twins.

    Science.gov (United States)

    Touwslager, Robbert N H; Gielen, Marij; Mulder, Antonius L M; Gerver, Willem J M; Zimmermann, Luc J; Dagnelie, Pieter C; Houben, Alfons J H M; Stehouwer, Coen D A; Derom, Catherine; Vlietinck, Robert; Loos, Ruth J F; Zeegers, Maurice P

    2013-10-01

    Accelerated infant growth is associated with an altered, mostly adverse adult cardiometabolic risk profile. The importance of genetic and environmental factors to these associations is unclear. The objective was to examine the importance of genetic and environmental factors in the associations between infant growth and adult cardiometabolic risk factors (anthropometric characteristics, lipids, insulin sensitivity, leptin, blood pressure, and fibrinogen) in twins. Cardiometabolic risk factors were assessed in 240 twin pairs (aged 18-34 y) from the East Flanders Prospective Twin Survey. Infant growth was defined as change in weight z score. We regressed intrapair differences in growth during 4 growth windows (0-1, 1-6, 6-12, and 12-24 mo) against intrapair differences in the risk factors in monozygotic and dizygotic twins separately. Within monozygotic twin pairs only, associations between infant growth and most adult lipids, glucose, leptin, and blood pressure (eg, systolic blood pressure: b = 5.95 mm Hg per change in z score, P = 0.01 in monozygotic twins; b = -1.64, P = 0.82 in dizygotic twins from 12 to 24 mo) were found. Within dizygotic twin pairs only, associations between growth and triglycerides and fibrinogen (eg, fibrinogen: b = 0.07 ln mg/dL per change in z score, P = 0.31 in monozygotic twins; b = 0.79, P = 0.01 in dizygotic twins from 0 to 1 mo) were identified. Most associations showed a detrimental effect of accelerated growth, but beneficial associations were also identified (eg, total-to-high-density-lipoprotein cholesterol ratio: b = -0.22 per change in z score from 1 to 6 mo, P = 0.008 in monozygotic twins). Our data showed that environmental factors play a role in the associations between infant growth and most adult lipids, glucose, leptin, and blood pressure, whereas genetic factors are involved regarding triglycerides and fibrinogen.

  20. Environmental factors shape the community of symbionts in the hoopoe uropygial gland more than genetic factors.

    Science.gov (United States)

    Ruiz-Rodríguez, Magdalena; Soler, Juan J; Martín-Vivaldi, Manuel; Martín-Platero, Antonio M; Méndez, María; Peralta-Sánchez, Juan M; Ananou, Samir; Valdivia, Eva; Martínez-Bueno, Manuel

    2014-11-01

    Exploring processes of coevolution of microorganisms and their hosts is a new imperative for life sciences. If bacteria protect hosts against pathogens, mechanisms facilitating the intergenerational transmission of such bacteria will be strongly selected by evolution. By disentangling the diversity of bacterial strains from the uropygium of hoopoes (Upupa epops) due to genetic relatedness or to a common environment, we explored the importance of horizontal (from the environment) and vertical (from parents) acquisition of antimicrobial-producing symbionts in this species. For this purpose, we compared bacterial communities among individuals in nonmanipulated nests; we also performed a cross-fostering experiment using recently hatched nestlings before uropygial gland development and some nestlings that were reared outside hoopoe nests. The capacity of individuals to acquire microbial symbionts horizontally during their development was supported by our results, since cross-fostered nestlings share bacterial strains with foster siblings and nestlings that were not in contact with hoopoe adults or nests also developed the symbiosis. Moreover, nestlings could change some bacterial strains over the course of their stay in the nest, and adult females changed their bacterial community in different years. However, a low rate of vertical transmission was inferred, since genetic siblings reared in different nests shared more bacterial strains than they shared with unrelated nestlings raised in different nests. In conclusion, hoopoes are able to incorporate new symbionts from the environment during the development of the uropygium, which could be a selective advantage if strains with higher antimicrobial capacity are incorporated into the gland and could aid hosts in fighting against pathogenic and disease-causing microbes.

  1. Environmental Factors Shape the Community of Symbionts in the Hoopoe Uropygial Gland More than Genetic Factors

    Science.gov (United States)

    Soler, Juan J.; Martín-Vivaldi, Manuel; Martín-Platero, Antonio M.; Méndez, María; Peralta-Sánchez, Juan M.; Ananou, Samir; Valdivia, Eva; Martínez-Bueno, Manuel

    2014-01-01

    Exploring processes of coevolution of microorganisms and their hosts is a new imperative for life sciences. If bacteria protect hosts against pathogens, mechanisms facilitating the intergenerational transmission of such bacteria will be strongly selected by evolution. By disentangling the diversity of bacterial strains from the uropygium of hoopoes (Upupa epops) due to genetic relatedness or to a common environment, we explored the importance of horizontal (from the environment) and vertical (from parents) acquisition of antimicrobial-producing symbionts in this species. For this purpose, we compared bacterial communities among individuals in nonmanipulated nests; we also performed a cross-fostering experiment using recently hatched nestlings before uropygial gland development and some nestlings that were reared outside hoopoe nests. The capacity of individuals to acquire microbial symbionts horizontally during their development was supported by our results, since cross-fostered nestlings share bacterial strains with foster siblings and nestlings that were not in contact with hoopoe adults or nests also developed the symbiosis. Moreover, nestlings could change some bacterial strains over the course of their stay in the nest, and adult females changed their bacterial community in different years. However, a low rate of vertical transmission was inferred, since genetic siblings reared in different nests shared more bacterial strains than they shared with unrelated nestlings raised in different nests. In conclusion, hoopoes are able to incorporate new symbionts from the environment during the development of the uropygium, which could be a selective advantage if strains with higher antimicrobial capacity are incorporated into the gland and could aid hosts in fighting against pathogenic and disease-causing microbes. PMID:25172851

  2. Sudden infant death syndrome, childhood thrombosis, and presence of genetic risk factors for thrombosis

    DEFF Research Database (Denmark)

    Larsen, T B; Nørgaard-Pedersen, B; Banner, Jytte

    2000-01-01

    in the child. This prompted us to investigate these genetic markers of thromboembolic disease in 121 cases of sudden infant death syndrome and in relevant controls, in the expectation of a more frequent occurrence of these markers if thrombosis is an etiological factor in sudden infant death syndrome......Sudden infant death syndrome or "cot death" has until the late eighties been a significant cause of death in children between the ages of 1 month and 1 year. Approximately two per 1000 children born alive dies of sudden infant death syndrome each year in Western Europe, North America, and Australia....... The vulnerability of the infant brain stem to ischemia has been suggested to be a conceivable cause of sudden infant death syndrome. This is compatible with a hypothesis that genetic risk factors for cerebral thrombosis could cause microinfarction in the brain stem during the first month of life, affecting vital...

  3. Genetic and modifying factors that determine the risk of brain tumors

    DEFF Research Database (Denmark)

    Montelli, Terezinha de Cresci Braga; Peraçoli, Maria Terezinha Serrão; Rogatto, Silvia Regina

    2011-01-01

    of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immuno-suppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well...... of these treatments, the prognosis for patients is poor. In this review, we highlight general aspects concerning genetic alterations in brain tumors, namely astrocytomas, glioblastomas, oligodendrogliomas, medulloblastomas and ependymomas. The influence of these genetic alterations in patients' prognosis is discussed....... Mutagen sensitivity is associated with cancer risk. The convincing studies that linked DNA damages and DNA repair alterations with brain tumors are also described. Another important modifying factor is immunity. General immune response against cancer, tumor microenvironment and immune response, mechanisms...

  4. Sudden infant death syndrome, childhood thrombosis, and presence of genetic risk factors for thrombosis

    DEFF Research Database (Denmark)

    Larsen, TB; Nørgaard-Pedersen, B; Lundemose, JB

    2000-01-01

    . The vulnerability of the infant brain stem to ischemia has been suggested to be a conceivable cause of sudden infant death syndrome. This is compatible with a hypothesis that genetic risk factors for cerebral thrombosis could cause microinfarction in the brain stem during the first month of life, affecting vital......Sudden infant death syndrome or "cot death" has until the late eighties been a significant cause of death in children between the ages of 1 month and 1 year. Approximately two per 1000 children born alive dies of sudden infant death syndrome each year in Western Europe, North America, and Australia...... in the child. This prompted us to investigate these genetic markers of thromboembolic disease in 121 cases of sudden infant death syndrome and in relevant controls, in the expectation of a more frequent occurrence of these markers if thrombosis is an etiological factor in sudden infant death syndrome...

  5. Summer eczema in exported Icelandic horses: influence of environmental and genetic factors

    Directory of Open Access Journals (Sweden)

    Broström Hans

    2006-05-01

    Full Text Available Abstract A cross sectional study was designed to estimate the prevalence of summer eczema (a chronic, recurrent seasonal dermatitis in exported Icelandic horses and the influence of environmental and genetic factors on the development of the disease. Among 330 horses, which had been exported to Germany, Denmark and Sweden, 114 (34.5% were found to have clinical signs of summer eczema. The prevalence was highest 2 years after export and the exposure to the biting midges Culicoides spp., was found to be the main risk factor for developing the disease. Genetic influence on the sensitivity for the disease was not established. It was concluded that exported Icelandic horses are predisposed for summer dermatitis and the fact that they are not introduced to the antigens of the biting midges early in live, due to it's absence in Iceland, is likely to explain the high prevalence of the disease after export.

  6. A twin and molecular genetics study of sleep paralysis and associated factors.

    OpenAIRE

    Denis, Dan; French, Christopher C.; Rowe, Richard; Zavos, Helena M S; Nolan, Patrick M.; Parsons, Michael J.; Gregory, Alice M

    2015-01-01

    Sleep paralysis is a relatively common but under-researched phenomenon. In this paper we examine prevalence in a UK sample and associations with candidate risk factors. This is the first study to investigate the heritability of sleep paralysis in a twin sample and to explore genetic associations between sleep paralysis and a number of circadian expressed single nucleotide polymorphisms. Analyses are based on data from the Genesis1219 twin/sibling study, a community sample of twins/siblings fr...

  7. A twin and molecular genetics study of sleep paralysis and associated factors.

    OpenAIRE

    Denis, Dan; French, Christopher C.; Rowe, Richard; Zavos, Helena M. S.; Nolan, Patrick M.; Parsons, Michael J.; Gregory, Alice M.

    2015-01-01

    Sleep paralysis is a relatively common but under-researched phenomenon. In this paper we examine prevalence in a UK sample and associations with candidate risk factors. This is the first study to investigate the heritability of sleep paralysis in a twin sample and to explore genetic associations between sleep paralysis and a number of circadian expressed single nucleotide polymorphisms. Analyses are based on data from the Genesis1219 twin/sibling study, a community sample of twins/siblings fr...

  8. Hydrogeomorphic Classification of Wetlands on Mt. Desert Island, Maine, Including Hydrologic Susceptibility Factors for Wetlands in Acadia National Park

    Science.gov (United States)

    Nielsen, Martha G.

    2006-01-01

    The U.S. Geological Survey, in cooperation with the National Park Service, developed a hydrogeomorphic (HGM) classification system for wetlands greater than 0.4 hectares (ha) on Mt. Desert Island, Maine, and applied this classification using map-scale data to more than 1,200 mapped wetland units on the island. In addition, two hydrologic susceptibility factors were defined for a subset of these wetlands, using 11 variables derived from landscape-scale characteristics of the catchment areas of these wetlands. The hydrologic susceptibility factors, one related to the potential hydrologic pathways for contaminants and the other to the susceptibility of wetlands to disruptions in water supply from projected future changes in climate, were used to indicate which wetlands (greater than 1 ha) in Acadia National Park (ANP) may warrant further investigation or monitoring. The HGM classification system consists of 13 categories: Riverine-Upper Perennial, Riverine-Nonperennial, Riverine- Tidal, Depressional-Closed, Depressional-Semiclosed, Depressional-Open, Depressional-No Ground-Water Input, Mineral Soil Flat, Organic Soil Flat, Tidal Fringe, Lacustrine Fringe, Slope, and Hilltop/Upper Hillslope. A dichotomous key was developed to aid in the classification of wetlands. The National Wetland Inventory maps produced by the U.S. Fish and Wildlife Service provided the wetland mapping units used for this classification. On the basis of topographic map information and geographic information system (GIS) layers at a scale of 1:24,000 or larger, 1,202 wetland units were assigned a preliminary HGM classification. Two of the 13 HGM classes (Riverine-Tidal and Depressional-No Ground-Water Input) were not assigned to any wetlands because criteria for determining those classes are not available at that map scale, and must be determined by more site-specific information. Of the 1,202 wetland polygons classified, which cover 1,830 ha in ANP, 327 were classified as Slope, 258 were

  9. Interaction of genetic predisposition and environmental factors in the pathogenesis of idiopathic orthostatic intolerance

    Science.gov (United States)

    Jordan, J.; Shannon, J. R.; Jacob, G.; Pohar, B.; Robertson, D.

    1999-01-01

    BACKGROUND: The hemodynamic and autonomic abnormalities in idiopathic orthostatic intolerance (IOI) have been studied extensively. However, the mechanisms underlying these abnormalities are not understood. If genetic predisposition were important in the pathogenesis of IOI, monozygotic twins of patients with IOI should have similar hemodynamic and autonomic abnormalities. METHODS: We studied two patients with IOI and their identical twins. Both siblings in the first twin pair had orthostatic symptoms, significant orthostatic tachycardia, increased plasma norepinephrine levels with standing, and a greater than normal decrease in systolic blood pressure with trimethaphan infusion. RESULTS: Both siblings had a normal response of plasma renin activity to upright posture. In the second twin pair, only one sibling had symptoms of orthostatic intolerance, an orthostatic tachycardia, and raised plasma catecholamines with standing. The affected sibling had inappropriately low plasma renin activity with standing and was 8-fold more sensitive to the pressor effect of phenylephrine than the unaffected sibling. CONCLUSIONS: We conclude that in some patients, IOI seems to be strongly influenced by genetic factors. In others, however, IOI may be mainly caused by nongenetic factors. These findings suggest that IOI is heterogenous, and that both genetic and environmental factors contribute individually or collectively to create the IOI phenotype.

  10. Use of a twin dataset to identify AMD-related visual patterns controlled by genetic factors

    Science.gov (United States)

    Quellec, Gwénolé; Abràmoff, Michael D.; Russell, Stephen R.

    2010-03-01

    The mapping of genotype to the phenotype of age-related macular degeneration (AMD) is expected to improve the diagnosis and treatment of the disease in a near future. In this study, we focused on the first step to discover this mapping: we identified visual patterns related to AMD which seem to be controlled by genetic factors, without explicitly relating them to the genes. For this purpose, we used a dataset of eye fundus photographs from 74 twin pairs, either monozygotic twins, who have the same genotype, or dizygotic twins, whose genes responsible for AMD are less likely to be identical. If we are able to differentiate monozygotic twins from dizygotic twins, based on a given visual pattern, then this pattern is likely to be controlled by genetic factors. The main visible consequence of AMD is the apparition of drusen between the retinal pigment epithelium and Bruch's membrane. We developed two automated drusen detectors based on the wavelet transform: a shape-based detector for hard drusen, and a texture- and color- based detector for soft drusen. Forty visual features were evaluated at the location of the automatically detected drusen. These features characterize the texture, the shape, the color, the spatial distribution, or the amount of drusen. A distance measure between twin pairs was defined for each visual feature; a smaller distance should be measured between monozygotic twins for visual features controlled by genetic factors. The predictions of several visual features (75.7% accuracy) are comparable or better than the predictions of human experts.

  11. Genetic and non-genetic factors affecting rabbit doe sexual receptivity as estimated from one generation of divergent selection

    Directory of Open Access Journals (Sweden)

    M. Theau.Clément

    2015-09-01

    Full Text Available Sexual receptivity of rabbit does at insemination greatly influences fertility and is generally induced by hormones or techniques known as “biostimulation”. Searching for more sustainable farming systems, an original alternative would be to utilise the genetic pathway to increase the does’receptivity. The purpose of the present study was to identify genetic and non-genetic factors that influence rabbit doe sexual receptivity, in the context of a divergent selection experiment over 1 generation. The experiment spanned 2 generations: the founder generation (G0 consisting of 140 rabbit does, and the G1 generation comprising 2 divergently selected lines (L and H lines with 70 does each and 2 successive batches from each generation. The selection rate of the G0 females to form the G1 lines was 24/140. The selection tests consisted of 16 to 18 successive receptivity tests at the rate of 3 tests per week. On the basis of 4716 tests from 275 females, the average receptivity was 56.6±48.2%. A batch effect and a test operator effect were revealed. The contribution of females to the total variance was 20.0%, whereas that of bucks was only 1.1%. Throughout the experiment, 18.2% of does expressed a low receptivity (< 34%, 50.7% a medium one and 33.1% a high one (>66%. Some does were frequently receptive, whereas others were rarely receptive. The repeatability of sexual receptivity was approximately 20%. The results confirmed the high variability of sexual receptivity of non-lactating rabbit does maintained without any biostimulation or hormonal treatment. A lack of selection response on receptivity was observed. Accordingly, the heritability of receptivity was estimated at 0.01±0.02 from an animal model and at 0.02±0.03 from a  sire and dam model. The heritability of the average receptivity of a doe was calculated as 0.04. In agreement with the low estimated heritability, the heritability determined was no different from zero

  12. Psychological factors, including alexithymia, in the prediction of cardiovascular risk in HIV infected patients: results of a cohort study.

    Directory of Open Access Journals (Sweden)

    Giustino Parruti

    Full Text Available BACKGROUND: Psychological factors are known predictors of cardiovascular disease in many clinical settings, but data are lacking for HIV infection. We carried out a prospective cohort study to evaluate potential psychological predictors of preclinical and clinical vascular disease in HIV patients. METHODOLOGY/PRINCIPAL FINDINGS: HIV patients were consecutively enrolled. Demographics, viral and immune parameters and traditional cardiovascular predictors were considered; Intima-Media Thickness (c-IMT, continuous measure and Carotid Plaques (CPs, focal thickening ≥1.5 mm were investigated by B-mode ultrasonography; depressive symptoms by the Beck Depression Inventory (BDI-II, Type D personality (Distressed Personality or Type D by the DS14, alexithymia by the Toronto Alexithymia Scale (TAS-20. Vascular outcomes included transient ischemic attacks or stroke, acute coronary syndrome, myocardial or other organ infarction. We enrolled 232 HIV subjects, 73.9% males, aged 44.5±9.9 y, 38.2% with AIDS diagnosis, 18.3% untreated. Mean Nadir CD4 T-cell counts were 237.5±186.2/mmc. Of them, 224 (96.5% attended IMT measurements; 201 (86.6% attended both IMT assessment and psychological profiling. Mean follow-up was 782±308 days. Fifty-nine patients (29.4% had CPs at baseline. Nineteen patients (9.5% had ≥1 vascular event; 12 (6.0% died due to such events (n = 4 or any cause. At baseline cross-sectional multivariate analysis, increasing age, total cholesterol, current smoking and Alexithymia score≥50 were significantly associated with both increased cIMT (linear regression and CPs (logistic regression. At follow-up analysis, log-rank tests and Cox's regression revealed that only older age (p = 0.001, current smoking (p = 0.019 and alexithymia score≥50 (p = 0.013 were independently associated with vascular events. CONCLUSIONS/SIGNIFICANCE: In HIV-infected subjects, the Alexithymic trait emerges as a strong predictor of increased IMT, presence of CPs

  13. Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy.

    Science.gov (United States)

    Sales-Marques, Carolinne; Cardoso, Cynthia Chester; Alvarado-Arnez, Lucia Elena; Illaramendi, Ximena; Sales, Anna Maria; Hacker, Mariana de Andréa; Barbosa, Mayara Garcia de Mattos; Nery, José Augusto da Costa; Pinheiro, Roberta Olmo; Sarno, Euzenir Nunes; Pacheco, Antonio Guilherme; Moraes, Milton Ozório

    2017-07-01

    The pathways that trigger exacerbated immune reactions in leprosy could be determined by genetic variations. Here, in a prospective approach, both genetic and non-genetic variables influencing the amount of time before the development of reactional episodes were studied using Kaplan-Meier survival curves, and the genetic effect was estimated by the Cox proportional-hazards regression model. In a sample including 447 leprosy patients, we confirmed that gender (male), and high bacillary clinical forms are risk factors for leprosy reactions. From the 15 single nucleotide polymorphisms (SNPs) at the 8 candidate genes genotyped (TNF/LTA, IFNG, IL10, TLR1, NOD2, SOD2, and IL6) we observed statistically different survival curves for rs751271 at the NOD2 and rs2069845 at the IL6 genes (log-rank p-values = 0.002 and 0.023, respectively), suggesting an influence on the amount of time before developing leprosy reactions. Cox models showed associations between the SNPs rs751271 at NOD2 and rs2069845 at IL6 with leprosy reactions (HRGT = 0.45, p = 0.002; HRAG = 1.88, p = 0.0008, respectively). Finally, IL-6 and IFN-γ levels were confirmed as high, while IL-10 titers were low in the sera of reactional patients. Rs751271-GT genotype-bearing individuals correlated (p = 0.05) with lower levels of IL-6 in sera samples, corroborating the genetic results. Although the experimental size may be considered a limitation of the study, the findings confirm the association of classical variables such as sex and clinical forms with leprosy, demonstrating the consistency of the results. From the results, we conclude that SNPs at the NOD2 and IL6 genes are associated with leprosy reactions as an outcome. NOD2 also has a clear functional pro-inflammatory link that is coherent with the exacerbated responses observed in these patients.

  14. Genetic aspects of human male infertility: the frequency of chromosomal abnormalities and Y chromosome microdeletions in severe male factor infertility.

    Science.gov (United States)

    Vicdan, Arzu; Vicdan, Kubilay; Günalp, Serdar; Kence, Aykut; Akarsu, Cem; Işik, Ahmet Zeki; Sözen, Eran

    2004-11-10

    The main purpose of this study is to detect the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions in patients with severe male factor infertility and fertile control subjects. The association between the genetic abnormality and clinical parameters was also evaluated. This study was carried out in 208 infertile and 20 fertile men. Results of 208 patients, 119 had non-obstructive azoospermia and 89 had severe oligoasthenoteratozoospermia (OAT). Seventeen out of 119 (14.3%) azoospermic patients and two out of 89 (2.2%) patients with OAT had Y chromosome microdeletions. In total, 19 cases with deletions were detected in 208 infertile men, with a frequency of 9.1%. The AZFc locus, mainly DAZ gene cluster was the most frequently deleted region. Five other cases with azoospermia (4.2%) and two cases with OAT (2.2%) had a chromosomal abnormality, with a total number of seven (3.4%). Including Y chromosome deletions and structural chromosome abnormalities, the rate of genetic abnormalities was 12.5% (26/208) in our patients. On the other hand, 20 men with proven fertility and fathers of five cases with microdeletions were genetically normal. Y chromosome deletions and chromosomal abnormalities were associated with various histological alterations in testis. Sertoli cell-only (SCO) syndrome and maturation arrest predominated in these cases, whereas hypospermatogenesis occurred more frequently in genetically normal patients. Various chromosomal abnormalities and deletions of Y chromosome can cause spermatogenic breakdown resulting in chromosomally derived infertility. All these findings strongly support the recommendation of genetic screening of infertile patients.

  15. Host genetic factors in susceptibility to HIV-1 infection and progression to AIDS

    Indian Academy of Sciences (India)

    Koushik Chatterjee

    2010-04-01

    HIV-1 infection has rapidly spread worldwide and has become the leading cause of mortality in infectious diseases. The duration for development of AIDS (AIDS progression) is highly variable among HIV–1 infected individuals, ranging from 2–3 years to no signs of AIDS development in the entire lifetime. Several factors regulate the rate at which HIV-1 infection progresses to AIDS. Host genetic factors play an important role in the outcome of such complex or multifactor diseases as AIDS and are also known to regulate the rate of disease progression. This review focuses on the major host genes reported to affect the progression to AIDS in HIV-1 infected individuals.

  16. Advances in behavioral genetics modeling using Mplus: applications of factor mixture modeling to twin data.

    Science.gov (United States)

    Muthén, Bengt; Asparouhov, Tihomir; Rebollo, Irene

    2006-06-01

    This article discusses new latent variable techniques developed by the authors. As an illustration, a new factor mixture model is applied to the monozygotic-dizygotic twin analysis of binary items measuring alcohol-use disorder. In this model, heritability is simultaneously studied with respect to latent class membership and within-class severity dimensions. Different latent classes of individuals are allowed to have different heritability for the severity dimensions. The factor mixture approach appears to have great potential for the genetic analyses of heterogeneous populations. Generalizations for longitudinal data are also outlined.

  17. Genetic and environmental factors that affect gestation length in dairy cattle.

    Science.gov (United States)

    Norman, H D; Wright, J R; Kuhn, M T; Hubbard, S M; Cole, J B; VanRaden, P M

    2009-05-01

    Genetic and environmental factors that might affect gestation length (GL) were investigated. Data included information from >11 million parturitions from 1999 through 2006 for 7 US dairy breeds. Effects examined were year, herd-year, month, and age within parity of conception; parturition code (sex and multiple-birth status); lactation length and standardized milk yield of cow; service sire; cow sire; and cow. All effects were fixed except for service sire, cow sire, and cow. Mean GL for heifers and cows, respectively, were 277.8 and 279.4 d for Holsteins, 278.4 and 280.0 d for Jerseys, 279.3 and 281.1 d for Milking Shorthorns, 281.6 and 281.7 d for Ayrshires, 284.8 and 285.7 d for Guernseys, and 287.2 and 287.5 d for Brown Swiss. Estimated standard deviations of GL were greatly affected by data restrictions but generally were approximately 5 to 6 d. Year effects on GL were extremely small, but month effects were moderate. For Holstein cows, GL was 2.0 d shorter for October conceptions than for January and February conceptions; 4.7 and 5.6 d shorter for multiple births of the same sex than for single-birth females and males, respectively; 0.8 d longer for lactations of or =501 d; and 0.6 d shorter for standardized yield of or =14,001 kg. Estimates for GL heritability from parities 2 to 5 were 33 to 36% for service sire and 7 to 12% for cow sire; corresponding estimates from parity 1 were 46 to 47% and 10 to 12%. Estimates of genetic correlations between effects of service sire and cow sire on GL were 0.70 to 0.85 for Brown Swiss, Holsteins, and Jerseys, which indicates that those traits likely are controlled by many of the same genes and can be used to evaluate each other. More accurate prediction of calving dates can help dairy producers to meet management requirements of pregnant animals and to administer better health care during high-risk phases of animals' lives. However, intentional selection for either shorter or longer GL is not recommended without

  18. THE EFFECT OF GENETIC AND ENVIRONMENTAL FACTORS TO FACIAL SHAPE IN DOWN’S SYNDROME PATIENTS

    Directory of Open Access Journals (Sweden)

    Margaretha Suharsini

    2006-04-01

    Full Text Available Down’s syndrome is caused by chromosomal aberration, namely 21 trisomy. Skeletal and neurological disorders are found in Down’s syndrome patients. Skeletal disorder may cause craniofacial growth abnormalities whereas neurological disorder may cause brain growth defects, which result in mental retardation, as well as neuromuscular disorder, which results in muscular hypotonia. The aim of this study was to prove that facial shape in Down’s syndrome patient was not only influenced by genetic factors, but also by environmental factors such as cognitive capability, oral muscular exercises and oral muscular tone. The population consisted of Down’s syndrome children aged 14 to 18 years from Sekolah Luar Biasa (Special School in Jakarta. Samples used in the study consisted of 25 Down’s syndrome patients. Clinical and cytogenic test were conducted to ensure a diagnosis. Lateral cephalograms were made to analyze facial shape by Fourier analysis on gonion angle. Intelligence Quotient (IQ and Social Quotient (SQ tests, electromyography examination of the masseter and temporal muscles, oral function examination and speech therapy questionnaires to the respondents were performed. The data were analyzed using path analysis. Based on the results of the study, it could be concluded that the genetic factor is the main factor causing Down’s syndrome facial shape abnormalities. The environmental factors such as oral muscular tone, cognitive capability, and oral muscular exercises may also play a role in Down’s syndrome facial shape.

  19. [Influences of genetic and environmental factors on smoking related behaviors among male twin adults in China].

    Science.gov (United States)

    Bao, Z Q; Yu, C Q; Wang, B Q; Cao, W H; Gao, W J; Lyu, J; Wang, S F; Pang, Z C; Cong, L M; Dong, Z; Wu, F; Wang, H; Wu, X P; Wang, D Z; Wang, X J; Wang, B Y; Li, L M

    2016-05-01

    To analyze the influences of genetic and environmental factors on smoking behavior, smoking cessation and onset age of smoking less than 20 years in male twin adults. A face-to-face questionnaire was conducted to collect data from 6 458 pair male twins aged ≥25 years registered in 9 provinces(municipality)in China. The heritability of three smoking related behaviors were calculated by using structural equation models. The ACE models were the best models of the three dimensions of smoking, i.e. smoking behavior, smoking cessation and onset age of smoking less than 20 years for male twins, and the corresponding heritability of these behaviors were 0.26(0.19-0.34), 0.27(0.19-0.37)and 0.05(0.00-0.14), respectively. When adjusted for area and age, the heritability of these three behaviors were 0.26(0.19-0.34), 0.31(0.00-0.74)and 0.05(0.00-0.14), respectively. All the three smoking related behaviors were affected by genetic factors, but environment factors had more effect on them. For smoking cessation, the heritability was highest, but the influence of environmental factors was lowest. Meanwhile, for onset age of smoking, the influence of environmental factors was highest.

  20. Evidence for an intrinsic factor promoting landscape genetic divergence in Madagascan leaf-litter frogs.

    Science.gov (United States)

    Wollenberg Valero, Katharina C

    2015-01-01

    The endemic Malagasy frog radiations are an ideal model system to study patterns and processes of speciation in amphibians. Large-scale diversity patterns of these frogs, together with other endemic animal radiations, led to the postulation of new and the application of known hypotheses of species diversification causing diversity patterns in this biodiversity hotspot. Both extrinsic and intrinsic factors have been studied in a comparative framework, with extrinsic factors usually being related to the physical environment (landscape, climate, river catchments, mountain chains), and intrinsic factors being clade-specific traits or constraints (reproduction, ecology, morphology, physiology). Despite some general patterns emerging from such large-scale comparative analyses, it became clear that the mechanism of diversification in Madagascar may vary among clades, and may be a multifactorial process. In this contribution, I test for intrinsic factors promoting population-level divergence within a clade of terrestrial, diurnal leaf-litter frogs (genus Gephyromantis) that has previously been shown to diversify according to extrinsic factors. Landscape genetic analyses of the microendemic species Gephyromantis enki and its widely distributed, larger sister species Gephyromantis boulengeri over a rugged landscape in the Ranomafana area shows that genetic variance of the smaller species cannot be explained by landscape resistance alone. Both topographic and riverine barriers are found to be important in generating this divergence. This case study yields additional evidence for the probable importance of body size in lineage diversification.

  1. Genetic variants and non-genetic factors predict circulating vitamin D levels in Hispanic and non-Hispanic White women: the Breast Cancer Health Disparities Study

    Science.gov (United States)

    Wang, Wei; Ingles, Sue Ann; Torres-Mejía, Gabriela; Stern, Mariana C; Stanczyk, Frank Z; Schwartz, Gary G; Nelson, David O; Fejerman, Laura; Wolff, Roger K; Slattery, Martha L; John, Esther M

    2014-01-01

    Genome-wide association studies (GWAS) have identified common polymorphisms in or near GC, CYP2R1, CYP24A1, and NADSYN1/DHCR7 genes to be associated with circulating levels of 25-hydroxyvitamin D [25(OH)D] in European populations. To replicate these GWAS findings, we examined six selected polymorphisms from these regions and their relation with circulating 25(OH)D levels in 1,605 Hispanic women (629 U.S. Hispanics and 976 Mexicans) and 354 non-Hispanic White (NHW) women. We also assessed the potential interactions between these variants and known non-genetic predictors of 25(OH)D levels, including body mass index (BMI), sunlight exposure and vitamin D intake from diet and supplements. The minor alleles of the two GC polymorphisms (rs7041 and rs2282679) were significantly associated with lower 25(OH)D levels in both Hispanic and NHW women. The CYP2R1 polymorphism, rs2060793, also was significantly associated with 25(OH)D levels in both groups. We found no significant associations for the polymorphisms in the CYP24A1. In Hispanic controls, 25(OH)D levels were significantly associated with the rs12785878T and rs1790349G haplotype in the NADSYN1/DHCR7 region. Significant interactions between GC rs2282679 and BMI and between rs12785878 and time spent in outdoor activities were observed. These results provide further support for the contribution of common genetic variants to individual variability in circulating 25(OH)D levels. The observed interactions between SNPs and non-genetic factors warrant confirmation. PMID:24596595

  2. The effect of ivermectin in seven strains of Aedes aegypti (Diptera: Culicidae) including a genetically diverse laboratory strain and three permethrin resistant strains.

    Science.gov (United States)

    Deus, K M; Saavedra-Rodriguez, K; Butters, M P; Black, W C; Foy, B D

    2012-03-01

    Seven different strains of Aedes aegypti (L.), including a genetically diverse laboratory strain, three laboratory-selected permethrin-resistant strains, a standard reference strain, and two recently colonized strains were fed on human blood containing various concentrations of ivermectin. Ivermectin reduced adult survival, fecundity, and hatch rate of eggs laid by ivermectin-treated adults in all seven strains. The LC50 of ivermectin for adults and the concentration that prevented 50% of eggs from hatching was calculated for all strains. Considerable variation in adult survival after an ivermectin-bloodmeal occurred among strains, and all three permethrin-resistant strains were significantly less susceptible to ivermectin than the standard reference strain. The hatch rate after an ivermectin bloodmeal was less variable among strains, and only one of the permethrin-resistant strains differed significantly from the standard reference strain. Our studies suggest that ivermectin induces adult mortality and decreases the hatch rate of eggs through different mechanisms. A correlation analysis of log-transformed LC50 among strains suggests that permethrin and ivermectin cross-resistance may occur.

  3. Epidemiology of Down syndrome: new insight into the multidimensional interactions among genetic and environmental risk factors in the oocyte.

    Science.gov (United States)

    Ghosh, Sujoy; Hong, Chang-Sook; Feingold, Eleanor; Ghosh, Papiya; Ghosh, Priyanka; Bhaumik, Pranami; Dey, Subrata Kumar

    2011-11-01

    Down syndrome birth is attributable to multiple maternal risk factors that include both genetic and environmental challenges, but there is limited understanding of the complicated interactions among these factors. In the present study, a case-control analysis of approximately 400 infants with or without suspected Down syndrome reported between 2003 and 2009 and their parents in and around Kolkata, India, was conducted. Maternal exposure to 2 environmental risk factors (smokeless chewing tobacco and oral contraceptive pills) was recorded, and families were genotyped with microsatellite markers to establish the origin of nondisjunction errors as well as recombination patterns of nondisjoined chromosome 21. With logistic regression models, the possible interactions among all of these risk factors, as well as with maternal age, were explored. Smokeless chewing tobacco was associated with significant risk for meiosis II nondisjunction and achiasmate (nonexchange) meiosis I error among young mothers. By contrast, the risk due to oral contraceptive pills was associated with older mothers. Study results suggest that the chewing tobacco risk factor operates independently of the maternal age effect, whereas contraceptive pill-related risk may interact with or exacerbate age-related risk. Moreover, both risk factors, when present together, exhibited a strong age-dependent effect.

  4. Excitation and charge transfer in He/sup +/ + H collisions. A molecular approach including two-electron translation factors

    Energy Technology Data Exchange (ETDEWEB)

    Errea, L.F.; Mendez, L.; Riera, A.

    1983-06-01

    In a previous paper we have pointed out that the common-translation-factor (CTF) method is the only one which, at present, and within the framework of the molecular model of atomic collisions, can be shown to be both convergent and computationally fast, even for many-electron systems. In this Communication we check that this second statement is correct, presenting, for the first time, a molecular calculation involving two-electron translation factors, for He/sup +/ + H collisions. A careful study of the sensitivity of the calculated cross sections to the choice of the CTF is performed, and conclusions on that sensitivity are drawn, for several types of processes.

  5. Common genetic risk factors for venous thrombosis in the Chinese population.

    Science.gov (United States)

    Tang, Liang; Wang, Hua-Fang; Lu, Xuan; Jian, Xiao-Rong; Jin, Bi; Zheng, Hong; Li, Yi-Qing; Wang, Qing-Yun; Wu, Tang-Chun; Guo, Huan; Liu, Hui; Guo, Tao; Yu, Jian-Ming; Yang, Rui; Yang, Yan; Hu, Yu

    2013-02-07

    Venous thrombosis is a major medical disorder caused by both genetic and environmental factors. Little is known about the genetic background of venous thrombosis in the Chinese population. A total of 1,304 individuals diagnosed with a first venous thrombosis and 1,334 age- and sex-matched healthy participants were enrolled in this study. Resequencing of THBD (encoding thrombomodulin) in 60 individuals with venous thrombosis and 60 controls and a functional assay showed that a common variant, c.-151G>T (rs16984852), in the 5' UTR significantly reduced the gene expression and could cause a predisposition to venous thrombosis. Therefore, this variant was genotyped in a case-control study, and results indicated that heterozygotes had a 2.80-fold (95% confidence interval = 1.88-4.29) increased risk of venous thrombosis. The THBD c.-151G>T variant was further investigated in a family analysis involving 176 first-degree relatives from 38 index families. First-degree relatives with this variant had a 3.42-fold increased risk of venous thrombosis, and their probability of remaining thrombosis-free was significantly lower than that of relatives without the variant. In addition, five rare mutations that might be deleterious were also identified in thrombophilic individuals by sequencing. This study is the largest genetic investigation of venous thrombosis in the Chinese population. Further study on genetics of thrombosis should focus on resequencing of THBD and other hemostasis genes in different populations.

  6. DNA sequence analysis of conserved and unique regions of swinepox virus: identification of genetic elements supporting phenotypic observations including a novel G protein-coupled receptor homologue.

    Science.gov (United States)

    Massung, R F; Jayarama, V; Moyer, R W

    1993-12-01

    Swinepox virus (SPV) contains a double-stranded cross-linked linear DNA genome of approximately 175 kilobase pairs with terminal inverted repetitions (TIRs) of 4.3 kb. The nucleotide sequence was determined for fragments from several regions of the genome including a 2.85-kb fragment from the central potentially conserved portion and two fragments within the presumed variable near-terminal regions which tend to be unique to a given poxvirus. The core sequence contains one partial and two complete open reading frames that are highly conserved and colinear with three contiguous ORFs within the HindIII D fragment of vaccinia virus (VV). The two near-terminal fragments, encompassing 14.2 and 3.6 kb, are respectively located 2.1 kb internal to the left and right cross-linked termini of the DNA and span the TIR junctions. The sequences encode 25 open reading frames including numerous proteins predicted to be membrane-bound or secreted in infected cells. Several ORFs unique to SPV were identified that may be involved in cell attachment, immune modulation, and pathogenesis including a novel poxvirus G protein-coupled receptor. In addition, several polypeptides encoded within the near-terminal regions of vaccinia virus DNA that function as host range or virulence factors are lacking within this region of swinepox virus including the VV growth factor, complement-binding protein, and ORFs C7L and K1L, associated with host range. The lack of these functional homologues could explain the characteristic attenuated phenotype and limited host range of SPV.

  7. Analytic validity of genetic tests to identify factor V Leiden and prothrombin G20210A.

    Science.gov (United States)

    Emadi, Ashkan; Crim, Matthew T; Brotman, Daniel J; Necochea, Alejandro J; Samal, Lipika; Wilson, Lisa M; Bass, Eric B; Segal, Jodi B

    2010-04-01

    The objective of this study is to systematically review methods for detecting Factor V Leiden or prothrombin G20210A. English-language literature from MEDLINE, EMBASE, The Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, PsycInfo(c), 2000-December 2008. Studies assessed methods for detection of these mutations in at least 10 human blood samples and reported concordance, discordance, or reproducibility. Two investigators abstracted data on the sample selection criteria, test operators, DNA extraction, experimental test, reference standard, commercial instruments, concordance rates, explanation of any discordance, and whether discordance resolved after repetition. We assessed strength of the evidence using the GRADE criteria. We reviewed 7,777 titles and included 66 articles. The majority of the reviewed studies used PCR-RFLP or AS-PCR as the reference standard. The studies demonstrated that commercially available and precommercial tests have high analytic validity with all having greater than 99% concordance with the reference standard. With a few exceptions, discordance resolved with repetition of the test, suggesting operator or administrative errors were responsible for the discordant results. In the quality assurance studies, greater than 98% of laboratories demonstrated high, even perfect, accuracy when asked to diagnose a sample with a known mutation. The majority of errors came from a limited number of laboratories. Although not all methods may be accurate, there is high-grade evidence that genetic tests for the detection of FVL and prothrombin G20210A have excellent analytic validity. There is high-grade evidence that most, but not all, clinical laboratories test for FVL and prothrombin G20210A accurately.

  8. Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia.

    Science.gov (United States)

    Wakita, S; Yamaguchi, H; Ueki, T; Usuki, K; Kurosawa, S; Kobayashi, Y; Kawata, E; Tajika, K; Gomi, S; Koizumi, M; Fujiwara, Y; Yui, S; Fukunaga, K; Ryotokuji, T; Hirakawa, T; Arai, K; Kitano, T; Kosaka, F; Tamai, H; Nakayama, K; Fukuda, T; Inokuchi, K

    2016-03-01

    We conducted a comprehensive analysis of 28 recurrently mutated genes in acute myeloid leukemia (AML) in 271 patients with de novo AML. Co-mutations were frequently detected in the intermediate cytogenetic risk group, at an average of 2.76 co-mutations per patient. When assessing the prognostic impact of these co-mutations in the intermediate cytogenetic risk group, overall survival (OS) was found to be significantly shorter (P=0.0006) and cumulative incidence of relapse (CIR) significantly higher (P=0.0052) in patients with complex molecular genetic abnormalities (CMGAs) involving three or more mutations. This trend was marked even among patients aged ⩽65 years who were also FLT3-ITD (FMS-like tyrosine kinase 3 internal tandem duplications)-negative (OS: P=0.0010; CIR: P=0.1800). Moreover, the multivariate analysis revealed that CMGA positivity was an independent prognostic factor associated with OS (P=0.0007). In stratification based on FLT3-ITD and CEBPA status and 'simplified analysis of co-mutations' using seven genes that featured frequently in CMGAs, CMGA positivity retained its prognostic value in transplantation-aged patients of the intermediate cytogenetic risk group (OS: P=0.0002. CIR: Pmutation analysis to have clinical usefulness and applicability.

  9. Twins and virtual twins: Do genetic (as well as experiential) factors affect developmental risks?

    Science.gov (United States)

    Segal, Nancy L; Tan, Tony Xing; Graham, Jamie L

    2015-08-01

    Factors underlying developmental delays and psychosocial risks are of interest to international adoption communities. The current study administered a Pre-Adoption Adversity (PAA) Questionnaire to mostly American parents raising (a) adopted Chinese twins or (b) same-age unrelated adopted siblings. A goal was to replicate earlier analyses of pre-adoption adversity/adjustment among adopted preschool-age Chinese girls. A second goal was to conduct genetic analyses of four content areas (Developmental Delays at Adoption, Initial Adaptation to Adoption, Crying/Clinging, and Refusal/Avoidance) derived from the PAA Questionnaire. A key finding was that age at adoption added less than other predictors to adoptees' externalizing and internalizing behaviors. Family factors (e.g., parental education) contributed significantly to behavioral outcomes among the adopted Chinese twins. Genetic effects were indicated for all four content areas, with shared environmental effects evident for Developmental Delays at Adoption and Crying/Clinging. Future investigators should consider incorporating genetically sensitive designs into developmental research programs.

  10. Characterization of Clinical and Genetic Risk Factors Associated with Dyslipidemia after Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Kazuyuki Numakura

    2015-01-01

    Full Text Available We determined the prevalence of dyslipidemia in a Japanese cohort of renal allograft recipients and investigated clinical and genetic characteristics associated with having the disease. In total, 126 patients that received renal allograft transplants between February 2002 and August 2011 were studied, of which 44 recipients (34.9% were diagnosed with dyslipidemia at 1 year after transplantation. Three clinical factors were associated with a risk of having dyslipidemia: a higher prevalence of disease observed among female than male patients P=0.021 and treatment with high mycophenolate mofetil P=0.012 and prednisolone P=0.023 doses per body weight at 28 days after transplantation. The genetic association between dyslipidemia and 60 previously described genetic polymorphisms in 38 putative disease-associated genes was analyzed. The frequency of dyslipidemia was significantly higher in patients with the glucocorticoid receptor (NR3C1 Bcl1 G allele than in those with the CC genotype P=0.001. A multivariate analysis revealed that the NR3C1 Bcl1 G allele was a significant risk factor for the prevalence of dyslipidemia (odds ratio = 4.6; 95% confidence interval = 1.8–12.2. These findings may aid in predicting a patient’s risk of developing dyslipidemia.

  11. [Role of genetic and environmental factors in the development of polycystic ovary syndrome].

    Science.gov (United States)

    Ságodi, László; Kiss-Tóth, Emőke; Barkai, László

    2013-04-28

    Polycystic ovary syndrome is the most common heterogeneous endocrine abnormality in women in the reproductive age. The syndrome remains an enigmatic disorder because the aetiology is still unclear. Familial aggreagation is relatively common among patients with polycystic ovary syndrome suggesting a significant genetic component, although the way of inheritance has not been established firmly. The authors review the relevant medical literature and suggest that genetic and environmental factors play a role in the development of polycystic ovary syndrome. To date, no gene has been identified that causes or contributes substantially to the development of a polycystic ovary syndrome phenotype. Polycystic ovarian syndrome is considered to be an oligogenic disorder in which the interaction of a number of genetic and environmental factors determines the heterogeneous clinical and biochemical phenotype. To summarize current evidence the authors conclude, that when we are able to identify and then modify environmental determinants, then we will be able to safeguard better the health of those patients who are predisposed to disease development due to genotype or previous environmental effects.

  12. Trait-based assessment of borderline personality disorder using the NEO Five-Factor Inventory: Phenotypic and genetic support

    Science.gov (United States)

    Few, Lauren R.; Miller, Joshua D.; Grant, Julia D.; Maples, Jessica; Trull, Timothy J.; Nelson, Elliot C.; Oltmanns, Thomas F.; Martin, Nicholas G.; Lynskey, Michael T.; Agrawal, Arpana

    2015-01-01

    The aim of the current study was to examine the reliability and validity of a trait-based assessment of borderline personality disorder (BPD) using the NEO Five-Factor Inventory. Correlations between the Five-Factor Inventory-BPD composite (FFI-BPD) and explicit measures of BPD were examined across six samples, including undergraduate, community, and clinical samples. The median correlation was .60, which was nearly identical to the correlation between measures of BPD and a BPD composite generated from the full Revised NEO Personality Inventory (i.e., NEO-BPD; r =.61). Correlations between FFI-BPD and relevant measures of psychiatric symptomatology and etiology (e.g., childhood abuse, drug use, depression, and personality disorders) were also examined and compared to those generated using explicit measures of BPD and NEO-BPD. As expected, the FFI-BPD composite correlated most strongly with measures associated with high levels of Neuroticism, such as depression, anxiety, and emotion dysregulation, and the pattern of correlations generated using the FFI-BPD was highly similar to those generated using explicit measures of BPD and NEO-BPD. Finally, genetic analyses estimated that FFI-BPD is 44% heritable, which is comparable to meta-analytic research examining genetics associated with BPD, and revealed that 71% of the genetic influences are shared between FFI-BPD and a self-report measure assessing BPD (Personality Assessment Inventory – Borderline subscale; Morey, 1991). Generally, these results support the use of FFI-BPD as a reasonable proxy for BPD, which has considerable implications, particularly for potential gene-finding efforts in large, epidemiological datasets that include the NEO FFI. PMID:25984635

  13. Coregulation of genetic programs by the transcription factors NFIB and STAT5.

    Science.gov (United States)

    Robinson, Gertraud W; Kang, Keunsoo; Yoo, Kyung Hyun; Tang, Yong; Zhu, Bing-Mei; Yamaji, Daisuke; Colditz, Vera; Jang, Seung Jian; Gronostajski, Richard M; Hennighausen, Lothar

    2014-05-01

    Mammary-specific genetic programs are activated during pregnancy by the common transcription factor signal transducer and activator of transcription (STAT) 5. More than one third of these genes carry nuclear factor I/B (NFIB) binding motifs that coincide with STAT5 in vivo binding, suggesting functional synergy between these two transcription factors. The role of NFIB in this governance was investigated in mice from which Nfib had been inactivated in mammary stem cells or in differentiating alveolar epithelium. Although NFIB was not required for alveolar expansion, the combined absence of NFIB and STAT5 prevented the formation of functional alveoli. NFIB controlled the expression of mammary-specific and STAT5-regulated genes and chromatin immunoprecipitation-sequencing established STAT5 and NFIB binding at composite regulatory elements containing histone H3 lysine dimethylation enhancer marks and progesterone receptor binding. By integrating previously published chromatin immunoprecipitation-sequencing data sets, the presence of NFIB-STAT5 modules in other cell types was investigated. Notably, genomic sites bound by NFIB in hair follicle stem cells were also occupied by STAT5 in mammary epithelium and coincided with enhancer marks. Many of these genes were under NFIB control in both hair follicle stem cells and mammary alveolar epithelium. We propose that NFIB-STAT5 modules, possibly in conjunction with other transcription factors, control cell-specific genetic programs.

  14. [Methylmercury exposure in the general population; toxicokinetics; differences by gender, nutritional and genetic factors].

    Science.gov (United States)

    González-Estecha, Montserrat; Bodas-Pinedo, Andrés; Guillén-Pérez, José Jesús; Rubio-Herrera, Miguel Ángel; Ordóñez-Iriarte, José M; Trasobares-Iglesias, Elena M; Martell-Claros, Nieves; Martínez-Álvarez, Jesús Román; Farré-Rovira, Rosaura; Herráiz-Martínez, Miguel Ángel; Martínez-Astorquiza, Txantón; Calvo-Manuel, Elpidio; Sáinz-Martín, María; Bretón-Lesmes, Irene; Prieto-Menchero, Santiago; Llorente-Ballesteros, M Teresa; Martínez-García, M José; Salas-Salvadó, Jordi; Bermejo-Barrera, Pilar; García-Donaire, José Antonio; Cuadrado-Cenzual, M Ángeles; Gallardo-Pino, Carmen; Moreno-Rojas, Rafael; Arroyo-Fernández, Manuel; Calle-Pascual, Alfonso

    2014-11-01

    Mercury is an environmental toxicant that causes numerous adverse effects on human health and natural ecosystems. The factors that determine the existance of adverse effects, as well as their severity are, among others: the chemical form of mercury (elemental, inorganic, organic), dosis, age, period of exposure, pathways of exposure and environmental, nutritional and genetic factors. In the aquatic cycle of mercury, once it has been deposited, it is transformed into methylmercury due to the action of certain sulphate-reducing bacteria, which bioaccumulates in the aquatic organisms and moves into the food chain. The methylmercury content of large, long-lived fish such as swordfish, shark, tuna or marlin, is higher. Methylmercury binds to protein in fish and is therefore not eliminated by cleaning or cooking the fish. Fetuses and small children are more vulnerable to the neurotoxic effects of methylmercury from the consumption of contaminated fish. Methylmercury is absorbed in the gastrointestinal tract and crosses the blood-brain barrier and the placenta. The intake of certain dietary components such as polyunsaturated fatty acids, selenium, fiber, thiol compounds, certain phytochemicals and other nutrients can modify methylmercury bioaccesibility and its toxicity. Apart from environmental factors, genetic factors can influence mercury toxicity and explain part of the individual vulnerability.

  15. Metabolic factors and genetic risk mediate familial type 2 diabetes risk in the Framingham Heart Study

    Science.gov (United States)

    Raghavan, Sridharan; Porneala, Bianca; McKeown, Nicola; Fox, Caroline S.; Dupuis, Josée; Meigs, James B.

    2015-01-01

    Aims/hypothesis Type 2 diabetes mellitus in parents is a strong determinant of diabetes risk in their offspring. We hypothesise that offspring diabetes risk associated with parental diabetes is mediated by metabolic risk factors. Methods We studied initially non-diabetic participants of the Framingham Offspring Study. Metabolic risk was estimated using beta cell corrected insulin response (CIR), HOMA-IR or a count of metabolic syndrome components (metabolic syndrome score [MSS]). Dietary risk and physical activity were estimated using questionnaire responses. Genetic risk score (GRS) was estimated as the count of 62 type 2 diabetes risk alleles. The outcome of incident diabetes in offspring was examined across levels of parental diabetes exposure, accounting for sibling correlation and adjusting for age, sex and putative mediators. The proportion mediated was estimated by comparing regression coefficients for parental diabetes with (βadj) and without (βunadj) adjustments for CIR, HOMA-IR, MSS and GRS (percentage mediated = 1 – βadj / βunadj). Results Metabolic factors mediated 11% of offspring diabetes risk associated with parental diabetes, corresponding to a reduction in OR per diabetic parent from 2.13 to 1.96. GRS mediated 9% of risk, corresponding to a reduction in OR per diabetic parent from 2.13 to 1.99. Conclusions/interpretation Metabolic risk factors partially mediated offspring type 2 diabetes risk conferred by parental diabetes to a similar magnitude as genetic risk. However, a substantial proportion of offspring diabetes risk associated with parental diabetes remains unexplained by metabolic factors, genetic risk, diet and physical activity, suggesting that important familial influences on diabetes risk remain undiscovered. PMID:25619168

  16. Deduction of bond length changes of symmetric molecules from experimental vibrational progressions, including a topological mass factor.

    Science.gov (United States)

    Su, Jing; Wei, Fan; Schwarz, W H E; Li, Jun

    2012-12-20

    The change ΔR(x) of bond length R(x) for atom X in a molecule upon electronic transition can be derived from the intensities I(i) of the vibrational stretching progression v = 0 → i of the electronic absorption or emission spectrum. In many cases, a simple model is sufficient for a reasonable estimate of ΔR(x). For symmetric molecules, however, conceptual problems in the literature of many decades are evident. The breathing modes of various types of symmetric molecules X(n) and AX(n) (A at the center) are here discussed. In the simplest case of a harmonic vibration of the same mode in the initial and final electronic states, we obtain ΔR(x) ≈ [2S/(ωm(x))](1/2)/w(1/2) (all quantities in atomic units). ω and S are respectively the observed vibrational quanta and the Huang-Rhys factor (corresponding, e.g., to the vibrational intensity ratio I(1)/I(0) ≈ S), m(x) is the mass of vibrating atom X, and w is a topological factor for molecule X(n) or AX(n). The factor 1/w(1/2) in the expression for ΔR(x) must not be neglected. The spectra and bond length changes of several symmetric molecules AX(n) and X(n) are discussed. The experimental bond length changes correctly derived with factor 1/w(1/2) are verified by reliable quantum chemical calculations.

  17. Role of Host Genetic Factors in the Outcome of Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Hubert E. Blum

    2009-08-01

    Full Text Available The natural history of hepatitis C virus (HCV infection is determined by a complex interplay between host genetic, immunological and viral factors. This review highlights genes involved in innate and adaptive immune responses associated with different outcomes of HCV infection. For example, an association of HCV clearance with certain HLA alleles has been demonstrated. The mechanisms responsible for these associations have been linked to specific T cell responses for some particular alleles (e.g., HLA-B27. Genetic associations involved in T cell regulation and function further underline the role of the adaptive immune response in the natural history of HCV infection. In addition, some genes involved in innate NK cell responses demonstrate the complex interplay between components of the immune system necessary for a successful host response to HCV infection.

  18. Catchment process affecting drinking water quality, including the significance of rainfall events, using factor analysis and event mean concentrations.

    Science.gov (United States)

    Cinque, Kathy; Jayasuriya, Niranjali

    2010-12-01

    To ensure the protection of drinking water an understanding of the catchment processes which can affect water quality is important as it enables targeted catchment management actions to be implemented. In this study factor analysis (FA) and comparing event mean concentrations (EMCs) with baseline values were techniques used to asses the relationships between water quality parameters and linking those parameters to processes within an agricultural drinking water catchment. FA found that 55% of the variance in the water quality data could be explained by the first factor, which was dominated by parameters usually associated with erosion. Inclusion of pathogenic indicators in an additional FA showed that Enterococcus and Clostridium perfringens (C. perfringens) were also related to the erosion factor. Analysis of the EMCs found that most parameters were significantly higher during periods of rainfall runoff. This study shows that the most dominant processes in an agricultural catchment are surface runoff and erosion. It also shows that it is these processes which mobilise pathogenic indicators and are therefore most likely to influence the transport of pathogens. Catchment management efforts need to focus on reducing the effect of these processes on water quality.

  19. Genetic factors control nicotine self-administration in isogenic adolescent rat strains.

    Directory of Open Access Journals (Sweden)

    Hao Chen

    Full Text Available Adult cigarette smokers usually become dependent on cigarettes during adolescence. Despite recent advances in addiction genetics, little data delineates the genetic factors that account for the vulnerability of humans to smoke tobacco. We studied the operant nicotine self-administration (SA behavior of six inbred strains of adolescent male rats (Fisher 344, Brown Norway, Dark Agouti, Spontaneous Hypertensive Rat, Wistar Kyoto and Lewis and six selected F1 hybrids. All rats were trained to press a lever to obtain food starting on postnatal day (PN 32, and then nicotine (0.03 mg/kg/infusion, i.v. reinforcement was made available on PN41-42 (10 consecutive daily 2 h sessions. Of the 12 isogenic strains, Fisher rats self-administered the fewest nicotine infusions (1.45 ± 0.36/d during the last 3 d, while Lewis rats took the most nicotine (13.0 ± 1.4/d. These strains sorted into high, intermediate and low self-administration groups in 2, 2, and 8 strains, respectively. The influence of heredity on nicotine SA (0.64 is similar to that reported for humans. Therefore, this panel of isogenic rat strains effectively models the overall impact of genetics on the vulnerability to acquire nicotine-reinforced behavior during adolescence. Separate groups of rats responded for food starting on PN41. The correlation between nicotine and food reward was not significant. Hence, the genetic control of the motivation to obtain nicotine is distinctly different from food reward, indicating the specificity of the underlying genetic mechanisms. Lastly, the behavior of F1 hybrids was not predicted from the additive behavior of the parental strains, indicating the impact of significant gene-gene interactions on the susceptibility to nicotine reward. Taken together, the behavioral characteristics of this model indicate its strong potential to identify specific genes mediating the human vulnerability to smoke cigarettes.

  20. Characterizing the role of brain derived neurotrophic factor genetic variation in Alzheimer's disease neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Robyn A Honea

    Full Text Available There is accumulating evidence that neurotrophins, like brain-derived neurotrophic factor (BDNF, may impact aging and Alzheimer's Disease. However, traditional genetic association studies have not found a clear relationship between BDNF and AD. Our goal was to test whether BDNF single nucleotide polymorphisms (SNPs impact Alzheimer's Disease-related brain imaging and cognitive markers of disease. We completed an imaging genetics study on 645 Alzheimer's Disease Neuroimaging Initiative participants (ND=175, MCI=316, AD=154 who had cognitive, brain imaging, and genetics data at baseline and a subset of those with brain imaging data at two years. Samples were genotyped using the Illumina Human610-Quad BeadChip. 13 SNPs in BDNF were identified in the dataset following quality control measures (rs6265(Val66Met, rs12273363, rs11030094, rs925946, rs1050187, rs2203877, rs11030104, rs11030108, rs10835211, rs7934165, rs908867, rs1491850, rs1157459. We analyzed a subgroup of 8 SNPs that were in low linkage disequilibrium with each other. Automated brain morphometric measures were available through ADNI investigators, and we analyzed baseline cognitive scores, hippocampal and whole brain volumes, and rates of hippocampal and whole brain atrophy and rates of change in the ADAS-Cog over one and two years. Three out of eight BDNF SNPs analyzed were significantly associated with measures of cognitive decline (rs1157659, rs11030094, rs11030108. No SNPs were significantly associated with baseline brain volume measures, however six SNPs were significantly associated with hippocampal and/or whole brain atrophy over two years (rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850. We also found an interaction between the BDNF Val66Met SNP and age with whole brain volume. Our imaging-genetics analysis in a large dataset suggests that while BDNF genetic variation is not specifically associated with a diagnosis of AD, it appears to play a role in AD

  1. At risk, or not at risk: Epidemiological approaches for assessing psychiatric (genetic) risk factors in the general population

    NARCIS (Netherlands)

    Breetvelt, E.J.

    2013-01-01

    This thesis “At risk, or not at risk” describes several approaches - cross-sectional, prospective, phenotype mining and forward genetics - for assessing psychiatric (genetic) risk factors in a general population study. The aims were 1) to investigate how routine and follow-up data from populationbas

  2. Cannabis Beyond Good and Evil. How genetic and epidemiological factors shape the relationship between cannabis and psychosis

    NARCIS (Netherlands)

    Schubart, C.D.

    2013-01-01

    The studies presented in this thesis aimed to identify genetic and non-genetic (epidemiological) factors that shape the association between cannabis use and psychosis. We showed that the age of first use of cannabis is a determinant for the strength of the association between cannabis use and psycho

  3. Common genetic influences on negative emotionality and a general psychopathology factor in childhood and adolescence.

    Science.gov (United States)

    Tackett, Jennifer L; Lahey, Benjamin B; van Hulle, Carol; Waldman, Irwin; Krueger, Robert F; Rathouz, Paul J

    2013-11-01

    Previous research using confirmatory factor analysis to model psychopathology comorbidity has supported the hypothesis of a broad general factor (i.e., a "bifactor"; Holzinger & Swineford, 1937) of psychopathology in children, adolescents, and adults, with more specific higher order internalizing and externalizing factors reflecting additional shared variance in symptoms (Lahey et al., 2012; Lahey, van Hulle, Singh, Waldman, & Rathouz, 2011). The psychological nature of this general factor has not been explored, however. The current study tested a prediction, derived from the spectrum hypothesis of personality and psychopathology, that variance in a general psychopathology bifactor overlaps substantially-at both phenotypic and genetic levels-with the dispositional trait of negative emotionality. Data on psychopathology symptoms and dispositional traits were collected from both parents and youth in a representative sample of 1,569 twin pairs (ages 9-17 years) from Tennessee. Predictions based on the spectrum hypothesis were supported, with variance in negative emotionality and the general factor overlapping substantially at both phenotypic and etiologic levels. Furthermore, stronger correlations were found between negative emotionality and the general psychopathology factor than among other dispositions and other psychopathology factors.

  4. Common Genetic Influences on Negative Emotionality and a General Psychopathology Factor in Childhood and Adolescence

    Science.gov (United States)

    Tackett, Jennifer L.; Lahey, Benjamin B.; Hulle, Carol Van; Waldman, Irwin; Krueger, Robert F.; Rathouz, Paul J.

    2014-01-01

    Previous research using confirmatory factor analysis to model psychopathology comorbidity supported the hypothesis of a broad general factor (i.e., a “bifactor”; Holzinger & Swineford, 1937) of psychopathology in children, adolescents, and adults, with more specific higher-order internalizing and externalizing factors reflecting additional shared variance in symptoms (Lahey et al., 2012; Lahey, Van Hulle, Singh, Waldman, & Rathouz, 2011). The psychological nature of this general factor has not been explored, however. The current study tests a prediction derived from the spectrum hypothesis of personality and psychopathology, that variance in a general psychopathology bifactor overlaps substantially—at both phenotypic and genetic levels—with the dispositional trait of negative emotionality. Data on psychopathology symptoms and dispositional traits were collected from both parents and youth in a representative sample of 1,569 twin pairs (ages 9–17) from Tennessee. Predictions based on the spectrum hypothesis were supported, with variance in negative emotionality and the general factor overlapping substantially at both phenotypic and etiologic levels. Furthermore, stronger correlations were found between negative emotionality and the general psychopathology factor than among other dispositions and other psychopathology factors. PMID:24364617

  5. Role of Genetic and Environmental Factors in the Development of Empathy

    Directory of Open Access Journals (Sweden)

    Yudina T.O.,

    2017-08-01

    Full Text Available The paper provides a review of studies on factors influencing empathy development in early childhood and on conditions promoting manifestation of empathy in children later in life. The outcomes of several studies shed light on the character of empathic response at early stages of child development, particularly in infancy and toddlerhood. This review covers research on the role of biological factors and mechanisms in empathy development (for instance, features of temperament and neuronal bases, as well as research on the relationship between genetic and environmental factors in the development of empathy in ontogenesis. Another part of the paper describes studies on the role of social conditions in the development of empathy in childhood: it focuses primarily on family relations and, in particular, on the mother/child relationship. The paper concludes with several suggestions concerning further research of the specified problem.

  6. A genetic association study between growth differentiation factor 5 (GDF 5 polymorphism and knee osteoarthritis in Thai population

    Directory of Open Access Journals (Sweden)

    Sura Thanyachai

    2011-09-01

    Full Text Available Abstract Objective Osteoarthritis (OA is a multi-factorial disease and genetic factor is one of the important etiologic risk factors. Various genetic polymorphisms have been elucidated that they might be associated with OA. Recently, several studies have shown an association between Growth Differentiation Factor 5(GDF5 polymorphism and knee OA. However, the role of genetic predisposing factor in each ethnic group cannot be replicated to all, with conflicting data in the literatures. Therefore, the aim of this study was to investigate the association between GDF5 polymorphism and knee OA in Thai population. Materials and Methods One hundred and ninety three patients aged 54-88 years who attended Ramathibodi Hospital were enrolled. Ninety cases with knee OA according to American College of Rheumatology criteria and one hundred and three cases in control group gave informed consent. Blood sample (5 ml were collected for identification of GDF5 (rs143383 single nucleotide polymorphism by PCR/RFLP according to a standard protocol. This study protocol was approved by the Ethics Committee on human experimentation of Ramathibodi Hospital Faculty of Medicine, Mahidol University. Odds ratios (OR and 95% confidence intervals were calculated for the risk of knee OA by genotype (TT, TC and CC and allele (T/C analyses. Results The baseline characteristics between two groups including job, smoking and activity were not different, except age and BMI. The entire cases and controls were in Hardy-Weinberg equilibrium (p > 0.05. The OA knee group (n = 90 had genotypic figure which has shown by TT 42.2% (n = 38, TC 45.6% (n = 41 and CC 12% (n = 11, whereas the control group (n = 103 revealed TT 32% (n = 33, TC 45.6% (n = 47, and CC 22.3% (n = 23, respectively. Genotypic TT increased risk of knee OA as compared to CC [OR = 2.41 (P = 0.04, 95%CI = 1.02-5.67]. In the allele analysis, the T allele was found to be significantly associated with knee OA [OR = 1.53 (P = 0

  7. The importance of genetic and shared environmental factors for the associations between job demands, control, support and burnout.

    Directory of Open Access Journals (Sweden)

    Victoria Blom

    Full Text Available Within occupational health research, one of the most influential models is the Job Demands-Control-Support model. Numerous studies have applied the model to different domains, with both physical and psychological health outcomes, such as burnout. The twin design provides a unique and powerful research methodology for examining the effects of environmental risk factors on burnout while taking familial factors (genetic and shared environment into account. The aim of the present study was to investigate the impact of familial factors on the associations of burnout with job demands, control and support. A total of 14,516 individuals from the Swedish Twin Registry, who were born between 1959 and 1986, and who participated in the Study of Twin Adults: Genes and Environment (STAGE by responding to a web-based questionnaire in 2005, were included in the analyses. Of these, there were 5108 individuals in complete same-sex twin pairs. Co-twin control analyses were performed using linear mixed modeling, comparing between-pairs effects and within-pair effects, stratified also by zygosity and sex. The results indicate that familial factors are of importance in the association between support and burnout in both women and men, but not between job demands and burnout. There are also tendencies towards familial factors being involved in the association between control and burnout in men. These results offer increased understanding of the mechanisms involved in the associations between work stress and burnout.

  8. Combining Telomerase Reverse Transcriptase Genetic Variant rs2736100 with Epidemiologic Factors in the Prediction of Lung Cancer Susceptibility.

    Science.gov (United States)

    Wang, Xu; Ma, Kewei; Chi, Lumei; Cui, Jiuwei; Jin, Lina; Hu, Ji-Fan; Li, Wei

    2016-01-01

    Genetic variants from a considerable number of susceptibility loci have been identified in association with cancer risk, but their interaction with epidemiologic factors in lung cancer remains to be defined. We sought to establish a forecasting model for identifying individuals with high-risk of lung cancer by combing gene single-nucleotide polymorphisms with epidemiologic factors. Genotyping and clinical data from 500 lung cancer cases and 500 controls were used for developing the logistic regression model. We found that lung cancer was associated with telomerase reverse transcriptase (TERT) rs2736100 single-nucleotide polymorphism. The TERT rs2736100 model was still significantly associated with lung cancer risk when combined with environmental and lifestyle factors, including lower education, lower BMI, COPD history, heavy cigarettes smoking, heavy cooking emission, and dietary factors (over-consumption of meat and deficiency in fish/shrimp, vegetables, dairy products, and soybean products). These data suggest that combining TERT SNP and epidemiologic factors may be a useful approach to discriminate high and low-risk individuals for lung cancer.

  9. Postnatal visual deprivation in rats regulates several retinal genes and proteins, including differentiation-associated fibroblast growth factor-2.

    Science.gov (United States)

    Prokosch-Willing, Verena; Meyer zu Hoerste, Melissa; Mertsch, Sonja; Stupp, Tobias; Thanos, Solon

    2015-01-01

    Little is known about the retinal cellular basis of amblyopia, which is a developmental disease characterized by impaired visual acuity. This study examined the retinal transcripts associated with experimentally induced unilateral amblyopia in rats. Surgical tarsorrhaphy of the eyelids on one side was performed in pups prior to eye opening at postnatal day 14, thereby preventing any visual experience. This condition was maintained for over 2 months, after which electroretinograms (ERGs) were recorded, the retinal ganglion cell (RGC) arrangement and number were determined using neuroanatomical tracing, the retinal transcripts were studied using microarray analysis, regulated mRNAs were confirmed with quantitative reverse-transcriptase PCR, and proteins were stained using Western blotting and immunohistochemistry. An attenuated ERG was found in eyes that were deprived of visual experience. Retrograde neuroanatomical staining disclosed a larger number of RGCs within the retina on the visually deprived side compared to the non-deprived, control side, and a multilayered distribution of RGCs. At the retinomic level, several transcripts associated with retinal differentiation, such as fibroblast growth factor 2 (FGF-2), were either up- or downregulated. Most of the transcripts could be verified at the mRNA level. To unravel the role of a differentiation-associated protein, we tested FGF-2 in dissociated postnatal retinal cell cultures and found that FGF-2 is a potent factor triggering ganglion cell differentiation. The data suggest that visual experience shapes the postnatal retinal differentiation, whereas visual deprivation induces changes at the functional, cellular and molecular levels within the retina.

  10. Broadening the etiological discourse on Alzheimer's disease to include trauma and posttraumatic stress disorder as psychosocial risk factors.

    Science.gov (United States)

    Burnes, David P R; Burnette, Denise

    2013-08-01

    Biomedical perspectives have long dominated research on the etiology and progression of Alzheimer's disease (AD); yet these approaches do not solely explain observed variations in individual AD trajectories. More robust biopsychosocial models regard the course of AD as a dialectical interplay of neuropathological and psychosocial influences. Drawing on this broader conceptualization, we conducted an extensive review of empirical and theoretical literature on the associations of trauma, posttraumatic stress disorder (PTSD) and AD to develop a working model that conceptualizes the role of psychosocial stressors and physiological mechanisms in the onset and course of AD. The proposed model suggests two pathways. In the first, previous life trauma acts as a risk factor for later-life onset of AD, either directly or mediated by PTSD or PTSD correlates. In the second, de novo AD experiential trauma is associated with accelerated cognitive decline, either directly or mediated through PTSD or PTSD correlates. Evidence synthesized in this paper indicates that previous life trauma and PTSD are strong candidates as psychosocial risk factors for AD and warrant further empirical scrutiny. Psychosocial and neurological-based intervention implications are discussed. A biopsychosocial approach has the capacity to enhance understanding of individual AD trajectories, moving the field toward 'person-centered' models of care.

  11. Splicing factors act as genetic modulators of TDP-43 production in a new autoregulatory TDP-43 Drosophila model.

    Science.gov (United States)

    Pons, Marine; Miguel, Laetitia; Miel, Camille; Avequin, Tracey; Juge, François; Frebourg, Thierry; Campion, Dominique; Lecourtois, Magalie

    2017-09-01

    TDP-43 is a critical RNA-binding factor associated with RNA metabolism. In the physiological state, maintaining normal TDP-43 protein levels is critical for proper physiological functions of the cells. As such, TDP-43 expression is tightly regulated through an autoregulatory negative feedback loop. TDP-43 is a major disease-causing protein in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). Several studies argue for a pathogenic role of elevated TDP-43 levels in these disorders. Modulating the cycle of TDP-43 production might therefore provide a new therapeutic strategy. In this study, we developed a new transgenic Drosophila model mimicking the TDP-43 autoregulatory feedback loop in order to identify genetic modulators of TDP-43 protein steady-state levels in vivo. First, we showed that our TDP-43_TDPBR Drosophila model recapitulates key features of the TDP-43 autoregulatory processes previously described in mammalian and cellular models, namely alternative splicing events, differential usage of polyadenylation sites, nuclear retention of the transcript and a decrease in steady-state mRNA levels. Using this new Drosophila model, we identified several splicing factors, including SF2, Rbp1 and Sf3b1, as genetic modulators of TDP-43 production. Interestingly, our data indicate that these three RNA-binding proteins regulate TDP-43 protein production, at least in part, by controlling mRNA steady-state levels. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Association between intake of dairy products and short-term memory with and without adjustment for genetic and family environmental factors: A twin study.

    Science.gov (United States)

    Ogata, Soshiro; Tanaka, Haruka; Omura, Kayoko; Honda, Chika; Hayakawa, Kazuo

    2016-04-01

    Previous studies have indicated associations between intake of dairy products and better cognitive function and reduced risk of dementia. However, these studies did not adjust for genetic and family environmental factors that may influence food intake, cognitive function, and metabolism of dairy product nutrients. In the present study, we investigated the association between intake of dairy products and short-term memory with and without adjustment for almost all genetic and family environmental factors using a genetically informative sample of twin pairs. A cross-sectional study was conducted among twin pairs aged between 20 and 74. Short-term memory was assessed as primary outcome variable, intake of dairy products was analyzed as the predictive variable, and sex, age, education level, marital status, current smoking status, body mass index, dietary alcohol intake, and medical history of hypertension or diabetes were included as possible covariates. Generalized estimating equations (GEE) were performed by treating twins as individuals and regression analyses were used to identify within-pair differences of a twin pair to adjust for genetic and family environmental factors. Data are reported as standardized coefficients and 95% confidence intervals (CI). Analyses were performed on data from 78 men and 278 women. Among men, high intake of dairy products was significantly associated with better short-term memory after adjustment for the possible covariates (standardized coefficients = 0.22; 95% CI, 0.06-0.38) and almost all genetic and family environmental factors (standardized coefficients = 0.38; 95% CI, 0.07-0.69). Among women, no significant associations were found between intake of dairy products and short-term memory. Subsequent sensitivity analyses were adjusted for small samples and showed similar results. Intake of dairy product may prevent cognitive declines regardless of genetic and family environmental factors in men. Copyright © 2015 Elsevier Ltd

  13. Complex analysis of Askaryan radiation: A fully analytic treatment including the LPM effect and Cascade Form Factor

    Science.gov (United States)

    Hanson, Jordan C.; Connolly, Amy L.

    2017-05-01

    The Askaryan effect describes coherent electromagnetic radiation from high-energy cascades in dense media with a collective charge. We present an analytic model of Askaryan radiation that accounts simultaneously for the three-dimensional form factor of the cascade, and quantum mechanical cascade elongation via the Landau-Pomeranchuk-Migdal effect. These calculations, and the associated open-source code, allow the user to avoid computationally intensive Monte Carlo cascade simulations. Searches for cosmogenic neutrinos in Askaryan-based detectors benefit from computational speed, because scans of Askaryan parameter-space are required to match neutrino signals. The Askaryan field is derived from cascade equations verified with Geant4 simulations, and compared with prior numerical and semi-analytic calculations. Finally, instructive cases of the model are transformed from the Fourier domain to the time-domain. Next-generation in situ detectors like ARA and ARIANNA can use analytic time-domain signal models to search for correlations with event candidates.

  14. Complex Analysis of Askaryan Radiation: A Fully Analytic Treatment including the LPM effect and Cascade Form Factor

    CERN Document Server

    Hanson, Jordan C

    2016-01-01

    The Askaryan effect describes coherent electromagnetic radiation from the collective charge within high-energy cascades in dense media. We present the first fully analytic model of Askaryan radiation that accounts simultaneously for the three-dimensional form factor of the electromagnetic cascade and the Landau-Pomeranchuk-Migdal (LPM) effect. Analytic calculations avoid computationally intensive Monte Carlo simulations of the cascades. Searches for cosmogenic neutrinos in Askaryan- based detectors benefit from computational speed, because neutrino event parameters affect the shape of the electromagnetic field, requiring scans of parameter space. The Askaryan field is derived and verified against Geant4 simulations, and compared with prior numerical and semi-analytic calculations. Finally, two special cases of the model are transformed from the Fourier domain to the time-domain, analytically. Next-generation in situ detectors like ARA and ARIANNA can use analytic time-domain signal models to search for phase ...

  15. Etiology of Waldenström macroglobulinemia: genetic factors and immune-related conditions.

    Science.gov (United States)

    Manasanch, Elisabet E; Kristinsson, Sigurdur Y; Landgren, Ola

    2013-04-01

    Epidemiologic studies provide an insight into the etiology of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, which indicates that repetitive immune stimulation and genetic factors play an important role. Here, the current understanding on the causes of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia are reviewed. Recent studies of the literature are discussed, and future population-based studies are proposed to further elucidate the molecular mechanisms that underlie these associations. Finally, the clinical implications of these data are outlined, and perspectives on clinical follow-up and counseling are provided.

  16. Genetic structure in the seabuckthorn carpenter moth (Holcocerus hippophaecolus in China: the role of outbreak events, geographical and host factors.

    Directory of Open Access Journals (Sweden)

    Jing Tao

    Full Text Available Understanding factors responsible for structuring genetic diversity is of fundamental importance in evolutionary biology. The seabuckthorn carpenter moth (Holcocerus hippophaecolus Hua is a native species throughout the north of China and is considered the main threat to seabuckthorn, Hippophae rhamnoides L. We assessed the influence of outbreaks, environmental factors and host species in shaping the genetic variation and structure of H. hippophaecolus by using Amplified Fragment Length Polymorphism (AFLP markers. We rejected the hypothesis that outbreak-associated genetic divergence exist, as evidenced by genetic clusters containing a combination of populations from historical outbreak areas, as well as non-outbreak areas. Although a small number of markers (4 of 933 loci were identified as candidates under selection in response to population densities. H. hippophaecolus also did not follow an isolation-by-distance pattern. We rejected the hypothesis that outbreak and drought events were driving the genetic structure of H. hippophaecolus. Rather, the genetic structure appears to be influenced by various confounding bio-geographical factors. There were detectable genetic differences between H. hippophaecolus occupying different host trees from within the same geographic location. Host-associated genetic divergence should be confirmed by further investigation.

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

    Science.gov (United States)

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

    2007-04-01

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

  18. Effect of genetic variants related to lipid metabolism as risk factors for cholelithiasis after bariatric surgery in Brazilian population.

    Science.gov (United States)

    Pinheiro-Júnior, Sidney; Pinhel, Marcela A S; Nakazone, Marcelo A; Pinheiro, Anielli; Amorim, Gisele F S; Florim, Greiciane M S; Mazeti, Camila M; Gregório, Michele L; Moschetta, Marina G; Brito, Gilberto B; Brienze, Sérgio L A; Nonino, Carla B; Brandão, Antonio C; Souza, Dorotéia R S

    2012-04-01

    The manifestation of cholelithiasis after bariatric surgery may depend on genetic factors related to lipid metabolism, including apolipoprotein E (APOE) and cholesteryl ester transfer protein (CETP) gene polymorphisms. We investigated the association between APOE HhaI and CETP TaqIB polymorphisms [PCR-RFLP] and occurrence of cholelithiasis over up to 8 months of follow-up after gastroplasty to Roux-en-Y gastric bypass in 220 patients distributed in Group 1 (G1) 114 with cholelithiasis postoperatively and Group 2 (G2) 106 without cholelithiasis, including biochemical and anthropometric profiles analyses. In our series, the allelic and genotypic distributions of CETP TaqIB and APOE HhaI polymorphisms were similar in both groups (P > 0.05). The subgroup analysis evidenced that 54% of the patients from G1, APOE*4 allele carriers compared with APOE*3/3 carriers, presented altered low-density lipoprotein cholesterol (LDL cholesterol) serum levels (P = 0.022) before bariatric surgery. The B1 allele for CETP was associated to more quickly elevation of HDL cholesterol levels just in individuals without cholelitiasis (P cholelithiasis was not associated with altered lipid profile. The CETP TaqIB and APOE HhaI polymorphisms do not seem to have association with gallstones in the late postoperative bariatric surgery, considering that these genetic variants do not differ subgroups of patients who are eligible to routine prophylactic cholecystectomy, at least in Brazilian population.

  19. Genetic risk factors for cerebrovascular disease in children with sickle cell disease: design of a case-control association study and genomewide screen

    Directory of Open Access Journals (Sweden)

    Brambilla Donald

    2003-07-01

    Full Text Available Abstract Background The phenotypic heterogeneity of sickle cell disease is likely the result of multiple genetic factors and their interaction with the sickle mutation. High transcranial doppler (TCD velocities define a subgroup of children with sickle cell disease who are at increased risk for developing ischemic stroke. The genetic factors leading to the development of a high TCD velocity (i.e. cerebrovascular disease and ultimately to stroke are not well characterized. Methods We have designed a case-control association study to elucidate the role of genetic polymorphisms as risk factors for cerebrovascular disease as measured by a high TCD velocity in children with sickle cell disease. The study will consist of two parts: a candidate gene study and a genomewide screen and will be performed in 230 cases and 400 controls. Cases will include 130 patients (TCD ≥ 200 cm/s randomized in the Stroke Prevention Trial in Sickle Cell Anemia (STOP study as well as 100 other patients found to have high TCD in STOP II screening. Four hundred sickle cell disease patients with a normal TCD velocity (TCD Discussion It is expected that this study will yield important information on genetic risk factors for the cerebrovascular disease phenotype in sickle cell disease by clarifying the role of candidate genes in the development of high TCD. The genomewide screen for a large number of SNPs may uncover the association of novel polymorphisms with cerebrovascular disease and stroke in sickle cell disease.

  20. Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

    DEFF Research Database (Denmark)

    Randall, Joshua C; Winkler, Thomas W; Kutalik, Zoltán

    2013-01-01

    Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,72...

  1. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

    NARCIS (Netherlands)

    Randall, Joshua C; Winkler, Thomas W; Kutalik, Zoltán; Berndt, Sonja I; Jackson, Anne U; Monda, Keri L; Kilpeläinen, Tuomas O; Esko, Tõnu; Mägi, Reedik; Li, Shengxu; Workalemahu, Tsegaselassie; Feitosa, Mary F; Croteau-Chonka, Damien C; Day, Felix R; Fall, Tove; Ferreira, Teresa; Gustafsson, Stefan; Locke, Adam E; Mathieson, Iain; Scherag, Andre; Vedantam, Sailaja; Wood, Andrew R; Liang, Liming; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Dermitzakis, Emmanouil T; Dimas, Antigone S; Karpe, Fredrik; Min, Josine L; Nicholson, George; Clegg, Deborah J; Person, Thomas; Krohn, Jon P; Bauer, Sabrina; Buechler, Christa; Eisinger, Kristina; Bonnefond, Amélie; Froguel, Philippe; Hottenga, Jouke-Jan; Prokopenko, Inga; Waite, Lindsay L; Harris, Tamara B; Smith, Albert Vernon; Shuldiner, Alan R; McArdle, Wendy L; Caulfield, Mark J; Munroe, Patricia B; Grönberg, Henrik; Chen, Yii-Der Ida; Li, Guo; Beckmann, Jacques S; Johnson, Toby; Thorsteinsdottir, Unnur; Teder-Laving, Maris; Khaw, Kay-Tee; Wareham, Nicholas J; Zhao, Jing Hua; Amin, Najaf; Oostra, Ben A; Kraja, Aldi T; Province, Michael A; Cupples, L Adrienne; Heard-Costa, Nancy L; Kaprio, Jaakko; Ripatti, Samuli; Surakka, Ida; Collins, Francis S; Saramies, Jouko; Tuomilehto, Jaakko; Jula, Antti; Salomaa, Veikko; Erdmann, Jeanette; Hengstenberg, Christian; Loley, Christina; Schunkert, Heribert; Lamina, Claudia; Wichmann, H Erich; Albrecht, Eva; Gieger, Christian; Hicks, Andrew A; Johansson, Asa; Pramstaller, Peter P; Kathiresan, Sekar; Speliotes, Elizabeth K; Penninx, Brenda; Hartikainen, Anna-Liisa; Jarvelin, Marjo-Riitta; Gyllensten, Ulf; Boomsma, Dorret I; Campbell, Harry; Wilson, James F; Chanock, Stephen J; Farrall, Martin; Goel, Anuj; Medina-Gomez, Carolina; Rivadeneira, Fernando; Estrada, Karol; Uitterlinden, André G; Hofman, Albert; Zillikens, M Carola; den Heijer, Martin; Kiemeney, Lambertus A; Maschio, Andrea; Hall, Per; Tyrer, Jonathan; Teumer, Alexander; Völzke, Henry; Kovacs, Peter; Tönjes, Anke; Mangino, Massimo; Spector, Tim D; Hayward, Caroline; Rudan, Igor; Hall, Alistair S; Samani, Nilesh J; Attwood, Antony Paul; Sambrook, Jennifer G; Hung, Joseph; Palmer, Lyle J; Lokki, Marja-Liisa; Sinisalo, Juha; Boucher, Gabrielle; Huikuri, Heikki; Lorentzon, Mattias; Ohlsson, Claes; Eklund, Niina; Eriksson, Johan G; Barlassina, Cristina; Rivolta, Carlo; Nolte, Ilja M; Snieder, Harold; Van der Klauw, Melanie M; Van Vliet-Ostaptchouk, Jana V; Gejman, Pablo V; Shi, Jianxin; Jacobs, Kevin B; Wang, Zhaoming; Bakker, Stephan J L; Mateo Leach, Irene; Navis, Gerjan; van der Harst, Pim; Martin, Nicholas G; Medland, Sarah E; Montgomery, Grant W; Yang, Jian; Chasman, Daniel I; Ridker, Paul M; Rose, Lynda M; Lehtimäki, Terho; Raitakari, Olli; Absher, Devin; Iribarren, Carlos; Basart, Hanneke; Hovingh, Kees G; Hyppönen, Elina; Power, Chris; Anderson, Denise; Beilby, John P; Hui, Jennie; Jolley, Jennifer; Sager, Hendrik; Bornstein, Stefan R; Schwarz, Peter E H; Kristiansson, Kati; Perola, Markus; Lindström, Jaana; Swift, Amy J; Uusitupa, Matti; Atalay, Mustafa; Lakka, Timo A; Rauramaa, Rainer; Bolton, Jennifer L; Fowkes, Gerry; Fraser, Ross M; Price, Jackie F; Fischer, Krista; Krjutå Kov, Kaarel; Metspalu, Andres; Mihailov, Evelin; Langenberg, Claudia; Luan, Jian'an; Ong, Ken K; Chines, Peter S; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Edkins, Sarah; Franks, Paul W; Hallmans, Göran; Shungin, Dmitry; Morris, Andrew David; Palmer, Colin N A; Erbel, Raimund; Moebus, Susanne; Nöthen, Markus M; Pechlivanis, Sonali; Hveem, Kristian; Narisu, Narisu; Hamsten, Anders; Humphries, Steve E; Strawbridge, Rona J; Tremoli, Elena; Grallert, Harald; Thorand, Barbara; Illig, Thomas; Koenig, Wolfgang; Müller-Nurasyid, Martina; Peters, Annette; Boehm, Bernhard O; Kleber, Marcus E; März, Winfried; Winkelmann, Bernhard R; Kuusisto, Johanna; Laakso, Markku; Arveiler, Dominique; Cesana, Giancarlo; Kuulasmaa, Kari; Virtamo, Jarmo; Yarnell, John W G; Kuh, Diana; Wong, Andrew; Lind, Lars; de Faire, Ulf; Gigante, Bruna; Magnusson, Patrik K E; Pedersen, Nancy L; Dedoussis, George; Dimitriou, Maria; Kolovou, Genovefa; Kanoni, Stavroula; Stirrups, Kathleen; Bonnycastle, Lori L; Njølstad, Inger; Wilsgaard, Tom; Ganna, Andrea; Rehnberg, Emil; Hingorani, Aroon; Kivimaki, Mika; Kumari, Meena; Assimes, Themistocles L; Barroso, Inês; Boehnke, Michael; Borecki, Ingrid B; Deloukas, Panos; Fox, Caroline S; Frayling, Timothy; Groop, Leif C; Haritunians, Talin; Hunter, David; Ingelsson, Erik; Kaplan, Robert; Mohlke, Karen L; O'Connell, Jeffrey R; Schlessinger, David; Strachan, David P; Stefansson, Kari; van Duijn, Cornelia M; Abecasis, Gonçalo R; McCarthy, Mark I; Hirschhorn, Joel N; Qi, Lu; Loos, Ruth J F; Lindgren, Cecilia M; North, Kari E; Heid, Iris M

    2013-01-01

    Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 i

  2. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

    NARCIS (Netherlands)

    Randall, Joshua C; Winkler, Thomas W; Kutalik, Zoltán; Berndt, Sonja I; Jackson, Anne U; Monda, Keri L; Kilpeläinen, Tuomas O; Esko, Tõnu; Mägi, Reedik; Li, Shengxu; Workalemahu, Tsegaselassie; Feitosa, Mary F; Croteau-Chonka, Damien C; Day, Felix R; Fall, Tove; Ferreira, Teresa; Gustafsson, Stefan; Locke, Adam E; Mathieson, Iain; Scherag, Andre; Vedantam, Sailaja; Wood, Andrew R; Liang, Liming; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Dermitzakis, Emmanouil T; Dimas, Antigone S; Karpe, Fredrik; Min, Josine L; Nicholson, George; Clegg, Deborah J; Person, Thomas; Krohn, Jon P; Bauer, Sabrina; Buechler, Christa; Eisinger, Kristina; Bonnefond, Amélie; Froguel, Philippe; Hottenga, Jouke-Jan; Prokopenko, Inga; Waite, Lindsay L; Harris, Tamara B; Smith, Albert Vernon; Shuldiner, Alan R; McArdle, Wendy L; Caulfield, Mark J; Munroe, Patricia B; Grönberg, Henrik; Chen, Yii-Der Ida; Li, Guo; Beckmann, Jacques S; Johnson, Toby; Thorsteinsdottir, Unnur; Teder-Laving, Maris; Khaw, Kay-Tee; Wareham, Nicholas J; Zhao, Jing Hua; Amin, Najaf; Oostra, Ben A; Kraja, Aldi T; Province, Michael A; Cupples, L Adrienne; Heard-Costa, Nancy L; Kaprio, Jaakko; Ripatti, Samuli; Surakka, Ida; Collins, Francis S; Saramies, Jouko; Tuomilehto, Jaakko; Jula, Antti; Salomaa, Veikko; Erdmann, Jeanette; Hengstenberg, Christian; Loley, Christina; Schunkert, Heribert; Lamina, Claudia; Wichmann, H Erich; Albrecht, Eva; Gieger, Christian; Hicks, Andrew A; Johansson, Asa; Pramstaller, Peter P; Kathiresan, Sekar; Speliotes, Elizabeth K; Penninx, Brenda; Hartikainen, Anna-Liisa; Jarvelin, Marjo-Riitta; Gyllensten, Ulf; Boomsma, Dorret I; Campbell, Harry; Wilson, James F; Chanock, Stephen J; Farrall, Martin; Goel, Anuj; Medina-Gomez, Carolina; Rivadeneira, Fernando; Estrada, Karol; Uitterlinden, André G; Hofman, Albert; Zillikens, M Carola; den Heijer, Martin; Kiemeney, Lambertus A; Maschio, Andrea; Hall, Per; Tyrer, Jonathan; Teumer, Alexander; Völzke, Henry; Kovacs, Peter; Tönjes, Anke; Mangino, Massimo; Spector, Tim D; Hayward, Caroline; Rudan, Igor; Hall, Alistair S; Samani, Nilesh J; Attwood, Antony Paul; Sambrook, Jennifer G; Hung, Joseph; Palmer, Lyle J; Lokki, Marja-Liisa; Sinisalo, Juha; Boucher, Gabrielle; Huikuri, Heikki; Lorentzon, Mattias; Ohlsson, Claes; Eklund, Niina; Eriksson, Johan G; Barlassina, Cristina; Rivolta, Carlo; Nolte, Ilja M; Snieder, Harold; Van der Klauw, Melanie M; Van Vliet-Ostaptchouk, Jana V; Gejman, Pablo V; Shi, Jianxin; Jacobs, Kevin B; Wang, Zhaoming; Bakker, Stephan J L; Mateo Leach, Irene; Navis, Gerjan; van der Harst, Pim; Martin, Nicholas G; Medland, Sarah E; Montgomery, Grant W; Yang, Jian; Chasman, Daniel I; Ridker, Paul M; Rose, Lynda M; Lehtimäki, Terho; Raitakari, Olli; Absher, Devin; Iribarren, Carlos; Basart, Hanneke; Hovingh, Kees G; Hyppönen, Elina; Power, Chris; Anderson, Denise; Beilby, John P; Hui, Jennie; Jolley, Jennifer; Sager, Hendrik; Bornstein, Stefan R; Schwarz, Peter E H; Kristiansson, Kati; Perola, Markus; Lindström, Jaana; Swift, Amy J; Uusitupa, Matti; Atalay, Mustafa; Lakka, Timo A; Rauramaa, Rainer; Bolton, Jennifer L; Fowkes, Gerry; Fraser, Ross M; Price, Jackie F; Fischer, Krista; Krjutå Kov, Kaarel; Metspalu, Andres; Mihailov, Evelin; Langenberg, Claudia; Luan, Jian'an; Ong, Ken K; Chines, Peter S; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Edkins, Sarah; Franks, Paul W; Hallmans, Göran; Shungin, Dmitry; Morris, Andrew David; Palmer, Colin N A; Erbel, Raimund; Moebus, Susanne; Nöthen, Markus M; Pechlivanis, Sonali; Hveem, Kristian; Narisu, Narisu; Hamsten, Anders; Humphries, Steve E; Strawbridge, Rona J; Tremoli, Elena; Grallert, Harald; Thorand, Barbara; Illig, Thomas; Koenig, Wolfgang; Müller-Nurasyid, Martina; Peters, Annette; Boehm, Bernhard O; Kleber, Marcus E; März, Winfried; Winkelmann, Bernhard R; Kuusisto, Johanna; Laakso, Markku; Arveiler, Dominique; Cesana, Giancarlo; Kuulasmaa, Kari; Virtamo, Jarmo; Yarnell, John W G; Kuh, Diana; Wong, Andrew; Lind, Lars; de Faire, Ulf; Gigante, Bruna; Magnusson, Patrik K E; Pedersen, Nancy L; Dedoussis, George; Dimitriou, Maria; Kolovou, Genovefa; Kanoni, Stavroula; Stirrups, Kathleen; Bonnycastle, Lori L; Njølstad, Inger; Wilsgaard, Tom; Ganna, Andrea; Rehnberg, Emil; Hingorani, Aroon; Kivimaki, Mika; Kumari, Meena; Assimes, Themistocles L; Barroso, Inês; Boehnke, Michael; Borecki, Ingrid B; Deloukas, Panos; Fox, Caroline S; Frayling, Timothy; Groop, Leif C; Haritunians, Talin; Hunter, David; Ingelsson, Erik; Kaplan, Robert; Mohlke, Karen L; O'Connell, Jeffrey R; Schlessinger, David; Strachan, David P; Stefansson, Kari; van Duijn, Cornelia M; Abecasis, Gonçalo R; McCarthy, Mark I; Hirschhorn, Joel N; Qi, Lu; Loos, Ruth J F; Lindgren, Cecilia M; North, Kari E; Heid, Iris M

    Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723

  3. Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD Collaborative Genetics Study.

    Science.gov (United States)

    Hasler, Gregor; Pinto, Anthony; Greenberg, Benjamin D; Samuels, Jack; Fyer, Abby J; Pauls, David; Knowles, James A; McCracken, James T; Piacentini, John; Riddle, Mark A; Rauch, Scott L; Rasmussen, Steven A; Willour, Virginia L; Grados, Marco A; Cullen, Bernadette; Bienvenu, O Joseph; Shugart, Yin-Yao; Liang, Kung-Yee; Hoehn-Saric, Rudolf; Wang, Ying; Ronquillo, Jonne; Nestadt, Gerald; Murphy, Dennis L

    2007-03-01

    Identification of familial, more homogenous characteristics of obsessive-compulsive disorder (OCD) may help to define relevant subtypes and increase the power of genetic and neurobiological studies of OCD. While factor-analytic studies have found consistent, clinically meaningful OCD symptom dimensions, there have been only limited attempts to evaluate the familiality and potential genetic basis of such dimensions. Four hundred eighteen sibling pairs with OCD were evaluated using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist and Severity scales. After controlling for sex, age, and age of onset, robust sib-sib intraclass correlations were found for two of the four YBOCS factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I (aggressive, sexual, and religious obsessions, and checking compulsions; p = .002). Smaller, but still significant, familiality was found for Factor III (contamination/cleaning; p = .02) and Factor II (symmetry/ordering/arranging; p = .04). Limiting the sample to female subjects more than doubled the familiality estimates for Factor II (p = .003). Among potentially relevant comorbid conditions for genetic studies, bipolar I/II and major depressive disorder were strongly associated with Factor I (p < .001), whereas ADHD, alcohol dependence, and bulimia were associated with Factor II (p < .01). Factor-analyzed OCD symptom dimensions in sibling pairs with OCD are familial with some gender-dependence, exhibit relatively specific relationships to comorbid psychiatric disorders and thus may be useful as refined phenotypes for molecular genetic studies of OCD.

  4. Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study

    Science.gov (United States)

    Ibáñez-Sanz, Gemma; Díez-Villanueva, Anna; Alonso, M. Henar; Rodríguez-Moranta, Francisco; Pérez-Gómez, Beatriz; Bustamante, Mariona; Martin, Vicente; Llorca, Javier; Amiano, Pilar; Ardanaz, Eva; Tardón, Adonina; Jiménez-Moleón, Jose J.; Peiró, Rosana; Alguacil, Juan; Navarro, Carmen; Guinó, Elisabet; Binefa, Gemma; Navarro, Pablo Fernández; Espinosa, Anna; Dávila-Batista, Verónica; Molina, Antonio José; Palazuelos, Camilo; Castaño-Vinyals, Gemma; Aragonés, Nuria; Kogevinas, Manolis; Pollán, Marina; Moreno, Victor

    2017-01-01

    Colorectal cancer (CRC) screening of the average risk population is only indicated according to age. We aim to elaborate a model to stratify the risk of CRC by incorporating environmental data and single nucleotide polymorphisms (SNP). The MCC-Spain case-control study included 1336 CRC cases and 2744 controls. Subjects were interviewed on lifestyle factors, family and medical history. Twenty-one CRC susceptibility SNPs were genotyped. The environmental risk model, which included alcohol consumption, obesity, physical activity, red meat and vegetable consumption, and nonsteroidal anti-inflammatory drug use, contributed to CRC with an average per factor OR of 1.36 (95% CI 1.27 to 1.45). Family history of CRC contributed an OR of 2.25 (95% CI 1.87 to 2.72), and each additional SNP contributed an OR of 1.07 (95% CI 1.04 to 1.10). The risk of subjects with more than 25 risk alleles (5th quintile) was 82% higher (OR 1.82, 95% CI 1.11 to 2.98) than subjects with less than 19 alleles (1st quintile). This risk model, with an AUROC curve of 0.63 (95% CI 0.60 to 0.66), could be useful to stratify individuals. Environmental factors had more weight than the genetic score, which should be considered to encourage patients to achieve a healthier lifestyle. PMID:28233817

  5. Assessing educational priorities in genetics for general practitioners and specialists in five countries: factor structure of the Genetic-Educational Priorities (Gen-EP) scale.

    NARCIS (Netherlands)

    Calefato, J.M.; Nippert, I.; Harris, H.J.; Kristoffersson, U.; Schmidtke, J.; Kate, L.P. ten; Anionwu, E.; Benjamin, C.; Challen, K.; Plass, A.M.; Harris, R.; Julian-Reynier, C.

    2008-01-01

    Purpose: A scale assessing primary care physicians' priorities for genetic education (The Gen-EP scale) was developed and tested in five European countries. The objective of this study was to determine its factor structure, to test scaling assumptions and to determine internal consistency. Methods:

  6. The role of molecular genetic factors in age-related macular degeneration.

    Science.gov (United States)

    Almeida, Luciana Negrão Frota de; Carolino, Rachel Melilo; Sperandio, Diogo Cazelli; Nehemy, Márcio Bittar; De Marco, L A

    2009-01-01

    Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Although the etiology of AMD remains largely unknown, numerous studies have suggested that both genes and environmental risk factors significantly influence the risk of developing AMD. Recently, single nucleotide polymorphisms, DNA sequence variations found within the complement factor H (CFH) gene, have been found to be strongly associated with the development of AMD. Several other genes have had at least one positive association finding and deserve further exploration. The purpose of this review is to provide an extensive report of the current data of AMD genetics and the contribution of this knowledge helps to the better understanding of its pathophysiology.

  7. Influence of Space Flight Factors on the Genetic Properties of Streptomyces Lividans 66 (PIJ702)

    Science.gov (United States)

    Tabakov, V. Yu.; Voeikova, T. A.; Tairbekov, M. G.; Goins, T. L.; Martinson, V. G.; Pyle, B. H.

    2006-01-01

    Gram-positive Streptomyces bacteria display genetic instability in response to external factors. Strain S. lividans 66 harbors the multicopy plasmid pIJ702 with selective and differential marker genes for antibiotic thiostrepton resistance and melanin production. Culture plates of modified ISP agar medium with and without thiostrepton were flown on Foton-M2. Suboptimal flight temperatures, which were simulated for asynchronous ground controls, resulted in slow growth and failure to differentiate and sporulate. Flight samples and asynchronous controls showed a high frequency of failing to express plasmid markers compared to laboratory controls. This was associated with loss of plasmid DNA and likely resulted from suboptimal temperatures for flight cultures and controls. Neither restriction fragment length polymorphism, nor polymerase chain reaction amplification coupled with denaturing gradient gel electrophoresis, revealed differences between pIJ702 DNA from flight vs. control clones. Mutations of the plasmid marker genes resulting from specific spaceflight factors, e.g., microgravity and radiation, were not detected.

  8. Interaction of genetic and exposure factors in the prevalence of berylliosis.

    Science.gov (United States)

    Richeldi, L; Kreiss, K; Mroz, M M; Zhen, B; Tartoni, P; Saltini, C

    1997-10-01

    Prevalence of berylliosis, a lung disorder driven by the activation of beryllium-specific T cells, is associated with a major histocompatibility complex (MHC) class II marker (HLA-DPB1Glu69) and with the type of industrial exposure. We evaluated the interaction between marker and exposure in a beryllium-exposed population in which the prevalence of berylliosis was associated with machining beryllium. The presence of the marker was associated with higher prevalence (HLA-DPB1Glu69-positive machinists 25%; HLA-DPB1Glu69-negative machinists 3.2%, P = 0.05) and predicted berylliosis independent of machining history (odds ratios 11.8 and 10.1). The study shows that in berylliosis the carrier status of a genetic susceptibility factor adds to the effect of process-related risk factors.

  9. Some Non Genetic Factors Effects on Morphostructural Growth of Local Kids in Tunisian Arid Area

    Directory of Open Access Journals (Sweden)

    Ben Ammar Elgaaied Amel

    2008-01-01

    Full Text Available Data corresponding of 276 local kids` periodic control, harvested during 4 years (2001-2005 under pastoral mode in Tunisian arid region, was used to study some factors effects upon body parts evolution after birth. Morphostructural variables were; body length, height-at-withers and heart girth. The linear measurement periodically registered at every control day from birth and till 5 months age. For each kid, performances were standardized at typical ages; birth, 30, 60, 90, 120 and 150 days. Statistical analysis were achieved by GLM procedure and SNK (a = 5% means comparison test to identify factors effects upon studied variables and the homogeneous classes. The kid`s body parts seem affected (p<0.05 by several environmental factors, sex, type of birth and age of dam. The type of birth and the age of dam exerts a high effect (p<0.01 on all characters after the birth. However, the factors statistical effects depend to the kid`s age. The sex acts differently on the morphometric characters before and afterwards of two month age. Thus, phenotypic individual differences can be elapsed by environmental factors of arid harsh conditions. Such conclusion underlines the necessity to study the particularities of the genetic expression of adapted populations towards restrictive resources.

  10. Clinical and genetic factors associated with suicide in mood disorder patients.

    Science.gov (United States)

    Antypa, Niki; Souery, Daniel; Tomasini, Mario; Albani, Diego; Fusco, Federica; Mendlewicz, Julien; Serretti, Alessandro

    2016-03-01

    Suicidality is a continuum ranging from ideation to attempted and completed suicide, with a complex etiology involving both genetic heritability and environmental factors. The majority of suicide events occur in the context of psychiatric conditions, preeminently major depression and bipolar disorder. The present study investigates clinical factors associated with suicide in a sample of 553 mood disorder patients, recruited within the 'Psy Pluriel' center, Centre Européen de Psychologie Médicale, and the Department of Psychiatry of Erasme Hospital (Brussels). Furthermore, genetic association analyses examining polymorphisms within COMT, BDNF, MAPK1 and CREB1 genes were performed in a subsample of 259 bipolar patients. The presence or absence of a previous suicide attempt and of current suicide risk were assessed. A positive association with suicide attempt was reported for younger patients, females, lower educated, smokers, those with higher scores on depressive symptoms and higher functional disability and those with anxiety comorbidity and familial history of suicidality in first- and second-degree relatives. Anxiety disorder comorbidity was the stronger predictor of current suicide risk. No associations were found with polymorphisms within COMT and BDNF genes, whereas significant associations were found with variations in rs13515 (MAPK1) and rs6740584 (CREB1) polymorphisms. From a clinical perspective, our study proposes several clinical characteristics, such as increased depressive symptomatology, anxiety comorbidity, functional disability and family history of suicidality, as correlates associated with suicide. Genetic risk variants in MAPK1 and CREB1 genes might be involved in a dysregulation of inflammatory and neuroplasticity pathways and are worthy of future investigation.

  11. Variation in salamander tail regeneration is associated with genetic factors that determine tail morphology.

    Directory of Open Access Journals (Sweden)

    Gareth J Voss

    Full Text Available Very little is known about the factors that cause variation in regenerative potential within and between species. Here, we used a genetic approach to identify heritable genetic factors that explain variation in tail regenerative outgrowth. A hybrid ambystomatid salamander (Ambystoma mexicanum x A. andersoni was crossed to an A. mexicanum and 217 offspring were induced to undergo metamorphosis and attain terrestrial adult morphology using thyroid hormone. Following metamorphosis, each salamander's tail tip was amputated and allowed to regenerate, and then amputated a second time and allowed to regenerate. Also, DNA was isolated from all individuals and genotypes were determined for 187 molecular markers distributed throughout the genome. The area of tissue that regenerated after the first and second amputations was highly positively correlated across males and females. Males presented wider tails and regenerated more tail tissue during both episodes of regeneration. Approximately 66-68% of the variation in regenerative outgrowth was explained by tail width, while tail length and genetic sex did not explain a significant amount of variation. A small effect QTL was identified as having a sex-independent effect on tail regeneration, but this QTL was only identified for the first episode of regeneration. Several molecular markers significantly affected regenerative outgrowth during both episodes of regeneration, but the effect sizes were small (<4% and correlated with tail width. The results show that ambysex and minor effect QTL explain variation in adult tail morphology and importantly, tail width. In turn, tail width at the amputation plane largely determines the rate of regenerative outgrowth. Because amputations in this study were made at approximately the same position of the tail, our results resolve an outstanding question in regenerative biology: regenerative outgrowth positively co-varies as a function of tail width at the amputation site.

  12. Variation in salamander tail regeneration is associated with genetic factors that determine tail morphology.

    Science.gov (United States)

    Voss, Gareth J; Kump, D Kevin; Walker, John A; Voss, S Randal

    2013-01-01

    Very little is known about the factors that cause variation in regenerative potential within and between species. Here, we used a genetic approach to identify heritable genetic factors that explain variation in tail regenerative outgrowth. A hybrid ambystomatid salamander (Ambystoma mexicanum x A. andersoni) was crossed to an A. mexicanum and 217 offspring were induced to undergo metamorphosis and attain terrestrial adult morphology using thyroid hormone. Following metamorphosis, each salamander's tail tip was amputated and allowed to regenerate, and then amputated a second time and allowed to regenerate. Also, DNA was isolated from all individuals and genotypes were determined for 187 molecular markers distributed throughout the genome. The area of tissue that regenerated after the first and second amputations was highly positively correlated across males and females. Males presented wider tails and regenerated more tail tissue during both episodes of regeneration. Approximately 66-68% of the variation in regenerative outgrowth was explained by tail width, while tail length and genetic sex did not explain a significant amount of variation. A small effect QTL was identified as having a sex-independent effect on tail regeneration, but this QTL was only identified for the first episode of regeneration. Several molecular markers significantly affected regenerative outgrowth during both episodes of regeneration, but the effect sizes were small (<4%) and correlated with tail width. The results show that ambysex and minor effect QTL explain variation in adult tail morphology and importantly, tail width. In turn, tail width at the amputation plane largely determines the rate of regenerative outgrowth. Because amputations in this study were made at approximately the same position of the tail, our results resolve an outstanding question in regenerative biology: regenerative outgrowth positively co-varies as a function of tail width at the amputation site.

  13. Genetic mapping and comparative expression analysis of transcription factors in cotton.

    Science.gov (United States)

    Chen, Xuemei; Jin, Xin; Li, Ximei; Lin, Zhongxu

    2015-01-01

    Transcription factors (TFs) play an important role in the regulation of plant growth and development. The study of the structure and function of TFs represents a research frontier in plant molecular biology. The findings of these studies will provide significant information regarding genetic improvement traits in crops. Currently, a large number of TFs have been cloned, and their function has been verified. However, relatively few studies that genetically map TFs in cotton are available. To genetically map TFs in cotton in this study, specific primers were designed for TF genes that were published in the Plant Transcription Factor Database. A total of 977 TF primers were obtained, and 31 TF polymorphic loci were mapped on 15 cotton chromosomes. These polymorphic loci were clearly preferentially distributed on chromosomes 5, 11, 19 and 20; and TFs from the same family mapped to homologous cotton chromosomes. In-silico mapping verified that many mapped TFs were mapped on their corresponding chromosomes or their homologous chromosomes' corresponding chromosomes in the diploid genomes. QTL mapping for fiber quality revealed that TF-Ghi005602-2 mapped on Chr19 was associated with fiber length. Eighty-five TF genes were selected for RT-PCR analysis, and 4 TFs were selected for qRT-PCR analysis, revealing unique expression patterns across different stages of fiber development between the mapping parents. Our data offer an overview of the chromosomal distribution of TFs in cotton, and the comparative expression analysis between Gossypium hirsutum and G. barbadense provides a rough understanding of the regulation of TFs during cotton fiber development.

  14. Host genetics and environmental factors regulate ecological succession of the mouse colon tissue-associated microbiota.

    Directory of Open Access Journals (Sweden)

    Philip Smith

    Full Text Available BACKGROUND: The integration of host genetics, environmental triggers and the microbiota is a recognised factor in the pathogenesis of barrier function diseases such as IBD. In order to determine how these factors interact to regulate the host immune response and ecological succession of the colon tissue-associated microbiota, we investigated the temporal interaction between the microbiota and the host following disruption of the colonic epithelial barrier. METHODOLOGY/PRINCIPAL FINDINGS: Oral administration of DSS was applied as a mechanistic model of environmental damage of the colon and the resulting inflammation characterized for various parameters over time in WT and Nod2 KO mice. RESULTS: In WT mice, DSS damage exposed the host to the commensal flora and led to a migration of the tissue-associated bacteria from the epithelium to mucosal and submucosal layers correlating with changes in proinflammatory cytokine profiles and a progressive transition from acute to chronic inflammation of the colon. Tissue-associated bacteria levels peaked at day 21 post-DSS and declined thereafter, correlating with recruitment of innate immune cells and development of the adaptive immune response. Histological parameters, immune cell infiltration and cytokine biomarkers of inflammation were indistinguishable between Nod2 and WT littermates following DSS, however, Nod2 KO mice demonstrated significantly higher tissue-associated bacterial levels in the colon. DSS damage and Nod2 genotype independently regulated the community structure of the colon microbiota. CONCLUSIONS/SIGNIFICANCE: The results of these experiments demonstrate the integration of environmental and genetic factors in the ecological succession of the commensal flora in mammalian tissue. The association of Nod2 genotype (and other host polymorphisms and environmental factors likely combine to influence the ecological succession of the tissue-associated microflora accounting in part for their

  15. Role of genetic and environmental factors in British twins with inflammatory bowel disease.

    Science.gov (United States)

    Ng, Siew C; Woodrow, Susannah; Patel, Nisha; Subhani, Javaid; Harbord, Marcus

    2012-04-01

    Twin studies provide insight into the complex interaction between genetic and environmental factors in the development of inflammatory bowel disease (IBD). We assessed associations between childhood environmental factors and development of Crohn's disease (CD) and ulcerative colitis (UC) in twins. Questionnaires on clinical demographics and exposure to environmental factors were sent to twins with IBD, their healthy co-twins, and their doctors. Kappa statistics were used to examine agreement between twin pairs and odds ratios were calculated by conditional logistic regression. In all, 250 IBD twin pairs (122 CD; 125 UC; 3 CD/UC; 28 concordant pairs) were analyzed. Concordant monozygotic twins with CD showed good agreement for disease location (κ 0.88; 95% confidence interval [CI]: 0.45-1.00), disease behavior (κ 1.00; 95% CI: 0.43-1.00), and moderate agreement for age at diagnosis and need for medical and surgical therapy. Concordant monozygotic twins with UC showed good agreement for disease extent (κ 0.60; CI 0.13-1.00) and use of thiopurines (κ 0.73; CI 0.10-1.00). In discordant twins, symptomatic childhood mumps infection (odds ratio [OR], 3.8; 95% CI, 1.2-11.3) and oral contraceptives (OR, 4.0; 1.1-14.2) were associated with CD. Smoking was associated with CD (OR, 4.3; 95% CI, 1.9-9.8) but inversely associated with UC (OR, 0.3; 95% CI, 0.1-0.9). Both CD and UC twins had suffered more "gastroenteritis" and spent more time with animals than their co-twins. Disease phenotype in CD and disease extent in UC appeared to be genetically influenced. Smoking is a risk factor for CD but is protective for UC. Early exposure to "infections" during childhood may be associated with the development of IBD. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  16. A twin and molecular genetics study of sleep paralysis and associated factors.

    Science.gov (United States)

    Denis, Dan; French, Christopher C; Rowe, Richard; Zavos, Helena M S; Nolan, Patrick M; Parsons, Michael J; Gregory, Alice M

    2015-08-01

    Sleep paralysis is a relatively common but under-researched phenomenon. In this paper we examine prevalence in a UK sample and associations with candidate risk factors. This is the first study to investigate the heritability of sleep paralysis in a twin sample and to explore genetic associations between sleep paralysis and a number of circadian expressed single nucleotide polymorphisms. Analyses are based on data from the Genesis1219 twin/sibling study, a community sample of twins/siblings from England and Wales. In total, data from 862 participants aged 22-32 years (34% male) were used in the study. This sample consisted of monozygotic and dizygotic twins and siblings. It was found that self-reports of general sleep quality, anxiety symptoms and exposure to threatening events were all associated independently with sleep paralysis. There was moderate genetic influence on sleep paralysis (53%). Polymorphisms in the PER2 gene were associated with sleep paralysis in additive and dominant models of inheritance-although significance was not reached once a Bonferroni correction was applied. It is concluded that factors associated with disrupted sleep cycles appear to be associated with sleep paralysis. In this sample of young adults, sleep paralysis was moderately heritable. Future work should examine specific polymorphisms associated with differences in circadian rhythms and sleep homeostasis further in association with sleep paralysis.

  17. Genetic risk factors for longitudinal changes in structural MRI in former organolead workers.

    Science.gov (United States)

    James, Bryan D; Caffo, Brian; Stewart, Walter F; Yousem, David; Davatzikos, Christos; Schwartz, Brian S

    2011-01-01

    This study examined associations between polymorphisms in three genes, apolipoprotein E (APOE), angiotensin converting enzyme (ACE), and vitamin D receptor (VDR), and longitudinal change in brain volumes and white matter lesions (WML) as well as effect modification by cardiovascular factors and tibia lead concentrations. Two MRIs, an average of 5 years apart, were obtained for 317 former organolead workers and 45 population-based controls. Both regions-of-interest and voxel-wise analyses were conducted. APOE ε3/ε4 and ε4/ε4 genotypes were associated with less decline in white matter volumes. There was some evidence of interaction between genetic polymorphisms and cardiovascular risk factors (ACE and high-density lipoprotein; VDR and diabetes) on brain volume decline. The VDR FokI ff genotype was associated with an increase in WML (no association for APOE or ACE). This study expands our understanding of how genetic precursors of dementia and cardiovascular diseases are related to changes in brain structure.

  18. Ecological and genetic factors linked to contrasting genome dynamics in seed plants.

    Science.gov (United States)

    Leitch, A R; Leitch, I J

    2012-05-01

    The large-scale replacement of gymnosperms by angiosperms in many ecological niches over time and the huge disparity in species numbers have led scientists to explore factors (e.g. polyploidy, developmental systems, floral evolution) that may have contributed to the astonishing rise of angiosperm diversity. Here, we explore genomic and ecological factors influencing seed plant genomes. This is timely given the recent surge in genomic data. We compare and contrast the genomic structure and evolution of angiosperms and gymnosperms and find that angiosperm genomes are more dynamic and diverse, particularly amongst the herbaceous species. Gymnosperms typically have reduced frequencies of a number of processes (e.g. polyploidy) that have shaped the genomes of other vascular plants and have alternative mechanisms to suppress genome dynamism (e.g. epigenetics and activity of transposable elements). Furthermore, the presence of several characters in angiosperms (e.g. herbaceous habit, short minimum generation time) has enabled them to exploit new niches and to be viable with small population sizes, where the power of genetic drift can outweigh that of selection. Together these processes have led to increased rates of genetic divergence and faster fixation times of variation in many angiosperms compared with gymnosperms.

  19. Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors

    Science.gov (United States)

    Haziza, Simon; Mohan, Nitin; Loe-Mie, Yann; Lepagnol-Bestel, Aude-Marie; Massou, Sophie; Adam, Marie-Pierre; Le, Xuan Loc; Viard, Julia; Plancon, Christine; Daudin, Rachel; Koebel, Pascale; Dorard, Emilie; Rose, Christiane; Hsieh, Feng-Jen; Wu, Chih-Che; Potier, Brigitte; Herault, Yann; Sala, Carlo; Corvin, Aiden; Allinquant, Bernadette; Chang, Huan-Cheng; Treussart, François; Simonneau, Michel

    2017-05-01

    Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities. Here we report a sensitive method to measure the changes in intraneuronal transport induced by brain-disease-related genetic risk factors using fluorescent nanodiamonds (FNDs). We show that the high brightness, photostability and absence of cytotoxicity allow FNDs to be tracked inside the branches of dissociated neurons with a spatial resolution of 12 nm and a temporal resolution of 50 ms. As proof of principle, we applied the FND tracking assay on two transgenic mouse lines that mimic the slight changes in protein concentration (∼30%) found in the brains of patients. In both cases, we show that the FND assay is sufficiently sensitive to detect these changes.

  20. Total and regional fat distribution is strongly influenced by genetic factors in young and elderly twins

    DEFF Research Database (Denmark)

    Malis, Charlotte; Rasmussen, Eva L; Poulsen, Pernille

    2005-01-01

    OBJECTIVE: Indirect estimates of obesity such as BMI seem to be strongly influenced by genetic factors in twins. Precise measurements of total and regional fat as determined by direct techniques such as DXA scan have only been applied in a few twin studies. The aim of the present study was to est......OBJECTIVE: Indirect estimates of obesity such as BMI seem to be strongly influenced by genetic factors in twins. Precise measurements of total and regional fat as determined by direct techniques such as DXA scan have only been applied in a few twin studies. The aim of the present study...... was to estimate the heritability (h(2)) of total and regional fat distribution in young and elderly Danish twins. RESEARCH METHODS AND PROCEDURES: Monozygotic (108) and dizygotic (88) twins in two age groups (25 to 32 and 58 to 66 years) underwent anthropometric measurements and DXA scans. Intraclass correlations...... and etiologic components of variance were estimated for total and regional fat percentages using biometric modeling. RESULTS: The intraclass correlations demonstrated higher correlations for all fat percentages among monozygotic twins as compared with dizygotic twins. The biometric modeling revealed a major...

  1. A forward genetic screen reveals essential and non-essential RNAi factors in Paramecium tetraurelia.

    Science.gov (United States)

    Marker, Simone; Carradec, Quentin; Tanty, Véronique; Arnaiz, Olivier; Meyer, Eric

    2014-06-01

    In most eukaryotes, small RNA-mediated gene silencing pathways form complex interacting networks. In the ciliate Paramecium tetraurelia, at least two RNA interference (RNAi) mechanisms coexist, involving distinct but overlapping sets of protein factors and producing different types of short interfering RNAs (siRNAs). One is specifically triggered by high-copy transgenes, and the other by feeding cells with double-stranded RNA (dsRNA)-producing bacteria. In this study, we designed a forward genetic screen for mutants deficient in dsRNA-induced silencing, and a powerful method to identify the relevant mutations by whole-genome sequencing. We present a set of 47 mutant alleles for five genes, revealing two previously unknown RNAi factors: a novel Paramecium-specific protein (Pds1) and a Cid1-like nucleotidyl transferase. Analyses of allelic diversity distinguish non-essential and essential genes and suggest that the screen is saturated for non-essential, single-copy genes. We show that non-essential genes are specifically involved in dsRNA-induced RNAi while essential ones are also involved in transgene-induced RNAi. One of the latter, the RNA-dependent RNA polymerase RDR2, is further shown to be required for all known types of siRNAs, as well as for sexual reproduction. These results open the way for the dissection of the genetic complexity, interconnection, mechanisms and natural functions of RNAi pathways in P. tetraurelia.

  2. Effect of yoga practices on pulmonary function tests including transfer factor of lung for carbon monoxide (TLCO) in asthma patients.

    Science.gov (United States)

    Singh, Savita; Soni, Ritu; Singh, K P; Tandon, O P

    2012-01-01

    Prana is the energy, when the self-energizing force embraces the body with extension and expansion and control, it is pranayama. It may affect the milieu at the bronchioles and the alveoli particularly at the alveolo-capillary membrane to facilitate diffusion and transport of gases. It may also increase oxygenation at tissue level. Aim of our study is to compare pulmonary functions and diffusion capacity in patients of bronchial asthma before and after yogic intervention of 2 months. Sixty stable asthmatic-patients were randomized into two groups i.e group 1 (Yoga training group) and group 2 (control group). Each group included thirty patients. Lung functions were recorded on all patients at baseline, and then after two months. Group 1 subjects showed a statistically significant improvement (Pyoga practice. Quality of life also increased significantly. It was concluded that pranayama & yoga breathing and stretching postures are used to increase respiratory stamina, relax the chest muscles, expand the lungs, raise energy levels, and calm the body.

  3. Lifestyle modification induced weight loss and changes of cardiometabolic risk factors including lowering of inflammatory response in obese children.

    Science.gov (United States)

    Motykova, Eva; Zlatohlavek, Lukáš; Prusikova, Martina; Lanska, Vera; Ceska, Richard; Vasickova, Ludmila; Vrablik, Michal

    2011-01-01

    Obesity is associated with increased inflammation which represents a link to atherosclerosis and cardiovascular disease. Lipoprotein associated phospholipase A2 (Lp-PLA2) is an independent marker of inflammation and atherosclerosis risk. To assess the impact of weight loss on metabolic markers of atherosclerosis including Lp-PLA2 we examined a group of Czech non-diabetic obese/overweight children exposed to a lifestyle intervention. Fourty unrelated overweight/obese non-diabetic Czech children (13.7 ± 2.1 years, average BMI at baseline 29.8 ± 2.6 kg/m2) underwent 4 weeks of lifestyle modification (reduction of energy intake to age matched optimum and supervised physical activity). Anthropometrical and biochemical variables were determined at baseline and after the intervention. Lp-PLA2 mass concentration was assessed using the ELISA kit. Wilcocson's rank test and Spearman's correlation were used for statistical analysis. A significant decrease of BMI and waist circumference was associated with significant changes of plasma lipoprotein and glycaemia levels. Mass concentration of Lp-PLA2 at the baseline was 402 ± 94 μg/ml, after the intervention 368 ± 105 μg/ml (p=0.008). Change in Lp-PLA2 was associated with triglyceride level decrease (p=0.009). Intensive lifestyle modification leading to body weight decrease results in significant changes of plasma lipoprotein levels and, also, a drop of Lp-PLA2 levels in paediatric obese patients. However, even after the intervention Lp-PLA2 concentrations in this patient group remain elevated suggesting possible increased atherosclerosis risk in later life. © 2011 Neuroendocrinology Letters

  4. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

    DEFF Research Database (Denmark)

    Rotger, Margalida; Glass, Tracy R; Junier, Thomas

    2013-01-01

    BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the set...

  5. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

    NARCIS (Netherlands)

    Rotger, Margalida; Glass, Tracy R; Junier, Thomas; Lundgren, Jens; Neaton, James D; Poloni, Estella S; van 't Wout, Angélique B; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P; Li, Xiuhong; Kingsley, Lawrence A; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A; Reiss, Peter; Weber, Rainer; Bucher, Heiner C; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E; Schölvinck, Elisabeth H.

    2013-01-01

    BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the settin

  6. The interindividual differences in the 3-demthylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors

    DEFF Research Database (Denmark)

    Rasmussen, Birgitte B; Brix, Thomas H; Kyvik, Kirsten O

    2002-01-01

    This study investigated the role of genetic factors (CYP1A2) in caffeine metabolism. The CYP1A2 activity was determined in 378 Danish twins following oral intake of a single dose of 200 mg caffeine and subsequent determination of the caffeine ratio (AFMU+1MU+1MX)/17DMU in a 6-h urine sample....... The mean (+/- SD) caffeine ratio was 5.9 +/- 3.4. The caffeine ratio was statistically significantly higher in men compared to women, in smoking men and women compared to non-smoking persons of the same gender and in women not taking oral contraceptives compared with women on oral contraceptives. Thus, we....... A biometrical model for the caffeine ratio including only additive genetic factors and unique environmental factors was the overall best fitting model. Estimates based on this model gave a heritability estimate of 0.725 (95% confidence interval 0.577-0.822). Unique environmental effects seem to account...

  7. Genetic, morphometric, and behavioral factors linked to the midsagittal area of the corpus callosum

    Directory of Open Access Journals (Sweden)

    Alex J Newbury

    2012-05-01

    Full Text Available TThe corpus callosum is the main commissure connecting left and right cerebral hemispheres, and varies widely in size. Differences in the midsagittal area of the corpus callosum (MSACC have been associated with a number of cognitive and behavioral phenotypes, including obsessive-compulsive disorders, psychopathy, suicidal tendencies, bipolar disorder, schizophrenia, autism, and attention deficit hyperactivity disorder. Although there is evidence to suggest that MSACC is heritable in normal human populations, there is surprisingly little evidence concerning the genetic modulation of this variation. Mice provide a potentially ideal tool to dissect the genetic modulation of MSACC. Here, we use a large genetic reference panel—the BXD recombinant inbred (RI line—to dissect the natural variation of the MSACC. We estimated the MSACC in over 300 individuals from nearly 80 strains. We found a 4-fold difference in MSACC between individual mice, and a 2.5 fold difference between strains. MSACC is a highly heritable trait (h2 = 0.60, and we mapped a suggestive QTL to the distal portion of Chr 14. Using sequence data and neocortical expression databases, we were able to identify eight positional and plausible biological candidate genes within this interval. Finally, we found that MSACC correlated with behavioral traits associated with anxiety and attention.

  8. Analysis of the RELN gene as a genetic risk factor for autism.

    Science.gov (United States)

    Skaar, D A; Shao, Y; Haines, J L; Stenger, J E; Jaworski, J; Martin, E R; DeLong, G R; Moore, J H; McCauley, J L; Sutcliffe, J S; Ashley-Koch, A E; Cuccaro, M L; Folstein, S E; Gilbert, J R; Pericak-Vance, M A

    2005-06-01

    Several genome-wide screens have indicated the presence of an autism susceptibility locus within the distal long arm of chromosome 7 (7q). Mapping at 7q22 within this region is the candidate gene reelin (RELN). RELN encodes a signaling protein that plays a pivotal role in the migration of several neuronal cell types and in the development of neural connections. Given these neurodevelopmental functions, recent reports that RELN influences genetic risk for autism are of significant interest. The total data set consists of 218 Caucasian families collected by our group, 85 Caucasian families collected by AGRE, and 68 Caucasian families collected at Tufts University were tested for genetic association of RELN variants to autism. Markers included five single-nucleotide polymorphisms (SNPs) and a repeat in the 5'-untranslated region (5'-UTR). Tests for association in Duke and AGRE families were also performed on four additional SNPs in the genes PSMC2 and ORC5L, which flank RELN. Family-based association analyses (PDT, Geno-PDT, and FBAT) were used to test for association of single-locus markers and multilocus haplotypes with autism. The most significant association identified from this combined data set was for the 5'-UTR repeat (PDT P-value=0.002). These analyses show the potential of RELN as an important contributor to genetic risk in autism.

  9. Identification of genetic bases of vibrio fluvialis species-specific biochemical pathways and potential virulence factors by comparative genomic analysis.

    Science.gov (United States)

    Lu, Xin; Liang, Weili; Wang, Yunduan; Xu, Jialiang; Zhu, Jun; Kan, Biao

    2014-03-01

    Vibrio fluvialis is an important food-borne pathogen that causes diarrheal illness and sometimes extraintestinal infections in humans. In this study, we sequenced the genome of a clinical V. fluvialis strain and determined its phylogenetic relationships with other Vibrio species by comparative genomic analysis. We found that the closest relationship was between V. fluvialis and V. furnissii, followed by those with V. cholerae and V. mimicus. Moreover, based on genome comparisons and gene complementation experiments, we revealed genetic mechanisms of the biochemical tests that differentiate V. fluvialis from closely related species. Importantly, we identified a variety of genes encoding potential virulence factors, including multiple hemolysins, transcriptional regulators, and environmental survival and adaptation apparatuses, and the type VI secretion system, which is indicative of complex regulatory pathways modulating pathogenesis in this organism. The availability of V. fluvialis genome sequences may promote our understanding of pathogenic mechanisms for this emerging pathogen.

  10. Genetic Syndromes, Maternal Diseases and Antenatal Factors Associated with Autism Spectrum Disorders (ASD).

    Science.gov (United States)

    Ornoy, Asher; Weinstein-Fudim, Liza; Ergaz, Zivanit

    2016-01-01

    Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal, and postnatal etiologies. In addition, ASD is often an important clinical presentation of some well-known genetic syndromes in human. We discuss these syndromes as well as the role of the more important prenatal factors affecting the fetus throughout pregnancy which may also be associated with ASD. Among the genetic disorders we find Fragile X, Rett syndrome, tuberous sclerosis, Timothy syndrome, Phelan-McDermid syndrome, Hamartoma tumor syndrome, Prader-Willi and Angelman syndromes, and a few others. Among the maternal diseases in pregnancy associated with ASD are diabetes mellitus (PGDM and/or GDM), some maternal autoimmune diseases like antiphospholipid syndrome (APLS) with anti-β2GP1 IgG antibodies and thyroid disease with anti-thyroid peroxidase (TPO) antibodies, preeclampsia and some other autoimmune diseases with IgG antibodies that might affect fetal brain development. Other related factors are maternal infections (rubella and CMV with fetal brain injuries, and possibly Influenza with fever), prolonged fever and maternal inflammation, especially with changes in a variety of inflammatory cytokines and antibodies that cross the placenta and affect the fetal brain. Among the drugs are valproic acid, thalidomide, misoprostol, and possibly SSRIs. β2-adrenergic receptor agonists and paracetamol have also lately been associated with increased rate of ASD but the data is too preliminary and inconclusive. Associations were also described with ethanol, cocaine, and possibly heavy metals, heavy smoking, and folic acid deficiency. Recent studies show that heavy exposure to pesticides and air pollution, especially particulate matter PM2.5 and PM10) during pregnancy is also associated with ASD. Finally, we have to remember that many of the associations mentioned in this review are only partially proven, and not

  11. Genetic Syndromes, Maternal Diseases and Antenatal Factors Associated with Autism Spectrum Disorders (ASD)

    Science.gov (United States)

    Ornoy, Asher; Weinstein- Fudim, Liza; Ergaz, Zivanit

    2016-01-01

    Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal, and postnatal etiologies. In addition, ASD is often an important clinical presentation of some well-known genetic syndromes in human. We discuss these syndromes as well as the role of the more important prenatal factors affecting the fetus throughout pregnancy which may also be associated with ASD. Among the genetic disorders we find Fragile X, Rett syndrome, tuberous sclerosis, Timothy syndrome, Phelan–McDermid syndrome, Hamartoma tumor syndrome, Prader-Willi and Angelman syndromes, and a few others. Among the maternal diseases in pregnancy associated with ASD are diabetes mellitus (PGDM and/or GDM), some maternal autoimmune diseases like antiphospholipid syndrome (APLS) with anti-β2GP1 IgG antibodies and thyroid disease with anti-thyroid peroxidase (TPO) antibodies, preeclampsia and some other autoimmune diseases with IgG antibodies that might affect fetal brain development. Other related factors are maternal infections (rubella and CMV with fetal brain injuries, and possibly Influenza with fever), prolonged fever and maternal inflammation, especially with changes in a variety of inflammatory cytokines and antibodies that cross the placenta and affect the fetal brain. Among the drugs are valproic acid, thalidomide, misoprostol, and possibly SSRIs. β2-adrenergic receptor agonists and paracetamol have also lately been associated with increased rate of ASD but the data is too preliminary and inconclusive. Associations were also described with ethanol, cocaine, and possibly heavy metals, heavy smoking, and folic acid deficiency. Recent studies show that heavy exposure to pesticides and air pollution, especially particulate matter < 2.5 and 10 μm in diameter (PM2.5 and PM10) during pregnancy is also associated with ASD. Finally, we have to remember that many of the associations mentioned in this review are

  12. The allergy adjuvant effect of particles – genetic factors influence antibody and cytokine responses

    Directory of Open Access Journals (Sweden)

    Løvik Martinus

    2005-06-01

    Full Text Available Abstract Background There is increasing epidemiological and experimental evidence for an aggravating effect of particulate air pollution on asthma and allergic symptoms and, to a lesser extent, on allergic sensitization. Genetic factors appear to influence not only the magnitude, but also the quality of the adjuvant effect of particles with respect to allergen-specific IgE (Th2-associated and IgG2a (Th1-associated responses. In the present study, we aimed to investigate how the genetic background influences the responses to the allergen and particles alone and in combination. We examined how polystyrene particles (PSP affected the IgE and IgG2a responses against the model allergen ovalbumin (OVA, after subcutaneous injection into the footpad of BALB/cA, BALB/cJ, NIH and C3H/HeN mice, Further, ex vivo IL-4, IFN-γ and IL-10 cytokine secretion by Con A-stimulated cells from the draining popliteal lymph node (PLN five days after injection of OVA and PSP separately or in combination was determined. Results PSP injected with OVA increased the levels of OVA-specific IgE antibodies in all strains examined. In contrast, the IgG2a levels were significantly increased only in NIH and C3H/HeN mice. PSP in the presence of OVA increased cell numbers and IL-4, IL-10 and IFN-γ levels in BALB/cA, NIH and C3H/HeN mice, with the exception of IFN-γ in NIH mice. However, each mouse strain had their unique pattern of response to OVA+PSP, OVA and PSP, and also their unique background cytokine response (i.e. the cytokine response in cells from mice injected with buffer only. Conclusion Genetic factors (i.e. the strain of mice influenced the susceptibility to the adjuvant effect of PSP on both secondary antibody responses and primary cellular responses in the lymph node, as well as the cellular responses to both OVA and PSP given separately. Interestingly, PSP alone induced cytokine responses in the lymph node in some of the mouse strains. Furthermore, we found that

  13. Do DSM-5 Section II personality disorders and Section III personality trait domains reflect the same genetic and environmental risk factors?

    Science.gov (United States)

    Reichborn-Kjennerud, T; Krueger, R F; Ystrom, E; Torvik, F A; Rosenström, T H; Aggen, S H; South, S C; Neale, M C; Knudsen, G P; Kendler, K S; Czajkowski, N O

    2017-09-01

    DSM-5 includes two conceptualizations of personality disorders (PDs). The classification in Section II is identical to the one found in DSM-IV, and includes 10 categorical PDs. The Alternative Model (Section III) includes criteria for dimensional measures of maladaptive personality traits organized into five domains. The degree to which the two conceptualizations reflect the same etiological factors is not known. We use data from a large population-based sample of adult twins from the Norwegian Institute of Public Health Twin Panel on interview-based DSM-IV PDs and a short self-report inventory that indexes the five domains of the DSM-5 Alternative Model plus a domain explicitly targeting compulsivity. Schizotypal, Paranoid, Antisocial, Borderline, Avoidant, and Obsessive-compulsive PDs were assessed at the same time as the maladaptive personality traits and 10 years previously. Schizoid, Histrionic, Narcissistic, and Dependent PDs were only assessed at the first interview. Biometric models were used to estimate overlap in genetic and environmental risk factors. When measured concurrently, there was 100% genetic overlap between the maladaptive trait domains and Paranoid, Schizotypal, Antisocial, Borderline, and Avoidant PDs. For OCPD, 43% of the genetic variance was shared with the domains. Genetic correlations between the individual domains and PDs ranged from +0.21 to +0.91. The pathological personality trait domains, which are part of the Alternative Model for classification of PDs in DSM-5 Section III, appears to tap, at an aggregate level, the same genetic risk factors as the DSM-5 Section II classification for most of the PDs.

  14. Genetic factors of individual differences in decision making in economic behavior: A Japanese twin study using the Allais problem

    Directory of Open Access Journals (Sweden)

    Chizuru eShikishima

    2015-11-01

    Full Text Available Why does decision making differ among individuals? People sometimes make seemingly inconsistent decisions with lower expected (monetary utility even when objective information of probabilities and rewards are provided. It is noteworthy, however, that a certain proportion of people do not provide anomalous responses, choosing the alternatives with higher expected utility, thus appearing to be more rational. We investigated the genetic and environmental influences on these types of individual differences in decision making using a classical Allais problem task. Participants were 1,199 Japanese adult twins aged 20–47. Univariate genetic analysis revealed that approximately a third of the Allais problem response variance was explained by genetic factors and the rest by environmental factors unique to individuals and measurement error. The environmental factor shared between families did not contribute to the variance. Subsequent multivariate genetic analysis clarified that decision making using the expected utility theory was associated with general intelligence and that the association was largely mediated by the same genetic factor. We approach the mechanism underlying two types of rational decision making from the perspective of genetic correlations with cognitive abilities.

  15. Genetic Factors of Individual Differences in Decision Making in Economic Behavior: A Japanese Twin Study using the Allais Problem.

    Science.gov (United States)

    Shikishima, Chizuru; Hiraishi, Kai; Yamagata, Shinji; Ando, Juko; Okada, Mitsuhiro

    2015-01-01

    Why does decision making differ among individuals? People sometimes make seemingly inconsistent decisions with lower expected (monetary) utility even when objective information of probabilities and reward are provided. It is noteworthy, however, that a certain proportion of people do not provide anomalous responses, choosing the alternatives with higher expected utility, thus appearing to be more "rational." We investigated the genetic and environmental influences on these types of individual differences in decision making using a classical Allais problem task. Participants were 1,199 Japanese adult twins aged 20-47. Univariate genetic analysis revealed that approximately a third of the Allais problem response variance was explained by genetic factors and the rest by environmental factors unique to individuals and measurement error. The environmental factor shared between families did not contribute to the variance. Subsequent multivariate genetic analysis clarified that decision making using the expected utility theory was associated with general intelligence and that the association was largely mediated by the same genetic factor. We approach the mechanism underlying two types of "rational" decision making from the perspective of genetic correlations with cognitive abilities.

  16. Association between subjective memory complaints and depressive symptoms after adjustment for genetic and family environmental factors in a Japanese twin study.

    Science.gov (United States)

    Tanaka, Haruka; Ogata, Soshiro; Omura, Kayoko; Honda, Chika; Kamide, Kei; Hayakawa, Kazuo

    2016-03-01

    The aim of this study was to investigate the association between subjective memory complaints (SMCs) and depressive symptoms, with and without adjustment for genetic and family environmental factors. We conducted a cross-sectional study using twins and measured SMCs and depressive symptoms as outcomes and explanatory variables, respectively. First, we performed regression analyses using generalized estimating equations to investigate the associations between SMCs and depressive symptoms without adjustment for genetic and family environmental factors (individual-level analyses). We then performed regression analyses for within-pair differences using monozygotic (MZ) and dizygotic (DZ) twin pairs and MZ twin pairs to investigate these associations with adjustment for genetic and family environmental factors by subtracting the values of one twin from those of co-twin variables (within-pair level analyses). Therefore, differences between the associations at individual- and within-pair level analyses suggested confounding by genetic factors. We included 556 twins aged ≥ 20 years. In the individual-level analyses, SMCs were significantly associated with depressive symptoms in both males and females [standardized coefficients: males, 0.23 (95% CI 0.08-0.38); females, 0.35 (95% CI 0.23-0.46)]. In the within-pair level analyses using MZ and same-sex DZ twin pairs, SMCs were significantly associated with depressive symptoms. In the within-pair level analyses using the MZ twin pairs, SMCs were significantly associated with depressive symptoms [standardized coefficients: males, 0.32 (95% CI 0.08-0.56); females, 0.24 (95% CI 0.13-0.42)]. This study suggested that SMCs were significantly associated with depressive symptoms after adjustment for genetic and family environmental factors.

  17. Evaluation of Animal Genetic and Physiological Factors That Affect the Prevalence of Escherichia coli O157 in Cattle

    Science.gov (United States)

    Jeon, Soo Jin; Elzo, Mauricio; DiLorenzo, Nicolas; Lamb, G. Cliff; Jeong, Kwang Cheol

    2013-01-01

    Controlling the prevalence of Escherichia coli O157 in cattle at the pre-harvest level is critical to reduce outbreaks of this pathogen in humans. Multilayers of factors including the environmental and bacterial factors modulate the colonization and persistence of E. coli O157 in cattle that serve as a reservoir of this pathogen. Here, we report animal factors contributing to the prevalence of E. coli O157 in cattle. We observe the lowest number of E. coli O157 in Brahman breed when compared with other crosses in an Angus-Brahman multibreed herd, and bulls excrete more E. coli O157 than steers in the pens where cattle were housed together. The presence of super-shedders, cattle excreting >105 CFU/rectal anal swab, increases the concentration of E. coli O157 in the pens; thereby super-shedders enhance transmission of this pathogen among cattle. Molecular subtyping analysis reveal only one subtype of E. coli O157 in the multibreed herd, indicating the variance in the levels of E. coli O157 in cattle is influenced by animal factors. Furthermore, strain tracking after relocation of the cattle to a commercial feedlot reveals farm-to-farm transmission of E. coli O157, likely via super-shedders. Our results reveal high risk factors in the prevalence of E. coli O157 in cattle whereby animal genetic and physiological factors influence whether this pathogen can persist in cattle at high concentration, providing insights to intervene this pathogen at the pre-harvest level. PMID:23405204

  18. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection.

    NARCIS (Netherlands)

    Pearson, E.R.; Pruhova, S.; Tack, C.J.J.; Johansen, A.; Castleden, H.A.; Lumb, P.J.; Wierzbicki, A.S.; Clark, P.M.; Lebl, J.; Pedersen, O.; Ellard, S.; Hansen, T.; Hattersley, A.T.

    2005-01-01

    AIMS/HYPOTHESIS: Heterozygous mutations in the gene of the transcription factor hepatocyte nuclear factor 4alpha (HNF-4alpha) are considered a rare cause of MODY with only 14 mutations reported to date. The description of the phenotype is limited to single families. We investigated the genetics and

  19. Shared Genetic Aetiology between Cognitive Ability and Cardiovascular Disease Risk Factors: Generation Scotland's Scottish Family Health Study

    Science.gov (United States)

    Luciano, Michelle; Batty, G. David; McGilchrist, Mark; Linksted, Pamela; Fitzpatrick, Bridie; Jackson, Cathy; Pattie, Alison; Dominiczak, Anna F.; Morris, Andrew D.; Smith, Blair H.; Porteous, David; Deary, Ian J.

    2010-01-01

    People with higher general cognitive ability in early life have more favourable levels of cardiovascular disease (CVD) risk factors in adulthood and CVD itself. The mechanism of these associations is not known. Here we examine whether general cognitive ability and CVD risk factors share genetic and/or environmental aetiology. In this large,…

  20. Paternal factor V Leiden and recurrent pregnancy loss: a new concept behind fetal genetics?

    Science.gov (United States)

    Udry, S; Aranda, F M; Latino, J O; de Larrañaga, G F

    2014-05-01

    In up to 50% of couples affected by recurrent pregnancy loss, no identifiable cause is established. Fetal and maternal factors may be equally important in the establishment and maintenance of the placental/maternal arteriovenous anastomoses. Therefore,the inheritance of thrombophilia-related genes may be an important factor in the pathophysiology of recurrent pregnancy loss. Most of the research on recurrent pregnancy loss and thrombophilia has focused on maternal factors, but little is known about the paternal contribution. On that basis, we studied the association between inherited paternal thrombophilias and recurrent pregnancy loss in a narrowly selective group of 42 Argentine males from couples that presented without any known risk factors for recurrent pregnancy loss. The genotypic distributions of factor (F) V Leiden and prothrombin G20210A among cases were compared with those from a reference group composed of 200 Argentine men. We found a significant difference in the distribution of FV Leiden between both groups (16.7% vs. 3.0%), but no difference was found in the distribution of prothrombin G20210A (2.4% vs.2.0%). Those couples with paternal FV Leiden carriage would be six times more likely to experience recurrent pregnancy loss despite no other apparent cause (OR = 6.47; 95% CI, 2.06–20.39). We found evidence of an association between the paternal carriage of FV Leiden and the predisposition to recurrent pregnancy loss, thereby supporting the hypothesis that genetic contributions from both parents are essential factors in the development of this obstetric disorder.

  1. KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

    Science.gov (United States)

    2012-01-01

    Introduction Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. Methods The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay. Results Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients. Conclusions Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients. PMID:23270786

  2. Association between smoking behaviour and genetic variants of glial cell line-derived neurotrophic factor

    Indian Academy of Sciences (India)

    ESZTER KOTYUK; NORA NEMETH; ZSOLT RONAI; ZSOLT DEMETROVICS; MARIA SASVARI-SZEKELY; ANNA SZEKELY

    2016-12-01

    Glial cell line-derived neurotrophic factor (GDNF) promotes development and differentiation of dopaminergic neurons, thus it has an important role in dopamine-related neuropsychiatric disorders. Since the role of dopamine system in smoking iswell established, we hypothesized that GDNF gene variants may affect smoking behaviour. Self-reported data on smoking behaviour (never smoked, quit, occasional, or regular smokers) and level of nicotine addiction (Hooked on Nicotine Checklist and Fagerstrom Nicotine Addiction Scale), anxiety, as well as buccal samples were obtained from 930 Hungarian young adults (18–35 years). Genetic analysis involved eight GDNF single-nucleotide polymorphisms (SNP) (rs1981844, rs3812047, rs3096140, rs2973041, rs2910702, rs1549250, rs2973050 and rs11111). Allele-wise association analyses of the eight GDNF SNPs provided a significant association between smoking behaviour and rs3096140 (P = 0.0039). The minor allele (C) was more frequent in those groups who smoked in some form (quit, occasional or regular smokers) as compared to those who neversmoked (P = 0.0046). This result remained significant after Bonferroni correction for multiple testing. In the ever smoking group, no significant differences were found in the level of nicotine addiction by the alleles of these polymorphisms. Also, nosignificant interaction of rs3096140 and smoking categories were observed on anxiety mean scores. Although previous data demonstrated an association between GDNF rs2910704 and severity of methamphetamine use to the best of our knowledge, this is the first study on the role of GDNF genetic variations in smoking behaviour. Our results suggest that GDNF rs3096140 might be involved in the genetic background of smoking, independent of anxiety characteristics.

  3. Association between smoking behaviour and genetic variants of glial cell line-derived neurotrophic factor.

    Science.gov (United States)

    Kotyuk, Eszter; Nemeth, Nora; Ronai, Zsolt; Demetrovics, Zsolt; Sasvari-Szekely, Maria; Szekely, Anna

    2016-12-01

    Glial cell line-derived neurotrophic factor (GDNF) promotes development and differentiation of dopaminergic neurons, thus it has an important role in dopamine-related neuropsychiatric disorders. Since the role of dopamine system in smoking is well established, we hypothesized that GDNF gene variants may affect smoking behaviour. Self-reported data on smoking behaviour (never smoked, quit, occasional, or regular smokers) and level of nicotine addiction (Hooked on Nicotine Checklist and Fagerstrom Nicotine Addiction Scale), anxiety, as well as buccal samples were obtained from 930 Hungarian young adults (18-35 years). Genetic analysis involved eight GDNF single-nucleotide polymorphisms (SNP) (rs1981844, rs3812047, rs3096140, rs2973041, rs2910702, rs1549250, rs2973050 and rs11111). Allele-wise association analyses of the eight GDNF SNPs provided a significant association between smoking behaviour and rs3096140 (P=0.0039). The minor allele (C) was more frequent in those groups who smoked in some form (quit, occasional or regular smokers) as compared to those who never smoked (P = 0.0046). This result remained significant after Bonferroni correction for multiple testing. In the ever smoking group, no significant differences were found in the level of nicotine addiction by the alleles of these polymorphisms. Also, no significant interaction of rs3096140 and smoking categories were observed on anxiety mean scores. Although previous data demonstrated an association between GDNF rs2910704 and severity of methamphetamine use to the best of our knowledge, this is the first study on the role of GDNF genetic variations in smoking behaviour. Our results suggest that GDNF rs3096140 might be involved in the genetic background of smoking, independent of anxiety characteristics.

  4. Admixture in Mexico City: implications for admixture mapping of type 2 diabetes genetic risk factors.

    Science.gov (United States)

    Martinez-Marignac, Veronica L; Valladares, Adan; Cameron, Emily; Chan, Andrea; Perera, Arjuna; Globus-Goldberg, Rachel; Wacher, Niels; Kumate, Jesús; McKeigue, Paul; O'Donnell, David; Shriver, Mark D; Cruz, Miguel; Parra, Esteban J

    2007-02-01

    Admixture mapping is a recently developed method for identifying genetic risk factors involved in complex traits or diseases showing prevalence differences between major continental groups. Type 2 diabetes (T2D) is at least twice as prevalent in Native American populations as in populations of European ancestry, so admixture mapping is well suited to study the genetic basis of this complex disease. We have characterized the admixture proportions in a sample of 286 unrelated T2D patients and 275 controls from Mexico City and we discuss the implications of the results for admixture mapping studies. Admixture proportions were estimated using 69 autosomal ancestry-informative markers (AIMs). Maternal and paternal contributions were estimated from geographically informative mtDNA and Y-specific polymorphisms. The average proportions of Native American, European and, West African admixture were estimated as 65, 30, and 5%, respectively. The contributions of Native American ancestors to maternal and paternal lineages were estimated as 90 and 40%, respectively. In a logistic model with higher educational status as dependent variable, the odds ratio for higher educational status associated with an increase from 0 to 1 in European admixture proportions was 9.4 (95%, credible interval 3.8-22.6). This association of socioeconomic status with individual admixture proportion shows that genetic stratification in this population is paralleled, and possibly maintained, by socioeconomic stratification. The effective number of generations back to unadmixed ancestors was 6.7 (95% CI 5.7-8.0), from which we can estimate that genome-wide admixture mapping will require typing about 1,400 evenly distributed AIMs to localize genes underlying disease risk between populations of European and Native American ancestry. Sample sizes of about 2,000 cases will be required to detect any locus that contributes an ancestry risk ratio of at least 1.5.

  5. Genetic networks controlled by the bacterial replication initiator and transcription factor DnaA in Bacillus subtilis.

    Science.gov (United States)

    Washington, Tracy A; Smith, Janet L; Grossman, Alan D

    2017-10-01

    DnaA is the widely conserved bacterial AAA+ ATPase that functions as both the replication initiator and a transcription factor. In many organisms, DnaA controls expression of its own gene and likely several others during growth and in response to replication stress. To evaluate the effects of DnaA on gene expression, separate from its role in replication initiation, we analyzed changes in mRNA levels in Bacillus subtilis cells with and without dnaA, using engineered strains in which dnaA is not essential. We found that dnaA was required for many of the changes in gene expression in response to replication stress. We also found that dnaA indirectly affected expression of several regulons during growth, including those controlled by the transcription factors Spo0A, AbrB, PhoP, SinR, RemA, Rok and YvrH. These effects were largely mediated by the effects of DnaA on expression of sda. DnaA activates transcription of sda, and Sda inhibits histidine protein kinases required for activation of the transcription factor Spo0A. We also found that loss of dnaA caused a decrease in the development of genetic competence. Together, our results indicate that DnaA plays an important role in modulating cell physiology, separate from its role in replication initiation. © 2017 John Wiley & Sons Ltd.

  6. Cell culture isolation and sequence analysis of genetically diverse US porcine epidemic diarrhea virus strains including a novel strain with a large deletion in the spike gene.

    Science.gov (United States)

    Oka, Tomoichiro; Saif, Linda J; Marthaler, Douglas; Esseili, Malak A; Meulia, Tea; Lin, Chun-Ming; Vlasova, Anastasia N; Jung, Kwonil; Zhang, Yan; Wang, Qiuhong

    2014-10-10

    The highly contagious and deadly porcine epidemic diarrhea virus (PEDV) first appeared in the US in April 2013. Since then the virus has spread rapidly nationwide and to Canada and Mexico causing high mortality among nursing piglets and significant economic losses. Currently there are no efficacious preventive measures or therapeutic tools to control PEDV in the US. The isolation of PEDV in cell culture is the first step toward the development of an attenuated vaccine, to study the biology of PEDV and to develop in vitro PEDV immunoassays, inactivation assays and screen for PEDV antivirals. In this study, nine of 88 US PEDV strains were isolated successfully on Vero cells with supplemental trypsin and subjected to genomic sequence analysis. They differed genetically mainly in the N-terminal S protein region as follows: (1) strains (n=7) similar to the highly virulent US PEDV strains; (2) one similar to the reportedly US S INDEL PEDV strain; and (3) one novel strain most closely related to highly virulent US PEDV strains, but with a large (197aa) deletion in the S protein. Representative strains of these three genetic groups were passaged serially and grew to titers of ∼5-6log10 plaque forming units/mL. To our knowledge, this is the first report of the isolation in cell culture of an S INDEL PEDV strain and a PEDV strain with a large (197aa) deletion in the S protein. We also designed primer sets to detect these genetically diverse US PEDV strains. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Effect of recombinant platelet-derived growth factor (Regranex) on wound closure in genetically diabetic mice.

    Science.gov (United States)

    Chan, Rodney K; Liu, Perry H; Pietramaggiori, Giorgio; Ibrahim, Shahrul I; Hechtman, Herbert B; Orgill, Dennis P

    2006-01-01

    Burns, especially those involving large surface areas, represent a complex wound healing problem. Platelet-derived growth factor (PDGF) is released by activated platelets to recruit inflammatory cells toward the wound bed. It has effects on promoting angiogenesis and granulation tissue formation. However, the effectiveness of topical PDGF on wound closure is variable, ranging from little improvement observed in pig models to dramatic improvement reported in a diabetic mouse model. Here, we sought to determine the effectiveness of commercially sold PDGF-BB (Regranex) on wound closure in genetically diabetic mice. C57BL/KsJ db+/db+ mice and its host strain bearing dorsal 1.5-cm wounds were divided into groups (n = 8 in each group) receiving topical application of either Regranex (10 microg/wound) or vehicle for 5 consecutive days after wounding. The rate of wound closure was analyzed using computerized planimetry. The amount of granulation tissue was determined histologically. Our data indicate that diabetic mice exhibit a significant delay in wound closure when compared with their host strain. Topical application of Regranex did not improve the time to wound closure but did significantly increase the amount of granulation tissue. Our current study using commercially available Regranex failed to reproduce the previously reported finding that PDGF improved wound closure in healing impaired genetically diabetic mice.

  8. Intraspecific variation in social organization by genetic variation, developmental plasticity, social flexibility or entirely extrinsic factors.

    Science.gov (United States)

    Schradin, Carsten

    2013-05-19

    Previously, it was widely believed that each species has a specific social organization, but we know now that many species show intraspecific variation in their social organization. Four different processes can lead to intraspecific variation in social organization: (i) genetic variation between individuals owing to local adaptation (between populations) or evolutionarily stable strategies within populations; (ii) developmental plasticity evolved in long-term (more than one generation) unpredictable and short-term (one generation) predictable environments, which is mediated by organizational physiological effects during early ontogeny; (iii) social flexibility evolved in highly unpredictable environments, which is mediated by activational physiological effects in adults; (iv) entirely extrinsic factors such as the death of a dominant breeder. Variation in social behaviour occurs between individuals in the case of genetic variation and developmental plasticity, but within individuals in the case of social flexibility. It is important to study intraspecific variation in social organization to understand the social systems of species because it reveals the mechanisms by which species can adapt to changing environments, offers a useful tool to study the ultimate and proximate causes of sociality, and is an interesting phenomenon by itself that needs scientific explanation.

  9. Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors

    Science.gov (United States)

    Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A.

    2016-01-01

    The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

  10. Genetic factors modulate the impact of pubertal androgen excess on insulin sensitivity and fertility.

    Directory of Open Access Journals (Sweden)

    Abigail R Dowling

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrine disorder of reproductive age women. The syndrome is caused by a combination of environmental influences and genetic predisposition. Despite extensive efforts, the heritable factors contributing to PCOS development are not fully understood. The objective of this study was to test the hypothesis that genetic background contributes to the development of a PCOS-like reproductive and metabolic phenotype in mice exposed to excess DHEA during the pubertal transition. We tested whether the PCOS phenotype would be more pronounced on the diabetes-prone C57BL/6 background than the previously used strain, BALB/cByJ. In addition, we examined strain-dependent upregulation of the expression of ovarian and extra-ovarian candidate genes implicated in human PCOS, genes containing known strain variants, and genes involved with steroidogenesis or insulin sensitivity. These studies show that there are significant strain-related differences in metabolic response to excess androgen exposure during puberty. Additionally, our results suggest the C57BL/6J strain provides a more robust and uniform experimental platform for PCOS research than the BALB/cByJ strain.

  11. Performance of genetic risk factors in prediction of trichloroethylene induced hypersensitivity syndrome

    Science.gov (United States)

    Dai, Yufei; Chen, Ying; Huang, Hanlin; Zhou, Wei; Niu, Yong; Zhang, Mingrong; Bin, Ping; Dong, Haiyan; Jia, Qiang; Huang, Jianxun; Yi, Juan; Liao, Qijun; Li, Haishan; Teng, Yanxia; Zang, Dan; Zhai, Qingfeng; Duan, Huawei; Shen, Juan; He, Jiaxi; Meng, Tao; Sha, Yan; Shen, Meili; Ye, Meng; Jia, Xiaowei; Xiang, Yingping; Huang, Huiping; Wu, Qifeng; Shi, Mingming; Huang, Xianqing; Yang, Huanming; Luo, Longhai; Li, Sai; Li, Lin; Zhao, Jinyang; Li, Laiyu; Wang, Jun; Zheng, Yuxin

    2015-01-01

    Trichloroethylene induced hypersensitivity syndrome is dose-independent and potentially life threatening disease, which has become one of the serious occupational health issues and requires intensive treatment. To discover the genetic risk factors and evaluate the performance of risk prediction model for the disease, we conducted genomewide association study and replication study with total of 174 cases and 1761 trichloroethylene-tolerant controls. Fifty seven SNPs that exceeded the threshold for genome-wide significance (P < 5 × 10−8) were screened to relate with the disease, among which two independent SNPs were identified, that is rs2857281 at MICA (odds ratio, 11.92; Pmeta = 1.33 × 10−37) and rs2523557 between HLA-B and MICA (odds ratio, 7.33; Pmeta = 8.79 × 10−35). The genetic risk score with these two SNPs explains at least 20.9% of the disease variance and up to 32.5-fold variation in inter-individual risk. Combining of two SNPs as predictors for the disease would have accuracy of 80.73%, the area under receiver operator characteristic curves (AUC) scores was 0.82 with sensitivity of 74% and specificity of 85%, which was considered to have excellent discrimination for the disease, and could be considered for translational application for screening employees before exposure. PMID:26190474

  12. Non Genetic Factors Affecting Pre-Weaning Weight and Growth Rate of Ettawah Grade Goats

    Directory of Open Access Journals (Sweden)

    A. Sodiq

    2012-04-01

    Full Text Available The present study was carried out to evaluate the effect of various non-genetic factors on live weights at different ages (at birth, 30, 60, 90, and 120 d of age, and on average daily gains (from birth to 30, 60, 90, and 120 d of Ettawah Grade kids. Data from 314 records kids at the national village breeding centre of Kaligesing Purworejo Central Java province were analyzed. Results showed that average live weights at birth (BW= 3.44 kg, 30 d of age (W30= 7.19 kg, 60 d of age (W60= 11.05 kg, 90 d of age (W90= 14.75 kg, 120 d of age (W120= 18.86 kg, and average daily gain from birth until 30 d of age (ADG30= 125.6 g, 60 d of age (ADG60= 126.97 g, 90 d of age (ADG90= 125.87 g, 120 d of age (ADG120= 128.78 g were influenced by sex, litter size, and age of dams. Means of BW, W30, W60, W90, W120, ADG30, ADG60, ADG90, and ADG120 of males were higher than females. Multiple (twin and triplets born kids were lighter than single. Mean of body weight and average daily gain increased with the dam’s age. The implication of these findings should be accounted in genetic evaluations and also should consider maternal ability for the improvement of Ettawah Grade.

  13. Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors.

    Science.gov (United States)

    Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A

    2016-09-01

    The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

  14. Genetic, environmental, and epigenetic factors in the development of personality disturbance.

    Science.gov (United States)

    Depue, Richard A

    2009-01-01

    A dimensional model of personality disturbance is presented that is defined by extreme values on interacting subsets of seven major personality traits. Being at the extreme has marked effects on the threshold for eliciting those traits under stimulus conditions: that is, the extent to which the environment affects the neurobiological functioning underlying the traits. To explore the nature of development of extreme values on these traits, each trait is discussed in terms of three major issues: (a) the neurobiological variables associated with the trait, (b) individual variation in this neurobiology as a function of genetic polymorphisms, and (c) the effects of environmental adversity on these neurobiological variables through the action of epigenetic processes. It is noted that gene-environment interaction appears to be dependent on two main factors: (a) both genetic and environmental variables appear to have the most profound and enduring effects when they exert their effects during early postnatal periods, times when the forebrain is undergoing exuberant experience-expectant dendritic and axonal growth; and (b) environmental effects on neurobiology are strongly modified by individual differences in "traitlike" functioning of neurobiological variables. A model of the nature of the interaction between environmental and neurobiological variables in the development of personality disturbance is presented.

  15. Factor structure and heritability of endophenotypes in schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS-1)

    OpenAIRE

    Seidman, LJ; Hellemann, G; Nuechterlein, KH; Greenwood, TA; Braff, DL; Cadenhead, KS; Calkins, ME; Freedman, R; Gur, RE; Gur, RC; Lazzeroni, LC; Light, GA; Olincy, A; Radant, AD; Siever, LJ

    2014-01-01

    © 2015 Elsevier B.V. Background: Although many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements. Methods: The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a mu...

  16. Genetic variants on 3q21 and in the Sp8 transcription factor gene (SP8 as susceptibility loci for psychotic disorders: a genetic association study.

    Directory of Open Access Journals (Sweden)

    Kenji Kondo

    Full Text Available BACKGROUND: Recent genome-wide association studies (GWASs investigating bipolar disorder (BD have detected a number of susceptibility genes. These studies have also provided novel insight into shared genetic components between BD and schizophrenia (SCZ, two major psychotic disorders. To examine the replication of the risk variants for BD and the pleiotropic effect of the variants associated with BD, we conducted a genetic association study of single nucleotide polymorphisms (SNPs that were selected based upon previous BD GWASs, which targeted psychotic disorders (BD and SCZ in the Japanese population. METHODS: Forty-eight SNPs were selected based upon previous GWASs. A two-stage analysis was conducted using first-set screening (for all SNPs: BD = 1,012, SCZ = 1,032 and control = 993 and second-set replication samples (for significant SNPs in the screening analysis: BD = 821, SCZ = 1,808 and control = 2,149. We assessed allelic association between BD, SCZ, psychosis (BD+SCZ and the SNPs selected for the analysis. RESULTS: Eight SNPs revealed nominal association signals for all comparisons (Puncorrected<0.05. Among these SNPs, the top two SNPs (associated with psychosis: Pcorrected = 0.048 and 0.037 for rs2251219 and rs2709722, respectively were further assessed in the second-set samples, and we replicated the signals from the initial screening analysis (associated with psychosis: Pcorrected = 0.0070 and 0.033 for rs2251219 and rs2709722, respectively. The meta-analysis between the current and previous GWAS results showed that rs2251219 in Polybromo1 (PBRM1 was significant on genome-wide association level (P = 5×10(-8 only for BD (P = 9.4×10(-9 and psychosis (P = 2.0×10(-10. Although the association of rs2709722 in Sp8 transcription factor (SP8 was suggestive in the Asian population (P = 2.1×10(-7 for psychosis, this signal weakened when the samples size was increased by including data from a

  17. Genetic Variants on 3q21 and in the Sp8 Transcription Factor Gene (SP8) as Susceptibility Loci for Psychotic Disorders: A Genetic Association Study

    Science.gov (United States)

    Kondo, Kenji; Ikeda, Masashi; Kajio, Yusuke; Saito, Takeo; Iwayama, Yoshimi; Aleksic, Branko; Yamada, Kazuo; Toyota, Tomoko; Hattori, Eiji; Ujike, Hiroshi; Inada, Toshiya; Kunugi, Hiroshi; Kato, Tadafumi; Yoshikawa, Takeo; Ozaki, Norio; Iwata, Nakao

    2013-01-01

    Background Recent genome-wide association studies (GWASs) investigating bipolar disorder (BD) have detected a number of susceptibility genes. These studies have also provided novel insight into shared genetic components between BD and schizophrenia (SCZ), two major psychotic disorders. To examine the replication of the risk variants for BD and the pleiotropic effect of the variants associated with BD, we conducted a genetic association study of single nucleotide polymorphisms (SNPs) that were selected based upon previous BD GWASs, which targeted psychotic disorders (BD and SCZ) in the Japanese population. Methods Forty-eight SNPs were selected based upon previous GWASs. A two-stage analysis was conducted using first-set screening (for all SNPs: BD = 1,012, SCZ = 1,032 and control = 993) and second-set replication samples (for significant SNPs in the screening analysis: BD = 821, SCZ = 1,808 and control = 2,149). We assessed allelic association between BD, SCZ, psychosis (BD+SCZ) and the SNPs selected for the analysis. Results Eight SNPs revealed nominal association signals for all comparisons (Puncorrected<0.05). Among these SNPs, the top two SNPs (associated with psychosis: Pcorrected = 0.048 and 0.037 for rs2251219 and rs2709722, respectively) were further assessed in the second-set samples, and we replicated the signals from the initial screening analysis (associated with psychosis: Pcorrected = 0.0070 and 0.033 for rs2251219 and rs2709722, respectively). The meta-analysis between the current and previous GWAS results showed that rs2251219 in Polybromo1 (PBRM1) was significant on genome-wide association level (P = 5×10−8) only for BD (P = 9.4×10−9) and psychosis (P = 2.0×10−10). Although the association of rs2709722 in Sp8 transcription factor (SP8) was suggestive in the Asian population (P = 2.1×10−7 for psychosis), this signal weakened when the samples size was increased by including data from a

  18. Age-related macular degeneration: genetic and environmental factors of disease.

    Science.gov (United States)

    Chen, Yuhong; Bedell, Matthew; Zhang, Kang

    2010-10-01

    Age-related macular degeneration (AMD) is the most common cause of visual impairment among the elderly in developed countries, and its prevalence is thus increasing as the population ages; however, treatment options remain limited because the etiology and pathogenesis of AMD are incompletely defined. Recently, much progress has been made in gene discovery and mechanistic studies, which clearly indicate that AMD involves the interaction of multiple genetic and environmental factors. The identification of genes that have a substantial impact on the risk for AMD is not only facilitating the diagnosis and screening of populations at risk but is also elucidating key molecular pathways of pathogenesis. Pharmacogenetic studies of treatment responsiveness among patients with the "wet" form of AMD are increasingly proving to be clinically relevant; pharmacogenetic approaches hold great promise for both identifying patients with the best chance for vision recovery as well as tailoring individualized therapies.

  19. Factors Affecting the Adoption of Genetically Modified Animals in the Food and Pharmaceutical Chains

    Directory of Open Access Journals (Sweden)

    Cristina Mora

    2013-03-01

    Full Text Available The production of genetically modified (GM animals is an emerging technique that could potentially impact the livestock and pharmaceutical industries. Currently, food products derived from GM animals have not yet entered the market whilst two pharmaceutical products have. The objective of this paper is twofold: first it aims to explore the socio-economic drivers affecting the use of GM animals and, second, to review the risks and benefits from the point of view of the life sciences. A scoping study was conducted to assess research relevant to understanding the main drivers influencing the adoption of GM applications and their potential risks and benefits. Public and producers’ acceptance, public policies, human health, animal welfare, environmental impact and sustainability are considered as the main factors affecting the application of GM animal techniques in livestock and pharmaceutical chains.

  20. Genetic, physiologic and ecogeographic factors contributing to variation in Homo sapiens: Homo floresiensis reconsidered.

    Science.gov (United States)

    Richards, Gary D

    2006-11-01

    A new species, Homo floresiensis, was recently named for Pleistocene hominid remains on Flores, Indonesia. Significant controversy has arisen regarding this species. To address controversial issues and refocus investigations, I examine the affinities of these remains with Homo sapiens. Clarification of problematic issues is sought through an integration of genetic and physiological data on brain ontogeny and evolution. Clarification of the taxonomic value of various 'primitive' traits is possible given these data. Based on this evidence and using a H. sapiens morphological template, models are developed to account for the combination of features displayed in the Flores fossils. Given this overview, I find substantial support for the hypothesis that the remains represent a variant of H. sapiens possessing a combined growth hormone-insulin-like growth factor I axis modification and mutation of the MCPH gene family. Further work will be required to determine the extent to which this variant characterized the population.

  1. Association mapping of genetic risk factors for chronic wasting disease in wild deer

    Science.gov (United States)

    Tomomi Matsumoto,; Samuel, Michael D.; Trent Bollinger,; Margo Pybus,; David W. Coltman,

    2013-01-01

    Chronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy affecting North American cervids. We assessed the feasibility of association mapping CWD genetic risk factors in wild white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus) using a panel of bovine microsatellite markers from three homologous deer linkage groups predicted to contain candidate genes. These markers had a low cross-species amplification rate (27.9%) and showed weak linkage disequilibrium (<1 cM). Markers near the prion protein and the neurofibromin 1 (NF1) genes were suggestively associated with CWD status in white-tailed deer (P = 0.006) and mule deer (P = 0.02), respectively. This is the first time an association between the NF1 region and CWD has been reported.

  2. [Tumor necrosis factor alfa in cardiovascular diseases: molecular biology and genetics].

    Science.gov (United States)

    Fragoso Lona, José Manuel; Sierra Martínez, Mónica; Vargas Alarcón, Gilberto; Barrios Rodas, Angélica; Ramírez Bello, Julián

    2013-01-01

    Cardiovascular diseases are a major public health problem globally. In 1997, cardiovascular disease caused 41% of deaths in the United States. It has been reported that about 60 million people in the United States have some form of cardiovascular disease. These entities are chronic conditions initiated by a dysregulation of the immune response. One gene and its protein product -tumor necrosis factor a (TNF-α)- a powerful pleiotropic cytokine with multiple cellular functions, plays a role in the inflammation, initiation, development, susceptibility, severity, and response to treatment, etc. of coronary artery disease (CAD). The focus of the present review is to summarize recent evidence showing the biological role of TNF-α in the initiation and progression of endothelial dysfunction and complications of atherosclerosis, and as a genetic variation of TNF-α confer susceptibility, severity, and treatment response in CAD: ST-segment elevation myocardial infarction and non-ST segment elevation myocardial infarction, unstable angina, and coronary restenosis.

  3. Genetic classification of Listeria monocytogenes serotype 4b strains, including epidemic clones, isolated from retail meat in the Tokyo metropolitan area.

    Science.gov (United States)

    Ochiai, Yoshitsugu; Mochizuki, Mariko; Yamada, Fumiya; Takano, Takashi; Hondo, Ryo; Ueda, Fukiko

    2014-01-01

    A food-borne pathogen, Listeria monocytogenes serotype 4b, has been frequently isolated from patients with listeriosis, and numerous outbreaks of listeriosis are associated with this serotype. In the present study, we performed subtyping of L. monocytogenes serotype 4b strains on the basis of genetic analyses. Thirty-four isolates of serotype 4b were classified into 8 genotypes, namely genotypes 12, 15, 16, 17, 18, 23, 24, and 25, on the basis of the sequence for the partial iap gene. Genetic analyses revealed that genotype 16 and genotypes 24 and 25 belong to epidemic clone I (ECI) and ECII, respectively, which have been frequently associated with listeriosis outbreaks in the United States and Europe. The genotype isolated most frequently from retail meats in the Tokyo metropolitan area was genotype 12 (52%), followed by genotype 16 (29%), which belongs to ECI. We suggest that ECI is a common subtype of L. monocytogenes in retail meat in the area under investigation. On the other hand, ECII isolates were confirmed to be present in retail meat in Japan but were rare.

  4. Genetic risk factors for myocardial infarction more clearly manifest for early age of first onset.

    Science.gov (United States)

    Titov, Boris V; Osmak, German J; Matveeva, Natalia A; Kukava, Nino G; Shakhnovich, Roman M; Favorov, Alexander V; Ruda, Mikhail Ya; Favorova, Olga O

    2017-07-06

    Epidemiological genetics established that heritability in determining the risk of myocardial infarction (MI) is substantially greater when MI occurs early in life. However, the genetic architecture of early-onset and late-onset MI was not compared. We analyzed genotype frequencies of SNPs in/near 20 genes whose protein products are involved in the pathogenesis of atherosclerosis in two groups of Russian patients with MI: the first group included patients with age of first MI onset <60 years (N = 230) and the second group with onset ≥60 years (N = 174). The control group of corresponding ethnicity consisted of 193 unrelated volunteers without cardiovascular diseases (93 individuals were over 60 years). We found that in the group of patients with age of onset <60 years, SNPs FGB rs1800788*T, TGFB1 rs1982073*T/T, ENOS rs2070744*C and CRP rs1130864*T/T were associated with risk of MI, whereas in patients with age of onset ≥60 years, only TGFB1 rs1982073*T/T was associated with risk of MI. Using APSampler software, we found composite markers associated with MI only in patients with early onset: FGB rs1800788*T + TGFB1 rs1982073*T; FGB rs1800788*T + LPL rs328*C + IL4 rs2243250*C; FGB rs1800788*T + ENOS rs2070744*C (Fisher p values of 1.4 × 10(-6) to 2.2 × 10(-5); the permutation p values of 1.1 × 10(-5) to 3.0 × 10(-4); ORs = 2.67-2.54). Alleles included in the combinations were associated with MI less significantly and with lower ORs than the combinations themselves. The result showed a substantially greater contribution of the genetic component in the development of MI if it occurs early in life, and demonstrated the usefulness of genetic testing for young people.

  5. Epigenetic and genetic factors predict women's salivary cortisol following a threat to the social self.

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    Shany Edelman

    Full Text Available Evidence suggests that the reactivity of the Hypothalamus-Pituitary-Adrenal axis (HPAA is modulated by both genetic and environmental variables. Of special interest are the underlying molecular mechanisms driving gender differences to psychosocial stressors. Epigenetic mechanisms that sculpt the genome are ideal candidates for mediating the effects of signals on the HPAA. In the current study, we analyzed by pyrosequencing, bisulfite-treated buccal DNA from male and female university students who participated in the Trier Social Stress Test (TSST. A linear regression model was used to ascertain the effects of sex, CpG methylation and genes on stress response. Total cortisol output (area under the curve, AUC was significantly predicted by glucocorticoid receptor (NR3C1 exon 1F methylation (averaged across 39 CpG sites solely in female subjects. A single CpG site located in the exon 1F noncanonical nerve growth factor-inducible protein A (NGFI-A transcription factor was a highly significant predictor of AUC in female subjects. Additionally, variations in the estrogen receptor alpha (ESR1 and the serotonin transporter promoter (5-HTTLPR genes were independent additive predictors of AUC. The full model accounted for half of the variance (50.06% in total cortisol output. Notably, this is the first demonstration that epigenetic changes at the GR exon 1F correlate with HPAA reactivity. These findings have important implications for understanding the molecular mechanisms underlying gender differences in stress-related disorders and underscore the unique value of modeling both epigenetic and genetic information in conferring vulnerability to stress.

  6. Epigenetic and genetic factors predict women's salivary cortisol following a threat to the social self.

    Science.gov (United States)

    Edelman, Shany; Shalev, Idan; Uzefovsky, Florina; Israel, Salomon; Knafo, Ariel; Kremer, Ilana; Mankuta, David; Kaitz, Marsha; Ebstein, Richard P

    2012-01-01

    Evidence suggests that the reactivity of the Hypothalamus-Pituitary-Adrenal axis (HPAA) is modulated by both genetic and environmental variables. Of special interest are the underlying molecular mechanisms driving gender differences to psychosocial stressors. Epigenetic mechanisms that sculpt the genome are ideal candidates for mediating the effects of signals on the HPAA. In the current study, we analyzed by pyrosequencing, bisulfite-treated buccal DNA from male and female university students who participated in the Trier Social Stress Test (TSST). A linear regression model was used to ascertain the effects of sex, CpG methylation and genes on stress response. Total cortisol output (area under the curve, AUC) was significantly predicted by glucocorticoid receptor (NR3C1) exon 1F methylation (averaged across 39 CpG sites) solely in female subjects. A single CpG site located in the exon 1F noncanonical nerve growth factor-inducible protein A (NGFI-A) transcription factor was a highly significant predictor of AUC in female subjects. Additionally, variations in the estrogen receptor alpha (ESR1) and the serotonin transporter promoter (5-HTTLPR) genes were independent additive predictors of AUC. The full model accounted for half of the variance (50.06%) in total cortisol output. Notably, this is the first demonstration that epigenetic changes at the GR exon 1F correlate with HPAA reactivity. These findings have important implications for understanding the molecular mechanisms underlying gender differences in stress-related disorders and underscore the unique value of modeling both epigenetic and genetic information in conferring vulnerability to stress.

  7. Comorbid obsessive-compulsive symptoms in schizophrenia: contributions of pharmacological and genetic factors

    Directory of Open Access Journals (Sweden)

    Frederike eSchirmbeck

    2013-08-01

    Full Text Available A large subgroup of around 25% of schizophrenia patients suffers from obsessive-compulsive symptoms (OCS and about 12% fulfil the diagnostic criteria of obsessive-compulsive disorder (OCD. The additional occurrence of OCS is associated with high subjective burden of disease, additional neurocognitive impairment, poorer social and vocational functioning, greater service utilization and high levels of anxiety and depression. Comorbid patients can be assigned to heterogeneous subgroups. One hypothesis assumes that second generation antipsychotics (SGAs, most importantly clozapine, might aggravate or even induce second-onset OCS. Several arguments support this assumption, most importantly the observed chronological order of first psychotic manifestation, start of treatment with clozapine and onset of OCS. In addition, correlations between OCS-severity and dose and serum levels and duration of clozapine treatment hint towards a dose-dependent side effect. It has been hypothesized that genetic risk-factors dispose patients with schizophrenia to develop OCS. One study in a South Korean sample reported associations with polymorphisms in the gene SLC1A1 (solute carrier family 1A1 and SGA-induced OCS. However, this finding could not be replicated in European patients. Preliminary results also suggest an involvement of polymorphisms in the BDNF gene (brain-derived neurotrophic factor and an interaction between markers of SLC1A1 and the gene DLGAP3 (disc large associated protein 3 as well as GRIN2B (N-methyl-D-aspartate receptor subunit 2B. Further research of well-defined samples, in particular studies investigating possible interactions of genetic risk-constellations and pharmacodynamic properties, are needed to clarify the assumed development of SGA-induced OCS. Results might improve pathogenic concepts and facilitate the definition of at risk populations, early detection and monitoring of OCS as well as multimodal therapeutic interventions.

  8. A candidate gene approach identifies an IL33 genetic variant as a novel genetic risk factor for GCA.

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    Ana Márquez

    Full Text Available Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition.A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within the IL1RL1 gene, previously associated with immune-related diseases, were genotyped using predesigned TaqMan assays.A consistent association between the rs7025417 polymorphism and GCA was evident in the overall meta-analysis, under both allele (P(MH = 0.041, OR = 0.88, CI 95% 0.78-0.99 and recessive (P(MH = 3.40E-03, OR = 0.53, CI 95% 0.35-0.80 models. No statistically significant differences between allele or genotype frequencies for the other IL33 and IL1RL1 genetic variants were detected in this pooled analysis.Our results clearly evidenced the implication of the IL33 rs7025417 polymorphism in the genetic network underlying GCA.

  9. Impact on total population health and societal cost-effectiveness of including tumour necrosis factor- antagonists in management of ankylosing spondylitis: a dynamic population modelling study

    NARCIS (Netherlands)

    A. Tran-Duy (An); A. Boonen (Annelies); M.A.F.J. van de Laar (Martin); J.L. Severens (Hans)

    2015-01-01

    markdownabstractAbstract Background: Sequential treatment of ankylosing spondylitis (AS) that includes tumour necrosis factor-α antagonists (anti-TNF agents) has been applied in most of the Western countries. Existing cost-effectiveness (CE) models almost exclusively presented the incremental

  10. The effects of socioeconomic status, clinical factors, and genetic ancestry on pulmonary tuberculosis disease in northeastern Mexico.

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    Bonnie N Young

    Full Text Available Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs. We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic

  11. The effects of socioeconomic status, clinical factors, and genetic ancestry on pulmonary tuberculosis disease in northeastern Mexico.

    Science.gov (United States)

    Young, Bonnie N; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L

    2014-01-01

    Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

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

    Science.gov (United States)

    Miller, David; Summers, Jonathan; Silber, Sherman

    2004-04-01

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

  13. Genetic Factors and Host Traits Predict Spore Morphology for a Butterfly Pathogen

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    Jacobus C. de Roode

    2013-08-01

    Full Text Available Monarch butterflies (Danaus plexippus throughout the world are commonly infected by the specialist pathogen Ophryocystis elektroscirrha (OE. This protozoan is transmitted when larvae ingest infectious stages (spores scattered onto host plant leaves by infected adults. Parasites replicate internally during larval and pupal stages, and adult monarchs emerge covered with millions of dormant spores on the outsides of their bodies. Across multiple monarch populations, OE varies in prevalence and virulence. Here, we examined geographic and genetic variation in OE spore morphology using clonal parasite lineages derived from each of four host populations (eastern and western North America, South Florida and Hawaii. Spores were harvested from experimentally inoculated, captive-reared adult monarchs. Using light microscopy and digital image analysis, we measured the size, shape and color of 30 replicate spores per host. Analyses examined predictors of spore morphology, including parasite source population and clone, parasite load, and the following host traits: family line, sex, wing area, and wing color (orange and black pigmentation. Results showed significant differences in spore size and shape among parasite clones, suggesting genetic determinants of morphological variation. Spore size also increased with monarch wing size, and monarchs with larger and darker orange wings tended to have darker colored spores, consistent with the idea that parasite development depends on variation in host quality and resources. We found no evidence for effects of source population on variation in spore morphology. Collectively, these results provide support for heritable variation in spore morphology and a role for host traits in affecting parasite development.

  14. Effect of genetic and environmental factors on the growth performance traits of Pak-Awassi sheep

    National Research Council Canada - National Science Library

    Asif Raza; Hubdar Ali Kaleri; Rameez Raja Kaleri; Asma Kaleri; Muhamad Bux; Mushtaque Ahmed Jalbani; Ali Ghulam; Depeesh Kumar; Abdul Karim

    2017-01-01

    Present research was carried out to investigate the genetic characteristics of Pak-Awassi Sheep with respect to the growth performance traits and estimation of the genetic parameters. The 10 years (2004-2013...

  15. A comparison of statistical methods for the discovery of genetic risk factors using longitudinal family study designs

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    Kelly M Burkett

    2015-11-01

    Full Text Available The etiology of immune-related diseases or traits is often complex, involving many genetic and environmental factors and their interactions. While methodological approaches focusing on an outcome measured at one time point have succeeded in identifying genetic factors involved in immune-related traits, they fail to capture complex disease mechanisms that fluctuate over time. It is increasingly recognized that longitudinal studies, where an outcome is measured at multiple time points, have great potential to shed light on complex disease mechanisms involving genetic factors. However, longitudinal data requires specialized statistical methods, especially in family studies where multiple sources of correlation in the data must be modeled. Using simulated data with known genetic effects, we examined the performance of different analytical methods for investigating associations between genetic factors and longitudinal phenotypes in twin data. The simulations were modeled on data from the Québec Newborn Twin Study, an ongoing population-based longitudinal study of twin births with multiple phenotypes, such as cortisol levels and body mass index, collected multiple times in infancy and early childhood and with sequencing data on immune-related genes and pathways. We compared approaches that we classify as (1 family-based methods applied to summaries of the observations over time, (2 longitudinal-based methods with simplifications of the familial correlation and (3 Bayesian family-based method with simplifications of the temporal correlation. We found that for estimation of the genetic main and interaction effects, all methods gave estimates close to the true values and had similar power. If heritability estimation is desired, approaches of type (1 also provide heritability estimates close to the true value. Our work shows that the simpler approaches are likely adequate to detect genetic effects; however, interpretation of these effects is more

  16. K-ras genetic mutation and influencing factor analysis for Han and Uygur nationality colorectal cancer patients.

    Science.gov (United States)

    Eli, Mayinur; Mollayup, Ablikim; Muattar; Liu, Chao; Zheng, Chao; Bao, Yong-Xing

    2015-01-01

    To investigate the K-ras genetic mutation status in colorectal cancer patients, compare the difference of K-ras genetic mutation rate in Han and Uygur nationality and analyze the influencing factor. 91 cases (52 cases of Han nationality and 39 cases of Uygur nationality) of colorectal biopsy or surgical ablation pathology specimen from the first affiliated hospital of Xinjiang Medical University during January, 2010 to March, 2013 were collected to detect the 12th and 13th code mutation status of K-ras gene exon 2 with pyrosequencing method and compare the difference of K-ras gene mutation rate between Han and Uygur nationality patients. Single factor analysis and multiple factor logistic regression analysis were utilized to analyze the influencing factor for K-ras genetic mutation. 33 cases of patients with K-ras genetic mutation were found from the 91 cases colorectal cancer patients and the total mutation rate was 36.3%. Among them, 24 cases (72.7%) were found with mutation only in the 12th code, 9 cases (27.3%) were found with mutation only in the 13th code and no one case was found with mutation in both the two codes. Mutation rate of the 12th code in the Uygur nationality was significantly higher than that in the Han nationality (P0.05). There were no associativity (P>0.05) between the K-ras genetic mutation and sex, age, smoking history, drinking history, tumor location, macropathology type, differentiation level, staging, invasive depth, lymph nodes transferring and metastasis in colorectal cancer patients (P>0.05). K-ras genetic mutation rate is high in colorectal cancer patients. The mutation rate of 12th code in Uygur nationality is higher than that in Han nationality. There is no significant associativity between K-ras genetic mutation rate and patients' clinical pathology characteristic.

  17. A comparison of a single genetic factor, two stress factors, and one psychosocial coping factors as predictors of depression in an Australian community sammple

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    Sharpley, Christopher F.

    2014-12-01

    Full Text Available Aim. Although both have shown significant effects upon depression in clinical samples, no direct comparison has been reported of the relative power of psychological resilience and the short form of the serotonin transporter gene 5-HTTLPR as predictors of depression in a community sample. Material and methods. In a sample set by a priori power analysis, 67 adult females and 59 adult males were used to enable a comparison between a single genetic factor, childhood stressors, recent stressors, psychological resilience and depression. Results. None of genotype, childhood or recent stressors was significantly associated with depression scores, but resilience was a significant inverse predictor of depression scores and also of the presence of clinically significant depression. Discussion. These data suggest that measures of an individual’s ability to resist or recover from stress may be useful in assessing vulnerability to depression when used with ‘at risk’ individuals in everyday practice.

  18. Heterogeneity of Genetic Damage in Cervical Nuclei and Lymphocytes in Women with Different Levels of Dysplasia and Cancer-Associated Risk Factors

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    Carlos Alvarez-Moya

    2015-01-01

    Full Text Available The comet assay can be used to assess genetic damage, but heterogeneity in the length of the tails is frequently observed. The aims of this study were to evaluate genetic damage and heterogeneity in the cervical nuclei and lymphocytes from patients with different levels of dysplasia and to determine the risk factors associated with the development of cervical cancer. The study included 97 females who presented with different levels of dysplasia. A comet assay was performed in peripheral blood lymphocytes and cervical epithelial cells. Significant genetic damage (P≤0.05 was observed only in patients diagnosed with nuclei cervical from dysplasia III (NCDIII and lymphocytes from dysplasia I (LDI. However, the standard deviations of the tail lengths in the cervical nuclei and lymphocytes from patients with dysplasia I were significantly different (P≤0.0001 from the standard deviations of the tail lengths in the nuclei cervical and lymphocytes from patients with DII and DIII (NCDII, NCDIII and LDII, LDIII, indicating a high heterogeneity in tail length. Results suggest that genetic damage could be widely present but only manifested as increased tail length in certain cell populations. This heterogeneity could obscure the statistical significance of the genetic damage.

  19. Heterogeneity of Genetic Damage in Cervical Nuclei and Lymphocytes in Women with Different Levels of Dysplasia and Cancer-Associated Risk Factors

    Science.gov (United States)

    Alvarez-Moya, Carlos; Reynoso-Silva, Mónica; Canales-Aguirre, Alejandro A.; Chavez-Chavez, José O.; Castañeda-Vázquez, Hugo; Feria-Velasco, Alfredo I.

    2015-01-01

    The comet assay can be used to assess genetic damage, but heterogeneity in the length of the tails is frequently observed. The aims of this study were to evaluate genetic damage and heterogeneity in the cervical nuclei and lymphocytes from patients with different levels of dysplasia and to determine the risk factors associated with the development of cervical cancer. The study included 97 females who presented with different levels of dysplasia. A comet assay was performed in peripheral blood lymphocytes and cervical epithelial cells. Significant genetic damage (P ≤ 0.05) was observed only in patients diagnosed with nuclei cervical from dysplasia III (NCDIII) and lymphocytes from dysplasia I (LDI). However, the standard deviations of the tail lengths in the cervical nuclei and lymphocytes from patients with dysplasia I were significantly different (P ≤ 0.0001) from the standard deviations of the tail lengths in the nuclei cervical and lymphocytes from patients with DII and DIII (NCDII, NCDIII and LDII, LDIII), indicating a high heterogeneity in tail length. Results suggest that genetic damage could be widely present but only manifested as increased tail length in certain cell populations. This heterogeneity could obscure the statistical significance of the genetic